bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant brain-heart coupling is associated with the severity and prognosis of hypoxic-ischemic brain injury after cardiac arrest
Authors: Hermann Bertrand , Candia-Rivera Diego , Sharshar Tarek , Gavaret Martine , Diehl Jean-Luc , Cariou Alain , Benghanem Sarah 
Published: March 2023

ABSTRACTBackground and ObjectivesApproximately 50% of post-cardiac arrest survivors remain comatose after 72h, a substantial proportion of which will have a poor neurological outcome, predominantly due to irreversible hypoxic-ischemic brain injury. Recent findings in healthy subjects and patients suggested that autonomic nervous system activity measured by brain-heart interactions could be reliable markers of consciousness and cognitive processing. Thus, we hypothesized that brain-heart interactions are associated with the severity of hypoxic-ischemic brain injury and the prognosis of these patients.MethodsIn post-cardiac arrest patients still comatose 48h after sedation weaning, brain-heart interaction markers were computed on 5 minutes of continuous EEG/ECG recording using a synthetic data generation model, gathering bidirectional interactions between EEG frequency bands (delta, theta and alpha) and heart-rate variability frequency bands (low and high frequency). The strength and complexity of the interactions were quantified using medians and refined composite multiscale entropy. Primary outcome was the severity of brain injury, assessed by: (i) standardized qualitative EEG classification, (ii) somatosensory evoked potentials (N20), and (iii) neuron-specific enolase levels. Secondary outcome was the 3-month neurological status, assessed by the Cerebral Performance Category score [good (1-2) vs. poor outcome (3-4-5)].ResultsBetween January 2007 and July 2021, 181 patients [116 males (64%), median age 61 years, age range 49-72 years] were admitted to ICU for a resuscitated cardiac arrest (76% out-of-hospital, 69% non-shockable rhythm). Poor neurological outcome was observed in 134 patients (74%). Qualitative EEG patterns suggesting high severity were associated with a decreased sympatho-vagal balance. Severity of EEG changes were proportional to higher absolute values of brain-to-heart coupling strength (p<2×10−3for all brain-to-heart frequencies) and lower values of complexity (all p-values<0.05 except for alpha-to-low frequency). Brain-to-heart coupling strength was significantly higher in patients with bilateral absent N20 and correlated with neuron-specific enolase levels at day 3. This aberrant brain-to-heart coupling (increased strength, decreased complexity) was also associated with 3-month poor neurological outcome.DiscussionOur results suggest that autonomic dysfunctions may well represent hypoxic-ischemic brain injury post-cardiac arrest pathophysiology. These results open avenues for integrative monitoring of autonomic functioning in critical care patients with potential prognostic applications.
Neighborhood Social Vulnerability and Interstage Weight Gain: Evaluating the Role of a Home Monitoring Program
Authors: Shustak Rachel J. , Huang Jing , Tam Vicky , Stagg Alyson , Giglia Therese M. , Ravishankar Chitra , Mercer-Rosa Laura , Guevara James P. , Gardner Monique M. 
Published: March 2023

ABSTRACTIntroductionPoor interstage (IS) weight gain is a risk factor for adverse outcomes in infants with hypoplastic left heart syndrome (HLHS). We sought to examine the association of neighborhood social vulnerability and IS weight gain and determine if this association is modified by enrollment in our institution’s Infant Single Ventricle Management and Monitoring Program (ISVMP).MethodsWe performed a retrospective single-center study of infants with HLHS before (2007-2010) and after (2011-2020) the introduction of the ISVMP. The primary outcome was IS weight gain, and the secondary outcome was IS growth failure. Multivariable linear and logistic regression models were used to examine the association between Social Vulnerability Index (SVI) and the outcomes. We introduced an interaction term into the models to test for effect modification by ISVMP.ResultsWe evaluated 217 ISVMP infants and 111 pre-ISVMP historical controls. SVI was associated with IS growth failure (P = 0.001), however, enrollment in ISVMP strongly attenuated this association (P = 0.04). Pre-ISVMP, high and middle vulnerability infants gained 4 gm/day less and were significantly more likely to experience growth failure than low vulnerability infants (high vs. low: aOR 12.5; 95% CI 2.5-62.2; middle vs. low: aOR 7.8; 95% CI 2.0-31.2). After the introduction of the ISVMP, outcomes did not differ by SVI tertile. Middle and high SVI infants enrolled in ISVMP gained 4 gm/day and 2 gm/day more, respectively, than pre-ISVMP controls.ConclusionIn infants with HLHS, high social vulnerability is a risk factor for poor IS weight gain. However, enrollment in ISVMP significantly reduces growth disparities.
An ultrasensitive method for detecting mutations from short and rare cell-free DNA
Authors: Wang Lin , Zhuang Yu , Yu Yue , Guo Zhiwei , Guo Qiaomei , Qiao Lihua , Wang Xueqing , Liang Xiaohui , Zhang Pengpeng , Li Qifan , Huang Chenjun , Cong Rong , Li Yinghui , Che Bin , Lin Guomin , Rao Mingming , Hu Rongjun , Lou Jiatao , Wang Wei , Yang Guohua 
Published: March 2023

