bluuebunny/crossref_metadata_2025 huggingface dataset:
Confinement induces internal flows in adherent cell aggregates
Authors: Yousafzai M. S. , Amiri S. , Sun Z. G. , Pahlavan ‪A. A. , Murrell M.
Published: May 2024

During mesenchymal migration, F-actin protrusion at the leading edge and actomyosin contraction determine the retrograde flow of F-actin within the lamella. The coupling of this flow to integrin-based adhesions determines the force transmitted to the extracellular matrix and the net motion of the cell. In tissues, motion may also arise from convection, driven by gradients in tissue-scale surface tensions and pressures. However, how migration coordinates with convection to determine the net motion of cellular ensembles is unclear. To explore this, we study the spreading of cell aggregates on adhesive micropatterns on compliant substrates. During spreading, a cell monolayer expands from the aggregate towards the adhesive boundary. However, cells are unable to stabilize the protrusion beyond the adhesive boundary, resulting in retraction of the protrusion and detachment of cells from the matrix. Subsequently, the cells move upwards and rearwards, yielding a bulk convective flow towards the centre of the aggregate. The process is cyclic, yielding a steady-state balance between outward (protrusive) migration along the surface, and ‘retrograde’ (contractile) flows above the surface. Modelling the cell aggregates as confined active droplets, we demonstrate that the interplay between surface tension-driven flows within the aggregate, radially outward monolayer flow and conservation of mass leads to an internal circulation.
Logical circuits in colloids
Authors: Roberts Nic , Raeisi Kheirabadi Noushin , Tsompanas Michail-Antisthenis , Chiolerio Alessandro , Crepaldi Marco , Adamatzky Andrew
Published: May 2024

Colloid-based computing devices offer remarkable fault tolerance and adaptability to varying environmental conditions due to their amorphous structure. An intriguing observation is that a colloidal suspension of ZnO nanoparticles in dimethylsulfoxide (DMSO) exhibits reconfiguration when exposed to electrical stimulation and produces spikes of electrical potential in response. This study presents a novel laboratory prototype of a ZnO colloidal computer, showcasing its capability to implement various Boolean functions featuring two, four and eight inputs. During our experiments, we input binary strings into the colloid mixture, where a logical ‘True’ state is represented by an impulse of an electrical potential. In contrast, the absence of the electrical impulse denotes a logical ‘False’ state. The electrical responses of the colloid mixture are recorded, allowing us to extract truth tables from the recordings. Through this methodological approach, we demonstrate the successful implementation of a wide range of logical functions using colloidal mixtures. We provide detailed distributions of the logical functions discovered and offer speculation on the potential impacts of our findings on future and emerging unconventional computing technologies. This research highlights the exciting possibilities of colloid-based computing and paves the way for further advancements.
Carbapenem-Resistant Citrobacter amalonaticus and VRE Bacteremia in an Immunocompetent Patient after Urologic Rezum Procedure
Authors: Midlick David , Harhay Jason , Summers Nathan A
Published: May 2024

2. Abstract

In this case, we present a 62-year-old man who presented with gross hematuria, fever, and chills one day after undergoing Rezum procedure and found to have carbapenem-resistant Citrobacter amalonaticus and vancomycin-resistant Enterococcus faecalis bacteremia. The patient was treated with daptomycin, eravacycline, and ceftalozane-tazobactam with positive results. We discuss our case and treatment of C. amalonaticus bacteremia, a pathogen with limited existing literature on its incidence, presentation, and treatment.
Usefulness of aortic valve calcification in patients with low flow aortic stenosis
Authors: Mogensen Nils Sofus Borg , Sanchez Dahl Jordi , Ali Mulham , Annabi Mohamed-Salah , Haujir Amal , Powers Andréanne , Carter-Storch Rasmus , Grenier-Delaney Jasmine , Møller Jacob Eifer , Øvrehus Kristian Altern , Pibarot Philippe , Clavel Marie-Annick
Published: May 2024

Background

Aortic valve calcification (AVC) has been shown to be a powerful assessment of aortic stenosis severity (AS) and predictor of adverse outcome. However, its accuracy in patients with low-flow AS has not yet been proven.

Objectives

To assess the predictive value of AVC in patients classical (CLF, i.e. low left ventricular ejection fraction [LVEF]) or paradoxical (PLF, i.e. low flow preserved LVEF) AS patients.

Methods

We prospectively include 641 patients, 319 (49.8%) with CLF-AS and 322 (50.2%) with PLF-AS who underwent Doppler-echocardiography and multidetector computed tomography. AVCratio was calculated as AVC divided by the sex-specific AVC threshold for AS-severity; AVC score ≥2,000 AU in males, and ≥1,200 AU in females. The primary endpoint of the study was all-cause mortality regardless of treatment.

