bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Stratification on Shoaling Internal Tidal Bores
Authors: Dauhajre Daniel P. , Molemaker M. Jeroen , McWilliams James C. , Hypolite Delphine 
Published: August 2021

AbstractIdealized simulations of a shoaling internal tide on a gently sloping, linear shelf provide a tool to investigate systematically the effects of stratification strength, vertical structure, and internal wave amplitude on internal tidal bores. Simulations that prescribe a range of uniform or variable stratifications and wave amplitudes demonstrate a variety of internal tidal bores characterized by shoreward-propagating horizontal density fronts with associated overturning circulations. Qualitatively, we observe three classes of solution: 1) bores, 2) bores with trailing wave trains, and 3) no bores. Very strong stratification (small wave) or very weak stratification (large wave) inhibits bore formation. Bores exist in an intermediate zone of stratification strength and wave amplitude. Within this intermediate zone, wave trains can trail bores if the stratification is relatively weak or wave amplitude large. We observe three types of bore that arise dependent on the vertical structure of stratification and wave amplitude: 1) a “backward” downwelling front (near uniform stratification, small to intermediate waves), 2) a “forward” upwelling front (strong pycnocline, small to large waves), and 3) a “double” bore with leading up and trailing downwelling front (intermediate pycnocline, intermediate to large waves). Visualization of local flow structures explores the evolution of each of these bore types. A frontogenetic diagnostic framework elucidates the previously undiscussed yet universal role of vertical straining of a stratified fluid that initiates formation of bores. Bores with wave trains exhibit strong nonhydrostatic dynamics. The results of this study suggest that mid-to-outer shelf measurements of stratification and cross-shore flow can serve as proxies to indicate the class of bore farther inshore.
Somatosensory dysfunction in patients with posttraumatic headache: A systematic review
Authors: Jessen Julia , Özgül Özüm S. , Höffken Oliver , Schwenkreis Peter , Tegenthoff Martin , Enax-Krumova Elena K 
Published: August 2021

Objectives Aim of the review is to summarize the knowledge about the sensory function and pain modulatory systems in posttraumatic headache and discuss its possible role in patients with posttraumatic headache. Background Posttraumatic headache is the most common complication after traumatic brain injury, and significantly impacts patients’ quality of life. Even though it has a high prevalence, its origin and pathophysiology are poorly understood. Thereby, the existing treatment options are insufficient. Identifying its mechanisms can be an important step forward to develop target-based personalized treatment. Methods We searched the PubMed database for studies examining pain modulation and/or quantitative sensory testing in individuals with headache after brain injury. Results The studies showed heterogenous alterations in sensory profiles (especially in heat and pressure pain perception) compared to healthy controls and headache-free traumatic brain injury-patients. Furthermore, pain inhibition capacity was found to be diminished in subjects with posttraumatic headache. Conclusions Due to the small number of heterogenous studies a distinct sensory pattern for patients with posttraumatic headache could not be identified. Further research is needed to clarify the underlying mechanisms and biomarkers for prediction of development and persistence of posttraumatic headache.
Genome-wide association study reveals susceptibility loci for self-reported headache in a large community-based Asian population
Authors: Tsao Yu-Chien , Wang Shuu-Jiun , Hsu Chia-Lin , Wang Yen-Feng , Fuh Jong-Ling , Chen Shih-Pin , Fann Cathy Shen-Jang 
Published: August 2021

