bluuebunny/crossref_metadata_2025 huggingface dataset:
The Flares of Low back pain with Activity Research Study (FLAReS): study protocol for a case-crossover study nested within a cohort study
Authors: Suri Pradeep , Tanus Adrienne D. , Torres Nikki , Timmons Andrew , Irimia Bianca , Friedly Janna L. , Korpak Anna , Daniels Clinton , Morelli Daniel , Hodges Paul W. , Costa Nathalia , Day Melissa A. , Heagerty Patrick J. , Jensen Mark P.
Published: April 2022

Background

Although it is generally accepted that physical activity and flares of low back pain (LBP) are related, evidence for the directionality of this association is mixed. The Flares of Low back pain with Activity Research Study (FLAReS) takes a novel approach to distinguish the short-term effects of specific physical activities on LBP flares from the cumulative effects of such activities, by conducting a longitudinal case-crossover study nested within a cohort study. The first aim is to estimate the short-term effects (≤ 24 h) of specific physical activities on LBP flares among Veterans in primary care in the Veterans Affairs healthcare system. The second aim is to estimate the cumulative effects of specific activities on LBP-related functional limitations at 1-year follow-up.

Methods

Up to 550 adults of working age (18—65 years) seen for LBP in primary care complete up to 36 “Scheduled” surveys over 1-year follow-up, and also complete unscheduled “Flare Window” surveys after the onset of new flares. Each survey asks about current flares and other factors associated with LBP. Surveys also inquire about activity exposures over the 24 h, and 2 h, prior to the time of survey completion (during non-flare periods) or prior to the time of flare onset (during flares). Other questions evaluate the number, intensity, duration, and/or other characteristics of activity exposures. Other exposures include factors related to mood, lifestyle, exercise, concurrent treatments, and injuries. Some participants wear actigraphy devices for weeks 1–4 of the study. The first aim will examine associations between 10 specific activity categories and participant-reported flares over 1-year follow-up. The second aim will examine associations between the frequency of exposure to 10 activity categories over weeks 1–4 of follow-up and long-term functional limitations at 12 months. All analyses will use a biopsychosocial framework accounting for potential confounders and effect modifiers.

Discussion

FLAReS will provide empirically derived estimates of both the short-term and cumulative effects of specific physical activities for Veterans with LBP, helping to better understand the role of physical activities in those with LBP.

Trial Registration

ClinicalTrials.govNCT04828330, registered April 2, 2021.
A novel model of traumatic femoral head necrosis in rats developed by microsurgical technique
Authors: Lv Yongxiang , Qiu Xing , Liu Gang , Wang Yunqing , Zhang Yazhong , Li Wenbo , Zhu Ziqiang
Published: April 2022

Background

Clinical angiography and vascular microperfusion confirmed that the femoral head retains blood supply after a collum femur fracture. However, no animal model accurately mimics this clinical situation. This study was performed to establish a rat model with retained viability of the femoral head and partial vasculature deprivation-induced traumatic caput femoris necrosis by surgery.

Methods

Thirty rats were randomly divided into three groups (n = 10 per group): normal group, sham-operated group (Control), and ischemic osteonecrosis group. The femoral head of the normal group of rats underwent a gross anatomy study and microangiography to identify femoral head blood supply. Microsurgical techniques were used to cauterize the anterior-superior retinacular vessels to induce osteonecrosis. Hematoxylin and Eosin (H&E) staining were used for femoral head histologic assessment. Morphologic assessments of the deformity in and trabecular bone parameters of the femoral head epiphysis were performed using micro-CT.

Results

The blood supply of the femoral head in rats primarily came from the anterior-superior, inferior, and posterior retinacular arteries. However, anterior-superior retinacular vasculature deprivation alone was sufficient in inducing femoral head osteonecrosis. H&E showed bone cell loss in nuclear staining, disorganized marrow, and trabecular structure. The bone volume (BV) decreased by 13% and 22% in the ischemic group after 5 and 10 weeks, respectively. The mean trabecular thickness (Tb.Th) decreased from 0.09 to 0.06 mm after 10 weeks. The trabecular spacing (Tb.Sp) increased from 0.03 to 0.05 mm after 5 weeks, and the epiphyseal height-to-diameter (H/D) ratio decreased.

Conclusions

We developed an original and highly selective rat model that embodied femoral head traumatic osteonecrosis induced by surgical anterior-superior retinacular vasculature deprivation.
Conversion of failed proximal femoral nail antirotation to uncemented or cemented femoral component fixation: a multicentre retrospective study with a median 10-year follow-up
Authors: Shi Wenbo , Zhang Yaodong , Xu Yangkai , Zeng Xianshang , Fu Hongjing , Yu Weiguang
Published: April 2022

Background

Conversion of a failed proximal femoral nail antirotation (PFNA) to a total hip arthroplasty (THA) is becoming increasingly universal. However, consensus has not been reached regarding which device (uncemented or hybrid THA) to use. The aim of this retrospective study was to compare the clinical outcomes of the conversion of failed PFNAs to uncemented versus hybrid THAs in the elderly population.

