bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ithildin library for efficient numerical solution of anisotropic reaction-diffusion problems in excitable media
Authors: Kabus Desmond , Cloet Marie , Zemlin Christian , Bernus Olivier , Dierckx Hans 
Published: May 2024

AbstractIthildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library’s versatility through a series of simulations in the context of the mono-domain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this paper in the name of open science.Author summaryWe present Ithildin, an open-source library for reaction-diffusion systems such as the electrical waves in cardiac tissue controlling the heart beat. We demonstrate the versatility of Ithildin by example simulations in various tissue models and geometries, from simple 2D simulations to detailed ones in ventricular geometry. Our simulations highlight key features of Ithildin, such as recording pseudo-electrograms or filament trajectories. We hope that our work will contribute to the growing understanding of cardiac electrophysiology and inform future experimental and theoretical studies.
PfHT1 controls glucose uptake in malaria parasite: molecular dynamics study in plasma membrane like environment reveals ligand induced conformational changes trigger closed conformation and alters binding pocket geometry
Authors: Ganguly Manisha , Maitra Hriddhi , Roychowdhury Amlan , Hazra Ditipriya 
Published: May 2024

AbstractPlasmodium falciparumhexose transporter 1 protein or PfHT1 is the major glucose transporter of the parasite and indispensable for its survival at the blood stage of infection. PfHT1 transports the hexose sugar to meet the energy demand of the parasite. Studying the mechanism of transport and designing structure specific inhibitors against PfHT1 is an intelligent strategy to kill malaria parasite by starving it out because at the blood stage the sole carbon source ofPlasmodium falciparumis glucose. In this study the conformational dynamics of PfHT1 has been studied in detail in the apo and holo (inhibitor bound) form using Molecular Dynamics Simulation. Which reveals that PfHT1 undergoes ligand induced closed state if compared with the apo form. The geometry of ligand binding pocket also shifts from the apo form in the presence of inhibitors. A de novo drug designing approach based on the skeleton of leads obtained from screening nearly 4500 compounds, has produced inhibitors of PfHT1 with higher specificity and affinity. The drug screening data as well as the conformational dynamics study was validated using Molecular Dynamics Simulation platform where a near physiological atmosphere was created for PfHT1 by constructing a lipid phase (phospholipid bilayer) sandwiched between aqueous phases (mimics extracellular and cytosolic polar environment).
The effect of climate change on the spread of predicted bluetongue in Australian livestock
Authors: Al-Riyami S , Firestone SM , Eagles D , Bradhurst R , Stevenson MA 
Published: May 2024

AbstractIntroductionThe frequency of vector-borne disease in human and animal populations has increased in recent years leading to concerns that even greater increases will occur as a result of climate change, driven by changes in the geographic distribution of insect vector habitat areas. In this study we investigate the effect of climate change on the expected spread of bluetongue (a viral disease of ruminants spread byCulicoidesmidges) using the Australian Animal Disease Spread model (AADIS).MethodsEstimates of average daily temperature across Australia for 2015 were obtained from the Australian Bureau of Meteorology. Predicted average daily temperatures using the CanESM2 model (emission scenario RCP 8.5) for 2025 and 2035 at a resolution of 5 km × 5 km were obtained from the Australian Climate Futures decision-support tool, managed by CSIRO. Two study areas in Australia were selected: the first in North Queensland and the second in Northern New South Wales. A total of 24 outbreak scenarios were run: mid-summer and mid-winter incursions for each study area for 2015, 2025 and 2035 with direct movement of animals in the AADIS model disabled and enabled for each. Model results were expressed as the number bluetongue-positive herds, (herds in which at least one animal was BTV positive) at the end of each 365 day simulation period.ResultsFor North Queensland, there was little change in the median predicted number of bluetongue positive herds for mid-summer and mid-winter 2025 and 2035 incursions (compared with 2015) and a moderate increase in the variability of predicted outbreak sizes when direct animal movements were disabled. For Northern New South Wales there were moderate increases in both the predicted number of bluetongue positive herds and the variability of predicted outbreak sizes for 2025 and 2035, compared with 2015. Compared with the direct animal movement disabled scenarios, there were marked increases in the predicted number of bluetongue positive herds as a function of simulation year for North Queensland. For Northern New south Wales this trend was not as distinct, but as for the direct movement disabled scenarios, the variability of predicted outbreak sizes for the 2035 incursions were greater than the variability of predicted outbreak sizes for the 2015 incursions.ConclusionClimate change will result in a greater portion of the land area of Australia with conditions suitable forCulicoidesmidges. Our findings show that under conditions of climate change and an outbreak of virulent bluetongue in Australia, the rapid imposition of effective restrictions of animal movement will be the single most important control measure to limit further spread of disease.
PATHOGEN GROWTH AND VIRULENCE DYNAMICS DRIVE THE HOST EVOLUTION AGAINST COINFECTIONS
Authors: Seal Srijan , Basu Dipendra Nath , Ghosh Kripanjali , Ramachandran Aryan , Kutum Rintu , Shelke Triveni , Gupta Ishaan , Khan Imroze 
Published: May 2024

