bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical-structure based Morphological Classification of Skin Eruptions and Linking to the Pathophysiological State of Chronic Spontaneous Urticaria
Authors: Seirin-Lee Sungrim , Matsubara Daiki , Yanase Yuhki , Kunieda Takuma , Takahagi Shunsuke , Hide Michihiro 
Published: November 2022

AbstractChronic spontaneous urticaria (CSU) is one of the most intractable human-specific skin diseases. However, as no experimental animal model exists, the mechanism underlying disease pathogenesisin vivoremains unclear, making the establishment of a curative treatment challenging. Here, using a novel approach combining mathematical modeling,in vitroexperiments and clinical data analysis, we show that the pathological state of CSU patients can be inferred by geometric features of the skin eruptions. Based on our hierarchical mathematical modelling and the analysis of 105 CSU patient eruption pattern geometries, analyzed by six dermatologists, we demonstrate that the eruption patterns can be classified into five categories, each with distinct histamine, basophils, mast cells and coagulation factors network signatures. Furthermore, our network analysis revealed that tissue factor degradation/activation likely determines boundary/area pattern, and that the state of spontaneous histamine release from mast cells may contribute to divergence of the boundary pattern. Thus, our study not only demonstrates that pathological states of diseases can be defined by geometric features but will also facilitate more accurate decision-making to manage CSU in the clinical setting.
Evasive spike variants elucidate the preservation of T cell immune response to the SARS-CoV-2 omicron variant
Authors: Solanki Arnav , Cornette James , Udell Julia , Vasmatzis George , Riedel Marc 
Published: November 2022

AbstractThe Omicron variants boast the highest infectivity rates among all SARS-CoV-2 variants. Despite their lower disease severity, they can reinfect COVID-19 patients and infect vaccinated individuals as well. The high number of mutations in these variants render them resistant to antibodies that otherwise neutralize the spike protein of the original SARS-CoV-2 spike protein. Recent research has shown that despite its strong immune evasion, Omicron still induces strong T Cell responses similar to the original variant. This work investigates the molecular basis for this observation using the neural network tools NetMHCpan-4.1 and NetMHCiipan-4.0. The antigens presented through the MHC Class I and Class II pathways from all the notable SARS-CoV-2 variants were compared across numerous high frequency HLAs. All variants were observed to have equivalent T cell antigenicity. A novel positive control system was engineered in the form of spike variants that did evade T Cell responses, unlike Omicron. These evasive spike proteins were used to statistically confirm that the Omicron variants did not exhibit lower antigenicity in the MHC pathways. These results suggest that T Cell immunity mounts a strong defense against COVID-19 which is difficult for SARS-CoV-2 to overcome through mere evolution.Author summary
Nav1.7 and Nav1.8 form supramolecular active clusters with TRKB in mouse and human DRG neurons during development of neuropathic pain
Authors: Sun Liting , Xian Hang , Shi Yunxin , Yang Taotan , Shuai Hongyan , Xia Ruilong , Wen Ting , Xia Wei , Qian Ran , Zhu Fengting , Liu Yuanying , Tian Zhicheng , Li Lamei , Cong Rui , Luo Ceng , Wu Shengxi , Shen Xiafeng , Yu Xin , Xie Rou-Gang , Peng Changgeng 
Published: November 2022