Results

During a median follow-up of 4.9 (4.3-5.9) years there were 265 deaths. After comprehensive adjustment, AVCratio was associated with all-cause mortality in CLF-AS (aHR=1.25 [1.01-1.56]; p<0.05) and PLF-AS (aHR=1.51[1.14-2.00]; p=0.004) patients. There was an interaction (p=0.001) between AVC and AS flow pattern (i.e. CLF vs. PLF) with regard to the prediction of mortality. The best AVCratio threshold to predict mortality was different in CLF-AS (AVCratio≥0.7) and PLF-AS (AVCratio≥1) patients. After comprehensive analysis, AVCratio as a dichotomic variable was associated with all-cause mortality in all groups (p≤0.001). The addition of AVCratio to the models improved all model’s predictive value (all net reclassification index >18%; all p≤0.05).

Conclusion

In patients with CLF or PLF AS, AVC is a major predictor of mortality. Thus, AVC should be used in low flow patients to stratify risk. Importantly, in patients with reduced LVEF, a non-severe AS (i.e. AVC 70% of severe) could be associated with reduce survival.

Clinical Perspective

What is new?

Aortic valve calcification is a powerful predictor of outcome in patients with low ejection fraction aortic stenosis and in patients with low-flow despite normal ejection fraction aortic stenosis.

In patient with low ejection fraction aortic stenosis, a non-severe calcification (AVCratio=0.7) is associated with increased mortality. An AVCratio of 0.7 correspond to an AVC of 840AU in female patients and 1,400AU in male patients.

What are the clinical implications?

AVC should be used in low ejection fraction and low flow patients to assess aortic stenosis severity and stratify risk.

A severe AVC, in patient with low-flow preserved ejection fraction, could help in clinical decision making.

A moderate-to-severe AVC (i.e. AVCratio>0.7), in patients with low ejection fraction, is detrimental and may be used to refine clinical decision making.
Challenges in Synthesising the Effects of Synchronous Remote-based Interventions on Suicidal Behaviours: A Systematic Review and Meta-Analysis
Authors: Comendador Laura , Jiménez-Villamizar María P. , Losilla Josep-Maria , Sanabria-Mazo Juan P. , Mateo-Canedo Corel , Cebrià Ana Isabel , Palao Diego , Sanz Antoni
Published: May 2024

Introduction

Suicide is one of the leading causes of preventable death worldwide. Evidence reported in the literature seems to support the impact of providing active contact for people that have attempted suicide. The current systematic review and meta-analysis aim to investigate the effects of suicide prevention strategies implemented through remote and synchronous technology-based interventions.

Methods

The systematic review and meta-analysis followed the PRISMA 2020 guidelines. The searches were conducted in PubMed, PsycInfo, Scopus, and Web of Science. Screening, selection process, data extraction, and risk of bias (RoB) assessment have been performed independently by two reviewers. A systematic review and narrative synthesis of the data has been performed. Data on adherence to treatment and suicide-related factors to explain heterogeneity were extracted. A meta-analysis was conducted to determine effect sizes (Hedge’sg) for suicidal ideation, odds ratios (OR) and 95% confidence intervals (95% CI) for lethal and non-lethal suicide behaviours. Data were pooled using a random-effects model. Subgroup analyses were performed by classifying the studies according to the evaluation period.

Results

A total of 26 publications were finally included. Synchronous remote-based interventions were effective in preventing repeated suicide attempts (OR = 0.75; 95% CI 0.62 – 0.90) and suicide deaths (Peto OR = 0.37; 95% CI 0.18 – 0.77); however, considerable heterogeneity was reported. The effects on suicidal ideation were not confirmed (Hedge’sg= 0.23; 95% CI −1.54 – 1.07).

Conclusions

The observed heterogeneity suggests that the effects should be considered under caution. Methodological and procedural guidelines are proposed to improve the quality of future research studies.
West African pre-pandemic cross-reactive antibody and cellular responses against SARS-CoV-2
Authors: Herrera Bobby Brooke , Chaplin Beth , MBoup Souleymane , Abdullahi Adam , He Michelle , Fisher Sydney M. , Akanmu Sulaimon , Chang Charlotte A , Hamel Donald J , Gupta Ravindra K. , Kanki Phyllis J
Published: May 2024

