bluuebunny/crossref_metadata_2025_split huggingface dataset:
The different risk factors for isolated diastolic hypertension and isolated systolic hypertension: a national survey
Authors: Xie Kun , Gao Xiufang , Bao Liwen , Shan Ying , Shi Haiming , Li Yong 
Published: September 2021

Abstract
Background
Hypertension is highly prevalent and is one of the modifiable risk factors for cardiovascular outcomes. Isolated diastolic hypertension (IDH), however, tends to be ignored due to insufficient recognition. We sought to depict the clinical manifestation of IDH and isolated systolic hypertension (ISH) to find a more efficient way to improve the management.

Methods
Patients with primary hypertension aged over 18 years were investigated from all over the country using convenience sampling during 2017–2019. IDH was defined as systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) ≥90 mmHg. ISH was defined as SBP ≥ 140 mmHg and DBP < 90 mmHg.

Results
A total of 8548 patients were screened, and 8475 participants were included. The average age was 63.67 ± 12.78 years, and males accounted for 54.4%. Among them, 361 (4.3%) had IDH, and 2096 had ISH (24.7%). Patients with IDH (54.84 ± 13.21 years) were much younger. Aging turned out to be negatively associated with IDH but positively associated with ISH. Multivariate logistic regression analysis showed BMI was a significant risk factor for IDH (OR 1.30, 95%CI 1.05–1.61, p = 0.018), but not for ISH (OR 1.05, 95%CI 0.95–1.16, p = 0.358). Moreover, smoking was significantly associated with IDH (OR 1.36, 95%CI 1.04–1.78, p = 0.026) but not with ISH (OR 1.04, 95%CI 0.90–1.21, p = 0.653).

Conclusions
Patients with IDH were much younger, and the prevalence decreased with aging. BMI and smoking were remarkably associated with IDH rather than ISH. Keeping fit and giving up smoking might be particularly efficient in the management of young patients with IDH.

Trial registration
NCT03862183, retrospectively registered on March 5, 2019.
Investigating geographical variation in the use of mental health services by area of England: a cross-sectional ecological study
Authors: Maconick Lucy , Sheridan Rains Luke , Jones Rebecca , Lloyd-Evans Brynmor , Johnson Sonia 
Published: September 2021

Abstract
Background
There is evidence of geographical variation in the use of mental health services in the UK and in international settings. It is important to understand whether this variation reflects differences in the prevalence of mental disorders, or if there is evidence of variation related to other factors, such as population socioeconomic status and access to primary care services.

Methods
This is a cross-sectional ecological study using Public Health England data. The unit of analysis was the population served by clinical commissioning groups (CCGs), National Health Service (NHS) catchment areas. The analysis explored associations between area characteristics and the number of people in contact with mental health services using regression modelling. Explanatory variables included age, gender, prevalence of severe mental illness (SMI), prevalence of common mental disorder (CMD), index of multiple deprivation (IMD), unemployment, proportion of the population who are Black and Minority Ethnic (BAME), population density, access to and recovery in primary care psychological therapies. Unadjusted results are reported, as well as estimates adjusted for age, prevalence of CMD and prevalence of SMI.

Results
The populations of 194 CCGs were included, clustered within 62 trusts (NHS providers of mental health services). The number of people in contact with mental health services showed wide variation by area (range from 1131 to 5205 per 100,000 population). Unemployment (adjusted IRR 1.11; 95% CI 1.05 to 1.17; p < 0.001) and deprivation (adjusted IRR 1.02 95% CI 1.01 to 1.04; p < 0.001) were associated with more people being in contact with mental health services. Areas with a higher proportion of the population who are BAME (IRR 0.95 95% CI 0.92 to 0.99 p = 0.007) had lower service use per 100,000 population. There was no evidence for association with access to primary care psychological therapies.

Conclusions
There is substantial variation in the use of mental health services by area of England. Social factors including deprivation, unemployment and population ethnicity continued to be associated with the outcome after controlling for the prevalence of mental illness. This suggests that there are factors that influence the local population use of mental health services in addition to the prevalence of mental disorder.
Phylogeography and population differentiation in Hepatozoon canis (Apicomplexa: Hepatozoidae) reveal expansion and gene flow in world populations
Authors: Vásquez-Aguilar Antonio Acini , Barbachano-Guerrero Arturo , Angulo Diego F. , Jarquín-Díaz Víctor Hugo 
Published: September 2021

Abstract
Background
Hepatozoon canis is a protozoan transmitted to dogs and other wild carnivores by the ingestion of ticks containing mature oocysts and is considered the principal cause of canine hepatozoonosis in the world. Here, we examined ribosomal RNA 18S gene sequence variation to determine the genetic differences and phylogeographic diversity of H. canis from various geographical areas around the world.

Methods
We used 550 publicly available sequences of H. canis from 46 countries to assess haplotype relationships, geographical structure, genetic diversity indices, and relationships among populations. We performed neutrality tests and pairwise comparisons of fixation index (FST) values between groups and pairwise comparisons of FST values between populations. To determine whether populations are structured, analyses of molecular variance (AMOVAs) and spatial analysis of molecular variance (SAMOVA) were performed.

