bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia–reperfusion injury
Authors: Archontakis‐Barakakis Paraschos , Mavridis Theodoros , Chlorogiannis David‐Dimitris , Barakakis Georgios , Laou Eleni , Sessler Daniel I. , Gkiokas George , Chalkias Athanasios
Published: December 2024

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia–reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised when ischaemia leads to a >50% decline in intestinal oxygen consumption. Restoration of perfusion and oxygenation provokes additional injury, resulting in mucosal damage and disruption of intestinal barrier function. The primary cellular mechanism for sensing hypoxia and for activating a cascade of cellular responses to mitigate the injury is a family of heterodimer proteins called hypoxia‐inducible factors (HIFs). The HIF system is connected to numerous biochemical and immunologic pathways induced by IRI and the concentration of those proteins increases during hypoxia and dysoxia. Activation of the HIF system leads to augmented transcription of specific genes in various types of affected cells, but may also augment apoptotic and inflammatory processes, thus aggravating gut injury.

Key points

During intestinal ischaemia, mitochondrial oxygen uptake is reduced when cellular oxygen partial pressure decreases to below the threshold required to maintain normal oxidative metabolism.

Upon reperfusion, intestinal hypoxia may persist because microcirculatory flow remains impaired and/or because available oxygen is consumed by enzymes, intestinal cells and neutrophils.
Differentiating reactive and neoplastic gamma‐delta (γδ) T‐cell expansions in the peripheral blood and bone marrow
Authors: Tariq Hamza , Ilyas Zubair , Fu Lucy , Liu Yijie , Chen Qing Ching , Wolniak Kristy , Chen Yi‐Hua
Published: December 2024

The clinical and immunophenotypic attributes of reactive γδ T‐cell expansions are less well characterized than their malignant counterparts, which can pose diagnostic challenges. This study aims to investigate the characteristics and long‐term clinical outcomes of reactive γδ T‐cell expansions. A retrospective review was performed to identify patients with expanded γδ T‐cell population (>15% of T‐cells) by flow cytometry in peripheral blood and/or bone marrow specimens over a 17‐year period. The cases were divided into reactive and malignant categories and their clinical and immunophenotypic findings were compared. Clinical follow‐up was performed. 97 patients were identified including 19 malignant and 78 reactive cases with a variety of underlying conditions. The median absolute γδ T‐cell count and median percentage of γδ T‐cells per total T‐cells were significantly lower in reactive vs. malignant cases (p = 0.0001 and p < 0.00001, respectively). Reactive cases showed more frequent brighter surface CD3 expression (87.1% vs. 42.1%; p < 0.0001), no discrete loss of CD7 (0% vs. 36.9%; p < 0.0001), less frequent lack of CD5 (25.7% vs. 42.4%; p < 0.0001), and no homogeneous CD56 expression (0% vs. 31.6%; p > 0.0001) as compared with malignant cases. Upon long‐term follow‐up, none of the reactive cases showed clinical evidence of malignant evolution. Reactive expansions of γδ T‐cells can be seen in a variety of conditions including hematologic neoplasms, autoimmune and post‐transplant states, and infections. Such cases have significantly lower γδ T‐cell counts and percentages and no discrete loss of CD7. Lack of CD5 on its own is not an indication of immunophenotypic aberrancy in γδ T‐cells. Upon long‐term clinical follow‐up, such reactive expansions show no evidence of evolution to γδ T‐cell malignancies.
Orthoallosteric EGFR‐TKIs: A New Paradigm in NSCLC Treatment Strategy Targeting the C797S Mutation
Authors: Ahmad Iqrar , Patel Harun M.
Published: December 2024

The remarkable clinical success of third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) has significantly advanced the treatment landscape for non‐small‐cell lung cancer (NSCLC). However, the emergence of the tertiary point mutation C797S poses a substantial obstacle to their clinical efficacy, leading to a dearth of FDA‐approved targeted therapies for patients harboring this mutation. Addressing this pressing clinical challenge necessitates the development of novel therapeutic agents targeting the clinically challenging EGFR mutation. This review delves into the design strategies, antitumor activity, and crucial protein–drug interactions of recently introduced Orthoallosteric fourth‐generation EGFR‐TKIs. These inhibitors are distinguished by their ability to simultaneously engage both the canonical orthosteric (ATP) binding site and the allosteric site. By shedding light on these key aspects, the review serves as a valuable resource for medicinal chemists, empowering them to propel the advancement of fourth‐generation EGFR inhibitors.
Preliminary Evidence That Shared Genetic Influences Underlie Comorbidity Between Self‐Reported Eating and Internalizing Disorders and Gastrointestinal Disease in Adult Women and Men
Authors: Mikhail Megan E. , Pascoe Laura A. , Burt S. Alexandra , Culbert Kristen M. , Klump Kelly L.
Published: December 2024

Introduction

Accumulating research suggests both eating disorders (EDs) and internalizing disorders (e.g., anxiety, depression) are associated with gastrointestinal disease (e.g., irritable bowel syndrome, inflammatory bowel disease). However, the mechanisms underlying comorbidity with gastrointestinal disease—and whether they may differ for eating and internalizing disorders—remain poorly understood. Addressing these gaps is a critical first step to refining etiologic models of comorbidity and identifying potential targets for intervention.