ABSTRACTCoinfections, or the simultaneous infection of hosts by multiple pathogens, are widespread in nature with significant negative impacts on global health. Can hosts evolve against such coinfections as effectively as they would against individual pathogens? Also, what roles do individual pathogens play during such evolution? Here, we combined theoretical models and experiments withTribolium castaneumpopulations evolving against two coinfecting bacterial pathogens, with contrasting growth and virulence dynamics, to reveal that fast-growing pathogens inflicting rapid mortality surges (i.e., fast-acting) restrict adaptive success against coinfections. While hosts rapidly evolved better survival against slow-growing bacteria causing long-lasting infections, evolution against coinfection was significantly delayed and resembled slow adaptation against fast-acting pathogens. Moreover, limited scopes of immunomodulation against fast-acting pathogens during coinfections can drive the observed adaptive patterns. Overall, we provide new insights into how adaptive dynamics and mechanistic bases against coinfections are critically regulated by individual pathogens’ growth and virulence dynamics.
SLAYER: A Computational Framework for Identifying Synthetic Lethal Interactions through Integrated Analysis of Cancer Dependencies
Authors: Cohen Ziv , Petrenko Ekaterina , Barisaac Alma Sophia , Abu-Zhayia Enas R. , Yanovich-Ben-Uriel Chen , Ayoub Nabieh , Aran Dvir 
Published: May 2024

AbstractSynthetic lethality represents a promising therapeutic approach in precision oncology, yet systematic identification of clinically relevant synthetic lethal interactions remains challenging. Here we present SLAYER (Synthetic Lethality AnalYsis for Enhanced taRgeted therapy), a computational framework that integrates cancer genomic data and genome-wide CRISPR knockout screens to identify potential synthetic lethal interactions. SLAYER employs parallel analytical approaches examining both direct mutation-dependency associations and pathway-mediated relationships across 808 cancer cell lines. Our integrative method identified 4,332 statistically significant interactions, which were refined to 142 high-confidence candidates through stringent filtering for effect size, druggability, and clinical prevalence. Systematic validation against protein interaction databases revealed a 15-fold enrichment of known associations among SLAYER predictions compared to random gene pairs. Through pathway-level analysis, we identified inhibition of the aryl hydrocarbon receptor (AhR) as potentially synthetically lethal with RB1 mutations in bladder cancer. Experimental studies demonstrated selective sensitivity to AhR inhibition in RB1-mutant versus wild-type bladder cancer cells, which probably operates through indirect pathway-mediated mechanisms rather than direct genetic interaction. In summary, by integrating mutation profiles, gene dependencies, and pathway relationships, our approach provides a resource for investigating genetic vulnerabilities across cancer types.
RANDOMIZED CONTROL STUDY TO ANALYSE THE EFFICACY BUDESONIDE NASAL DOUCHING ON ALLERGIC FUNGAL RHINOSINUSITIS
Authors: TR Sowparnika , Ramaneeshwaran  , Bhalla Ashu Seith , Madan Karan , Gupta Yashdeep , Srivastava Rupesh K , Viswanathan Ganesh Kumar , Singh Gagandeep , Thakar Alok , Kumar Rakesh , Sikka Kapil , Pachaury Shuchita Singh , Verma Hitesh 
Published: May 2024

