bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis
Authors: Hong Jingjing , Li Tingting , Chao Yulin , Xu Yidan , Zhu Zhini , Zhou Zixuan , Gu Weijie , Qu Qianhui , Li Dianfan 
Published: January 2024

AbstractThe secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66−2.84 Å), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling.
Molecular basis of human trace amine-associated receptor 1 activation
Authors: Zilberg Gregory , Parpounas Alexandra K. , Warren Audrey L. , Yang Shifan , Wacker Daniel 
Published: January 2024

AbstractThe human trace amine-associated receptor 1 (hTAAR1, hTA1) is a key regulator of monoaminergic neurotransmission and the actions of psychostimulants. Despite preclinical research demonstrating its tractability as a drug target, its molecular mechanisms of activation remain unclear. Moreover, poorly understood pharmacological differences between rodent and human TA1 complicate the translation of findings from preclinical disease models into novel pharmacotherapies. To elucidate hTA1’s mechanisms on the molecular scale and investigate the underpinnings of its divergent pharmacology from rodent orthologs, we herein report the structure of the human TA1 receptor in complex with a Gαs heterotrimer. Our structure reveals shared structural elements with other TAARs, as well as with its closest monoaminergic orthologue, the serotonin receptor 5-HT4R. We further find that a single mutation dramatically shifts the selectivity of hTA1 towards that of its rodent orthologues, and report on the effects of substituting residues to those found in serotonin and dopamine receptors. Strikingly, we also discover that the atypical antipsychotic medication and pan-monoaminergic antagonist asenapine potently and efficaciously activates hTA1. Together our studies provide detailed insight into hTA1 structure and function, contrast its molecular pharmacology with that of related receptors, and uncover off-target activities of monoaminergic drugs at hTA1.
Purely self-rectifying memristor-based passive crossbar array for artificial neural network accelerators
Authors: Jeon Kanghyeok , Ryu Jin Joo , Im Seongil , Seo Hyun Kyu , Eom Taeyong , Ju Hyunsu , Yang Min Kyu , Jeong Doo Seok , Kim Gun Hwan 
Published: January 2024

AbstractMemristor-integrated passive crossbar arrays (CAs) could potentially accelerate neural network (NN) computations, but studies on these devices are limited to software-based simulations owing to their poor reliability. Herein, we propose a self-rectifying memristor-based 1 kb CA as a hardware accelerator for NN computations. We conducted fully hardware-based single-layer NN classification tasks involving the Modified National Institute of Standards and Technology database using the developed passive CA, and achieved 100% classification accuracy for 1500 test sets. We also investigated the influences of the defect-tolerance capability of the CA, impact of the conductance range of the integrated memristors, and presence or absence of selection functionality in the integrated memristors on the image classification tasks. We offer valuable insights into the behavior and performance of CA devices under various conditions and provide evidence of the practicality of memristor-integrated passive CAs as hardware accelerators for NN applications.
A suberized exodermis is required for tomato drought tolerance
Authors: Cantó-Pastor Alex , Kajala Kaisa , Shaar-Moshe Lidor , Manzano Concepción , Timilsena Prakash , De Bellis Damien , Gray Sharon , Holbein Julia , Yang He , Mohammad Sana , Nirmal Niba , Suresh Kiran , Ursache Robertas , Mason G. Alex , Gouran Mona , West Donnelly A. , Borowsky Alexander T. , Shackel Kenneth A. , Sinha Neelima , Bailey-Serres Julia , Geldner Niko , Li Song , Franke Rochus Benni , Brady Siobhan M. 
Published: January 2024

AbstractPlant roots integrate environmental signals with development using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates flow of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation but is absent in the tomato endodermis. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here we demonstrate that the suberin regulatory network has the same parts driving suberin production in the tomato exodermis and the Arabidopsis endodermis. Despite this co-option of network components, the network has undergone rewiring to drive distinct spatial expression and with distinct contributions of specific genes. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response and that the exodermal barrier serves an equivalent function to that of the endodermis and can act in its place.
An ensemble learning model for continuous cognition assessment based on resting-state EEG
Authors: Sun Jingnan , Sun Yike , Shen Anruo , Li Yunxia , Gao Xiaorong , Lu Bai 
Published: January 2024