Background The genetic substrate for headache in the general population has not been identified in Asians. We investigated susceptible genetic variants for self-reported headache in a large community-based Asian population. Methods We conducted a genome-wide association study in participants recruited from a community-based cohort to identify the genetic variants associated with headache in Taiwanese. All participants received a structured questionnaire for self-reported headache. A total of 2084 patients with “self-reported headache” and 11,822 age- and sex-matched controls were enrolled. Gene enrichment analysis using the Genotype-Tissue Expression version 6 database was performed to explore the potential function of the identified variants. Results We identified two novel loci, rs10493859 in TGFBR3 and rs13312779 in FGF23, that are functionally relevant to vascular function and migraine to be significantly associated with self-reported headache after adjusting age, sex and top 10 principal components ( p = 8.53 × 10−11 and p = 1.07 × 10−8, respectively). Gene enrichment analysis for genes with GWAS suggestive significance ( p < 10−6) demonstrated that the expression of these genes was significantly enriched in the artery ( p = 8.18 × 10−4) and adipose tissue ( p = 8.95 × 10−4). Conclusion Our results suggest that vascular dysfunction might play important roles in the pathogenesis of self-reported headache in Asian populations.
Could erectile dysfunction be a side effect of CGRP inhibition? A case report
Authors: Al-Hassany Linda , Vries Tessa de , Carpay Johannes A , MaassenVanDenBrink Antoinette 
Published: August 2021

Background Recently, antimigraine drugs targeting the calcitonin gene-related peptide pathway have been approved for clinical use as preventive migraine medication. Case report We present a case of a 54-year-old male migraine patient, who reported erectile dysfunction as a possible side effect of treatment with galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide. His potency recovered after treatment discontinuation. Discussion As calcitonin gene-related peptide is involved in mammalian penile erection, erectile dysfunction is a conceivable side effect associated with calcitonin gene-related peptide inhibition. Postmarketing surveillance will elucidate the actual incidence of erectile dysfunction in patients using these new antimigraine drugs, and determine whether a causal relationship between calcitonin gene-related peptide inhibition and erectile dysfunction exists. This would be relevant not only because of the direct sexual consequences of erectile dysfunction, but also considering the potential cardiovascular consequences of calcitonin gene-related peptide (receptor) blockade and the association of both migraine and erectile dysfunction with cardiovascular disease. Conclusion Erectile dysfunction might be an overlooked, but reversible side effect in male migraine patients using monoclonal antibodies that inhibit the calcitonin gene-related peptide pathway, including galcanezumab. This paper may raise clinical awareness and suggest that this potential side effect needs to be studied further.
Involving practice nurse and other assistant clinical staff members in the management of low back pain: A qualitative interview study from Danish general practice
Authors: Knudsen Randi H , Thomsen Janus L , Andersen Camilla Aakjaer , Afzali Tamana , Riis Allan 
Published: August 2021

Objectives: Involving practice nurse and other assistant clinical staff members in providing information and education to patients with low back pain at follow-up appointments may release more time and improve care in general practice. However, this requires a shift in the division of tasks, and general practitioners’ barriers and facilitators for this are currently unknown. The objectives were to explore general practitioners’ experiences and perceptions of including assistant clinical staff members in the management of low back pain. Methods: This is a semi-structured interview study in Danish general practice. General practitioners with a variation in demographics and experience with task-delegation to clinical staff were recruited for in-depth interviews. We used a phenomenological approach to guide the data collection and the analysis in order to gain insight into the subjective experiences of the general practitioners and to understand the phenomenon of ‘delegating tasks to practice staff’ from the perspective of the general practitioners’ lifeworld. Analysis was conducted using an inductive descriptive method. The sample size was guided by information power. Results: We conducted five interviews with general practitioners. All general practitioners had experience with task delegation, but there was a variation in which tasks the general practitioners delegated and to which types of clinical staff members. The following themes were derived from the analysis: general practice organisation, delegating to clinical staff members, doctor–patient relationship, exercise instruction, clinical pathway for patients and external support. Conclusion: General practitioners consider patients with low back pain to be a heterogeneous group with a variety of treatment needs and a patient group without any predetermined content or frequency of consultations; this can be a barrier for delegating these patients to clinical staff members.
Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation
Authors: Silva Camila Meirelles S. , Wanderley Carlos Wagner S. , Veras Flavio P. , Sonego Fabiane , Nascimento Daniele C. , Gonçalves Augusto V. , Martins Timna V. , Cólon David F. , Borges Vanessa F. , Brauer Verônica S. , Damasceno Luis Eduardo A. , Silva Katiussia P. , Toller-Kawahisa Juliana E. , Batah Sabrina S. , Souza Ana Letícia J. , Monteiro Valter S. , Oliveira Antônio Edson R. , Donate Paula B. , Zoppi Daniel , Borges Marcos C. , Almeida Fausto , Nakaya Helder I. , Fabro Alexandre T. , Cunha Thiago M. , Alves-Filho José Carlos , Zamboni Dario S. , Cunha Fernando Q. 
Published: August 2021

