bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged shedding of SARS COV-2 in an asymptomatic patient– a case report
Authors: Kaur Mandeep , Singh Meenakshi , Dogra Girish , Awasthi Vandana , Dua Ajit 
Published: May 2023

Background- There have been few reports of asymptomatic SARS-CoV2 patients who have shed viruses for unusually prolonged period. These cases are generally identified during contact tracing of positive SARS-CoV2 patients and remain a stumbling block for control of transmission and spread of SARS-CoV2 viral infection. We are reporting a similar case of asymptomatic SARS-CoV2 carriage in respiratory secretions of a patient for two months.
Materials and methods- The present case study discusses about an asymptomatic young male patient who was tested positive for SARS-CoV2 after a recent travel. His nasopharyngeal samples showed consistent positivity for SARS-CoV2 from June 2021 till August 2021 when tested by Real Time RT PCR and the Ct values always remained less than 25. His clinical investigations were within normal limits except for high D-dimer levels and his HIV serology was negative during initial work up. He received second dose of COVID vaccine during quarantine period. Upon six months follow up of the patient, it was learned that he died of HIV infection in March 2022.
Discussion and conclusions- The persistence of SARS-CoV2 could be attributed to either COVID vaccination taken during quarantine period or may be due to HIV infection which might have been missed during the window period. This report suggests that there is high risk for silent spread of SARS-CoV2 by asymptomatic persons, thus it would be imperative to include such asymptomatic patients too for dynamic surveillance.
Clinical performance and safety of Cerviron®vaginal ovules in the local treatment of non-specific vaginitis: a national, multicentric clinical investigation
Authors: Toader Daniela Oana , Olaru Raluca Alexandra , Iliescu Dominic-Gabriel , Petrita Ramona , Calancea Florentina Liliana , Petre Izabella 
Published: May 2023

AbstractPurposeNon-specific vaginitis is a distinct clinical entity with particular microscopic and immunologic features. Currently, there is no standard of care for women with non-specific vaginitis. The aim of our study was to assess the change in vaginal symptoms score after a 3-months treatment with Cerviron®medical device in participants with abnormal vaginal discharge and with specific signs and symptoms. As secondary objectives, the study analyzed other clinical and microscopic features, such as vaginal discharge aspect, change in vaginal pH, change in vaginal microbiome, and vaginal inflammation.MethodsThe study population included 47 participants suffering from symptomatic vulvovaginitis, distinct from candidiasis, trichomoniasis or bacterial vaginosis. The study design included 2 research sites from Romania. The treatment protocol consisted of 1 ovule/day inserted intravaginally, during 15 consecutive days. The total study duration was 3 months.FindingsCerviron®had a positive impact on the vaginal symptoms score for 72.34% of the study participants. Topical administration of Cerviron®balanced vaginal pH values and significantly reduced signs of inflammation between study visits.ImplicationsCerviron®shows curative effects that supports its use as a stand-alone treatment in women with non-specific vaginitis.ClinicalTrials.govidentifier:NCT04735705.A second clinical investigation is ongoing to evaluate its clinical efficacy in postoperative care of cervical and vaginal wounds, traumatic or secondary to surgical interventions.
Effects of Adapted Mindfulness Training on Interoception and Adherence to the Dietary Approaches to Stop Hypertension (DASH) Diet: The MB-BP Randomized Clinical Trial
Authors: Loucks Eric B. , Kronish Ian M. , Saadeh Frances B. , Scarpaci Matthew M. , Proulx Jeffrey A. , Gutman Roee , Britton Willoughby B. , Schuman-Olivier Zev 
Published: May 2023