Methods

Consecutive elderly patients with prior failed PFNAs treated with uncemented or hybrid THA from January 2008 to December 2019 were retrospectively identified from two medical centres. The primary outcome was implant survival after THA revision; secondary outcomes were the functional outcomes assessed using the Harris Hip Score (HHS) and the incidence of key THA-related complications.

Results

A total of 236 patients (uncemented THA, n = 116; hybrid THA, n = 120) were eligible for this study. Kaplan–Meier survival curves demonstrated that the 10-year cumulative survival rates were 0.801 (95% confidence interval [CI], 0.783–0.852) in the uncemented THA group versus 0.925 (95% CI, 0.861–0.964) in the hybrid THA group (hazard ratio [HR] 0.36 [95% CI 0.24–0.56], p = 0.004). From the 72nd month after the revision to the last follow-up, functional outcomes differed considerably between cohorts (each p < 0.05), and the rate of key THA-related complications was comparable between cohorts (p = 0.004).

Conclusion

For elderly patients with prior failed PFNAs who experienced uncemented or hybrid THA, hybrid THA revision may provide a clinically significant improvement over uncemented THA revision with regard to implant survival, functional outcomes, and THA-related complications compared to uncemented THA revision.
Comparison of post-operative bleeding incidence in laser hemorrhoidoplasty with and without hemorrhoidal artery ligation: a double-blinded randomized controlled trial
Authors: Lim Shu Yu , Rajandram Retnagowri , Roslani April Camilla
Published: April 2022

Introduction

The effectiveness of hemorrhoidal artery ligation supplementation in reducing the incidence of post laser hemorrhoidoplasty bleeding has not been investigated.

Methods

This was a double-blind, randomized controlled trial comparing post-operative bleeding incidence in patients undergoing laser hemorrhoidoplasty (LHP) only versus LHP with hemorrhoidal artery ligation (HAL). Outcome measures included post-operative bleeding and its severity (i.e. verbal rating scale and Clavien-Dindo classification), presence of perianal swelling and pain score (visual analog score) at 1-day, 1-week and 6-weeks post-operatively. Statistical tests were performed and a value of P < 0.05 was considered significant.

Results

Seventy-six patients were randomized. There was no difference in median operating time. The bleeding incidence was highest at 1-week post-operatively (17.1%), and decreased to 1.3% at 6-weeks. There was no significant difference in bleeding incidence between both groups at any of the measured timepoints (P > 0.05). Severity of bleeding and incidence of post-operative perianal swelling were similar in both groups (P > 0.05). There was no difference in median pain scores.

Conclusion

Supplementation of HAL to LHP does not reduce the post-operative bleeding incidence. LHP is sufficient as a stand-alone procedure for treating haemorrhoids.

Trial registration: National Registration Number is NMRR-15-1112-24065 (IIR). The trial start date was 1st January 2015 with the ClinicalTrials.gov identifier and registration number as NCT04667169.
Relationship between skeletal bone mineral density and subjective masticatory difficulty
Authors: Hong Seok Woo , Kang Jeong-Hyun
Published: April 2022

Background

Masticatory ability is an essential factor for sustaining quality of life and social and systemic well-being, particularly in elderly. This study aimed to reveal the association between subjective masticatory difficulty and skeletal bone mineral density (BMD).

Methods

Data from the Korean National Health and Nutrition Examination Survey, which was conducted from 2008 to 2011 were analyzed. This study included 13,092 Koreans (5656 males, 7436 females) over 50 years of age. Masticatory difficulty was evaluated based on a self-reported questionnaire. Areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass were determined using dual-energy X-ray absorptiometry. Data about the sociodemographic characteristics, physical activity, number of teeth present, sum of decayed, missing, and filled permanent teeth (DMFT) index and Community Periodontal Index (CPI) were collected. Multivariate logistic regression analysis was conducted to analyze associations between subjective masticatory difficulty and BMD, adjusting for the confounding covariates.

Results

Significant differences were observed in the areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass accordance with the presence of subjective masticatory difficulty in both males and females. The number of teeth, DMFT, and CPI score did not show significant differences based on the presence of self-reported satisfaction of chewing performance in both males and females. Results from multivariate logistic regression demonstrated that the subjective masticatory difficulty showed significant interactions with skeletal BMD and the associations between masticatory satisfaction and BMD of the total hip and femoral neck were more prominent in females compared to those in males.