The COVID-19 pandemic had a severe impact globally, yet African populations exhibited unexpectedly lower rates of severe disease and mortality. We investigated the potential role of pre-existing immunity in shaping the epidemiology of COVID-19 in Africa. Leveraging paired plasma and peripheral blood mononuclear cells collected from Senegalese female sex workers prior to the COVID-19 pandemic, we observed substantial levels of pre-existing cross-reactive immunity to SARS-CoV-2, stemming from prior exposure to seasonal human coronaviruses (hCoVs). Our antibody analysis revealed a 23.5% (47/200) seroprevalence rate against SARS-CoV-2 nucleocapsid (N). Of these SARS-CoV-2 N-reactives, 85.1% (40/47), 44.7% (21/47), and 95.7% (45/47) showed antibody reactivity against hCoV-229E or hCoV-OC43 spike (S) and/or N or hCoV-HKU1 S. Our analysis of cellular responses also demonstrated cross-reactivity to SARS-CoV-2 with 82.2% (37/45) and 84.4% (38/45) showing IFN-γ responses against S and N, respectively. These findings suggest that prior hCoV exposure may induce cross-reactive adaptive immunity, potentially contributing to protection against COVID-19. A unique pre-pandemic subject had cross-reactive SARS-CoV-2 S antibodies with detectable neutralization and cellular responses. Our study provides unique insights into the dynamics of hCoV and SARS-CoV-2 immunity in West African populations and underscores the importance of understanding the role of pre-existing immunity in shaping COVID-19 outcomes globally.
Wearable Data Reveals distinct Characteristics of Individuals with Persistent Symptoms after a SARS-CoV-2 Infection
Authors: Ledebur Katharina , Wiedermann Marc , Puta Christian , Thurner Stefan , Klimek Peter , Brockmann Dirk
Published: May 2024

Evidence on long-term health effects of SARS-CoV-2 infection remains scarce. Using a wearable-derived behavioral and physiological dataset (n = 20,815), we identified 137 individuals characterized by self-reported persistent fatigue and shortness of breath following a SARS-CoV-2 infection. Compared with symptom-free COVID-19 positive and negative controls, these individuals had higher resting heart rates (mean difference 2.37/1.49 bpm) and lower daily step counts (mean 3,030/2,909 steps fewer), even at least three weeks prior to SARS-CoV-2 infection. In addition, persistent COVID-19 symptoms were associated with a significant reduction in mean quality of life (WHO-5, EQ-5D), even before infection. Analysis of individual wearable time series suggests that individuals with persistent symptoms may have been more exposed to pre-existing health conditions/lower fitness levels prior to SARS-CoV-2 infection. Our study demonstrates the potential of wearable devices to track physiological and physical activity dynamics under natural conditions in the context of infectious and chronic diseases.
Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study
Authors: Pasman Joëlle A. , Bergstedt Jacob , Harder Arvid , Gong Tong , Xiong Ying , Hägg Sara , Fang Fang , Treur Jorien L. , Choi Karmel W. , Sullivan Patrick F. , Lu Yi
Published: May 2024

Background

Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables.

Methods

A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation.

Outcomes

Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses.

Interpretation

This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder.
Common pediatric surgical conditions and associated health-seeking behaviors in Pakistan: an urban and rural comparative assessment
Authors: Qazi Saqib Hamid , Meerza Syed Saqlain Ali , Dogar Sohail Asghar , Padhani Zahra Ali , Mirani Mushtaq , Jamali Muhammad Khan , Lakhani Sohail , Muhammad Sajid , Anwar Muhammad , Islam Saleem , Khan Sadaf , Abbas Anjum , Khan Zahid Ali , Khatoon Sana , Sheikh Imtiaz , Bux Rasool , Ali Rafey , Naqvi Hassan , Rizvi Arjumand , Chahudary Imran Ahmed , Rashid Rizwan Haroon Ur , Abbas Syed Akbar , Memon Abdul Sami , Tabassum Sadia , Bhatti Zara , Rehman Abdur , Soofi Sajid , Das Jai K
Published: May 2024

Approximately five billion people do not have access to necessary surgical treatment globally and up to 85% of children in LMICs are affected with conditions requiring surgical care by the age of 15 years. It is crucial to identify common surgical conditions in children in Pakistan to inform healthcare professionals and policymakers for effective resource allocation. This is a representative cross-sectional household survey conducted on children aged 5-10 years. It is to assess existing surgical diseases and healthcare-seeking behaviors in the two largest provinces (Sindh and Punjab) of Pakistan. Data was collected through a validated cross-sectional survey tool [Surgeons OverSeas Assessment of Surgical Need (SOSAS)]. Caregivers were asked about their child’s recent and past surgical conditions in six distinct anatomical regions and pictures were taken of identified conditions after appropriate consent for further diagnosis. Health-seeking behaviors including the kind of treatment sought, the nature of care received, and the reasons for not receiving care were noted. The study found that 13.5% of children with a surgical condition, had similar distribution across the urban (13.2%) and rural (13.7) areas. The greatest number of surgical conditions were found to be on the head and neck region (57.7%), while the back accounted for the least number of conditions (1.7%). Our results outline a need for organizing all entities (governmental, non-governmental, and private) involved in child health to ensure efficient resource allocation to cater to existing surgical problems.
Evaluating the Effectiveness and Safety of Large Language Model in Generating Type 2 Diabetes Mellitus Management Plans: A Comparative Study with Medical Experts Based on Real Patient Records
Authors: Mondal Agnibho , Naskar Arindam , Roy Choudhury Bhaskar , Chakraborty Sambudhya , Biswas Tanmay , Sinha Sumanta
Published: May 2024

Background

The integration of large language models (LLMs) such as GPT-4 into healthcare presents potential benefits and challenges. While LLMs have shown promise in applications ranging from scientific writing to personalized medicine, their practical utility and safety in clinical settings remain under scrutiny. Concerns about accuracy, ethical considerations and bias necessitate rigorous evaluation of these technologies against established medical standards.

