bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-navigating the “Island of Reil”: a systematic review of real-time fMRI neurofeedback training of insula activity
Authors: Zhang Yuan , Zhang Qiong , Becker Benjamin , Kendrick Keith M. , Yao Shuxia 
Published: March 2022

ABSTRACTReal-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity or connectivity, with demonstrated feasibility in experimental and therapeutic applications. The crucial role of the insula in emotional and salience processing makes it a popular target in rtfMRI studies although there is no systematic review of their efficacy. To promote our understanding of mechanisms underlying insula regulation and thereby facilitate therapeutic translation, the present review identified 22 preclinical and clinical studies and found that rtfMRI-based NF training is efficient for modulating insula activity (> 86%) and its associated behavioral and neural changes. Based on findings, continuous feedback for multiple training sessions, specific strategies validated before application, inclusion of a practice session, and choosing appropriate localization strategies are suggested as guidelines. We also recommend standardization of training protocol design, statistical analyses and results reports for future studies. In summary, the present review informs both fundamental research and therapeutic translation of NF training as an intervention in mental disorders, particularly those with insula dysfunction.
Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to the Heart post Myocardial Infarction
Authors: Sullivan Holly L. , Liang Yifei , Worthington Kendra , Luo Colin , Gianneschi Nathan C. , Christman Karen L. 
Published: March 2022

AbstractIn this paper, we describe block copolymer amphiphiles consisting of a hydrophilic matrix metalloproteinase (MMP) peptide substrate, and a hydrophobic small molecule MMP inhibitor PD166793 for the treatment of acute myocardial infarction. These resulting drug loaded peptide-polymer amphiphiles (PPAs) assemble in aqueous solution to yield drug loaded micellar nanoparticles. Following minimally invasive intravenous injection, these nanoparticles preferentially exit the vasculature and are physically trapped at the infarcted region of the heart due to MMP-induced peptide cleavage and aggregation. This MMP directed active assembly prevents the material from leaking out into the blood stream, enabling long-term retention. Further, we show that the conjugated MMP inhibitor (PD166793) is inactivated in the core of the micelles and can be released upon the action of proteases and esterases, leading to MMP inhibition. This work establishes a promising targeted nanoparticle platform for delivering small molecule therapeutics to the heart.
Is virtual care the new normal? Evidence supporting Covid-19’s durable transformation on healthcare delivery
Authors: Mandal Soumik , Wiesenfeld Batia , Mann Devin M. , Lawrence Katharine , Chunara Rumi , Testa Paul A. , Nov Oded 
Published: March 2022

ABSTRACTObjectiveDespite the surge of telemedicine use during the early stages of the coronavirus-19 (COVID-19) pandemic, research has not evaluated the extent to which the growth of telemedicine has been sustained during recurring pandemic waves. This study provides data on the long-term durability of video-based telemedicine visits and their impact on urgent and non-urgent healthcare delivery from one large health system in New York City.Materials and MethodsElectronic health record (EHR) data of patients between January 1st, 2020 and November 30th, 2021 were used to conduct the analyses and longitudinal comparisons of telemedicine or in-person visit volumes. Patients’ diagnosis data were used to differentiate COVID-19 suspected visits from non-COVID-19 ones while comparing the visit types.ResultsWhile COVID-19 prompted an increase in telemedicine visits and a simultaneous decline in in-person clinic visits, telemedicine use has stabilized since then for both COVID-19 and non-COVID suspected visits. For COVID-19 suspected visits, utilization of virtual urgent care facilities is higher than the trend. The data further suggests that virtual healthcare delivery supplements, rather than replaces, in-person care.DiscussionThe COVID-19 pandemic has transformed the use of telemedicine as a means of healthcare delivery, and the data presented here suggests that this is an enduring transformation.ConclusionTelemedicine use increased with the surge of infection cases during the pandemic, but evidence suggests that it will persist after the pandemic, especially for younger patients, for both urgent and non-urgent care. These findings have implications for the healthcare delivery system, insurers and policymakers.
The Adaptive Olfactory Measure of Threshold (ArOMa-T): A rapid test of olfactory function
Authors: Weir Elisabeth M. , Hannum Mackenzie E. , Reed Danielle R. , Joseph Paule V. , Munger Steven D. , Hayes John E. , Gerkin Richard C. 
Published: March 2022