Conclusions

The skeletal BMD, particularly areal BMD of the femoral neck was significantly associated with subjective masticatory difficulty in elderly, especially in elder females.
Perceptions and attitude of women of Luderitz, Namibia on Pap smear and cervical cancer prevention
Authors: Hausiku Lucia , Kouame Koffi , Aboua Yapo Guillaume
Published: April 2022

Background

Cervical cancer is one of the leading malignancies globally and has taken third place in Namibia amongst women aged 15–44 years. Infection with the Human Immunodeficiency Virus (HIV) has been proven to increase women’s susceptibility to developing cervical carcinoma. Sadly, Namibia carries a twin burden of HIV and cervical cancer. Namibians are aware of HIV/AIDS, but remain poorly informed about cervical cancer. Furthermore, among those who are aware of the disease, low utilisation of screening tests have been reported.

Objective

The purpose was to explore perceptions and attitudes held by women about cervical cancer, reasons for low uptake of Pap smear testing amongst those who are aware of the malignancy as well as unearth motivation factors that has fuelled women to go for screening.

Methodology

A descriptive, cross-sectional study was conducted using convenience sampling as a sampling technique. The survey instrument used was a self-administered questionnaire. It consisted of both closed and open ended questions. A total of 136 women were surveyed.

Results and conclusion

The level of awareness for cervical cancer (92.6%) and Pap smear (93.4%) were high. Most were able to identify that Pap smear test is used for screening for pre-cancerous lesions. However, knowledge about the impact of a HIV positive status along with co infection with HPV as the leading causes for progression of invasive cervical carcinoma was not well known. Knowledge about the other risk factors such as multiple sexual partners (39.7%), early sex debut (34.9%) and smoking was poorly demonstrated. This suggests that a high awareness level does not necessarily translate into having a good perception or understanding of a disease. A good attitude towards screening was observed although less than half of the study population reported ever having a test done.
Medical teachers’ experience of emergency remote teaching during the COVID-19 pandemic: a cross-institutional study
Authors: Chan Enoch , Khong Mei Li , Torda Adrienne , Tanner Julian A. , Velan Gary M. , Wong Gordon T. C.
Published: April 2022

Background

The COVID-19 pandemic and the consequent social distancing measures caused unprecedented disruption for medical and healthcare education. This study examined medical teachers’ experience with emergency remote teaching during the pandemic and their acceptance of online teaching after the pandemic.

Methods

In this sequential mixed methods study, online surveys were disseminated to teachers (n = 139) at two Asia–Pacific medical schools to evaluate their experience with emergency remote teaching during the pandemic. Subsequently, in-depth interviews were conducted with teachers from both institutions (n = 13). Each interviewee was classified into an adopter category based on Rogers’ Diffusion of Innovations Theory. Interview transcripts were analyzed thematically, and the descriptive themes were mapped to broader themes partly based on the Technology Acceptance Model and these included: (i) perceived usefulness of online teaching, (ii) perceived ease of delivering online teaching, (iii) experience with institutional support and (iv) acceptance of online teaching after the pandemic.

Results

Our participants described accounts of successes with their emergency remote teaching and difficulties they experienced. In general, most participants found it difficult to deliver clinical skills teaching remotely and manage large groups of students in synchronous online classes. With regards to institutional support, teachers with lower technological literacy required just-in-time technical support, while teachers who were innovative in their online teaching practices found that IT support alone could not fully address their needs. It was also found that teachers’ acceptance of online teaching after the pandemic was influenced by their belief about the usefulness of online teaching.

Conclusions

This study demonstrated that our participants managed to adapt to emergency remote teaching during this pandemic, and it also identified a myriad of drivers and blockers to online teaching adoption for medical teachers. It highlights the need for institutes to better support their teaching staff with diverse needs in their online teaching.
Supporting medical students to support peers: a qualitative interview study
Authors: Graves Jane , Flynn Eleanor , Woodward-Kron Robyn , Hu Wendy C. Y.
Published: April 2022

Background

Students may be the first to recognise and respond to psychological distress in other students. Peer support could overcome medical student reluctance to seek help despite their high rates of mental ill-health. Yet, despite the adoption of peer support programs, there is little evidence of impact on students. Peer support programs may assume that medical students accept and view peer support positively. We explored these assumptions by asking students about their experiences and views on peer support.

Methods

Qualitative semi-structured interviews exploring peer support experiences and views on peer support were conducted with ten medical students at two contrasting medical schools. Informed by a constructivist stance, interview transcripts underwent thematic analysis.

Results

Three groups of themes were identified: participants’ experiences of peer support encounters, concerns about providing support, and views on students’ roles in peer support. Participants readily recalled signs of peer distress. Encounters were ad hoc, informal, and occurred within relationships based on friendship or by being co-located in the same classes or placements. Concerns about initiating and offering support included lack of expertise, maintaining confidentiality, stigma from a mental health diagnosis, and unclear role boundaries, with implications for acceptance of student roles in peer support.

Conclusions

Our study emphasised the centrality of social relationships in enabling or discouraging peer support. Relationships developed during medical studies may anticipate the collegial relationships between medical professionals. Nevertheless, only some students are willing to undertake peer support roles. We suggest different strategies for promoting informal peer support that can be offered by any student, to those promoting formal support roles for selected students. Future research focusing on the impact for both the students who receive, and on the students who provide peer support is called for.
From ideal to real: a qualitative study of the implementation of in situ interprofessional simulation-based education
Authors: Ju Mindy , Bochatay Naike , Robertson Kathryn , Frank James , O’Brien Bridget , van Schaik Sandrijn
Published: April 2022

Background

Despite the widespread adoption of interprofessional simulation-based education (IPSE) in healthcare as a means to optimize interprofessional teamwork, data suggest that IPSE may not achieve these intended goals due to a gap between the ideals and the realities of implementation.

Methods

We conducted a qualitative case study that used the framework method to understand what and how core principles from guidelines for interprofessional education (IPE) and simulation-based education (SBE) were implemented in existing in situ IPSE programs. We observed simulation sessions and interviewed facilitators and directors at seven programs.

Results

We found considerable variability in how IPSE programs apply and implement core principles derived from IPE and SBE guidelines with some principles applied by most programs (e.g., “active learning”, “psychological safety”, “feedback during debriefing”) and others rarely applied (e.g., “interprofessional competency-based assessment”, “repeated and distributed practice”). Through interviews we identified that buy-in, resources, lack of outcome measures, and power discrepancies influenced the extent to which principles were applied.

Conclusions

To achieve IPSE’s intended goals of optimizing interprofessional teamwork, programs should transition from designing for the ideal of IPSE to realities of IPSE implementation.
Clinical variation in the organization of clinical pathways in esophagogastric cancer, a mixed method multiple case study
Authors: Luijten J. C. H. B. M. , Vissers P. A. J. , Brom L. , de Bièvre M. , Buijsen J. , Rozema T. , Mohammad N. Haj , van Duijvendijk P. , Kouwenhoven E. A. , Eshuis W. J. , Rosman C. , Siersema P. D. , van Laarhoven H. W. M. , Verhoeven R. H. A. , Nieuwenhuijzen G. A. P. , Westerman M. J.
Published: April 2022

Background

Among esophagogastric cancer patients, the probability of having undergone treatment with curative intent has been shown to vary, depending on the hospital of diagnosis. However, little is known about the factors that contribute to this variation. In this study, we sought to understand the organization of clinical pathways and their association with variation in practice.

Methods

A mixed-method study using quantitative and qualitative data was conducted. Quantitative data were obtained from the Netherlands Cancer Registry (e.g., outpatient clinic consultations and diagnostic procedures). For qualitative data, thematic content analysis was performed using semi-structured interviews (n = 30), observations of outpatient clinic consultations (n = 26), and multidisciplinary team meetings (MDTM, n = 16) in eight hospitals, to assess clinicians’ perspectives regarding the clinical pathways.

Results

Quantitative analyses showed that patients more often underwent surgical consultation prior to the MDTM in hospitals associated with a high probability of receiving treatment with curative intent, but more often consulted with a geriatrician in hospitals associated with a low probability of such treatment. The organization of clinical pathways was analyzed quantitatively at three levels: regional, local, and patient levels. At a regional level, hospitals differed in terms of the number of patients discussed during the MDTM. At the local level, the revision of radiological images and restaging after neoadjuvant treatment varied. At the patient level, some hospitals routinely conduct fitness tests, whereas others estimated the patient’s physical fitness during an outpatient clinic consultation. Few clinicians performed a standard geriatric consultation in older patients to assess their mental fitness and frailty.

Conclusion

Surgical consultation prior to MDTM was more often conducted in hospitals associated with a high probability of receiving treatment with curative intent, whereas a geriatrician was consulted more often in hospitals associated with a low probability of receiving such treatment.
An exploratory survey study of disorder and its association with safety culture in four hospitals
Authors: Churruca Kate , Ellis Louise A. , Long Janet C. , Pomare Chiara , Liauw Winston , O’Donnell Caroline M. , Braithwaite Jeffrey
Published: April 2022

Background

Signs of disorder in neighbourhoods (e.g., litter, graffiti) are thought to influence the behaviour of residents, potentially leading to violations of rules and petty criminal behaviour. Recently, these premises have been applied to the hospital context, with physical and social disorder found to have a negative association with patient safety. Building on these results, the present study investigates whether physical and social disorder differ between hospitals, and their relationship to safety culture.

Methods

We conducted a cross sectional survey with Likert-style and open response questions administered in four Australian hospitals. All staff were invited to participate in the pilot study from May to September 2018. An analysis of variance (ANOVA) was used to examine differences in disorder by hospital, and hierarchical linear regression assessed the relationship of physical and social disorder to key aspects of safety culture (safety climate, teamwork climate). Open responses were analysed using thematic analysis to elaborate on manifestations of hospital disorder.

Results

There were 415 survey respondents. Significant differences were found in perceptions of physical disorder across the four hospitals. There were no significant differences between hospitals in levels of social disorder. Social disorder had a significant negative relationship with safety and teamwork climate, and physical disorder significantly predicted a poorer teamwork climate. We identified five themes relevant to physical disorder and four for social disorder from participants’ open responses; the preponderance of these themes across hospitals supported quantitative results.