Objective

To compare the completeness, necessity, dosage accuracy and overall safety of type 2 diabetes management plans created by GPT-4 with those devised by medical experts.

Methods

This study involved a comparative analysis using anonymized patient records from a healthcare setting in West Bengal, India. Management plans for 50 Type 2 diabetes patients were generated by GPT-4 and three blinded medical experts. These plans were evaluated against a reference management plan based on American Diabetes Society guidelines. Completeness, necessity and dosage accuracy were quantified and an error score was devised to assess the quality of the generated management plans. The safety of the management plans generated by GPT-4 was also assessed.

Results

Results indicated that medical experts’ management plans had fewer missing medications compared to those generated by GPT-4 (p=0.008). However, GPT-4 generated management plans included fewer unnecessary medications (p=0.003). No significant difference was observed in the accuracy of drug dosages (p=0.975). The overall error scores were comparable between human experts and GPT-4 (p=0.301). Safety issues were noted in 16% of the plans generated by GPT-4, highlighting potential risks associated with AI-generated management plans.

Conclusion

The study demonstrates that while GPT-4 can effectively reduce unnecessary drug prescriptions, it does not yet match the performance of medical experts in terms of plan completeness and safety. The findings support the use of LLMs as supplementary tools in healthcare, underscoring the need for enhanced algorithms and continuous human oversight to ensure the efficacy and safety of AI applications in clinical settings. Further research is necessary to improve the integration of LLMs into complex healthcare environments.
Campylobactercolonization and undernutrition in infants in rural Eastern Ethiopia: a longitudinal community-based birth cohort study
Authors: Chen Dehao , McKune Sarah Lindley , Yang Yang , Usmane Ibsa Aliyi , Ahmed Ibsa Abdusemed , Amin Jafer Kedir , Ibrahim Abdulmuen Mohammed , Seran Abadir Jemal , Shaik Nurmohammad , Ojeda Amanda , Hassen Bahar Mummed , Deblais Loic , Ahmedo Belisa Usmael , Hassen Kedir Abdi , Bhrane Mussie , Li Xiaolong , Singh Nitya , Roba Kedir Teji , French Nigel P. , Rajashekara Gireesh , Manary Mark J. , Hassen Jemal Yusuf , Havelaar Arie Hendrik
Published: May 2024

Background

Campylobacteris associated with environmental enteric dysfunction (EED) and malnutrition in children.Campylobacterinfection could be a critical link between determinants of livestock fecal exposure and health outcomes in low-resource smallholder settings.

Methods

We followed a birth cohort of 106 infants in a community of rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed socio-demographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, andCampylobacterspp. was quantified using genus-specific qPCR. In month 13, we collected stool and urine samples to assay for biomarkers of EED. We employed regression analyses to assess the associations of household determinants withCampylobactercolonization, EED, and growth faltering.

Results

TheCampylobacterload in infant stools increased with age. The mean length-for-age z-score (LAZ) decreased from −0.45 at 3-4 months of age to −2.06 at 13 months, while the prevalence of stunting increased from 3% to 51%. The prevalence of EED at 13 months of age was 56%. A higherCampylobacterload was associated with more frequent diarrhea. Prelacteal feeding significantly increasedCampylobacterload in the first month of life. Over the whole follow-up period,Campylobacterload was increased by keeping chickens unconfined at home and unsanitary disposal of infant stools, while decreased by mother’s handwashing with soap. Longitudinally,Campylobacterload waspositivelyassociated with food insecurity, introduction of complementary foods, and raw milk consumption. There were no significant associations betweenCampylobacterload, EED, and LAZ.

Conclusions

This study found that most determinants associated with an increase in Campylobacter infection were related to suboptimal feeding practices and hygiene. Findings related to livestock-associated risks were inconclusive. Though stunting, EED, andCampylobacterprevalence rates all increased tohighlevels by the end of the first year of life, no significant association between them was identified. While additional research is needed to investigate whether findings from this study are replicated in other populations, community efforts to improve infant and young child feeding practices, including age at introduction of complementary foods and exclusive breastfeeding, and WaSH at the household level, could reduce (cross-) contamination at the point of exposure.
Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke
Authors: Choi Sylvia E. , Bucci Tommaso , Huang Jia-Yi , Yiu Kai-Hang , Tsang Christopher T. W. , Lau Kui Kai , Hill Andrew , Irving Greg , Lip Gregory Y. H. , Abdul-Rahim Azmil H.
Published: May 2024

Background

Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. We aimed to investigate the benefits of statins in patients with atrial fibrillation (AF) and recent ischaemic stroke (IS), which remain unclear.

Methods

This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed-up for 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI).

