# Scientific Reports

Online ISSN: 2045-2322
Recent publications
Article
We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged < 18y with a diagnosis code of sepsis upon admission in Queensland, Australia were compared for 16 participating and 32 non-participating hospitals before and after pathway implementation. Monte Carlo simulation was used to generate uncertainty intervals. Policy impacts were estimated using difference-in-difference analysis comparing observed and expected results. We compared 1055 patient episodes before (77.6% in-pathway) and 1504 after (80.5% in-pathway) implementation. Reductions were likely for non-intensive length of stay (− 20.8 h [− 36.1, − 8.0]) but not intensive care (–9.4 h [− 24.4, 5.0]). Non-pathway utilisation was likely unchanged for interhospital transfers (+ 3.2% [− 5.0%, 11.4%]), non-intensive (− 4.5 h [− 19.0, 9.8]) and intensive (+ 7.7 h, [− 20.9, 37.7]) care length of stay. After difference-in-difference adjustment, estimated savings were 596 [277, 942] non-intensive and 172 [148, 222] intensive care days. The program was cost-saving in 63.4% of simulations, with a mean value of $97,019 [−$857,273, \$1,654,925] over 24 months. A paediatric sepsis pathway in Queensland emergency departments was associated with potential reductions in hospital utilisation and costs.

Article
Invasive aspergillosis (IA) may occur as a serious complication of hematological malignancy. Delays in antifungal therapy can lead to an invasive disease resulting in high mortality. Currently, there are no well-established blood circulating microRNA biomarkers or laboratory tests which can be used to diagnose IA. Therefore, we aimed to define dysregulated miRNAs in hematology and oncology (HO) patients to identify biomarkers predisposing disease. We performed an in-depth analysis of high-throughput small transcriptome sequencing data obtained from the whole blood samples of our study cohort of 50 participants including 26 high-risk HO patients and 24 controls. By integrating in silico bioinformatic analyses of small noncoding RNA data, 57 miRNAs exhibiting significant expression differences ( P < 0.05) were identified between IA-infected patients and non-IA HO patients. Among these, we found 36 differentially expressed miRNAs (DEMs) irrespective of HO malignancy. Of the top ranked DEMs, we found 14 significantly deregulated miRNAs, whose expression levels were successfully quantified by qRT-PCR. MiRNA target prediction revealed the involvement of IA related miRNAs in the biological pathways of tumorigenesis, the cell cycle, the immune response, cell differentiation and apoptosis.

Article
The optimal scheduling problem of integrated energy system (IES) has the characteristics of high-dimensional nonlinearity. Using the traditional Grey Wolf Optimizer (GWO) to solve the problem, it is easy to fall into a local optimum in the process of optimization, resulting in a low-quality scheduling scheme. Aiming at the dispatchability of electric and heat loads, this paper proposes an electric and heat comprehensive demand response model considering the participation of dispatchers. On the basis of incentive demand response, the group aggregation model of electrical load is constructed, and the electric load response model is constructed with the goal of minimizing the deviation between the dispatch signal and the load group aggregation characteristic model. Then, a heat load scheduling model is constructed according to the ambiguity of the human body's perception of temperature. On the basis of traditional GWO, the Fuzzy C-means (FCM) clustering algorithm is used to group wolves, which increases the diversity of the population, uses the Harris Hawk Optimizer (HHO) to design the prey to search for the best escape position, and reduces the local The optimal probability, and the use of Particle Swarm Optimizer (PSO) and Bat Optimizer (BO) to design the moving modes of different positions, increase the ability to find the global optimum, so as to obtain an Improved Gray Wolf Optimizer (IGWO), and then efficiently solve the model. IGWO can improve the defect of insufficient population diversity in the later stage of evolution, so that the population diversity can be better maintained during the entire evolution process. While taking into account the speed of optimization, it improves the algorithm's ability to jump out of the local optimum and realizes continuous deep search. Compared with the traditional intelligent Optimizer, IGWO has obvious improvement and achieved better results. At the same time, the comprehensive demand response that considers the dispatcher's desired signal improves the accommodation of new energy and reduces the operating cost of the system, and promotes the benign interaction between the source and the load.

Article
Deep hashing method is widely applied in the field of image retrieval because of its advantages of low storage consumption and fast retrieval speed. There is a defect of insufficiency feature extraction when existing deep hashing method uses the convolutional neural network (CNN) to extract images semantic features. Some studies propose to add channel-based or spatial-based attention modules. However, embedding these modules into the network can increase the complexity of model and lead to over fitting in the training process. In this study, a novel deep parameter-free attention hashing (DPFAH) is proposed to solve these problems, that designs a parameter-free attention (PFA) module in ResNet18 network. PFA is a lightweight module that defines an energy function to measure the importance of each neuron and infers 3-D attention weights for feature map in a layer. A fast closed-form solution for this energy function proves that the PFA module does not add any parameters to the network. Otherwise, this paper designs a novel hashing framework that includes the hash codes learning branch and the classification branch to explore more label information. The like-binary codes are constrained by a regulation term to reduce the quantization error in the continuous relaxation. Experiments on CIFAR-10, NUS-WIDE and Imagenet-100 show that DPFAH method achieves better performance.

Article
Biomarkers predictive of drug-specific outcomes are important tools for personalized medicine. In this study, we present an integrative analysis to identify miRNAs that are predictive of drug-specific survival outcome in cancer. Using the clinical data from TCGA, we defined subsets of cancer patients who suffered from the same cancer and received the same drug treatment, which we call cancer-drug groups. We then used the miRNA expression data in TCGA to evaluate each miRNA’s ability to predict the survival outcome of patients in each cancer-drug group. As a result, the identified miRNAs are predictive of survival outcomes in a cancer-specific and drug-specific manner. Notably, most of the drug-specific miRNA survival markers and their target genes showed consistency in terms of correlations in their expression and their correlations with survival. Some of the identified miRNAs were supported by published literature in contexts of various cancers. We explored several additional breast cancer datasets that provided miRNA expression and survival data, and showed that our drug-specific miRNA survival markers for breast cancer were able to effectively stratify the prognosis of patients in those additional datasets. Together, this analysis revealed drug-specific miRNA markers for cancer survival, which can be promising tools toward personalized medicine.

