bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social complexity affects cognitive abilities but not brain structure in a Poecilid fish
Authors: Triki Zegni , Zhou Tunhe , Argyriou Elli , Sousa de Novais Edson , Servant Oriane , Kolm Niclas 
Published: August 2023

AbstractComplex cognitive performance is suggested to be the out-turn of complex social life, allowing individuals to achieve higher fitness through sophisticated “Machiavellian” strategies. Although there is ample support for this concept, especially when comparing species, most of the evidence is correlative. Here we provide an experimental investigation of how group size and composition may affect brain and cognitive development in the guppy (Poecilia reticulata). For six months, we reared sexually mature female guppies in one of three different social treatments: (i) three female guppies; (ii) three female guppies mixed with three female splash tetras (Copella arnoldi), a species that co-occurs with the guppy in the wild; and (iii) six female guppies. We then tested the guppies’ performance in inhibitory control, associative learning and reversal learning tasks to evaluate their self-control, operant conditioning and cognitive flexibility capabilities. Afterwards, we estimated their brain size and the size of major brain regions using X-ray imaging technology. We found that individuals in larger groups of six individuals, in both same and mixed species treatments, outperformed individuals from the smaller groups of three guppies in reversal learning, with no apparent differences in the inhibitory control and associative learning tasks. This is rare evidence of how living in larger social groups improves cognitive flexibility, supporting that social pressures play an important role in shaping individual cognitive development. Interestingly, social manipulation had no apparent effect on brain morphology, but relatively larger telencephalons were associated with better individual performance in reversal learning. This suggests alternative mechanisms beyond brain region size enabled greater cognitive flexibility in individuals from larger groups.
Improved Activity and Kinetics of Endoglucanase Biofuel Enzyme with Addition of an AzoTAB Surfactant
Authors: Seidel Zumra Peksaglam , Ted Lee C. 
Published: August 2023

AbstractEndoglucanases degradeβ-1,4-glycosidic bonds of crystalline cellulose into insoluble or soluble cellooligosaccharides at the solid-liquid interface. The enhanced activity and kinetics of endoglucanase fromAspergillus nigerwith addition of a light responsive azobenzene trimethyl ammonium bromide (azoTAB) surfactant is studied. AzoTAB is a photoresponsive surfactant that exists as a relatively-hydrophobictransisomer under visible light (434 nm) and a relatively-hydrophiliccisisomer under UV light (350 nm). Endoglucanase catalytic activity can be controlled with light illumination slightly for microcrystalline cellulose natural substate (∼15%) and significantly for p-nitrophenol-based model substrate (∼2-fold) by switching between thetrans(higher enzyme binding affinity, resulting higher enzyme unfolding) andcisform of azoTAB. Endoglucanase activity increases 45% towards avicel crystalline substate and 4-fold towards 4-nitrophenyl β-D-cellobioside substrate in the presence of 0.4 mM azoTAB under UV light (90%cisand 10%transisomers). In comparison, endoglucanase catalytic activity increases 5-10% towards crystalline cellulose substrate with the addition of sodium dodecyl benzene sulfonate (SDBS), sodium dodecyl sulfate (SDS) and dodecyl trimethyl ammonium (DTAB). 0.4 mM AzoTAB-UV addition leads to an increase of maximum endoglucanase adsorption (Emax) from 7.89 mg enzyme/g avicel to 12.92 mg enzyme/g avicel and catalytic enzyme efficiency (kcat/KM) from 0.031 L/(mg.s) to 0.061 L/(mg.s). It is found that adsorbed enzyme concentration on substrate correlates to enzyme specific activity for azoTAB containing reaction. Additionally, 40-50% activity enhancement and increased bound enzyme to substrate are detected with azoTAB addition at different enzyme, substrate, and inhibitor concentrations. Improvement of substrate properties of azoTAB addition is associated with lower reciprocal terms of Michaelis constant (KM), the adsorption coefficient (Kad) and fractal parameter (h) values similar to the presence of other surfactants in this study and the literature. Furthermore, 45-50% activity enhancement via azoTAB surfactant preserved for all three cellulase enzyme mixture of endoglucanase, cellohydrolase andβ-glucosidase. Consequently, azoTAB can be applied as profitable additive for the heterogenous enzymatic cellulose hydrolysis, resulting in a 30% decrease in the enzyme load based on the specific activity, adsorption, and fractal kinetics results.
Transcobalamin Receptor Autoantibodies in Central Vitamin B12 Deficiency
Authors: Pluvinage John V. , Ngo Thomas , Bartley Christopher M. , Bodansky Aaron , Alvarenga Bonny D. , Zorn Kelsey C. , Fouassier Camille , Zamecnik Colin , McCann Adrian , Huynh Trung , Browne Weston , Tubati Asritha , Kondapavulur Sravani , Anderson Mark S. , Green Ari J. , Green Ralph , Douglas Vanja , Louine Martineau , Cree Bruce , Hauser Stephen , Seeley William , Holmes Brandon B. , Wells James A. , Spudich Serena , Farhadian Shelli , Ramachandran Prashanth , Gillum Leslie , Hales Chadwick M. , Smith Bryan , Nath Avindra , Suh Gina , Flanagan Eoin P. , Gelfand Jeffrey M. , DeRisi Joseph L. , Pleasure Samuel J. , Wilson Michael R. 
Published: August 2023