AbstractMany widely-used psychophysical olfactory tests have limitations that can create barriers to adoption outside research settings. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and past experience with the odor. Conversely, typical threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially-available olfactory tests are slow and may require a trained administrator, making them impractical for use in a short wellness visit or other broad clinical assessment. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T) – a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant – delivery card – in a non-clinical sample of individuals (n=534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 9.6% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (∼3.2-fold lower for females) and age (∼8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, these data indicate the ArOMa-T can determine odor detection thresholds. The ArOMa-T may be particularly valuable in clinical or field settings where rapid and portable assessment of olfactory function is needed.
Chromosomal microarray analyses from 5,778 patients with neurodevelopmental disorders and congenital anomalies in Brazil
Authors: Krepischi Ana C. V. , Villela Darine , da Costa Silvia Souza , Mazzonetto Patricia C. , Migliavacca Michele P. , Milanezi Fernanda , Santos Juliana G. , Guarischi-Sousa Rodrigo , Campana Gustavo , Kok Fernando , Schlesinger David , Kitajima Joao Paulo , Campagnari Francine , Vianna-Morgante Angela M. , Pearson Peter L. , Rosenberg Carla 
Published: March 2022

ABSTRACTChromosomal microarray analysis (CMA) has been recommended and practiced routinely since 2010 in USA and Europe as the first-tier cytogenetic test for patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. However, in Brazil, the use of CMA is still limited, due to its high cost and complexity of the combination of private and public health systems. Although the country has one of the world largest single payer public healthcare system, nearly all patients referred for CMA come from the private sector. This reflects on the small number of CMA studies in Brazilian cohorts. This study is by far the largest Brazilian cohort (n=5,788) studied by CMA and results from a joint collaboration formed by the University of Sao Paulo and three private genetic diagnostic centers to investigate the genetic bases of neurodevelopmental disorders and congenital abnormalities. It is common practice to investigate the inheritance of VUS; however, our results indicate an extremely low cost-benefit of this approach, and strongly suggest that in cases of limited budget, investigation of the parents of VUS carriers using CMA should not be prioritized. Another aspect discussed is the classification of variants of low penetrance, once CNV classification is mostly designed to Mendelian or highly-penetrant variants.
Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study
Authors: Ma Jiantao , Huang Allen , Yan Kaiyu , Sun Xianbang , Joehanes Roby , Huan Tianxiao , Levy Daniel , Liu Chunyu 
Published: March 2022

AbstractBackgroundThe relations of alcohol consumption and gene expression remain to be elucidated in large study samples.ObjectivesTo study the relationship between alcohol consumption, gene expression, and cardiovascular disease (CVD) risk factors.MethodsWe performed cross-sectional association analysis of whole blood derived gene expression levels with alcohol consumption in 5,531 Framingham Heart Study (FHS) participants (mean age 55 years; 54% women) by splitting the sample into a discovery sample and a replication sample (2:1 ratio) using independent pedigrees. We also examined the cross-sectional association of alcohol-associated genes with three CVD risk factors: obesity, hypertension, and diabetes. Linear mixed models or generalized estimation equations were used to quantify associations accounting for familial relationship and multiple covariates.ResultsWe identified 25 alcohol-associated genes (false discovery rate < 0.05 in the discovery sample and Bonferroni corrected P < 0.05 in the replication sample). We further showed cross-sectional associations of 16 alcohol-associated genes with obesity, nine genes with hypertension, and eight genes with diabetes (all P < 0.002). For example, we observed decrease in expression of PROK2 (β = -0.0018; 95%CI: -0.0021, -0.0007; P = 6.5e-5) and PAX5 (β = -0.0014; 95%CI: -0.0021, -0.0007; P = 6.5e-5) per 1 g/day increase in alcohol consumption. Consistent with our previous observation on the inverse association of alcohol consumption with obesity and positive association of alcohol consumption with hypertension, we found that PROK2 was positively associated with obesity (OR = 1.42; 95%CI: 1.17, 1.72; P = 4.5e-4) and PAX5 was negatively associated with hypertension (OR = 0.73; 95%CI: 0.59, 0.89; P = 1.6e-3). We also observed that alcohol consumption was positively associated with expression of ABCA13 (β = 0.0012; 95%CI: 0.0007, 0.0017; P = 1.3e-6) and ABCA13 was positively associated with diabetes (OR = 2.57; 95%CI: 1.73, 3.84; P = 3.5e-06); this finding, however, was inconsistent with our observation on the inverse association between alcohol consumption and diabetes.ConclusionsWe observed that alcohol consumption was associated with whole blood expression levels of 25 genes in middle aged to older adults in the FHS. In addition, complex relationships may exist between alcohol-associated genes and CVD risk factors.
Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury
Authors: Palikuqi Brisa , Rispal Jeremie , Vaka Deedepya , Boffelli Dario , Klein Ophir 
Published: March 2022

SummaryThe intestinal epithelium undergoes continuous renewal and has an exceptional capacity to regenerate after injury. Maintenance and proliferation of intestinal stem cells (ISCs) is regulated by their surrounding niche, largely through Wnt signaling. However, it remains undetermined which niche cells produce signals during different injury states, and the role of endothelial cells (ECs) as a component of the ISC niche during homeostasis and after injury has been underappreciated. Here, we show that lymphatic endothelial cells (LECs) reside in proximity to crypt epithelial cells and secrete molecules that support epithelial renewal and repair. The LECs are an essential source of Wnt signaling in the small intestine, as loss of LEC-derived Rspo3 leads to a lower number of stem and progenitor cells and hinders recovery after cytotoxic injury. Together, our findings identify LECs as an essential niche component for optimal intestinal recovery after cytotoxic injury.
Molecular Dynamic Investigation of H5N1 Influenza Virus Dual H274Y-I222K Mutation Resistance to Peramivir
Authors: Buthelezi Ndumiso M. , Mtambo Sphamandla E. , Amoako Daniel G. , Somboro Anou M. , Yakubu Elliasu , Khan Rene B. , Mhlongo Ndumiso N. , Kumalo Hezekiel M. 
Published: March 2022

AbstractIn light of the rapid rise of an influenza pandemic, the constant genetic mutations of H5N1 influenza viruses pose a threat. Mutations at the sialic site are often responsible for multiple drug resistance. To design effective new inhibitors, it is necessary to undertake research into the mechanism of resistance of influenza viruses and their rapid mutations. The molecular dynamic simulation technique has been an instrumental tool in understanding how proteins function from an atomic perspective. A thorough investigation has not been conducted using molecular dynamics to examine the impact of these mutations (I222K, H274Y, and H274Y-I222K) on Peramivir. This study investigates the effects of I222K, H274Y, H274Y-I222K substitution on the neuraminidase–Peramivir complex and identifies responsible residues for complex conformations. The mutations caused distorted Peramivir orientation in the enzyme active site, which affected the inhibitor’s binding. In the presence of various mutations, interaction between protein and ligand became less thermodynamically favorable. We observed the following trend in binding free energy difference: WT<I222<H274Y<H274Y-I222K. As a result of the thermodynamic instability of the mutant complexes, Peramivir’s potency is reduced due to impaired binding interactions. Wild type complex displays thermodynamic stability and strong protein-ligand interactions due to their high total energy contributions and low residue flexibility. Based on the energy decomposition analysis, Arg117, Arg224, and Arg292 contributed the largest residual energy for the binding of Peramivir to wild type and mutants. These residues are thought to play a key role in the formation of the binding pocket between Peramivir and neuraminidase. This study provides a basis for investigating the effects of other mutations on Peramivir’s efficacy against the H5N1 virus.
The ZuCo Benchmark on Cross-Subject Reading Task Classification with EEG and Eye-Tracking Data
Authors: Hollenstein Nora , Tröndle Marius , Plomecka Martyna , Kiegeland Samuel , Özyurt Yilmazcan , Jäger Lena A. , Langer Nicolas 
Published: March 2022

AbstractWe present a new machine learning benchmark for reading task classification with the goal of advancing EEG and eye-tracking research at the intersection between computational language processing and cognitive neuroscience. The benchmark task consists of a cross-subject classification to distinguish between two reading paradigms: normal reading and task-specific reading. The data for the benchmark is based on the Zurich Cognitive Language Processing Corpus (ZuCo 2.0), which provides simultaneous eye-tracking and EEG signals from natural reading. The training dataset is publicly available, and we present a newly recorded hidden testset. We provide multiple solid baseline methods for this task and discuss future improvements. We release our code and provide an easy-to-use interface to evaluate new approaches with an accompanying public leaderboard:www.zuco-benchmark.com.HighlightsWe present a new machine learning benchmark for reading task classification with the goal of advancing EEG and eye-tracking research.We provide an interface to evaluate new approaches with an accompanying public leaderboard.The benchmark task consists of a cross-subject classification to distinguish between two reading paradigms: normal reading and task-specific reading.The data is based on the Zurich Cognitive Language Processing Corpus of simultaneous eye-tracking and EEG signals from natural reading.
The choice of the objective function in flux balance analysis is crucial for predicting replicative lifespans in yeast
Authors: Schnitzer Barbara , Österberg Linnea , Cvijovic Marija 
Published: March 2022