Conclusions

Findings indicate that physical and social disorder are important to consider in attempting to holistically understand a hospital’s safety culture. Interventions that target aspects of physical and social disorder in a hospital may hold value in improving safety culture and patient safety.
Improved intention, self-efficacy and social influence in the workspace may help low vision service workers to discuss depression and anxiety with visually impaired and blind adults
Authors: van Munster Edine P. J. , van der Aa Hilde P. A. , Verstraten Peter , Heymans Martijn W. , van Nispen Ruth M. A.
Published: April 2022

Background

Depression and anxiety are common in visually impaired and blind adults, but often remain untreated in those who receive support from low vision service (LVS) organizations. This study aims to determine factors associated with discussing mental health by LVS workers.

Methods

A self-administered cross-sectional survey in one hundred LVS workers was performed. Data on current practice, symptom attribution, and determinants of the Integrated Change Model (i.e. predisposing and environmental factors, awareness, attitude, self-efficacy, social influence, confidence and barriers) were investigated. Multivariable logistic regression analysis was performed to determine predictors of discussing mental health problems in this population. Subsequently, internal validation was conducted using a bootstrapping method.

Results

Around 80% of the participants often discussed mental health with clients. Five factors were found to predict discussion of mental health: female gender (OR = 4.51; 95% confidence interval (CI) 0.98 to 21.61), higher education (OR = 3.39; CI 1.19 to 9.66), intention to discuss mental health problems (OR = 3.49; CI 1.20 to 10.15), higher self-efficacy (OR = 1.11; CI 1.02 to 1.20), and higher perceived social influence (OR = 1.15; CI 1.05 to 1.27). Good discrimination after internal validation was reflected by the area under the curve (0.850).

Conclusions

Previous studies indicate clients want healthcare providers to initiate discussions about mental health. However, still 20% of LVS workers do not discuss suspected depression or anxiety. In order to improve this, LVS organizations could address mental health as part of their care and provide training to ensure intention to discuss mental health problems, improve self-efficacy and create a supportive environment between colleagues.
Changed health behavior improves subjective well-being and vice versa in a follow-up of 9 years
Authors: Stenlund Säde , Koivumaa-Honkanen Heli , Sillanmäki Lauri , Lagström Hanna , Rautava Päivi , Suominen Sakari
Published: April 2022

Background

Previous research on health behavior and subjective well-being has mainly focused on interindividual differences or explored certain domains of health behavior. Good health behavior and subjective well-being at baseline can predict each other after a follow-up. In the present cohort study, we explored the outcomes of change for an individual i.e., how changed health behavior is reflected in subsequent subjective well-being and vice versa.

Methods

Data (n = 10,855) originates from a population-based Health and Social Support (HeSSup) study on working-age Finns in 2003 and 2012. A composite measure of health behavior included physical activity, dietary habits, alcohol consumption, and smoking status (range 0–4, worst–best) and a composite measure of subjective well-being (with reversed scoring) included three life assessments, i.e., interest, happiness, and ease in life, and perceived loneliness (range 4–20, best–worst). Different multiple linear regression models were used to study how changes in health behavior predict subjective well-being and the opposite, how changes in subjective well-being predict health behavior.

Results

A positive change in health behavior from 2003 to 2012 predicted better subjective well-being (i.e., on average 0.31 points lower subjective well-being sum score), whereas a negative change predicted poorer subjective well-being (i.e., 0.37 points higher subjective well-being sum score) (both: p < 0.001) compared to those study subjects who had no change in health behavior. Similarly, when a positive and negative change in subjective well-being was studied, these figures were 0.071 points better and 0.072 points worse (both: p < 0.001) health behavior sum score, respectively. When the magnitude of the effect of change was compared to the range of scale of the outcome the effect of health behavior change appeared stronger than that of subjective well-being.

Conclusion

Changes in health behavior and subjective well-being have long-term effects on the level of the other, the effect of the first being slightly stronger than vice versa. These mutual long-term benefits can be used as a motivator in health promotion on individual and societal levels.
Metastatic basal cell carcinoma of buccal mucosa: a report of a rare case
Authors: Kimura Taku , Sakata Ken-ichiro , Sato Jun , Ouchi Chisato , Ohga Noritaka , Yanagawa-Matsuda Aya , Hida Kyoko , Kitagawa Yoshimasa
Published: April 2022

Background

Basal cell carcinoma (BCC) is the most common cancer worldwide. Most of BCCs can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, metastasis is rarely observed. Metastatic BCCs generally have an aggressive phenotype and are refractory to conventional treatment.

Case presentation

We describe a rare case of BCC in which a series of local relapses culminated in metastasis into the oral cavity 10 years after the first diagnosis of cutaneous BCC. We performed surgical resection and postoperative radiotherapy in this patient; 11 months after the final course of radiotherapy, the BCC remains stable, and the patient continues to be monitored regularly.