Abstract
Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.
Arhgef2 regulates mitotic spindle orientation in hematopoietic stem cells and is essential for productive hematopoiesis
Authors: Chan Derek C. H. , Xu Joshua , Vujovic Ana , Wong Nicholas , Gordon Victor , de Rooij Laura P. M. H. , Moreira Steven , Joyce Cailin E. , La Rose Jose , Sandí María-José , Doble Bradley W. , Novina Carl D. , Rottapel Robert K. , Hope Kristin J. 
Published: August 2021

Abstract
How hematopoietic stem cells (HSCs) coordinate their divisional axis and whether this orientation is important for stem cell–driven hematopoiesis is poorly understood. Single-cell RNA sequencing data from patients with Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome, show that ARHGEF2, a RhoA-specific guanine nucleotide exchange factor and determinant of mitotic spindle orientation, is specifically downregulated in SDS hematopoietic stem and progenitor cells (HSPCs). We demonstrate that transplanted Arhgef2−/− fetal liver and bone marrow cells yield impaired hematopoietic recovery and a production deficit from long-term HSCs, phenotypes that are not the result of differences in numbers of transplanted HSCs, their cell cycle status, level of apoptosis, progenitor output, or homing ability. Notably, these defects are functionally restored in vivo by overexpression of ARHGEF2 or its downstream activated RHOA GTPase. By using live imaging of dividing HSPCs, we show an increased frequency of misoriented divisions in the absence of Arhgef2. ARHGEF2 knockdown in human HSCs also impairs their ability to regenerate hematopoiesis, culminating in significantly smaller xenografts. Together, these data demonstrate a conserved role for Arhgef2 in orienting HSPC division and suggest that HSCs may divide in certain orientations to establish hematopoiesis, the loss of which could contribute to HSC dysfunction in bone marrow failure.
Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis
Authors: Fu Jinjuan , Tang Yuanjuan , Zhang Zhen , Tong Lin , Yue Rongchuan , Cai Lin 
Published: August 2021

AbstractBackgroundIt is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown.MethodsAdult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis.ResultsWe found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection.ConclusionOur data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.
Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3
Authors: Yuan Xiaoqiu , Li Tiefeng , Shi Lei , Miao Jinhao , Guo Yongfei , Chen Yu 
Published: August 2021

Abstract
Background
Intervertebral disc degeneration (IVDD) is the breakdown of the discs supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clinical interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed.

Methods
Nucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms’ tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an enzyme-linked immunosorbent assay. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quantitative reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation.

Results
The human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1β (IL-1β) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p.

Conclusions
The results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.
Time series analysis of hemorrhagic fever with renal syndrome in mainland China by using an XGBoost forecasting model
Authors: Lv Cai-Xia , An Shu-Yi , Qiao Bao-Jun , Wu Wei 
Published: August 2021

Abstract
Background
Hemorrhagic fever with renal syndrome (HFRS) is still attracting public attention because of its outbreak in various cities in China. Predicting future outbreaks or epidemics disease based on past incidence data can help health departments take targeted measures to prevent diseases in advance. In this study, we propose a multistep prediction strategy based on extreme gradient boosting (XGBoost) for HFRS as an extension of the one-step prediction model. Moreover, the fitting and prediction accuracy of the XGBoost model will be compared with the autoregressive integrated moving average (ARIMA) model by different evaluation indicators.

Methods
We collected HFRS incidence data from 2004 to 2018 of mainland China. The data from 2004 to 2017 were divided into training sets to establish the seasonal ARIMA model and XGBoost model, while the 2018 data were used to test the prediction performance. In the multistep XGBoost forecasting model, one-hot encoding was used to handle seasonal features. Furthermore, a series of evaluation indices were performed to evaluate the accuracy of the multistep forecast XGBoost model.