AbstractVitamin B12 is critical for hematopoiesis and myelination.1Deficiency can cause neurologic deficits including loss of coordination, spasticity, and cognitive decline.2,3,4However, diagnosis relies on vitamin B12 measurement in the blood which may not accurately reflect levels in the brain. Here, we discovered an autoimmune cause of vitamin B12 deficiency restricted to the central nervous system (CNS), termed autoimmune B12 central deficiency (ABCD). Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Patient immunoglobulins impaired cellular uptake of vitamin B12in vitro. Despite normal serum levels, vitamin B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic vitamin B12 supplementation were associated with increased CSF B12 levels and clinical improvement. Autoantibodies targeting the same epitope of CD320 were identified in 7 other patients with neurologic deficits of unknown etiology and in 6 percent of healthy controls. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. These findings elucidate a new autoimmune cause of metabolic neurologic disease that may be amenable to immunomodulatory treatment and/or nutritional supplementation.
Knowledge, Attitude and Practices (KAP) towards ketogenic Diet and its risk among Bangladeshi Population: A Cross Sectional Study
Authors: Tanha Arifa Farzana , Chandra Pradip , Haque Tasnima , Rahman Mohammad Mahmudur 
Published: August 2023

AbstractIn recent years, the ketogenic diet has become more popular in Bangladesh. Despite the potential negative effects, people are increasingly embracing and adjusting to this diet. Accounting for this manner, the current study addresses a gap that has existed as no research has been done on grown-up adults’ knowledge, attitudes, and practices about the ketogenic diet and its possible risks. To assess their Knowledge, Attitude, and Practice of the Ketogenic Diet and its risks, a descriptive cross-sectional study of the adult Bangladeshi population was carried out. A number of questions were asked to participants regarding their demographics, sources of dietary knowledge, attitudes toward the diet, understanding of the Ketogenic Diet, and views on it. Descriptive statistics were used to analyze the data. Out of 383 participants, women (63.20%) and people under the age of 30 (68.15%) dominated the study. 359 (93.70%) of the participants reported having inadequate knowledge about the ketogenic diet. Around 43.42% of Participants who ever followed KD were assessed to have a healthy BMI. The results revealed a significant association between respondents’ perceptions of KD as a typical weight loss treatment and their knowledge score. Social media was the main source of information for followers (60.53%), while peers were the source of information for 30.26% of respondents. Participants who ever followed the ketogenic diet were less aware of its risks and often considered it safe to follow for a long period believing its benefits outweighed any possible drawbacks. The findings of the current study suggest that Bangladeshis are not well-informed about the therapeutic applications of the ketogenic diet. It appears that pre-diet counselling is essential for everyone to understand every component and proper approach for following this diet.
Predicting the onset of internalizing disorders in early adolescence using deep learning optimized with AI
Authors: de Lacy Nina , Ramshaw Michael J. 
Published: August 2023

