bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancancer survival prediction using a deep learning architecture with multimodal representation and integration
Authors: Fan Ziling , Jiang Zhangqi , Liang Hengyu , Han Chao 
Published: January 2023

AbstractMotivationUse of multi-omics data carrying comprehensive signals about the disease is strongly desirable for understanding and predicting disease progression, cancer particularly as a serious disease with a high mortality rate. However, recent methods currently fail to effectively utilize the multi-omics data for cancer survival prediction and thus significantly limiting the accuracy of survival prediction using omics data.ResultsIn this work, we constructed a deep learning model with multimodal representation and integration to predict the survival of patients using multi-omics data. We first developed an unsupervised learning part to extract high-level feature representations from omics data of different modalities. Then, we used an attention-based method to integrate feature representations, produced by the unsupervised learning part, into a single compact vector and finally we fed the vector into fully connected layers for survival prediction. We used multimodal data to train the model and predict pancancer survival, and the results show that using multimodal data can lead to higher prediction accuracy compared to using single modal data. Furthermore, we used the concordance index and the 5-fold cross-validation method for comparing our proposed method with current state-of-the-art methods and our results show that our model achieves better performance on the majority of cancer types in our testing datasets.Availability and implementationhttps://github.com/ZhangqiJiang07/MultimodalSurvivalPrediction.Supplementary informationSupplementary data are available at Bioinformatics online.
GOThresher: a program to remove annotation biases from protein function annotation datasets
Authors: Joshi Parnal , Banerjee Sagnik , Hu Xiao , Khade Pranav M , Friedberg Iddo 
Published: January 2023

Abstract

Motivation
Advances in sequencing technologies have led to a surge in genomic data, although the functions of many gene products coded by these genes remain unknown. While in-depth, targeted experiments that determine the functions of these gene products are crucial and routinely performed, they fail to keep up with the inflow of novel genomic data. In an attempt to address this gap, high-throughput experiments are being conducted in which a large number of genes are investigated in a single study. The annotations generated as a result of these experiments are generally biased towards a small subset of less informative Gene Ontology (GO) terms. Identifying and removing biases from protein function annotation databases is important since biases impact our understanding of protein function by providing a poor picture of the annotation landscape. Additionally, as machine learning methods for predicting protein function are becoming increasingly prevalent, it is essential that they are trained on unbiased datasets. Therefore, it is not only crucial to be aware of biases, but also to judiciously remove them from annotation datasets.

Results
We introduce GOThresher, a Python tool that identifies and removes biases in function annotations from protein function annotation databases.

Availability and implementation
GOThresher is written in Python and released via PyPI https://pypi.org/project/gothresher/ and on the Bioconda Anaconda channel https://anaconda.org/bioconda/gothresher. The source code is hosted on GitHub https://github.com/FriedbergLab/GOThresher and distributed under the GPL 3.0 license.

Supplementary information
Supplementary data are available at Bioinformatics online.
CAPLA: improved prediction of protein–ligand binding affinity by a deep learning approach based on a cross-attention mechanism
Authors: Jin Zhi , Wu Tingfang , Chen Taoning , Pan Deng , Wang Xuejiao , Xie Jingxin , Quan Lijun , Lyu Qiang 
Published: January 2023

Abstract

Motivation
Accurate and rapid prediction of protein–ligand binding affinity is a great challenge currently encountered in drug discovery. Recent advances have manifested a promising alternative in applying deep learning-based computational approaches for accurately quantifying binding affinity. The structure complementarity between protein-binding pocket and ligand has a great effect on the binding strength between a protein and a ligand, but most of existing deep learning approaches usually extracted the features of pocket and ligand by these two detached modules.