Method

Participants included female and male twins ages 18–65 from the population‐based MSU Twin Registry (N = 5883). Lifetime history of EDs, internalizing disorders, and gastrointestinal disease was assessed via questionnaire. We first examined whether EDs and internalizing disorders were independently associated with gastrointestinal disease phenotypically. We then used trivariate Cholesky decomposition twin models to investigate whether EDs and internalizing disorders were related to gastrointestinal disease through overlapping or distinct genetic/environmental pathways.

Results

Eating (OR = 2.54, p = 0.009) and internalizing (OR = 2.14, p < 0.001) disorders were independently associated with gastrointestinal disease. Conclusions were unchanged after adjusting for important covariates (e.g., body mass index, age) and did not significantly differ across sex. Twin models suggested genetic influences shared by all three conditions explained their co‐occurrence, with 31% of the variance in EDs and 12% of the variance in gastrointestinal disease attributable to genetic influences shared with internalizing disorders.

Conclusion

Shared genetic mechanisms may contribute to comorbidity between EDs, internalizing disorders, and gastrointestinal disease. Identifying overlapping molecular pathways could potentially lead to novel interventions that simultaneously address all three conditions.
Population persistence, phenotypic divergence, and metabolic adaptation in yarrow (Achillea millefolium L.)
Authors: Losapio Gianalberto , Doussot Baptiste , Araniti Fabrizio , Bruno Leonardo , Guevara Roger , Dirzo Rodolfo
Published: December 2024

Climate change threatens biodiversity as populations can persist if they migrate or adapt to the rapidly changing conditions of the Anthropocene. However, the metabolic mechanisms underlying plant population persistence under the long‐term trends of increasing temperature and drought remain unclear. Here, we investigate the persistence and adaptation of yarrow (Achillea millefolium L.) populations over 100 years of climate change. We resurveyed historical sites spanning a broad climatic gradient (from 1 m to 3200 m above sea level) and analyzed metabolic diversity in a common‐garden experiment. We report that nine out of ten populations persisted locally, showing phenotypic and metabolic differentiation. The only population potentially extirpated is that of the hottest and driest site. A complex interaction between increasing temperatures and changing precipitation patterns shaped plant growth across populations. Populations from warmer sites in coastal and mountain regions grew taller than 100 years ago, whereas populations from drier sites in lowlands and foothills became shorter. Furthermore, we document differentiation in metabolic diversity involving plant defenses and stress response. These findings suggest that ongoing adaptation is constrained by long‐term changes in temperature and precipitation as well as by local biotic interactions. Preserving locally adapted populations and their metabolic diversity is key for conservation efforts in the face of accelerating climate change.
Numerical model and effect of site condition on the coupled dynamic characteristics of water storage tank of AP1000 shield building
Authors: Liu Jia , Li Jianbo , Li Zhiyuan , Sun Yongtao
Published: December 2024

Since the Fukushima nuclear incident in 2011, the focus on nuclear safety has intensified significantly, leading to heightened demands for nuclear power plant modeling to go beyond the mere dynamic analysis of soil–structure interaction (SSI) or fluid–structure interaction (FSI). In current engineering practice, FSI is typically described using simplified forms, such as loads or added mass. However, this approach lacks a comprehensive analytical framework that integrates refined FSI analysis with soil–structure interaction (SSI). This study analyzes the dynamic response of the nuclear island structural system using a fully coupled fluid–structure–soil interaction (FSSI) model. The effectiveness and validity of the model are verified through case comparisons. Simulations were conducted using the parameters of five different types of nuclear power engineering sites for both homogeneous and layered foundations. The results indicated that the hydrodynamic pressure response and acceleration amplification of layered foundations significantly exceeded those of homogeneous foundations, underscoring the importance of considering layered sites in the comprehensive complex modeling of nuclear power projects.
Low‐Temperature Thermochronologic Analysis and Geologic Significance of the Northern Part of the Western Margin of the Ordos Basin: A Case Study of the Moergou Profile in the Zhuozishan Area, Inner Mongolia, China
Authors: Guangyuan Xing , Zhanli Ren , Kai Qi , Sasa Guo , Yanzhao Liu
Published: December 2024

The northern part of the western margin of the Ordos Basin is located between the Alxa Block, the Central Asian Orogenic Belt, and the Ordos Basin, with a special structural location, making it an ideal area for studying surface action processes and tectonic dynamic evolution. Since the Mesozoic era, the region has undergone multiple stages of tectonic deformation and exhumation, but the exhumation events of different strata have significant differences. In this paper, we use apatite fission track (AFT) to study the Middle–Upper Proterozoic to Upper Paleozoic samples from the Moergou profile in the Zhuozishan area of Wuhai City. The central ages of the three sandstone samples are 153 ± 6.6, 125 ± 6, and 135 ± 5 Ma. The thermal history simulation results indicate that the area has undergone multiple cooling periods since the Mesozoic era, including (i) Late Jurassic (160–150 Ma), (ii) Late Early Cretaceous (130–110 Ma), and (iii) Cenozoic (~20 Ma). Additionally, we have discovered that the Changcheng System near the core of the Zhuozishan anticline was uplifted earlier and at a faster rate than the Taiyuan Formation located on both wings. The research area was affected by the Yanshanian orogeny and began to rapidly uplift from the Late Jurassic to the Early Cretaceous. The maximum paleogeothermal temperature was reached in the Late Jurassic and then rapidly uplifted to a partial annealing zone. Since the Miocene, it rapidly rose to the surface. The Late Jurassic tectonic exhumation indicated by thermochronology corresponds to the formation of thrust‐fold structures in the western margin.
Semantic Integration Demands Modulate Large‐Scale Network Interactions in the Brain
Authors: Nieberlein Laura , Martin Sandra , Williams Kathleen A. , Gussew Alexander , Cyriaks Sophia D. , Scheer Maximilian , Rampp Stefan , Prell Julian , Hartwigsen Gesa
Published: December 2024