AbstractOne critical manifestation of neurological deterioration is the sign of cognitive decline. Causes of cognitive decline include but are not limited to: aging, cerebrovascular disease, Alzheimer’s disease, and trauma. Currently, the primary tool used to examine cognitive decline is scale. However, scale examination has drawbacks such as its clinician subjectivity and inconsistent results. This study attempted to use resting-state EEG to construct a cognitive assessment model that is capable of providing a more scientific and robust evaluation on cognition levels. In this study, 75 healthy subjects, 99 patients with Mild Cognitive Impairment (MCI), and 78 patients with dementia were involved. Their resting-state EEG signals were collected twice, and the recording devices varied. By matching these EEG and traditional scale results, the proposed cognition assessment model was trained based on Adaptive Boosting (AdaBoost) and Support Vector Machines (SVM) methods, mapping subjects’ cognitive levels to a 0–100 test score with a mean error of 4.82 (<5%). This study is the first to establish a continuous evaluation model of cognitive decline on a large sample dataset. Its cross-device usability also suggests universality and robustness of this EEG model, offering a more reliable and affordable way to assess cognitive decline for clinical diagnosis and treatment as well. Furthermore, the interpretability of features involved may further contribute to the early diagnosis and superior treatment evaluation of Alzheimer’s disease.
The HLA-DRB1*09:01-DQB1*03:03 haplotype is associated with the risk for late-onset Alzheimer’s disease in APOE $${{\varepsilon }}$$4–negative Japanese adults
Authors: Shigemizu Daichi , Fukunaga Koya , Yamakawa Akiko , Suganuma Mutsumi , Fujita Kosuke , Kimura Tetsuaki , Watanabe Ken , Mushiroda Taisei , Sakurai Takashi , Niida Shumpei , Ozaki Kouichi 
Published: January 2024

AbstractLate-onset Alzheimer’s disease (LOAD) is the most common cause of dementia among those older than 65 years. The onset of LOAD is influenced by neuroinflammation. The human leukocyte antigen (HLA) system is involved in regulating inflammatory responses. Numerous HLA alleles and their haplotypes have shown varying associations with LOAD in diverse populations, yet their impact on the Japanese population remains to be elucidated. Here, we conducted a comprehensive investigation into the associations between LOAD and HLA alleles within the Japanese population. Using whole-genome sequencing (WGS) data from 303 LOAD patients and 1717 cognitively normal (CN) controls, we identified four-digit HLA class I alleles (A, B, and C) and class II alleles (DRB1, DQB1, and DPB1). We found a significant association between the HLA-DRB1*09:01-DQB1*03:03 haplotype and LOAD risk in APOE$${\rm{\varepsilon }}$$
ε
4–negative samples (odds ratio = 1.81, 95% confidence interval = 1.38–2.38, P = 2.03$${\times 10}^{-5}$$

×
10

−
5

). These alleles not only showed distinctive frequencies specific to East Asians but demonstrated a high degree of linkage disequilibrium in APOE$${\rm{\varepsilon }}$$
ε
4–negative samples (r2 = 0.88). Because HLA class II molecules interact with T-cell receptors (TCRs), we explored potential disparities in the diversities of TCR α chain (TRA) and β chain (TRB) repertoires between APOE$${\rm{\varepsilon }}$$
ε
4–negative LOAD and CN samples. Lower diversity of TRA repertoires was associated with LOAD in APOE$${\rm{\varepsilon }}$$
ε
4-negative samples, irrespective of the HLA DRB1*09:01-DQB1*03:03 haplotype. Our study enhances the understanding of the etiology of LOAD in the Japanese population and provides new insights into the underlying mechanisms of its pathogenesis.
Ocular complaints and diagnoses in spaceflight
Authors: Meer Elana , Grob Seanna R. , Lehnhardt Kris , Sawyer Aenor 
Published: January 2024

AbstractThe NASA human system risk board (HSRB) has long focused on trauma and acute medical illness as a key contributor to high level in-flight medical risk. However, ocular issues, trauma, and complaints during spaceflight are poorly characterized. In a retrospective case series, the NASA data from the life sciences data archieve (LSDA) and the lifetime surveillance of astronaught health (LSAH) was queried for eye related complaints and conditions in spaceflight across international space station (ISS) missions and space shuttle (STS) missions. The ISS dataset included missions from the year 2000 to 2020, and the STS dataset included missions from 1981 to 2011. Data were reviewed and segmented into categories of ocular complaints. 135 STS missions and 63 ISS missions were included in this analysis. Ocular events were only noted across 83 STS missions (61.5%) and 41 ISS missions (65.1%). Overall, the most common ocular complaints were eye irritation (n = 80, 33.1%), ocular foreign body or foreign body sensation (n = 55, 22.7%), dry eye syndromes (n = 38, 15.7%), epiphora or excessive tearing (n = 19, 7.85%). Of all ocular complaints or diagnoses, 9 (3.72%) were considered higher severity (keratitis, corneal ulcer, chemical exposure, and corneal abrasion). However, seemingly none required evacuation from mission. Improved depiction of ocular symptoms and diagnoses, and a more standard classification system and process to describe ocular symptoms, diagnoses, and treatments in space is crucial to provide more effective and comprehensive treatments.
Risk factors associated with age at onset of Parkinson’s disease in the UK Biobank
Authors: Huang Yuanfeng , Chen Qian , Wang Zheng , Wang Yijing , Lian Aojie , Zhou Qiao , Zhao Guihu , Xia Kun , Tang Beisha , Li Bin , Li Jinchen 
Published: January 2024