AbstractBackgroundCell-free DNA (cfDNA) promises to serve as surrogate biomarkers for non-invasive molecular diagnostics. Disease-specific cfDNA, such as circulating tumor DNA (ctDNA), was short and rare, making the detection performance of the current targeted sequencing methods unsatisfying.MethodsThrough introducing a linear pre-amplification process and optimizing the adapter ligation with customized reagents, we developed the One-PrimER Amplification (OPERA) system. In this study, we examined its performance in detecting mutations of low variant allelic frequency (VAF) in various samples with short-sized DNA fragments.ResultsIn cell line-derived samples containing sonication-sheared DNA fragments with 50-150 bp (peak at 70-80 bp), OPERA was capable of detecting mutations as low as 0.0025% VAF, while CAPP-Seq only detected mutations of >0.03% VAF. Both single nucleotide variant and insertion/deletion can be detected by OPERA. In synthetic fragments as short as 80 bp with low VAF (0.03%-0.1%), the detection sensitivity of OPERA was significantly higher compared to that of droplet digital polymerase chain reaction. The error rate was 5.9×10−5errors per base after de-duplication in plasma samples collected from healthy volunteers. By suppressing “single-strand errors”, the error rate can be further lowered by >5 folds inEGFRT790M hotspot. In plasma samples collected from lung cancer patients, OPERA detected mutations in 57.1% stage I patients with 100% specificity and achieved a sensitivity of 30.0% in patients with tumor volume of less than 1 cm3.ConclusionsOPERA can effectively detect mutations in rare and highly-fragmented DNA.Trial registrationThis study has been registered on ChiCTR (ChiCTR1900024028) at 23rdJune 2019. Keywords: cell-free DNA; library preparation; liquid biopsy; mutation; next-generation sequencing.
Does one session of dry needling effect vital capacity in people with Parkinsons Disease?
Authors: Tahara Ariany Klein , Gastaldi Ada Clarice , Chinaglia Abel Gonçalves , Monteiro Rafael Luiz Martins , Tumas Vitor , Pereira Santiago Paulo Roberto 
Published: March 2023