The ability to integrate semantic information into the context of a sentence is essential for human communication. Several studies have shown that the predictability of a final keyword based on the sentence context influences semantic integration on the behavioral, neurophysiological, and neural level. However, the architecture of the underlying network interactions for semantic integration across the lifespan remains unclear. In this study, 32 healthy participants (30–75 years) performed an auditory cloze probability task during functional magnetic resonance imaging (fMRI), requiring lexical decisions on the sentence's final words. Semantic integration demands were implicitly modulated by presenting sentences with expected, unexpected, anomalous, or pseudoword endings. To elucidate network interactions supporting semantic integration, we combined univariate task‐based fMRI analyses with seed‐based connectivity and between‐network connectivity analyses. Behavioral data revealed typical semantic integration effects, with increased integration demands being associated with longer response latencies and reduced accuracy. Univariate results demonstrated increased left frontal and temporal brain activity for sentences with higher integration demands. Between‐network interactions highlighted the role of task‐positive and default mode networks for sentence processing with increased semantic integration demands. Furthermore, increasing integration demands led to a higher number of behaviorally relevant network interactions, suggesting that the increased between‐network coupling becomes more relevant for successful task performance as integration demands increase. Our findings elucidate the complex network interactions underlying semantic integration across the aging continuum. Stronger interactions between various task‐positive and default mode networks correlated with more efficient processing of sentences with increased semantic integration demands. These results may inform future studies with healthy old and clinical populations.
Development of the SPEAR Model: Separate Phases of Encoding and Retrieval Are Necessary for Storing Multiple Overlapping Associative Memories
Authors: Hasselmo Michael E.
Published: December 2024

In keeping with the historical focus of this special issue of Hippocampus, this paper reviews the history of my development of the SPEAR model. The SPEAR model proposes that separate phases of encoding and retrieval (SPEAR) allow effective storage of multiple overlapping associative memories in the hippocampal formation and other cortical structures. The separate phases for encoding and retrieval are proposed to occur within different phases of theta rhythm with a cycle time on the order of 125 ms. The same framework applies to the slower transition between encoding and consolidation dynamics regulated by acetylcholine. The review includes description of the experimental data on acetylcholine and theta rhythm that motivated this model, the realization that existing associative memory models require these different dynamics, and the subsequent experimental data supporting these dynamics. The review also includes discussion of my work on the encoding of episodic memories as spatiotemporal trajectories, and some personal description of the episodic memories from my own spatiotemporal trajectory as I worked on this model.
An anti‐junk food ad from a sports commercial break reduced junk food consumption inclinations, yet junk food ads had minimal to no impact
Authors: Hollett Ross C. , Butt Julia , Mills Brennen , Godrich Stephanie L. , Trapp Gina S. A. , Devine Amanda
Published: December 2024

Background

In Australia, there are concerns that unrestricted junk food advertising during sports broadcasts increases short‐term junk food consumption among viewers. Therefore, the present study aimed to estimate the impact of junk food and anti‐junk food advertising on consumption inclinations.

Methods

We conducted a content analysis across a sample (N = 16) of Australian Football League (AFL) and National Rugby League (NRL) matches to determine the prevalence of junk food and anti‐junk food advertising video clips. We also exposed participants (N = 428) to a single randomly selected junk food advertisement or a single anti‐junk food advertisement and measured the immediate impact on craving and consumption intentions for both healthy weight and high body mass index (BMI) participants.

Results

Junk food and anti‐junk food advertising video clips comprised 10.85% and .003% of all advertisements across the broadcasts, respectively. For both healthy and overweight participants, junk food advertisement exposure did not increase immediate craving or consumption intentions. However, decreases were observed in craving and consumption intentions following an anti‐junk food advertisement.

Conclusions

Junk food advertising prevalence across national sports was high. Junk food advertisements did not increase immediate inclinations to consume junk food, but an anti‐junk food advertisement was effective in reducing immediate craving and consumption intentions, particularly for healthy BMI participants.

So What?