AbstractInternalizing disorders (depression, anxiety, somatic symptom disorder) are among the most common mental health conditions that can substantially reduce daily life function. Early adolescence is an important developmental stage for the increase in prevalence of internalizing disorders and understanding specific factors that predict their onset may be germane to intervention and prevention strategies. We analyzed ∼6,000 candidate predictors from multiple knowledge domains (cognitive, psychosocial, neural, biological) contributed by children of late elementary school age (9-10 yrs) and their parents in the ABCD cohort to construct individual-level models predicting the later (11-12 yrs) onset of depression, anxiety and somatic symptom disorder using deep learning with artificial neural networks. Deep learning was guided by an evolutionary algorithm that jointly performed optimization across hyperparameters and automated feature selection, allowing more candidate predictors and a wider variety of predictor types to be analyzed than the largest previous comparable machine learning studies. We found that the future onset of internalizing disorders could be robustly predicted in early adolescence with AUROCs ≥∼0.90 and ≥∼80% accuracy. Each disorder had a specific set of predictors, though parent problem behavioral traits and sleep disturbances represented cross-cutting themes. Additional computational experiments revealed that psychosocial predictors were more important to predicting early adolescent internalizing disorders than cognitive, neural or biological factors and generated models with better performance. We also observed that the accuracy of individual-level models was highly correlated to the relative importance of their constituent predictors, suggesting that principled searches for predictors with higher importance or effect sizes could support the construction of more accurate individual-level models of internalizing disorders. Future work, including replication in additional datasets, will help test the generalizability of our findings and explore their application to other stages in human development and mental health conditions.
Comparisons of new-onset peripheral arterial disease in Type 2 diabetes mellitus patients exposed to SGLT2I, DPP4I or GLP1a: a population-based cohort study
Authors: Chou Oscar Hou-In , Luo Zhiyao , Chung Cheuk To Skylar , Chan Jeffrey , Li Huixian , Lakhani Ishan , Lee Sharen , Zhang Qingpeng , Liu Tong , Wong Wing Tak , Cheung Bernard Man Yung , Lip Gregory Y. H. , Tse Gary , Leung Fung Ping , Zhou Jiandong 
Published: August 2023

AbstractBackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2I) have been suggested to have beneficial effects against atherosclerotic cardiovascular disease. The comparative risks of new onset peripheral arterial disease (PAD) between SGLT2Is, dipeptidyl peptidase-4 inhibitors (DPP4Is) and glucagon-like peptide-1 receptor agonist (GLP1a) remain unknown.ObjectiveThis real-world study aims to compare the risks of PAD upon exposure to SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I).MethodsThis was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 using a territory-wide registry in Hong Kong. The primary outcome was new-onset PAD. The secondary outcome was all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was applied to identify significant associations. A three-arm sensitivity analysis including the GLP1a cohort was conducted.ResultsThis cohort included 75470 T2DM patients (median age: 62.3 years old [SD: 12.8]; 55.79 % males). The SGLT2I and DPP4I groups consisted of 28753 patients and 46717 patients, respectively. After matching, 186 and 256 patients suffered from PAD in the SGLT2I and DPP4I groups respectively, over a median follow-up of 5.6 years. SGLT2I use was associated with lower risks of PAD (Hazard ratio [HR]: 0.85; 95% Confidence Interval [CI]: 0.67-0.98) compared to DPP4I use after adjustments for demographics, comorbidities, medications, renal function, and diabetic laboratory tests. Similar associations were observed in subgroup analyses in male patients above 65 years old, with hypertension, and low HbA1c levels. In the sensitivity analysis, SGLT2I was not associated with lower risks of PAD compared to GLP1a (HR: 0.88; 95% CI: 0.65-1.18). The results remained consistent in the competing risk and the sensitivity analyses.ConclusionsSGLT2I use amongst T2DM patients was associated with lower risks of new-onset PAD and PAD-related outcomes when compared to DPP4I after adjustments.Illustrated Abstract
Functional characterization of ATP13A2 variants associated with distinct neurodegenerative disorders
Authors: Vrijsen Stephanie , El Asrar Rania Abou , Houdou Marine , Van Den Haute Chris , Baekelandt Veerle , Lyons Joseph A. , Eggermont Jan , Vangheluwe Peter 
Published: August 2023