AbstractNeuropathic pain affects 7-10% of the global population, and one of its characteristics is sensitization of somatosensory nervous system. Altered expression of ion channels and receptors has been found to be involved in neuronal hyperexcitability after injury to somatosensory nervous system, it is, however, unknown that if ion channels and receptors could gain qualitative changes on the level of structure organization when they are excessively expressed in same one neuron during the development of neuropathic pain. Here we show first that not only the expression of voltage-gated sodium channels Nav1.7 (SCN9A), Nav1.8 (SCN10A) and TRKB (also named NTRK2) increased in DRG neurons of patients with over 3-month severe neuropathic pain induced by brachial plexus avulsion (BPA), but also Nav1.7 and Nav1.8 formed supramolecular active clusters with or without TRKB in DRG neurons of mice with chronic neuropathic pain induced by spared nerve injury or diabetic neuropathy and of BPA pain patients with neuropathic pain. Nav1.7, Nav1.8 and TRKB might function in a coordinated manner in orderly organized supramolecular active clusters to geometrically increase the hyperexcitability of pathological DRG neurons. Our findings suggest that supramolecular active clusters of Nav1.7, Nav1.8 and TRKB might need be targeted for curing neuropathic pain, and that inhibition of both Nav1.7 and Nav1.8 might be required to achieve efficient relief of neuropathic pain.
Remote and semi-automated methods to conduct a randomized clinical trial
Authors: Cafaro Teresa , LaRiccia Patrick J. , Bandomer Brigid , Goldstein Helen , Brobyn Tracy L. , Hunter Krystal , Roy Satyajeet , Ng Kevin Q. , Mitrev Ludmil V. , Tsai Alan , Thwing Denise , Maag Mary Ann , Chung Myung K. , van Helmond Noud 
Published: November 2022

ABSTRACTBackgroundDesigning and conducting randomized controlled trials is not possible for some institutions and researchers due to their associated costs and personnel requirements. Advances in telehealth for patient care and clinical trial methods adaptations were hastened due to the coronavirus 2019 pandemic. We conducted subject recruitment, screening, informed consent, study product distribution, and data collection remotely using Research Electronic Data Capture (REDCap) and other readily available applications for a prospective randomized clinical trial on vitamin D3 supplementation to prevent influenza-like illness in healthcare workers.ObjectivesTo describe how to efficiently and cost-effectively conduct a randomized clinical trial using remote and semi-automated methods.MethodsA previously described prospective, controlled, trial in healthcare workers at a tertiary university hospital that used Zelen’s design to facilitate enrollment is used as a model. A random group of healthcare workers were invited to participate in the study through email. Following an automated process, interested individuals could schedule a HIPAA compliant, video-facilitated consent interview. Following e-consenting, participants received vitamin D3 supplementation bottles by mail and electronic surveys via email. Adherence to the study intervention was monitored through survey data review and vitamin D3 safety was monitored via real-time automated warnings to study staff if any symptoms, health changes, hospitalizations, or pregnancies were reported on monthly surveys.ResultsA small study staff of 10 team members were able to screen 406 subjects and enroll 299 subjects over a 3-month period using completely remote methods. Adherence to vitamin D3 supplementation was high (87%) over 9 months. Survey data completeness was 98.5% over 9 months. Participants and study staff scored the system usability 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team staff of 2 members while safety monitoring was conducted by 3-4 team members.ConclusionsThe remote and automated methods developed to conduct a randomized controlled trial produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can significantly minimize costs and time without sacrificing safety or quality, thereby offering greater equity in scientific research. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials.Trial RegistrationNCT04596657
Effects of Postnatal Glucocorticoids on Brain Structure in Preterm Infants, A Scoping Review
Authors: Robles Isabella , Eidsness Margarita Alethea , Travis Katherine E. , Feldman Heidi M , Dubner Sarah E. 
Published: November 2022

ABSTRACTGlucocorticoids (GC) are used in neonatal intensive care units to prevent or reduce the severity of chronic lung disease in preterm infants and have been implicated in impaired neurodevelopment. Our objective was to identify what is known about the effects of postnatal GC treatment in human preterm infants on structural brain development and to identify gaps in the literature. Following Arksey and O’Malley’s scoping review methodological framework, we searched scientific literature databases for original research on human preterm infants, postnatal GCs, and brain structure. 11 studies assessed the effects of GCs on structural brain outcomes. 56 studies reported brain injury, but not structure. Dexamethasone was consistently associated with decreased total and regional brain volumes, including cerebellar volumes. Hydrocortisone was often, but not always associated with absence of brain volume differences. No studies examined the impact of inhaled GC on brain structure. Additional research on the effects of neonatal GCs after preterm birth on a variety of structural brain measures is required for understanding contributions to neurodevelopment and informing practice guidelines.
Additive pre-diagnostic and diagnostic value of routine bloodbased biomarkers in the detection of colorectal cancer in the UK Biobank cohort
Authors: Tanriver Gizem , Kocagoncu Ece 
Published: November 2022