AbstractFlux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though motivated by evolutionary arguments, has not been directly connected to related measures. Here, we used an available multi-scale mathematical model of yeast replicative ageing, integrating cellular metabolism, nutrient sensing and damage accumulation, to systematically test the effect of commonly used objective functions on features of replicative ageing in budding yeast, such as the number of cell divisions and the corresponding time between divisions. The simulations confirmed that assuming maximal growth is essential for reaching realistic lifespans. The usage of the parsimonious solution or the additional maximisation of a growth-independent energy cost can improve lifespan predictions, explained by either increased respiratory activity using resources otherwise allocated to cellular growth or by enhancing antioxidative activity, specifically in early life. Our work provides a new perspective on choosing the objective function in FBA by connecting it to replicative ageing.
Idetification of CACNA1B (p.K567R) mutation responsible for familiar AVNRT
Authors: Luo Rong , Cao Xin , Zheng Chenqing , Huang Jichang , Liu Mingjiang , He Tao , Jiang Panpan , Yang Xu , Yang Zhenglin , Wu Xiushan , Li Xiaoping 
Published: March 2022

AbstractAtrioventricular nodal reentry tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia (PSVT). The exact cause of AVNRT has not yet been found. However, an increasing number of reports suggest that AVNRT is hereditary, but no precise pathogenic gene has been found so far. In our study, we found that a point mutation of CACNA1B (p.K567R) which encoded the α1 subunit of N-type calcium channel (Cav 2.2), was cosegregated with AVNRT in one family. Previous research showed that overexpression and point mutations of human CACNA1B in zebrafish embryos may be related to abnormal heart rate. Telemetric ECG recordings showed that rats with a CACNA1B point mutation displayed sporadic supraventricular tachycardia and altered QRS complex morphology. In addition, the CACNA1B (p.K567R) rats presented a double path phenomenon and AVNRT induction by intracardiac electrophysiological examination. Indexes of heart rate variance in CACNA1B mutation rats showed an in cardiac sympathetic activity and an imbalance of cardiac sympathetic and parasympathetic activity. Single-cell RNA sequencing indicated that the number of neurons in the superior cervical ganglion (SCG) of mutant rats was higher than in wild-type (WT) rats, accompanied by an increased expression of CACNA1B. Functional enrichment in SCG proteomics suggests that point mutant rats have abnormalities in synaptic function and ion transport, which could lead to the release of neurotransmitters. This could affect the cardiac autonomic neural activity and lead to an imbalance in sympathetic and parasympathetic activity and the subsequent occurrence of AVNRT. Our findings indicate that CACNA1B (p.K567R) is the pathogenic gene of AVNRT in familial AVNRT and confirm that CACNA1B is the first definitive AVNRT pathogenic gene that has been discovered.
Performance evaluation of a non-invasive one-step multiplex RT-qPCR assay for detection of SARS-CoV-2 direct from human saliva
Authors: Jenkins Harry H. , Tellechea Lopez Ana A. , Tarantini Francesco Saverio , Tomlin Hannah , Scales Danielle , Lee I-Ning , Wu Siyu , Hyde Ralph , Lis-Slimak Katarzyna , Byaruhanga Timothy , Thompson Jamie L. , Pijuan-Galito Sara , Doolan Lara , Kaneko Kazuyo , Gwynne Penny , Reffin Caroline , Park Emily , Dey Jayasree , Hill Jack , Arendt-Tranholm Asta , Stroud Amy , Petrie Moira , Denning Chris , Benest Andrew V. , Seedhouse Claire 
Published: March 2022

AbstractPolymerase chain reaction (PCR) has proven to be the gold-standard for SARS-CoV-2 detection in clinical settings. The most common approaches rely on nasopharyngeal specimens obtained from swabs, followed by RNA extraction, reverse transcription and quantitative PCR. Although swab-based PCR is sensitive, swabbing is invasive and unpleasant to administer, reducing patient compliance for regular testing and resulting in an increased risk of improper sample collection. To overcome these obstacles, we developed a non-invasive one-step RT-qPCR assay performed directly on saliva specimens. The University of Nottingham Asymptomatic Testing Service (UoNATS) protocol simplifies sample collection and bypasses the need for RNA extraction, additives, or extraneous processing steps, thus helping to encourage more regular testing and reducing processing time and costs. We have evaluated the assay against the performance criteria specified by the UK regulatory bodies and attained accreditation (BS EN ISO/IEC 17025:2017) for SARS-CoV-2 diagnostic testing by the United Kingdom Accreditation Service (UKAS). We observed a sensitivity of 1 viral copy per microlitre of saliva and demonstrated a concordance of >99.4% between our results and those of other accredited testing facilities. We concluded that saliva is a stable medium with surprising longevity, and allows for a highly precise, repeatable, and robust testing method.