bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asthma and atopic dermatitis as risk factors for rheumatoid arthritis: a bidirectional mendelian randomization study
Authors: Chen Chuiji , Su Le , Duan Wenhao , Zheng Yansen , Zhang Dianzhong , Wang Yucai 
Published: March 2023

Abstract
Background
Previous observational studies have shown an association between asthma, atopic dermatitis (AD) and rheumatoid arthritis (RA). However, the bidirectional cause-effect chain between asthma and AD and RA has not been proven yet.

Methods
We performed bidirectional two-sample Mendelian randomization (TSMR) and selected single nucleotide polymorphisms (SNPs) associated with asthma, AD, and RA as instrumental variables. All of the SNPs were obtained from the latest genome-wide association study in Europeans. Inverse variance weighted (IVW) was the main method used in MR analysis. MR-Egger, weighted model, simple model, and weighted median were used for quality control. The robustness of the results was tested by sensitivity analysis.

Results
Asthma was found to be the largest effect size for RA susceptibility using the IVW method (OR, 1.35;95%CI, 1.13–1.60; P, 0.001), followed by AD (OR, 1.10;95%CI, 1.02–1.19; P, 0.019). In contrast, there was no causal relationship between RA and asthma (IVW: P = 0.673) or AD (IVW: P = 0.342). No pleiotropy or heterogeneity was found in the sensitivity analysis.

Conclusion
Findings from this study showed a causal relationship between genetic susceptibility to asthma or AD and increased risk of RA, but do not support a causal relationship between genetic susceptibility to RA and asthma or AD.
The link between glycemic control measures and eye microvascular complications in a clinical cohort of type 2 diabetes with microRNA-223-3p signature
Authors: Da’as Sahar I. , Ahmed Ikhlak , Hasan Waseem H. , Abdelrahman Doua A. , Aliyev Elbay , Nisar Sabah , Bhat Ajaz Ahmad , Joglekar Mugdha V. , Hardikar Anandwardhan A. , Fakhro Khalid A. , Akil Ammira S. Al-Shabeeb 
Published: March 2023

Abstract
Background
Type 2 diabetes (T2D) is a critical healthcare challenge and priority in Qatar which is listed amongst the top 10 countries in the world, with its prevalence presently at 17% double the global average. MicroRNAs (miRNAs) are implicated in the pathogenesis of (T2D) and long-term microvascular complications including diabetic retinopathy (DR).

Methods
In this study, a T2D cohort that accurately matches the characteristics of the general population was employed to find microRNA (miRNA) signatures that are correlated with glycemic and β cell function measurements. Targeted miRNA profiling was performed in (471) T2D individuals with or without DR and (491) (non-diabetic) healthy controls from the Qatar Biobank. Discovery analysis identified 20 differentially expressed miRNAs in T2D compared to controls, of which miR-223-3p was significantly upregulated (fold change:5.16, p = 3.6e−02) and positively correlated with glucose and hemoglobin A1c (HbA1c) levels (p-value = 9.88e−04 and 1.64e−05, respectively), but did not show any significant associations with insulin or C-peptide. Accordingly, we performed functional validation using a miR-223-3p mimic (overexpression) under control and hyperglycemia-induced conditions in a zebrafish model.

Results
Over-expression of miR-223-3p alone was associated with significantly higher glucose (42.7 mg/dL, n = 75 vs 38.7 mg/dL, n = 75, p = 0.02) and degenerated retinal vasculature, and altered retinal morphology involving changes in the ganglion cell layer and inner and outer nuclear layers. Assessment of retinal angiogenesis revealed significant upregulation in the expression of vascular endothelial growth factor and its receptors, including kinase insert domain receptor. Further, the pancreatic markers, pancreatic and duodenal homeobox 1, and the insulin gene expressions were upregulated in the miR-223-3p group.

