bluuebunny/crossref_metadata_2025 huggingface dataset:
Ebola Virus–Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort
Authors: Bond Nell G , Shore Kayla R , Engel Emily J , Coonan Erin E , Al-Hasan Foday , Gbakie Michael A , Kamara Fatima K , Kanneh Lansana , Momoh Mambu , Kanneh Ibrahim M , Sandi John D , Elliott Debra , Ficenec Samuel C , Smira Ashley R , Fischer William A , Wohl David A , Robinson James E , Shaffer Jeffrey G , Garry Robert F , Samuels Robert J , Grant Donald S , Schieffelin John S
Published: May 2024

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013–2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms—ophthalmologic and auditory—are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody.
Mapping model between lateral responses of bridges under random traffic loads based on data-driven approach
Authors: Yang Gan , Chen Shizhi , Wang Junfeng , Zhang Shuying
Published: May 2024

The lateral distribution characteristic of a bridge is one of the important features reflecting its in-service state. Conventional deterministic indicators often struggle to consider this time-varying feature. In this study, a data-driven approach is employed to establish the mapping model among responses at the different lateral positions using the eXtreme Gradient Boosting model optimized by the Bayesian optimization algorithm. The proposed method is validated based on both data from a bridge health monitoring system equipped on an actual bridge and data from numerical simulation. At different lateral positions of the actual bridge, the overall coefficient of determination (R2) of the strain response mapped by the model is above 0.991, and the overall root mean squared error (RMSE) of the strain response mapped by the model are below 1.159 με. The numerical simulation method is used to consider a variety of working conditions with different road surface roughness and different traffic densities. Under different working conditions, the overall R2 of the deflection response mapped by the model is still above 0.961, and the overall RMSE of the deflection response mapped by the model is below 0.249 mm. These indicate that the proposed model can consider time-varying mapping relationships among responses at different lateral positions, and has good accuracy and applicability.
Antibiotic utilization patterns in Tanzania: a retrospective longitudinal study comparing pre- and intra-COVID-19 pandemic era using Tanzania Medicines and Medical Devices Authority data
Authors: Sangeda Raphael Z , William Sahani M , Masatu Faustine C , Bitegeko Adonis , Mwalwisi Yonah H , Nkiligi Emmanuel A , Horumpende Pius G , Fimbo Adam M
Published: May 2024

Background

Antimicrobial resistance (AMR) is a growing public health concern globally, and misuse of antibiotics is a major contributor.

Objective

This study investigated antibiotic utilization patterns before and during the COVID-19 pandemic in Tanzania using data from the Tanzania Medicines and Medical Devices Authority (TMDA).

Methods

This retrospective longitudinal study analysed secondary data. The study compared antibiotics consumption in defined daily doses per 1000 inhabitants per day (DID) in two distinct eras: 2018–2019 as the pre-COVID-19 era and 2020–2021 as the intra-COVID-19 era. A sample t-test was conducted using Statistical Package for the Social Sciences.

Results

The study analysed 10 614 records and found an overall increase in antibiotics consumption from 2018 to 2021. We found that the consumption was 61.24 DID in the intra-COVID-19 era and 50.32 DID in the pre-COVID-19 era. Levofloxacin had the highest percentage increase in use, with a 700% increase in DID during the intra-COVID-19 era. Azithromycin had a 163.79% increase, while cefotaxime had a 600% increase. By contrast, some antibiotics exhibited a decrease in usage during the intra-COVID-19 era, such as nalidixic acid, which had a 100% decrease, and cefpodoxime, which had a 66.67% decrease.

Conclusions

Increased antibiotic consumption during the COVID-19 pandemic highlights the importance of implementing effective antimicrobial stewardship strategies to prevent AMR, especially during pandemics.
Organ Donation by the Imminently Dead: Addressing the Organ Shortage and the Dead Donor Rule
Authors: Chen Sarah , Sade Robert M , Entwistle John W
Published: May 2024

The dead donor rule (DDR) has facilitated the saving of hundreds of thousands of lives. Recent advances in heart donation, however, have exposed how DDR has limited donation of all organs. We propose advancing the moment in the dying process at which death can be determined to increase substantially the supply of organs for transplantation. We justify this approach by identifying certain flaws in the Uniform Determination of Death Act and proposing a modification of that law that permits earlier procurement of healthier organs in greater numbers.
A positive correlation of serum SFRP1 levels with the risk of developing type 2 diabetes mellitus: a case-control study
Authors: Alhilfi Ahmed Salim Najm , Afrisham Reza , Sefidan Alireza Monadi , Fadaei Reza , Moradi Nariman , Saed Lotfollah , Einollahi Nahid
Published: May 2024

Objective

Secreted frizzled-related protein 1 (SFRP1) is an adipokine whose production is significantly altered in metabolic disorders. Considering the relationship between dysfunction of Wnt/β-catenin signaling and metabolic disorders as well as the inhibitory effects of SFRP1 on this signaling pathway, the present work aimed to investigate the correlation between serum SFRP1 levels and type 2 diabetes mellitus (T2DM) and its developing risk factors for the first time.