Article
In the present study, we elucidated the effect of grain-based (GB) diet containing both soluble and insoluble fibers and purified ingredients-based (PIB) diet containing only insoluble fiber, namely cellulose on mice gut microbiome using whole shotgun based metagenomic sequencing. Although the fiber content in both diet types is the same (5%) the presence of soluble fiber only in the GB diet differentiates it from the PIB diet. The taxonomic analysis of sequenced reads reveals a significantly higher enrichment of probiotic Lactobacilli in the GB group as compared to the PIB group. Further, the enhancement of energy expensive cellular processes namely, cell cycle control, cell division, chromosome partitioning, and transcription is observed in the GB group which could be due to the metabolization of the soluble fiber for faster energy production. In contrast, a higher abundance of cellulolytic bacterial community namely, the members of family Lachnospiraceae and Ruminococcaceae and the metabolism functions are found in the PIB group. The PIB group shows a significant increase in host-derived oligosaccharide metabolism functions indicating that they might first target the host-derived oligosaccharides and self-stored glycogen in addition to utilising the available cellulose. In addition to the beneficial microbial community variations, both the groups also exhibited an increased abundance of opportunistic pathobionts which could be due to an overall low amount of fiber in the diet. Furthermore, backtracing analysis identified probiotic members of Lactobacillus , viz., L. crispatus ST1 , L. fermentum CECT 5716 , L. gasseri ATCC 33323 , L. johnsonii NCC 533 and L. reuteri 100-23 in the GB group, while Bilophila wadsworthia 3_1_6 , Desulfovibrio piger ATCC 29098 , Clostridium symbiosum WAL-14163 , and Ruminococcaceae bacterium D16 in the PIB group. These data suggest that Lactobacilli , a probiotic community of microorganisms, are the predominant functional contributors in the gut of GB diet-fed mice, whereas pathobionts too coexisted with commensals in the gut microbiome of the PIB group. Thus at 5% fiber, GB modifies the gut microbial ecology more effectively than PIB and the inclusion of soluble fiber in the GB diet may be one of the primary factors responsible for this impact.

Article
Leaves and flowers of Amorphophallus konjac do not develop simultaneously thus unique features can be elucidated through study of flowering transformation in A. konjac. In this study, transcriptome libraries of A. konjac leaf buds (LB) and flower buds (FB) were constructed followed by high-throughput sequencing. A total of 68,906 unigenes with an average length of 920 bp were obtained after library assembly. Out of these genes, 24,622 unigenes had annotation information. A total of 6859 differentially expressed genes (DEGs) were identified through differential expression analysis using LB as control. Notably, 2415 DEGs were upregulated whereas 4444 DEGs were downregulated in the two transcriptomes. Go and KEGG analysis showed that the DEGs belonged to 44 functional categories and were implicated in 98 metabolic pathways and 38 DEGs involved in plant hormone signal transduction. Several genes were mined that may be involved in A. konjac flower bud differentiation and flower organ development. Eight DEGs were selected for verification of RNA-seq results using qRT-PCR analysis. Two FLOWERING LOCUS T ( FT ) genes named AkFT1 and AkFT2 were identified though homologous analysis may be the florigen gene implicated in modulation of A. konjac flowering. These genes were significantly upregulated in flower buds compared with the expression levels on leaf buds. Overexpression of AkFT genes though heterologous expression in Arabidopsis showed that the transgenics flowered at a very early stage relative to wild type plants. These findings indicate that AkFT1 and AkFT2 function as regulation genes in A. konjac flowering development and the two genes may present similar functions during flowering transition.

Article
Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose–response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.

Article
Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.

Article
It is well known that green urban commons enhance mental and physical well-being and improve local biodiversity. We aim to investigate how these outcomes are related in an urban system and which variables are associated with better outcomes. We model the outcomes of an urban common—box gardening—by applying the Social-Ecological Systems (SES) framework. We expand the SES framework by analyzing it from the perspective of social evolution theory. The system was studied empirically through field inventories and questionnaires and modeled quantitatively by Structural Equation Modeling (SEM). This method offers powerful statistical models of complex social-ecological systems. Our results show that objectively evaluated ecological outcomes and self-perceived outcomes are decoupled: gardening groups that successfully govern the natural resource ecologically do not necessarily report many social, ecological, or individual benefits, and vice versa. Social capital, box location, gardener concerns, and starting year influenced the changes in the outcomes. In addition, the positive association of frequent interactions with higher self-perceived outcomes, and lack of such association with relatedness of group members suggests that reciprocity rather than kin selection explains cooperation. Our findings exemplify the importance of understanding natural resource systems at a very low “grassroot” level.

Article
The doubly labelled water (DLW) method is widely used to determine energy expenditure. In this work, we demonstrate the addition of the third stable isotope, ¹⁷ O, to turn it into triply labelled water (TLW), using the three isotopes measurement of optical spectrometry. We performed TLW ( ² H, ¹⁸ O and ¹⁷ O) measurements for the analysis of the CO 2 production (r CO2 ) of mice on different diets for the first time. Triply highly enriched water was injected into mice, and the isotope enrichments of the distilled blood samples of one initial and two finals were measured by an off-axis integrated cavity output spectroscopy instrument. We evaluated the impact of different calculation protocols and the values of evaporative water loss fraction. We found that the dilution space and turnover rates of ¹⁷ O and ¹⁸ O were equal for the same mice group, and that values of r CO2 calculated based on ¹⁸ O– ² H, or on ¹⁷ O– ² H agreed very well. This increases the reliability and redundancy of the measurements and it lowers the uncertainty in the calculated r CO2 to 3% when taking the average of two DLW methods. However, the TLW method overestimated the r CO2 compared to the indirect calorimetry measurements that we also performed, much more for the mice on a high-fat diet than for low-fat. We hypothesize an extra loss or exchange mechanism with a high fractionation for ² H to explain this difference.

