Temple University

Ultrathin superconducting MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> films are desirable for device applications and for exploration of new quantum phenomena in reduced dimensions. We have reported recently that smooth ultrathin MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> films can be grown on carbon-terminated SiC substrates using Hybrid Physical-Chemical Vapor Deposition (HPCVD). In this work, we present a thickness dependence study of HPCVD-grown ultrathin MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> films on C-terminated SiC with a focus on the thinnest superconducting films. The thickness of a nominally 2 nm thick MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film, controlled by deposition time based on thickness calibration data from thicker films, was confirmed by cross-sectional imaging via scanning transmission electron microscopy. We obtained a superconducting transition temperature T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> = 27.2 K, a self-field critical current density J <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> (3K, 0T) = 2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , and a normal-state sheet resistance near the transition R_s = 44.5 Ω/sq in a 2 nm thick MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film while its root-mean-square roughness was 0.62 nm. These characteristics make the HPCVD-grown ultrathin MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> films highly attractive for superconducting electronic applications.

Ultrathin superconducting films with high transition temperature and high critical magnetic field are desirable for many potential applications, such as single photon detector and hybrid superconductor-topological material structure for quantum computing. MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> is one of the highest T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> s -wave superconductors and therefore is very promising for these applications. In this work, we studied the superconducting transition of ultrathin MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film with film thickness in the nanometer scale. The T c of the nominal 3 nm- thick film is above 30 K. The upper critical field exhibits a good agreement with the phenomenological Ginzburg-Landau expression for a 2D superconducting film, i.e. , $B^{\bot}_{c2} \,\alpha \, 1 - T/T_{c}$ for an out-of-plane magnetic field and $B^{\Vert}_{c2} \, \alpha \, (1- T/T_{c})^{0.5}$ for an in-plane magnetic field. The extrapolation of upper critical field yields $B^{\bot}_{c2} (0\rm{K})=7.5\,T$ and $B^{\Vert}_{c2} (0\rm{K})=70\,T$ in a 3 nm- thick film. The large anisotropy indicates that the superconductivity of ultrathin MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> film is strongly 2D in nature. The angular dependence of the upper critical field $B_{c2}(\theta)$ shows a sharp cusp feature when the magnetic field is parallel to the film. The 2D Tinkham model could describe the trend of angular dependent upper critical field, which once again indicates the 2D superconducting nature of the MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> films.

Review usefulness represents a vital indicator for evaluating the quality of online reviews in the tourism industry, and various heuristic cues have been recognized as determinants of this indicator. This study constructs a comprehensive conceptual framework based on the heuristic-systematic model to observe how two systematic cues, namely, review novelty and inconsistency, shape the perceived usefulness of reviews. Through an empirical analysis based on 1,744,693 reviews of 62,543 restaurants in the United States, we unveil a positive effect of review novelty on review usefulness but a negative effect of review inconsistency. We also underscore the moderating effects of several heuristic cues in the model, including review valence, reviewer expertise, and restaurant popularity. These results indicate that systematic and heuristic cues simultaneously and interactively determine review usefulness. The findings present theoretical implications to the literature and practical implications to hospitality professionals and designers/managers of review platforms.

Smart biomaterials can sense and react to physiological or external environmental stimuli (e.g., mechanical, chemical, electrical, or magnetic signals). The last decades have seen exponential growth in the use and development of smart dental biomaterials for antimicrobial applications in dentistry. These biomaterial systems offer improved efficacy and controllable bio-functionalities to prevent infections and extend the longevity of dental devices. This review article presents the current state-of-the-art of design, evaluation, advantages, and limitations of bioactive and stimuli-responsive and autonomous dental materials for antimicrobial applications. First, the importance and classification of smart biomaterials are discussed. Second, the categories of bioresponsive antibacterial dental materials are systematically itemized based on different stimuli, including pH, enzymes, light, magnetic field, and vibrations. For each category, their antimicrobial mechanism, applications, and examples are discussed. Finally, we examined the limitations and obstacles required to develop clinically relevant applications of these appealing technologies.

