University of San Simón

The benefit of treatment with tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR-TKI) for lung adenocarcinoma (ADC), stratified by ethnicity, has not yet been fully elucidated. We searched PubMed, Embase, and Cochrane databases for studies that investigated EGFR-TKI for lung ADC. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. A total of 18 studies, comprising 4,497 patients with lung ADC randomized to TKIs or chemotherapy alone. TKIs significantly improved OS (HR 0.91; 95% CI 0.88–0.95), PFS (HR 0.60; 95% CI 0.38–0.97), and ORR (HR 0.34; 95% CI 0.25–0.48) in Asian patients, compared with the chemotherapy alone. In Caucasian patients, TKIs significantly improved PFS compared with chemotherapy alone (HR 0.34; 95% CI 0.25–0.48) and ORR(RR 2.35; 95% CI: 1.05–5.28). TKIs significantly reduced any adverse events of any grade in patients with mixed ethnicity (RR 0.86; 95% CI 0.76–0.98) and any adverse events of grade ≥ 3 in Caucasian patients (RR 0.67; 95% CI 0.51–0.89). This is the first meta-analysis to reveal the ethnic influence on the outcomes of oncologic treatments for patients with lung ADC. In collaboration with in-depth molecular characterization, these data will allow the creation of a clinical–pathological predictive model to increase the magnitude of the expected benefit for patients from different ethnic groups.

The introduction of non-native fish species into new environments has raised global concerns due to potential ecological impacts on recipient ecosystems. A previous study focusing on the introduced fish species Arapaima gigas in Bolivian Amazon waters showed that its isotopic niche significantly overlapped with most co-occurring native fish species, suggesting potential competition. To evaluate this hypothesis, we extended here the investigation by comparing the trophic position and isotopic niche width of eleven abundant native fish species inhabiting both colonized and non-colonized floodplain lakes. We found lower trophic positions in colonized versus non-colonized lakes only for native piscivores, mostly driven by a shift towards increased dietary proportion of detritivorous fishes. Conversely, results showed that the isotopic niche width of most fish species analyzed (i.e. 10 over 11 species) did not significantly decrease in colonized compared to non-colonized lakes. Our overall results suggest potentially low competitive interactions between A. gigas and native fishes, with the notable exception of piscivorous species. We attribute our findings to the high abundance of available resources in Amazon oxbow lakes.

Objective: This systematic review and meta-analysis aimed to determine the degree to which pancreaticobiliary maljunction (PBM) increases the risk of different types of biliary cancer (BC). Methods: A systematic review and meta-analysis were carried out using the following databases: PubMed, Embase, Cochrane Library, Scopus, Web of Science, and Science Direct. We systematically searched from inception to April 2024. The search terms included were derived from the keywords "Pancreaticobiliary Maljunction" OR "Anomalous Pancreaticobiliary Junction" AND "Cancer" OR "Malignancy". Studies that provided data comparing BC rates in relation to PBM presence or vice versa were included. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. The random-effects model was used. Results: Fifteen studies were included with a total sample of 8604 patients, of whom 5015 (58.29%) were female with a mean age of 54.58 years. Patients with PBM had 8.42 (95% CI = 3.57-19.87) more risk of developing any type of BC, with a higher risk of GBC than BDC (OR = 16.91 vs. OR = 3.36, p-value = 0.003). There was a higher risk of having PBM in patients with GBC than BDC only when considering the Asian population (OR = 3.12, 95% CI = 1.09-8.94). Meta-regression analysis revealed that neither mean age (p = 0.087) nor percentage of female patients in the study population (p = 0.197) were statistically associated with the variations in OR for the risk of BC based on the presence of PBM. Conclusions: There is a significant association between PBM and the risk of having BC, mainly GBC when compared to BDC. Most of the studies published reported data from Japanese patients, which limits the generalization of the results. The age of patients and sex were not significantly associated with the relation between PBM and BC. Further prospective studies in broader populations will provide additional details to take measures for screening and early management of PBM and BC.