Article
To design highly efficient and broadband nanometer-sized absorbers based on the atomically thin transition metal dichalcogenides (TMDCs), we propose utilizing inclined gold gratings on MoS 2 monolayer. In the case of gold gratings with zero inclination, coverage of the absorption spectrum in the entire visible range occurs between the values of 42% to 73%. Considerable increase in the absorbed light occurs by introducing 13 nm inclination to the gold gratings with equal values of the grating’s period and width as 60 nm. With the application of this grating, maximum absorption of 88% is reached and the absorption bandwidth covers the entire visible spectrum with only 12% variation of the absorption value relative to this maximum (88%). Footprints of resonant excitation of two different modes in the absorber structure are evident: the named “reflection” mode and localized surface plasmons (LSPs). Inclination of the gratings leads the LSP modes to slide toward the MoS 2 and causes a remarkable increment in the absorption efficiency. An impressive absorption value of 56% in MoS 2 monolayer is gained by the gold grating’s inclination of 17 nm. The designed absorber paves a new way in designing TMDC-based absorbers with extended bandwidths and higher efficiencies.

Article
Automated classification and detection of brain abnormalities like a tumor(s) in reconstructed microwave (RMW) brain images are essential for medical application investigation and monitoring disease progression. This paper presents the automatic classification and detection of human brain abnormalities through the deep learning-based YOLOv5 object detection model in a portable microwave head imaging system (MWHI). Initially, four hundred RMW image samples, including non-tumor and tumor(s) in different locations are collected from the implemented MWHI system. The RMW image dimension is 640 × 640 pixels. After that, image pre-processing and augmentation techniques are applied to generate the training dataset, consisting of 4400 images. Later, 80% of images are used to train the models, and 20% are used for testing. Later, from the 80% training dataset, 20% are utilized to validate the models. The detection and classification performances are evaluated by three variations of the YOLOv5 model: YOLOv5s, YOLOv5m, and YOLOv5l. It is investigated that the YOLOv5l model performed better compared to YOLOv5s, YOLOv5m, and state-of-the-art object detection models. The achieved accuracy, precision, sensitivity, specificity, F1-score, mean average precision (mAP), and classification loss are 96.32%, 95.17%, 94.98%, 95.28%, 95.53%, 96.12%, and 0.0130, respectively for the YOLOv5l model. The YOLOv5l model automatically detected tumor(s) accurately with a predicted bounding box including objectness score in RMW images and classified the tumors into benign and malignant classes. So, the YOLOv5l object detection model can be reliable for automatic tumor(s) detection and classification in a portable microwave brain imaging system as a real-time application.

Article
Knowledge about the activity of single neurons is essential in understanding the mechanisms of synchrony generation, and particularly interesting if related to pathological conditions. The generation of interictal spikes—the hypersynchronous events between seizures—is linked to hyperexcitability and to bursting behaviour of neurons in animal models. To explore its cellular mechanisms in humans we investigated the activity of clustered single neurons in a human in vitro model generating both physiological and epileptiform synchronous events. We show that non-epileptic synchronous events resulted from the finely balanced firing of excitatory and inhibitory cells, which was shifted towards an enhanced excitability in epileptic tissue. In contrast, interictal-like spikes were characterised by an asymmetric overall neuronal discharge initiated by excitatory neurons with the presumptive leading role of bursting pyramidal cells, and possibly terminated by inhibitory interneurons. We found that the overall burstiness of human neocortical neurons is not necessarily related to epilepsy, but the bursting behaviour of excitatory cells comprising both intrinsic and synaptically driven bursting is clearly linked to the generation of epileptiform synchrony.

Article
The acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response and neutrophils play a central role in its pathogenesis. Neutrophils express the integrin Mac-1 on their surface which adopts a resting and activated conformation depending on leukocyte activation. The aim of this study was to investigate the anti-inflammatory effects of the unique activation-specific anti-Mac-1 DARPin ‘F7’ in a mouse model of ARDS. ARDS was induced by intratracheal lipopolysaccharide (LPS) instillation and the acute (day 1–4) and chronic phase (day 5–10) were studied. After expression and purification, F7, a control DARPin and PBS, were applied daily via the intraperitoneal route. Survival and weight loss were recorded. Histological analysis of lung sections, flow cytometric leukocyte analysis of blood and bronchioalveolar lavage (BALF) were performed. Moreover, protein concentration and cytokine levels were determined in the BALF. Treatment with F7 improved survival and reduced weight loss significantly compared to treatment with the control DARPin or PBS. Neutrophil count in the BALF and peripheral blood were significantly reduced in mice treated with F7. Histology revealed significantly reduced pulmonary inflammation in the F7 treated group. Treatment with DARPin F7 inhibited neutrophil accumulation, reduced signs of local and systemic inflammation and improved survival in a mouse model of ARDS. F7 may be a novel anti-inflammatory drug candidate for the treatment of severe ARDS.

Article
Neuroimaging studies have suggested a link between the intensity of chronic low back pain intensity and structural and functional brain alterations. However, chronic pain results from the coordination and dynamics among several brain networks that comprise the dynamic pain connectome. Here, we use resting-state functional magnetic resonance imaging and measures of static (sFC) and dynamic functional connectivity (dFC) variability in the typical (0.01–0.1 Hz) and five specific (slow-6 to slow-2) frequency bands to test hypotheses regarding disruption in this variability in low back-related leg pain (LBLP) patients who experience chronic pain and numbness. Twenty-four LBLP patients and 23 healthy controls completed clinical assessments, and partial correlational analyses between altered sFC and dFC variability and clinical measures were conducted. We found a lower within-network sFC in the ascending nociceptive pathway (Asc) and a lower cross-network sFC between nodes of the salience network and the Asc in the typical frequency band. In the slow-5 frequency band, a lower within-network sFC was found in the Asc. Abnormal cross-network sFC was found between nodes of the salience network-Asc (slow-5 and slow-6) and the default mode network-Asc (slow-4 and slow-6). Furthermore, cross-network abnormalities in the typical and certain specific frequency bands were linked to clinical assessments. These findings indicate that frequency-related within- and cross-network communication among the nodes in the dynamic pain connectome is dysfunctional in LBLP patients and that selecting specific frequencies may be potentially useful for detecting LBLP-related brain activity.

Article
The L-shell X-ray emissions of iodine are investigated as a function of the incident energy for I ²²⁺ ions impacting on Fe target in the energy region near the Bohr velocity. Six distinct L-subshell X-rays, Lι, Lα 1, 2 , Lβ 1, 3, 4 , Lβ 2, 15 , Lγ 1 and Lγ 2, 3, 4, 4 ' , are observed. Compared to the atomic data, the energy of the experimental X ray shifts to the higher energy side. The relative intensity ratios of Lι, Lβ 1, 3, 4 , Lβ 2, 15 , to Lα 1, 2 , Lι to Lβ 2, 15 and Lγ 2, 3, 4, 4/ to Lγ 1 are enhanced, but has no obvious change with the increase of projectile energy in the present energy region. That is interpreted by the multiple ionization effect of the M-, N- and O-shell electrons.