AbstractSubstantial evidence shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from the UK Biobank were included in this study. We evaluated the effects of polygenic risk scores (PRS), nongenetic risk factors, and their interaction on the AAO using Mann–Whitney U tests and regression analyses. We further identified the genes interacting with nongenetic risk factors for the AAO using genome-wide environment interaction studies. We newly found physical activity (P < 0.0001) was positively associated with AAO and excessive daytime sleepiness (P < 0.0001) was negatively associated with AAO, and reproduced the positive associations of smoking and non-steroidal anti-inflammatory drug intake and the negative association of family history with AAO. In the dose-dependent analyses, smoking duration (P = 1.95 × 10−6), coffee consumption (P = 0.0150), and tea consumption (P = 0.0008) were positively associated with AAO. Individuals with higher PRS had younger AAO (P = 3.91 × 10−5). In addition, we observed a significant interaction between the PRS and smoking for AAO (P = 0.0316). Specifically, several genes, including ANGPT1 (P = 7.17 × 10−7) and PLEKHA6 (P = 4.87 × 10−6), may influence the positive relationship between smoking and AAO. Our data suggests that genetic and nongenetic risk factors are associated with the AAO of PD and that there is an interaction between the two.
Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate
Authors: Desalegn Girmay , Tamilselvi Chitradevi S. , Lemme-Dumit Jose M. , Heine Shannon J. , Dunn Dylan , Ndungo Esther , Kapoor Neeraj , Oaks Edwin V. , Fairman Jeff , Pasetti Marcela F. 
Published: January 2024

AbstractDiarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.
Process optimization of osmotic membrane distillation for the extraction of valuable resources from water streams
Authors: Morciano Matteo , Malaguti Marco , Ricceri Francesco , Tiraferri Alberto , Fasano Matteo 
Published: January 2024

AbstractThe rising demand for sustainable wastewater management and high-value resource recovery is pressing industries involved in, e.g., textiles, metals, and food production, to adopt energy-efficient and flexible liquid separation methods. The current techniques often fall short in achieving zero liquid discharge and enhancing socio-economic growth sustainably. Osmotic membrane distillation (OMD) has emerged as a low-temperature separation process designed to concentrate valuable elements and substances in dilute feed streams. The efficacy of OMD hinges on the solvent’s migration from the feed to the draw stream through a hydrophobic membrane, driven by the vapor pressure difference induced by both temperature and concentration gradients. However, the intricate interplay of heat and mass processes steering this mechanism is not yet fully comprehended or accurately modeled. In this research, we conducted a combined theoretical and experimental study to explore the capabilities and thermodynamic limitations of OMD. Under diverse operating conditions, the experimental campaign aimed to corroborate our theoretical assertions. We derived a novel equation to govern water flux based on foundational principles and introduced a streamlined version for more straightforward application. Our findings spotlight complex transport-limiting and self-adjusting mechanisms linked with temperature and concentration polarization phenomena. Compared with traditional methods like membrane distillation and osmotic dilution, which are driven by solely temperature or concentration gradients, OMD may provide improved and flexible performance in target applications. For instance, we show that OMD—if properly optimized—can achieve water vapor fluxes 50% higher than osmotic dilution. Notably, OMD operation at reduced feed temperatures can lead to energy savings ranging between 5 and 95%, owing to the use of highly concentrated draw solutions. This study underscores the potential of OMD in real-world applications, such as concentrating lithium in wastewater streams. By enhancing our fundamental understanding of OMD’s potential and constraints, we aim to broaden its adoption as a pivotal liquid separation tool, with focus on sustainable resource recovery.
Humanoid facial expressions as a tool to study human behaviour
Authors: Lombardi G. , Sciutti A. , Rea F. , Vannucci F. , Di Cesare G. 
Published: January 2024