Given the potential efficacy of health promotion adverts, governments should consider investing in a higher frequency of health messages during broadcasts that are known to readily promote junk food, such as national sports.
Ketorolac disturbs proteasome functions and induces mitochondrial abnormality‐associated apoptosis
Authors: Kumar Prashant , Kinger Sumit , Dubey Ankur Rakesh , Jagtap Yuvraj Anandrao , Choudhary Akash , Karmakar Surojit , Lal Girdhari , Kumar Amit , Bhattacharyya Sudipta , Poluri Krishna Mohan , Mishra Amit
Published: December 2024

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are recommended to treat moderate‐to‐severe pain. Previous studies suggest that NSAIDs can suppress cellular proliferation and elevate apoptosis in different cancer cells. Ketorolac is an NSAID and can reduce the cancer cells' viability. However, molecular mechanisms by which Ketorolac can induce apoptosis and be helpful as an anti‐tumor agent against carcinogenesis are unclear. Here, we observed treatment with Ketorolac disturbs proteasome functions, which induces aggregation of aberrant ubiquitinated proteins. Ketorolac exposure also induced the aggregation of expanded polyglutamine proteins, results cellular proteostasis disturbance. We found that the treatment of Ketorolac aggravates the accumulation of various cell cycle‐linked proteins, which results in pro‐apoptotic induction in cells. Ketorolac‐mediated proteasome disturbance leads to mitochondrial abnormalities. Finally, we have observed that Ketorolac treatment depolarized mitochondrial membrane potential, released cytochrome c into cytoplasm, and induced apoptosis in cells, which could be due to proteasome functional depletion. Perhaps more in‐depth research is required to understand the details of NSAID‐based anti‐proliferative molecular mechanisms that can elevate apoptosis in cancer cells and generate anti‐tumor potential with the combination of putative cancer drugs.
Evaluating feedback frequency preference and its relation to task performance
Authors: Thibodeaux Janea J. , Taylor Pierce M. , Bacotti Janelle K. , Morris Samuel L.
Published: December 2024

Many researchers have evaluated how characteristics of feedback may influence trainee performance, but relatively little attention has been allocated to directly assessing trainee preference for feedback characteristics and its relation to performance. Thus, the primary purpose of this study was to use a within‐subject experimental design to directly assess trainee preference for the frequency of feedback and its relation to task performance. A secondary objective was to evaluate how trainee preferences varied across specific task components based on component complexity. Thirty‐five undergraduate students completed two arbitrary tasks and were given the opportunity to request feedback after each component of the task. For 85.71% of our participants, an inverse relation was observed between preference for feedback frequency and task performance. Participants requested feedback less often as performance improved. Feedback preferences also varied with the complexity of each component of the task. Implications for training, supervision, and feedback practices are discussed.
Noisy monetary policy announcements
Authors: Dahlhaus Tatjana , Gambetti Luca
Published: December 2024

We address two main questions. First, do monetary policy announcements contain noise? Second, if yes, what are the effects of policy noise on the economy? The answer to the first question is “yes.” The answer to the second is “small,” except on federal funds rate expectations. In sum, we find that the bulk of fluctuations in the path factor are driven by noise. The results are obtained using dynamic rotations to identify the monetary policy shock in a VAR estimated with US data. Finally, we show that announcements about future tightening are mainly interpreted as Delphic over our sample period.
Design and Validation of a Multimodal Diffuse Reflectance and Spatially Offset Raman Spectroscopy System for In Vivo Applications
Authors: Mordi April , Karunakaran Varsha , Marium Mim Umme , Marple Eric , Rajaram Narasimhan
Published: December 2024

We report on the development of a multimodal spectroscopy system, combining diffuse reflectance spectroscopy (DRS) and spatially offset Raman spectroscopy (SORS). A fiber optic probe was designed with spatially offset source–detector fibers to collect subsurface measurements for each modality, as well as ball lens‐coupled fibers for superficial measurements. The system acquires DRS, zero‐offset Raman spectroscopy (RS) and SORS with good signal‐to‐noise ratio. Measurements on chicken breast tissue demonstrate that both DRS and RS can acquire spectra from similar depths within tissue. Measurements acquired from the skin of a human volunteer demonstrate distinct Raman peaks at 937 and 1755 cm−1 that were unique to the zero‐offset ball lens configuration and 718 and 1089 cm−1 for the spatially offset setting. We also identified Raman peaks corresponding to melanin that were prominent in the superficial measurements obtained with the ball lens‐coupled fibers but not in the spatially offset fibers.
Triptophenolide Improves Rheumatoid Arthritis and Progression by Inducing Macrophage Toxicity
Authors: Pu Xiuxiu , Ye Qiao
Published: December 2024

To investigate the role and mechanism of triptophenolide (TRI) in resisting rheumatoid arthritis (RA). Network pharmacology analysis results suggested that TRI was related to multiple inflammation‐related signaling proteins, and possessed the stable structural configuration. In animal experiments, TRI suppressed RA in mice, inhibited tissue inflammation, and improved synovial injury. Moreover, TRI can suppress RA via multiple signaling pathways, and inhibiting pyroptosis is one of the feasible treatments for improving RA.
Examining Longitudinal Relations Between Eating Disorder Symptoms and Negative Emotion Variability in Military Members
Authors: Clancy Olivia M. , Forrest Lauren , Smith April R.
Published: December 2024

Up to a third of service members and Veterans experience disordered eating. Disordered eating can be maintained through negative reinforcement of painful and unpleasant emotions such as guilt, shame, sadness, and hostility. Hostility is a negative emotion that may be particularly relevant for service members and Veterans, yet hostility's relation to disordered eating remains understudied. Further, variability in emotions may be particularly relevant, given that variability in emotions is often a stronger predictor of psychopathology than mean levels. Thus, the goal of the present study was to assess a potential bidirectional relationship between disordered eating symptoms and individuals' variability of hostility, stress, anxiety, sadness, and shame. Participants (N = 94, Mage = 32.2, 75.8% men; 81.8% White) completed 30 days of ecological momentary assessment (EMA) with four assessments per day along with baseline and follow‐up measures including the Eating Pathology Symptom Interview (EPSI), which assessed eight disordered eating symptom domains. Hierarchical regressions revealed that higher baseline levels of Binge Eating and Excessive Exercise predicted greater intraindividual hostility variability. Further, more hostility variability predicted higher Cognitive Restraint at 1‐month follow‐up. Baseline disordered eating symptoms were not associated with intraindividual variability in stress, anxiety, sadness, or shame. However, greater intraindividual variability in shame predicted higher Muscle Building at 1‐month follow‐up. Hostility variability was the only emotion that was predicted by, and predictive of, disordered eating symptoms. These findings suggest that hostility may be a relevant treatment target for service members with disordered eating.
TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression
Authors: Li Chao , Enciso‐Martinez Agustin , Koning Roman I. , Shahsavari Mona , ten Dijke Peter
Published: December 2024

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. The cytokine transforming growth factor‐β (TGF‐β) facilitates cancer progression via EVs secreted by cancer cells, which act on recipient cells in the tumour microenvironment. However, the mechanisms of how TGF‐β affects cancer cell EV release and composition are incompletely understood. Here, we systematically investigate the effects of TGF‐β on the release and protein composition of EVs from breast cancer cells. TGF‐β suppresses the transcription of RAB27B mediated by SMAD3 and thereby hampers EV release. Using click chemistry and quantitative proteomics, we found that TGF‐β increases the quantity of protein cargo and changes the composition of EVs by downregulating RAB27B expression. The recomposed EVs, induced by TGF‐β or RAB27B depletion, inhibit CD8+ T cell‐mediated breast cancer killing. Our findings reveal the critical roles of TGF‐β and RAB27B in cancer development by regulating EV release and composition and thus provide potential targets to improve cancer immunotherapy.
Assessing intrinsic capacity for person‐centred HIV care: a cross‐sectional study in ageing populations in Malaysia and Hong Kong
Authors: Rajasuriar Reena , Hisham Syaza , Lim John Son , Cheong Jean Yi , Ho Wen Ying , Yap Siew Hwei , Zulhaimi Nurul Syuhada , Neelamegam Malinee , Cheung Catherine , Wong Vivian , Yusof Ruhana Che , Hasmukharay Kejal , Kamaruzzaman Shahrul Bahyah , Omar Sharifah Faridah Syed , Chong Meng Li , Wong Pui Li , Lui Grace Chung‐Yan
Published: December 2024

Introduction

WHO's Integrated Care for Older People (ICOPE) proposes we measure the functional construct of intrinsic capacity (IC) to monitor and identify individuals with age‐associated vulnerabilities. Assessments of IC may be useful to address the evolving, non‐HV care needs of ageing people with HIV (PWH). However, to date, its utility within the context of HIV has not been assessed.

Methods

Participants included 200 PWH attending out‐patient care (2021−2023) in Universiti Malaya Medical Centre, Malaysia and 101 community controls aged 35 years and above. The ICOPE framework was adapted to derive aggregate IC scores (ranging 0–6) encompassing the five domains of cognition, sensory (hearing and vision), mobility, mood and vitality. Multivariable analyses were used to explore the association of IC scores in PWH with multiple health outcomes including frailty, difficulties performing instrumental activities of daily living (IADL) and inflammatory markers. Area under the receiver operator characteristic (AUC‐ROC) was calculated to predict frailty and IADL deficits in the current cohort and an independent cohort of 275 PWH from Hong Kong (HK).

Results

Median (interquartile range, IQR) age among PWH and controls were 50 (42−56) and 50 (39−59) years, respectively. There were more males among PWH (83% vs. 56%, p<0.001). All PWH received antiretroviral therapy (ART) for a median duration of 11 (8−14) years. Aggregate IC scores were lower in PWH but not significantly different compared to controls, (5.4 vs. 5.6, p = 0.093) and PWH performed significantly worse than controls only in the cognitive domain. Aggregate IC scores in PWH was independently associated with frailty (OR 0.17 95% CI 0.07−0.42, p<0.001), IADL deficits (OR 0.25 95% CI 0.14−0.46, p<0.001) and all other patient‐reported outcomes assessed. Aggregate IC scores correlated with IL‐6 but not sCD14 and sCD163 levels. IC scores performed well in identifying PWH with frailty (AUC‐ROC ≥ 0.80) in the HK and Malaysian cohorts but more modestly (AUC‐ROC ≥ 0.64) for IADL deficits.

Conclusions

IC is a good composite measure to monitor non‐HIV, age‐associated physical and social vulnerabilities in PWH on ART and should complement disease‐based monitoring in routine HIV care. Assessments of IC should be validated in larger, longitudinal cohorts of PWH from diverse settings.
Assessment of adverse events stratified by timing of leadless pacemaker implantation with cardiac implantable electronic devices extraction due to infection: A systematic review and meta‐analysis
Authors: Inoue Naoya , Ito Yuji , Imaizumi Takahiro , Morikawa Shuji , Murohara Toyoaki
Published: December 2024

Background

Removal of cardiac implantable electronic devices (CIEDs) is strongly recommended for CIED‐related infections, and leadless pacemakers (LPs) are increasingly used for reimplantation. However, the optimal timing and safety of LP implantation after CIED removal for infection remains unclear.