Article
Information about cholesterol subcellular localization and transport pathways inside cells is essential for understanding and treatment of cholesterol-related diseases. However, there is a lack of reliable tools to monitor it. This work follows the fate of Sterolight, a BODIPY-labelled sterol, within the cell and demonstrates it as a suitable probe for visualization of sterol/lipid trafficking. Sterolight enters cells through an energy-independent process and knockdown experiments suggest caveolin-1 as its potential cellular carrier. Intracellular transport of Sterolight is a rapid process, and transfer from ER and mitochondria to lysosomes and later to lipid droplets requires the participation of active microtubules, as it can be inhibited by the microtubule disruptor nocodazole. Excess of the probe is actively exported from cells, in addition to being stored in lipid droplets, to re-establish the sterol balance. Efflux occurs through a mechanism requiring energy and may be selectively poisoned with verapamil or blocked in cells with mutated cholesterol transporter NPC1. Sterolight is efficiently transferred within and between different cell populations, making it suitable for monitoring numerous aspects of sterol biology, including the live tracking and visualization of intracellular and intercellular transport.

Article
The current study aimed to determination of cytotoxicity, antioxidant, anti-inflammatory, anti-hemolytic, and anticoagulant activities of phenolic compounds extracted from olive oil mill wastewater (OMW) issue from the cold extraction of olive oil from Khenchela eastern in Algeria. The LC–MS (liquid chromatography–mass spectrometry) results were revealed the presence of 20 phenolic compounds in the extract of OMW and mostly consisted of Kaempferol, 4,5-di-O-caffeoyquinic acid, quinic acid, and caffeic acid. The extracts possessed effective reducing power (FRAP) and high radical scavenging activity against DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS + (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) free radicals, and it inhibited cytochrome c reduction in a dose-dependent manner. They exert a protective effect on red blood cells, and they were found to exhibit the highest inhibitory effect anti-inflammatory activity using inhibition of protein denaturation (IPD) and membrane stabilizing potential (MSP) tests (80.46 ± 3.81 µg/mL and 87.43 ± 0.66 µg/mL) more than the standard used. The extract also showed the greatest anticoagulant activity in both the endogenous and exogenous routes (44.77 ± 0.25 s and 15.84 ± 0.12 s, respectively). Based on these findings, it is reasonable to infer that OMW is a good source of natural phenolic compounds with potential antioxidant, anti-inflammatory, and anticoagulant properties.

Article
Autism Spectrum Disorder (ASD) diagnosis is still based on behavioral criteria through a lengthy and time-consuming process. Much effort is being made to identify brain imaging biomarkers and develop tools that could facilitate its diagnosis. In particular, using Machine Learning classifiers based on resting-state fMRI (rs-fMRI) data is promising, but there is an ongoing need for further research on their accuracy and reliability. Therefore, we conducted a systematic review and meta-analysis to summarize the available evidence in the literature so far. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across the 55 studies that offered sufficient information for quantitative analysis. Our results indicated overall summary sensitivity and specificity estimates of 73.8% and 74.8%, respectively. SVM stood out as the most used classifier, presenting summary estimates above 76%. Studies with bigger samples tended to obtain worse accuracies, except in the subgroup analysis for ANN classifiers. The use of other brain imaging or phenotypic data to complement rs-fMRI information seems promising, achieving higher sensitivities when compared to rs-fMRI data alone (84.7% versus 72.8%). Finally, our analysis showed AUC values between acceptable and excellent. Still, given the many limitations indicated in our study, further well-designed studies are warranted to extend the potential use of those classification algorithms to clinical settings.

Article
In this work, we have analyzed natural samples collected at three hydrothermal areas of Iceland by Raman spectroscopy. The studied high-latitude regions are considered environmentally and mineralogically appropriate Martian analogues since they are rich in weathered basalts that have been altered by hydrothermalism to mineral phases such as silica, clay minerals, sulfates, oxides, and sulfur. The main objective of this work was to assess the relation of the spectroscopic signatures of alteration to hydrothermal processes and biomediation, considering previous studies focused on the detection of lipid biomarkers in the same samples. The recorded Raman spectra, taken with optical parameters similar to the ExoMars 2022 Raman spectrometer, showed structural modifications in all secondary minerals in the form of peak shifts (in the case of sulfur and clay minerals), changes in the relative ratio intensity (in anatase) and/or shape broadening (in sulfates and hematite). These results reveal the suitability of Raman spectroscopy to examine areas rich in water-altered minerals, where a mixture of crystalline and amorphous phases can co-exist. The detection of silica is singularly interesting since, on the one hand, it can imply the past existence of hydrothermal hot springs rich in nutrient and redox gradients and, on the other hand, provides excellent matrix for biosignature preservation. The data can be helpful as an astrobiological database for the forthcoming missions to Mars, where potential upwelling groundwater systems could have altered the mineral phases in a similar way to that observed in this work.

Article
Para -aminosalicylic acid (PAS) is an antibiotic that was largely used for the multi-therapy of tuberculosis in the twentieth century. To try to overcome the inconvenience of its low efficacy and poor tolerance, we searched for novel chemical entities able to synergize with PAS using a combination screening against growing axenic Mycobacterium tuberculosis . The screening was performed at a sub-inhibitory concentration of PAS on a library of about 100,000 small molecules. Selected hit compounds were analyzed by dose–response and further probed with an intracellular macrophage assay. Scaffolds with potential additive effect with PAS are reported, opening interesting prospects for mechanism of action studies. We also report here evidence of a yet unknown bio-activation mechanism, involving activation of pyrido[1,2-a]pyrimidin-4-one (PP) derivatives through the Rv3087 protein.