Conclusion
Our zebrafish model validates a novel correlation between miR-223-3p and DR development. Targeting miR-223-3p in T2D patients may serve as a promising therapeutic strategy to control DR in at-risk individuals.
Gargle sample is an effective option in a novel fully automated molecular point-of-care test for influenza: a multicenter study
Authors: Kaku Norihito , Urabe Tomohito , Iida Tetsuya , Yun Chyuns , Nishida Yoshiyuki , Onitsuka Yasunori , Hashiguchi Kohji , Hirose Kiyoto , Tomonaga Akimitsu , Izumikawa Koichi , Mukae Hiroshi , Yanagihara Katsunori 
Published: March 2023

Abstract
Background
We conducted a multicenter study to evaluate the performance of a novel fully automated molecular point-of-care test using transcription-reverse transcription concerted reaction that can detect influenza A and B within 15 min in nasopharyngeal swabs and gargle samples (TRCsatFLU).

Methods
Patients who visited or were hospitalized at eight clinics and hospitals with influenza-like illnesses between December 2019 and March 2020 participated in this study. We collected nasopharyngeal swabs from all patients and gargle samples from patients whom the physician judged fit to perform gargling. The result of TRCsatFLU was compared to a conventional reverse transcription-polymerase chain reaction (RT-PCR). If the results of TRCsatFLU and conventional RT-PCR were different, the samples were analyzed by sequencing.

Results
We evaluated 233 nasopharyngeal swabs and 213 gargle samples from 244 patients. The average age of the patients was 39.3 ± 21.2. Of the patients, 68.9% visited a hospital within 24 h of symptom onset. The most common symptoms were fever (93.0%), fatigue (79.5%), and nasal discharge (64.8%). All patients in whom the gargle sample was not collected were children. Influenza A or B was detected in 98 and 99 patients in nasopharyngeal swabs and gargle samples using TRCsatFLU, respectively. Four and five patients in nasopharyngeal swabs and gargle samples, respectively, with different TRCsatFLU and conventional RT-PCR results. Influenza A or B was detected using sequencing in all samples with different results. Based on the combined conventional RT-PCR and sequencing results, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TRCsatFLU for influenza detection in nasopharyngeal swabs were 0.990, 1.000, 1.000, and 0.993, respectively. In the gargle samples, the sensitivity, specificity, PPV, and NPV of the TRCsatFLU for detecting influenza were 0.971, 1.000, 1.000, and 0.974, respectively.

Conclusions
The TRCsatFLU showed great sensitivity and specificity for the detection of influenza in nasopharyngeal swabs and gargle samples.
Trial registration: This study was registered in the UMIN Clinical Trials Registry (reference number: UMIN000038276) on October 11, 2019. Before sample collection, written informed consent for the participation and publication of this study was obtained from all participants.
Successful treatment of acute myocardial injury of Duchenne muscular dystrophy with steroids: a case report
Authors: Oğuz Merve , Gürses Dolunay , Ufuk Furkan , Yılmaz Münevver , Güngör Olcay 
Published: March 2023

Abstract
Background
Duchenne muscular dystrophy (DMD) is an X-linked muscular disease which is caused by the absence of dystrophin. Troponin elevation with acute chest pain may indicate acute myocardial injury in these patients. We report a case of DMD that presented with ACP and troponin elevation, who was diagnosed with acute myocardial injury, and successfully treated with corticosteroids.

Case presentation
A 9-year-old with DMD was admitted to the emergency department with the complaint of acute chest pain. His electrocardiogram (ECG) revealed inferior ST elevation and serum troponin T was elevated. The transthoracic echocardiography (TTE) demonstrated inferolateral and anterolateral hypokinesia with depressed left ventricular function. An ECG-gated coronary computed tomography angiography ruled out acute coronary syndrome. Cardiac magnetic resonance imaging revealed mid-wall to sub-epicardial late gadolinium enhancement at the basal to the mid inferior lateral wall of the left ventricle and corresponding hyperintensity on T2-weighted imaging, consistent with acute myocarditis. A diagnosis of acute myocardial injury associated with DMD was made. He was treated with anticongestive therapy and 2 mg/kg/day of oral methylprednisolone. Chest pain resolved the next day, and ST-segment elevation returned to normal on the third day. Troponin T decreased in the sixth hour of oral methylprednisolone treatment. TTE on the fifth day revealed improved left ventricular function.