Conclusions

Because metastatic BCC is refractory to current treatment and difficult to control, his treatment history and the pathohistological features of BCC had to be considered in posttreatment planning.
Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood
Authors: Wu Bang-Sheng , Chen Shu-Fen , Huang Shu-Yi , Ou Ya-Nan , Deng Yue-Ting , Chen Shi-Dong , Dong Qiang , Yu Jin-Tai
Published: April 2022

Background

Genome-wide association studies (GWAS) have revealed numerous loci associated with stroke. However, the underlying mechanisms at these loci in the pathogenesis of stroke and effective stroke drug targets are elusive. Therefore, we aimed to identify causal genes in the pathogenesis of stroke and its subtypes.

Methods

Utilizing multidimensional high-throughput data generated, we integrated proteome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and Bayesian colocalization analysis to prioritize genes that contribute to stroke and its subtypes risk via affecting their expression and protein abundance in brain and blood.

Results

Our integrative analysis revealed that ICA1L was associated with small-vessel stroke (SVS), according to robust evidence at both protein and transcriptional levels based on brain-derived data. We also identified NBEAL1 that was causally related to SVS via its cis-regulated brain expression level. In blood, we identified 5 genes (MMP12, SCARF1, ABO, F11, and CKAP2) that had causal relationships with stroke and stroke subtypes.

Conclusions

Together, via using an integrative analysis to deal with multidimensional data, we prioritized causal genes in the pathogenesis of SVS, which offered hints for future biological and therapeutic studies.
Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators
Authors: Huang Zi-xuan , Qu Peng , Wang Kan-kan , Zheng Jie , Pan Meng , Zhu Hai-qin
Published: April 2022

Pemphigus is an autoimmune skin disease. Ectopic lymphoid-like structures (ELSs) were found to be commonly present in the pemphigus lesions, presumably supporting in situ desmoglein (Dsg)-specific antibody production. Yet functional phenotypes and the regulators of Lymphoid aggregates in pemphigus lesions remain largely unknown. Herein, we used microarray technology to profile the gene expression in skin lesion infiltrating mononuclear cells (SIMC) from pemphigus patients. On top of that, we compared SIMC dataset to peripheral blood mononuclear cells (PBMC) dataset to characterize the unique role of SIMC. Functional enrichment results showed that mononuclear cells in skin lesions and peripheral blood both had over-represented IL-17 signaling pathways while neither was characterized by an activation of type I Interferon signaling pathways. Cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) results showed that naïve natural killer cells (NK cells) were significantly more abundant in pemphigus lesions, and their relative abundance positively correlated with B cells abundance. Meanwhile, plasma cells population highly correlated with type 1 macrophages (M1) abundance. In addition, we also identified a lncRNA LINC01588 which might epigenetically regulate T helper 17 cells (Th17)/regulatory T cells (Treg) balance via the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Here, we provide the first transcriptomic characterization of lesion infiltrating immune cells which illustrates a distinct interplay network between adaptive and innate immune cells. It helps discover new regulators of local immune response, which potentially will provide a novel path forward to further uncover pemphigus pathological mechanisms and develop targeted therapy.
The prevalence and genotype distribution of human papillomavirus among women in Guangxi, southern China
Authors: Wei Liuting , Ma Liping , Qin Lingyan , Huang Zhihu
Published: April 2022

Background

Human papillomavirus is a primary cause of cervical cancer and genital warts. HPV vaccine can prevent high-grade cervical lesions as well as cervical cancer. The aim of this study was to analyze the prevalence and genotype distribution of human papillomavirus among women in Guangxi before and after the HPV vaccine was approved for use in China.

Methods

From January 2016 to May 2021, 41,140 women were tested for HPV infection. HPV genotyping included 15 high-risk HPV (HR-HPV) and 6 low-risk HPV (LR-HPV) genotypes. Total prevalence, annual trend, and specific age group prevalence and genotype distribution were analyzed.

Results

The overall HPV infection rate was 18.10% among Guangxi women self-referred to clinic for gynecologic problems in southern China. During 2016–2018, the prevalence of HPV infection showed an upward trend, from 18.21% in 2016 to 21.99% in 2018, and later it showed a downward trend, from 18.35% in 2019 to 12.26% in May 2021. Pure HR-HPV genotypes (14.36%) were found in more infections than pure LR-HPV genotypes (2.77%) and mixed genotypes (0.97%). Two peaks of HPV infection were found in the ≤ 25 years (22.94%) and 56–65 years (21.25%) groups. The six most prevalent HR-HPV genotypes were HPV 52 (4.06%), 16 (2.70%), 58 (2.24%), 51 (1.87%), 39 (1.52%), and 53 (1.52%). The three most prevalent LR-HPV genotypes were HPV 6 (1.31%), CP8304 (1.01%), and 11 (0.82%). Infection with a single HR-HPV genotype was the most common type of infection, with an overall infection rate of 12.30%. Infection with two HPV genotypes was the most common multiple HR-HPV infection type, with an infection rate of 2.35%.