Article
Organoid cell culture methodologies are enabling the generation of cell models from healthy and diseased tissue. Patient-derived cancer organoids that recapitulate the genetic and histopathological diversity of patient tumours are being systematically generated, providing an opportunity to investigate new cancer biology and therapeutic approaches. The use of organoid cultures for many applications, including genetic and chemical perturbation screens, is limited due to the technical demands and cost associated with their handling and propagation. Here we report and benchmark a suspension culture technique for cancer organoids which allows for the expansion of models to tens of millions of cells with increased efficiency in comparison to standard organoid culturing protocols. Using whole-genome DNA and RNA sequencing analyses, as well as medium-throughput drug sensitivity testing and genome-wide CRISPR-Cas9 screening, we demonstrate that cancer organoids grown as a suspension culture are genetically and phenotypically similar to their counterparts grown in standard conditions. This culture technique simplifies organoid cell culture and extends the range of organoid applications, including for routine use in large-scale perturbation screens.

Article
To unveil a novel switching mechanism in liquid crystal (LC)-based phase shifters for the THz range, we analyse how the dimensions of the electrode structures enable a new type of switching, namely, THz in-plane and THz out-of-plane (TIP–TOP) switching. Specifically, we determine how varying these electrode dimensions influences the LC in-plane states with the corresponding phase shifts by calculating these effects in virtual devices. Interestingly, we found that significant dimensional effects of the in-plane electrode structures statically and dynamically influence the phase shift and response time of LC switching. Analysing the electromagnetic fields in the TIP–TOP cell clearly reveals that these dimensional effects are due to changes in the electric field strengths caused by lateral bus-line electrodes that were originally assumed not to contribute to the switching. Further, we discover that the ultimate dimensional effect produces a novel type of LC switching, which results in hexadirectional switching between the initial, intrinsic in-plane, and out-of-plane reorientations of the LCs, suggesting a broader range of phase shifts while maintaining a rapid response.

Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accompanied by chronic neurological sequelae such as cognitive decline and mood disorder, but the underlying mechanisms have not yet been elucidated. We explored the possibility that the brain-infiltrating SARS-CoV-2 spike protein contributes to the development of neurological symptoms observed in COVID-19 patients in this study. Our behavioral study showed that administration of SARS-CoV-2 spike protein S1 subunit (S1 protein) to mouse hippocampus induced cognitive deficit and anxiety-like behavior in vivo. These neurological symptoms were accompanied by neuronal cell death in the dorsal and ventral hippocampus as well as glial cell activation. Interestingly, the S1 protein did not directly induce hippocampal cell death in vitro. Rather, it exerted neurotoxicity via glial cell activation, partially through interleukin-1β induction. In conclusion, our data suggest a novel pathogenic mechanism for the COVID-19-associated neurological symptoms that involves glia activation and non-cell autonomous hippocampal neuronal death by the brain-infiltrating S1 protein.

Article
It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients ( n = 42), with or without cirrhosis, and their age-and sex-matched controls ( n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae , Peptostreptococcaceae , Staphylococcaceae, Morganellaceae, Pasteurellaceae , Succinivibrionaceae, and Moraxellaceae . Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.

Article
This study investigated the performance of 24 commercial disinfectants present on the market during last year according to the manufacturer’s instructions. Recently, national and international organizations of public health performed studies on disinfection products due to the increasing awareness of the potential and growing risks on human health, such as skin damage and reactions in the mucosal lining, especially for the healthcare workers in their frequent daily use. However, there are many limitations in the common cleaning/disinfection products on market as in the selection of effective disinfectants to decontaminate inanimate surfaces. We analyzed the disinfection power of hydrogen peroxide, quaternary ammonium compounds, alcohols, phenols and aldehydes used as active principles according to international guidelines. The antimicrobial properties were assessed by broth microdilution, and antibiofilm properties against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ); their virucidal efficacy was tested against Herpes simplex virus type 1 (HSV-1) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quaternary ammonium compounds demonstrated better efficacy than others and in some cases ready to use products had also virucidal and antimicrobial activities after dilution at 0.125%. The scientific evidence indicates that many commercial products are used at high concentrations and high doses and this could have deleterious effects both on human health and the environment. A lower concentration of active ingredients would avoid the excessive release of chemicals into the environment and improve skin tolerance, ensuring the health and safety protection of workers, including the healthcare operators at their workplace.

Article
Crop growth monitoring and yield estimate information can be obtained via appropriate metrics such as the leaf area index (LAI) and biomass. Such information is crucial for guiding agricultural production, ensuring food security, and maintaining sustainable agricultural development. Traditional methods of field measurement and monitoring typically have low efficiency and can only give limited untimely information. Alternatively, methods based on remote sensing technologies are fast, objective, and nondestructive. Indeed, remote sensing data assimilation and crop growth modeling represent an important trend in crop growth monitoring and yield estimation. In this study, we assimilate the leaf area index retrieved from Sentinel-2 remote sensing data for crop growth model of the simple algorithm for yield estimation (SAFY) in wheat. The SP-UCI optimization algorithm is used for fine-tuning for several SAFY parameters, namely the emergence date (D 0 ), the effective light energy utilization rate (ELUE), and the senescence temperature threshold (STT) which is indicative of biological aging. These three sensitive parameters are set in order to attain the global minimum of an error function between the SAFY model predicted values and the LAI inversion values. This assimilation of remote sensing data into the crop growth model facilitates the LAI, biomass, and yield estimation. The estimation results were validated using data collected from 48 experimental plots during 2014 and 2015. For the 2014 data, the results showed coefficients of determination (R ² ) of the LAI, biomass and yield of 0.73, 0.83 and 0.49, respectively, with corresponding root-mean-squared error (RMSE) values of 0.72, 1.13 t/ha and 1.14 t/ha, respectively. For the 2015 data, the estimated R ² values of the LAI, biomass, and yield were 0.700, 0.85, and 0.61, respectively, with respective RMSE values of 0.83, 1.22 t/ha, and 1.39 t/ha, respectively. The estimated values were found to be in good agreement with the measured ones. This shows high applicability of the proposed data assimilation scheme in crop monitoring and yield estimation. As well, this scheme provides a reference for the assimilation of remote sensing data into crop growth models for regional crop monitoring and yield estimation.

