bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variants Assessing Crohn’s Disease Pattern in Pediatric Inflammatory Bowel Disease Patients by a Clinical Exome Survey
Authors: Noel Dago Dougba , Marinella Pinelli , Mauro Giacomelli , Tripodi Serena Ilaria , Pin Alessia , Serena Arrigo , Matteo Bramuzzo , Giuseppe Fuoti Maurizio , Patrizia Alvisi , Stefano Calza , Tommasini Alberto , Raffaele Badolato 
Published: December 2021

Background: Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders that comprise Crohn’s disease (CD) and ulcerative colitis (UC). Recent discoveries have brought much attention to the genetic predisposition of patients with IBD. Here we evaluate the interaction between IBD genetic risk factors susceptibility and CD occurrence in an IBD pediatric patient population, performing a clinical exome survey. Methods: From February 2018 to April 2019, we collected blood samples from 7 pediatric patients with IBD concerns from several collaborating health centers and/or hospitals. Blood samples were processed by extracting and sequencing DNA for a clinical exome survey. Shophia-DDM-v3-4 platform allowed sequenced reads alignment on hg19 genome as well as genetic variant calling. Both IBD risk and pathogenic genetic variants covered by at least 20 reads were selected for subjacent analysis. Results: Normality and Bartlett tests of both risk and pathogenic genetic variants suggested random and heterogeneous distribution of these variants in this group of IBD pediatric patients. P value clustering analysis by processing 157 IBD risk factors revealed genetic heterogeneity in IBD population and suggested two pathways influencing IBD development. In particular, (1) genetic variants associated with autoimmune and (2) metabolic diseases and CD risk factors (rs2066844 and rs2241880 single nucleotide polymorphism variants, respectively, of genes NOD2 and ATG16L) were identified in distinct clusters of IBD patients ( P < .05). Moreover, the heterogeneous distribution of the following variants rs10065172 (IRGM), rs1805010 (IL4R), rs5030737 (MBL2), and rs33995883 (LRRK2) in this group of IBD patients was consistent with their random distribution in that population. Conclusion: Our study revealed specific genetic variants linked to CD susceptibility, autoimmune and/or innate immunodeficiency as well as to metabolic defects, as favoring factors of IBD, suggesting the valuable role of next generation sequencing (NGS) approaches in IBD molecular diagnostic procedures.
Unruptured Intradural Posterior Circulation Dissecting/Fusiform Aneurysms Natural History and Treatment Outcome
Authors: Dmytriw Adam Andrew , Alrashed Abdullah , Enriquez-Marulanda Alejandro , Medhi Gorky , Mendes Pereira Vitor 
Published: December 2021

Background The natural history and outcome of unruptured posterior circulation dissecting fusiform aneurysms is not fully understood. These have a high risk of morbidity and mortality, not only due to natural history but also due to the challenging and controversial treatment approaches currently available compared to other types of intracranial aneurysms. Methods We performed a retrospective study of a prospectively collected aneurysm database at a quaternary neurovascular hospital. We included consecutive patients with unruptured intradural vertebrobasilar dissecting aneurysms between January 2000 and July 2016 who were followed to 2020. Description of baseline, procedural, and outcomes data was performed. Comparisons of patient who had aneurysm rupture on follow-up, increase in 2 or more points of mRS in follow-up and progression of the aneurysm was performed. Results Seventy patients with 78 fusiform posterior circulation aneurysms were identified. Thirty-nine (55.7%) patients were male with a mean age of 51.7 years (SD ± 17.6). When multiple, aneurysms were more likely to be fusiform (60%) than saccular (40.0%). Baseline diameter (measured on CTA/MRA/DSA), length as well as symptomatic presentation were significantly higher in aneurysms which grew over time. Coronary disease, diabetes and growth were associated an >2 increase in mRS. Diabetes as well as initial symptomatic presentation were associated with rupture. Conclusions Unruptured dissecting/fusiform aneurysm are associated with a considerable rate of rupture during follow-up. Growth is associated with morbidity even in the absence of rupture. Initial large size, coronary disease, diabetes, and to a lesser extent female gender may merit closer follow-up and/or prophylactic treatment.
Patient, carer and healthcare professional perspectives on increasing calorie intake in Amyotrophic Lateral Sclerosis
Authors: Coates Elizabeth , Zarotti Nicolò , Williams Isobel , White Sean , Halliday Vanessa , Beever Daniel , Hackney Gemma , Stavroulakis Theocharis , White David , Norman Paul , McDermott Christopher ,   on behalf of the HighCALS group
Published: December 2021