Results

Of 20,902 patients with AF and recent IS, 7,500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7±11.5; 5,277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41–0.48, p<0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p<0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p<0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p<0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p<0.001), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p<0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnicities, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity and optimal LDL-C levels.

Conclusions

Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.
Viral and host network analysis of the human cytomegalovirus transcriptome in latency
Authors: Collins-McMillen Donna , Oliveira Pessoa Diogo De , Zarrella Kristen , Parkins Christopher J. , Daily Michael , Moorman Nathaniel J. , Kamil Jeremy P. , Caposio Patrizia , Padi Megha , Goodrum Felicia D.
Published: May 2024

HCMV genesUL135andUL138play opposing roles regulating latency and reactivation in CD34+human progenitor cells (HPCs). Using the THP-1 cell line model for latency and reactivation, we designed an RNA sequencing study to compare the transcriptional profile of HCMV infection in the presence and absence of these genes. The loss ofUL138results in elevated levels of viral gene expression and increased differentiation of cell populations that support HCMV gene expression and genome synthesis. The loss ofUL135results in diminished viral gene expression during an initial burst that occurs as latency is established and no expression of eleven viral genes from the ULb’ region even following stimulation for differentiation and reactivation. Transcriptional network analysis revealed host transcription factors with potential to regulate the ULb’ genes in coordination with pUL135. These results reveal roles forUL135andUL138in regulation of viral gene expression and potentially hematopoietic differentiation.
Unraveling factors responsible for pathogenic differences in Lassa virus strains
Authors: Taniguchi Satoshi , Saito Takeshi , Paroha Ruchi , Huang Cheng , Paessler Slobodan , Maruyama Junki
Published: May 2024

Lassa virus (LASV) is the etiological agent of Lassa fever (LF), a severe hemorrhagic disease with potential for lethal outcomes. Apart from acute symptoms, LF survivors often endure long-term complications, notably hearing loss, which significantly impacts their quality of life and socioeconomic status in endemic regions of West Africa. Classified as a Risk Group 4 agent, LASV poses a substantial public health threat in affected areas. Our laboratory previously developed a novel lethal guinea pig model of LF utilizing the clinical isolate LASV strain LF2384. However, the specific pathogenic factors underlying LF2384 infection in guinea pigs remained elusive. In this study, we aimed to elucidate the differences in the immunological response induced by LF2384 and LF2350, another LASV isolate from a non-lethal LF case within the same outbreak. Through comprehensive immunological gene profiling, we compared the expression kinetics of key genes in guinea pigs infected with LASV LF2384 and LF2350. Our analysis revealed differential expression patterns for several immunological genes, including CD94, CD19-2, CD23, IL-7, and CIITA, during LF2384 and LF2350 infection. Moreover, through the generation of recombinant LASVs, we sought to identify the specific viral genes responsible for the observed pathogenic differences between LF2384 and LF2350. Our investigations pinpointed the L protein as a crucial determinant of pathogenicity in guinea pigs infected with LASV LF2384.

Author summary

Lassa virus (LASV) is known to cause lethal hemorrhagic fever, Lassa fever, and is classified as a Risk Group-4 agent, which need to be handled in the highest biocontainment laboratories, biosafety level-4 (BSL-4), due to its high pathogenicity and the lack of preventive or treatment methods. LASV infection has a huge impact on public health and socioeconomics in endemic areas, however, its pathogenic mechanism is still largely unknown. In order to unveil the mechanisms of LASV pathogenesis, we compared the pathogenicity of two LASV isolates, which have opposite phenotypes in guinea pigs. Additionally, we determined the viral factor responsible for pathogenic differences between LASV isolates using reverse genetics. In summary, our study provides valuable insights into the immunological and virological factors underlying the pathogenic differences between LASV strains associated with lethal and non-lethal LF cases. Understanding these distinctions is essential for informing strategies for the diagnosis, treatment, and prevention of LF.
Comparative metagenomics of tropical reef fishes show conserved core gut functions across hosts and diets with diet-related functional gene enrichments
Authors: Wu Derek G. , Harris Cassandra R , Kalis Katie M , Bowen Malique , Biddle Jennifer F , Farag Ibrahim F
Published: May 2024