ABSTRACTINTRODUCTIONAllergic Fungal Rhinosinusitis is a hypersensitivity against fungal antigens. Primary surgical management is complimented with medical management in preoperative and postoperative phases for better intraoperative field & to limit the recurrence. The effect of systemic steroids & itraconazole showed promising outcomes as a solo agent or in combination under preoperative status. Recent studies showed auspicious conclusions with steroid-based nasal douches. The current study aims to assess the effectiveness of medical management in combination with steroid-based nasal douches.METHODOLOGYThis prospective study will recruit 40 clinico-radiological proven cases of AFRS after ethical approval. The study population will be randomized into two groups based on a computer program. Group A will receive systemic itraconazole and steroids & Group B will receive additional budesonide nasal douching. The outcomes will be studied clinically by SNOT-22 scoring system & Meltzer nasal polyp scoring system, biochemically with absolute eosinophil counts, aspergillus specific IgE and total IgE, radiologically with Lund-Mackay system and 20-point CT scoring system after 6 weeks of initiation of the treatment.ETHICS AND DISSEMINATIONWe received an AIIMS ethical board. Ref no-AIIMSA00641 dated 21.03.24 & CTRI (Clinical Trial Registry India) acknowledgement number - REF/2024/03/081566 dated 29. 03.24. We will follow the ethical committee protocol and instructions received from reviewers.STRENGTHSAFRS is a bothersome illness both for treating doctors and patients. This study is a pilot study on a combination of past and recently proven medical therapies for AFRS.The study will generate data on new or complete medical management for AFRS.The duration of planned treatment is 6 weeks. The study will generate data for future studies where prolonged medical treatment can be planned.LIMITATIONSThis will be a single-centred study. The validation for the expected outcome will require a multicentric study.The study topic is planned for an MS student thesis so the follow-up period will be 3-6 months.
Relapse prediction in multiple myeloma patients treated with isatuximab, carfilzomib, and dexamethasone
Authors: Myklebust Even Moa , Schjesvold Fredrik , Frigessi Arnoldo , Leder Kevin , Foo Jasmine , Köhn-Luque Alvaro 
Published: May 2024

AbstractMultiple myeloma (MM) patients experience repeated cycles of treatment response and relapse, yet despite close monitoring of disease status through M protein measurements, no standard model exists for relapse prediction in MM. We investigate the feasibility of predicting relapse using a hierarchical Bayesian model of subpopulation dynamics by training and testing the model on 229 patients from the IKEMA trial.After observing between 11 and 18 treatment cycles, the model predicted relapse within six cycles with an average sensitivity between 60 and 80 %, and an average specificity between 60 and 90 %. A model of linear extrapolation is preferable when patients have been observed for less than 6 cycles, but for longer observation windows the hierarchical Bayesian model is preferred. Including available baseline and longitudinal covariate information did not improve predictive accuracy. A survival analysis showed that two model parameters separated patients into groups with significantly different PFS (p <0.001).Statement of SignificanceCurrently, no standard model exists for relapse prediction in multiple myeloma. A personalized model of M protein development could guide the frequency of follow-up measurements, reduce uncertainty for patients, and give clinicians more time to choose the best subsequent treatment for each patient. Furthermore, models that predict relapse are required to study the effect of changing treatment in advance of relapse rather than in response to it. Our work addresses this need by developing a hierarchical Bayesian model of subpopulation dynamics for prediction of future M protein values. We validate the model on a patient cohort treated with state-of-theart CD38 inhibitor therapy and show that it can accurately predict relapse within the next six treatment cycles, highlighting the promise of mathematical modeling in multiple myeloma and for personalized medicine in general.Declaration of InterestsF.S. received honorarium from Sanofi, Janssen, BMS, Oncopeptides, Abbvie, GSK, and Pfizer. The authors declare that they have no other conflicts of interest.
Explanations for higher-than-expected mortality from April 2021: a scoping review
Authors: Scott Fiona , McCartney Gerry , Walsh David , Wild Sarah , Rae David , Ramsay Julie , Donaghy Grant , Douglas Margaret 
Published: May 2024