AbstractBesides action vitality forms, facial expressions represent another fundamental social cue which enables to infer the affective state of others. In the present study, we proposed the iCub robot as an interactive and controllable agent to investigate whether and how different facial expressions, associated to different action vitality forms, could modulate the motor behaviour of participants. To this purpose, we carried out a kinematic experiment in which 18 healthy participants observed video-clips of the iCub robot performing a rude or gentle request with a happy or angry facial expression. After this request, they were asked to grasp an object and pass it towards the iCub robot. Results showed that the iCub facial expressions significantly modulated participants motor response. Particularly, the observation of a happy facial expression, associated to a rude action, decreased specific kinematic parameters such as velocity, acceleration and maximum height of movement. In contrast, the observation of an angry facial expression, associated to a gentle action, increased the same kinematic parameters. Moreover, a behavioural study corroborated these findings, showing that the perception of the same action vitality form was modified when associated to a positive or negative facial expression.
Improving long COVID-related text classification: a novel end-to-end domain-adaptive paraphrasing framework
Authors: Somayajula Sai Ashish , Litake Onkar , Liang Youwei , Hosseini Ramtin , Nemati Shamim , Wilson David O. , Weinreb Robert N. , Malhotra Atul , Xie Pengtao 
Published: January 2024

AbstractThe emergence of long COVID during the ongoing COVID-19 pandemic has presented considerable challenges for healthcare professionals and researchers. The task of identifying relevant literature is particularly daunting due to the rapidly evolving scientific landscape, inconsistent definitions, and a lack of standardized nomenclature. This paper proposes a novel solution to this challenge by employing machine learning techniques to classify long COVID literature. However, the scarcity of annotated data for machine learning poses a significant obstacle. To overcome this, we introduce a strategy called medical paraphrasing, which diversifies the training data while maintaining the original content. Additionally, we propose a Data-Reweighting-Based Multi-Level Optimization Framework for Domain Adaptive Paraphrasing, supported by a Meta-Weight-Network (MWN). This innovative approach incorporates feedback from the downstream text classification model to influence the training of the paraphrasing model. During the training process, the framework assigns higher weights to the training examples that contribute more effectively to the downstream task of long COVID text classification. Our findings demonstrate that this method substantially improves the accuracy and efficiency of long COVID literature classification, offering a valuable tool for physicians and researchers navigating this complex and ever-evolving field.
Diagnostic validation study of rapid urinary tract infection diagnosis kit at peripheral health facilities of West Bengal, India
Authors: Chakraborty Debjit , Debnath Falguni , Majumdar Agniva , Chakrabarti Atreyi , Sharma Monica , Walia Kamini , Deb Alok Kumar , Dutta Shanta 
Published: January 2024

AbstractPatients reporting to the outpatient departments of peripheral health care settings in India with symptoms of urinary tract infection (UTI) receive one or the other antibiotic before culture confirmation and out of the total culture confirmed UTI cases, in less than one third cases the prescribed antibiotics matches to the antibiotic sensitivity test result. Hence, in this study, an indigenous point-of-care (POCT) rapid diagnostic kit (Rapidogram) for UTI was validated against conventional urine culture and sensitivity to understand its possible applicability at peripheral health care settings. This cross-sectional study was conducted during November 2021 to June 2022 in OPDs of two peripheral hospitals. A sample size of 300 was calculated using prevalence of urinary tract infection (UTI) as 33% for sensitivity and specificity using Buderer’s formula. Urine specimens were collected following standard aseptic procedures from the recruited suspected UTI cases and transferred to laboratory maintaining the cold chain. The validation work up was done in two sections: lab validation and field validation. Out of 300 urine samples, 29 were found positive for the growth of UTI pathogen by both methods and 267 were found negative by both methods. Thus, the kit shows very high specificity (99.6%; 97.9–99.9%) and considerably high sensitivity (90.6%; 74.9–98.0%). We also observed higher PPV, NPV, test accuracy (> 96%). Diagnostic Odds Ratio and Youden index were respectively 2581 and 0.89. Clinical data showed that 44% of the suspected UTI cases were prescribed at least one antibiotic before urine test. Mostly they received Norfloxacin whereas the mostly identified organism E.coli was sensitive to Nitrofurantoin. In the context of absence of microbiology facility at peripheral setting and rampant empirical use of antibiotics in UTI, this highly specific and sensitive POCT for UTI may be used as it not only identifies the organism, also shows the antibiotic sensitivity pattern.