Fish gut microbial communities are important for the breakdown and energy harvesting of the host diet. Microbes within the fish gut are selected by environmental and evolutionary factors. To understand how fish gut microbial communities are shaped by diet, three tropical fish species (hawkfish, Paracirrhites arcatus; yellow tang, Zebrasoma flavescens; and triggerfish, Rhinecanthus aculeatus) were fed piscivorous (fish meal pellets), herbivorous (seaweed), and invertivorous (shrimp) diets, respectively. From fecal samples, a total of 43 metagenome assembled genomes (MAGs) were recovered from all fish diet treatments. Each host-diet treatment harbored distinct microbial communities based on taxonomy, with Proteobacteria, Bacteroidota, and Firmicutes being the most represented. Based on their metagenomes, MAGs from all three host-diet treatments demonstrated a baseline ability to degrade proteinaceous, fatty acid, and simple carbohydrate inputs and carry out central carbon metabolism, lactate and formate fermentation, acetogenesis, nitrate respiration, and B vitamin synthesis. The herbivorous yellow tang harbored more functionally diverse MAGs with some complex polysaccharide degradation specialists, while the piscivorous hawkfish MAGs were more specialized for the degradation of proteins. The invertivorous triggerfish gut MAGs lacked many carbohydrate degrading capabilities, resulting in them being more specialized and functionally uniform. Across all treatments, several MAGs were able to participate in only individual steps of the degradation of complex polysaccharides, suggestive of microbial community networks that degrade complex inputs.
Engineering drive-selection balance for localised population suppression with neutral dynamics
Authors: Willis Katie , Burt Austin
Published: May 2024

Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localised. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here we describe a way to create this balance involving a toxin-antidote genetic construct that causes recessive lethality, encodes a genomic editor that makes dominant lethal edits in the genome, and provides protection against the action or consequences of the editing. Computer modelling shows that this design can be 100-fold more efficient than sterile males, increasing to 1000-fold more when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.
Virtual patient analysis identifies strategies to improve the performance of predictive biomarkers for PD-1 blockade
Authors: Arulraj Theinmozhi , Wang Hanwen , Deshpande Atul , Varadhan Ravi , Emens Leisha A. , Jaffee Elizabeth M. , Fertig Elana J. , Santa-Maria Cesar A. , Popel Aleksander S.
Published: May 2024

Patients with metastatic triple-negative breast cancer (TNBC) show variable responses to PD-1 inhibition. Efficient patient selection by predictive biomarkers would be desirable, but is hindered by the limited performance of existing biomarkers. Here, we leveraged in-silico patient cohorts generated using a quantitative systems pharmacology model of metastatic TNBC, informed by transcriptomic and clinical data, to explore potential ways to improve patient selection. We tested 90 biomarker candidates, including various cellular and molecular species, by a cutoff-based biomarker testing algorithm combined with machine learning-based feature selection. Combinations of pre-treatment biomarkers improved the specificity compared to single biomarkers at the cost of reduced sensitivity. On the other hand, early on-treatment biomarkers, such as the relative change in tumor diameter from baseline measured at two weeks after treatment initiation, achieved remarkably higher sensitivity and specificity. Further, blood-based biomarkers had a comparable ability to tumor- or lymph node-based biomarkers in identifying a subset of responders, potentially suggesting a less invasive way for patient selection.
Machine learning identifies activation of RUNX/AP-1 as drivers of mesenchymal and fibrotic regulatory programs in gastric cancer
Authors: Razavi-Mohseni Milad , Huang Weitai , Guo Yu A. , Shigaki Dustin , Ho Shamaine Wei Ting , Tan Patrick , Skanderup Anders J. , Beer Michael A.
Published: May 2024

Gastric cancer (GC) is the fifth most common cancer worldwide and is a heterogeneous disease. Among GC subtypes, the mesenchymal phenotype (Mes-like) is more invasive than the epithelial phenotype (Epi-like). Although gene expression of the epithelial-to-mesenchymal transition (EMT) has been studied, the regulatory landscape shaping this process is not fully understood. Here we use ATAC-seq and RNA-seq data from a compendium of GC cell lines and primary tumors to detect drivers of regulatory state changes and their transcriptional responses. Using the ATAC-seq data, we developed a machine learning approach to determine the transcription factors (TFs) regulating the subtypes of GC. We identified TFs driving the mesenchymal (RUNX2, ZEB1, SNAI2, AP-1 dimer) and the epithelial (GATA4, GATA6, KLF5, HNF4A, FOXA2, GRHL2) states in GC. We identified DNA copy number alterations associated with dysregulation of these TFs, specifically deletion ofGATA4and amplification ofMAPK9. Comparisons with bulk and single-cell RNA-seq data sets identified activation toward fibroblast-like epigenomic and expression signatures in Mes-like GC. The activation of this mesenchymal fibrotic program is associated with differentially accessible DNAcis-regulatory elements flanking upregulated mesenchymal genes. These findings establish a map of TF activity in GC and highlight the role of copy number driven alterations in shaping epigenomic regulatory programs as potential drivers of GC heterogeneity and progression.
Fragile dislocation modes in obstructed atomic topological phases
Authors: Malavé Gabriel , Schifferli Jorge , Soto-Garrido Rodrigo , Orellana Pedro A. , Juričić Vladimir
Published: May 2024

We here introduce the concept of fragile dislocation modes, which are localized only in a fraction of a topological phase while otherwise leaking into the bulk continuum. As we demonstrate here, such dislocation modes are hosted in an obstructed atomic topological phase in the two-dimensional Su-Schrieffer-Heeger model but only in a finite region with an indirect gap at high energy. They are realized as chiral pairs at finite energies with protection stemming from a combination of the chiral (unitary particle-hole) and the point group (C4v) symmetries, but only when the indirect gap is open. In this regime, we corroborate the stability of the defect modes by following their localization and also by explicitly adding a weak chemical potential disorder. Our findings should, therefore, be consequential for the experimental observation of such modes in designer topological crystals and classical metamaterials.