AbstractObjectivesMany countries have continued to experience a higher-than-expected number of deaths following the peaks in mortality observed in the first year of the Covid-19 pandemic. This scoping review aims to identify the different explanations proposed for sustained higher-than-expected mortality beyond the first pandemic year.Study designScoping reviewMethodsA systematic search of databases and grey literature sources was completed to identify English-language records proposing or investigating hypotheses for higher-than-expected mortality from April 2021 onwards in (sub)populations of high-income countries. Papers focused on survival following a diagnosis or intervention were excluded. Results were summarised narratively, and existing research prioritisation frameworks were adapted and applied to identify the hypotheses proposed as highest priority for further research.ResultsSeventy eligible papers were identified. Most were opinion pieces or simply presented trends; few included investigation of suggested hypotheses. Numerous explanations for higher-than-expected mortality were proposed, with hypotheses relating to direct Covid-19 mortality, sequalae of Covid-19 infection, the health service impacts of the pandemic, wider pandemic impacts and socioeconomic factors identified as highest-priority for further research.ConclusionsThe causes of continued higher-than-expected mortality are likely to be multiple and potentially interactive. This review will help to shape research into current mortality trends, with a critical understanding of this topic essential for achieving evidence-informed policy.
Circulation of DENV-2 serotype associated with increased risk of cumulative incidence of severe dengue and dengue with warning signs: A 16-year retrospective study in Peru
Authors: Cañari-Casaño Jorge L. , Paz-Soldan Valerie A. , Lescano Andres G. , Morrison Amy C. 
Published: May 2024

AbstractBackgroundDengue poses a significant public health challenge in Peru and other endemic countries worldwide. While severe dengue is known to be associated with secondary infection at the individual level, the factors that elevate the risk of severe dengue at the population level remain poorly understood. This study leverages over 16 years of secondary data from a Peruvian dengue surveillance system to assess which type of serotype-specific circulation is associated with an increased risk of cumulative incidence of severe dengue or dengue with warning signs (SD-DWS).MethodologyThis is a retrospective analysis of secondary data using the Peruvian Ministry of Health databases of dengue cases and serotyping. A mixed negative binomial regression model for repeated measures over time was employed to estimate the association between the cumulative incidence of reported SD-DWS cases per 100,000 inhabitants and serotype-specific circulation. Crude and adjusted incidence ratios (IRR) were estimated.Principal findingsThe study analyzed data from 2007 to 2022 across 19 regions of Peru, totaling 304 region-years. Data from nearly 58,000 serotype identification reports and 57,966 cases of SD-DWS were analyzed. The regions with most cumulative incidence of SD-DWS per 100,000 inhabitants during 2007 to 2022 were Madre de Dios (3859), Loreto (1518), Ucayali (1492), Tumbes (1335), and Piura (722). The adjusted model revealed a higher risk of cumulative incidence of SD-DWS when there was specific circulation of DENV-123 (aIRR 7.57 CI 4.00 – 14.31), DENV-12 (aIRR 4.66 CI 2.57 – 8.44), DENV-23 (aIRR 3.55 CI 1.75 – 7.21), or when there was circulation of DENV-2 alone or co-circulating with other serotypes (aIRR 27.7 CI 15.46 -49.63).ConclusionsCirculation of DENV-2 was associated with higher average incidence rate ratios of SD-DWS.Author summaryWe investigated how the circulation of different dengue virus (DENV) serotypes are associated with the incidence of severe dengue and dengue with warning signs in Peru, a country where dengue is endemic. We analyzed 16 years of data from the dengue surveillance system, including nearly 58,000 serotype identification reports and 57,966 cases of severe dengue and dengue with warning signs. We found that regions with specific circulation of DENV-2, either alone or in combination with other serotypes, had higher incidence rates of severe dengue and dengue with warning signs. Our findings highlight the importance of monitoring DENV serotype circulation to manage and prevent severe dengue, especially in regions where DENV-2 is prevalent.
X-Chromosome-wide association study for Alzheimer’s disease
Authors: Le Borgne Julie , Gomez Lissette , Heikkinen Sami , Amin Najaf , Ahmad Shahzad , Choi Seung Hoan , Bis Joshua , Grenier-Boley Benjamin , Rodriguez Omar Garcia , Kleineidam Luca , Young Juan , Tripathi Kumar Parijat , Wang Lily , Varma Achintya , van der Lee Sven , Damotte Vincent , de Rojas Itziar , Palmal Sagnik , Giedraitis Vilmantas , Ghidoni Roberta , Fernandez Victoria , Kehoe Patrick Gavin , Frikke-Schmidt Ruth , Tsolaki Magda , Sánchez-Juan Pascual , Sleegers Kristel , Ingelsson Martin , Haines Jonathan , Farrer Lindsay , Mayeux Richard , Wang Li-San , Sims Rebecca , DeStefano Anita , Schellenberg Gerard D. , Seshadri Sudha , Amouyel Philippe , Williams Julie , van der Flier Wiesje , Ramirez Alfredo , Pericak-Vance Margaret , Andreassen Ole , Van Duijn Cornelia , Hiltunen Mikko , Ruiz Agustín , Dupuis Josée , Martin Eden , Lambert Jean-Charles , Kunkle Brian , Bellenguez Céline 
Published: May 2024