AbstractBackgroundSurvival rates from colorectal cancer (CRC) are drastically higher if the disease is detected and treated earlier. Current screening guidelines involve stool-based tests and colonoscopies, whose acceptability and uptake remains low. Routinely collected blood-based biomarkers may offer a low-cost alternative or aid for detecting CRC.MethodsHere we aimed to evaluate the pre-diagnostic and diagnostic value of a wide-range of multimodal biomarkers in the UK Biobank dataset, including sociodemographic, lifestyle, medical, physical, and blood and urine-based measures in detecting CRC. We performed a Cox proportional hazard and a tree-boosting model alongside feature selection methods to determine optimal combination of biomarkers.ResultsIn addition to the modifiable lifestyle factors of obesity, alcohol consumption and cardiovascular health, we showed that blood-based biomarkers that capture the immune response, lipid profile, liver and kidney function are associated with CRC risk. Following feature selection, the final Cox and tree-boosting models achieved a C-index of 0.67 and an AUC of 0.76 respectively.ConclusionsWe show that blood-based biomarkers collected in routine examinations are sensitive to preclinical and clinical CRC. They may provide an additive value and improve diagnostic accuracy of current screening tools at no additional cost and help reduce burden on the healthcare system.
Knowledge and information sources of Helicobacter pylori among Jordanian population: a cross-sectional study
Authors: Alaridah Nader , F. Jarrar Raba’a , Joudeh Rayan M. , Aljarawen Mallak , Jum’ah Mohammad , Nassr Hasan , AlHmoud Raad Riad , Allouzi Abdullah , Wadi Eslam M. , Abu-Humaidan Anas H. A. 
Published: November 2022

AbstractIn 2017, the Jordanian Ministry of Health reported that gastric cancer was one of Jordan’s most commonly diagnosed cancers. Gastric cancer is often linked to Helicobacter pylori, one of the foremost risk factors. Despite the high prevalence of H. pylori in Jordan, no information is available regarding the general population’s awareness of the harmful effects of this pathogen. The study aims to assess the knowledge and the impact of the source of knowledge on H. pylori among the general population in Jordan. A cross-sectional study involving 933 participants was conducted between May and July of 2021. After meeting the inclusion criteria and consenting to participate in this study, participants completed the questionnaire. The questionnaire was conducted interview-based, covering the following sections: sociodemographic data and knowledge related to H. pylori infection. 63% of the participants had a high level of education, 70.5% got their information about H. pylori infection from non-medical sources, and 68.7% had a low level of knowledge. Working in the medical field and attaining information from medical resources showed a significant association with a high level of knowledge, on the other hand, having a history of self-reported or family member of H.pylori infection also showed a significant association with a high level of knowledge. The Mann-Whitney U test showed that the mean ranks of all knowledge items in the medical source group significantly exceed those of the non-medical source group (p-values < 0.05). In Jordan, the awareness of H. pylori was unsatisfying, similar to other countries. Nevertheless, misconceptions in knowledge about H. pylori were identified and further awareness must be spread and advocated. Close observation of the non-medical sources of information is essential for delivering to the general population the sufficient amount of knowledge needed.
Assessing the spatial-temporal risks of SARS-CoV-2 infection for healthcare-workers in the hospital using behavioural indices from routine data
Authors: Wilson-Aggarwal Jared , Gotts Nick , Arnold Kellyn , Spyer Moira J , Houlihan Catherine F , Nastouli Eleni , Manley Ed 
Published: November 2022