Published by the American Physical Society
2024
Giant Two-Level Systems in a Granular Superconductor
Authors: Kristen M. , Voss J. N. , Wildermuth M. , Bilmes A. , Lisenfeld J. , Rotzinger H. , Ustinov A. V.
Published: May 2024

Disordered thin films are a common choice of material for superconducting, high impedance circuits used in quantum information or particle detector physics. A wide selection of materials with different levels of granularity are available, but, despite low microwave losses being reported for some, the high degree of disorder always implies the presence of intrinsic defects. Prominently, quantum circuits are prone to interact with two-level systems (TLS), typically originating from solid state defects in the dielectric parts of the circuit, like surface oxides or tunneling barriers. We present an experimental investigation of TLS in granular aluminum thin films under applied mechanical strain and electric fields. The analysis reveals a class of strongly coupled TLS having electric dipole moments up to 30  eÅ, an order of magnitude larger than dipole moments commonly reported for solid state defects. Notably, these large dipole moments appear more often in films with a higher resistivity. Our observations shed new light on granular superconductors and may have implications for their usage as a quantum circuit material.

Published by the American Physical Society
2024
Emerging Mesoscale Flows and Chaotic Advection in Dense Active Matter
Authors: Keta Yann-Edwin , Klamser Juliane U. , Jack Robert L. , Berthier Ludovic
Published: May 2024

We study two models of overdamped self-propelled disks in two dimensions, with and without aligning interactions. Both models support active mesoscale flows, leading to chaotic advection and transport over large length scales in their homogeneous dense fluid states, away from dynamical arrest. They form streams and vortices reminiscent of multiscale flow patterns in turbulence. We show that the characteristics of these flows do not depend on the specific details of the active fluids, and result from the competition between crowding effects and persistent propulsions. This observation suggests that dense active suspensions of self-propelled particles present a type of “active turbulence” distinct from collective flows reported in other types of active systems.

Published by the American Physical Society
2024
Investigating faculty perspectives on written qualifying exams in physics
Authors: Basir Shiva , Burkholder Eric
Published: May 2024

Doctoral qualifying exams are considered essential in assessing a student’s readiness for research and advanced studies. Despite their significant role in many physics programs, questions have been raised about their format, execution, and relevance. Our research investigates perceptions held by faculty members regarding the graduate doctoral examination (GDE), a written qualifying exam in Auburn University’s physics department doctoral program. We used a combination of semistructured interviews and a survey to probe their viewpoints about the purpose and necessity of written qualifying exams, their role in student preparation for these exams, and the efficacy of these exams in measuring students’ comprehensive knowledge and potential for success in physics. Despite the general consensus on the necessity of the GDE, faculty members expressed doubts about its ability to accurately predict students’ future research success and its alignment with other graduate program elements such as coursework. Proposed modifications ranged from an emphasis on oral assessments and research presentations to a complete overhaul of the examination structure. Despite these suggestions for change, the lack of agreement on a specific alternative underscores the complexity of executing substantial modifications to the GDE. Our study contributes to the ongoing dialogue on optimizing doctoral qualifying exams to better serve students and academic institutions.

Published by the American Physical Society
2024
Suppression of the skyrmion Hall effect in synthetic ferrimagnets with gradient magnetization
Authors: Bo Lan , Zhang Xichao , Mochizuki Masahito , Zhang Xuefeng
Published: May 2024

Magnetic skyrmions are promising building blocks for future spintronic devices. However, the skyrmion Hall effect (SkHE) remains an obstacle for practical applications based on the in-line transport of skyrmions. Here, we numerically study the static properties and current-driven dynamics of synthetic ferrimagnetic skyrmions. Inspired by graded-index magnonics, we introduce a linear gradient of saturation magnetization (Ms) in the skyrmion-hosting sample, which effectively modulates the skyrmion Hall angle and suppresses the SkHE. Micromagnetic simulations reveal that ferrimagnetic skyrmions could exhibit greater susceptibility to the variation of Ms as compared to their ferromagnetic counterparts. The Thiele analysis is also applied to support the simulation results, which elucidates that the Ms gradient dynamically modifies the intrinsic normalized size of skyrmions, consequently impacting the SkHE. Our results pave the way to the graded-index skyrmionics, which offers novel insights for designing ferrimagnet-based skyrmionic devices.

Published by the American Physical Society
2024
Chirality dependent photon transport and helical superradiance
Authors: Peter Jonah S. , Ostermann Stefan , Yelin Susanne F.
Published: May 2024

Chirality, or handedness, is a geometrical property denoting a lack of mirror symmetry. Chirality is ubiquitous in nature and is associated with the nonreciprocal interactions observed in complex systems ranging from biomolecules to topological materials. Here, we demonstrate that chiral arrangements of dipole-coupled atoms or molecules can facilitate the helicity-dependent superradiant emission of light. We show that the collective modes of these systems experience an emergent spin-orbit coupling that leads to chirality-dependent photon transport and nontrivial topological properties. These phenomena are fully described within the electric dipole approximation, resulting in very strong optical responses. Our results demonstrate an intimate connection between chirality, superradiance, and photon helicity and provide a comprehensive framework for studying electron transport dynamics in chiral molecules using cold atom quantum simulators.

Published by the American Physical Society
2024
Morphological instability at topological defects in a three-dimensional vertex model for spherical epithelia
Authors: Drozdowski Oliver M. , Schwarz Ulrich S.
Published: May 2024

Epithelial monolayers are a central building block of complex organisms. Topological defects have emerged as important elements for single cell behavior in flat epithelia. Here we theoretically study such defects in a three-dimensional vertex model for spherical epithelia like cysts or intestinal organoids. We find that they lead to the same generic morphological instability to an icosahedral shape as it is known from spherical elastic shells like virus capsids, polymerized vesicles, or buckyballs. We derive analytical expressions for the effective stretching and bending moduli as a function of the parameters of the vertex model, in excellent agreement with computer simulations. These equations accurately predict both the buckling of a flat epithelial monolayer under uniaxial compression and the faceting transition around the topological defects in spherical epithelia. We further show that localized apico-basal tension asymmetries allow them to reduce the transition threshold to small system sizes.

Published by the American Physical Society
2024
Neural Wave Functions for Superfluids
Authors: Lou Wan Tong , Sutterud Halvard , Cassella Gino , Foulkes W. M. C. , Knolle Johannes , Pfau David , Spencer James S.
Published: May 2024

Understanding superfluidity remains a major goal of condensed matter physics. Here, we tackle this challenge utilizing the recently developed fermionic neural network (FermiNet) wave function [D. Pfau , .] for variational Monte Carlo calculations. We study the unitary Fermi gas, a system with strong, short-range, two-body interactions known to possess a superfluid ground state but difficult to describe quantitatively. We demonstrate key limitations of the FermiNet in studying the unitary Fermi gas and propose a simple modification based on the idea of an antisymmetric geminal power singlet (AGPs) wave function. The new AGPs FermiNet outperforms the original FermiNet significantly in paired systems, giving results which are more accurate than fixed-node diffusion Monte Carlo and are consistent with experiment. We prove mathematically that the new , which differs from the original only by the method of antisymmetrization, is a strict generalization of the original FermiNet architecture, despite the use of fewer parameters. Our approach shares several advantages with the original FermiNet: The use of a neural network removes the need for an underlying basis set; sand the flexibility of the network yields extremely accurate results within a variational quantum Monte Carlo framework that provides access to unbiased estimates of arbitrary ground-state expectation values. We discuss how the method can be extended to study other superfluid.

Published by the American Physical Society
2024
Topology optimization for magnetic circuits with continuous adjoint method in 3D
Authors: Houta Zakaria , Messine Frederic , Huguet Thomas
Published: May 2024

Purpose

The purpose of this paper is to present a new approach to optimizing the design of 3D magnetic circuits. This approach is based on topology optimization, where derivative calculations are performed using the continuous adjoint method. Thus, the continuous adjoint method for magnetostatics has to be developed in 3D and has to be combined with penalization, filtering and homotopy approaches to provide an efficient optimization code.

Design/methodology/approach

To provide this new topology optimization code, this study starts from 2D magnetostatic results to perform the sensitivity analysis, and this approach is extended to 3D. From this sensitivity analysis, the continuous adjoint method is derived to compute the gradient of an objective function of a 3D topological optimization design problem. From this result, this design problem is discretized and can then be solved by finite element software. Thus, by adding the solid isotropic material with penalization (SIMP) penalization approach and developing a homotopy-based optimization algorithm, an interesting means for designing 3D magnetic circuits is provided.

Findings

In this paper, the 3D continuous adjoint method for magnetostatic problems involving an objective least-squares function is presented. Based on 2D results, new theoretical results for developing sensitivity analysis in 3D taking into account different parameters including the ferromagnetic material, the current density and the magnetization are provided. Then, by discretizing, filtering and penalizing using SIMP approaches, a topology optimization code has been derived to address only the ferromagnetic material parameters. Based on this efficient gradient computation method, a homotopy-based optimization algorithm for solving large-scale 3D design problems is developed.

Originality/value

In this paper, an approach based on topology optimization to solve 3D magnetostatic design problems when an objective least-squares function is involved is proposed. This approach is based on the continuous adjoint method derived for 3D magnetostatic design problems. The effectiveness of this topology optimization code is demonstrated by solving the design of a 3D magnetic circuit with up to 100,000 design variables.