Ectoine, an osmolyte produced by various microorganisms, has numerous commercial applications. Vreelandella boliviensis (formerly called Halomonas boliviensis) generates high ectoine concentrations, i.e., 78.6 g/L. This study investigated three cultivation strategies for ectoine production in a non-aseptic air-lift bioreactor. The first strategy was performed in a repeated-batch mode with 5% (w/v) NaCl to induce cell growth, followed by the addition of solid NaCl to a final concentration of 12.5% (w/v) to prompt ectoine production. A maximum dry cell weight of 13.8 g/L at 46.5 h, a maximum ectoine concentration of 1.37 g/L at 37.5 h, and a maximum volumetric productivity of 0.93 g/L/d at 34.5 h were reached. The second strategy employed a three-step repeated-batch cultivation method. In the first step, cells were grown at the optimum salt concentration, harvested by centrifugation, and cultivated in a replenished medium for the second step. In the third step, the cells were harvested again and grown in a fresh medium containing 12.5% (w/v) NaCl. This strategy improved dry cell weight to 32 g/L, ectoine concentration to 4.37 g/L, and productivity to 1.76 g/L/day at 60 h of cultivation. The third strategy consisted of continuous cultivations that were investigated using different NaCl concentrations. The highest ectoine concentration of 2.83 g/L and productivity of 3.49 g/L/d were obtained with 8.5% (w/v) NaCl at a dilution rate of 0.05 (1/h). This study is the first to report ectoine production by V. boliviensis in continuous air-lift bioreactors under non-aseptic conditions.

In the current study, I report a single-site mimicry complex involving 20 arthropods from 12 families in five orders resembling the small turtle ant Cephalotes pusillus. The complex is the most species-rich single-site complex with predominately Batesian mimics that has been reported so far. Considering that small turtle ants are likely less defended than highly noxious butterflies or aculeate Hymenoptera with potent stingers, possible factors explaining the high species richness of the complex may include high model abundance, small body size and easy to develop morphological resemblance.

Leaf and wood functional traits of trees are related to growth, reproduction, and survival, but the degree of phylogenetic conservatism in these relationships is largely unknown. In this study, we describe the variability of strategies involving leaf, wood and demographic characteristics for tree genera distributed across the Amazon Region, and quantify phylogenetic signal for the characteristics and their relationships. Leaf and wood traits are aligned with demographic variables along two main axes of variation. The first axis represents the coordination of leaf traits describing resource uptake and use, wood density, seed mass, and survival. The second axis represents the coordination between size and growth. Both axes show strong phylogenetic signal, suggesting a constrained evolution influenced by ancestral values, yet the second axis also has an additional, substantial portion of its variation that is driven by functional correlations unrelated to phylogeny, suggesting simultaneously higher evolutionary lability and coordination. Synthesis. Our results suggest that life history strategies of tropical trees are generally phylogenetically conserved, but that tree lineages may have some capability of responding to environmental changes by modulating their growth and size. Overall, we provide the largest‐scale synopsis of functional characteristics of Amazonian trees, showing substantial nuance in the evolutionary patterns of individual characteristics and their relationships. Read the free Plain Language Summary for this article on the Journal blog.

Background The 24-h urine protein (24-hUP) excretion is the gold standard for evaluating proteinuria. This study aimed to evaluate the diagnostic efficacy of protein/creatinine ratio (PCR) for estimating 24-hUP at various levels of renal function and proteinuria levels. Methods A cross-sectional study was conducted between December 2021 and December 2023 in Salvador, Bahia-Brazil, as an extension of previously published data from the TUNARI study. The study included 217 samples from 152 patients with various levels of renal function and proteinuria. PCR in isolated samples and 24-hUP were determined conventionally within a 24-h timeframe. Patients were classified into three groups according to the level of renal function (Group 1 = 10 to < 30 mL/min, Group 2 = 30–60 mL/min, and Group 3 = > 60 mL/min) and level of proteinuria (< 0.3 g/day, 0.3–3.5 g/day, and > 3.5 g/day). The data were analyzed using the Spearman correlation (rs), coefficient of determination (r²), Bland–Altman plots and receiver operating characteristic (ROC) curve. Likelihood ratios, positive (LR +), and negative (LR-) were derived from the sensitivity and specificity of PCR. Results Mean age was 41.5 ± 15.7 years, 61.8% were women, 36.8% Black and 52% Mixed-race. Glomerulopathies constituted 80.3%; 46.1% with lupus nephritis. Of the total urine samples, we observed a high correlation between PCR in the total sample of 24-hUP sample (rs = 0.86, p < 0.001) across different levels of renal function. However, agreement between PCR and 24-hUP was reduced at higher levels of proteinuria. The ROC analysis showed an AUC of 0.95 (95% CI = 0.92, 0.98), sensitivity of 91% and specificity of 86.5% (LR + 6.7; LR- 0.1), with an optimal cut-off of 0.77. These results were similar across renal function levels. Proteinuria ≤ 0.3 g/day showed a high sensitivity of 83.3% and specificity of 90%, with an area under (AUC) of 0.85 (95% CI = 0.71; 0.94). In the 24-hUP range > 0.3–3.5 g/day, the sensitivity was 64.1%, the specificity was 84.6%, and the AUC was 0.76 (95% CI = 0.67; 0.84), PCR detected all cases > 3.5 g/day. Conclusions PCR is a suitable measure to be used as an indicator of 24-hUP at different levels of renal function, but may have limitations at higher levels of proteinuria. Analysis of PCR by proteinuria level found that agreement as well as sensitivity decreases at higher levels, but it maintains good specificity and is able to identify nephrotic range proteinuria.