This systematic review and meta‐analysis aimed to assess complication rates (all‐cause mortality and reinfection) when LP implantation was performed simultaneously with or after CIED removal.

Methods

Studies published from 2015 to September 2024 were searched in PubMed, Cochrane Library, and Google Scholar. Observational studies and case series on CIED removal and LP implantation were eligible. The primary outcomes were all‐cause mortality and reinfection post‐LP implantation. Pooled estimates were obtained using the Freedman‐Tukey double arcsine transformation. Study quality was assessed using the MINORS criteria, with data extraction and independent assessment by two authors.

Results

Of 396 records, 16 studies were included in the analysis, with 653 patients (mean age:76.9 years). The incidence of isolated pocket infections was 46.7% (95% CI: 32.7%–61.2%) and systemic infections at 46.3% (95% CI: 29.5%–64.0%). The primary outcome incidence was 19.4% (95% CI: 12.8%–28.3%, I2: 0%) for simultaneous CIED extraction and LP implantation compared with 7.79% (4.37%–13.5%, I2: 4%) for LP implantation after CIED extraction (p = .009). All‐cause mortality rates were 22.8% (95% CI: 15.9%–31.6%, I2: 0%) for simultaneous implantation and 8.71% (4.46%–16.3%, I2: 21%) after extraction (p = 0.008). Reinfection was not observed in any of these studies.

Conclusion

Simultaneous CIED extraction and LP implantation due to infection may be associated with an increased risk of all‐cause mortality.
Impacts of Solar Geoengineering on Projected Climate of South Asia
Authors: Hussain Athar , Khan Muhammad Ali , Sipra Hassaan
Published: December 2024

Solar geoengineering (SG) is an interim solution to combat global warming, which involves scattering back a tiny fraction of the incoming sunlight. Hence, SG and its potential impacts are important to study for the identification of changing weather patterns over regions of climate vulnerable South Asia. This study explores the projected spatio‐temporal patterns of two meteorological parameters, temperature and precipitation, under SG numerical experiment (stratospheric aerosol injection), relative to projected climate change. Furthermore, future projections of same meteorological parameters without SG under a representative concentration pathway (RCP 4.5) will also be studied for comparative analysis. Offsetting climate parameters are associated with multiple risk factors. Thus, both SG and non‐SG scenarios will be studied for the future time period. The results indicate that the temperature reduces by −0.62°C under the SG G4 scenario and spatial distribution patterns of temperature also depicts an overall cooling effects during the G4 implementation (2020–2029) and continuation (2030–2069) phase. Moreover, on a regional scale, a cold bias (less severe) is projected as compared to projected climate under RCP 4.5. Our findings show that, precipitation is also projected to be decreased by −0.02 mm day−1. Dry bias pattern is projected during implementation phase only. The G4 based SG continuation and termination (2070–2090) phases depict no drastic change in precipitation over South Asia.
The Influence of the Eastern‐Type and Western‐Type Southern Branch Troughs on Precipitation in Winter and Its Structural Characteristics
Authors: Bianba Zhuoga , Yang Cheng , Zhou Shunwu , Qian Zhitong , Liu Shengsheng , Li Ke , Yao Xiuping
Published: December 2024

Using 30 years of NCEP/NCAR reanalysis data from winter (January), along with daily precipitation data from the China Meteorological Administration (CMA), this study employed an objective recognition method to classify southern branch troughs (SBTs) into eastern and western types. Subsequently, an analysis was conducted to identify the structural characteristics of each type and evaluate their effects on precipitation. The findings reveal that the eastern and western SBTs are located at different coordinates at 500 hPa, each affecting distinct precipitation zones. Specifically, the eastern SBT influences regions east of 90° E, particularly Yunnan, while the western SBT primarily impacts areas west of 90° E, with a pronounced effect on southern Tibet. Dynamic analysis indicates that both types of SBTs manifest as baroclinic troughs, though the western type exhibits stronger dynamic conditions than the eastern type. Both SBTs types are characterised by warm, moist advection ahead of the trough and cold, dry advection behind it. The eastern SBT shows more favourable thermal conditions than the western SBTs. Water vapour associated with both types of SBTs is concentrated at the front of the troughs below 450 hPa, with convergence observed below 700 hPa. Additionally, the eastern SBTs generate more pronounced water vapour convergence compared to the western SBT. Notably, torrential precipitation related to the eastern SBTs is driven by water vapour from the outer circulation of the western Pacific subtropical high, with additional moisture from the Bay of Bengal. In contrast, the water vapour associated with the western SBT primarily originates from the Arabian Sea and is supplemented by moisture from the Bay of Bengal.
Characteristics of Marine Heat Extreme Evolution in the Northern Indian Ocean
Authors: Gupta Hitesh , Deogharia Rahul , Sil Sourav , Dey Dipanjan
Published: December 2024