AbstractBackgroundHypertension is a major cause of cardiovascular disease. The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP). However, adherence is typically low. Mindfulness training adapted to improving health behaviors that lower BP could improve DASH adherence, in part through improved interoceptive awareness relevant to dietary consumption. The primary objective of the MB-BP trial was to evaluate effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on interoceptive awareness. Secondary objectives assessed whether MB-BP impacts DASH adherence, and explored whether interoceptive awareness mediates DASH dietary changes.MethodsParallel-group phase 2 randomized clinical trial conducted from June 2017-November 2020 with 6 months follow-up. Data analyst was blinded to group allocation. Participants had elevated unattended office BP (≥120/80 mmHg). We randomized 201 participants to MB-BP (n=101) or enhanced usual care control (n=100). Loss-to-follow-up was 11.9%. Outcomes were the Multidimensional Assessment of Interoceptive Awareness (MAIA; range 0-5) score, and the DASH adherence score (range 0-11) assessed via a 163-item Food Frequency Questionnaire.ResultsParticipants were 58.7% female, 81.1% non-Hispanic white, with mean age 59.5 years. Regression analyses demonstrated that MB-BP increased the MAIA score by 0.54 (95% CI: 0.35,0.74; p<.0001) at 6 months follow-up vs. control. MB-BP increased the DASH score by 0.62 (95% CI: 0.13,1.11; p=0.01) at 6 months vs. control, in participants with poor DASH adherence at baseline.ConclusionsA mindfulness training program adapted to improving health behaviors that lower BP improved interoceptive awareness and DASH adherence. MB-BP could support DASH dietary adherence in adults with elevated BP.Clinical Trial RegistrationClinicaltrials.govidentifierNCT03859076(https://clinicaltrials.gov/ct2/show/NCT03859076; MAIA) andNCT03256890(https://clinicaltrials.gov/ct2/show/NCT03256890; DASH diet adherence).
Neuregulin-1 protects against respiratory viral induced mortality
Authors: Hussain Syed-Rehan A , Rohlfing Michelle , Santoro Jennifer , Resiliac Jenny , Chen Phylip , Peeples Mark E. , Grayson Mitchell H 
Published: May 2023

AbstractRespiratory viral infections due to RNA viruses such as respiratory syncytial virus (RSV) and influenza lead to significant morbidity and mortality. Using a natural rodent pathogen similar to RSV, Sendai virus (SeV), we found that mice made atopic with house dust mite before viral infection all survived a normally lethal SeV infection.Moreover, adoptive transfer of CD11c+cells from atopic mice delayed viral mortality. Neuregulin-1 (NRG1) message was highly expressed in CD11c+cells from atopic mice and atopic lungs and bronchoalveolar lavage fluid had elevated levels of NRG1 protein. Administration of NRG1 protected non-atopic mice from death and associated with reduced alveolar epithelium permeability. Utilizing anin vitrosystem of well-differentiated human bronchial epithelial cells and mouse tracheal epithelial cells NRG1 reduced RSV and SeV titers. Expression of genes that play a role in airway epithelium integrity and stability were altered by NRG1; potentially regulating viral induced dysregulation of the epithelia and suggesting NRG1 mediated maintenance of homeostasis. In conclusion, our studies demonstrate atopy induced NRG1 likely plays a novel role in survival from severe respiratory viral infections and may have therapeutic value to prevent mortality from these infections.SignificanceSevere respiratory viral infections are associated with significant mortality in infants and the elderly; however, allergic disease can protect from these outcomes. This study identified a protein called neuregulin-1 (NRG1), produced by cells of the immune system in allergic mice, that provides a survival advantage against respiratory viral infection. NRG1 pretreatment in non-atopic mice infected with a lethal dose of a rodent RNA virus (Sendai virus), similar to human respiratory syncytial virus, significantly reduced death. Further, NRG1 pretreatment reduced viral replication in human and mouse airway epithelial cell cultures. These studies signify a potential therapeutic role of NRG1 in modulating the severity of respiratory viral infections.
Characteristics and phenotypes of a COPD cohort in Uganda
Authors: Alupo Patricia , Mugenyi Levicatus , Katagira Winceslaus , Alex Kayongo , Joanitah Nalunjogi , Siddharthan Trishul , Hurst John R , Kirenga Bruce , Jones Rupert 
Published: May 2023

ABSTRACTIntroductionChronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition with varied clinical and pathophysiologic characteristics. Although there is increasing evidence that COPD in low- and middle-income countries may have different clinical characteristics from that in high income countries, little is known about COPD phenotypes in these settings. We describe the clinical characteristics and risk factor profile of a COPD population in Uganda.MethodsWe cross sectionally analyzed the baseline clinical characteristics of 323 COPD patients aged 30 years and above who were attending two national referral outpatient facilities in Kampala, Uganda between July 2019 and March 2021. Logistic regression was used to determine factors associated with spirometric disease severity.ResultsThe median age was 62 years; 51.1% females; 93.5% scored CAT >10; 63.8% mMRC >2; 71.8% had wheezing; 16.7% HIV positive; 20.4% had a history of pulmonary tuberculosis; 50% with blood eosinophilic count >3%, 51.7% had 3 or more exacerbations in the past year. Greater severity by GOLD stage was inversely related to age, (aOR=0.95, 95%CI=0.92, 0.97), and obesity compared to underweight (aOR=0.25, 95%CI=0.07, 0.82). Regarding clinical factors, more severe airflow obstruction was associated with SPO2<93% (aOR=3.79, 95%CI=2.05, 7.00), mMMRC≥2 (aOR=2.21, 95%CI=1.08, 4.53), and a history of severe exacerbations (aOR=2.64, 95%CI=1.32, 5.26).ConclusionCOPD patients in this population had specific characteristics and risk factor profiles including HIV and TB meriting tailored preventative approaches. Further studies are needed to better understand the pathophysiological mechanisms at play and the therapeutic implications of these findings.Key messagesWhat is already known on this topic.COPD is a heterogeneous condition with the greatest burden in LMICs yet there is limited understanding of disease characteristics in this setting.What this study addsA cohort of patients with COPD recruited in hospital clinics in Uganda showed a high burden of disease with frequent exacerbations – 86% were GOLD category D. The cohort had a high exposure to biomass smoke and only 38% were past or present smokers.How this study might affect research, practice, or policyThere is need for more research into effective strategies to prevent and treat COPD in LMICs - it cannot be assumed that guidelines derived in high-income countries will apply.
RNAseqCovarImpute: a multiple imputation procedure that outperforms complete case and single imputation differential expression analysis
Authors: Baker Brennan H. , Sathyanarayana Sheela , Szpiro Adam A. , MacDonald James , Paquette Alison G. 
Published: May 2023

AbstractMissing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here we present a multiple imputation (MI) method that accommodates high dimensional transcriptomic data by binning genes, creating separate MI datasets and differential expression models within each bin, and pooling results with Rubin’s rules. Simulation studies using real and synthetic data show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R package, “RNAseqCovarImpute” that integrates with the limma-voom pipeline.
The Computational Analysis ofPlasmodium falciparumHeat Shock Proteins Reveals an Interplay with Polyamines
Authors: Sesethu Godlo , Nombalentle Maxam , Yamnkela Mthembu , Anelisa Mpumza , Makumire Stanley , Mkwetshana Noxolo , Govender Krishna K , Makhoba Xolani H 
Published: May 2023

AbstractThe current drugs available in the market are not effective due to growing numbers of resistance to the causative agent of malaria. There are variousPlasmodiumparasites, of whichPlasmodium falciparumis the main cause of morbidity and mortality reported worldwide. Therefore, there is an urgent need to come up with an innovative and effective treatment for this disease. Polyamines play a major role in the parasite’s well-being and growth, while heat shock proteins keep the proteomics of the parasite in good shape. In this study,In Silicoanalysis of the interaction between putrescine, spermidine, spermine, and heat shock proteins was carried out to establish the binding site for drug discovery. Computational tools such as Bioedit, PROCHECK, KNIME Hub, and Schrodinger were used. The results revealed interactions between polyamines and heat shock proteins with glutamine and aspartic acid being common amino acids where interaction occurs between the chaperones and polyamines. MD shows a strong interaction between PfHsp70-1 and putrescine, but the best interaction is observed for PfHsp70-1 and spermidine. Based on these results, a follow-up study will be conducted to establish the synthesis of drugs that will be used as targets for both polyamines and heat shock proteins to eradicate malaria.Author’s summaryThe emanation and spread of Plasmodium parasites that are resistant to antimalarial therapy is one of the main problems in the treatment of malaria. This is a result of the Plasmodium parasite’s ongoing evolution and the creation of novel strategies for surviving drug toxicity. Studies of antimalarial drug development have been focused on polyamine biosynthesis by targeting precursors such as ornithine decarboxylase, adenosylmethionine decarboxylase, and spermidine synthase and protein-protein interactions betweenPlasmodium falciparumchaperones spotting out Hsp90, Hsp70, and Hsp40 as potential targets with little attention being paid to the interaction between polyamines and molecular chaperones. Therefore, to study these interactions the binding sites of all 3D structures were identified using SiteMap, and a docking was performed using the Schrödinger software with OPLS4 force field and XP.
Anin silicoCardiomyocyte Reveals the Impact of Changes in CAMKII Signalling on Cardiomyocyte Contraction Kinetics in Hypertrophic Cardiomyopathy
Authors: Adeniran Ismail , Wadee Hafsa , Degens Hans 
Published: May 2023

AbstractHypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of thisin silicostudy was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism and crossbridge cycling in HCM at the single cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways; and b) increased Ca2+sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine to ATP ratio (−9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half sarcomere model, we also compared the fraction of detached, weakly bound and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply : demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.
Cell type specific polyploidization in the royal fat body of termite queens
Authors: Nozaki Tomonari , Tasaki Eisuke , Matsuura Kenji 
Published: May 2023

AbstractTissue-specific endopolyploidy is widespread among plants and animals and its role in organ development and function has long been investigated. In insects, the fat body cells of sexually mature females produce substantial amounts of egg yolk precursor proteins (vitellogenins) and exhibit high polyploid levels, which is considered crucial for boosting egg production. Termites are social insects with a reproductive division of labor, and the fat bodies of mature termite queens exhibit higher ploidy levels than those of other females. The fat bodies of mature termite queens are known to be histologically and cytologically specialized in protein synthesis. However, the relationship between such modifications and polyploidization remains unknown. In this study, we investigated the relationship among cell type, queen maturation, and ploidy levels in the fat body of the termiteReticulitermes speratus. We first confirmed that the termite fat body consists of two types of cells, that is, adipocytes, metabolically active cells, and urocytes, urate- storing cells. Our ploidy analysis using flow cytometry has shown that the fat bodies of actively reproducing queens had more polyploid cells than those of newly emerged and pre-reproductive queens, regardless of the queen phenotype (adult or neotenic type). Using image-based analysis, we found that adipocytes became polyploid during queen differentiation and subsequent sexual maturation. These results suggest that polyploidization in the termite queen fat body is associated with sexual maturation and is regulated in a cell type-specific manner. Our study findings have provided novel insights into the development of insect fat bodies and provide a basis for future studies to understand the functional importance of polyploidy in the fat bodies of termite queens.
Accelerating the Characterization of Dynamic DNA Origami Devices with Deep Neural Networks
Authors: Wang Yuchen , Jin Xin , Castro Carlos 
Published: May 2023

AbstractMechanical characterization of dynamic DNA nanodevices is essential to facilitate their use in applications like molecular diagnostics, force sensing, and nanorobotics that rely on device reconfiguration and interactions with other materials. A common approach to evaluate the mechanical properties of dynamic DNA nanodevices is by quantifying conformational distributions, where the magnitude of fluctuations correlates to the stiffness. This is generally carried out through manual measurement from experimental images, which is a tedious process and a critical bottleneck in the characterization pipeline. While many tools to support analysis of static of molecular structures, there is a need for tools to facilitate the rapid characterization of dynamic DNA devices that undergo large conformational fluctuations. Here, we develop a data processing pipeline based on Deep Neural Networks (DNNs) to address this problem. The YOLOv5 and Resnet50 network architecture were used for the two key subtasks: particle detection and pose (i.e. conformation) estimation. We demonstrate effective network performance (F1 score of 0.85 in particle detection) and good agreement with experimental distributions with limited user input and small training sets. We also demonstrate this pipeline can be applied to multiple nanodevices, providing a robust approach for the rapid characterization of dynamic DNA devices.
BOLD cerebrovascular reactivity MRI to identify tissue reperfusion failure after EVT in patients with LVO acute stroke
Authors: Bellomo Jacopo , Sebök Martina , Stumpo Vittorio , van Niftrik Christiaan HB , Meisterhans Darja , Piccirelli Marco , Michels Lars , Reolon Beno , Schubert Tilman , Kulcsar Zsolt , Luft Andreas R , Wegener Susanne , Regli Luca , Fierstra Jorn 
Published: May 2023

ABSTRACTBackground and purposeIn acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment and collateral recruitment, which can be derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.MethodsFrom the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.ResultsIncluded patients (n=21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 18.51%; IQR, 8.44-59.09). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.ConclusionsPatients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy.