bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the mechanism of chloroplast singlet oxygen signaling in theArabidopsis thaliana accelerated cell death 2mutant
Authors: Lemke Matthew D. , Abate Alexa N. , Woodson Jesse D.
Published: January 2024

As sessile organisms, plants have evolved complex signaling mechanisms to sense stress and acclimate. This includes the use of reactive oxygen species (ROS) generated during dysfunctional photosynthesis to initiate signaling. One such ROS, singlet oxygen (1O2), can trigger retrograde signaling, chloroplast degradation, and programmed cell death. However, the signaling mechanisms are largely unknown. Several proteins (e.g., PUB4, OXI1, EX1) are proposed to play signaling roles across threeArabidopsis thalianamutants that conditionally accumulate chloroplast1O2(fluorescent in blue light(flu),chlorina 1(ch1), andplastid ferrochelatase 2(fc2)). We previously demonstrated that these mutants reveal at least two chloroplast1O2signaling pathways (represented byfluandfc2/ch1). Here, we test if the1O2-accumulating lesion mimic mutant,accelerated cell death 2(acd2), also utilizes these pathways. Thepub4-6allele delayed lesion formation inacd2and restored photosynthetic efficiency and biomass. Conversely, anoxi1mutation had no measurable effect on these phenotypes.acd2mutants were not sensitive to excess light (EL) stress, yetpub4-6andoxi1both conferred EL tolerance within theacd2background, suggesting that EL-induced1O2signaling pathways are independent from spontaneous lesion formation. Thus,1O2signaling inacd2may represent a third (partially overlapping) pathway to control cellular degradation.
PVRL2 Suppresses Anti-tumor Immunity Through PVRIG- and TIGIT-Independent Pathways
Authors: Yang Jiuling , Wang Li , Byrnes James R. , Kirkemo Lisa L. , Driks Hannah , Belair Cassandra D. , Aguilar Oscar A. , Lanier Lewis L. , Wells James A. , Fong Lawrence , Blelloch Robert
Published: January 2024

PVRL2 is believed to act as an immune checkpoint protein in cancer; however, most insight into PVRL2’s role is inferred from studies on its known receptor PVRIG. Here, we directly study PVRL2. PVRL2 levels are high in tumor cells and tumor-derived exosomes. Deletion of PVRL2 in multiple syngeneic mouse models of cancer shows a dramatic reduction in tumor growth that is immune dependent. This effect can be even greater than seen with deletion of PD-L1. PVRL2 functions by suppressing CD8 T and NK cells in the tumor microenvironment. Unexpectedly, the effect of PVRL2 loss on tumor growth remains in the absence of PVRIG. In contrast, PVRIG loss shows no additive effect in the absence of PVRL2. TIGIT blockade combined with PVRL2 deletion results in the greatest reduction in tumor growth. This effect is not recapitulated by the combined deletion of PVRL2 with its paralog PVR, the ligand for TIGIT. These data uncover PVRL2 as a distinct inhibitor of the anti-tumor immune response with functions beyond that of its known receptor PVRIG. Importantly, the data provide a strong rationale for combinatorial targeting of PVRL2 and TIGIT for cancer immunotherapy.
Amphicarpic development in the emerging model organismCardamine chenopodiifolia
Authors: Emonet Aurélia , Pérez-Antón Miguel , Neumann Ulla , Dunemann Sonja , Huettel Bruno , Koller Robert , Hay Angela
Published: January 2024

Amphicarpy is an unusual trait where two fruit types develop: one above and the other below ground. This trait is not found in conventional model species, therefore, its development and molecular genetics remain under-studied. Here, we establishCardamine chenopodiifoliaas an emerging experimental system to study amphicarpy.

We characterized the development ofC. chenopodiifolia, focusing on differences in morphology and cell wall histochemistry between above- and below-ground fruit. We generated a reference transcriptome using PacBio full-length transcript sequencing (IsoSeq) and used a combination of short and long read sequencing to analyse differential gene expression between above- and below-ground fruit valves.

C. chenopodiifoliahas two contrasting modes of seed dispersal. The main shoot fails to bolt and initiates floral primordia that bury underground where they self-pollinate and set seed. By contrast, axillary shoots bolt to position flowers and exploding seed pods above ground. Morphological differences between aerial explosive fruit and subterranean non-explosive fruit were reflected in a large number of differentially regulated genes involved in photosynthesis, secondary cell wall formation and defence responses.