Article
Mendelian variants can determine both insemination success and neonatal survival and thus influence fertility and rearing success of cattle. We present 24 deficient homozygous haplotype regions in the Holstein population of Switzerland and provide an overview of the previously identified haplotypes in the global Holstein breed. This study encompasses massive genotyping, whole-genome sequencing (WGS) and phenotype association analyses. We performed haplotype screenings on almost 53 thousand genotyped animals including 114 k SNP data with two different approaches. We revealed significant haplotype associations to several survival, birth and fertility traits. Within haplotype regions, we mined WGS data of hundreds of bovine genomes for candidate causal variants, which were subsequently evaluated by using a custom genotyping array in several thousand breeding animals. With this approach, we confirmed the known deleterious SMC2 :p.Phe1135Ser missense variant associated with Holstein haplotype (HH) 3. For two previously reported deficient homozygous haplotypes that show negative associations to female fertility traits, we propose candidate causative loss-of-function variants: the HH13-related KIR2DS1: p.Gln159* nonsense variant and the HH21-related NOTCH3: p.Cys44del deletion. In addition, we propose the RIOX1: p.Ala133_Glu142del deletion as well as the PCDH15: p.Leu867Val missense variant to explain the unexpected low number of homozygous haplotype carriers for HH25 and HH35, respectively. In conclusion, we demonstrate that with mining massive SNP data in combination with WGS data, we can map several haplotype regions and unravel novel recessive protein-changing variants segregating at frequencies of 1 to 5%. Our findings both confirm previously identified loci and expand the spectrum of undesired alleles impairing reproduction success in Holstein cattle, the world's most important dairy breed.

Article
The RYR1 gene codes for a ryanodine receptor which is a calcium release channel in the skeletal muscle sarcoplasmic reticulum. It is associated with Malignant Hyperthermia (MH) and congenital myopathies including Central Core Disease (CCD), Multiminicore Disease (MMD) and Congenital Fibre-Type Disproportion (CFTD). There is currently little information on the epidemiology of RYR1 variants in Asians. Our study aims to describe the RYR1 variant landscape in a Singapore cohort unselected for RYR1 -associated conditions. Data was retrieved from the SG10K pilot project, where whole genome sequencing was performed on volunteers unselected and undetermined for RYR1 -associated conditions. Variants were classified based on pathogenicity using databases ClinVar and InterVar. Allele frequencies of pathogenic variants were compared between Chinese, Indians and Malays. Using databases ExAC, GnomAD and GenomeAsia 100k study, we further compared local allele frequencies to those in Europe, America and Asia. Data was analysed using R Commander. Significant P value was set at p < 0.05. Majority of the RYR1 variants were missense mutations. We identified four pathogenic and four likely pathogenic RYR1 variants. All were related to the aforementioned RYR1 -associated conditions. There were 6 carriers of RYR1 pathogenic variants amongst 4810 individuals, corresponding to an allele frequency of 0.06%. The prevalence of pathogenic variants was the highest amongst Indians (4 in 1127 individuals) ( p = 0.030). Majority of pathogenic and likely pathogenic mutations were missense and located in mutational hotspots. These variants also occurred at higher frequencies in Asians than globally. This study describes the variant landscape of the RYR1 gene in Singapore. This knowledge will facilitate genetic screening for RYR1-related conditions.

Article
Miniature varifocal lenses are crucial for many applications requiring compact optical systems. Here, utilizing electro-mechanically actuated 0.5-mm aperture infrared Alvarez meta-optics, we demonstrate 3.1 mm (200 diopters) focal length tuning with an actuation voltage below 40 V. This constitutes the largest focal length tuning in any low-power electro-mechanically actuated meta-optic, enabled by the high energy density in comb-drive actuators producing large displacements at relatively low voltage. The demonstrated device is produced by a novel nanofabrication process that accommodates meta-optics with a larger aperture and has improved alignment between meta-optics via flip-chip bonding. The whole fabrication process is CMOS compatible and amenable to high-throughput manufacturing.

Article
Presowing seed treatment is the first step in growing crops and obtaining a predicted high-quality yield. It plays a vital role in an integrated plant protection system. When treating seeds before sowing, it is crucial to avoid seed damage by the machine working bodies to obtain the planned harvest. For that reason, when designing new machines, it is necessary to exclude the use of auger working bodies and reduce the treatment speed. This paper analyzes the interaction of seeds with the working surfaces of centrifugal disk distribution bodies of pressown seed treatment machines. This paper considers the influence of geometric and kinematic factors on the distribution of particles at the outlet of the disk working body. Theoretical dependences that allow determining the relative speed of seed escape from the blades of a centrifugal disk have been obtained. An experimental plant allowing testing of the effectiveness of the proposed technical solution has been designed and manufactured. Theoretical and experimental studies allowed us to determine the conditions necessary for uniform chemical treatment of seeds and reduce the impact of centrifugal-type working bodies on seeds when treated with chemical or biological preparations before sowing.

Article
The structural and dynamical properties of the binary mixture of Menthol (MEN) and Fatty acids (FAs) were investigated using molecular dynamics simulations. To this end, the relationship between the structural and dynamical properties of the eutectic mixtures of MEN and FAs with different molar percentages of FAs are studied. Structural properties of the eutectic mixtures were characterized by calculating the combined distribution functions (CDFs), radial distribution functions (RDFs), angular distribution functions (ADFs), hydrogen bonding networks, and spatial distribution functions (SDF). Additionally, our Results indicated robust interactions between menthol and Caprylic acid molecules Finally, the transport properties of the mixtures were investigated using the mean square displacement (MSD) of the centers of mass of the species, self-diffusion coefficients and vector reorientation dynamics (VRD) of bonds. Overall, our simulation results indicated that intermolecular interactions have a significant effect on the dynamic properties of species.

Article
Targeted drug delivery is one such precision method of delivering medication inside the human body which can vanquish all the limitations of the conventional chemotherapeutic techniques. In the present study, two types of nanoparticles (NPs) were chosen for the in-vitro pH-responsive release study of the drug, Imatinib, namely anatase Titanium Dioxide nanoparticles (TiO 2 NPs) and iron-capped TiO 2 NPs, designated as Fe@TiO 2 NPs. The novelty of this work lies behind the use of commercially available iron supplement ‘Autrin’ meant for human consumption, as the material to coat the TiO 2 NPs to synthesize Fe@TiO 2 NPs. The synthesized NPs were analyzed by XRD, HR‐TEM, SAED, EDX and VSM. UV–Vis spectroscopy was performed for absorption studies. Fe@TiO 2 NPs showed superparamagnetic behavior and thus they are able to ensure the facile transfer of Imatinib via external magnetic fields. The results obtained from in-vitro drug release studies depicted that both TiO 2 NPs and Fe@TiO 2 NPs showed a controlled pH-sensitive delivery of the loaded Imatinib molecules. Moreover, both types of NPs do not result in the formation of ROS under human physiological conditions. These results can lay the foundation to the development of efficacious targeted drug delivery systems in the healthcare sector.

Article
In 1965 Duwez et al. reported having generated an amorphous, stable phase of palladium-silicon in the region 15 to 23 atomic percent, at.%, silicon. These pioneering efforts have led to the development of solid materials that are now known as Bulk Metallic Glasses, BMG. In 2019 Rodríguez et al. discovered, computationally, that bulk amorphous Pd becomes magnetic, and so does porous/amorphous Pd. Puzzled by these results, the study of several solid binary systems in the Pd-rich zone was undertaken; in particular, the study of the glassy metallic alloy a -Pd $$_{100-c}$$ 100 - c Si $$_{c}$$ c , for $$0 \le c \le 22$$ 0 ≤ c ≤ 22 , ( c in at.%) to see what their topology is, what their electronic properties are and to inquire about their magnetism. In this work it is shown that this metallic glass is in fact magnetic in the region $$0 \le c < 15$$ 0 ≤ c < 15 . Collaterally $$\alpha$$ α and $$\beta$$ β magnetization curves are shown where the net magnetic moment is presented. The topology and the position of the first few peaks of the pair distribution functions, which agrees well with experiment, are also discussed. The BMGs produced experimentally so far are limited in size, but despite this limitation, recent industrial efforts have developed some useful devices that may revolutionize technology.

Article
Adoption of robotic-assisted surgery has steadily increased as it improves the surgeon’s dexterity and visualization. Despite these advantages, the success of a robotic procedure is highly dependent on the availability of a proficient surgical assistant that can collaborate with the surgeon. With the introduction of novel medical devices, the surgeon has taken over some of the surgical assistant’s tasks to increase their independence. This, however, has also resulted in surgeons experiencing higher levels of cognitive demands that can lead to reduced performance. In this work, we proposed a neurotechnology-based semi-autonomous assistant to release the main surgeon of the additional cognitive demands of a critical support task: blood suction. To create a more synergistic collaboration between the surgeon and the robotic assistant, a real-time cognitive workload assessment system based on EEG signals and eye-tracking was introduced. A computational experiment demonstrates that cognitive workload can be effectively detected with an 80% accuracy. Then, we show how the surgical performance can be improved by using the neurotechnological autonomous assistant as a close feedback loop to prevent states of high cognitive demands. Our findings highlight the potential of utilizing real-time cognitive workload assessments to improve the collaboration between an autonomous algorithm and the surgeon.

Article
Since it emerged in December of 2019, COVID-19 has placed a huge burden on medical care in countries throughout the world, as it led to a huge number of hospitalizations and mortalities. Many medical centers were overloaded, as their intensive care units and auxiliary protection resources proved insufficient, which made the effective allocation of medical resources an urgent matter. This study describes learned survival prediction models that could help medical professionals make effective decisions regarding patient triage and resource allocation. We created multiple data subsets from a publicly available COVID-19 epidemiological dataset to evaluate the effectiveness of various combinations of covariates—age, sex, geographic location, and chronic disease status—in learning survival models (here, “Individual Survival Distributions”; ISDs) for hospital discharge and also for death events. We then supplemented our datasets with demographic and economic information to obtain potentially more accurate survival models. Our extensive experiments compared several ISD models, using various measures. These results show that the “gradient boosting Cox machine” algorithm outperformed the competing techniques, in terms of these performance evaluation metrics, for predicting both an individual’s likelihood of hospital discharge and COVID-19 mortality. Our curated datasets and code base are available at our Github repository for reproducing the results reported in this paper and for supporting future research.

Article
Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI. Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Article
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacein with several reported protective/antiproliferative properties may control highly neurotoxic astrocytes (AbAs) obtained from spinal cord cultures of symptomatic hSOD1G93A rats, and if it could be neuroprotective in this ALS experimental model. At concentrations lower than those reported as protective, violacein selectively killed aberrant astrocytes. Treatment of hSOD1G93A rats with doses equivalent to the concentrations that killed AbAs caused a marginally significant delay in survival, partially preserved the body weight and soleus muscle mass and improved the integrity of the neuromuscular junction. Reduced motor neuron death and glial reactivity was also found and likely related to decreased inflammation and matrix metalloproteinase-2 and -9. Thus, in spite that new experimental designs aimed at extending the lifespan of hSOD1G93A rats are needed, improvements observed upon violacein treatment suggest a significant therapeutic potential that deserves further studies.

Article
The effectiveness of containment measures has been shown to depend on both epidemiological and sociological mechanisms, most notably compliance with national lockdown rules. Yet, there has been growing discontent with social distancing rules during national lockdowns across several countries, particularly among certain demographic and socio-economic groups. Using a highly granular dataset on compliance of over 105,000 individuals between March and May 2020 in the United Kingdom (UK), we find that compliance with lockdown policies was initially high in the overall population during the earlier phase of the pandemic, but that compliance fell substantially over time, especially among specific segments of society. Warmer temperatures increased the non-compliance of individuals who are male, divorced, part-time employed, and/or parent of more than two children. Thus, while epidemiologically the virus spread was naturally more limited during the warmer period of 2020, sociologically the higher temperature led to lower individual-level compliance with public health measures. As long as new strains emerge, governments may therefore be required to complement vaccination campaigns with targeted and time limited restrictions. Since non-complying individuals at the beginning of the pandemic share certain characteristics with vaccination sceptics, understanding their compliance behaviour will remain essential for future policymaking.

Article
We investigated the physiological changes during the fattening period and production characteristics in Japanese Black steers bred and raised using the typical feeding system in Japan. Here, 21 Japanese Black steers aged 12 months were used, with experimental period divided into early (12–14 months of age), middle (15–22 months), and late fattening phases (23–30 months). The liver transcriptome, blood metabolites, hormones, and rumen fermentation characteristics were analyzed. Blood triglyceride and non-esterified fatty acid concentrations increased, whereas blood ketone levels decreased, with fattening phases. Blood insulin increased with fattening phases and was positively correlated with carcass weight and marbling in late fattening phases. Rumen fermentation characteristics showed high propionate levels and low butyrate levels in late fattening phases, likely due to increased energy intake. Genes related to glucose metabolism, such as SESN3, INSR, LEPR, and FOXO3 , were down-regulated in late fattening phases. Genes related to lipid metabolism, such as FABP4, were up-regulated, whereas FADS1 and FADS2 were down-regulated. These findings suggest that the physiological changes resulted from changes in the energy content and composition of diets. Liver metabolism changed with changes in fat metabolism. Insulin was strongly associated with physiological changes and productivity in Japanese Black cattle.