Conclusions

The cervical HPV infection rate of women in Guangxi is very high, and there is significant age specificity. There is a need to increase HPV vaccination of young people and the screening of middle-aged and elderly people.
Challenging the dogma to “always operate” acute hip fractures: a proof-of-concept pilot study for nonoperative management of undisplaced femoral neck fractures
Authors: Vinas-Rios Juan Manuel , Wölm Jan-Henning , Sellei Richard Martin , Ladenburger Andreas
Published: April 2022

Background

The notion that all acute hip fractures are a surgical entity requiring either surgical fracture fixation or hip replacement represents a historic dogma, particularly within the orthopaedic community of the United States. The present study from a European regional trauma center was designed to challenge the notion that stable and undisplaced femoral neck fractures represent an absolute indication for surgical management.

Methods

The purpose of this study was to investigate the hypothesis that stable and undisplaced femoral neck fractures of the Garden types 1 and 2 can be safely managed nonoperatively. A retrospective observational cohort study was carried out at a regional orthopaedic trauma center in Germany from January 1, 2016 to June 30, 2021. The inclusion criteria specified patients older than 18 years suffering a < 24 h, traumatic, femoral neck fracture Garden types 1 and 2. Exclusion criteria included Garden types 3 and 4 femoral neck fractures, pregnancy, active infection or previous surgery, tumor-associated fractures, medical history of femoral neck necrosis, vascular injury associated with femoral neck fractures, nerve injury associated to a femoral neck fracture and ≥ 24 h femoral neck fracture. The primary intention of this research was to identify deterioration of fracture retention with an ensuing unplanned trip to the operating room in femoral neck fractures Garden types 1 and 2. Secondary were included unplanned readmissions and complications such as surgical site infection.

Results

A total of 41 undisplaced femoral neck fractures (Garden types 1 and 2) were included in this study;n = 20 were in the resulting admission operatively treated (group 1) andn = 21 were treated conservatively. The mean age in group 1 was 76 years; women (70%). In group 2 it was 81 years with a female dominance (71.4%). Admission status: Garden types 1 and 2, group 1n = 13/7 and group 2n = 15/6. Subsequent femoral neck fracture displacement (Y/N) (in case of operation, before operation) group 1n = 14/6 and group 2n = 6/15.

Conclusion

According with our results, patients sustaining Garden type 1 femoral neck fractures, depending on age and comorbidities, should be treated conservatively with weight bearing and under physiotherapeutic instructions. In case of femoral neck fractures Garden type 2, a surgical treatment should be performed in order to avoid femoral neck fractures to slip after weight bearing by lacking of fracture impaction.
Verrucae pedis in children with juvenile idiopathic arthritis and other paediatric rheumatic diseases: a cross‐sectional study
Authors: Ferrari Jill
Published: April 2022

Background

Verrucae pedis (verrucae / VPs) are a common viral infection of the skin seen in children. There are limited studies of the prevalence, duration and impact of verrucae pedis in children who are immunosuppressed. The studies available suggest that, in these children, the warts are more widespread and are more long‐standing. The primary aim of this study was to determine the prevalence of verrucae pedis in children attending rheumatology clinics who may have some degree of immunosuppression due to their prescribed medication and compare this to the reported prevalence in the healthy population.

Method

Children attending out‐patient rheumatology appointments were recruited. The young people were aged between four and 17 years old. A visual inspection of both feet was used to identify potential verrucae. Diagnosis of a verruca pedis was confirmed on observation of the typical clinical features. The location, duration of presence, previous treatments, presence of verrucae in other family members and psychological impact was recorded.

Results

A total of 71 children were included. Of the group, 55 children had no verrucae present, 16 children had one or more verrucae. The prevalence of verrucae was 22.5%. Medication impacting on the immune system was prescribed in 80% of the group. There appeared to be no greater chance of having verrucae if taking immunosuppressive medication than compared to having no medication (OR = 1.1, 95%CI 0.26 to 4.48, p = 0.46). Children with verrucae tended to be between 9 and 12 years old. In total, 37.5% of the young people with verrucae had lesions reportedly present for 24 months or more. Two‐thirds of the participants were not concerned about verrucae being present and most participants with a verruca were not aware of what a verruca was, but despite this the majority of participants (81%) had sought treatment for the verrucae.

