bluuebunny/crossref_metadata_2025_split huggingface dataset:
Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure with Pulmonary Hypertension
Authors: Jani Vivek , Aslam M. Imran , Fenwick Axel J. , Ma Weikang , Gong Henry , Milburn Gregory , Nissen Devin , Salazar Ilton Cubero , Hanselman Olivia , Mukherjee Monica , Halushka Marc K. , Margulies Kenneth B. , Campbell Kenneth , Irving Thomas C. , Kass David A. , Hsu Steven 
Published: March 2023

ABSTRACTRationaleRight ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in heart failure patients with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction.ObjectiveTo determine components of myocyte contractile depression in HFrEF-PH, identify those reflected by clinical RV indices, and elucidate their underlying biophysical mechanisms.Methods and ResultsResting, calcium- and load-dependent mechanics were measured in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 HFrEF-PH patients undergoing cardiac transplantation and 9 organ-donor controls. Unsupervised machine learning using myocyte mechanical data with the highest variance yielded two HFrEF-PH subgroups that in turn mapped to patients with depressed (RVd) or compensated (RVc) clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in RVd, while surprisingly, many other major myocyte contractile measures including peak power, maximum unloaded shortening velocity, and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick-filament defects, myofibrillar structure was assessed by X-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in RVd but not RVc, as compared to controls. This corresponded to reduced myosin ATP turnover in RVd myocytes, indicating less myosin in a cross-bridge ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Lastly, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human HF.ConclusionsWhile there are multiple RV myocyte contractile deficits In HFrEF-PH, clinical indices primarily detect reduced isometric calcium-stimulated force related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.
CO-ADMINISTRATION OF RESVERATROL RESCUED LEAD-INDUCED TOXICITY INDROSOPHILA MELANOGASTER
Authors: Abdulazeez R. , Highab S. M. , Onyawole U.F. , Jeje M.T. , Musa H. , Shehu D. M. , Ndams I. S. 
Published: March 2023

AbstractLead toxicity poses a significant environmental concern linked to diverse health issues, including cognitive impairments, behavioral abnormalities, reproductive defects, and oxidative stress at the cellular level. This study explores the potential mitigating effects of resveratrol on lead-induced toxicity inDrosophila melanogaster. AdultD. melanogasterof the Harwich strain, aged three days, were orally exposed to lead (60 mg/L), Succimer (10 mg/kg), and varying doses of resveratrol (50, 100, and 150 mg/kg). The investigation encompassed the assessment of selected biological parameters, biochemical markers (ALP, AST, TB, CB, Na, Ca, Ur, Cr), oxidative stress indicators (MDA), and antioxidant enzymes (SOD and CAT). Resveratrol exhibited a dose-dependent enhancement of egg-laying, eclosion rate, filial generation output, locomotor activity, and life span inD. melanogaster, significantly to 150 mg/kg of diet. Most of the investigated biochemical parameters showed significant rescue in lead-exposed fruit flies when co-treated with resveratrol (p < 0.05). However, oxidative stress, as indicated by MDA levels, remained unaffected by resveratrol in this study. The findings suggest that resveratrol effectively protects against lead toxicity inDrosophila melanogasterand may hold therapeutic potential as an agent for managing lead poisoning in humans.
Assessing the implementation of user-centred design standards on assistive technology for persons with visual impairments: A systematic review
Authors: Ortiz-Escobar Luisa María , Chavarria Mario Andres , Schönenberger Klaus , Hurst-Majno Samia , Stein Michael Ashley , Mugeere Anthony , Rivas-Velarde Minerva 
Published: March 2023