Results
The dataset of H. canis yielded 76 haplotypes. Differentiation among populations indicated that there is no phylogeographical structure (GST = 0.302 ± 0.0475). Moreover, when samples were grouped by continents a significant FST was obtained, meaning that populations were genetically differentiated. The AMOVA showed that 57.4% of the genetic variation was explained by differences within populations when all locations were treated as a single group and revealed that there is no population structure when populations are grouped into two, three, and four groups (FCT, p > 0.05), suggesting that dispersal between populations is high. SAMOVA revealed significant FCT values for groups K = 5. The Tajima’s D and Fu’s Fs show that populations have undergone recent expansion, and the mismatch distribution analysis showed population expansion (multimodal distribution).

Conclusions
The current molecular data confirmed that H. canis does not show phylogeographic or population structure. The haplotypes exhibit low genetic differentiation, suggesting a recent expansion due to gene flow among populations. These results provide pivotal information required for future detailed population genetic analysis or to establish control strategies of this parasite.

Graphical abstract
MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7
Authors: Zhou Qian-Yang , Yang Hui-Min , Liu Ji-Xin , Xu Na , Li Jing , Shen Li-Ping , Zhang Yu-Zhao , Koda Stephane , Zhang Bei-Bei , Yu Qian , Chen Jia-Xu , Zheng Kui-Yang , Yan Chao 
Published: September 2021

Abstract
Background
Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-β1-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-β/Smad signaling pathway are still poorly understood. Accumulating evidence demonstrates that miRNAs act as an important regulator of activation of HSCs during liver fibrosis.

Methods
The target of miR-497 was determined by bioinformatics analysis combined with a dual-luciferase activity assay. LX-2 cells were transfected with miR-497 inhibitor and then stimulated with TGF-β1 or excretory/secretory products of C. sinensis (CsESPs), and activation of LX-2 was assessed using qPCR or western blot. In vivo, the mice treated with CCl4 were intravenously injected with a single dose of adeno-associated virus serotype 8 (AAV8) that overexpressed anti-miR-497 sequences or their scramble control for 6 weeks. Liver fibrosis and damage were assessed by hematoxylin and eosin (H&E) staining, Masson staining, and qPCR; the activation of the TGF-β/Smad signaling pathway was detected by qPCR or western blot.

Results
In the present study, the expression of miR-497 was increased in HSCs activated by TGF-β1 or ESPs of C. sinensis. We identified that Smad7 was the target of miR-497 using combined bioinformatics analysis with luciferase activity assays. Transfection of anti-miR-497 into HSCs upregulated the expression of Smad7, leading to a decrease in the level of p-Smad2/3 and subsequent suppression of the activation of HSCs induced by TGF-β1 or CsESPs. Furthermore, miR-497 inhibitor delivered by highly-hepatotropic (rAAV8) inhibited TGF-β/smads signaling pathway by targeting at Smad7 to ameliorate CCL4-induced liver fibrosis.

Conclusions
The present study demonstrates that miR-497 promotes liver fibrogenesis by targeting Smad7 to promote TGF-β/Smad signaling pathway transduction both in vivo and in vitro, which provides a promising therapeutic strategy using anti-miR-497 against liver fibrosis.

Graphical Abstract
Migrated fish bone into the neck: a case report
Authors: Thuduvage Vasanthika Sanjeewanie 
Published: September 2021

Abstract
Background
Impaction of foreign body is a common condition presented to ear, nose, and throat department among Asian population. The commonest foreign body seen among this population has been documented as fish bone. Fish bone can migrate to lateral neck space or related organs around the neck and chest. By presenting this case report, we aim to emphasize the importance of taking proper history and make clinicians aware of the possibility of a fish bone migrating into different spaces. This will help to prevent diagnosis delay leading to complications due to migrated fish bone.

Case presentation
A 50-year-old female Sinhalese patient presented to ear, nose, and throat department with right-sided neck pain for 2 days, who had a history of suspected fish bone impaction a few days ago that subsided without any investigations or treatments. She did not have any symptoms related to throat, and neck examination showed mild swelling and tenderness. Computer tomography revealed a migrated fish bone into the lateral neck close to carotid artery, and the fish bone was removed by neck exploration under general anesthesia without any complications.