Conclusion

Children with Juvenile Idiopathic Arthritis and other rheumatic conditions have no greater prevalence of verrucae compared to the general population. The verrucae present were of a similar clinical type and did not seem to be more widespread or have atypical features, which has been reported in other immunocompromised populations. The percentage of lesions remaining beyond 24 months was found to be slightly greater than has been reported in other healthy populations. The children in this study seemed to be less emotionally concerned about their verrucae, despite this most families had sought treatment for the verrucae.
Earlier point-of-care ultrasound, shorter length of stay in patients with acute flank pain
Authors: Wang Pei-Hsiu , Chen Jia-Yu , Ling Dean-An , Lee An-Fu , Ko Ying-Chih , Lien Wan-Ching , Huang Chien-Hua
Published: April 2022

Background

The effects of early integration of point-of-care ultrasound (PoCUS) into patient care are uncertain. This study aims to investigate the effects of early PoCUS on patients with acute flank pain.

Methods

Adult non-traumatic patients with acute flank pain receiving PoCUS were enrolled. Expert physicians reviewed the medical records and made the “final diagnosis” for the cause of acute flank pain. The primary outcome was the relationship between the door to ultrasound (US) time and length of stay (LOS). The secondary outcomes included the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the sonographic diagnosis, compared with the final diagnosis.

Results

Eight hundred and eighty-eight patients were included in the analysis. Patients receiving early PoCUS (≤120 min) had a shorter LOS (128 vs. 217 min, p < 0.0001). Patients in the late POCUS group (> 120 min) had a trend to receive more CT scans. The disease distribution, sensitivity, specificity, PPV, and NPV were similar in patients receiving early or late PoCUS for target diagnoses. After adjusting for the confounders, early PoCUS (OR, 2.77, 95% CIs, 1.93–3.98) had a positive impact on shorter LOS. In addition, the effect of early PoCUS became more prominent (OR, 4.91, 95% CIs, 3.39–7.13) on LOS in less than 3 h.

Conclusions

Early integration of PoCUS is significantly related to shorter LOS in patients with acute flank pain without increasing morbidity and mortality. Our results suggested “PoCUS early” in these patients to possibly alleviate emergency department crowding.

Trial registration NCT04149041 at the ClinicalTrial.gov.
Identifying clinical subtypes in sepsis-survivors with different one-year outcomes: a secondary latent class analysis of the FROG-ICU cohort
Authors: Soussi Sabri , Sharma Divya , Jüni Peter , Lebovic Gerald , Brochard Laurent , Marshall John C. , Lawler Patrick R. , Herridge Margaret , Ferguson Niall , Del Sorbo Lorenzo , Feliot Elodie , Mebazaa Alexandre , Acton Erica , Kennedy Jason N. , Xu Wei , Gayat Etienne , Dos Santos Claudia C. ,   the FROG-ICU, Soussi Sabri , Mebazaa Alexandre , Gayat Etienne ,   CCCTBG trans-trial group study for InFACT - the International Forum for Acute Care Trialists, Soussi Sabri , Brochard Laurent , Marshall John C. , Herridge Margaret , Dos Santos Claudia C.
Published: April 2022

Background

Late mortality risk in sepsis-survivors persists for years with high readmission rates and low quality of life. The present study seeks to link the clinical sepsis-survivors heterogeneity with distinct biological profiles at ICU discharge and late adverse events using an unsupervised analysis.

Methods

In the original FROG-ICU prospective, observational, multicenter study, intensive care unit (ICU) patients with sepsis on admission (Sepsis-3) were identified (N = 655). Among them, 467 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct sepsis-survivors clinical classes using readily available data at ICU discharge. The primary endpoint was one-year mortality after ICU discharge.

Results

At ICU discharge, two distinct subtypes were identified (A and B) using 15 readily available clinical and biological variables. Patients assigned to subtype B (48% of the studied population) had more impaired cardiovascular and kidney functions, hematological disorders and inflammation at ICU discharge than subtype A. Sepsis-survivors in subtype B had significantly higher one-year mortality compared to subtype A (respectively, 34% vs 16%, p < 0.001). When adjusted for standard long-term risk factors (e.g., age, comorbidities, severity of illness, renal function and duration of ICU stay), subtype B was independently associated with increased one-year mortality (adjusted hazard ratio (HR) = 1.74 (95% CI 1.16–2.60); p = 0.006).

Conclusions

A subtype with sustained organ failure and inflammation at ICU discharge can be identified from routine clinical and laboratory data and is independently associated with poor long-term outcome in sepsis-survivors.

Trial registration NCT01367093; https://clinicaltrials.gov/ct2/show/NCT01367093.

Graphical Abstract
Predicting RNA splicing from DNA sequence using Pangolin
Authors: Zeng Tony , Li Yang I
Published: April 2022

Recent progress in deep learning has greatly improved the prediction of RNA splicing from DNA sequence. Here, we present Pangolin, a deep learning model to predict splice site strength in multiple tissues. Pangolin outperforms state-of-the-art methods for predicting RNA splicing on a variety of prediction tasks. Pangolin improves prediction of the impact of genetic variants on RNA splicing, including common, rare, and lineage-specific genetic variation. In addition, Pangolin identifies loss-of-function mutations with high accuracy and recall, particularly for mutations that are not missense or nonsense, demonstrating remarkable potential for identifying pathogenic variants.