AbstractThe COVID-19 pandemic has emphasised the need to rapidly assess infection risks for healthcare workers within the hospital environment. Using data from the first year of the pandemic, we investigated whether an individual’s COVID-19 test result was associated with behavioural markers derived from routinely collected hospital data two weeks prior to a test. The temporal and spatial context of behaviours were important, with the highest risks of infection during the first wave, for staff in contact with a greater number of patients and those with greater levels of activity on floors handling the majority of COVID-19 patients. Infection risks were higher for BAME staff and individuals working more shifts. Night shifts presented higher risks of infection between waves of COVID-19 patients. Our results demonstrate the epidemiological relevance of deriving markers of staff behaviour from electronic records, which extend beyond COVID-19 with applications for other communicable diseases and in supporting pandemic preparedness.
An atlas of genetic regulation and disease associations of microRNAs
Authors: Mustafa Rima , Mens Michelle M.J. , van Hilten Arno , Huang Jian , Roshchupkin Gennady , Huan Tianxiao , Broer Linda , Elliott Paul , Levy Daniel , Ikram M. Arfan , Evangelou Marina , Dehghan Abbas , Ghanbari Mohsen 
Published: November 2022

AbstractMicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Identification of genetic variants influencing the transcription of miRNAs can provide an understanding of their genetic regulation and implication in human disease. Here we present genome-wide association studies of 2,083 plasma circulating miRNAs measured by next-generation sequencing in 2,178 participants of the Rotterdam Study to identify miRNA-expression quantitative trait loci (miR-eQTLs). We report 4,310 cis- and trans-miR-eQTLs for 64 miRNAs that have been replicated across independent studies. Many of these miR-eQTLs overlap with gene expression, protein, and metabolite-QTLs and with disease-associated variants. The consequences of perturbation in miRNA transcription on a wide range of clinical conditions are systematically investigated in phenome-wide association studies, with their causality tested using Mendelian randomization. Integration of genomics and miRNAs enables interrogation of the genetic architecture of miRNAs, revealing their clinical importance, and providing valuable resources for future studies of miRNAs in human disease.
Intra- and inter-rater reliability, agreement, and minimal detectable change of the handheld dynamometer in individuals with symptomatic hip osteoarthritis
Authors: Vaz Gilvan Ferreira , Freire Felipe Florêncio , Gonçalves Henrique Mansur , de Aviz Marcus Alexandre Brito , Martins Wagner Rodrigues , Durigan João Luiz Quagliotti 
Published: November 2022

AbstractIntroductionThe handheld dynamometer has been validated to measure muscle strength in different muscle groups. However, to date, it has not been tested in individuals who experience pain induced by hip osteoarthritis. The current study aimed to evaluate the intra- and inter-rater reliability, agreement, and minimal detectable change of the Lafayette handheld dynamometer, model 1165, to assess the peak force (Pk) and average peak force (Af) of hip muscles in individuals with symptomatic hip osteoarthritis.MethodsTwenty participants with hip osteoarthritis (mean ± SD age: 58.7±15.3 years; body mass index: 28.8±4.2 kg/m2) and a pain intensity on the Visual Analogue Scale0020 ≥ 4 (8.05±1.2) were recruited to participate in this study. Pk and Af of hip flexors (seated position), abductors and adductors (supine position), and extensors (prone position) were collected in a single day by two independent raters, each one obtaining test and retest in randomly ordered separate sessions.ResultsThe intra-rater intraclass correlation coefficient (ICC) was classified as good (>0.75) or excellent (≥0.90) for all muscle groups, and all inter-rater ICCs were classified as excellent. Rater A had a lower standard error of measurement compared to rater B, ranging from 0.15 to 0.58 kilogram-force (Kgf) compared with 0.34 to 1.25 kg, respectively. However, the inter-rater comparison showed a minimal detectable change < 10% for all Pk and Af measures (except Af for the abductor muscle group). Finally, the inter-rater Bland-Altman analysis demonstrated good agreement for abductors, adductors, and extensors.ConclusionDespite pain and dysfunction related to hip osteoarthritis, the handheld dynamometer was shown to be a reliable tool to assess hip muscle strength, with good to excellent intra- and inter-rater ICCs, satisfactory agreement, and small values for minimal detectable change.
The FXR agonist obeticholic acid does not stimulate liver regeneration in hepatectomized mice
Authors: van Mierlo Kim M.C. , Dahrenmoller Carola , Lebrun Valérie , Jansen Peter L.M. , Dejong Cornelis H.C. , Leclercq Isabelle A. , Olde Damink Steven W.M. , Schaap Frank G. 
Published: November 2022