ABSTRACTRespiratory function problems are caused by both motor and non-motor symptoms of Parkinson’s disease (PD). One major problem involving the changes in respiratory function in people with PD is a decrease in chest movement caused by musculoskeletal problems around the neck and upper trunk. The relationship between these respiratory changes and pulmonary volume in people with PD can lead to the main cause of mortality as the disease progresses. Dry needling technique (DNT) is a myofascial release technique that has been reported to provide an immediate effect on pain, decreased muscle spasm or tightness and lead to restoration of range of motion of upper trunk by using needles to stimulate hypersensitive and painful nodules in the musculature called trigger points (TP). However, to date, the use of this technique has not been reported to release muscle tightness or pain in people with PD. The present study aimed to explore the effects of a single session of bilateral DNT to the trapezius muscles trigger point on chest expansion and vital capacity which could lead to improvements in respiratory function in people with PD. Thirty-eight people with PD were randomly allocated to DN and Sham needling treatment groups. The maximum and mean volumes of vital capacity were assessed by using a ventilometer at pre-intervention, immediately after intervention, and one-week follow-up. Mixed Model Analysis of Variance (MM ANOVA) tests with post hoc pairwise comparisons were used to test the differences between groups and assessment time points. No interaction effects were found between groups and assessment time points for maximum and mean vital capacity volume. In addition, no statistically significant main effects of DNT were found for both groups and assessment time points for either maximum or mean vital capacity volume. These findings can provide evidence that a single session of dry needling does not help to improve respiratory function in people with PD. However, slight improvements in vital capacity were observed in the DN group, which may be clinically relevant when considering progressive neurodegenerative disease. More sessions of dry needling need to be explored over a greater time period to determine if longer term effect are possible with this treatment.
Identifying potential risk genes and pathways for neuropsychiatric and substance use disorders using intermediate molecular mediator information
Authors: Gedik Huseyin , Nguyen Tan Hoang , Peterson Roseann E. , Chatzinakos Christos , Riley Brien P. , Vladimirov Vladimir I. , Bacanu Silviu-Alin 
Published: March 2023

AbstractNeuropsychiatric and substance use disorders (NPSUD) have a complex etiology that includes environmental and polygenic risk factors with significant cross-trait rG. Genome Wide Association Studies (GWAS) of NPSUD yield numerous association signals. However, for most of these regions, we do not yet have a firm understanding of either the specific risk variants or the effects of these variants. Post-GWAS methods allow researchers to use GWAS summary statistics and functional genomics data to infer the likely molecular mediators (transcript, protein and methylation abundances) for the effect of variants on disorders. One group of post-GWAS approaches is commonly referred to as transcriptome/proteome/methylome wide association studies, which are abbreviated as T/P/MWAS (or collectively as XWAS). Since these approaches use biological mediators, the multiple testing burden is reduced to the number of genes (∼20,000) instead of millions GWAS SNPs leading to increased signal detection. In this work, our aim is to uncover likely risk genes for NPSUD by performing XWAS analyses in two tissues – blood and brain. Firstly, XWAS using the Summary-data based Mendelian Randomization (SMR), which takes GWAS summary statistics, reference xQTL data and a reference LD panel as inputs, was conducted to identify putative causal risk genes. Second, given the large comorbidities among NPSUD and the shared cis-xQTLs between blood and brain, we improved XWAS signal detection in NPSUD for underpowered analyses by performing joint concordance analyses between XWAS results i) across the two tissues and ii) across NPSUD. All XWAS signals i) were adjusted for HEIDI (non-causality) p-values and ii) used to test for pathway enrichment. The results suggest that there were widely shared gene/protein signals within the Major Histocompatibility (MHC) region on chromosome 6 (BTN3A2andC4A)and elsewhere in the genome (RERE, FURIN, ZDHHC5andNEK4). The identification of putative molecular genes and pathways underlying risk may offer new targets for therapeutic development. Some of our analyses’ more immediate actionable signals might relate to vitamins, i.e., i) inKYAT3(a part of the kynurenine pathway with vitamin B6 as a cofactor) for post-traumatic stress disorder and ii) omega-3 and vitamin D pathways for bipolar disorder.
Effect of experimental hookworm infection on insulin resistance in people at risk of Type 2 Diabetes: a randomized, placebo-controlled trial
Authors: Pierce Doris R. , McDonald Malcolm , Merone Lea , Becker Luke , Thompson Fintan , Lewis Chris , Field Matthew A. , Rahman Tony , Croese John , Loukas Alex , McDermott Robyn , Giacomin Paul R. 
Published: March 2023

ABSTRACTThe reduced prevalence of insulin resistance and type 2 diabetes (T2D) in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomized controlled trial of hookworm infection in 40 people at risk of T2D involved treatment with either 20 or 40Necator americanusthird-stage larvae (L3) or Placebo. Primary outcome was safety, with homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), and body mass being the key metabolic outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced transient gastrointestinal symptoms. FBG and HOMA-IR were significantly lowered in both hookworm-treated groups at 1-year, and body mass was significantly lowered after L3-20 treatment at 2-years. Overall, hookworm infection was well tolerated in people at risk of T2D, and were associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.
Serial passaging affects stromal cell mechanosensitivity on hyaluronic acid hydrogels
Authors: Sumey Jenna L. , Harrell Abigail M. , Johnston Peyton C. , Caliari Steven R. 
Published: March 2023

