bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of a Case of Toe Hair-Thread Tourniquet Syndrome With Hirasè Technique
Authors: Tamborini Federico , Sallam Davide , Maggiulli Francesca , Pellegatta Igor , Corno Martina , Cherubino Mario , Valdatta Luigi 
Published: September 2021

Abstract
Hair-thread tourniquet syndrome (HTTS) is an uncommon condition that affects mostly babies, usually a few months old. It happens when a strand of hair or cloth fiber encircles an appendage causing a condition of total or subtotal ischemia (West J Med 1976;125:335–336). This condition has been described several times in the recent literature. Appendages involved include toes, fingers, genitalia, uvula, and neck (N Engl J Med 1965;273:866–867). The mechanism of injury usually involves the fiber cutting the skin deeply through soft tissues, veins, and arteries. As HTTS occurs in small babies and hidden parts of the body, sometimes this event can be very difficult to detect and irritability may be the only symptom. The treatment consists of releasing the circumferential constriction and restoring the arteriovenous flow also with microsurgical techniques if vessel interruption is present. Unfortunately, the fiber or the thread often penetrates so deep that, once an HTTS is recognized, it may be very challenging to identify and trim. The authors present a case of HTTS of the second toe of the right foot in a 2-month-old baby treated with surgical release and Hirasè technique. After the thread was successfully cut and removed, the forefoot was covered with aluminum foil, and a bag with ice was immediately put all around. After 3 days, we observed a complete survival of the toe without any sign of necrosis. Later control at 6 months showed complete restitutio ad integrum of the affected digit with a normal perfusion and absence of any onychopathy. Hirasè technique represents a simple, safe, and low-cost option of treatment for HTTS.
Incidental Detection of Sacral Insufficiency Fracture on 68Ga-FAPI PET/MR
Authors: Lv Yuhu , Lan Xiaoli , Qin Chunxia 
Published: September 2021

Abstract
A 61-year-old woman with low-set rectal adenocarcinoma (cT4bN1Mx) received radiotherapy and chemotherapy for 4 months, and then she underwent 18F-FDG PET/CT and 68Ga-FAPI PET/MR. Obviously increased 68Ga-FAPI uptake was unexpectedly revealed on both sides of the sacrum with low 18F-FDG uptake, which was diagnosed as insufficiency fracture based on the imaging features, advanced patient age, and radiotherapy history. The possibility of insufficiency fracture should be considered when accidental, symmetrically increased sacral 68Ga-FAPI uptake appears in cancer patients, and differential diagnosis should be carefully made.
Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy
Authors: Choudhary Manish C. , Chew Kara W. , Deo Rinki , Flynn James P. , Regan James , Crain Charles R. , Moser Carlee , Hughes Michael , Ritz Justin , Ribeiro Ruy M. , Ke Ruian , Dragavon Joan A. , Javan Arzhang C. , Nirula Ajay , Klekotka Paul , Greninger Alexander L. , Fletcher Courtney V. , Daar Eric S. , Wohl David A. , Eron Joseph J. , Currier Judith S. , Parikh Urvi M. , Sieg Scott F. , Perelson Alan S. , Coombs Robert W. , Smith Davey M. , Li Jonathan Z. ,   for the ACTIV-2/A5401 Study Team
Published: September 2021

ABSTRACTResistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if in vivo emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.003). There were no treatment-emergent resistance mutations among the 48 participants who received bamlanivimab 7000mg. Participants with emerging mAb resistant virus had significantly higher pre-treatment nasopharyngeal and anterior nasal viral load. Intensive respiratory tract viral sampling revealed the dynamic nature of SARS-CoV-2 evolution, with evidence of rapid and sustained viral rebound after emergence of resistance mutations, and worsened symptom severity. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest and associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment, resulting in prolonged high level respiratory tract viral loads and clinical worsening. Careful virologic assessment should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.
Localising Vaccination Services: Qualitative Insights on an Orthodox Jewish Collaboration with Public health during the UK coronavirus Vaccine Programme
Authors: Kasstan Ben , Mounier-Jack Sandra , Letley Louise , Gaskell Katherine M , Roberts Chrissy H , Stone Neil RH , Lal Sham , Eggo Rosalind M , Marks Michael , Chantler Tracey 
Published: September 2021

AbstractEthnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation.Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders’ response to situated (context-specific) challenges and concerns.Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.
Vascular flow simulations using SimVascular and OpenFOAM
Authors: Yogeswaran Swetha , Liu Fei 
Published: September 2021

