bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell exhaustion is associated with the risk of papillary thyroid carcinoma and can be a predictive and sensitive biomarker for diagnosis
Authors: Zhu Chumeng , Dai Yuechu , Zhang Hui , Ruan Yanyun , Zhou Yong , Dai Yingjie , Fan Lilong , Jia Tianjun , Lu Hongsheng , Chen Qi 
Published: August 2021

Abstract
Background
The incidence of papillary thyroid carcinoma (PTC) has been steadily increasing over the past decades. Hashimoto’s thyroiditis (HT) is the most common autoimmune disease, and is related to the pathogenesis of PTC. Programmed death-1 (PD-1) is currently used for the treatment of PTC, but there are very few studies on the clinical value of PD-1 in the diagnosis and targeted therapy of PTC.

Methods
The expression of T, B, NK cells and PD-1 in the peripheral blood of 132 patients with PTC (PTC group), 48 patients with nodular goiter (NG group) and 63 healthy subjects (HP group) were detected by flow cytometry. The expression of plasma T3, T4, FT3, FT4, TSH, TGAb and TPO was detected by chemiluminescence immunoassay. Among 132 PTC, 49 PTC&HT and 83 PTC&noHT were included. Among 48 NG, 10 NG&HT and 38 NG&noHT were included. The expressions of programmed death- ligand1(PD-L1) in tumor tissues of PTC group and thyroid tissues of NG group, PD-1 and CD3 in tumor infiltration lymphocyte (TIL) were detected by immunohistochemistry.

Results
The expression of FT3, TGAb, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC and NG was significantly higher than that in the HP group. Moreover, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ expression had significant differences between the PTC group and the NG group. In addition, the expression of TGAb, TPO, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was significantly higher than that in the PTC&noHT group. While, the expression of B cells, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was higher than that in NG&HT group. PD-1 showed a significant correlation with PTC lymph node metastasis. CD3+PD-1+ and CD3+CD4+PD-1+ was higher in N1 stage than in N0 stage. Immunohistochemical results showed that the expression of PD-1, CD3 and PD-L1 in PTC was significantly higher than that in NG.

Conclusions
T cell exhaustion might act as a biomarker for the differential diagnosis of PTC and NG. Patients with PTC&HT have obvious T cell exhaustion and increased expression of PD-1, PD-L1.Targeting the PD-1/PD-L1 pathway could be a new approach to prevent malignant transformation from HT to PTC&HT in the future.
Lack of in-brace x-rays in compliant AIS patients wearing full-time TLSO braces associates with failure
Authors: Alvarez Isabel , Poppino Kiley , Karol Lori , McIntosh Amy L. 
Published: August 2021

Abstract
Background
In-brace correction and brace compliance with thoraco-lumbo-sacral orthotic (TLSO) braces are associated with successful treatment of adolescent idiopathic scoliosis (AIS). This paper compares patients who had consistent radiographic documentation of in-brace correction to those who did not.

Methods
All skeletally immature (Risser 0-2) patients were treated for AIS (25-45°) with full-time TLSO braces that had compliance temperature monitors. All patients wore their braces at least 12 h a day. Brace failure was defined as curve progression to a surgical magnitude (≥ 50°). All patients were followed until brace discontinuation.

Results
Ninety patients (F 82, M 8) with an average age of 12.1 (10.1-15.0) years, Risser grade 0 (0-2), BMI percentile 48.5 (0.0-98.8), and daily brace wear of 16.5 (12.1-21.6) h/day were treated for 24.3 (8.0-66.6) months. Patients went through 1.7 (1-4) braces on average. Forty-two out of 90 (46.7%) patients had some amount of brace time with an unknown in-brace correction, which, on average, was 66.1% of their total treatment course (11.5-100). On univariate analysis, patients that did not have a repeat in-brace x-ray with major brace adjustments or new brace fabrication tended to be more skeletally immature (Risser 0 and tri-radiate open, p = 0.028), wear more braces throughout their treatment (2.0 vs 1.4, p < 0.001), were treated for a longer period of time (27 vs 22 months, p = 0.022), and failed bracing more often (47.6% vs 22.9%, p = 0.014).

Conclusions
Patients who did not have new in-brace x-rays with major brace adjustments and/or new brace fabrication were 3.1 (95% CI 1.2-7.6) times more likely to fail bracing than patients who were re-checked with new in-brace x-rays.

Trial registration
ClinicalTrials.gov—NCT02412137, initial registration date April 2015

Level of evidence
III
Functional microRNA targetome undergoes degeneration-induced shift in the retina
Authors: Chu-Tan Joshua A. , Cioanca Adrian V. , Feng Zhi-Ping , Wooff Yvette , Schumann Ulrike , Aggio-Bruce Riemke , Patel Hardip , Rutar Matt , Hannan Katherine , Panov Konstantin , Provis Jan , Natoli Riccardo 
Published: August 2021

Abstract
Background
MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration.

Methods
To identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein).

Results
Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage.