Background The International Society of Nephrology proposes an acute kidney disease (AKD) management strategy that includes a risk score to aid AKD identification in low- and low-middle-income countries (LLMICs). We investigated the performance of the risk score and determined kidney and patient outcomes from AKD at multiple LLMIC sites. Methods and findings Adult patients presenting to healthcare facilities in Bolivia, Brazil, South Africa, and Nepal were screened using a symptom-based risk score and clinical judgment. Those at AKD risk underwent serum creatinine testing, predominantly with a point-of-care (POC) device. Clinical data were collected prospectively between September 2018 and November 2020. We analyzed risk score performance and determined AKD outcomes at discharge and over follow-up of 90 days. A total of 4,311 patients were at increased risk of AKD, and 2,922 (67.8%) had AKD confirmed. AKD prevalence was 80.2% in patients enrolled based on the risk score and 32.5% when enrolled on clinical judgment alone (p < 0.0001). The area under the receiver operating characteristic curve was 0.73 for the risk score to detect AKD. Death during admission occurred in 84 (2.9%) patients with AKD and 3 (0.2%) patients without kidney disease (p < 0.0001). Death after discharge occurred in 206 (9.7%) AKD patients, and 1865 AKD patients underwent reassessment of kidney function after discharge; 902 (48.4%) patients had persistent kidney disease including 740 (39.7%) patients reclassified with de novo or previously undiagnosed chronic kidney disease (CKD). The study was pragmatically designed to assess outcomes as part of routine healthcare, and there was heterogeneity in clinical practice and outcomes between sites, in addition to selection bias during cohort identification. Conclusions The use of a risk score can aid AKD identification in LLMICs. High rates of persistent kidney disease and mortality after discharge highlight the importance of AKD follow-up in low-resource settings.

Hemobilia is a relatively uncommon but important cause of gastrointestinal bleeding. It occurs due to abnormal communications between the biliary system and surrounding vasculature, often caused by surgical interventions, trauma, infections, or malignancies. The rise of advanced hepato-pancreato-biliary techniques, including radiofrequency ablation and transjugular intrahepatic portosystemic shunt (TIPS) placement, necessitates careful evaluation for the potential presence of hemobilia during the post-procedural period of these patients. Hemobilia can be difficult to diagnose, as common symptoms like jaundice, abdominal pain, and gastrointestinal bleeding are not always present together. Imaging techniques such as Doppler ultrasound, contrast-enhanced computed tomography (CT), and angiography are critical for identifying the source of bleeding. Treatment typically focuses on achieving hemostasis and ensuring proper bile flow, with options including endoscopic techniques, angiography with transcatheter arterial embolization, and, in severe cases, surgical intervention. This review highlights recent advances in diagnostic and therapeutic approaches, emphasizing the need for early recognition and tailored interventions to improve patient outcomes.

Increasing climatic and human pressures are changing the world's water resources and hydrological processes at unprecedented rates. Understanding these changes requires comprehensive monitoring of water resources. Hydrogeodesy, the science that measures the Earth's solid and aquatic surfaces, gravity field, and their changes over time, delivers a range of novel monitoring tools that are complementary to traditional hydrological methods. It encompasses geodetic technologies such as Altimetry, Interferometric Synthetic Aperture Radar (InSAR), Gravimetry, and Global Navigation Satellite Systems (GNSS). Beyond quantifying these changes, there is a need to understand how hydrogeodesy can contribute to more ambitious goals dealing with water‐related and sustainability sciences. Addressing this need, we combine a meta‐analysis of over 3,000 articles to chart the range, trends, and applications of satellite‐based hydrogeodesy with an expert elicitation that systematically assesses the potential of hydrogeodesy. We find a growing body of literature relating to the advancements in hydrogeodetic methods, their accuracy and precision, and their inclusion in hydrological modeling, with a considerably smaller portion related to understanding hydrological processes, water management, and sustainability sciences. The meta‐analysis also shows that while lakes, groundwater and glaciers are commonly monitored by these technologies, wetlands or permafrost could benefit from a wider range of applications. In turn, the expert elicitation envisages the potential of hydrogeodesy to help solve the 23 Unsolved Questions of the International Association of Hydrological Sciences and advance knowledge as guidance toward a safe operating space for humanity. It also highlights how this potential can be maximized by combining hydrogeodetic technologies simultaneously, exploiting artificial intelligence, and accurately integrating other Earth science disciplines. Finally, we call for a coordinated way forward to include hydrogeodesy in tertiary education and broaden its application to water‐related and sustainability sciences in order to exploit its full potential.

Background: Robotic metabolic and bariatric surgery (RMBS) has emerged as an innovative approach in the treatment of severe obesity by combining the ergonomic precision of robotic technology and instrumentation with the established benefits of weight loss surgery. This study employs a bibliometric approach to identify local research trends and worldwide patterns in RMBS. Materials & Methods: The research methodology used “robotic” and “metabolic” or “bariatric surgery” to search Web of Science. Articles that were published prior to December 31st, 2023, were included. The analyses were developed using the Rayyan and Bibliometric, in R Studio. Results: 265 articles from 51 different journals were included. Scientific production of RMBS experienced a significant annual growth rate of 21.96% from 2003 to 2023, resulting in an average of 12.6 papers published per year. A high correlation (R2 = 0.94) was found between the year and number of articles. The mean number of citations per document was 13.25. Approximately 90% of the journals were classified as zone 3, according to the Bradford categorization. International collaboration was identified in 10.57% of cases, with the University of California and the University of Illinois being the most common organizations. The countries with the highest number of corresponding authors, in descending order, were the United States of America, China, and Switzerland. Conclusion: Scientific production in RMBS has experienced sustained growth since the first original publications in 2003. While it has not yet reached the volume, impact, and international collaboration seen in studies related to non-robotic metabolic and bariatric surgery, RBMS holds potential that remains to be explored. Graphical abstract

Background Patients with COVID-19 may experience a persistent increase in the blood urea nitrogen over creatinine ratio (PI-BUN/Cr). Its elevation could reflect multiple underlying pathophysiological processes beyond prerenal injury but also warrants nuanced interpretation due to its complex interplay with various factors, underscoring the importance of investigating its effects on mortality and acute kidney injury in this population. Methods We analized a retrospective and longitudinal cohort of patients admitted to a single center in Mexico City for patients with severe COVID-19. Between March 5, 2020 and August 25, 2021, we included patients with confirmed positive diagnosis for SARS-CoV-2, age > 18 years, disease severity was defined by clinical data of respiratory distress syndrome and a ratio of partial oxygen pressure to inspired oxygen fraction < 300 mmHg on admission. We excluded patients with End Stage Kidney Disease. Data was obtained from electronic medical records. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of measurements in the hospital. The outcomes included: risk factors to mortality and AKI in-hospital. Results The cohort included 3,007 patients with a median age of 54.6 ± 14.5 years. 35% of patients died; 44.6% developed PI-BUN/Cr ratio and 71.4% AKI. Mortality was associated with older age > 60 years [Hazard ratio (HR)] = 1.45, 95% CI: 1.28–1.65; p < 0.001); male (HR 1.25, 95% CI 1.09–1.44; p = 0.002) and AKI (HR 3.29, 95% CI 2.42–4.46; p < 0.001); PI-BUN/CR & Non-AKI (HR = 2.82, 95% CI: 1.61–4.93; p < 0.001); Non PI-BUN/CR & AKI (HR = 5.47, 95% CI: 3.54–8.44; p < 0.001); and PI-BUN/CR & AKI (HR = 4.26, 95% CI: 2.75–6.62, p < 0.001). Only hiperuricemia was a risk factor for AKI (HR = 1.71, 95% CI: 1.30–2.25, p < 0.001). Conclusions While PI-BUN/Cr alone may not directly associate with mortality, its capacity to sub-phenotype patients according to their AKI status holds significant promise in offering valuable insights into patient prognosis and outcomes. Understanding the nuanced relationship between PI-BUN/Cr and AKI enhances our comprehension of renal function dynamics. It equips healthcare providers with a refined tool for risk stratification and personalized patient management strategies.

Subjective well-being (SWB) is often described as being U-shaped over adulthood, declining to a midlife slump and then improving thereafter. Improved SWB in later adulthood has been considered a paradox given age-related declines in health and social losses. While SWB has mostly been studied in high-income countries, it remains largely unexplored in rural subsistence populations lacking formal institutions that reliably promote social welfare. Here, we evaluate the age profile of SWB among three small-scale subsistence societies ( n = 468; study 1), forest users from 23 low-income countries ( n = 6987; study 2), and Tsimane’ horticulturalists ( n = 1872; study 3). Across multiple specifications, we find variability in SWB age profiles. In some cases, we find no age-related differences in SWB or even inverted U-shapes. Adjusting for confounders reduces observed age effects. Our findings highlight variability in average well-being trajectories over the life course. Ensuring successful aging will require a greater focus on cultural and socioecological determinants of individual trajectories.