Conclusion
Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with DMD. Acute chest pain attacks with elevated troponin in patients with DMD without coronary artery disease may indicate acute myocardial injury. Recognition and appropriate treatment of acute myocardial injury episodes in DMD patients may delay the development of cardiomyopathy.
Thick shells and medially wedged posts increase foot orthoses medial longitudinal arch stiffness: an experimental study
Authors: Pelaez Ana Sofia Tavera , Farahpour Nader , Griffiths Ian B. , Moisan Gabriel 
Published: March 2023

AbstractBackgroundFoot orthoses (FOs) are commonly prescribed devices to attenuate biomechanical deficits and improve physical function in patients with musculoskeletal disorders. It is postulated that FOs provide their effects through the production of reaction forces at the foot‐FOs interface. An important parameter to provide these reaction forces is their medial arch stiffness. Preliminary results suggest that adding extrinsic additions to FOs (e.g., rearfoot posts) increases their medial arch stiffness. A better understanding of how FOs medial arch stiffness can be modulated by changing structural factors is necessary to better customise FOs for patients. The objectives of this study were to compare FOs stiffness and force required to lower the FOs medial arch in three thicknesses and two models (with and without medially wedged forefoot‐rearfoot posts).MethodsTwo models of FOs, 3D printed in Polynylon‐11, were used: (1) without extrinsic additions (mFO), and (2) with forefoot‐rearfoot posts and a 6o medial wedge (FO6MW). For each model, three thicknesses (2.6 mm, 3.0 mm, and 3.4 mm) were manufactured. FOs were fixed to a compression plate and vertically loaded over the medial arch at a rate of 10 mm/minute. Two‐way ANOVAs and Tukey post‐hoc tests with Bonferroni corrections were used to compare medial arch stiffness and force required to lower the arch across conditions.ResultsRegardless of the differing shell thicknesses, the overall stiffness was 3.4 times greater for FO6MW compared to mFO (p < 0.001). FOs with 3.4 mm and 3.0 mm thicknesses displayed 1.3‐ and 1.1‐ times greater stiffness than FOs with a thickness of 2.6 mm. FOs with a thickness of 3.4 mm also exhibited 1.1 times greater stiffness than FOs with a thickness of 3.0 mm. Overall, the force to lower the medial arch was up to 3.3 times greater for FO6MW than mFO and thicker FOs required greater force (p < 0.001).ConclusionsAn increased medial longitudinal arch stiffness is seen in FOs following the addition of 6o medially inclined forefoot‐rearfoot posts, and when the shell is thicker. Overall, adding forefoot‐rearfoot posts to FOs is significantly more efficient than increasing shell thickness to enhance these variables should that be the therapeutic aim.
Immunohistochemical markers of prognosis in adult granulosa cell tumors of the ovary – a review
Authors: Jung Dennis , Almstedt Katrin , Battista Marco J. , Seeger Alexander , Jäkel Jörg , Brenner Walburgis , Hasenburg Annette 
Published: March 2023

Abstract
Background
Granulosa cell tumors (GCT) are rare malignant ovarian tumors. The two subtypes, adult and juvenile granulosa cell tumors, differ in clinical and molecular characteristics. GCT are low-malignant tumors and are generally associated with favorable prognosis. However, relapses are common even years and decades after diagnosis. Prognostic and predictive factors are difficult to assess in this rare tumor entity. The purpose of this review is to provide a comprehensive overview of the current state of knowledge on prognostic markers of GCT to identify patients with a high risk of recurrence.