Conclusions
This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.
The impact of frailty Screening of Older adults with muLtidisciplinary assessment of those At Risk during emergency hospital attendance on the quality, safety and cost-effectiveness of care (SOLAR): a randomised controlled trial.
Authors: Leahy Aoife , McNamara Rachel , Reddin Catriona , Corey Gillian , Carroll Ida ,   The SOLAR team, O’Neill Aoife , Flannery Darragh , Devlin Collette , Barry Louise , MacCarthy Brian , Cummins Niamh , Shanahan Elaine , Shchetkovsky Denys , Ryan Damien , O’Connor Margaret , Galvin Rose 
Published: August 2021

Abstract
Background
Older people account for 25% of all Emergency Department (ED) admissions. This is expected to rise with an ageing demographic. Older people often present to the ED with complex medical needs in the setting of multiple comorbidities. Comprehensive Geriatric Assessment (CGA) has been shown to improve outcomes in an inpatient setting but clear evidence of benefit in the ED setting has not been established. It is not feasible to offer this resource-intensive assessment to all older adults in a timely fashion. Screening tools for frailty have been used to identify those at most risk for adverse outcomes following ED visit. The overall aim of this study is to examine the impact of CGA on the quality, safety and cost-effectiveness of care in an undifferentiated population of frail older people with medical complaints who present to the ED and Acute Medical Assessment Unit.

Methods
This will be a parallel 1:1 allocation randomised control trial. All patients who are ≥ 75 years will be screened for frailty using the Identification of Seniors At Risk (ISAR) tool. Those with a score of ≥ 2 on the ISAR will be randomised. The treatment arm will undergo geriatric medicine team-led CGA in the ED or Acute Medical Assessment Unit whereas the non-treatment arm will undergo usual patient care. A dedicated multidisciplinary team of a specialist geriatric medicine doctor, senior physiotherapist, specialist nurse, pharmacist, senior occupational therapist and senior medical social worker will carry out the assessment, as well as interventions that arise from that assessment. Primary outcomes will be the length of stay in the ED or Acute Medical Assessment Unit. Secondary outcomes will include ED re-attendance, re-hospitalisation, functional decline, quality of life and mortality at 30 days and 180 days. These will be determined by telephone consultation and electronic records by a research nurse blinded to group allocation.

Ethics and dissemination
Ethical approval was obtained from the Health Service Executive (HSE) Mid-Western Regional Hospital Research Ethics Committee (088/2020). Our lay dissemination strategy will be developed in collaboration with our Patient and Public Involvement stakeholder panel of older people at the Ageing Research Centre and we will present our findings in peer-reviewed journals and national and international conferences.

Trial registration
ClinicalTrials.gov NCT04629690. Registered on November 16, 2020
Impact of vitamin D level in diabetic people with peripheral neuropathy
Authors: Assy Mohammad H. , Draz Nashwa A. , Fathy Sabah E. , Hamed Mohammad G. 
Published: August 2021

Abstract
Background
Diabetes mellitus (DM) is a metabolic disease which is complicated by occurrence of diabetic peripheral neuropathy (DPN). Vitamin D deficiency contributes to the etiology and progression of type 2 DM and development of micro-vascular complications so in this study we assessed vitamin D level in diabetic patients to evaluate the association between vitamin D level and occurrence of diabetic neuropathy and to assess if there is relationship with certain subtypes of diabetic neuropathy. This case–control study was conducted on 80 type 2 diabetic patients divided into four groups equally. (A): Diabetic patients with painful diabetic neuropathy. (B): Diabetic patients with painless diabetic neuropathy. (C): Diabetic patients with painless neuropathy, but have neuropathic ulcer. (D): Diabetic patients without neuropathy. All patients underwent clinical, neurological examination and nerve conduction study. Then CBC and vitamin D were estimated in the studied groups.

Results
Vitamin D level among the studied painful diabetic neuropathy group (A) ranged from 5.3 to 40.5 ng/dl with mean 17.4 ± 10.9. 70% of them had deficient vitamin D level. In the painless diabetic neuropathy group (B), vitamin D level ranged from 6.5 to 35.5 ng/dl with mean 18.9 ± 8.49. 60% of them had deficient vitamin D level, while only 5% of the diabetic patients without neuropathy had deficient vitamin D level. There is significant negative correlation between vitamin D level and score of neuropathy where the lower vitamin D level the higher neuropathy score.

Conclusion
Lower vitamin D levels were found in diabetic patients with neuropathy especially those with painful neuropathy.
Trends in pattern of tuberculosis in Sharkia Governorate at Ministry of Health and Population Chest Hospitals from 2016 to 2019
Authors: El-Shabrawy Mohamed , Ibrahim Dalia A. , Walaa Mohammad , Hamed Mona S. , Abdelmoaty Ahmed A. , El-Shafei Maher , Alsadik Maha E. 
Published: August 2021

Abstract

Background
Tuberculosis is a communicable disease that is one of the leading cause of death from a single infectious agent (ranking above human immunodeficiency virus/acquired immunodeficiency syndrome). The aim of this work was to study the trend of applying the tuberculosis control program at the ministry of health and population chest hospitals, Sharkia, Egypt.