AbstractATP13A2 is a late endolysosomal transporter that exports the polyamines spermine and spermidine from the organellar lumen to the cytosol. Loss-of-function variants inATP13A2are causative for Kufor-Rakeb syndrome (KRS, a recessive juvenile-onset parkinsonism with dementia) and have also been identified in early-onset PD (EOPD) and hereditary spastic paraplegia (HSP). Furthermore, candidate pathogenic ATP13A2 variants have been identified in neuronal ceroid lipofuscinosis (NCL; M854R), multiple system atrophy (MSA; Y1020C) and amyotrophic lateral sclerosis (ALS; I411M) suggesting that ATP13A2 may be implicated in a broader range of neurodegenerative disorders. Since the functional consequences of the NCL, MSA, and ALS variants have not yet been examined, we here characterized these ATP13A2 variants in terms of subcellular localization, cellular polyamine uptake, and transport activity. We found that the homozygous NCL-associated M854R variant results in an instable protein with low expression levels, leading to complete loss of ATPase and cellular polyamine uptake activity. The heterozygous MSA-linked Y1020C variant is properly localized and presents only partially decreased ATPase activity without affecting cellular polyamine uptake. The ALS-associated I411M variant is also correctly localized and exhibits a minor effect on cellular polyamine uptake, however, without a significant impact on ATPase activity. Taken together, only the homozygous NCL variant of ATP13A2 causes a complete loss-of-function, validating that ATP13A2 dysfunction is implicated in NCL. The ALS and MSA variants only presented a subtle functional defect, questioning whether these heterozygous variants are pathogenic and whether ATP13A2 dysfunction may cause MSA or ALS.
Enhancing In Vitro SMN Protein Expression and Cell Viability through Xeno-Nucleic Acid-Based ASOs in Spinal Muscular Atrophy
Authors: Kilic Ozum , Babar Hale Ahsen , Inci Cemre Can , Odabas Sibel Pinar , Yelgen Gamze , Oltan Sevgi , Kulac Sila , Tastan Cihan 
Published: August 2023

SUMMARYSpinal Muscular Atrophy (SMA) stands as a devastating ailment arising from the dearth of functional SMN (Survival Motor Neuron) protein due to genetic anomalies within the SMN1 gene. This condition is marked by the consequential attrition of motor neurons, precipitating a progressive decline in muscular strength and culminating in the disruption of neuromuscular junctions. Existing therapeutic approaches encompassing Zolgensma, Nursinersen, and Evrysdi employ innovative genetic therapeutic strategies involving transgene delivery, Antisense Oligonucleotide (ASO) technology, and modulation of pre-mRNA processing to enhance functional SMN protein expression. However, the ASO therapeutics remain suboptimal in establishing a sustained panacea for SMA, as they inadequately maintain consistent levels of functional SMN protein expression. In this study, we present a discerning inquiry into focusing on XNA-DNA-ASO products that exhibit enhanced safety and stability compared to conventional DNA/RNA-ASO sequences. Through precise targeting of the ISSN-1 region within SMN2 gene’s intron 7, our approach seeks to amplify SMN protein expression. Employing Xeno Nucleic Acid (XNA) bases, known for their augmented hydrophobicity and stability, our strategy surmounts previous limitations associated with chemical modifications, showcasing heightened endonuclease resistance. Comparative analyses with conventional DNA/RNA-ASO products substantiate the superiority of XNA-DNA-ASO sequences, underscoring elevated SMN protein expression and reduced toxicity. In a comprehensive evaluation, our gene therapy paradigm is scrutinized within a type 1 SMA fibroblast cell line. Utilizing diverse analytical methodologies, encompassing Annexin V-PI analysis for cytotoxicity, MTT assays for mitochondrial activity, and flow cytometry for SMN protein expression profile, we gauge therapeutic impact and potential toxicity. In conclusion, our investigation not only spotlights the promise of XNA-DNA-ASO sequences but also holds implications for refining SMA treatment strategies, converging on minimized dosages, lowered toxicity, and heightened therapeutic efficacy, thus shaping the landscape of gene therapy for SMA.
NYUS.2: an Automated Machine Learning Prediction Model for the Large-scale Real-time Simulation of Grapevine Freezing Tolerance in North America
Authors: Wang Hongrui , Moghe Gaurav D. , Kovaleski Al P. , Keller Markus , Martinson Timothy E. , Wright A. Harrison , Franklin Jeffrey L. , Hébert-Haché Andréanne , Provost Caroline , Reinke Michael , Atucha Amaya , North Michael G. , Helwi Pierre , Centinari Michela , Londo Jason P. 
Published: August 2023