Marine Heat Extremes (MHEs) are events of anomalously high Sea Surface Temperature (SST) during which SST values exceed a certain pre‐defined threshold. These MHEs have profound influence over weather patterns, air‐sea interaction and the health of marine ecosystems. This study investigates the long‐term evolution of MHEs in the Northern Indian Ocean (NIO) from 1900 to 2020. We utilised two normalised indices, the Normalised Extreme Frequency Index (NEFI) for frequency and the Normalised Extreme Heat Index (NEHI) for the intensity of MHEs, to objectively compare the MHE attributes across different periods and regions of the NIO. The analysis reveals non‐linearly increasing NEFI, with the Western Equatorial Indian Ocean (WEIO) experiencing the fastest rise, followed by the Eastern Equatorial Indian Ocean (EEIO), Arabian Sea (AS) and Bay of Bengal (BoB). MHE intensity shows exponential growth, with its mean‐based regimes becoming shorter and shifting more frequently. A new regime has been emerging since the last decade. Analysis of the spatial extent of the MHEs indicates that the WEIO is the fastest‐growing region of the NIO. Similar observations were found upon removing sub‐decadal variabilities, which include the potential effects of El Niño‐Southern Oscillation and Indian Ocean Dipole, highlighting the long‐term warming associated with global warming. The study also links the increasing mean SST to the rising frequency and intensity of MHEs, which is predominantly driven by the net surface heat‐flux, which is a combined effect of local and pantropical air‐sea interaction. The surface warming is outpacing subsurface warming, thereby strengthening thermal stratification over time, potentially impacting vertical mixing and upwelling, which can, in turn, lead to further surface warming.
Rapid Assessment of Tablet Quality Based on Raman Spectroscopy Analysis: Investigating the Effect of Storage Conditions on the Degradation of Active Pharmaceutical Ingredient (API) of Acetaminophen Tablet
Authors: Mohammadian M. Keshavarz , Tavassoli S. H. , Karimi S.
Published: December 2024

The effectiveness and safety of drugs may be compromised by the degradation of APIs during preparation processes or after they have been released to market. This study has investigated the degradation of 500‐mg Acetaminophen tablet (C8H9NO2) when stored under unfavorable conditions such as increased temperature and high levels of humidity. To quantify the amount of API, the Raman intensity variations of characteristic peaks of API and polyvinylpyrrolidone (PVP) (C6H9NO) are explored. By considering various sources of error in all experiments, the reliability of the extracted data set from Raman spectrums and the quality of results obtained using the utilized technique for predicting API is investigated at standard room temperature. The results demonstrate an acceptable precision in the range of pharmacopeia monograph. Then, the effect of temperature and humidity variations on the amount of API is investigated based on the related Raman spectra. The results show that the API's quantity starts to decrease after about 60 min at the temperature of 45°C ± 2°C and the relative humidity (RH) of 75% ± 2%. According to our results, when tablets are kept under the unfavorable conditions, the degradation pattern of API follows a logarithmic trend.
Stock identification and age prediction of Red Mullet Mullus barbatus in the western Black Sea (Türkiye) as inferred from otolith shape descriptors
Authors: Yildiz Taner , Cömert Nurdan , Kahraman Abdullah E. , Karakulak F. Saadet
Published: December 2024

Objective

In this study, we applied shape analysis to differentiate two Red Mullet Mullus barbatus stocks in the western Black Sea and assessed the generalized linear model (GLM) for age prediction based on otolith dimensions and weight.

Methods

Sagittal otoliths from 259 fish were collected by commercial bottom trawl vessels in İğneada and Şile, Türkiye, between October 2017 and April 2018. Otolith shape was described using wavelet transformation (contour shape) along with four morphometric characteristics (otolith length, area, width, and perimeter) and six shape indices (circularity, rectangularity, form factor, roundness, ellipticity, and aspect ratio) to reveal differences between the two regions. Shape indices were explored using multivariate statistical methods, including multivariate analysis of variance (MANOVA) and canonical discriminant analysis (CDA). Canonical analysis of principal coordinates (CAP) provided an overview of the differentiation in the otolith outline shape between the two stocks by using the wavelet coefficients. The GLMs predicted age using otolith size parameters, shape indices, and otolith weight.

Result

The MANOVA showed no significant differences between sexes but notable differences between right and left otoliths. The CDA achieved a discrimination rate of 65.7% for age 1 and 64.8% for age 3, indicating distinct local populations. The otolith contours varied between Red Mullet sampled in the two regions, with CAP achieving an overall accuracy of 67.1% for both regions, 68.12% accuracy for İğneada, and 66.20% accuracy for Şile. The GLMs identified otolith length, weight, width, and perimeter and fish sex as key factors, with otolith length being the most significant predictor for age estimation.

Conclusion

The close alignment of observed and estimated ages highlights the potential for using otolith length in age estimation.
Protein engineering in the deep learning era
Authors: Zhou Bingxin , Tan Yang , Hu Yutong , Zheng Lirong , Zhong Bozitao , Hong Liang
Published: December 2024