Tools established inC. chenopodiifolia, such as a reference transcriptome, draft genome assembly and stable plant transformation, pave the way to explore under-studied traits and discover new biological mechanisms.
A Bioengineered Platform for Enhanced Observability of Patterned Gastrointestinal Organoid Monolayers with Bilateral Access
Authors: Hofer Moritz , Duque-Correa Maria A. , Lutolf Matthias P.
Published: January 2024

Studying the physiology and pathology of gastrointestinal (GI) tissues requires tools that can accurately mimic their complex architecture and functionalityin vitro. Organoids have emerged as one such promising tool, though their closed structures with poorly accessible lumen and limited observability makes readouts challenging. In this study, we introduce a bioengineered organoid platform that generates bilaterally accessible 3D tissue models, allowing independent manipulation of both the apical and basal sides of patterned epithelial monolayers. We successfully constructed gastric, small intestinal, caecal, and colonic epithelial models that faithfully reproduce tissue-respective geometries and exhibit high physiological relevance, evidenced by the regionalization of stem cells and transcriptional resemblance to real epithelia. The gained observability allowed single-cell tracking over time and studies into the motility of cells in immersion and air-liquid interface cultures. Additionally, this model recapitulatedTrichuris murisinfection of the caecum epithelium, allowing the first live imaging of syncytial tunnel formation. Overall, this platform offers accessible organoids with improved observability, making it a valuable tool for investigating the dynamics of GI epithelial cells and their interactions with pathogens.
Discovery of SARS-CoV-2 papain-like protease (PLpro) inhibitors with efficacy in a murine infection model
Authors: Garnsey Michelle R. , Robinson Matthew C. , Nguyen Luong T. , Cardin Rhonda , Tillotson Joseph , Mashalidis Ellene , Yu Aijia , Aschenbrenner Lisa , Balesano Amanda , Behzadi Amin , Boras Britton , Chang Jeanne S. , Eng Heather , Ephron Andrew , Foley Tim , Ford Kristen K. , Frick James M. , Gibson Scott , Hao Li , Hurst Brett , Kalgutkar Amit S. , Korczynska Magdalena , Lengyel-Zhand Zsofia , Gao Liping , Meredith Hannah R. , Patel Nandini C. , Polivkova Jana , Rai Devendra , Rose Colin R. , Rothan Hussin , Sakata Sylvie K. , Vargo Thomas R. , Qi Wenying , Wu Huixian , Liu Yiping , Yurgelonis Irina , Zhang Jinzhi , Zhu Yuao , Zhang Lei , Lee Alpha A.
Published: January 2024

Vaccines and first-generation antiviral therapeutics have provided important protection against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease (Mpro) have demonstrated clinical efficacy, known PLproinhibitors have to date lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLprotranslates toin vivoefficacy in a preclinical setting. Herein, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLproinhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.
Scorpion α-toxin LqhαIT specifically interacts with a glycan at the pore domain of voltage-gated sodium channels
Authors: Phulera Swastik , Dickson Callum J. , Schwalen Christopher J. , Khoshouei Maryam , Cassell Samantha J. , Sun Yishan , Condos Tara , Whicher Jonathan , Weihofen Wilhelm A.
Published: January 2024

Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. Numerous protein toxins have been identified that modulate Nav gating, and structures of Nav channels in complex with these toxins helped elucidate the molecular mechanisms of voltage-dependent channel gating. The deathstalker scorpion α-toxin LqhαIT exerts a strong action potential prolonging effect on Nav channels. Biochemical studies show that LqhαIT features a functionally essential epitope at its C-terminus that is not shared with related scorpion α-toxins. To elucidate the mechanism of action of LqhαIT, we determined a 3.9 Å cryo-electron microscopy (cryo-EM) structure of LqhαIT in complex with the Nav channel fromPeriplaneta americana(NavPas). We found that LqhαIT binds to voltage sensor domain 4 and traps it in a “S4 down” conformation to stabilize the open state. To promote binding, the functionally essential C-terminal epitope of LqhαIT forms an extensive interface with the glycan scaffold linked to Asn330 of NavPas that augments a small protein-protein interface between NavPas and LqhαIT. A combination of molecular dynamics simulations, structural comparisons, and prior mutagenesis experiments demonstrate the functional importance of this toxin-glycan interaction. These findings help establish a structural basis for the specificity achieved by scorpion α-toxins and provide crucial insights for the development and optimization of new Nav channel modulators.
Language models enable zero-shot prediction of RNA secondary structures including pseudoknots
Authors: Gong Tiansu , Bu Dongbo
Published: January 2024

Current deep learning-based models for predicting RNA secondary structures face challenges in achieving high generalization ability. At the same time, a vast repository of unlabeled non-coding RNA (ncRNA) sequences remains untapped for structure prediction tasks. To address this challenge, we trained RNA-km, a foundation language model that enables zero-shot prediction of RNA secondary structures including pseudoknots. For the end, we incorporated specific modifications into the language model training process, including k-mer masking strategy and relative positional encoding. RNA-km are trained on 23 million ncRNA sequences in a self-supervised manner, gaining the advantages of high generalization ability. For a target RNA sequence, we make a zero-shot secondary structure prediction with the attention maps provided by RNA-km and a specified minimum-cost flow algorithm. Our results on popular benchmark datasets demonstrate that RNA-km exhibits high generalization abilities, excelling in zero-shot predictions for RNA secondary structures. In addition, the attention maps provided by the model capture intricate structural relationships, as evidenced by accurate pseudoknot predictions and precise identification of long-distance base pairs. We anticipate that RNA-km enhances the predictive capacity and robustness of existing models, thereby improving their ability to accurately predict structures for novel RNA sequences.
RAPID HEMATOCRIT ESTIMATION USING A FOLD-CREASE INDUCED FAST FLOWING PAPER SENSOR
Authors: Dash Amaan , Mukhopadhyay Manikuntala , Shaw Jyoti , Bhattacharya Maitreyee , DasGupta Sunando
Published: January 2024

Increased evaporative losses and flow obstructions can present substantial impediments to current paper analytical devices (µPADs) for efficient on-site testing of biological fluids. Strategic enhancements in wicking rates of paper may thereby counter these limitations and enable on-demand healthcare monitoring. Therefore, herein we have leveraged the features of paper fold-crease regions, for the very first time, and developed a novel fast-flowing platform using laser printing to accelerate fluid flow through paper. A series of extensive experiments have been conducted to optimize the design and maximize wicking rates of µPADs for smaller liquid volumes, making it well-suited for analysing biofluids. The investigation delves into structural alterations within the creased regions, employing both static and dynamic force application strategies. A first-generation Washburn type model in excellent agreement with the experimental findings is developed, providing a comprehensive insight into the fundamental physics involved. Finally, the folded channels are utilized for a distance-based hematocrit sensor employing grade-1 filter paper at very low-cost, simplified fabrication, lesser sample volume and faster analysis. The findings of this work unveil a plethora of potentialities for employing paper and paper folds to develop affordable medical devices with advanced analytical functionalities, specifically tailored for the resource-constrained settings.

Graphical Abstract
Functional validation ofEIF2AK4(GCN2) missense variants associated with pulmonary arterial hypertension
Authors: Emanuelli Giulia , Zhu JiaYi , Morell Nicolas W , Marciniak Stefan J
Published: January 2024

Pulmonary arterial hypertension (PAH) is a disorder with a large genetic component. Biallelic mutations ofEIF2AK4, which encodes the kinase GCN2, are causal in two ultra-rare subtypes of PAH, pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis.EIF2AK4variants of unknown significance have also been identified in patients with classical PAH, though their relationship to disease remains unclear. To provide patients with diagnostic information and enable family testing, the functional consequences of such rare variants must be determined, but existing computational methods are imperfect. We applied a suite of bioinformatic and experimental approaches to sixteenEIF2AK4variants that had been identified in patients. By experimentally testing the functional integrity of the integrated stress response (ISR) downstream of GCN2, we determined that existing computational tools have insufficient sensitivity to reliably predict impaired kinase function. We determined experimentally that severalEIF2AK4variants identified in patients with classical PAH had preserved function and are therefore likely to be non-pathogenic. The dysfunctional variants of GCN2 that we identified could be subclassified into three groups: misfolded, kinase-dead, and hypomorphic. Intriguingly, members of the hypomorphic group were amenable to paradoxical activation by a type-1.5 GCN2 kinase inhibitor. This experiment approach may aid in the clinical stratification ofEIF2AK4variants and potentially identify hypomorophic alleles receptive to pharmacological activation.
Highly parameterized polygenic scores tend to overfit to population stratification via random effects
Authors: Aw Alan J. , McRae Jeremy , Rahmani Elior , Song Yun S.
Published: January 2024

Polygenic scores (PGSs), increasingly used in clinical settings, frequently include many genetic variants, with performance typically peaking at thousands of variants. Such highly parameterized PGSs often include variants that do not pass a genome-wide significance threshold. We propose a mathematical perspective that renders the effects of many of these nonsignificant variants random rather than causal, with the randomness capturing population structure. We devise methods to assess variant effect randomness and population stratification bias. Applying these methods to 141 traits from the UK Biobank, we find that, for many PGSs, the effects of non-significant variants are considerably random, with the extent of randomness associated with the degree of overfitting to population structure of the discovery cohort. Our findings explain why highly parameterized PGSs simultaneously have superior cohort-specific performance and limited generalizability, suggesting the critical need for variant randomness tests in PGS evaluation. Supporting code and a dashboard are available athttps://github.com/songlab-cal/StratPGS.
Unveiling Endoglin non canonical regulation: spotlight on the new role of the uPAR pathway
Authors: Munsch Gaëlle , Proust Carole , Deiber Clémence , Meguerditchian Caroline , Caro Ilana , Tusseau Maud , Guilhem Alexandre , Mohamed Shirine ,   INVENT consortium, Goyenvalle Aurélie , Debette Stéphanie , Jaspard-Vinassa Béatrice , Dupuis-Girod Sophie , Trégouët David-Alexandre , Soukarieh Omar
Published: January 2024

Endoglin, encoded byENG, is a transmembrane glycoprotein crucial for endothelial cell biology. Loss-of-functionENGvariants cause Hereditary Hemorrhagic Telangiectasia (HHT). Despite advances in HHT diagnosis and management, the molecular origin of some cases and the source of clinical heterogeneity remain unclear.

We propose a comprehensivein silicoanalysis of all 5’UTRENGsingle nucleotide variants that could lead to Endoglin deficiency by altering upstream Open Reading Frames (upORFs). Experimentally, we confirm that variants creating uAUG-initiated overlapping upORFs associate with reduced Endoglin levelsin vitroand characterize the effect of a uCUG-creating variant identified in two suspected HHT patients.

Using plasma proteogenomics resources, we identify eight loci associated with soluble Endoglin levels, includingABOand uPAR-pathway loci and experimentally demonstrate the association between uPAR and Endoglin in endothelial cells.

This study provides new insights into Endoglin’s molecular determinants, opening avenues for improved HHT management and other diseases involving Endoglin.

Key points

New insights on the characterization ofENGnon-coding variants, in particular those altering upstream Open Reading Frames in the 5’UTR.

Leverage of large-scale plasma proteogenomics results combined with functional assays revealed new actors in Endoglin regulation.
Transfer learning with randomized controlled trial data for postprandial glucose prediction
Authors: Hotta Shinji , Kytö Mikko , Koivusalo Saila , Heinonen Seppo , Marttinen Pekka
Published: January 2024

In recent years, numerous methods have been introduced to predict glucose levels using machine-learning techniques on patients’ daily behavioral and continuous glucose data. Nevertheless, a definitive consensus remains elusive regarding modeling the combined effects of diet and exercise for optimal glucose prediction. A notable challenge is the propensity for observational patient datasets from uncontrolled environments to overfit due to skewed feature distributions of target behaviors; for instance, diabetic patients seldom engage in high-intensity exercise post-meal. In this study, we introduce a unique Bayesian transfer learning framework using randomized controlled trial (RCT) data, primarily targeting postprandial glucose prediction. Initially, we gathered balanced training data from RCTs on healthy participants by randomizing behavioral conditions. Subsequently, we pretrained the model’s parameter distribution using RCT data from the healthy cohort. This pretrained distribution was then adjusted, transferred, and utilized to determine the model parameters for each patient. Our framework’s efficacy was appraised using data from 68 gestational diabetes mellitus patients in uncontrolled settings. The evaluation underscored the enhanced performance attained through our framework. Furthermore, when modeling the joint impact of diet and exercise, the synergetic model proved more precise than its additive counterpart.
Prevalence of Internet Usage Complaints Among Undergraduate Students
Authors: Nnaemeka Emmanuel Mgbedo , Zavradashvili Nana
Published: January 2024

Internet access has aided lots of students in achieving academic purposes. This study aimed to examine the prevalence of internet usage complaints on students health, during mandatory online studies among undergraduate students from the University of Georgia (UG), Tbilisi. This cross-sectional was conducted among undergraduate students from UG using a web designed questionnaire. The survey contained sociodemographic characteristics, internet access, and health complains. The study was reviewed and approved by the Institutional Review Board (IRB). Most of participants were females (70.5%), from School of Health Sciences (207, 32.9%), in first year of study (354, 56.2%), and usually spend time on social media (Facebook, Instagram, Twitter, WhatsApp, etc.) (315, 50%). Students reported different complaints such as internet craving, feeling guilty after internet use, internet dyscontrol, back, and neck pain. There was no significant difference in sociodemographic variables. Our findings suggested that the prolonged use of internet could have some health implications among students.
Characterization and comparison of immunity against MPXV for individuals infected with MPXV or vaccinated with modified vaccinia Ankara vaccines
Authors: Wiedemann Aurélie , Surénaud Mathieu , Hubert Mathieu , Zaragoza José-Luis Lopez , Ribeiro Alexandre , Rodrigues Cécile , Foucat Emile , Diombera Harouna , Krief Corinne , Schwartz Olivier , Lelièvre Jean-Daniel , Lévy Yves
Published: January 2024

The 2022 monkeypox virus (MPXV) outbreak has revitalized questions about immunity against MPXV and vaccinia-based vaccines (VAC-V), but studies are limited. We analyzed immunity against MPXV in individuals infected with MPXV or vaccinated with the licensed modified vaccinia Ankara vaccine (MVA)-BN or an experimental MVA-HIVB vaccine. The frequency of neutralizing antibody (NAb) responders was higher among MPXV-infected individuals than MVA vaccinees. Both MVA vaccines induced similar and strong humoral responses. Similarly, we show a higher frequency and magnitude (5-fold) of T-cell responses, mainly mediated by CD8+T cells, against a peptide pool containing selected sequences from MPXV, Variola, and VAC-V in MPXV-infected individuals than MVA vaccinees. We describe a hierarchy of cross-reactive T-cell responses against five peptide pools that are highly homologous between VAC-V and MPXV 2022, with the highest frequency of responders against MVA-121L and MVA-018L proteins. Both vaccines stimulated a notable frequency of polyfunctional CD4+and CD8+T-cell responses, with a subset of CD4+T cells showing a mixed cytokine profile. Finally, we found that smallpox vaccination in childhood positively affected humoral but not T-cell vaccine responses, whereas these responses were not affected in people living with HIV. These findings contribute to deciphering and monitoring the profile of immunity to MPXV and MVA. In the context of a potential threat of the reemergence of smallpox following bioterrorism, the diversification and availability of potent vaccines is crucial. The comparable immunogenicity of both MVA vaccines emphasizes the potential utility of MVA-HIVB as a valuable new tool for controlling MPXV outbreaks.
Factors Associated with Delayed Hospital Arrival after Stroke Onset: An Observational Study in Thanh Hoa Province, Vietnam
Authors: Truong Hoa Thi , Nguyen Sam Hoanh , Le Cuong Van , Tokuno Shinichi , Kuchiba Aya , Nakahara Shinji
Published: January 2024

Background

Delayed hospital arrival lowers the proportion of patients with stroke receiving recanalization therapy and results in poor outcomes. This study investigated the factors associated with pre-hospital delays in hospital arrival after stroke onset in the Thanh Hoa Province, Vietnam.

Methods

Clinical data were collected from stroke patients within 7 days of symptom onset who were prospectively registered in this study. Patients and/or their relatives were interviewed using a structured questionnaire about patient social demographics, address, post-stroke support actions, and stroke awareness. Pre-hospital delay in hospital arrival was dichotomized into ≤ 4.5 hours and > 4.5 hours, and multivariable logistic regression analysis was used to investigate factors associated with the delay.

Result

Of the 328 participants analyzed, 181 (55.4%) arrived at the hospital 4.5 hours after the symptom onset. The patients’ and relatives’ awareness of stroke was poor. Pre-hospital delays were longer for patients living > 10 km away from a healthcare facility and those with secondary or lower education levels, with odds ratios of 2.07 and 1.98, respectively. Seeking care at a district or private hospital as the first point of healthcare or non-use of emergency medical services did not show significant associations.

Discussion

The study revealed that most patients with stroke did not arrive at the hospital in time for recanalization therapy. Moreover, the low stroke awareness among patients and their relatives is concerning. Further research is needed to investigate the reasons for pre-hospital delays and develop targeted interventions to improve stroke awareness and reduce these delays.
Extended Reality for Neuraxial Anesthesia and Pain Procedures: A Scoping Review
Authors: Cho James S. , Thaker Devaunsh M. , Jotwani Rohan , Hao David
Published: January 2024

Background

Extended reality technology, encompassing augmented reality, mixed reality, and virtual reality, has the potential to enhance the teaching and performance of neuraxial procedures. The diverse applications of extended reality include immersive simulations and novel modes of procedural navigation.

Objectives

This scoping review aims to explore the preclinical, clinical, and educational applications of extended reality for neuraxial procedures while suggesting directions for future research.

Evidence review

A systematic search was conducted across PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar until December 2023. Additional sources were identified via citation searching of relevant articles. The findings are reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).

Findings

41 studies, including three pending clinical trials were included. The majority of included studies were published after 2015. Extended reality technology was applied in diverse ways for teaching, simulation, and navigation, but only four of the completed studies described clinical use. For the display of visuals, computer screens were most commonly used, followed by head-mounted devices, laser projectors, and semi-transparent mirrors.

Conclusions

Interest in utilizing extended reality technology for neuraxial procedures is growing. Preliminary work shows promise for this technology in both education and clinical practice, but achieving accurate image registration without disrupting existing workflows remains an ongoing barrier to clinical testing. Additional research is needed to assess the cost-effectiveness and reliability of this technology.
Reliable prediction of childhood obesity using only routinely collected EHRs is possible
Authors: Gupta Mehak , Phan Thao-Ly T. , Eckrich Daniel , Bunnell H. Timothy , Beheshti Rahmatollah
Published: January 2024

Objective

Identifying children at high risk of developing obesity can offer a critical time to change the course of the disease before it establishes. Numerous studies have tried to achieve this; but practical limitations remain, including (i) relying on data not present in routinely available pediatric data (like prenatal data), (ii) focusing on a single age prediction (hence, not tested across ages), and (iii) not achieving good results or adequately validating those.

Methods

A customized sequential deep learning model was built to predict the risk of childhood obesity, focusing especially on capturing the temporal patterns. The model was trained only on routinely collected EHRs, containing a list of features identified by a group of clinical experts, and sourced from 36,191 diverse children aged 0 to 10. The model was evaluated using extensive discrimination, calibration, and utility analysis; and was validated temporally, geographically, and across various subgroups.

Results

Our results are mostly better (and never worse) than all previous studies, including those that focus on single-age predictions or link EHRs to external data. Specifically, the model consistently achieved an area under the curve (AUROC) of above 0.8 (with most cases around 0.9) for predicting obesity within the next 3 years for children 2 to 7. The validation results show the robustness of the model. Furthermore, the most influential predictors of the model match important risk factors of obesity.

Conclusions

Our model is able to predict the risk of obesity for young children using only routinely collected EHR data, greatly facilitating its integration with the periodicity schedule. The model can serve as an objective screening tool to inform prevention efforts, especially by helping with very delicate interactions between providers and families in primary care settings.
SKSR1 identified as key virulence factor inCryptosporidiumby genetic crossing
Authors: He Wei , Sun Lianbei , Hou Tianyi , Yang Zuwei , Yang Fuxian , Zhang Shengchen , Wang Tianpeng , Li Na , Guo Yaqiong , Sibley L. David , Feng Yaoyu , Xiao Lihua
Published: January 2024