Methods

This case-control study measured serum levels of SFRP1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin, and fasting insulin using enzyme-linked immunosorbent assay kits in 80 T2DM patients and 80 healthy individuals. Biochemical parameters were determined using the AutoAnalyzer instrument.

Results

The T2DM group had higher levels of SFRP1 compared with the controls (146.8100 ± 43.61416 vs 81.9531 ± 32.78545 pg/mL; P < .001). There was a positive correlation between SFRP1 and insulin (r = 0.327, P = .003), TNF-α (r = 0.420, P < .001) as well as homeostatic model assessment for insulin resistance (r = 0.328, P = .003) in the T2DM group. In addition, 10-unit changes in SFRP1 levels showed the risk of T2DM in both the unadjusted (odds ratio [OR] [95% CI] = 1.564 [1.359-1.800]) and adjusted models accounting for age, gender, and body mass index (OR [95% CI] = 1.564 [1.361-1.799]; P < .001). A cut-off value of SFRP1 (105.83 pg/mL) was identified to distinguish between the T2DM patients and the healthy subjects, with sensitivity of 75.0% and specificity of 80.0%.

Conclusion

According to our research, there was a significant and positive link between the amount of SFRP1 and the likelihood of developing T2DM as well as the related factors like insulin resistance index and TNF-α. These results indicated that SFRP1 might have a potential role in the development of T2DM.
Impact of culture medium on the interpretation of qRT-PCR data in HepG2 incubated with lactobacilli
Authors: Nováková Mária , Vyletelová Veronika , Hlubinová Barbora , Kiňová Sepová Hana , Pašková Ľudmila
Published: May 2024

Recently, an increasing number of studies have investigated the mechanism of action of lactobacilli in the treatment of non-alcoholic fatty liver disease. Using four computational tools (NormFinder, geNorm, Delta Ct, and BestKeeper), six potential reference genes (RGs) were analyzed in the human liver cell line HepG2 cultivated 24 h in the presence of two strains of heat-killed lactobacilli, Limosilactobacillus reuteri E and Lactiplantibacillus plantarum KG4, respectively, in different cultivation media [Dulbecco´s Modified Eagle´s Medium (DMEM) high glucose or Roswell Park Memorial Institute (RPMI)]. The analysis revealed that the suitability of RG was similar between the two lactobacilli but quite different between the two media. The commonly used RGs, 18S rRNA and glyceraldehyde-3-phosphate dehydrogenase were the most unstable in DMEM high glucose. Normalization of the mRNA expression of the target gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) to different RGs resulted in different expression profiles. This demonstrates that validation of candidate RGs under specific experimental conditions is crucial for the correct interpretation of quantitative polymerase chain reaction data. In addition, the choice of media has a profound impact on the effect of lactobacilli on lipogenesis at the gene expression level, as shown by the transcription factor SREBP-1c.
Dynamic superiorities in Defeasible Logic
Authors: Olivieri Francesco
Published: May 2024

In many logical rule-based systems, it often happens that opposite statements can be concluded, hence superiorities (or priorities) among rules are needed to solve such conflicts. Since the specific circumstances describing the scenario at hand determine which rules may apply, we thus need a mechanism able to compute such superiorities dynamically, case-by-case. We formalise a non-monotonic logic able to dynamically compute superiorities over rules. Finally, we advance efficient algorithms to compute the (positive and negative) conclusions of such theories, and prove their computational properties.
AggreProt: a web server for predicting and engineering aggregation prone regions in proteins
Authors: Planas-Iglesias Joan , Borko Simeon , Swiatkowski Jan , Elias Matej , Havlasek Martin , Salamon Ondrej , Grakova Ekaterina , Kunka Antonín , Martinovic Tomas , Damborsky Jiri , Martinovic Jan , Bednar David
Published: May 2024

