bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders
Authors: Song Weichen , Qian Wei , Wang Weidi , Yu Shunying , Lin Guan Ning 
Published: June 2021

Abstract
Background
Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown.

Results
Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10− 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer’s disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10− 5). By combining all observations, we found that the overall p-value for DTI − Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI − Bipolar disorder (BP) (λ = 2.64) and DTI − AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10− 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation.

Conclusions
As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.
Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses
Authors: Ramu Sangeetha , Akbarshahi Hamid , Mogren Sofia , Berlin Frida , Cerps Samuel , Menzel Mandy , Hvidtfeldt Morten , Porsbjerg Celeste , Uller Lena , Andersson Cecilia K. 
Published: June 2021

AbstractBackgroundMast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However, effects of MC mediators on bronchial epithelial immune response have been less studied. The aim of this study is to investigate the direct effects of stimulation with MC proteases, tryptase and chymase, on inflammatory and anti-viral responses in human bronchial epithelial cells (HBECs).MethodCultured BEAS-2b cells and primary HBECs from 3 asthmatic patients were stimulated with tryptase or chymase (0.1 to 0.5 μg/ml) for 1, 3, 6 and 24 h. To study the effects of MC mediators on the anti-viral response, cells were stimulated with 10 μg/ml of viral mimic Poly (I:C) for 3 and 24 h following pre-treatment with 0.5 μg/ml tryptase or chymase for 3 h. Samples were analysed for changes in pro-inflammatory and anti-viral mediators and receptors using RT-qPCR, western blot and Luminex.ResultsTryptase and chymase induced release of the alarmin ATP and pro-inflammatory mediators IL-8, IL-6, IL-22 and MCP-1 from HBECs. Moreover, tryptase and chymase decreased the expression of E-cadherin and zonula occludens-1 expression from HBECs. Pre-treatment of HBECs with tryptase and chymase further increased Poly (I:C) induced IL-8 release at 3 h. Furthermore, tryptase significantly reduced type-I and III interferons (IFNs) and pattern recognition receptor (PRR) expression in HBECs. Tryptase impaired Poly (I:C) induced IFN and PRR expression which was restored by treatment of a serine protease inhibitor. Similar effects of tryptase on inflammation and anti-viral responses were also confirmed in primary HBECs from asthmatic patients.ConclusionMC localization within the epithelium and the release of their proteases may play a critical role in asthma pathology by provoking pro-inflammatory and alarmin responses and downregulating IFNs. Furthermore, MC proteases induce downregulation of epithelial junction proteins which may lead to barrier dysfunction. In summary, our data suggests that mast cells may contribute towards impaired anti-viral epithelial responses during asthma exacerbations mediated by the protease activity of tryptase.
Human microbiota modulation via QseC sensor kinase mediated in the Escherichia coli O104:H4 outbreak strain infection in microbiome model
Authors: Machado Ribeiro Tamara Renata , Salgaço Mateus Kawata , Adorno Maria Angela Tallarico , da Silva Miriam Aparecida , Piazza Roxane Maria Fontes , Sivieri Katia , Moreira Cristiano Gallina 
Published: June 2021

Abstract
Background
The intestinal microbiota plays a crucial role in human health, adjusting its composition and the microbial metabolites protects the gut against invading microorganisms. Enteroaggregative E. coli (EAEC) is an important diarrheagenic pathogen, which may cause acute or persistent diarrhea (≥14 days). The outbreak strain has the potent Shiga toxin, forms a dense biofilm and communicate via QseBC two-component system regulating the expression of many important virulence factors.

Results
Herein, we investigated the QseC histidine sensor kinase role in the microbiota shift during O104:H4 C227–11 infection in the colonic model SHIME® (Simulator of the Human Intestinal Microbial Ecosystem) and in vivo mice model. The microbiota imbalance caused by C227–11 infection affected ỿ-Proteobacteria and Lactobacillus spp. predominance, with direct alteration in intestinal metabolites driven by microbiota change, such as Short-chain fatty acids (SCFA). However, in the absence of QseC sensor kinase, the microbiota recovery was delayed on day 3 p.i., with change in the intestinal production of SCFA, like an increase in acetate production. The higher predominance of Lactobacillus spp. in the microbiota and significant augmented qseC gene expression levels were also observed during C227–11 mice infection upon intestinal depletion. Novel insights during pathogenic bacteria infection with the intestinal microbiota were observed. The QseC kinase sensor seems to have a role in the microbiota shift during the infectious process by Shiga toxin-producing EAEC C227–11.