SummaryAccurate and real-time monitoring of grapevine freezing tolerance is crucial for the sustainability of the grape industry in cool climate viticultural regions. However, on-site data is limited. Current prediction models underperform under diverse climate conditions, which limits the large-scale deployment of these methods.We combined grapevine freezing tolerance data from multiple regions in North America and generated a predictive model based on hourly temperature-derived features and cultivar features using AutoGluon, an automatic machine learning engine. Feature importance was quantified by AutoGluon and SHAP value. The final model was evaluated and compared with previous models for its performance under different climate conditions.The final model achieved an overall 1.36 °C root-mean-square error during model testing and outperformed two previous models using three test cultivars at all testing regions. Two feature importance quantification methods identified five shared essential features. Detailed analysis of the features indicates that the model might have adequately extracted some biological mechanisms during training.The final model, named NYUS.2, was deployed along with two previous models as an R shiny-based application in the 2022-2023 dormancy season, enabling large-scale and real-time simulation of grapevine freezing tolerance in North America for the first time.
PfAgo-based dual signal amplification biosensor for rapid and highly sensitive detection of alkaline phosphatase activity
Authors: Ke Weikang , Qin Yuqing , Zhou Bosheng , Hu Yonggang 
Published: August 2023

AbstractDeveloping rapid and highly sensitive methods for alkaline phosphatase (ALP) activity analysis is significant for the clinical diagnosis and treatment of diseases. Here, aPyrococcus furiosusArgonaute (PfAgo)-based biosensor is presented for ALP activity detection in which the ALP-catalyzed hydrolysis of 3’-phosphate-modified functional DNA activates the strand displacement amplification, and the amplicon -mediates the fluorescent reporter cleavage as a guide sequence ofPfAgo. Under the dual amplification mode ofPfAgo-catalyzed multiple-turnover cleavage activity and pre-amplification technology, the developed method was successfully applied in ALP activity analysis with a detection limit (LOD) of 0.0013 U L−1(3σ) and a detection range of 0.0025 U L−1to 1 U L−1within 90 min. ThePfAgo-based method exhibits satisfactory analytic performance in the presence of the potential interferents and in complex human serum samples. The proposed method shows several advantages, such as rapid, highly sensitive, low-cost, and easy operation, and has great potential in disease evolution fundamental studies and clinical diagnosis applications.
ediTONSIL: Activation-Neutral Gene Editing of CD4 T cells in Human ex Vivo Tonsil Cultures
Authors: Morath K. , Sadhu L. , Dyckhoff G. , Gapp Madeleine , Keppler Oliver T. , Fackler O.T. 
Published: August 2023

MotivationCD4 T cells are central players of adaptive immunity that rapidly change activation states in response to exogenous T cell receptor (TCR) stimulation. While molecular processes in activated human CD4 T cells from peripheral blood are well studied, resting CD4 T cells are refractory to gene-editing transduction and transfection methods without prior activation. Knowledge on the molecular biology of truly resting CD4 T cells is therefore lacking. We present here the culture and editing workflow ediTONSIL that allows for gene editing of tissue-resident CD4 T cells without compromising their activation state or immunological function. This will enable molecular mechanistic analyses of this cell type in their native/physiological tissue context.SummaryThe molecular and immunological properties of resting CD4 T cell biology are understudied due to the lack of suitable gene editing methods. Here we describe theex vivoculture and gene editing methodology ediTONSIL for tissue-resident CD4 T cells from human tonsil tissue. CRISPR/Cas9 RNP nucleofection under optimized culture conditions and cytokine concentrations results in knock out efficacies of over 90%, which are e.g. sufficient to prevent HIV-1 infection when targeting the viral entry co-receptor CXCR4. EdiTONSIL does not impair tonsil CD4 T cell viability, activation state or immunocompetence and does not require exogenous activation. Editing can be performed on multiple cell types in bulk cultures or of CD4 T cells previously isolated from tonsils that can be added back to the non-CD4 T cell fraction post gene editing to reassemble into immunocompetent organotypic lymphoid aggregate structures. This highly efficient and versatile workflow for gene editing of tonsillar CD4 T cells enables the dissection of molecular mechanisms inex vivocultures of human lymphoid tissue and can be adapted to other tonsil-resident cell types.Graphical Abstract