Results
There were 200,237 HFRS cases in China from 2004 to 2018. A long-term downward trend and bimodal seasonality were identified in the original time series. According to the minimum corrected akaike information criterion (CAIC) value, the optimal ARIMA (3, 1, 0) × (1, 1, 0)12 model is selected. The index ME, RMSE, MAE, MPE, MAPE, and MASE indices of the XGBoost model were higher than those of the ARIMA model in the fitting part, whereas the RMSE of the XGBoost model was lower. The prediction performance evaluation indicators (MAE, MPE, MAPE, RMSE and MASE) of the one-step prediction and multistep prediction XGBoost model were all notably lower than those of the ARIMA model.

Conclusions
The multistep XGBoost prediction model showed a much better prediction accuracy and model stability than the multistep ARIMA prediction model. The XGBoost model performed better in predicting complicated and nonlinear data like HFRS. Additionally, Multistep prediction models are more practical than one-step prediction models in forecasting infectious diseases.
Canine olfactory detection and its relevance to medical detection
Authors: Jendrny Paula , Twele Friederike , Meller Sebastian , Osterhaus Albertus Dominicus Marcellinus Eras , Schalke Esther , Volk Holger Andreas 
Published: August 2021

AbstractThe extraordinary olfactory sense of canines combined with the possibility to learn by operant conditioning enables dogs for their use in medical detection in a wide range of applications. Research on the ability of medical detection dogs for the identification of individuals with infectious or non-infectious diseases has been promising, but compared to the well-established and–accepted use of sniffer dogs by the police, army and customs for substances such as money, explosives or drugs, the deployment of medical detection dogs is still in its infancy. There are several factors to be considered for standardisation prior to deployment of canine scent detection dogs. Individual odours in disease consist of different volatile organic molecules that differ in magnitude, volatility and concentration. Olfaction can be influenced by various parameters like genetics, environmental conditions, age, hydration, nutrition, microbiome, conditioning, training, management factors, diseases and pharmaceuticals. This review discusses current knowledge on the function and importance of canines’ olfaction and evaluates its limitations and the potential role of the dog as a biomedical detector for infectious and non-infectious diseases.
A systematic review of the sensitivity and specificity of lateral flow devices in the detection of SARS-CoV-2
Authors: Mistry Dylan A. , Wang Jenny Y. , Moeser Mika-Erik , Starkey Thomas , Lee Lennard Y. W. 
Published: August 2021

Abstract
Background
Lateral flow devices (LFDs) are viral antigen tests for the detection of SARS-CoV-2 that produce a rapid result, are inexpensive and easy to operate. They have been advocated for use by the World Health Organisation to help control outbreaks and break the chain of transmission of COVID-19 infections. There are now several studies assessing their accuracy but as yet no systematic review. Our aims were to assess the sensitivity and specificity of LFDs in a systematic review and summarise the sensitivity and specificity of these tests.

Methods
A targeted search of Pubmed and Medxriv, using PRISMA principles, was conducted identifying clinical studies assessing the sensitivity and specificity of LFDs as their primary outcome compared to reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2. Based on extracted data sensitivity and specificity was calculated for each study. Data was pooled based on manufacturer of LFD and split based on operator (self-swab or by trained professional) and sensitivity and specificity data were calculated.

Results
Twenty-four papers were identified involving over 26,000 test results. Sensitivity from individual studies ranged from 37.7% (95% CI 30.6–45.5) to 99.2% (95% CI 95.5–99.9) and specificity from 92.4% (95% CI 87.5–95.5) to 100.0% (95% CI 99.7–100.0). Operation of the test by a trained professional or by the test subject with self-swabbing produced comparable results.

Conclusions
This systematic review identified that the performance of lateral flow devices is heterogeneous and dependent on the manufacturer. Some perform with high specificity but a great range of sensitivities were shown (38.32–99.19%). Test performance does not appear dependent on the operator. Potentially, LFDs could support the scaling up of mass testing to aid track and trace methodology and break the chain of transmission of COVID-19 with the additional benefit of providing individuals with the results in a much shorter time frame.