AbstractThere is tremendous interest in developing hydrogels as tunablein vitrocell culture platforms to study cell response to mechanical cues in a controlled manner. However, little is known about how common cell culture techniques, such as serial expansion on tissue culture plastic, affect subsequent cell behavior when cultured on hydrogels. In this work we leverage a methacrylated hyaluronic acid hydrogel platform to study stromal cell mechanotransduction. Hydrogels are first formed through thiol-Michael addition to model normal soft tissue (e.g., lung) stiffness (E~ 1 kPa). Secondary crosslinking via radical photopolymerization of unconsumed methacrylates allows matching of early- (E~ 6 kPa) and late-stage fibrotic tissue (E~ 50 kPa). Early passage (P1) primary human mesenchymal stromal cells (hMSCs) display increased spreading, myocardin-related transcription factor-A (MRTF-A) nuclear localization, and focal adhesion size with increasing hydrogel stiffness. However, late passage (P5) hMSCs show reduced sensitivity to substrate mechanics with lower MRTF-A nuclear translocation and smaller focal adhesions on stiffer hydrogels compared to early passage hMSCs. Similar trends are observed in an immortalized human lung fibroblast line. Overall, this work highlights the implications of standard cell culture practices on investigating cell response to mechanical signals usingin vitrohydrogel models.
Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity
Authors: Moirangthem Romila , Cordela Sapir , Khateeb Dina , Mandelboim Michal , Jönsson Friederike , Bruel Timothée , Bar-On Yotam 
Published: March 2023

AbstractTargeting multiple viral proteins is pivotal for sustained viral suppression. In recent years, several broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed. However, the impact of dual neutralization of these two glycoproteins on the course of infection has not been thoroughly tested. Here we demonstrate that a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase has a dual antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We further show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over antibody combination as it results in an improved neutralization capacity and augmented antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice. These findings suggest that dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.
Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells
Authors: Liu Silvia , Yu Yan-Ping , Ren Bao-Guo , Ben-Yehezkel Tuval , Obert Caroline , Smith Mat , Wang Wenjia , Ostrowska Alina , Soto-Gutierrez Alejandro , Luo Jian-Hua 
Published: March 2023

AbstractThe protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate Long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPseq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection (UMAP) analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen (HLA) molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPseq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.
Prevalence of Cardiometabolic Disease Risk Factors in People living with HIV Initiating Anti-retroviral Therapy at a High-Volume HIV Clinic in Kampala, Uganda
Authors: Amutuhaire Willington , Mulindwa Frank , Castelnuovo Barbara , Brusselaers Nele , Schwarz Jean-Marc , Edrisa Mutebi , Dujanga Simon , Salata Robert A. , Yendewa George A. 
Published: March 2023

ABSTRACTBackgroundCardiometabolic diseases are a leading cause of HIV-related morbidity and mortality, yet routine screening is not undertaken in high burden countries. We aimed to assess the prevalence and risk factors of the metabolic syndrome (MetS) and its components in adult Ugandan people living with HIV (PLHIV) initiating dolutegravir-based antiretroviral therapy (ART).MethodsWe analyzed baseline data of PLHIV aged ≥ 18 years enrolled in the GLUMED (Glucose metabolism changes in Ugandan HIV patients on Dolutegravir) Study from January to October 2021. MetS was defined as having 3 or more of the following: abdominal obesity, hypertension (HTN), elevated fasting glucose, elevated triglycerides and low high-density lipoprotein cholesterol. Multiple logistic regression was used to assess associations between potential risk factors and MetS and its components.Results309 PLHIV were analyzed (100% ART-naive, 59.2% female, median age 31 years and median CD4 count 318 cells/mm3). The prevalence of MetS was 13.9%. The most common cardiometabolic condition was dyslipidemia (93.6%), followed by abdominal obesity (34.0%), hyperglycemia (18.4%), and HTN (8.1%). In adjusted analysis, MetS was associated with age > 40 years (odds ratio 3.33, 95% confidence interval 1.45-7.67) and CD4 count > 200 cells/mm3(3.79, 1.23-11.63). HTN was associated with age > 40 years (2.96, 1.32-6.64), and dyslipidemia was associated with urban residence (4.99, 1.35-18.53).ConclusionCardiometabolic risk factors were common in this young Ugandan cohort of PLHIV initiating dolutegravir-based ART, underscoring the need for programmatic implementation of surveillance and management of comorbidities in Uganda and similar settings.Key pointsIn Ugandan HIV patients initiating antiretroviral treatment, the prevalence of cardiometabolic risk factors was substantial: metabolic syndrome 13.9%, dyslipidemia 93.6%, abdominal obesity 34.0%, hyperglycemia 18.4%, and hypertension 8.1%. This highlights the need for early screening and management of comorbidities.
Rapid evolution of pre-zygotic reproductive barriers in allopatric populations
Authors: Mahilkar Anjali , Nagendra Prachitha , Venkataraman Pavithra , Deshmukh Saniya , Saini Supreet 
Published: March 2023

AbstractAdaptive divergence leading to speciation is the major evolutionary process generating diversity in life forms. The most commonly observed form of speciation is allopatric speciation which requires that gene flow be prevented between populations by physical or temporal barriers, as they adapt to their respective environments. Eventually, these adaptive responses drive the populations far apart in the genotypic space such that individuals from the two populations become reproductively isolated. A widely accepted theory is that speciation simply occurs as a by-product of adaptive response of the populations1,2. Several ecological and laboratory examples of allopatric speciation exist3–6. However, we know little about the nature (pre- or post-zygotic) of barriers that arise first in this process. Understanding the first barriers that arise between populations is key, as populations diverge towards becoming distinct species. In recent years, fungi been used as model organisms to answer questions related to evolution of reproductive isolation3,7–9. Here we show rapid evolution of pre-zygotic barriers between allopatric yeast populations. We further demonstrate that these pre-zygotic barriers arise due to altered mating kinetics of the evolved population. Moreover, our non-adaptive evolution experiments with yeast under limited selection pressure also show rapid emergence of reproductive isolation. Overall, our results show that evolution of pre-zygotic reproductive barriers can occur as result of natural selection or drift. These barriers result because of altered mating kinetics or mate preference.One sentence summaryPre-zygotic barriers to gene flow can arise due to adaptation or drift.
The genetic and physiological basis ofArabidopsis thalianatolerance toPseudomonas viridiflava
Authors: Duque-Jaramillo Alejandra , Ulmer Nina , Alseekh Saleh , Bezrukov Ilja , Fernie Alisdair R. , Skirycz Aleksandra , Karasov Talia L. , Weigel Detlef 
Published: March 2023

SUMMARYThe opportunistic pathogenPseudomonas viridiflavacolonizes more than fifty agricultural crop species and is the most commonPseudomonasin the phyllosphere of EuropeanArabidopsis thalianapopulations. Belonging to theP. syringaecomplex, it is genetically and phenotypically distinct from well-characterizedP. syringae sensu stricto. Despite its prevalence, we lack knowledge of howA. thalianaresponds to its native isolates at the molecular level. Here, we characterize the host response in anA. thaliana-P. viridiflavapathosystem.We measured host and pathogen growth in axenic infections, and used immune mutants, transcriptomics, and metabolomics to determine defense pathways influencing susceptibility toP. viridiflavainfection.Infection withP. viridiflavaincreased jasmonic acid (JA) levels and the expression of ethylene defense pathway marker genes. The immune response in a susceptible host accession was delayed compared to a tolerant one. Mechanical injury rescued susceptibility, consistent with an involvement of JA.The JA/ethylene pathway is important for suppression ofP. viridiflava, yet suppression capacity varies between accessions. Our results shed light on howA. thalianacan suppress the ever-presentP. viridiflava, but further studies are needed to understand howP. viridiflavaevades this suppression to spread broadly acrossA. thalianapopulations.