Conclusions
The QseC role in C227–11 infection helps to unravel the intestine microbiota modulation and its metabolites during SHIME® and in vivo models, besides they contribute to elucidate bacterial intestinal pathogenesis and the microbiota relationships.
Diabetic microvascular complications are associated with reduced global longitudinal strain independent of atherosclerotic coronary artery disease in asymptomatic patients with diabetes mellitus: a cross-sectional study
Authors: Pararajasingam Gokulan , Heinsen Laurits Juhl , Larsson Johanna , Andersen Thomas Rueskov , Løgstrup Brian Bridal , Auscher Søren , Hangaard Jørgen , Møgelvang Rasmus , Egstrup Kenneth 
Published: June 2021

Abstract
Background
Reduced left ventricular function, assessed by global longitudinal strain (GLS), is sometimes observed in asymptomatic patients with diabetes mellitus (DM) and is often present in patients with diabetes-related microvascular complications. Our aim was to assess the association between microvascular complications, coronary artery plaque burden (PB) and GLS in asymptomatic patients with DM and non-obstructive coronary artery disease (CAD).

Methods
This cross-sectional study included patients with DM without any history, symptoms or objective evidence of obstructive CAD. All patients were identified in the outpatient Clinic of Endocrinology at Odense University Hospital Svendborg. An echocardiography and a coronary computed tomography angiography were performed to assess GLS and the degree of CAD, respectively. A coronary artery stenosis < 50% was considered non-obstructive. A linear regression model was used to evaluate the impact of potential confounders on GLS with adjustment of body mass index (BMI), mean arterial pressure (MAP), microvascular complications, type of diabetes, tissue Doppler average early diastolic mitral annulus velocity (e’) and PB.

Results
Two hundred and twenty-two patients were included, of whom 172 (77%) had type 2 DM and 50 (23%) had type 1 diabetes. One hundred and eleven (50%) patients had microvascular complications. GLS decreased as the burden of microvascular complications increased (P-trend = 0.01): no microvascular complications, GLS (− 16.4 ± 2.5%), 1 microvascular complication (− 16.0 ± 2.5%) and 2–3 microvascular complications (− 14.9 ± 2.8%). The reduction in GLS remained significant after multivariable adjustment (β 0.50 [95% CI 0.11–0.88], p = 0.01). BMI (β 0.12 [95% CI 0.05–0.19]) and MAP (β 0.05 [95% CI 0.01–0.08]) were associated with reduced GLS. In addition, an increased number of microvascular complications was associated with increased PB (β 2.97 [95% CI 0.42–5.51], p = 0.02) in a univariable linear regression model, whereas there was no significant association between PB and GLS.

Conclusions
The burden of microvascular complications was associated with reduced GLS independent of other cardiovascular risk factors in asymptomatic patients with DM and non-obstructive CAD. In addition, the burden of microvascular complications was associated with increasing PB, whereas PB was not associated with GLS.
Experiences of community-dwelling older people with dementia participating in a person-centred multidimensional interdisciplinary rehabilitation program
Authors: Sondell Anna , Lampinen Josefine , Conradsson Mia , Littbrand Håkan , Englund Undis , Nilsson Ingeborg , Lindelöf Nina 
Published: June 2021

Abstract
Background
There is great need for development of feasible rehabilitation for older people with dementia. Increased understanding of this population’s experiences of rehabilitation participation is therefore important. The aim of this study was to explore the experiences of community-dwelling older people with dementia participating in a person-centred multidimensional interdisciplinary rehabilitation program.

Methods
Sixteen older people with dementia were interviewed about their experiences of participation in a person-centred multidimensional interdisciplinary rehabilitation program. The program comprised assessments by a comprehensive team of rehabilitation professionals followed by a rehabilitation period of 16 weeks, including interventions based on individualized rehabilitation goals conducted with the support of the rehabilitation team. The rehabilitation was performed in the participants’ homes, in the community and at an outpatient clinic, including exercise with social interaction in small groups offered twice a week to all participants. The interviews were conducted at the end of the rehabilitation period and analysed with qualitative content analysis.

Results
The analysis resulted in one overarching theme: Empowered through participation and togetherness and four sub-themes: Being strengthened through challenges; Gaining insights, motives, and raising concerns about the future; Being seen makes participation worthwhile; and Feelings of togetherness in prosperity and adversity. The participants increased their self-esteem by daring and coping in the rehabilitation. The insights about themselves and their condition motivated them to continue with their prioritized activities, but also raised concerns about how the future would play out. Collaboration in the group and being seen and acknowledged by staff strengthened their own motivation and self-efficacy.

Conclusion
According to community-dwelling older people with dementia, a person-centred multidimensional interdisciplinary rehabilitation program was experienced as viable and beneficial. The participants seemed empowered through the rehabilitation and expressed mostly positive experiences and perceived improvements. Providers of interdisciplinary rehabilitation programs for this group should consider aspects raised by the participants e.g. the positive experience of being challenged in both exercise and daily activities; the importance of being seen and feeling secure; the benefits and challenges of collaboration with others in the same situation; and the generation of new perspectives of current and future situation.
Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009–2019
Authors: Aniskevich Aliaksandra , Shimanskaya Iryna , Boiko Iryna , Golubovskaya Tatyana , Golparian Daniel , Stanislavova Iryna , Jacobsson Susanne , Adaskevich Aliaksandr , Unemo Magnus 
Published: June 2021

Abstract
Background
Limited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea.