Results
In this work, a new deep learning approach based on the cross-attention mechanism named CAPLA was developed for improved prediction of protein–ligand binding affinity by learning features from sequence-level information of both protein and ligand. Specifically, CAPLA employs the cross-attention mechanism to capture the mutual effect of protein-binding pocket and ligand. We evaluated the performance of our proposed CAPLA on comprehensive benchmarking experiments on binding affinity prediction, demonstrating the superior performance of CAPLA over state-of-the-art baseline approaches. Moreover, we provided the interpretability for CAPLA to uncover critical functional residues that contribute most to the binding affinity through the analysis of the attention scores generated by the cross-attention mechanism. Consequently, these results indicate that CAPLA is an effective approach for binding affinity prediction and may contribute to useful help for further consequent applications.

Availability and implementation
The source code of the method along with trained models is freely available at https://github.com/lennylv/CAPLA.

Supplementary information
Supplementary data are available at Bioinformatics online.
Kidney and blood pressure regulation—latest evidence for molecular mechanisms
Authors: Suzumoto Yoko , Zucaro Laura , Iervolino Anna , Capasso Giovambattista 
Published: January 2023

ABSTRACT
Hypertension is one of the major health problems leading to the development of cardiovascular diseases. Despite a rapid expansion in global hypertension prevalence, molecular mechanisms leading to hypertension are not fully understood largely due to the complexity of pathogenesis involving several factors. Salt intake is recognized as a leading determinant of blood pressure, since reduced dietary salt intake is related to lower morbidity and mortality, and hypertension in relation to cardiovascular events. Compared with salt-resistant populations, salt-sensitive individuals exhibit high sensitivity in blood pressure responses according to changes in salt intake. In this setting, the kidney plays a major role in the maintenance of blood pressure under the hormonal control of the renin–angiotensin–aldosterone system. In the present review, we summarize the current overview on the molecular mechanisms for modulation of blood pressure associated with renal ion channels/transporters including sodium–hydrogen exchanger isoform 3 (NHE3), Na+-K+-2Cl– cotransporter (NKCC2), sodium–chloride cotransporter (NCC), epithelial sodium channel (ENaC) and pendrin expressed in different nephron segments. In particular, recent studies on experimental animal models with deletion of renal ion channels led to the identification of several crucial physiological mechanisms and molecules involved in hypertension. These findings could further provide a potential for novel therapeutic approaches applicable on human patients with hypertension.
Extreme tolerance for nocturnal emergence at low body temperatures in a high-latitude lizard: implications for future climate warming
Authors: Chukwuka Christian O , Monks Joanne M , Cree Alison 
Published: January 2023

AbstractHigh-latitude lizards live in environments where ambient air temperature at night is frequently below retreat temperatures, which likely has implications for nocturnal emergence and activity. However, patterns of lizard activity at night under current temperate climates are poorly understood, a situation that limits our understanding of potential effects of climate change. We investigated patterns of nocturnal emergence and activity in the cold-adapted, viviparous gecko (Woodworthia ‘Otago/Southland’). We measured operative environmental temperature (Te) available to geckos that emerged at night and simultaneously assessed nighttime emergence activity using time-lapse trail cameras. Also, we assessed field body temperature (Tb) of emerged geckos of various life history groups at night using thermography to understand how current weather conditions affect field Tb of emerged geckos. Our results show that Te, nocturnal emergence activity and field-active Tb increased with nighttime air temperature. Nocturnal emergence was highest in spring and summer but also occurred in autumn and (unexpectedly) in winter. Geckos were active over a broad range of Tb down to 1.4°C (a new record low for lizards) and on rock surfaces typically warmer than air temperature or Tb. We conclude that this nocturnal, high-latitude lizard from the temperate zone is capable of activity at low winter temperatures, but that current climate limits emergence and activity at least in autumn and winter. Activity levels for cool-temperate reptiles will probably increase initially as climates warm, but the consequences of increased nocturnal activity under climate change will probably depend on how climate change affects predator populations as well as the focal species’ biology.
Proteomic profiling identifies novel independent relationships between inflammatory proteins and myocardial infarction
Authors: Valdes-Marquez Elsa , Clarke Robert , Hill Michael , Watkins Hugh , Hopewell Jemma C 
Published: January 2023

Abstract

Background
Inflammation has been implicated in the pathogenesis of coronary heart disease, but the relevance and independence of individual inflammatory proteins is uncertain.

Objective
To examine the relationships between a spectrum of inflammatory proteins and myocardial infarction (MI).

Methods and results
A panel of 92 inflammatory proteins was assessed using an OLINK multiplex immunoassay among 432 MI cases (diagnosed &lt; 66 years) and 323 controls. Logistic regression was used to estimate associations between individual proteins and MI, after adjustment for established cardiovascular risk factors and medication use, and stepwise regression to identify proteins with independent effects. Machine learning techniques (Boruta analysis and LASSO regression) and bioinformatic resources were used to examine the concordance of results with those obtained by conventional methods and explore the underlying biological processes to inform the validity of the associations. Among the 92 proteins studied, 62 (67%) had plasma concentrations above the lower limit of detection in at least 50% of samples. Of these, 15 individual proteins were significantly associated with MI after covariate adjustment and correction for multiple testing. Five of these 15 proteins (CDCP1, CD6, IL1–8R1, IL-6, and CXCL1) were independently associated with MI, with up to three-fold higher risks of MI per doubling in plasma concentrations. Findings were further validated using machine learning techniques and biologically focused analyses.

Conclusions
This study, demonstrating independent relationships between five inflammatory proteins and MI, provides important novel insights into the inflammatory hypothesis of MI and the potential utility of proteomic analyses in precision medicine.
Reasons mothers of young children delayed or skipped preventive health care during the first year of the COVID-19 pandemic
Authors: Heersping Grace E , Waring Molly E 
Published: January 2023

Abstract

Background
Preventive health care provides opportunity for preventive screenings and health promotion. Mothers of young children may disproportionately experience barriers to preventive care during the COVID-19 pandemic.

Methods
We examined delaying and skipping preventive health care during the first year of the COVID-19 pandemic among mothers and described reasons for delaying or skipping care. Mothers of children aged 0–12 years from the United States completed an online survey in February/March 2021 and reported receipt of preventive care during the COVID-19 pandemic, reasons for delaying or skipping care, demographics, and experiences with COVID-19.

Results
Participants (N = 306) were on average 35.9 (SD: 6.2) years old, racially/ethnically diverse, and 74.8% had at least a Bachelor’s degree. From March 2020 to March 2021, 16.0% delayed and 20.6% skipped their physical examination, and 20.9% had not planned on receiving a physical examination. The most common reasons for delaying and skipping care were COVID-19 infection concerns, perception that delaying care would not negatively impact health, provider rescheduling, time, and childcare.

Conclusions
Primary care teams may need to re-engage mothers who skipped preventive care during the pandemic, including addressing concerns about COVID-19 infection.
Lissencephaly-1 mutations enhance traumatic brain injury outcomes in Drosophila
Authors: Katzenberger Rebeccah J , Ganetzky Barry , Wassarman David A 
Published: January 2023

Abstract
Traumatic brain injury (TBI) outcomes vary greatly among individuals, but most of the variation remains unexplained. Using a Drosophila melanogaster TBI model and 178 genetically diverse lines from the Drosophila Genetic Reference Panel (DGRP), we investigated the role that genetic variation plays in determining TBI outcomes. Following injury at 20–27 days old, DGRP lines varied considerably in mortality within 24 h (“early mortality”). Additionally, the disparity in early mortality resulting from injury at 20–27 vs 0–7 days old differed among DGRP lines. These data support a polygenic basis for differences in TBI outcomes, where some gene variants elicit their effects by acting on aging-related processes. Our genome-wide association study of DGRP lines identified associations between single nucleotide polymorphisms in Lissencephaly-1 (Lis-1) and Patronin and early mortality following injury at 20–27 days old. Lis-1 regulates dynein, a microtubule motor required for retrograde transport of many cargoes, and Patronin protects microtubule minus ends against depolymerization. While Patronin mutants did not affect early mortality, Lis-1 compound heterozygotes (Lis-1x/Lis-1y) had increased early mortality following injury at 20–27 or 0–7 days old compared with Lis-1 heterozygotes (Lis-1x/+), and flies that survived 24 h after injury had increased neurodegeneration but an unaltered lifespan, indicating that Lis-1 affects TBI outcomes independently of effects on aging. These data suggest that Lis-1 activity is required in the brain to ameliorate TBI outcomes through effects on axonal transport, microtubule stability, and other microtubule proteins, such as tau, implicated in chronic traumatic encephalopathy, a TBI-associated neurodegenerative disease in humans.
Cognitive Frailty and Functional Disability Among Community-Dwelling Older Adults: A Systematic Review
Authors: Tang Kar Foong , Teh Pei-Lee , Lee Shaun Wen Huey 
Published: January 2023

AbstractBackground and ObjectivesThis review aimed to summarize the association between cognitive frailty (presence of frailty and cognitive impairment) and the risk of disabilities in activities of daily living (ADL), instrumental ADL (IADL), mobility, or other functional disabilities among older adults.Research Design and MethodsPubMed, Embase, CINAHL Plus, and PsycINFO were searched from January 2001 to May 14, 2022, for observational studies that reported cognitive frailty among community-dwelling individuals aged 60 years and above. Results were narratively synthesized.ResultsEleven studies encompassing 44 798 participants were included, with a prevalence of cognitive frailty ranging from 1.4% to 39.3%. Individuals with cognitive frailty were more likely to develop disabilities in ADL and IADL compared to robust (absence of frailty and cognitive impairment) individuals. Significant disability burden and elevated risk of combined ADL/IADL disability or physical limitation among participants with cognitive frailty were reported. There was limited evidence on the association between cognitive frailty and mobility disability.Discussion and ImplicationsIndividuals with cognitive frailty were likely at higher risk of developing functional disability and incurring higher disability burden than robust individuals, but evidence remains limited for those with prefrailty with cognitive impairment. Further research on this gap and standardization of cognitive frailty assessments would facilitate comparisons across populations.PROSPERO RegistrationCRD42021232222
Mexican Federal Law for the Protection of Cultural Heritage of Indigenous and Afro-Mexican Peoples and Communities
Authors: Santamaria Hernández Esteban 
Published: January 2023

Abstract
The present work analyses the new Mexican Federal Law for the Protection of Cultural Heritage of Indigenous and Afro-Mexican Peoples and Communities (Mexican sui generis law) against the benchmarks provided by the literature specialized in traditional knowledge (TK), traditional cultural expressions (TCEs) and genetic resources (GE). Having identified the elements that should be taken into consideration by any sui generis law, the work examines the consistency between them and the newly approved Mexican statute.
Life after death: uses in practice in the fifteenth century
Authors: Hicks Michael 
Published: January 2023

Abstract
This article documents a considerable increase in the percentage of manorial lords in fifteenth-century England who had enfeoffed their lands in use (trusts). Enfeoffments to use were the principal mechanism that enabled manorial lords to resettle their lands. The recent publication of inquisitions post-mortem for 1483–5 and wills for 1479–86 reveal how uses proliferated. Long-term uses appear to have been quite rare. Panels of feoffees were diminished by deaths and were rarely replaced by new panels. The article demonstrates how the uses were employed. While evasion of feudal incidents was a prime aim, this research shows how uses enabled deceased manorial lords to spend their landed incomes for religious purposes, for the benefit of spouses, daughters and younger sons subject to their conditions, and to postpone the succession of heirs for years and even decades after the lord’s death.
No more parades? Navy Weeks, naval theatre and navalism, 1927–38
Authors: Thompson Rowan 
Published: January 2023

Abstract
Despite calls for ‘no more parades’ following the First World War, and while the period was supposedly inhospitable to militaristic and martial ceremony, ‘naval theatre’, navalism and cultural displays of militarism all enjoyed significant resonance in the popular civic ritual of interwar Britain. One of the most prominent forms of naval theatre in this period was the annual celebration of Navy Weeks. First staged at Portsmouth, then extended to Plymouth and Chatham the following year, Navy Weeks were held between 1927 and 1938 and allowed members of the public to be brought into direct touch with the work, life and routine of the Royal Navy. Instituted to aid naval charities, the event also provided a public platform for the admiralty to promote the navy for the preservation of nation and empire, as well as encouraging naval education among the British public. Navy Weeks represented a site of modernity, technological innovation and military prestige. However, the event equally promoted naval heritage, tradition and the long-standing significance of the Royal Navy to Britain’s status as a maritime nation.
Are ideas getting cheaper? The European evidence
Authors: Antonelli Cristiano , Fusillo Fabrizio 
Published: January 2023

Abstract
Recent economics of knowledge studies have highlighted the strong positive effects that the limited exhaustibility of knowledge and its cumulability exert on the recombinant generation of new technological knowledge. While existing empirical investigations primarily focus on the knowledge generation and technology production functions, the analysis of the cost of knowledge has received less attention. This paper aims to fill this gap by investigating the dynamics and determinants of patent costs in the European Union in the period 1992–2012. The analysis of patent unit costs in European countries, measured as the amount of research and development (R&D) expenditure per patent application to the European Patent Office (EPO), shows a steady decline and clear convergence toward lower levels, both in time and across countries. We find that a larger stock of patents and a higher technological variety and coherence of its composition are associated with a sharper reduction in patent costs. Our findings suggest that, in Europe, ideas have been getting cheaper.
Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults
Authors: Forte-Soto Pablo , Albayaty Muna , Brooks Dennis , Arends Rosalinda H , Tillinghast John , Aksyuk Anastasia A , Bouquet Jerome , Chen Cecil , Gebre Asfiha , Kubiak Robert J , Pilla Reddy Venkatesh , Seegobin Seth , Streicher Katie , Templeton Alison , Esser Mark T 
Published: January 2023

Abstract

Background
AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab).

Methods
This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated AZD7442 administered intramuscularly (300 mg) or intravenously (300, 1000, or 3000 mg) in healthy adults (aged 18–55 years). The primary end point was safety and tolerability. Secondary end points included pharmacokinetics and antidrug antibodies.

Results
Between 18 August and 16 October 2020, a total of 60 participants were enrolled; 50 received AZD7442, and 10 received placebo. Adverse events (all of mild or moderate intensity) occurred in 26 participants (52.0%) in the AZD7442 groups and 8 (80.0%) in the placebo group. No infusion or injection site or hypersensitivity reactions occurred. Tixagevimab and cilgavimab had mean half-lives of approximately 90 days (range, 87.0–95.3 days for tixagevimab and 79.8–­91.1 days for cilgavimab) and similar pharmacokinetic profiles over the 361-day study period. SARS-CoV-2–specific neutralizing antibody titers provided by AZD7442 were maintained above those in plasma from convalescent patients with coronavirus disease 2019 (COVID-19).

Conclusions
AZD7442 was well tolerated in healthy adults, showing a favorable safety profile across all doses. Depending on the SARS-CoV-2 variant, pharmacokinetic analyses suggest the AZD7442 could offer protection for ≥6 months against symptomatic COVID-19 after a single 300-mg intramuscular administration.

Clinical trials registration
NCT04507256.
Defining Variability in Evaluation and Management of Children with Chronic Osteomyelitis
Authors: Moorthy Ganga S , Boutzoukas Angelique E , Benjamin Daniel K , Polgreen Philip M , Beekmann Susan E , Bradley John S , Dehority Walter 
Published: January 2023

Abstract
Pediatric chronic osteomyelitis is a rare, debilitating condition lacking management guidelines. In a national survey of 162 pediatric infectious disease physicians through the Emerging Infections Network, tremendous variability in diagnostic approaches and management was noted, highlighting a need for a prospective study to better define the spectrum of pathogens and disease.