Recombinant proteins play pivotal roles in numerous applications including industrial biocatalysts or therapeutics. Despite the recent progress in computational protein structure prediction, protein solubility and reduced aggregation propensity remain challenging attributes to design. Identification of aggregation-prone regions is essential for understanding misfolding diseases or designing efficient protein-based technologies, and as such has a great socio-economic impact. Here, we introduce AggreProt, a user-friendly webserver that automatically exploits an ensemble of deep neural networks to predict aggregation-prone regions (APRs) in protein sequences. Trained on experimentally evaluated hexapeptides, AggreProt compares to or outperforms state-of-the-art algorithms on two independent benchmark datasets. The server provides per-residue aggregation profiles along with information on solvent accessibility and transmembrane propensity within an intuitive interface with interactive sequence and structure viewers for comprehensive analysis. We demonstrate AggreProt efficacy in predicting differential aggregation behaviours in proteins on several use cases, which emphasize its potential for guiding protein engineering strategies towards decreased aggregation propensity and improved solubility. The webserver is freely available and accessible at https://loschmidt.chemi.muni.cz/aggreprot/.
Deep DNAshape webserver: prediction and real-time visualization of DNA shape considering extendedk-mers
Authors: Li Jinsen , Rohs Remo
Published: May 2024

Sequence-dependent DNA shape plays an important role in understanding protein–DNA binding mechanisms. High-throughput prediction of DNA shape features has become a valuable tool in the field of protein–DNA recognition, transcription factor–DNA binding specificity, and gene regulation. However, our widely used webserver, DNAshape, relies on statistically summarized pentamer query tables to query DNA shape features. These query tables do not consider flanking regions longer than two base pairs, and acquiring a query table for hexamers or higher-order k-mers is currently still unrealistic due to limitations in achieving sufficient statistical coverage in molecular simulations or structural biology experiments. A recent deep-learning method, Deep DNAshape, can predict DNA shape features at the core of a DNA fragment considering flanking regions of up to seven base pairs, trained on limited simulation data. However, Deep DNAshape is rather complicated to install, and it must run locally compared to the pentamer-based DNAshape webserver, creating a barrier for users. Here, we present the Deep DNAshape webserver, which has the benefits of both methods while being accurate, fast, and accessible to all users. Additional improvements of the webserver include the detection of user input in real time, the ability of interactive visualization tools and different modes of analyses. URL: https://deepdnashape.usc.edu
Survey Data and Subjective Beliefs in Business Cycle Models
Authors: Bhandari Anmol , Borovička Jaroslav , Ho Paul
Published: May 2024

This paper develops a theory of subjective beliefs that departs from rational expectations, and shows that biases in household beliefs have quantitatively large effects on macroeconomic aggregates. The departures are formalized using model-consistent notions of pessimism and optimism which are supported by extensive time-series and cross-sectional evidence from household surveys. The role subjective beliefs play in aggregate fluctuations is quantified in a business cycle model with goods and labour market frictions. Consistent with the survey evidence, an increase in pessimism generates upward biases in unemployment and inflation forecasts and lowers economic activity. The underlying belief distortions reduce aggregate demand and propagate through frictional goods and labour markets. As a by-product of the analysis, solution techniques that preserve the effects of time-varying belief distortions in the class of linear solutions are developed.
Matrotrophy and polyandry partially regulate postcopulatory mechanisms and sexual selection in a bimodal viviparous salamander
Authors: Alarcón-Ríos Lucía , Velo-Antón Guillermo
Published: May 2024

The evolution of matrotrophic viviparity creates new scenarios within which evolutionary processes can operate, including postcopulatory events, family conflicts, and selective processes, which are expected to intensify with polyandry. We evaluated the effect of matrotrophic viviparity and polyandry on the reproductive output and offspring fitness of a bimodal reproductive vertebrate, the fire salamander (Salamandra salamandra), which presents two forms of viviparity: larviparity (i.e. females deliver many aquatic larvae) and pueriparity (i.e. females deliver a few terrestrial juveniles). Polyandry is present in both strategies, but matrotrophy only occurs in pueriparity. Analyses of paternity and offspring life-history traits in 18 pueriparous and 13 larviparous mother–offspring arrays suggest the presence of sibling conflicts in pueriparous salamanders, especially with polyandry. However, these postcopulatory processes did not increase reproductive skew in the pueriparous strategy compared to the larviparous one or lead to fitness differences across sires within a clutch, suggesting other selective processes operating earlier in the reproductive sequence. Observed male–female pairs were found to be genetically more similar than other potential pairings, although no relationship between males’ genetic traits and reproductive success was detected. This work advances our understanding of how sibling conflicts and sexual selection affect the evolution of viviparous matrotrophy and mating strategies.
Postoperative Delirium Screening Characteristics in Pediatric Intestinal, Liver, and Renal Transplant Recipients: Single-Center Retrospective Cohort Study*
Authors: Patel Sagar , Pfeiffer Brent , Haddock De Jesus Rosa , Garcia Jennifer , Chandar Jayanthi , Alladin Amanda
Published: May 2024

OBJECTIVES:

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD).

DESIGN:

Retrospective analysis of a single-center cohort, 2016–2022.

SETTING:

Twenty-four-bed PICU in a high-volume transplant center.

PATIENTS:

All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022.

MEASUREMENTS AND MAIN RESULTS:

We identified 211 pediatric transplant recipients: intestinal (n= 36), liver (n= 78), and renal (n= 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen (p< 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms (p< 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively).

CONCLUSIONS:

In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.
Optimal Diagnostic and Treatment Practices for Facial Dysostosis Syndromes: A Clinical Consensus Statement Among European Experts
Authors: Van Roey Victor L. , Irvine Willemijn F.E. ,   All Expert Panel Members of the Facial Dysostosis Consensus Statement
Published: May 2024

Facial dysostosis syndromes (FDS) are rare congenital conditions impacting facial development, often leading to diverse craniofacial abnormalities. This study addresses the scarcity of evidence on these syndromes about optimal diagnostic and treatment practices. To overcome this scarcity, European experts from ERN CRANIO collaborated to develop a clinical consensus statement through the Delphi consensus method. A systematic search of Embase, MEDLINE/PubMed, Cochrane, and Web of Science databases was conducted until February 2023. The quality of evidence was evaluated using various tools depending on the study design. Statements were subsequently formed based on literature and expert opinion, followed by a Delphi process with expert health care providers and patient representatives. In total, 92 experts from various specialties and three patient representatives were involved in the Delphi process. Over 3 voting rounds, consensus was achieved on 92 (46.9%), 58 (59.2%), and 19 (70.4%) statements, respectively. These statements cover the topics of general care; craniofacial reconstruction; the eyes and lacrimal system; upper airway management; genetics; hearing; speech; growth, feeding, and swallowing; dental treatment and orthodontics; extracranial anomalies; and psychology and cognition. The current clinical consensus statement provides valuable insights into optimal diagnostic and treatment practices and identifies key research opportunities for FDS. This consensus statement represents a significant advancement in FDS care, underlining the commitment of health care professionals to improve the understanding and management of these rare syndromes in Europe.
A Randomized Controlled Trial of the Implementation of BREASTChoice, a Multilevel Breast Reconstruction Decision Support Tool With Personalized Risk Prediction
Authors: Politi Mary C. , Myckatyn Terence M. , Cooksey Krista , Olsen Margaret A. , Smith Rachel M. , Foraker Randi , Parrish Katelyn , Phommasathit Crystal , Brock Guy , Janse Sarah , Guglielmino Janine , Peled Anne , Mills Paul B. , Jackson Sherrill , Lee Clara N.
Published: May 2024

Objective:

To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness.

Background:

BREASTChoice, is a multilevel decision tool that (1) educates patients about breast reconstruction, (2) estimates personalized risk of complications, (3) clarifies patient preferences, and (4) informs clinicians about patients’ risk and preferences.

Methods:

A multisite randomized controlled trial enrolled adult women with stage 0 to III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses.

Results:

A total of 23/25 eligible clinicians enrolled. A total of 369/761 (48%) contacted patients enrolled and were randomized. Patients’ average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs 67.4, P=0.08; PP: mean 71.4 vs 67.4, P=0.03), especially when stratified by site (ITT: P=0.04, PP: P=0.01), age (ITT: P=0.04, PP: P=0.02), and race (ITT: P=0.04, PP: P=0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability.

Conclusions:

BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.
The formal demography of kinship VI: Demographic stochasticity, variance, and covariance in the kinship network
Authors: Caswell Hal
Published: May 2024

Background

The matrix model for kinship networks includes many demographic processes but is deterministic, projecting expected values of age-stage distributions of kin. It provides no information on (co)variances. Because kin populations are small, demographic stochasticity is expected to create appreciable inter-individual variation.

Objectives

To develop a stochastic kinship model to project (co)variances of kin age-stage distributions, and functions thereof, including demographic stochasticity.

Methods

Kin populations are described by multitype branching processes. Means and covariances are projected using matrices that are generalizations of the deterministic model. The analysis requires only an age-specific mortality and fertility schedule. Both linear and non-linear transformations of the kin age distribution are treated as outputs accompanying the state equations.

Results

The stochastic model follows the same mathematical framework as the deterministic model, modified to treat initial conditions as mixture distributions. Variances in numbers of most kin are compatible with Poisson distributions. Variances for parents and ancestors are compatible with binomial distributions. Prediction intervals are provided, as are probabilities of having at least one or two kin of each type. Prevalences of conditions are treated either as fixed or random proportions. Dependency ratios and their variances are calculated for any desired group of kin types. An example compares Japan under 1947 rates (high mortality, high fertility) and 2019 rates (low mortality, low fertility).