Methods
Systematic research for adult ovarian granulosa cell tumors and prognosis revealed n = 409 English full text results from 1965 to 2021. Of these articles, n = 35 were considered for this review after title and abstract screening and topic-specific matching. A specific search for pathologic markers with prognostic relevance for GCT identified n = 19 articles that were added to this review.

Results
FOXL2 mutation and FOXL2 mRNA were inverse and immunohistochemical (IHC) expression of CD56, GATA-4 and SMAD3 was associated with reduced prognosis. IHC analysis of estrogen receptor, Anti-Mullerian hormone (AMH) and inhibin was not associated with prognosis for GCT. Analyses of mitotic rate, Ki-67, p53, β-catenin and HER2 revealed inconsistent results.
A privacy protection approach in edge-computing based on maximized dnn partition strategy with energy saving
Authors: Chaopeng Guo , Zhengqing Lin , Jie Song 
Published: March 2023

AbstractWith the development of deep neural network (DNN) techniques, applications of DNNs show state-of-art performance. In the cloud edge collaborative mode, edge devices upload the raw data, such as texts, images, and videos, to the cloud for processing. Then, the cloud returns prediction or classification results. Although edge devices take advantage of the powerful performance of DNN, there are also colossal privacy protection risks. DNN partition strategy can effectively solve the privacy problems by offload part of the DNN model to the edge, in which the encoded features are transmitted rather than original data. We explore the relationship between privacy and the intermedia result of the DNN. The more parts offloaded to the edge, the more abstract features we can have, indicating more conducive to privacy protection. We propose a privacy protection approach based on a maximum DNN partition strategy. Besides, a mix-precision quantization approach is adopted to reduce the energy use of edge devices. The experiments show that our method manages to increase at most 20% model privacy in various DNN architecture. Through the energy-aware mixed-precision quantization approach, the model’s energy consumption is reduced by at most 5x comparing to the typical edge-cloud solution.
Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection
Authors: Li Jiarui , Jing Qiuyu , Li Jie , Hua Mingxi , Di Lin , Song Chuan , Huang Yanyi , Wang Jianbin , Chen Chen , Wu Angela Ruohao 
Published: March 2023

Abstract
Background
The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity.

Results
We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period.

Conclusions
Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.
Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10−/− mouse model of inflammatory bowel disease
Authors: Armstrong Heather , Rahbari Mandana , Park Heekuk , Sharon David , Thiesen Aducio , Hotte Naomi , Sun Ning , Syed Hussain , Abofayed Hiatem , Wang Weiwei , Madsen Karen , Wine Eytan , Mason Andrew 
Published: March 2023

Abstract

Background
Following viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain-specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-10−/−) model derived from the SvEv mouse, had evidence of increased Mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wild type. MMTV is endemic in several mouse strains as an endogenously encoded Betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut-associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10−/− model.

Results
Viral preparations extracted from IL-10−/− weanling stomachs revealed augmented MMTV load compared to the SvEv wild type. Illumina sequencing of the viral genome revealed that the two largest contigs shared 96.4–97.3% identity with the mtv-1 endogenous loci and the MMTV(HeJ) exogenous virus from the C3H mouse. The MMTV sag gene cloned from IL-10−/− spleen encoded the MTV-9 superantigen that preferentially activates T-cell receptor Vβ-12 subsets, which were expanded in the IL-10−/− versus the SvEv colon. Evidence of MMTV cellular immune responses to MMTV Gag peptides was observed in the IL-10−/− splenocytes with amplified interferon-γ production versus the SvEv wild type. To address the hypothesis that MMTV may contribute to colitis, we used HIV reverse transcriptase inhibitors, tenofovir and emtricitabine, and the HIV protease inhibitor, lopinavir boosted with ritonavir, for 12-week treatment versus placebo. The combination antiretroviral therapy with known activity against MMTV was associated with reduced colonic MMTV RNA and improved histological score in IL-10−/− mice, as well as diminished secretion of pro-inflammatory cytokines and modulation of the microbiome associated with colitis.