AbstractApplications of computational fluid dynamics (CFD) techniques to aid in the diagnosis and treatment of cardiovascular disease have entered the research domain in recent years, due to their ability to provide valuable patient-specific information without risks associated with highly invasive procedures. SimVascular [1] [2] is an open-source software which allows streamlined processing and CFD blood flow analysis of medical imaging data. OpenFOAM [3] is a proven open-source software which allows for versatile modeling of various fluid dynamics phenomena. In this study, both SimVascular and OpenFOAM simulations are set up with identical computational mesh, similar numerical schemes, boundary conditions, and material properties, to model blood flow in the coronary artery of a 10 year old patient with Coarctation of the Aorta (CoA) who underwent end-to-side anastomosis. Difference in the flow fields such as flow rate, pressure, vorticity, and wall shear stress between SimVascular and OpenFOAM are analyzed. Similar results are obtained in both simulations up to a certain model time, before the results become drastically different. Both the similarities and differences are documented and discussed.
Bacterial and Fungal Co-Infections among ICU COVID-19 Hospitalized Patients in a Palestinian Hospital: Incidence and Antimicrobial Stewardship
Authors: Naseef Hani A. , Mohammad Ula , Al-Shami Nimeh , Sahoury Yousef , Abukhalil Abdallah D. , Farraj Mohammad 
Published: September 2021

AbstractDiagnosis of co-infections with multiple pathogens among hospitalized COVID-19 patients can be jointly challenging and very essential for appropriate treatment, shortening hospital stay and preventing antimicrobial resistance. This study proposes to investigate the burden of bacterial and fungal co-infections outcomes on COVID-19 patients. It is a single centre cross-sectional study of hospitalized COVID-19 patients at Beit-Jala hospital in Palestine. The study included 321 hospitalized patients admitted to the ICU between June 2020 and March 2021 aged ≥ 20 years, with a confirmed diagnosis of COVID-19 via RT-PCR conducted on a nasopharyngeal swab. The patient’s information was gathered using graded data forms from electronic medical reports. The diagnosis of bacterial and fungal infection was proved through the patient’s clinical presentation and positive blood or sputum culture results. All cases had received empirical antimicrobial therapy before the ICU admission, and different regimens during the ICU stay. The rate of bacterial co-infection was 51.1%, mainly from gram-negative isolates (Enterobacter species and K.pneumoniae). The rate of fungal co-infection caused by A.fumigatus was 48.9%, and the mortality rate was 8.1%. However, it is unclear if it had been attributed to SARS-CoV-2 or coincidental.
Causal reasoning over knowledge graphs leveraging drug-perturbed and disease-specific transcriptomic signatures for drug discovery
Authors: Domingo-Fernández Daniel , Gadiya Yojana , Patel Abhishek , Mubeen Sarah , Rivas-Barragan Daniel , Diana Chris W. , Misra Biswapriya B. , Healey David , Rokicki Joe , Colluru Viswa 
Published: September 2021

AbstractNetwork-based approaches are becoming increasingly popular for drug discovery as they provide a systems-level overview of the mechanisms underlying disease pathophysiology. They have demonstrated significant early promise over other methods of biological data representation, such as in target discovery, side effect prediction and drug repurposing. In parallel, an explosion of -omics data for the deep characterization of biological systems routinely uncovers molecular signatures of disease for similar applications. Here, we present RPath, a novel algorithm that prioritizes drugs for a given disease by reasoning over causal paths in a knowledge graph (KG), guided by both drug-perturbed as well as disease-specific transcriptomic signatures. First, our approach identifies the causal paths that connect a drug to a particular disease. Next, it reasons over these paths to identify those that correlate with the transcriptional signatures observed in a drug-perturbation experiment, and anti-correlate to signatures observed in the disease of interest. The paths which match this signature profile are then proposed to represent the mechanism of action of the drug. We demonstrate how RPath consistently prioritizes clinically investigated drug-disease pairs on multiple datasets and KGs, achieving better performance over other similar methodologies. Furthermore, we present two applications showing how one can deconvolute the predictions made by RPath as well as predict novel targets. Finally, we have made the source code and data publicly available at https://github.com/enveda/RPath.
Maximized redundant and synergistic information transfers predict the rise in the output gene expression noise in a generic class of coherent type-1 feed-forward loop networks
Authors: Aziz Momin Md Sorique , Biswas Ayan 
Published: September 2021

AbstractWe apply the partial information decomposition principle to a generic coherent type-1 feed-forward loop (C1-FFL) motif with tunable direct and indirect transcriptional regulations of the output gene product and quantify the redundant, synergistic, and unique information transfers from the regulators to their target output species. Our results which are obtained within the small-noise regime of a Gaussian framework reveal that the redundant and synergistic information transfers are antagonistically related to the output noise. Most importantly, these two information flavors are maximized prior to the minimization and subsequent growth of the output noise. Therefore, we hypothesize that the dynamic information redundancy and synergy maxima may possibly be utilized as efficient statistical predictors to forecast the increasing trend of the fluctuations associated with the output gene expression dynamics in the C1-FFL class of network motifs. Our core analytical finding is supported by exact stochastic simulation data and furthermore validated for a diversified repertoire of biologically plausible parameters. Since, the output gene product serves essential physiological purposes in the cell, a predictive estimate of its noise level is supposed to be of considerable biophysical utility.
Hobotnica: exploring molecular signature quality
Authors: Stupnikov Alexey , Sizykh Alexey , Favorov Alexander , Afsari Bahman , Wheelan Sarah , Marchionni Luigi , Medvedeva Yulia A. 
Published: September 2021

AbstractA Molecular Features Set (MFS), is a result of vast diversity of bioinformatics pipelines. In case when MFS is used for further analysis to distinguish between phenotypes, it is often referred to as a signature. Lack of the “gold standard” for most experimental data modalities makes it hard to provide valid estimation for a particular MFS’s quality. Yet, this goal can partially be achieved by analyzing inner-sample Distance Matrix (DM) and their power to distinguish between phenotypes.The quality of a DM can be assessed by summarizing its power to quantify the differences of inner-phenotype and outer-phenotype distances. This estimation of the DM quality can be construed as a measure of the MFS’s quality.Here we propose Hobotnica, an approach to estimate MFS’s quality by their ability to stratify data, and assign them significance scores, that allows for collating various signatures and comparing their quality for contrasting groups.
Angiotensin II Inhibits the A-type K+ Current of Hypothalamic Paraventricular Nucleus Neurons in Rats with Heart Failure: Role of MAPK-ERK1/2 Signaling
Authors: Roy Ranjan K. , Ferreira-Neto Hildebrando Candido , Felder Robert B. , Stern Javier E. 
Published: September 2021

ABSTRACTANGII-mediated sympathohumoral activation constitutes a key pathophysiological mechanism in heart failure (HF). While the hypothalamic paraventricular nucleus (PVN) is recognized as a major site mediating ANGII effects in HF, the precise mechanisms by which ANGII influences sympathohumoral outflow from the PVN remain unknown. ANGII activates the ubiquitous intracellular MAPK signaling cascades and recent studies revealed a key role for ERK1/2 MAPK signaling in ANGII-mediated sympathoexcitation in HF rats. Importantly, ERK1/2 was reported to inhibit the transient outward potassium current (IA) in hippocampal neurons. Given that IA is a critical determinant of the PVN neuronal excitability, and that downregulation of IA in the brain has been reported in cardiovascular disease states, including HF, we investigated here whether ANGII modulates IA in PVN neurons via the MAPK-ERK pathway, and, whether these effects are altered in HF rats. Patch-clamp recordings from identified magnocellular neurosecretory (MNNs) and presympathetic (PS) PVN neurons revealed that ANGII inhibited IA in both PVN neuronal types, both in sham and HF rats. Importantly, ANGII effects were blocked by inhibiting MAPK-ERK signaling as well as by inhibiting EGFR, a gateway to MAPK-ERK signaling. While no differences in basal IA magnitude were found between sham and HF rats under normal conditions, MAPK-ERK blockade resulted in significantly larger IA in both PVN neuronal types in HF rats. Taken together, our studies show that ANGII-induced ERK1/2 activity inhibits IA and increases the excitability of presympathetic and neuroendocrine PVN neurons, contributing to the neurohumoral overactivity than promotes progression of the HF syndrome.GRAPHICAL ABSTRACT
Injury-induced Erk1/2 signaling enhances Ca2+ activity and is necessary for regeneration of spinal cord and skeletal muscle
Authors: Levin Jacqueline B. , Borodinsky Laura N. 
Published: September 2021

ABSTRACTThe transition of stem cells from quiescence to proliferation enables tissues to self-repair. The signaling mechanisms driving these stem-cell-status decisions are still unclear. Ca2+ and the extracellular signal-regulated kinase (Erk1/2) are two signaling pathways that have the potential to coordinate multiple signals to promote a specific cellular response. They both play important roles during development but their roles during regeneration are not fully deciphered. Here we show in Xenopus laevis larvae that both Ca2+ and Erk1/2 signaling pathways are activated after tail amputation. In response to injury, we find that Erk1/2 signaling is activated in neural and muscle stem cells and is necessary for spinal cord and skeletal muscle regeneration. Finally, we show in vivo that Erk1/2 action is necessary for an injury-induced increase in intracellular store-dependent Ca2+ dynamics in skeletal muscle-associated tissues but that in spinal cord, injury increases Ca2+ influx-dependent Ca2+ activity independent of Erk1/2 signaling. This study suggests that precise temporal and tissue-specific activation of Ca2+ and Erk1/2 pathways is essential for regulating tissue regeneration.
Brain stimulation boosts perceptual learning by altering sensory GABAergic plasticity and functional connectivity
Authors: Karlaftis Vasilis M , Frangou Polytimi , Higgins Cameron , Vidaurre Diego , Ziminski Joseph J , Stagg Charlotte J , Emir Uzay E , Kourtzi Zoe 
Published: September 2021

AbstractInterpreting cluttered scenes —a key skill for successfully interacting with our environment— relies on our ability to select relevant sensory signals while filtering out noise. Training is known to improve our ability to make these perceptual judgements by altering local processing in sensory brain areas. Yet, the brain-wide network mechanisms that mediate our ability for perceptual learning remain largely unknown. Here, we combine transcranial direct current stimulation (tDCS) with multi-modal brain measures to modulate cortical excitability during training on a signal-in-noise task (i.e. detection of visual patterns in noise) and test directly the link between processing in visual cortex and its interactions with decision-related areas (i.e. posterior parietal cortex). We test whether brain stimulation alters inhibitory processing in visual cortex, as measured by magnetic resonance spectroscopy (MRS) of GABA and functional connectivity between visual and posterior parietal cortex, as measured by resting state functional magnetic resonance imaging (rs-fMRI). We show that anodal tDCS during training results in faster learning and decreased GABA+ during training, before these changes occur for training without stimulation (i.e. sham). Further, anodal tDCS decreases occipito-parietal interactions and time-varying connectivity across the visual cortex. Our findings demonstrate that tDCS boosts learning by accelerating visual GABAergic plasticity and altering interactions between visual and decision-related areas, suggesting that training optimises gain control mechanisms (i.e. GABAergic inhibition) and functional inter-areal interactions to support perceptual learning.
Proteome signatures of reductive stress cardiomyopathy
Authors: Sunny Sini , David Cynthia L. , Parsawar Krishna , Jones Dean P. , Rajasekaran Namakkal S. 
Published: September 2021

AbstractNuclear factor erythroid 2-related factor 2 (NRF2), a redox sensor, is vital for cellular redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2-TG) exhibit reductive stress (RS). In this study, we identified novel protein biomarkers for RS-induced cardiomyopathy using Tandem Mass Tag (TMT) proteomic analysis in heart tissues of TG (CaNrf2-TG) and non-transgenic (NTg) mice at 6-7 months of age (N= 4/group). A total of 1105 proteins were extracted from 22544 spectra. Of note, about 560 proteins were differentially expressed in TG vs. NTg hearts, indicating a global impact of RS on myocardial proteome. From a closer analysis of the proteome datasets, we identified over 32 proteins that were significantly altered in response to RS. Among these, 20 were upregulated and 12 were downregulated in the hearts of TG vs. NTg mice, suggesting that these proteins could be putative signatures of RS. Scaffold analysis revealed a clear distinction between TG vs NTg hearts. Of note, we observed several proteins with redox (#185; cysteine residues), NEM-adducts (#81), methionine-loss (#21) and acetylation (#1) modifications in TG vs. NTg hearts due to chronic RS. The majority of the differentially expressed proteins (DEPs) that are significantly altered in RS mice were found to be involved in stress related pathways such as antioxidants, NADPH, protein quality control (PQC), etc. Interestingly, proteins that were involved in mitochondrial respiration, lipophagy and cardiac rhythm were dramatically decreased in TG hearts. Of note, we identified the glutathione family of proteins as the significantly changed subset of the proteome in TG heart. Surprisingly, our comparative analysis of NGS based transcriptome and TMT-proteome indicated ∼50% of the altered proteins in TG myocardium was found to be negatively correlated with their transcript levels. Modifications at cysteine/NEM-adducts (redox), methionine or lysine residues in multiple proteins in response to chronic RS might be associated with impaired PQC mechanisms, thus causing pathological cardiac remodeling.
Graphical Abstract