Contribution

Previous versions of the kinship model have acknowledged their limitation to expected values. That limitation is now removed; means and variances are easily and quickly calculated with minimal modification of code.
A generative foundation model for antibody sequence understanding
Authors: Barton Justin , Gaspariunas Aretas , Yadin David A. , Dias Jorge , Nice Francesca L. , Minns Danielle H. , Snudden Olivia , Povall Chelsea , Valle Tomas Sara , Dobson Harry , Farmery James H. R. , Leem Jinwoo , Galson Jacob D.
Published: May 2024

Here we introduce FAbCon, a generative antibody-specific language model comprising 2.4 billion parameters. A commonly accepted wisdom in developing large language models is that increasing model scale will translate to higher performance on downstream tasks. Starting from a 144-million parameter setup, we show that progressively larger models achieve greater accuracy in predicting antigen binding and can also be used to design new antibodies with good predicted developability potential. FAbCon is available onhuggingface.co/alchemab.
The maternal vGluT2 and embryonic mGluR3 signaling relay system controls offspring wing dimorphism in pea aphid
Authors: Yuan Yiyang , Wang Yanyan , Ye Wanwan , Xie Liqiang , Yuan Erliang , Guo Huijuan , Wang Shifan , Dong Fang , Zhu-Salzman Keyan , Ge Feng , Sun Yucheng
Published: May 2024

Transgenerational phenotypic plasticity (TPP) refers to the phenomenon that environmental conditions experienced by one generation can influence the phenotype of subsequent generations to adapt to the environment without modification of their DNA sequences. Aphid wing dimorphism is a textbook example of TPP by which a maternal aphid perceives the environmental cues to decide the wing morph of her offspring. However, the signaling mechanism from mother to daughter remains unclear. In this study, we showed that the population density and physical contact caused high proportion of winged offspring in the pea aphidAcyrthosiphon pisum. Itsvesicular glutamate transporter 2(ApvGluT2) andmetabotropic glutamate receptor 3(ApmGluR3) were identified by tissue-specific RNA-seq as differentially expressed genes in the head and embryo respectively between solitary and more densely housed maternal aphids. Elevated expression of brainApvGluT2and embryonicApmGluR3led to increases in the winged proportion. Knockdown of either gene inhibited phosphorylation of ApFoxO in embryos. Furthermore, EMSA showed that dephosphorylated ApFoxO directly bound to the promotor ofhedgehog(ApHh), a morphogen gene for wing development, to repress its transcription in stage 20 embryos, causing a lower winged proportion. Our results demonstrated that brainvGluT2and embryonicmGluR3coordinately relayed the maternal physical contact signals and control wing development in offspring, showcasing a novel regulatory mechanism underlying physical contact-dependent, transgenerational wing dimorphism in aphids.
Genesis: A modular protein language modelling approach to immunogenicity prediction
Authors: O’Brien Hugh , Salm Max , Morton Laura T , Szukszto Maciej , O’Farrell Felix , Boulton Charlotte , King Laurence , Bola Supreet Kaur , Becker Pablo , Craig Andrew , Nielsen Morten , Samuels Yardena , Swanton Charles , Mansour Marc R , Hadrup Sine Reker , Quezada Sergio A
Published: May 2024

Neoantigen immunogenicity prediction is a highly challenging problem in the development of personalised medicines. Low reactivity rates in called neoantigens result in a difficult prediction scenario with limited training datasets. Here we describe Genesis, a modular protein language modelling approach to immunogenicity prediction for CD8+ reactive epitopes. Genesis comprises of a pMHC encoding module trained on three pMHC prediction tasks, an optional TCR encoding module and a set of context specific immunogenicity prediction head modules. Compared with state-of-the-art models for each task, Genesis’ encoding module performs comparably or better on pMHC binding affinity, eluted ligand prediction and stability tasks. Genesis outperforms all compared models on pMHC immunogenicity prediction (Area under the receiver operating characteristic curve=0.619, average precision: 0.514), with a 7% increase in average precision compared to the next best model. Genesis shows further improved performance on immunogenicity prediction with the integration of TCR context information. Genesis performance is further analysed for interpretability, which locates areas of weakness found across existing immunogenicity models and highlight possible biases in public datasets.
Performance effects from different shutdown methods of three electrode materials for the power-to-gas application with electromethanogenesis
Authors: Rohbohm Nils , Lang Maren , Erben Johannes , Gemeinhardt Kurt , Patel Nitant , Ilic Ivan K. , Hafenbradl Doris , Rodrigo Quejigo Jose , Angenent Largus T.
Published: May 2024