Background Colorectal cancer (CRC) represents the second leading cause of cancer-related mortality worldwide, with a significant portion of patients presenting with metastatic disease at diagnosis. Resistance to initial anti-EGFR therapy, a key treatment for RAS wild-type metastatic CRC, remains a major challenge. This study aimed to assess the efficacy and safety of rechallenge with anti-EGFR therapy in patients with metastatic CRC who have progressed after prior treatments. Methods A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus. Studies were included if they were randomized controlled trials (RCTs) or observational studies involving patients with EGFR-mutated metastatic CRC who received anti-EGFR therapy as a rechallenge. Endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events. Statistical analyses were performed using the DerSimonian/Laird random effect model, with heterogeneity assessed via I² statistics. R, version 4.2.3, was used for statistical analyses. Results Fourteen studies were included with 520 patients; 50.3% were male, and the median age was 63 years old. The median progression-free survival (mPFS) ranged between 2.4 and 4.9 months, while the median overall survival (mOS) ranged from 5 to 17.8 months. Our pooled analysis demonstrated an objective response rate (ORR) of 17.70% (95% CI, 8.58–26.82%) and a disease control rate (DCR) of 61.72% (95% CI, 53.32–70.11%), both with significant heterogeneity (I², 84% and 80%, respectively; p < 0.01). In the subgroup analysis, cetuximab showed an ORR of 18.31% (95% CI, 4.67–31.94%), and panitumumab an ORR of 10.9% (95% CI, 0.00–26.82%), while the combination of both resulted in an ORR of 29.24% (95% CI, 0.00–65.84%). For DCR, cetuximab resulted in 62.1% (95% CI, 49.32–74.87%), panitumumab in 63.05% (95% CI, 52.13–73.97%), and the combination in 60.34% (95% CI, 31.92–88.77%), all with significant heterogeneity. Adverse events included anemia (15.39%), diarrhea (4.20%), hypomagnesemia (6.40%), neutropenia (22.57%), and skin rash (13.22%). Conclusions Rechallenge with anti-EGFR therapy in metastatic CRC patients shows moderate efficacy with manageable safety profiles. These findings highlight the need for careful patient selection and monitoring to optimize outcomes. Further studies are warranted to refine strategies for maximizing the therapeutic benefits of anti-EGFR rechallenge. Graphical Abstract

This study aimed at evaluating the effects of non‐fermented and fermented pseudocereal flours, quinoa and canihua, on iron and zinc bioavailability in Wistar rats. Two diets prepared with 92% fermented quinoa or 79.5% fermented canihua were compared with diets prepared with the same amount of non‐fermented pseudocereals. Other two quinoa diets were prepared with 60% non‐fermented or fermented quinoa and compared with a refence diet which was free of phytates. Body weight, feed efficiency ratio, and the absorption, retention and bioavailability of iron and zinc were evaluated. While body weight and feed efficiency ratio were higher (p < 0.05) in animals after non‐fermented diets, the results of mineral absorption and bioavailability were consistently higher in the diets containing fermented pseudocereals. Iron concentration in the livers of animals after the fermented quinoa (92%) and canihua diet (79.5%), were 34% and 30% higher than after the diets with non‐fermented pseudocereals. Zinc bioavailability, indicated by zinc in femur of animals fed the 60% fermented quinoa diet was 53.2 μg g⁻¹ ZnInt g⁻¹ BW, comparable to that in animals fed a reference diet with no phytates (58.2 μg g⁻¹ ZnInt g⁻¹ BW), and significantly higher (p < 0.05) than in animals fed the non‐fermented quinoa diet (34.5 μg g⁻¹ ZnInt g⁻¹ BW). Zinc bioavailability was mainly influenced by phytate content in the diet (R² = 0.665 and p = 0.000). The retention of iron in the liver (2220 μg g⁻¹ FeInt g⁻¹ BW) was higher in the diet containing 60% of fermented quinoa than in the non‐fermented diet (1429 μg g⁻¹ ZnInt g⁻¹ BW). Differences in iron absorption were mainly impacted by iron content in the diets (R² = 0.828 and p = 0.000). In conclusion, the addition of fermented pseudocereals to diets increased the bioavailability of iron and zinc in Wistar rats. These findings will encourage further research into fermented pseudocereals and their potential health effects.