AbstractDespite scientific and technological advances in the field of assistive technology (AT) for people with visual impairment (VI), technological designs are frequently based on a poor understanding of the physical and social context of use, resulting in devices that are less than optimal for their intended beneficiaries. To resolve this situation, user-centred approaches in the development process of AT have been widely adopted in recent years. However, there is a lack of systematization on the application of this approach. This systematic review registered in PROSPERO (CRD42022307466), assesses the application of the ISO 9241-210 human-centred design principles in allegedly “user-centred designed” AT developments for persons with VI (see S1 PROSPERO Protocol). The results point to a wide variation of the depth of understanding of user needs, a poor characterization of the application of the User Centred Design (UCD) approach in the initial design phases or in the early prototyping, and a vague description of user feedback and device iteration. Among the principles set out in ISO 9241-210, the application of 5.6: “the design team includes multidisciplinary skills and perspectives” is the one for which the least evidence is found. The results show there is not enough evidence to fully assess the impact of UCD in 1. promoting innovation regarding AT products and practices, and 2. Judging if AT produced following such standards is leading to better user access, wellbeing outcomes and satisfaction. To address this gap it is necessary to, first, generate better implementation of UCD in AT development and second, to strengthen evidence regarding the implementation and outcomes of using UCD for AT. To better engage with the realities of persons with VI, we propose capacity building across development teams regarding UCD, its principles and components; better planning for UCD implementation; and cross-fertilization across engineering disciplines and social and clinical science.
NASCarD (Nanopore Adaptive Sampling with Carrier DNA): A rapid, PCR-free method for whole genome sequencing of pathogens in clinical samples
Authors: Terrazos Miani Miguel A. , Borcard Loïc , Gempeler Sonja , Baumann Christian , Bittel Pascal , Leib Stephen L , Neuenschwander Stefan , Ramette Alban 
Published: March 2023

ABSTRACTWhole-genome sequencing (WGS) represents the main technology for SARS-CoV-2 lineage characterization in diagnostic laboratories worldwide. The rapid, near-full-length sequencing of the viral genome is commonly enabled by high-throughput sequencing of PCR amplicons derived from cDNA molecules. Here, we present a new approach, called NASCarD (Nanopore adaptive sampling with carrier DNA), which allows low amount of nucleic acids to be sequenced while selectively enriching for sequences of interest, hence limiting the production of non-target sequences. Using clinical samples positive for SARS-CoV-2 during the Omicron wave, we demonstrate how the method leads to up to >100x coverage of the full genome sequences of the target organism as compared to standard shotgun metatranscriptomics approach. It provides complete and accurate genome sequence reconstruction within seven hours at a competitive cost. The new approach may have applications beyond SARS-CoV-2 sequencing for other DNA or RNA pathogens in clinical samples.
Expanding the role of village malaria workers in Cambodia: implementation and evaluation of four health education packages
Authors: Betrian Mipharny , Umans Dafne , Vanna Moul , Ol Sam , Adhikari Bipin , Davoeung Chan , Callery James J , Sovann Yok , Peto Thomas J , Maude Richard J , van der Pluijm Rob W , Bunreth Voeunrung , Grobusch Martin P. , van Vugt Michèle , Lubell Yoel , von Seidlein Lorenz , Dondorp Arjen M , Sovannaroth Siv , Lek Dysoley , Tripura Rupam 
Published: March 2023