AbstractBackgroundPostresectional liver failure (PLF) is a dreaded complication after partial hepatectomy (PH). Data from animal experiments indicate that endogenous ligands (i.e. bile salts) can stimulate liver regeneration and prevent liver injury after PH, via hepatic Fxr and the ileal Fxr-Fgf15 axis.AimTo investigate whether exogenous activation of the Fxr pathway with the semi-synthetic bile acid derivative obeticholic acid (OCA) could stimulate postresectional liver regeneration in mice.MethodsTwelve weeks old male C57BL6/J mice were pre-treated with OCA (10 mg/kg/day) or vehicle, and after 7 days subjected to 70% PH. Mice were sacrificed at 24, 48 and 72 hrs after PH, and liver injury, secretory function, and regenerative indices were assessed. In a second study, OCA pre-treated mice received oral sucrose supplementation in the postoperative trajectory, and a group of mice receiving intraperitoneal injection of FGF19 was included as a positive control group. Here, mice were sacrificed at 48 hours after PH.ResultsNo effect could be detected on liver mass recovery after PH, although responses ofCyp7a1,Cyp8b1and other Fxr target genes implied general effectiveness of OCA treatment. OCA had no consistent effects on the number of Ki-67+hepatocytes and mitotic figures around the peak of proliferation (i.e. 48 hrs) after PH, having no effect or increasing these regenerative indices in the consecutive experiments. Hepatic bile salt content, an important determinant of PH-induced liver regeneration, at this time point was not affected by OCA. After pretreatment of mice with FGF19, a reduced expression of ileal bile salt-regulated genesFgf15andSlc51bindicating FGF19-mediated repression of bile salt synthesis was seen, but this did not stimulate postresectional liver regeneration in mice.ConclusionDespite the activation of hepatic and ileal Fxr as shown by induction of target genes, treatment with OCA or FGF19 did not result in accelerated liver regeneration after PH and liver bile salt content was not influenced. We speculate that bile salt homeostasis and endogenous bile salt signaling is already optimal in unaffected livers for proper progression of regeneration after PH. It will be interesting to study the effects of Fxr agonism on liver regeneration after PH, and prevention of PLF in the context of compromised bile salt homeostasis/signaling prior to PH.
Nucleotide-free structures of Kif20A illuminate the atypical allostery in this mitotic kinesin-6
Authors: Ranaivoson Fanomezana Moutse , Crozet Vincent , Benoît Matthieu P.M.H. , Khalid Amna Abdalla Mohammed , Kikuti Carlos , Sirkia Helena , Marjou Ahmed El , Asenjo Ana B. , Sosa Hernando , Schmidt Christoph F. , Rosenfeld Steven S. , Houdusse Anne 
Published: November 2022

AbstractKIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-EM microtubule-bound KIF20A structure that reveal the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that work to favor fast dissociation of ADP, particularly in contrast to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation thus highlight the role of extended insertions in shaping the motor mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker 4-times longer than kinesin-1 is required for the activity of this motor.