Industrial applications of microbial electrochemical systems will require regular maintenance shutdowns, involving inspections and component replacements to extend the lifespan of the system. Here, we examined the impact of such shutdowns on the performance of three electrode materials (i.e., platinized titanium, graphite, and nickel) as cathodes in a microbial electrochemical system that would be used for electromethanogenesis in power-to-gas applications. We focused on methane (CH4) production from hydrogen (H2) and carbon dioxide (CO2) usingMethanothermobacter thermautotrophicus. We showed that the platinized titanium cathode resulted in high volumetric CH4production rates and Coulombic efficiencies. Using a graphite cathode would be more cost-effective than using the platinized titanium cathode in microbial electrochemical systems but showed an inferior performance. The microbial electrochemical system with the nickel cathode showed improvements compared to the graphite cathode. Additionally, this system with a nickel cathode demonstrated the fastest recovery during a shutdown experiment compared to the other two cathodes. Fluctuations in pH and nickel concentrations in the catholyte during power interruptions affected CH4production recovery in the system with the nickel cathode. This research enhances understanding of the integration of biological and electrochemical processes in microbial electrochemical systems, providing insights into electrode selection and operating strategies for effective and sustainable CH4production.
GTP cyclohydrolase II(gch2) and axanthism in ball pythons: a new vertebrate model for pterin-based pigmentation
Authors: Garcia-Elfring Alan , Roffey Heather L. , Abergas Jaren M. , Hendry Andrew P. , Barrett Rowan D. H.
Published: May 2024

Pterin pigments are responsible for many of the bright colours observed across the animal kingdom. However, unlike melanin, the genetics of pterin-based pigmentation has received relatively little attention in animal colouration studies. Here, we investigate a lineage of axanthic ball pythons (Python regius) found in captivity as a model system to study pterin pigmentation in vertebrates. By crowdsourcing shed skin samples from commercial breeders and applying a case-control study design, we utilized whole-genome pool sequencing (pool-seq) and variant annotation. We identified a premature stop codon in the geneGTP cyclohydrolase II(gch2), which is associated with the axanthic phenotype. GCH2 catalyzes the first rate-limiting step in riboflavin biosynthesis. This study provides the first identification of an axanthism-associated gene in vertebrates and highlights the utility of ball pythons as a model to study pterin-based pigmentation.
Effect of senolytic drugs in young female mice chemically induced to estropause
Authors: Ávila Bianca M , Zanini Bianka M , Luduvico Karina P , Oliveira Thais L , Hense Jéssica D , Garcia Driele N , Prosczek Juliane , Stefanello Francielle M , da Cruz Pedro H , Giongo Janice L , Vaucher Rodrigo A , Mason Jeffrey B , Masternak Michal M , Schneider Augusto
Published: May 2024

Aims

This study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs.

Main methods

Estropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D+Q) or fisetin were given by oral gavage once a month from five to 11 months of age.

Key findings

VCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues, but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause.

Significance

Overall, the findings suggest that estropause leads to minor metabolic changes in young females, and senolytics had no protective effects despite increased ovarian senescence.
The frequency dependence of prestin-mediated fast electromotility for mammalian cochlear amplification
Authors: Takahashi Satoe , Zhou Yingjie , Cheatham Mary Ann , Homma Kazuaki
Published: May 2024

Prestin’s voltage-driven motor activity confers sound-elicited somatic electromotility in auditory outer hair cells (OHCs) and is essential for the exquisite sensitivity and frequency selectivity of mammalian hearing. Lack of prestin results in hearing threshold shifts across frequency, supporting the causal association of variants in the prestin-coding gene,SLC26A5, with human hearing loss, DFNB61. However, cochlear function can tolerate reductions in prestin-mediated OHC electromotility. We found that two deafness-associated prestin variants, p.A100T and p.P119S, do not deprive prestin of its fast motor function but significantly reduce membrane expression, leading to large reductions in OHC electromotility that were only ∼30% of wildtype (WT). Mice harboring these missense variants suffered congenital hearing loss that was worse at high frequencies; however, they retained WT-like auditory brainstem response thresholds at 8 kHz, which is processed at the apex of the mouse cochlea. This observation suggests the increasing importance of prestin-driven cochlear amplification at higher frequencies relevant to mammalian hearing. The observation also suggests the promising clinical possibility that small enhancements of OHC electromotility could significantly ameliorate DFNB61 hearing loss in human patients.