Objectives Research suggests that higher Body Mass Index is associated with improved survival in people with Amyotrophic Lateral Sclerosis (pwALS). Yet, understanding of the barriers and enablers to increasing calorie intake is limited. This study sought to explore these issues from the perspective of pwALS, informal carers, and healthcare professionals. Methods Interviews with 18 pwALS and 16 informal carers, and focus groups with 51 healthcare professionals. Data were analysed using template analysis and mapped to the COM-B model and Theoretical Domains Framework (TDF). Results All three COM-B components (Capability, Opportunity and Motivation) are important to achieving high calorie diets in pwALS. Eleven TDF domains were identified: Physical skills (ALS symptoms); Knowledge (about high calorie diets and healthy eating); Memory, attention, and decision processes (reflecting cognitive difficulties); Environmental context/resources (availability of informal and formal carers); Social influences (social aspects of eating); Beliefs about consequences (healthy eating vs. high calorie diets); Identity (interest in health lifestyles); Goals (sense of control); Reinforcement (eating habits); and Optimism and Emotion (low mood, poor appetite). Discussion To promote high calorie diets for pwALS, greater clarity around the rationale and content of recommended diets is needed. Interventions should be tailored to patient symptoms, preferences, motivations, and opportunities.
Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study
Authors: Spindelboeck Walter , Halwachs Bettina , Bayer Nadine , Huber-Krassnitzer Bianca , Schulz Eduard , Uhl Barbara , Gaksch Lukas , Hatzl Stefan , Bachmayr Victoria , Kleissl Lisa , Kump Patrizia , Deutsch Alexander , Stary Georg , Greinix Hildegard , Gorkiewicz Gregor , Högenauer Christoph , Neumeister Peter 
Published: December 2021

Introduction: Treatment-refractory, acute graft- versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear. The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD. Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs. Results: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit ( p = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure ( p = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8+ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response. Conclusion: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.
Season of birth is associated with multiple sclerosis and disease severity
Authors: Stridh P , Huang J , Hedström AK , Alfredsson L , Olsson T , Hillert J , Manouchehrinia A , Kockum I 
Published: December 2021

Background The latitude gradient in multiple sclerosis incidence indicates that low sun exposure and therefore vitamin D deficiency is associated with multiple sclerosis risk. Objective Investigation of the effect of month of birth, which influences postnatal vitamin D levels, on multiple sclerosis risk and severity in Sweden. Methods Patients and population-based controls were included from three nationwide cohorts. Differences in month of birth between cases and controls were analyzed using logistic regression and examined for effect modification by calendar year and geographic region at birth. Results Males had a reduced risk of multiple sclerosis if born in the winter and increased risk if born in the early fall. Individuals born before 1960 had an increased risk if born in summer or fall. Being born in late summer and early fall was associated with more severe disease. Conclusions We identified a birth cohort effect on the association between the month of birth and multiple sclerosis, with a more significant effects for births before 1960. This coincides with a period of lower breastfeeding rates, recommended intake of vitamin D, and sun exposure, resulting in a lower vitamin D exposure during the fall/winter season for infants born in the summer.
Patients’ and clinicians’ perceptions of oral anticoagulants in atrial fibrillation: a systematic narrative review and meta-analysis
Authors: Osasu Yeyenta Mina , Cooper Richard , Mitchell Caroline 
Published: December 2021

Abstract
Background
Atrial fibrillation (AF) increases the risk of developing a stroke by 20%. AF related strokes are associated with greater morbidity. Historically, warfarin was the anticoagulant of choice for stroke prevention in patients with AF but lately patients are being switched or started on direct oral anticoagulants (DOACs). DOACs are promoted as safer alternatives to warfarin and it is expected that they will be associated with fewer challenges both for patients and healthcare professionals. This systematic narrative review aimed to explore perspectives of patients and professionals on medicines optimisation of oral anticoagulation with vitamin K antagonists and DOACs in atrial fibrillation.

Methods
Prospero registration CRD42018091591. Systematic searches undertaken of research studies (qualitative and quantitative), published February 2018 to November 2020 from several databases (Web of Science, Scopus, Medline Via Ovid, CINHAL via Ebsco, and PubMED via NCBI) following PRISMA methodology. Data were organised using Covidence software. Two reviewers independently assessed the quality of the included studies and synthesized the findings (thematic analysis approach).

Results
Thirty-four studies were included. Studies were critically appraised using established critical appraisal tools (Qualsyst) and a risk of bias was assigned. Clinicians considered old age and the associated complexities such as co-morbidities and the increased potential for bleeding as potential barriers to optimising anticoagulation. Whereas patients’ health and medication beliefs influenced adherence. Notably, structured patient support was important in enhancing safety and effective anticoagulation. For both patients and clinicians, confidence and experience of safe anticoagulation was influenced by the presence of co-morbidities, poor knowledge and understanding of AF and the purpose of anticoagulation.

Conclusion
Age, complex multimorbidity and polypharmacy influence prescribing, with DOACs being perceived to be safer than warfarin. This systematic narrative review suggests that interventions are needed to support patient self-management. There are residual anxieties associated with long term anticoagulation in the context of complexities.

Trial registration
Not applicable.
Doctor-patient relationship improved during COVID-19 pandemic, but weakness remains
Authors: Zhou Yanan , Ma Yuejiao , Yang Winson Fu Zun , Wu Qiuxia , Wang Qianjin , Wang Dongfang , Ren Honghong , Luo Yinli , Yang Dong , Liu Tieqiao , Wu Xiaoming 
Published: December 2021

Abstract
Objective
To assess the quality of the doctor-patient relationship (DPR) in China and possible influencing factors during the COVID-19 period from the patient’s perspective.

Methods
An online survey was carried out nationwide from March 12, 2020 to March 30, 2020 in China via a convenience sampling strategy. Patients who met the inclusion criteria were invited to complete a questionnaire regarding the quality of DPR, including sociodemographic information, the Patient-Doctor Relationship Questionnaire (PDRQ-9), and influencing factors for DPR during the pandemic.

Results
A total of 1903 patients were included. Our result showed that participants had a higher PDRQ-9 score during the COVID-19 pandemic (4.18 ± 0.51) than that before the COVID-19 pandemic (3.86 ± 0.67). Importance-performance analysis (IPA) revealed that doctor-patient communication, patient satisfaction, consultation time, doctor’s attitude, and medical knowledge were specific aspects that needed to be prioritized to improve the DPR. Multiple linear regression analysis suggested that positive media reports, telemedicine, and national policies had a significantly positive effect on the DPR during the pandemic (P < 0.05).

Conclusion
In general, the DPR had been improved during the COVID-19 pandemic. Our research found the key points that needed to be prioritized to improve the DPR during the pandemic, which may provide effective suggestions for building a harmonious DPR in the future.
Prerequisites for providing effective support to family caregivers within the primary care setting – results of a study series in Germany
Authors: Wangler Julian , Jansky Michael 
Published: December 2021

Abstract
Background
General Practitioners are considered to be well placed to monitor home-care settings and to respond specifically to family caregivers. To do this, they must be sensitive to the needs and expectations of caregivers. In order to determine the current status of GP care in terms of the support given to family caregivers, a series of studies were conducted to gather the perspectives of both caregivers and GPs. The results are used to derive starting points as to which measures would be sensible and useful to strengthen support offered to family caregivers in the primary care setting.

Methods
Between 2020 and 2021, three sub-studies were conducted: a) an online survey of 612 family caregivers; b) qualitative interviews with 37 family caregivers; c) an online survey of 3556 GPs.

Results
Family caregivers see GPs as a highly skilled and trustworthy central point of contact; there are many different reasons for consulting them on the subject of care. In the perception of caregivers, particular weaknesses in GP support are the absence of signposting to advisory and assistance services and, in many cases, the failure to involve family caregivers in good time. At the same time, GPs do not always have sufficient attention to the physical and psychological needs of family caregivers. The doctors interviewed consider the GP practice to be well suited to being a primary point of contact for caregivers, but recognise that various challenges exist. These relate, among other things, to the timely organisation of appropriate respite services, targeted referral to support services or the early identification of informal caregivers.

Conclusions
GP practices can play a central role in supporting family caregivers. Caregivers should be approached by the practice team at an early stage and consistently signposted to help and support services. In order to support care settings successfully, it is important to consider the triadic constellation of needs, wishes and stresses of both the caregiver and the care recipient. More training and greater involvement of practice staff in the support and identification of caregivers seems advisable.
Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study
Authors: Stanevich O. V. , Fomina D. S. , Bakulin I. G. , Galeev S. I. , Bakin E. A. , Belash V. A. , Kulikov A. N. , Lebedeva A. A. , Lioznov D. A. , Polushin Yu. S. , Shlyk I. V. , Vorobyev E. A. , Vorobyeva S. V. , Surovceva T. V. , Bakulina N. V. , Lysenko M. A. , Moiseev I. S. 
Published: December 2021

Abstract
Background
Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib.

Methods
The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020.

Results
Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6–14.6%]) vs 13.0% (95% CI [7.5–18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31–1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11–1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8–16 mg dexamethasone).

Conclusions
Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration.
Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date
Toscana virus encephalitis in Southwest Germany: a retrospective study
Authors: Dersch R. , Sophocleous A. , Cadar D. , Emmerich P. , Schmidt-Chanasit J. , Rauer S. 
Published: December 2021

Abstract
Background
Toscana virus (TOSV) is an arthropod-borne virus transmitted by phlebotomine sandflies (Phlebotomus sp.) widespread throughout the Mediterranean having the potential to cause meningoencephalitis in humans. In Germany, the vectors of TOSV are introduced recently and become endemic especially in Southwestern Germany. As TOSV is not investigated regularly in patients with meningoencephalitis, cases of TOSV-neuroinvasive disease may remain mostly undetected.

Methods
We conducted a retrospective cohort study on patients with meningoencephalitis without identification of a causal pathogen from 2006 to 2016. Serologic assessment for anti-TOSV-IgG and IgM was performed on serum and CSF. Demographic, clinical and CSF data from TOSV-positive patients were compared to a cohort of patients with meningoencephalitis due to enterovirus. Informed consent was obtained from all included patients.

Results
We found 138 patients with meningoencephalitis without identified causal pathogen. From 98 of these patients CSF and serum was available for further testing. Additionally, we included 27 patients with meningoencephalitis due to enterovirus. We identified two patients with serological confirmed TOSV-neuroinvasive disease (TOSV-IgM and IgG positive, 2%) and two patients with possible TOSV-neuroinvasive disease (isolated TOSV-IgM positive, 2%). Overall, TOSV-neuroinvasive was detected in 4% of our cases with suspected viral meningoencephalitis. None of them had a history of recent travel to an endemic area.

Conclusions
We found cases of TOSV-neuroinvasive disease in our German cohort of patients with meningoencephalitis. As no recent history of travel to an endemic area was reported, it remains probable that these cases resemble autochthonous infections, albeit we cannot draw conclusions regarding the origin of the respective vectors. TOSV could be considered in patients with meningoencephalitis in Germany.
Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation
Authors: Chacon-Alberty Lourdes , Ye Shengbin , Daoud Daoud , Frankel William C. , Virk Hassan , Mase Jonathan , Hochman-Mendez Camila , Li Meng , Sampaio Luiz C. , Taylor Doris A. , Loor Gabriel 
Published: December 2021

Abstract
Background
Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR.

Methods
In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression.

Results
After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h.

Conclusions
Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.