Methods
N. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009–2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified β-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher’s exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance.

Results
In total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced β-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018–2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment.

Conclusions
The gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.
Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings
Authors: Guerrero Juan I. , Barragán Luis A. , Martínez Juan D. , Montoya Juan P. , Peña Alejandra , Sobrino Fidel E. , Tovar-Spinoza Zulma , Ghotme Kemel A. 
Published: June 2021

Abstract
Background
SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system’s involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings.

Methods
We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19.

Results
A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system’s involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients.

Conclusions
Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19’s central and peripheral neurological involvement and generate therapeutic decision-making strategies.

Registration
This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140
Prevalence of visceral artery involvement in patients with peripheral artery disease found on run-off MRA
Authors: Streckenbach Felix , Meinel Felix G. , Ammermann Felix , Busse Anke , Neumann Andreas , Heller Thomas , Weber Marc-André , Beller Ebba 
Published: June 2021

Abstract
Background
In patients with peripheral artery disease (PAD), run-off MR-angiography (MRA) is a commonly performed diagnostic test to obtain high-resolution images for evaluation of the arterial system from the aorta through the distal run-off vessels. The aim of this study was to investigate the prevalence of visceral artery involvement (VAI) in patients with PAD and leg symptoms examined with run-off MRA.

Methods
We retrospectively analyzed 145 patients (median age 68 years, range 27–91) who underwent MRA due to known or suspected PAD at our institution between 2012 and 2018. MRA examinations were re-evaluated for visceral artery stenosis. Patient dossiers were reviewed to determine cardiovascular risk factors, kidney function and Fontaine stage of PAD.

Results
Involvement of at least one visceral artery with ≥ 50% diameter stenosis was found in 72 (50%) patients. There were no differences in age, gender, MRA indication, Fontaine stage, levels of C-reactive protein (CRP), cardiovascular risk factors or vascular comorbidities between patients with and without VAI. Renal artery (RA) involvement with ≥ 50% diameter stenosis was observed in 28 (20%) of patients. Patients with involvement of the RA were more likely to suffer from hypertension (79 vs. 54%, p = 0.019) and reduced renal function (glomerular filtration rate 70 vs. 88 mL/min/1.73m2, p = 0.014).

Conclusion
Visceral artery stenosis can be seen in half of patients with known or suspected PAD and leg symptoms on run-off MRA. Investigating for RA stenosis in patients with PAD and hypertension and/or impaired renal function may have high diagnostic yield.
Cognitive performance in dialysis patients - "when is the right time to test?"
Authors: Karakizlis Hristos , Thiele Stefanie , Greene Brandon , Hoyer Joachim 
Published: June 2021

Abstract
Background
Cognitive impairment in chronic kidney disease, especially in end stage renal disease, is a public health problem. Nevertheless, the cause of chronic kidney disease still remains unclear. A prevalence of cognitive impairment in patients with end stage renal disease of up to 87% has been found.

Methods
The study at hand deals with the research on the – potential – effect of timing on cognitive performance when testing cognitive impairment in hemodialysis patients during the dialysis cycle. We tested cognitive performance with a neuropsychological test battery (RBANS, Repeatable Battery for the Assessment of Neuropsychological Status) on two occasions while patients were on dialysis as well as on a dialysis-free day. In addition, all participants were rated using the Geriatric Depression Scale (GDS) and several demographic and clinical variables were recorded in order to investigate their possible influence on cognitive performance.
The patients were recruited in three dialysis centers in the central region of Hesse, Germany. Twenty-six participants completed the 3 testings during a period of 6 weeks. The testing was carried out in the dialysis centers.

Results
Looking at the total scale score, patients achieved the best cognitive performance in the RBANS during the first 2 h on dialysis with 81.1 points. When comparing the scores of the three measurement occasions (first 2 h, Timepoint 1 vs. last 2 h, Timepoint 2 vs. dialysis free day, Timepoint 3, however, no significant difference in the total scale score was detected. But patients showed significantly better cognitive performance in language in the first 2 h (p < 0.001) as well as in the last 2 h (p < 0.001) compared with the dialysis-free day.

Conclusion
Due to the high prevalence of cognitive impairment, there is an increasing need to assess cognitive function in dialysis patients. Our data show that the time point of testing (first 2 h on hemodialysis vs. last 2 h on hemodialysis vs. Hemodialysis free day) had no influence of cognitive function in hemodialysis patients in routine indications.