Cryptosporidium parvumis a major cause of severe diarrhea. Although isolates of this zoonotic parasite exhibit significant differences in infectivity and virulence, the genetic determinants for these traits are not clear. In this study, we used classical genetics to cross twoC. parvumisolates of different virulence and used bulked segregant analysis of whole-genome sequence data from the progeny to identify quantitative trait loci (QTL) associated withCryptosporidiuminfectivity and virulence. Of the 26 genes in three QTL, two had loss-of-function mutations in the low-virulence isolates. Deletion of theSKSR1gene or expression of the frame-shift mutant sequence reduced the pathogenicity of infectionin vivo. SKSR1 is a polymorphic secretory protein expressed in small granules and secreted into the parasite-host interface. These results demonstrate that SKSR1 is an important virulence factor inCryptosporidium,and suggest that this extended family may contribute to pathogenesis.
Population genetics, phylogeography and gene flow of mainland and island vampire bat (Desmodus rotundus)populations: an investigation into mainland-island bat movement
Authors: Seetahal Janine F.R. , Streicker Daniel G. , Beerli Peter , Sahadeo Nikita , Lemey Philippe , Sanchez-Vazquez Manuel J. , Broos Alice , Bergner Laura , Ramkissoon Vernie , Mahabir Ron , Tihul Praimnauth , Hartley Dane , Sauers Astrid Van , Karg Gianna , Mohammed Ryan S. , Biek Roman , Oura Christopher A.L. , Carrington Christine V.F.
Published: January 2024

Movement of animals and plants from mainland populations contributes to the genetic diversity and viability of geographically isolated island biota, but also carries risks of pathogen introductions. The bat fauna of the island of Trinidad reflects species diversity on the neighbouring South American mainland and includes the common vampire bat (Desmodus rotundus). We determined relationships between Trinidad and mainland vampire bat populations and the extent of mainland-island movement by comparing the genetic structure (nuclear and mitochondrial) and morphology of the TrinidadianD. rotunduspopulation to populations in neighbouring regions of the South American mainland and estimating evolutionary histories and patterns of gene flow.

Results indicate that TrinidadianD. rotundusare genetically and morphologically distinct from mainland populations, although limited unidirectional male-biased mainland to island gene flow occurs at an estimated rate of 3.3 migrants per year. Two geographically-definedDesmoduscytochromebclades were identified within Trinidad (i.e., one restricted to the South-Western peninsula which grouped with Venezuelan sequences and the other found throughout the rest of the island which grouped with sequences from Suriname and Guyana) suggesting long-standing female philopatry. The geographic distribution of these clades mirrors that of two previously identified geographically defined rabies virus (RABV) lineages introduced to Trinidad from the mainland. This finding suggests that bat dispersals and RABV introductions occur via both the northern and south-western island peninsulas, with subsequent male-driven intra-island viral spread enabled by bat nuclear homogeneity of these populations. These study findings will contribute to the development of contemporary evidence-based vampire bat population control and rabies prevention programs within island populations.
Scale-Dependent Coding of the Hippocampus in Relational Memory
Authors: Ding Wei , Lin Yijing , Zhang Bo , Liu Jia
Published: January 2024

Memory, woven into the very fabric of consciousness, serves as a time-traveling vessel in the mind, using detailed recollections not just for nostalgic reflection but as an abstract map for charting unknown futures. Here, we employed fMRI to investigate how the hippocampus (HPC) encodes detailed experiences into abstract knowledge (i.e., formation) and uses this knowledge for decision making (i.e., utilization) when human participants learned and then utilized spatial-temporal relations in a relational memory task. We found a functional gradient along the anterior-posterior axis of the HPC, characterized by representational similarity and functional connectivity with the autobiographical network. Here, the posterior HPC was more actively engaged in memory formation, whereas the anterior HPC was predominantly involved in memory utilization. Our computational modeling of relational memory further established a causal link between this functional gradient and the HPC’s well-documented anatomical gradient, as optimal task performance arose from a combination of a fine-grained representation of past experiences by the posterior HPC and a coarser representation of abstract knowledge for future planning by the anterior HPC. This scale-dependent coding scheme led to the emergence of grid-like, heading direction-like, and place-like units in our neural network model, analogous to those discovered in biological brains. Taken together, our study revealed the HPC’s functional gradient in representing relational memory, and further connected it to the anatomical gradient of place cells, supporting a unified framework where both spatial and episodic memory rely on relational representations that integrate spatial localization with temporal continuity.
Two-Pole Nature of the
Λ(1405)
Resonance from Lattice QCD
Authors: Bulava John , Cid-Mora Bárbara , Hanlon Andrew D. , Hörz Ben , Mohler Daniel , Morningstar Colin , Moscoso Joseph , Nicholson Amy , Romero-López Fernando , Skinner Sarah , Walker-Loud André ,   Baryon Scattering (BaSc) Collaboration
Published: January 2024

This Letter presents the first lattice QCD computation of the coupled channel πΣ−K¯N scattering amplitudes at energies near 1405 MeV. These amplitudes contain the resonance Λ(1405) with strangeness S=−1 and isospin, spin, and parity quantum numbers I(JP)=0(1/2−). However, whether there is a single resonance or two nearby resonance poles in this region is controversial theoretically and experimentally. Using single-baryon and meson-baryon operators to extract the finite-volume stationary-state energies to obtain the scattering amplitudes at slightly unphysical quark masses corresponding to mπ≈200  MeV and mK≈487  MeV, this study finds the amplitudes exhibit a virtual bound state below the πΣ threshold in addition to the established resonance pole just below the K¯N threshold. Several parametrizations of the two-channel K matrix are employed to fit the lattice QCD results, all of which support the two-pole picture suggested by SU(3) chiral symmetry and unitarity.

Published by the American Physical Society
2024
Experimental Characterization of Defect-Induced Phonon Lifetime Shortening
Authors: Liu Boyao , Kelsall Jack , Ward David J. , Jardine Andrew P.
Published: January 2024

We present the first direct experimental measurement of defect-induced lifetime shortening of acoustic surface phonons. Defects are found to contribute a temperature-independent component to the linewidths of Rayleigh wave phonons on a Ni(111) surface. We also characterized the increase in phonon scattering with both surface defect density and phonon wave vector. A quantitative estimate of the scattering rate between phonon modes and surface line defects is extracted from the experimental data for the first time.

Published by the American Physical Society
2024
Structural transformation of dusty plasma crystal in dc discharge plasma by changing confinement ring bias
Authors: Jaiswal S. , Belt Connor , Kananovich Anton , Aguirre E. M.
Published: January 2024

We report an experimental study of the structural transition of a stable complex plasma crystal to a solid-liquid phase coexistence by the controlled adjustment of the confinement potential, while keeping all other parameters constant. The experiments are carried out on a tabletop linear dusty plasma experimental device, which consists of a circular powered electrode and an extended grounded cathode plate. A stationary crystal of melamine formaldehyde particles is formed in a background of argon plasma inside a confining ring that is isolated from the cathode by a ceramic cover. The stable crystal structure breaks in the core region and transitions to a coexistent state by carefully changing the confining potential, thereby modifying the sheath structure. The transition is confirmed by evaluating the variation in different characteristic parameters such as the pair correlation function, local bond order parameter, and dust kinetic temperature as a function of confining bias potential. It is found that melting in the core is due to the onset of dust fluctuations in the layers beneath the topmost layer, which grow in amplitude as the confining bias potential is reduced below a threshold value. The present technique of changing confinement provides a unique feature to study structural transitions of plasma crystals without affecting the overall plasma parameters.

Published by the American Physical Society
2024
Classification of Lifshitz invariant in multiband superconductors: An application to Leggett modes in the linear response regime in Kagome lattice models
Authors: Nagashima Raigo , Tian Sida , Haenel Rafael , Tsuji Naoto , Manske Dirk
Published: January 2024

Multiband superconductors are sources of rich physics arising from multiple order parameters, which show unique collective dynamics including Leggett mode as relative phase oscillations. Previously, it has been pointed out that the Leggett mode can be optically excited in the linear response regime, as demonstrated in a one-dimensional model for multiband superconductors [T. Kamatani , ]. Here we identify the linear coupling term in the Ginzburg-Landau free energy to be the so-called Lifshitz invariant, which takes the form of d·(Ψi*∇Ψj−Ψj*∇Ψi), where d is a constant vector and Ψi and Ψj(i≠j) represent superconducting order parameters. We classify all pairs of irreducible representations of order parameters in the crystallographic point groups that allow for the existence of the Lifshitz invariant. We emphasize that the Lifshitz invariant can appear even in systems with inversion symmetry. The results are applied to a model of

s

-wave superconductors on a Kagome lattice with various bond orders, for which in some cases we confirm that the Leggett mode appears as a resonance peak in a linear optical conductivity spectrum based on microscopic calculations. We discuss a possible experimental observation of the Leggett mode by a linear optical response in multiband superconductors.

Published by the American Physical Society
2024
Four-Dimensional Mesoscale Liquid Model of Nucleus Resolves Chromatin's Radial Organization
Authors: Laghmach Rabia , Di Pierro Michele , Potoyan Davit A.
Published: January 2024

Recent advances chromatin capture, imaging techniques, and polymer modeling have dramatically enhanced quantitative understanding of chromosomal folding. However, the dynamism inherent in genome architectures due to physical and biochemical forces and their impact on nuclear architecture and cellular functions remains elusive. While imaging of chromatin in four dimensions is becoming more common, there is a conspicuous lack of physics-based computational tools appropriate for revealing the forces that shape nuclear architecture and dynamics. To this end, we have developed a multiphase liquid model of the nucleus, which can resolve chromosomal territories, compartments, and nuclear lamina using a physics-based and data-informed free-energy function. The model enables rapid hypothesis-driven prototyping of nuclear dynamics in four dimensions, thereby facilitating comparison with whole nucleus imaging experiments. As an application, we model the nucleus and map phase diagram of various possible nuclear morphologies. We shed light on the interplay of adhesive and cohesive interactions which give rise to distinct radial organization seen in conventional, inverted, and senescent nuclear architectures. The results also show the highly dynamic nature of the radial organization, the disruption of which leads to significant variability in domain coarsening dynamics and consequently variability of chromatin architecture. The model also highlights the impact of oblate nuclear geometry and heterochromatin-subtype interactions on the global chromatin architecture and local asymmetry of chromatin compartments.

Published by the American Physical Society
2024
Deciphering the crystal structure of a novel nanobody against the NEIL1 DNA glycosylase
Authors: Thompson Marlo K. , Sharma Nidhi , Thorn Andrea , Prakash Aishwarya
Published: January 2024

Nanobodies (VHHs) are single-domain antibodies with three antigenic CDR regions and are used in diverse scientific applications. Here, an ∼14 kDa nanobody (A5) specific for the endonuclease VIII (Nei)-like 1 or NEIL1 DNA glycosylase involved in the first step of the base-excision repair pathway was crystallized and its structure was determined to 2.1 Å resolution. The crystals posed challenges due to potential twinning and anisotropic diffraction. Despite inconclusive twinning indicators, reprocessing in an orthorhombic setting and molecular replacement in space group P21212 enabled the successful modeling of 96% of residues in the asymmetric unit, with final R
work and R
free values of 0.199 and 0.229, respectively.
Effectiveness of digital rhetoric persuasion on GenZ consumer purchasing decisions
Authors: Gupta Hemant , Parmar Bhaveshkumar J.
Published: January 2024

Purpose

The study aims to analyze the effectiveness of digital rhetoric persuasion on GenZ purchase decision. Digital rhetoric (DR) is an art of persuasion used in social media communication to shape and influence the course of an individual. It has been used in social media advertisements (SMAs) to increase its perceived effectiveness. GenZ consumers are more vibrant than previous generations’ consumers because of high levels of literacy and capacity to adapt to new technology. Therefore, understanding the effects of rhetorical support decisions to act on and mold consumers’ reasoning and judgment is particularly significant in relation to GenZ purchasing decisions and the rhetorical persuasive methods. Concurrently, the moderating effect of generation cohort theory also needs to be examined.

Design/methodology/approach

The threshold model for consumers’ purchase decisions in the form of logistic regression has been applied to examine the impact of DR through SMAs on the purchase intention (PI) of GenZ consumers. Simultaneously, the moderating effect of generation cohort theory is being examined by comparative analysis of different generations’ PI moderation by DR effect.

Findings

The results of the current study reveal that DR via SMAs has a positive and significant influence on GenZ consumers’ PI, whereas other older generation consumers do not get similarly affected by the same.

Originality/value

In an emerging economy like India, where 30% of the population belongs to the GenZ category and the digital advertising industry is growing by double digits, the present study takes a novel approach to examine the impact of DR via SMAs on GenZ consumers’ PI. Concurrently, it also provides an understanding of the moderation effect of generation cohort theory on perceived effectiveness of DR.
Nexus among blockchain technology adoption and firm performance: perspective from mediating and moderating effects
Authors: Abu Afifa Malik Muneer , Nguyen Tho Hoang , Nguyen Lien Thuy Le , Tran Thuy Hong Thi , Dao Nhan Thanh
Published: January 2024

Purpose

This study aims to examine the relationship between blockchain technology (BCT) adoption and firm performance (FIP) mediated by cyber-security risk management (CSRM) in the context of Vietnam, a developing country. Besides, the mediating effect of risk-taking tendency (RTT) has been considered in the BCT–CSRM nexus.

Design/methodology/approach

Data is collected using a survey questionnaire of Vietnamese financial firms through strict screening steps to ensure the representativeness of the population. The ending pattern of 449 responses has been used for analysis.

Findings

The findings of partial least squares structural equation modeling demonstrated that CSRM has a positive effect on FIP and acts as a mediator in the BCT–FIP nexus. Furthermore, RTT moderates the relationship between BCT and CSRM significantly.

Practical implications

This study introduces the attractive attributes of applying BCT to CSRM. Accordingly, managers should rely on BCT and take advantage of it to improve investment resources, business activities and functional areas to enhance their firm's CSRM. Especially, managers should pay attention to enhancing their RTT, which improves FIP.

Originality/value

This study supplements the previous literature in the context of CSRM by indicating favorable effects of BCT and RTT. Additionally, this study identifies the effectiveness of RTT as well as its moderating role. Ultimately, this paper has been managed as a pioneering empirical study that integrates BCT, RTT and CSRM in the same model in a developing country, specifically Vietnam.
A survey of the most prevalent sustainability initiatives at universities
Authors: Farag Karin , Aktas Can Baran
Published: January 2024

Purpose

The purpose of this study is to identify the most prevalent initiatives undertaken by leading universities in sustainability and offer a roadmap for other institutions seeking to undertake similar actions and contribute to more effective implementation of sustainability practices.

Design/methodology/approach

By using a quantitative assessment approach, the study sheds light on successful initiatives implemented by universities worldwide, spanning six categories: transportation, waste management, curriculum, food and dining, water and energy. Each category is clearly related to one or more of the 17 sustainable development goals. A cluster analysis was also applied to identify regional trends in preferred initiatives.

Findings

The study underlines the importance of integrating sustainability principles into the curricula of higher education institutions (HEIs) as well as educating staff members on energy and water management. The most common and impactful initiatives in the studied six categories have been identified. Many of the initiatives mentioned in the study do not just result in reducing ecological footprint but also provide economic savings as well. Differences among regions and countries were observed in the implementation of initiatives. Cultural and habitual factors should not be disregarded during the selection process of initiatives.

Originality/value

The findings of this study may help universities to take their first steps toward implementing initiatives that can effectively promote sustainable development. Results will aid other HEIs in planning for next steps while outlining the more common initiatives.