SIGNIFICANCE

Prestin is abundantly expressed in the auditory outer hair cells and is essential for normal cochlear operation. Hence, reduction of prestin expression is often taken as indicative of reduced cochlear function in diseased or aged ears. However, this assumption overlooks the fact that cochlear function can tolerate large reductions in prestin motor activity. DFNB61 mouse models generated and characterized in this study provide an opportunity to gauge the amount of prestin motor activity needed to sustain normal hearing sensitivity. This knowledge is crucial not only for understanding the pathogenic roles of deafness-associated variants that impair OHC electromotility but also for unraveling how prestin contributes to cochlear amplification.
Cross-generational plasticity in Atlantic silversides (Menidia menidia) under the combined effects of hypoxia and acidification
Authors: Murray Christopher S. , Mays Ayanna , Long Matthew , Aluru Neelakanteswar
Published: May 2024

We investigated the potential for cross-generational plasticity to influence how offspring respond to hypoxia and ocean acidification (hereafter HypOA) in the coastal forage fish Atlantic silverside (Menidia menidia). Mature wild silversides were treated with a control [dissolved oxygen (DO):100% air saturation (a.s.) /pCO2: 650 µatm] or HypOA conditions [DO: 40% a.s. /pCO2: 2300 µatm] for 10 days prior to spawning. Their offspring were reared under both treatments in factorial experimental design. Parental acclimation to HypOA altered several offspring traits, including increased embryo survival under HypOA and an overall reduction in post-hatch growth rate. Offspring from HypOA-treated parents that were reared under control conditions had larger eyes across the developmental period. When compared against the overall control group, larvae directly exposed to HypOA exhibited 2,416 differentially expressed transcripts (DETs). Although most of these DETs were specific to individual parental treatments, the most enriched Gene Ontology terms were conserved across parental treatments, including terms related to neurotransmitter secretion, nervous system development, axon pathfinding, calcium channel activity, proteolysis, and extracellular matrix organization. Larvae from HypOA-treated parents that were reared under control conditions exhibited a shift in constitutive gene expression similar to that seen in larvae directly exposed to HypOA. This highly consistent finding indicates that parental acclimation before fertilization promotes the transcriptional frontloading of genes in offspring. This effect may have primed regulatory functions in offspring that sense and respond to low DO and elevatedpCO2conditions. Though, our results suggest that this altered developmental phenotype may have some negative fitness consequences for offspring.
CosGeneGate Selects Multi-functional and Credible Biomarkers for Single-cell Analysis
Authors: Liu Tianyu , Long Wenxin , Cao Zhiyuan , Wang Yuge , He Chuan Hua , Zhang Le , Strittmatter Stephen M. , Zhao Hongyu
Published: May 2024

Selecting representative genes or marker genes to distinguish cell types is an important task in single-cell sequencing analysis. Although many methods have been proposed to select marker genes, the genes selected may have redundancy and/or do not show cell-type-specific expression patterns to distinguish cell types. Here we present a novel model, named CosGeneGate, to select marker genes for more effective marker selections. CosGeneGate is inspired by combining the advantages of selecting marker genes based on both cell-type classification accuracy and marker gene specific expression patterns. We demonstrate the better performance of the marker genes selected by CosGeneGate for various downstream analyses than the existing methods with both public datasets and newly sequenced datasets. The non-redundant marker genes identified by CosGeneGate for major cell types and tissues in human can be found at the website as follows:https://github.com/VivLon/CosGeneGate/blob/main/markergene list.xlsx.
Causal network perturbation analysis identifies known and novel type-2 diabetes driver genes
Authors: Zhao Yue , Ansarullah  , Kumar Parveen , Mahoney J. Matthew , He Hao , Baker Candice , George Joshy , Li Sheng
Published: May 2024

The molecular pathogenesis of diabetes is multifactorial, involving genetic predisposition and environmental factors that are not yet fully understood. However, pancreatic β-cell failure remains among the primary reasons underlying the progression of type-2 diabetes (T2D) making targeting β-cell dysfunction an attractive pathway for diabetes treatment. To identify genetic contributors to β-cell dysfunction, we investigated single-cell gene expression changes in β-cells from healthy (C57BL/6J) and diabetic (NZO/HlLtJ) mice fed with normal or high-fat, high-sugar diet (HFHS). Our study presents an innovative integration of the causal network perturbation assessment (ssNPA) framework with meta- cell transcriptome analysis to explore the genetic underpinnings of type-2 diabetes (T2D). By generating a reference causal network andin silicoperturbation, we identified novel genes implicated in T2D and validated our candidates using the Knockout Mouse Phenotyping (KOMP) Project database.
Multi-region Multiomic Random Forest Toxicity Modeling of Radiation Pneumonitis
Authors: Nair Saurabh S. , Salazar Ramon M. , Leone Alexandra O. , Xu Ting , Liao Zhongxing , Court Laurence E. , Niedzielski Joshua S.
Published: May 2024

Purpose

Radiation pneumonitis (RP) is a major dose-limiting toxicity resulting from non-small-cell lung cancer (NSCLC) radiotherapy. Multiomic features (radiomics and dosiomics) could provide additional predictive information as compared to traditionally used clinical and dose-volume histogram (DVH) parameters. We aimed to investigate the utility of multiomic features to improve RP toxicity models.

Methods

Out of 329 NSCLC patients considered, 85 patients (25.84%) were found to have toxicity ≥ grade 2 RP per CTCAE v5.0. A total of 422 radiomic and dosiomic features were extracted. Four toxicity prediction model types were created using clinical factors together with respective features from one of the following groups: (a) DVH (base model), (b) whole lung radiomics and dosiomics (WL-RD), (c) multi-region radiomics and dosiomics (MR - RD) and (d) multi-region DVH, radiomics and dosiomics (MR-DVHRD). Toxicity models were created using a random forest classifier with a Monte Carlo cross-validation approach of 100 iterations, and a training/test split of 80%/20%, respectively. Model predictive performance was evaluated by area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPRC).

Results

The AUC and AUPRC values (mean ± standard deviation) for the 4 model types were 0.81±0.04/0.70±0.06 (base model), 0.82±0.05/0.73±0.08 (WL-RD, p<0.05), 0.83±0.06/0.75±0.08 (MR–RD, p<0.05), and 0.82±0.05/0.72±0.08 (MR-DVHRD, p<0.05), respectively, wherein a paired test compared the performance metrics of omic models with the base model built on each iteration of cross0020validation.

Conclusions

All multiomic model types outperformed the base DVH model. MR-RD model had the best performance among all model types.
Integration of Electrochemical Sensing and Machine Learning to Detect Tuberculosis via Methyl Nicotinate in Patient Breath
Authors: Jeppson Mary A. , Rasmussen Zachary , Castro Robert , Nalugwa Talemwa , Kisakye Esther , Mangeni Wilson , Andama Alfred , Jaganath Devan , Cattamanchi Adithya , Mohanty Swomitra K.
Published: May 2024

Tuberculosis (TB) remains a significant global health issue; making early, accurate, and inexpensive point-of-care detection critical for effective treatment. This paper presents a clinical demonstration of an electrochemical sensor that detects methyl-nicotinate (MN), a volatile organic biomarker associated with active pulmonary tuberculosis. The sensor was initially tested on a patient cohort comprised of 57 adults in Kampala, Uganda, of whom 42 were microbiologically confirmed TB-positive and 15 TB-negative. The sensor employed a copper(II) liquid metal salt solution with a square wave voltammetry method tailored for MN detection using commercially available screen-printed electrodes. An exploratory machine learning analysis was performed using XGBOOST. Utilizing this approach, the sensor was 78% accurate with 71% sensitivity and 100% specificity. These initial results suggest the sensing methodology is effective in identifying TB from complex breath samples, providing a promising tool for non-invasive and rapid TB detection in clinical settings.
Stem Cell Therapies for Cartilage Defects: A Protocol for Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Sharma Siddhartha , Dadra Ankit , Kumar Prasoon , Ashima  , Gohil Riddhi , Patel Sandeep , Dhillon Mandeep S.
Published: May 2024

Background

Cartilage defects, arising from trauma, degenerative conditions, or genetic factors, pose significant challenges in orthopedic practice due to the limited regenerative capacity of articular cartilage. Traditional treatments like physical therapy and pain management often fail to restore tissue effectively. Recently, stem cell therapy has emerged as a promising regenerative medicine approach, potentially enhancing cartilage repair and improving joint function. This review investigates the efficacy of stem cell therapy in treating cartilage defects, focusing on pain reduction, disability, safety, quality of life, and cartilage regeneration compared to conventional care.

Methods

A PRISMA compliant systematic review and meta-analysis will be conducted by searching the PubMed, Embase, Web of Science, and Cochrane CENTRAL databases. Studies evaluating adult patients with cartilage defects of any etiology treated with various stem cell therapies will be included. Randomized controlled trials (RCTs) reporting these outcomes will be included, while non-randomized trials, non-comparative studies, non-human studies, and non-English publications will be excluded. Outcome measures will include validated functional outcome scores, rates of complications and adverse effects and healing of cartilage defects. Meta-analysis will be conducted for studies with similar interventions and outcomes, using fixed or random- effects models based on heterogeneity assessed by the I2 statistic. The quality of evidence will be assessed using GRADE criteria.