Conclusion
In conclusion, migrated fish bone should be suspected if patient is having persistent symptoms mainly in the neck without having difficulty swallowing and who gives a history of fish bone impaction and having negative laryngoscopic examination. Proper history taking is very important in the assessment of these patients to prevent misdiagnosis of the condition. Clinicians should aware that migrated fish bones are not uncommon and that early suspicion can prevent later diagnosis and complications.
Targeted strategies for the management of wildlife diseases: the case of brucellosis in Alpine ibex
Authors: Lambert Sébastien , Thébault Anne , Rossi Sophie , Marchand Pascal , Petit Elodie , Toïgo Carole , Gilot-Fromont Emmanuelle 
Published: September 2021

AbstractThe management of infectious diseases in wildlife reservoirs is challenging and faces several limitations. However, detailed knowledge of host–pathogen systems often reveal heterogeneity among the hosts’ contribution to transmission. Management strategies targeting specific classes of individuals and/or areas, having a particular role in transmission, could be more effective and more acceptable than population-wide interventions. In the wild population of Alpine ibex (Capra ibex—a protected species) of the Bargy massif (French Alps), females transmit brucellosis (Brucella melitensis) infection in ~90% of cases, and most transmissions occur in the central spatial units (“core area”). Therefore, we expanded an individual-based model, developed in a previous study, to test whether strategies targeting females or the core area, or both, would be more effective. We simulated the relative efficacy of realistic strategies for the studied population, combining test-and-remove (euthanasia of captured animals with seropositive test results) and partial culling of unmarked animals. Targeting females or the core area was more effective than untargeted management options, and strategies targeting both were even more effective. Interestingly, the number of ibex euthanized and culled in targeted strategies were lower than in untargeted ones, thus decreasing the conservation costs while increasing the sanitary benefits. Although there was no silver bullet for the management of brucellosis in the studied population, targeted strategies offered a wide range of promising refinements to classical sanitary measures. We therefore encourage to look for heterogeneity in other wildlife diseases and to evaluate potential strategies for improving management in terms of efficacy but also acceptability.
Recent aspects of ketogenic diet in neurological disorders
Authors: Kwon Hye Eun , Kim Heung Dong 
Published: September 2021

AbstractThe ketogenic diet (KD) is a high-fat, low-carbohydrate diet, in which fat is used as the primary energy source through the production of ketone bodies (KBs) in place of glucose. The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s. The clinical and basic scientific knowledge that supports the anti-seizure efficacy, safety, and feasibility of using the KD in patients with epilepsy is huge. Additionally, the International Ketogenic Diet Study Group’s consensus guidelines provide practical information in 2009 and 2018. The KD is a broad-spectrum therapy for drug resistant epilepsy and is gaining attention as a potential therapy for other neurological disorders. This article will review recent aspects on the use of the KD, including its mechanisms of action, KD alternatives, expanding its use across different age groups and regions, its use as a treatment for other neurologic disorders, and future research subjects.
Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma
Authors: Sonneveld Pieter , Dimopoulos Meletios A. , Beksac Meral , van der Holt Bronno , Aquino Sara , Ludwig Heinz , Zweegman Sonja , Zander Thilo , Zamagni Elena , Wester Ruth , Hajek Roman , Pantani Lucia , Dozza Luca , Gay Francesca , Cafro AnneMaria , De Rosa Luca , Morelli Annamaria , Gregersen Henrik , Gulbrandsen Nina , Cornelisse Petra , Troia Rosella , Oliva Stefania , van de Velden Vincent , Wu KaLung , Ypma Paula F. , Bos Gerard , Levin Mark-David , Pour Luca , Driessen Christoph , Broijl Annemiek , Croockewit Alexandra , Minnema Monique C. , Waage Anders , Hveding Cecilie , van de Donk Niels W. C. J. , Offidani Massimo , Palumbo Giuseppe A. , Spencer Andrew , Boccadoro Mario , Cavo Michele 
Published: September 2021

PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
Association of MAFLD With Diabetes, Chronic Kidney Disease, and Cardiovascular Disease: A 4.6-Year Cohort Study in China
Authors: Liang Yebei , Chen Hongli , Liu Yuexing , Hou Xuhong , Wei Li , Bao Yuqian , Yang Chunguang , Zong Geng , Wu Jiarui , Jia Weiping 
Published: September 2021

Abstract

Context
In 2020, the terminology of metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD).

Objectives
This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases.

Methods
A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models.

Results
The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes.

Conclusion
The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non–fatty liver.
Colonic Lactulose Fermentation Has No Impact on Glucagon-like Peptide-1 and Peptide-YY Secretion in Healthy Young Men
Authors: Christiansen Charlotte Bayer , Veedfald Simon , Hartmann Bolette , Gauguin Astrid Marie , Møller Søren , Moritz Thomas , Madsbad Sten , Holst Jens Juul 
Published: September 2021

Abstract

Context
The colon houses most of humans’ gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products.

Objective
To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state.

Methods
Ten healthy young men were studied on 3 occasions after an overnight fast. On 2 study days, lactulose (20 g) was given orally and compared to water intake on a third study day. For 1 of the lactulose visits, participants underwent a full colonic evacuation. Over a 6-h study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen, and gut peptide secretion, paracetamol, and short-chain fatty acid levels were measured in plasma.

Results
Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (P = 0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting and that fermentation and peptide secretion are not acutely related.

Conclusion
Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.
Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men
Authors: Holt Rune , Petersen Jørgen Holm , Dinsdale Elsa , Knop Filip Krag , Juul Anders , Jørgensen Niels , Blomberg Jensen Martin 
Published: September 2021

AbstractContextVitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator.ObjectiveThis work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men.MethodsA single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported.ResultsMen receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group.ConclusionHigh-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.