Spinal muscular atrophy (SMA) is a neuromuscular disease that affects as many as 1 in 6000 individuals at birth, making it the leading genetic cause of infant mortality. A growing number of studies indicate that SMA is a multi-system disease. The cerebellum has received little attention even though it plays an important role in motor function and widespread pathology has been reported in the cerebella of SMA patients. In this study, we assessed SMA pathology in the cerebellum using structural and diffusion magnetic resonance imaging, immunohistochemistry, and electrophysiology with the SMNΔ7 mouse model. We found a significant disproportionate loss in cerebellar volume , decrease in afferent cerebellar tracts, selective lobule-specific degeneration of Purkinje cells, abnormal lobule foliation and astrocyte integrity, and a decrease in spontaneous firing of cerebellar output neurons in the SMA mice compared to controls. Our data suggest that defects in cerebellar structure and function due to decreased survival motor neuron (SMN) levels impair the functional cerebellar output affecting motor control, and that cerebellar pathology should be addressed to achieve comprehensive treatment and therapy for SMA patients.

Purpose Genomic alterations of BRAF and NRAS are oncogenic drivers in malignant melanoma and other solid tumors. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan‑RAF inhibitor. This first-in-human phase 1 study explored the safety and antitumor activity of tovorafenib. Methods This two-part study in adult patients with relapsed or refractory advanced solid tumors included a dose escalation phase and a dose expansion phase including molecularly defined cohorts of patients with melanoma. Primary objectives were to evaluate the safety of tovorafenib administered once every other day (Q2D) or once weekly (QW), and to determine the maximum-tolerated and recommended phase 2 dose (RP2D) on these schedules. Secondary objectives included evaluation of antitumor activity and tovorafenib pharmacokinetics. Results Tovorafenib was administered to 149 patients (Q2D n = 110, QW n = 39). The RP2D of tovorafenib was defined as 200 mg Q2D or 600 mg QW. In the dose expansion phase, 58 (73%) of 80 patients in Q2D cohorts and 9 (47%) of 19 in the QW cohort had grade ≥ 3 adverse events. The most common of these overall were anemia (14 patients, 14%) and maculo-papular rash (8 patients, 8%). Responses were seen in 10 (15%) of 68 evaluable patients in the Q2D expansion phase, including in 8 of 16 (50%) patients with BRAF mutation-positive melanoma naïve to RAF and MEK inhibitors. In the QW dose expansion phase, there were no responses in 17 evaluable patients with NRAS mutation-positive melanoma naïve to RAF and MEK inhibitors; 9 patients (53%) had a best response of stable disease. QW dose administration was associated with minimal accumulation of tovorafenib in systemic circulation in the dose range of 400–800 mg. Conclusions The safety profile of both schedules was acceptable, with QW dosing at the RP2D of 600 mg QW preferred for future clinical studies. Antitumor activity of tovorafenib in BRAF-mutated melanoma was promising and justifies continued clinical development across multiple settings. ClinicalTrials.gov identifier NCT01425008.

Comparing the evolution of distantly related viruses can provide insights into common adaptive processes related to shared ecological niches. Phylogenetic approaches, coupled with other molecular evolution tools, can help identify mutations informative on adaptation, whilst the structural contextualization of these to functional sites of proteins may help gain insight into their biological properties. Two zoonotic betacoronaviruses capable of sustained human-to-human transmission have caused pandemics in recent times (SARS-CoV-1 and SARS-CoV-2), whilst a third virus (MERS-CoV) is responsible for sporadic outbreaks linked to animal infections. Moreover, two other betacoronaviruses have circulated endemically in humans for decades (HKU1 and OC43). To search for evidence of adaptive convergence between established and emerging betacoronaviruses capable of sustained human-to-human transmission (HKU1, OC43, SARS-CoV-1 and SARS-CoV-2), we developed a methodological pipeline to classify shared non-synonymous mutations as putatively denoting homoplasy (repeated mutations that do not share direct common ancestry) or stepwise evolution (sequential mutations leading towards a novel genotype). In parallel, we look for evidence of positive selection, and draw upon protein structure data to identify potential biological implications. We find 30 candidate mutations, from which four [codon sites 18121 (nsp14/residue 28), 21623 (spike/21), 21635 (spike/25) and 23948 (spike/796); SARS-CoV-2 genome numbering] further display evolution under positive selection and proximity to functional protein regions. Our findings shed light on potential mechanisms underlying betacoronavirus adaptation to the human host and pinpoint common mutational pathways that may occur during establishment of human endemicity.

Background Revisional bariatric surgeries are increasing for weight recurrence and return of co-morbidities. Herein, we compare weight loss and clinical outcomes following primary Roux-en-Y Gastric Bypass (P-RYGB), adjustable gastric banding to RYGB (B-RYGB), and sleeve gastrectomy to RYGB (S-RYGB) to determine if primary versus secondary RYGB offer comparable benefits. Methods Participating institutions’ EMRs and MBSAQIP databases were used to identify adult patients who underwent P-/B-/S-RYGB from 2013 to 2019 with a minimum one-year follow-up. Weight loss and clinical outcomes were assessed at 30 days, 1 year, and 5 years. Our multivariable model controlled for year, institution, patient and procedure characteristics, and excess body weight (EBW). Results 768 patients underwent RYGB: P-RYGB n = 581 [75.7%]; B-RYGB n = 106 [13.7%]; S-RYGB n = 81 [10.5%]. The number of secondary RYGB procedures increased in recent years. The most common indications for B-RYGB and S-RYGB were weight recurrence/nonresponse (59.8%) and GERD (65.4%), respectively. Mean time from index operation to B-RYGB or S-RYGB was 8.9 and 3.9 years, respectively. After adjusting for EBW, 1 year %TWL (total weight loss) and %EWL (excess weight loss) were greater after P-RYGB (30.4%, 56.7%) versus B-RYGB (26.2%, 49.4%) or S-RYGB (15.6%, 37%). Overall comorbidity resolution was comparable. Secondary RYGB patients had a longer adjusted mean length of stay (OR 1.17, p = 0.071) and a higher risk of pre-discharge complications or 30-day reoperation. Conclusion Primary RYGB offers superior short-term weight loss outcomes compared to secondary RYGB, with decreased risk of 30-day reoperation.

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Objective: To evaluate rates of superimposed preeclampsia in pregnant individuals with echocardiography-diagnosed cardiac geometric changes in the setting of chronic hypertension. Study design: This was a retrospective study of pregnant individuals with chronic hypertension who delivered singleton pregnancies at 20 weeks' gestation or greater at a tertiary care center. Analyses were limited to individuals who had an echocardiogram during any trimester. Cardiac changes were categorized as normal morphology, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy according to the American Society of Echocardiography guidelines. Our primary outcome was early-onset superimposed preeclampsia defined as delivery at less than 34 weeks' gestation. Other secondary outcomes were also examined. Adjusted odds ratios (aOR) with 95% confidence intervals (95%CI) were calculated, controlling for pre-specified covariates. Results: Of the 168 individuals who delivered from 2010 to 2020, 57 (33.9%) had normal morphology, 54 (32.1%) had concentric remodeling, 9 (5.4%) had eccentric hypertrophy, and 48 (28.6%) had concentric hypertrophy. Non-Hispanic black individuals presented over 76% of the cohort. Rates of the primary outcome in individuals with normal morphology, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were 15.8%, 37.0%, 22.2%, and 41.7%, respectively (P =0.01). Compared to individuals with normal morphology, individuals with concentric remodeling were more likely to have the primary outcome (aOR 3.28; 95%CI 1.28-8.39), fetal growth restriction (crude OR 2.98; 95%CI 1.05-8.43), and iatrogenic preterm delivery <34 weeks' gestation (aOR 2.72; 95%CI 1.15-6.40). Compared to individuals with normal morphology, individuals with concentric hypertrophy were more likely to have the primary outcome (aOR 4.16; 95%CI 1.57-10.97), superimposed preeclampsia with severe features at any gestational age (aOR 4.75; 95%CI 1.94-11.62), iatrogenic preterm delivery < 34 weeks' gestation (aOR 3.60; 95%CI 1.47-8.81), and neonatal intensive care unit admission (aOR 4.82; 95%CI 1.90-12.21). Conclusion: Concentric remodeling and concentric hypertrophy were associated with increased odds of early-onset superimposed preeclampsia.

Importance Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown. Objective To determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality. Design, Setting, and Participants Observational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022. Exposures Mucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments. Main Outcomes and Measures The primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease. Results Among the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively. Conclusions and Relevance In participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.