Conclusions
This study suggests that immunogenetically manipulated mice with deletion of IL-10 may have reduced capacity to contain MMTV infection in a mouse-strain-specific manner, and the antiviral inflammatory responses may contribute to the complexity of IBD with the development of colitis and dysbiosis.
The Cognitive Daisy (COG-D) for improving care for residents with dementia in care homes: protocol of a feasibility RCT
Authors: Pollux Petra M. J. , Surr Claire , Cohen Judith , Huang Chao , Wolverson Emma , Mountain Pauline , Turner Rebecca , Hawkesford-Webb Emma , Winter Bethany , Hudson John M. 
Published: March 2023

Abstract
Background
Cognitive problems associated with dementia affect a large proportion of older adults living in residential care. Knowledge of cognitive impairments is important for providing person-centred care (PCC). The impact of specific cognitive impairments on residents’ needs is often overlooked in dementia training and information about residents’ individual cognitive profiles are frequently underspecified in care-plans, potentially undermining the delivery of PCC. This can lead to reduced resident quality of life and increased distressed behaviours—a major cause of staff stress and burnout. The COG-D package was developed to fill this gap. Daisies provide a visual representation of a resident’s individual cognitive strengths and weaknesses in a colourful flower (Daisy) representing five cognitive domains. By viewing a resident’s Daisy, care-staff can flexibly adjust in-the-moment care-decisions and can consult Daisies in care-plans for longer-term planning. The primary aim of this study is to assess the feasibility of implementing the COG-D package in residential care homes for older adults.

Methods/design
This 24-month feasibility cluster randomized controlled trial involves a 6-month intervention of the use of Cognitive Daisies in 8–10 residential care homes for older adults after training of care staff on the use of Cognitive Daisies in daily care (basic training) and on conducting the COG-D assessments with residents (advanced training). The key feasibility outcomes include % residents recruited, % COG-D assessments completed, and % staff completing the training. Candidate outcome measures for residents and staff will be obtained at baseline, and at 6 and 9 months post-randomization. COG-D assessments of residents will be repeated 6 months after the first assessment. A process evaluation will assess intervention implementation and barriers and facilitators to this through care-plan audits, interviews and focus groups with staff, residents, and relatives. Feasibility outcomes will be analysed against progression criteria to a full trial.

Discussion
The results of this study will provide important information about the feasibility of using COG-D in care homes and will inform the design of a future large-scale cluster RCT to assess the effectiveness and cost-effectiveness of the COG-D intervention in care homes.

Trial registration
This trial was registered on 28/09/2022 (ISRCTN15208844) and is currently open to recruitment.
Who supports refugees? Diversity assent and pro-refugee engagement in Germany
Authors: Drouhot Lucas G. , Schönwälder Karen , Petermann Sören , Vertovec Steve 
Published: March 2023

AbstractDuring the 2015 “summer of welcome”, the mass arrival of refugees to Germany triggered widely publicised acts of pro-refugee solidarity among citizens. To date, scholarship has largely focused on hostility towards immigrants—including refugees-, and few studies shed light on the determinants of acceptance, so that refugee solidarity remains poorly understood. In this paper, we hypothesise that pro-refugee engagement does not just reflect humanitarian concerns, but also a more general acceptance of socio-cultural diversity in German society. Relying on unique survey data gathered in 2019–2020, we show that a majority of urban Germans indeed engaged in some form of support. We employ latent class analysis to capture the spectrum of diversity attitudes within the urban population. A series of regression models show that diversity attitudes are powerful predictors of pro-refugee engagement. Overall, our study helps advancing immigration scholarship by demonstrating that widespread support for refugees is strongly associated with more general diversity assent.