AbstractDue to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To finally address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10−8) but identified four X-chromosome-wide significant loci (P ≤ 1.7 × 10−6). Two signals locate in theFRMPD4andDMDgenes, while the two others are more than 300 kb away from the closest protein coding genesNLGN4XandGRIA3. Overall, this XWAS found no common genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.
Prevalence and Factors Associated with Moderate-to-Severe Anaemia Among Virally Suppressed People with HIV at a Tertiary Hospital in Zambia
Authors: Kamvuma Kingsley , Masenga Sepiso K. , Hamooya Benson M. , Chanda Warren , Munsaka Sody 
Published: May 2024

AbstractObjectiveAnaemia is associated with an increased risk of disease progression and all-cause mortality among HIV-infected individuals, regardless of the type of anaemia, but the magnitude of the risk is greater with more severe anaemia. Although anaemia PLWH has been extensively studied, the focus has primarily been on its prevalence and association with disease progression in untreated or poorly controlled HIV cases. This study aimed to investigate the prevalence, and factors associated with moderate-to-severe anaemia among virally suppressed HIV patients at a tertiary hospital in Zambia.MethodsWe conducted a cross-sectional study of ART treated PLWH for at least 6 months between October 2023 and February 2024 at Livingstone University Teaching Hospital (LUTH). Sociodemographic, clinical, and laboratory were the data collected. Anaemia was defined based on the World Health Organisation (WHO) classification, as haemoglobin concentration lower than normal i.e. <12 g/dl in females and <13 g/dl in males. The primary outcome was moderate-to-severe anaemia defined as haemoglobin level below 10.9 g/dl based World Health Organisation (WHO) classification. Logistic regression was performed to identify factors associated with moderate-to-severe anaemia.ResultsAmong 823 participants with viral suppression, the overall prevalence of anaemia and moderate-to-severe anaemia was 29.4% (n=242; 95% confidence interval (CI): 26.3-32.6) and 14.2% (n=117, 95% CI: 11.7-18), respectively. Females exhibited significantly higher odds of moderate-to-severe anaemia compared to males (adjusted odds ratio (AOR) 2.65; 95% confidence interval (CI): 1.21-5.81). Lower lymphocyte count (AOR 0.542; 95% CI: 0.33-0.90), higher BMI (AOR 1.06; 95% CI: 1.01-1.12), and Microcytosis (AOR 14.35; 95% CI: 7.33 - 28.08) were associated with increased odds of anaemia. Participants on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens had a higher likelihood of anaemia compared to those on integrase strand transfer inhibitor (INSTI) regimens (AOR 5.16; 95% CI: 1.02-26.24).ConclusionWe found a higher prevalence of anaemia and moderate-to-severe anaemia in virally suppressed PLWH, suggesting factors beyond HIV contribute to the persistence of anaemia in this cohort. Female gender, lower lymphocyte count, higher BMI, low mean corpuscular volume, and NNRTI-based ART regimens were independently associated with moderate-to-severe anaemia. Further research is warranted to explain the underlying mechanisms and optimize clinical management to improve outcomes among virally suppressed PLWH.