Advances in deep learning have significantly aided protein engineering in addressing challenges in industrial production, healthcare, and environmental sustainability. This review frames frequently researched problems in protein understanding and engineering from the perspective of deep learning. It provides a thorough discussion of representation methods for protein sequences and structures, along with general encoding pipelines that support both pre‐training and supervised learning tasks. We summarize state‐of‐the‐art protein language models, geometric deep learning techniques, and the combination of distinct approaches to learning from multi‐modal biological data. Additionally, we outline common downstream tasks and relevant benchmark datasets for training and evaluating deep learning models, focusing on satisfying the particular needs of protein engineering applications, such as identifying mutation sites and predicting properties for candidates' virtual screening. This review offers biologists the latest tools for assisting their engineering projects while providing a clear and comprehensive guide for computer scientists to develop more powerful solutions by standardizing problem formulation and consolidating data resources. Future research can foresee a deeper integration of the communities of biology and computer science, unleashing the full potential of deep learning in protein engineering and driving new scientific breakthroughs.
Analysis and Optimisation of Obstacle‐Crossing Performance of Electric Shovel Based on DEM‐MBD Coupling Method
Authors: Chen Zeren , Guan Wei , Li Ruibin , Li Guang , Xue Duomei , Liu Zhengbin , Wang Guoqiang
Published: December 2024

To study and enhance the obstacle‐crossing performance of the electric shovel, an obstacle‐crossing model that employs a coupling methodology integrating the discrete element method (DEM) and multi‐body dynamics (MBD) is constructed. Secondly, the influence of grouser height (GH), track velocity (TV), slope inclination (SI) and slope height (SH) on obstacle‐crossing performance is investigated through DEM‐MBD simulation, with the objective of obtaining an obstacle‐crossing surrogate model through the Kriging method and Box‐Behnken experimental design. On this basis, two optimisation solutions for the obstacle‐crossing performance of the electric shovel are proposed based on a genetic algorithm (GA), and the corresponding obstacle‐crossing performances are analysed. The results demonstrate that the coupling effect between SI and SH exerts a considerable influence on the ground pressure coefficient (GPC), power and disturbance potential energy (DPE). When the optimal TV and GH are set at 0.1 m/s and 9.38 mm, the GPC, power and disturbance kinetic energy (DKE) are observed to diminish to varying degrees, thereby indicating that the obstacle‐crossing performance of the electric shovel has been enhanced.
Early Childhood in Precolonial South America: Breastfeeding, Infant Mortality, and Stable Isotopes Analysis in Southeastern Shell Mound Builders During the Middle Holocene (7th–5th Millennium BP)
Authors: Di Giusto Marina , Herrscher Estelle , Jaouen Klervia , Bastos Murilo , Mion Leïa , Wesolowski Veronica
Published: December 2024

This article presents and discusses isotopic data on breastfeeding, weaning, and complementary diet during early childhood in Middle Holocene southeastern Brazil. The study focuses on human individuals from two contemporaneous shell mounds, Piaçaguera (7151–5668 yBP) and Moraes (6791–5590 yBP), which show distinct patterns of infant mortality. We conducted δ15N and δ13C analyses on collagen extracted from subadult bones (Piaçaguera: n = 13; Moraes: n = 13) and sequential dentine slices from permanent (Piaçaguera: n = 7; Moraes: n = 11) and deciduous teeth (Moraes: n = 5). Our findings indicate that weaning ended between 2 and 4 years old in Piaçaguera, with complementary foods similar to the adults. At Moraes, weaning ended between 2 and 5 years old, with a higher consumption of freshwater fish during early childhood and by pregnant women. The weaning ages at Piaçaguera and Moraes align with those documented in other precolonial South American groups. However, our study suggests different dietary preferences and strategies within each group, possibly linked to distinct patterns of infant mortality, particularly evident in the Moraes group.
Clinician Perspectives on the Management of Hearing Loss in Patients With Limited English Proficiency
Authors: Govindan Aparna , Singer Adina , Zekavat Lily , Jia Tianyi , Wong Kevin , Kuang Jianjing , Cosetti Maura K. , Hwa Tiffany P.
Published: December 2024

Objective

Clinicians face challenges in managing the growing population of patients with limited English proficiency (LEP) and hearing loss (HL) in the United States. This study seeks to investigate provider perspectives on evaluating, counseling, and treating HL in LEP patients.

Study Design

Prospective descriptive study.

Setting

Tertiary care center.

Methods

Researchers employed a mixed methods design: (1) structured clinician interviews, (2) cross‐sectional, national electronic survey, both regarding perspectives on managing hearing loss in LEP patients. Structured interviews were analyzed using modified grounded theory.

Results

Twenty‐nine providers participated in interviews (16 otologists, 13 audiologists). The most reported non‐English language was Spanish, followed by Chinese languages. Four thematic domains were derived: barriers to care, cochlear implant (CI) candidacy evaluation, counseling, and ideal resources. Major barriers were patient desire (97%; n = 28), and lack of validated tests (72%; n = 21). Methods of CI evaluation included improvising on validated speech perception testing (59%; n = 17) and use of non‐speech evaluation (52%; n = 15). One‐quarter forgoes speech testing in non‐Spanish‐speaking patients (24%; n = 7). Suggestions to improve management include in‐person interpreters (62%; n = 18) and testing battery in all languages (31%; n = 9). National survey results (n = 87 providers) demonstrated that respondents were significantly less confident in the methods of speech perception testing and in counseling on surgical hearing rehabilitation in LEP.

Conclusion

Clinicians encounter challenges in managing LEP patients with HL, including limitations in audiometric and CI candidacy assessment, communication barriers, information accessibility, and cultural competency. Opportunities for improving care include developing language‐specific test batteries, linguistically and culturally appropriate education materials, and cultural competency training.