Article
Sarcopenia is thought to be related to the microbiome, but not enough reports in chronic liver disease (CLD) patients. In addition to the differences in microbiome, the role of the microbiome in the gut is also important to be clarified because it has recently been shown that the microbiome may produce branched-chain amino acids (BCAAs) in the body. In this single-center study, sixty-nine CLD patients were divided by skeletal muscle mass index (SMI) into low (L-SMI: n = 25) and normal (N-SMI: n = 44). Microbiome was analyzed from stool samples based on V3-4 region of bacterial 16S rRNA). L-SMI had a lower Firmicutes/Bacteroidetes ratio than N-SMI. At the genus level, Coprobacillus , Catenibacterium and Clostridium were also lower while the Bacteroides was higher. Predictive functional profiling of the L-SMI group showed that genes related to nitrogen metabolism were enriched, but those related to amino acid metabolism, including BCAA biosynthesis, were lower. The genes related to 'LPS biosynthesis' was also higher. The microbiome of CLD patients with low muscle mass is characterized not only by high relative abundance of gram-negative bacteria with LPS, but also by the possibility of low potential for amino acid synthesis including BCAAs.

Article
Lung cancer is one of the most common malignancies in the United States, and the common metastatic sites in advanced non-small cell lung cancer (NSCLC) are bone, brain, adrenal gland, and liver, respectively, among which patients with liver metastases have the worst prognosis. We retrospectively analyzed 1963 patients diagnosed with NSCLC combined with liver metastases between 2010 and 2015. Independent prognostic factors for patients with liver metastases from NSCLC were identified by univariate and multivariate Cox regression analysis. Based on this, we developed a nomogram model via R software and evaluated the performance and clinical utility of the model by calibration curve, receiver operating characteristic curves, and decision curve analysis (DCA). The independent prognostic factors for NSCLC patients with liver metastases included age, race, gender, grade, T stage, N stage, brain metastases, bone metastases, surgery, chemotherapy, and tumor size. The area under the curve predicting OS at 6, 9, and 12 months was 0.793, 0.787, and 0.784 in the training cohort, and 0.767, 0.771, and 0.773 in the validation cohort, respectively. Calibration curves of the nomogram showed high agreement between the outcomes predicted by the nomogram and the actual observed outcomes, and the DCA further demonstrated the value of the clinical application of the nomogram. By analyzing the Surveillance, Epidemiology, and End Results database, we established and verified a prognostic nomogram for NSCLC patients with liver metastases, to personalize the prognosis of patients. At the same time, the prognostic nomogram has a satisfactory accuracy and the results are a guide for the development of patient treatment plans.

Article
In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group. We investigated the influence of age on the safety analysis, including the incidence of chemotherapeutic adverse events and the efficacy analysis, including OS. There were no remarkable differences in OS between the elderly ( n = 60) and the non-elderly groups ( n = 294). In the elderly group, median OS was 12.7 and 17.7 months for those who received GC ( n = 20) and GS ( n = 40), respectively. The prevalence of all-grade adverse events was similar between the elderly and the non-elderly groups. However, among the elderly group, Grade ≥ 3 hematological adverse events were more frequently observed in the GC arm than in the GS arm. The clinical outcomes of combination chemotherapy in elderly patients with advanced BTC were comparable to non-elderly patients. GS may be the more favorable treatment for elderly patients with advanced BTC.

Article
Obesity is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, ‘obesity paradox’ is observed in patients with coronary artery disease while defining obesity by body mass index (BMI). The purpose of this study is to identify a better anthropometric parameter to predict cardiovascular events in patients with ASCVD. The study was conducted using the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. A total of 6,920 adult patients with stable ASCVD, enrolled from January 2010 to November 2014, were included, with a mean age of 65.9 years, 73.9% males, and a mean BMI of 26.3 kg/m ² at baseline. These patients were followed up for a median of 2.5 years. The study endpoint was the composite major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Multivariable Cox proportional hazards regression showed a significant positive association between waist-to-BMI ratio and MACE (adjusted hazard ratio 1.69 per cm‧m ² /kg increase in waist-to-BMI ratio, 95% CI 1.12–2.49, p = 0.01) after adjusting for potential risk factors and confounders. Traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, or newer waist-based indices, such as body roundness index and a body shape index, did not show any significant linear associations ( p = 0.09, 0.30, 0.89, 0.54, 0.79 and 0.06, respectively). In the restricted cubic spline regression analysis, the positive dose–response association between waist-to-BMI ratio and MACE persisted across all the range of waist-to-BMI ratio. The positive dose–response association was non-linear with a much steeper increase in the risk of MACE for waist-to-BMI ratio > 3.6 cm‧m ² /kg. In conclusion, waist-to-BMI ratio may function as a positive predictor for the risk of MACE in established ASCVD patients.

Article
Abstract Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 ± 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies.

Article
This prospective multicenter study, established by the Japanese Ministry of Health, Labour and Welfare and involving 27 institutions, aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL), in order to address the controversy surrounding the role of instrumented fusion in cases of posterior surgical decompression for OPLL. 478 patients were considered for participation in the study; from among them, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, there were no significant differences among the participants in terms of patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments. The overall risk of perioperative complications was found to be lower with LM (odds ratio [OR] 0.40, p = 0.006), and the rate of C5 palsy occurrence was significantly lower with LM (OR 0.11, p = 0.0002) than with PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p < 0.0001) in patients who had PF was significantly smaller than in those who had LM. However, multivariable logistic regression analysis showed no significant difference among the participants in JOA score, JOA recovery rate, or JOACMEQ improvement at two years. In contrast, OPLL progression was greater in the LM group than in the PF group (OR 2.73, p = 0.0002). Both LM and PF for cervical myelopathy due to OPLL had resulted in comparable postoperative outcomes at 2 years after surgery.

Top-cited authors
• University of Massachusetts Medical School
• Kobe University
• Shimane University
• Kobe University