AbstractBackgroundEarly access to correct diagnosis and appropriate treatment is essential for malaria elimination, and in Cambodia this relies on village malaria workers (VMWs). Decreasing malaria transmission leave VMWs with diminished roles. Activities related to the control of other health conditions could keep these community health workers relevant.MethodsDuring 2022, 120 VMWs attended training at local health centres on four health education packages: 1. hygiene and sanitation; 2. disease surveillance; 3. management of mild illness; 4. vaccination and antenatal care. All training and evaluation sessions were documented through meeting minutes, and 19 focus group discussions (FGDs) were conducted among VMWs and health centre personnel. Audio-records of FGDs were transcribed and translated in English and underwent thematic analysis.ResultsVMWs reported strong interest in the training and welcomed the expansion of their roles thus assuring their continued relevance. VMWs prioritized disease surveillance and management of mild illness among the available training packages because these topics were seen as most relevant. While training was considered comprehensible and important, the low literacy among VMWs was an impediment suggesting training materials need to be delivered visually. Since VMWs have limited resources, incentives could ensure that VMWs are motivated to undertake additional roles and responsibilities.ConclusionsThe transformation of VMWs into community health workers with roles beyond malaria is a promising approach for sustaining health care provision in remote areas. Training needs to consider the low scientific literacy, time constraints and limited resources of VMWs.
Deep learning model for prenatal congenital heart disease (CHD) screening generalizes to the community setting and outperforms clinical detection
Authors: Athalye Chinmayee , van Nisselrooij Amber , Rizvi Sara , Haak Monique , Moon-Grady Anita J. , Arnaout Rima 
Published: March 2023

AbstractObjectiveCongenital heart defects (CHD) are still missed despite nearly universal prenatal ultrasound screening programs, which may result in severe morbidity or even death. Deep machine learning (DL) can automate image recognition from ultrasound. The aim of this study was to apply a previously developed DL model trained on images from a tertiary center, to fetal ultrasound images obtained during the second-trimester standard anomaly scan in a low-risk population.MethodsAll pregnancies with isolated severe CHD in the Northwestern region of the Netherlands between 2015 and 2016 with available stored images were evaluated, as well as a sample of normal fetuses’ examinations from the same region. We compared initial clinical diagnostic accuracy (made in real time), model accuracy, and performance of blinded human experts with access only to the stored images (like the model). We analyzed performance by study characteristics such as duration, quality (independently scored by study investigators), number of stored images, and availability of screening views.ResultsA total of 42 normal fetuses and 66 cases of isolated CHD at birth were analyzed. Of the abnormal cases, 31 were missed and 35 were detected at the time of the clinical anatomy scan (sensitivity 53 percent). Model sensitivity and specificity was 91 and 93 percent, respectively. Blinded human experts (n=3) achieved sensitivity and specificity of 55±10 percent (range 47-67 percent) and 71±13 percent (range 57-83 percent), respectively. There was a statistically significant difference in model correctness by expert-grader quality score (p=0.04). Abnormal cases included 19 lesions the model had not encountered in its training; the model’s performance (15/19 correct) was not statistically significantly different on previously encountered vs. never before seen lesions (p=0.07).ConclusionsA previously trained DL algorithm out-performed human experts in detecting CHD in a cohort in which over 50 percent of CHD cases were initially missed clinically. Notably, the DL algorithm performed well on community-acquired images in a low-risk population, including lesions it had not been previously exposed to. Furthermore, when both the model and blinded human experts had access to stored images alone, the model outperformed expert humans. Together, these findings support the proposition that use of DL models can improve prenatal detection of CHD.
Deep audio embeddings for vocalisation clustering
Authors: Best Paul , Marxer Ricard , Paris Sébastien , Glotin Hervé 
Published: March 2023

AbstractThe study of non-human animals’ communication systems generally relies on the transcription of vocal sequences using a finite set of discrete units. This set is referred to as a vocal repertoire, which is specific to a species or a sub-group of a species. When conducted by human experts, the formal description of vocal repertoires can be laborious and/or biased. This motivates computerised assistance for this procedure, for which machine learning algorithms represent a good opportunity. Unsupervised clustering algorithms are suited for grouping close points together, provided a relevant representation. This paper therefore studies a new method for encoding vocalisations, allowing for automatic clustering to alleviate vocal repertoire characterisation. Borrowing from deep representation learning, we use a convolutional auto-encoder network to learn an abstract representation of vocalisations. We report on the quality of the learnt representation, as well as of state of the art methods, by quantifying their agreement with expert labelled vocalisation types from 7 datasets of other studies across 6 species (birds and marine mammals). With this benchmark, we demonstrate that using auto-encoders improves the relevance of vocalisation representation which serves repertoire characterisation using a very limited number of settings. We also publish a Python package for the bioacoustic community to train their own vocalisation auto-encoders or use a pretrained encoder to browse vocal repertoires and ease unit wise annotation.
Improving the sensitivity of fluorescence-based immunoassays by time-resolved and spatial-resolved measurements
Authors: Kremer Ran , Roth Shira , Bross Avital , Danielli Amos , Noam Yair 
Published: March 2023

AbstractDetection of target molecules, such as proteins, antibodies, or specific DNA sequences, is critical in medical laboratory science. Commonly used assays rely on tagging the target molecules with fluorescent probes. These are then fed to high-sensitivity detection systems. Such systems typically consist of a photodetector or camera and use time-resolved measurements that require sophisticated and expensive optics. Magnetic modulation biosensing (MMB) is a novel, fast, and sensitive detection technology that has been used successfully to detect viruses such as Zika and SARS-CoV-2. While this powerful tool is known for its high analytical and clinical sensitivity, the current signal-processing method for detecting the target molecule and estimating its dose is based on time-resolved measurements only.To improve the MMB-system performance, we propose here a novel signal processing algorithm that uses both temporally and spatially resolved measurements. We show that this combination significantly improves the sensitivity of the MMB-based assay. To evaluate the new method statistically, we performed multiple dose responses of Human Interleukin 9 (IL −8) on different days. Compared to standard time-resolved methods, the new algorithm provides a 2-3 fold improvement in detection limit and a 25% improvement in quantitative resolution.
ATR-FTIR spectra of polysaccharide isolated fromEuphorbia caducifoliaand its chemical modifications: A study of Principal component analysis
Authors: Venumadhav Kusuma , Seshagirirao Kottapalli 
Published: March 2023

AbstractPolysaccharides are the carbohydrates composed of same or different types of saccharides in an organized manner with glycosidic bonds. These are useful for various industrial applications mainly in food and pharmaceutical companies. Modifications of the polysaccharides change its structure and lead to the physical as well as functional differences. Mostly, chemical methods are used to modify its structure to study the structure-activity relationship in interest towards its physical properties like solubility and biological activities among various types of molecular modifications. In this study, a polysaccharide isolated from stems ofEuphorbia caducifoliaand modified its structure chemically by substituting different groups by sulfonation, carboxymethylation, acetylation and phosphorylation with various degree of substitutions. Molecular modifications of the polysaccharides showed the impact on water solubility as a physiochemical property. Thus, ATR-FTIR spectroscopy was employed along with a chemometric analysis, i.e., Principal components analysis (PCA) to understand and identify the chemical moieties differed from the unmodified polysaccharide. From PCA analysis, PC1and PC2components suffice to differentiate the modified polysaccharides with its native form.
Purification and characterization of a novel anti-tumour galactose binding lectin fromEuphorbia caducifolialatex
Authors: Venumadhav Kusuama , Seshagirirao Kottapalli 
Published: March 2023

AbstractA galactose specific lectin was isolated from the latex ofEuphorbia caducifoliato investigate the therapeutical aspects protein. Protein was purified from latex serum with two different affinity matrices and confirmed to contain 8 isoforms called isolectin with a molecular weight of 32 and 32.5 kDa. Preliminary studies state the specificity towards galactose, but its affinity with lactose is more favourable even at low concentrations. Circular spectrometry suggests the predominance β conformation is high in comparison to others as like most of the other latex lectins. Haemagglutination activity of the protein with different thermal and pH ranges shows maximum activity at pH 6-8 and 60-70°C. In therapeutically, it is noticed that the galactose specific lectin showed mitogenicity with human macrophages and anti-cancer properties on human cervical cancer cells.
A Consensus Model of Glucose-Stimulated Insulin Secretion in the Pancreaticβ-Cell
Authors: Deepa Maheshvare M. , Raha Soumyendu , König Matthias , Pal Debnath 
Published: March 2023

ABSTRACTThe pancreas plays a critical role in maintaining glucose homeostasis through the secretion of hormones from the islets of Langerhans. Glucose-stimulated insulin secretion (GSIS) by the pancreaticβ-cell is the main mechanism for reducing elevated plasma glucose. Here we present a systematic modeling workflow for the development of kinetic pathway models using the Systems Biology Markup Language (SBML). Steps include retrieval of information from databases, curation of experimental and clinical data for model calibration and validation, integration of heterogeneous data including absolute and relative measurements, unit normalization, data normalization, and model annotation. An important factor was the reproducibility and exchangeability of the model, which allowed the use of various existing tools. The workflow was applied to construct the first consensus model of GSIS in the pancreaticβ-cell based on experimental and clinical data from 39 studies spanning 50 years of pancreatic, islet, andβ-cell research in humans, rats, mice, and cell lines. The model consists of detailed glycolysis and equations for insulin secretion coupled to cellular energy state (ATP/ADP ratio). Key findings of our work are that in GSIS there is a glucose-dependent increase in almost all intermediates of glycolysis. This increase in glycolytic metabolites is accompanied by an increase in energy metabolites, especially ATP and NADH. One of the few decreasing metabolites is ADP, which, in combination with the increase in ATP, results in a large increase in ATP/ADP ratios in theβ-cell with increasing glucose. Insulin secretion is dependent on ATP/ADP, resulting in glucose-stimulated insulin secretion. The observed glucose-dependent increase in glycolytic intermediates and the resulting change in ATP/ADP ratios and insulin secretion is a robust phenomenon observed across data sets, experimental systems and species. Model predictions of the glucose-dependent response of glycolytic intermediates and insulin secretion are in good agreement with experimental measurements. Our model predicts that factors affecting ATP consumption, ATP formation, hexokinase, phosphofructokinase, and ATP/ADP-dependent insulin secretion have a major effect on GSIS. In conclusion, we have developed and applied a systematic modeling workflow for pathway models that allowed us to gain insight into key mechanisms in GSIS in the pancreaticβ-cell.
S-acylation and tonoplast localization of the Geminivirus Rep-Interacting Kinase/SnRK1-Activating Kinase (GRIK/SnAK) proteins differentially regulate salt and energy stress responses in Arabidopsis
Authors: Crepin Nathalie , Rolland Filip 
Published: March 2023

AbstractSnRK1 and SnRK3.11/SOS2 are key protein kinases in plant cellular energy and salt stress signaling, respectively. Using cellular assays, we confirm that the GRIK/SnAK (Geminivirus Rep-Interacting Kinase/SnRK1-Activating Kinase) proteins act as their main activating upstream kinases in Arabidopsis, catalyzing T-loop phosphorylation on the SnRK1α1 T175 and SOS2 T168 residues. Remarkably, SnRK1α1 phosphorylation on the neighbouring S176 residue competes with GRIK-mediated T175 phosphorylation to negatively regulate SnRK1 activity. Cellular assays and transgenic plants also revealed that the GRIK proteins, via N-terminal S-acylation, are predominantly localized at the tonoplast, where they interact with SnRK1α1 and SOS2. We optimized a leaf mesophyll protoplast-based Acyl PEG Exchange (APE) protocol to further explore GRIK protein S-acylation and tonoplast recruitment and identified the amino acid residues involved. GRIK1 tonoplast localization is likely mediated by initial membrane sampling via N-terminal domain hydrophobicity and local S-acylation, independently of a secretory pathway. Finally,grik1-1 grik2-1double KO mutants complemented with a non-S-acylatable mutant GRIK1 protein exhibit increased salt sensitivity (reduced SOS2 activity) but hyperactive SnRK1 signaling, demonstrating the differential importance of GRIK subcellular localization for Arabidopsis salt and energy stress responses.