Objective Risk factors of early- and late-onset preeclampsia among pregnant individuals with chronic hypertension are not well described in the literature. We hypothesized that early- and late-onset superimposed preeclampsia (SIPE) have different risk factors. Therefore, we aimed to examine the risk factors of early- and late-onset SIPE among individuals with chronic hypertension. Study Design This was a retrospective case-control study of pregnant individuals with chronic hypertension who delivered at 22 weeks’ gestation or greater at an academic institution. Early-onset SIPE was defined as SIPE diagnosed before 34 weeks’ gestation. To identify risk factors, we first compared individuals' characteristics between individuals who developed early- and late-onset SIPE and those who did not. We then compared characteristics between individuals who developed early-onset SIPE and late-onset SIPE. Characteristics with p-values of less than 0.05 by bivariable variables were analyzed by simple and multivariable logistic regression models to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Missing values were imputed with multiple imputation. Results Of 839 individuals, 156 (18.6%) had early-onset, 154 (18.4%) had late-onset SIPE, and 529 (63.1%) did not have SIPE. The multivariate logistic regression model showed serum creatinine ≥ 0.7 mg/dL compared to less than 0.7 mg/dL (aOR: 2.89 [95% CI: 1.63-5.13]), increase of creatinine (1.33 [1.16-1.53]), nulliparity compared to multiparity (1.77 [1.21-2.60]), and pregestational diabetes (1.70 [1.11-2.62]) were risk factors for early-onset SIPE. The multivariate logistic regression model showed nulliparity compared to multiparity (1.53 [1.05-2.22]) and pregestational diabetes (1.74 [1.14-2.64]) was a risk factor for late-onset SIPE. Serum creatinine ≥ 0.7 mg/dL (2.90 [1.36-6.15]) and increase of creatinine (1.33 [1.10-1.60]) were significantly associated with early-onset SIPE compared to late-onset SIPE. Conclusion Kidney dysfunction seemed to be associated with the pathophysiology of early-onset SIPE. Nulliparity and PDM were common risk factors for both early- and late-onset SIPE.

There is a dearth of research on incarceration among young Black sexual minority men (SMM). The current study aimed to assess the prevalence and association between unmet socioeconomic and structural needs and history of incarceration among young Black SMM. Between 2009 and 2015, young Black SMM (N = 1,774) in Dallas and Houston Texas were recruited to participate in an annual, venue-based, cross-sectional survey. We found that 26% of the sample reported any lifetime history of incarceration. Additionally, participants with unmet socioeconomic and structural needs (unemployment, homelessness, financial insecurity and limited educational attainment) were more likely to have a history of incarceration. It is imperative that interventions are developed to address the basic, social, and economic needs of young Black SMM with a history of incarceration or who are at risk for incarceration.

Background Mammalian gonadal sex is determined by the presence or absence of a Y chromosome and the subsequent production of sex hormones contributes to secondary sexual differentiation. However, sex chromosome-linked genes encoding dosage-sensitive transcription and epigenetic factors are expressed well before gonad formation and have the potential to establish sex-biased expression that persists beyond the appearance of gonadal hormones. Here, we apply a comparative bioinformatics analysis on a pair of published single-cell datasets from mouse and human during very early embryogenesis—from two-cell to pre-implantation stages—to characterize sex-specific signals and to assess the degree of conservation among early acting sex-specific genes and pathways. Results Clustering and regression analyses of gene expression across samples reveal that sex initially plays a significant role in overall gene expression patterns at the earliest stages of embryogenesis which potentially may be the byproduct of signals from male and female gametes during fertilization. Although these transcriptional sex effects rapidly diminish, sex-biased genes appear to form sex-specific protein–protein interaction networks across pre-implantation stages in both mammals providing evidence that sex-biased expression of epigenetic enzymes may establish sex-specific patterns that persist beyond pre-implantation. Non-negative matrix factorization (NMF) on male and female transcriptomes generated clusters of genes with similar expression patterns across sex and developmental stages, including post-fertilization, epigenetic, and pre-implantation ontologies conserved between mouse and human. While the fraction of sex-differentially expressed genes (sexDEGs) in early embryonic stages is similar and functional ontologies are conserved, the genes involved are generally different in mouse and human. Conclusions This comparative study uncovers much earlier than expected sex-specific signals in mouse and human embryos that pre-date hormonal signaling from the gonads. These early signals are diverged with respect to orthologs yet conserved in terms of function with important implications in the use of genetic models for sex-specific disease.