Results
This retrospective cross-sectional study was carried out using medical records from the tuberculosis registry at Ministry of Health and Population chest hospitals, Sharkia Governorate. The investigated variables included demographic characteristics, type of tuberculosis infection, and affected organs. All data were coded and statistically analyzed. A total 1404 cases of tuberculosis were notified between 2016 and 2019 with male predominance, where 67.1% were males and 32.9% were females. The highest number of tuberculosis patients was from the reproductive age groups. During the 4-year study period, the highest percentage of cases was new cases and the highest frequency of cases was during 2017 and the lowest frequency was during 2016. There was a decline in the total number of cases in 2018 and 2019 after sharp increase of total cases in 2017: pulmonary tuberculosis cases showed a sharp decline in 2017; however, there was an increase in extrapulmonary tuberculosis cases during 2017 then a slight decrease in 2018 and 2019. Of the pulmonary tuberculosis cases, 83.8% were smear-positive tuberculosis.

Conclusions
Pulmonary smear-positive and new cases were the most common among the recorded cases of tuberculosis. Productive age groups represented large percentage of the studied cases of tuberculosis. Lymph node and bones were the most common sites of extrapulmonary tuberculosis among reported cases in this study.
Incidence of completed suicide and suicide attempts in a global prospective study of Huntington's disease
Authors: van Duijn Erik , Fernandes A. Raquel , Abreu Daisy , Ware Jennifer J. , Neacy Eileen , Sampaio Cristina 
Published: August 2021

BackgroundRisk of death from suicide in Huntington's disease is notably elevated relative to that in the general population, although the incidence within HD populations has not been precisely defined. Robust incidence estimates of suicidal behavior can serve as references for HD therapeutic research and post-marketing surveillance to help evaluate the suicidality risk of novel therapeutics.AimsTo estimate the incidence rate of completed suicide and suicide attempt in the global, prospective HD cohort study Enroll-HD that records these events per protocol.MethodA total of 20 912 participants were available for analysis (HD gene-expansion carriers (HDGECs)n= 15 924; non-HDGECs n = 4988) representing a collective observation period of 53 390 participant-years. Each observed event was subject to clinical review and evaluation. We generated incidence rates (events per 100 000 person-years) for suicides and suicide attempts using all available data, as well as by year of study and geographical region. Proportionate mortality statistics for suicide and respective 95% confidence intervals were also generated.ResultsThe overall incidence rate of suicide in HDGECs was 72 per 100 000 person-years, and 8 per 100 000 person-years in non-HDGECs. Proportionate mortality attributable to suicide in HDGECs was 4.6%. For suicide attempts, the global overall incidence rate observed in HDGECs was 306–375 per 100 000 person-years, and 23–38 per 100 000 person-years in non-HDGECs.ConclusionsThe incidence estimates calculated here can be used as a reference to help evaluate drug safety and may also be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available.
COVID-19 Staff Wellbeing Survey: longitudinal survey of psychological well-being among health and social care staff in Northern Ireland during the COVID-19 pandemic
Authors: Jordan Julie-Ann , Shannon Ciaran , Browne Dympna , Carroll Emma , Maguire Jennifer , Kerrigan Keith , Hannan Sinead , McCarthy Thomas , Tully Mark A. , Mulholland Ciaran , Dyer Kevin F. W. 
Published: August 2021

Background
Throughout the coronavirus disease 2019 (COVID-19) pandemic, health and social care workers have faced unprecedented professional demands, all of which are likely to have placed considerable strain on their psychological well-being.

Aims
To measure the national prevalence of mental health symptoms within healthcare staff, and identify individual and organisational predictors of well-being.

Method
The COVID-19 Staff Wellbeing Survey is a longitudinal online survey of psychological well-being among health and social care staff in Northern Ireland. The survey included four time points separated by 3-month intervals; time 1 (November 2020; n = 3834) and time 2 (February 2021; n = 2898) results are presented here. At time 2, 84% of respondents had received at least one dose of a COVID-19 vaccine. The survey included four validated psychological well-being questionnaires (depression, anxiety, post-traumatic stress and insomnia), as well as demographic and organisational measures.

Results
At time 1 and 2, a high proportion of staff reported moderate-to-severe symptoms of depression (30–36%), anxiety (26–27%), post-traumatic stress (30–32%) and insomnia (27–28%); overall, significance tests and effect size data suggested psychological well-being was generally stable between November 2020 and February 2021 for health and social care staff. Multiple linear regression models indicated that perceptions of less effective communication within their organisation predicted greater levels of anxiety, depression, post-traumatic stress and insomnia.

Conclusions
This study highlights the need to offer psychological support to all health and social care staff, and to communicate with staff regularly, frequently and clearly regarding COVID-19 to help protect staff psychological well-being.
Excess mortality in depressive and anxiety disorders: The Lifelines Cohort Study
Authors: Oude Voshaar R. C. , Aprahamian I. , Borges M. K. , van den Brink R. H. S. , Marijnissen R. M. , Hoogendijk E. O. , van Munster B. , Jeuring H. W. 
Published: August 2021

Abstract

Background
To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status.

Methods
A cohort study (Lifelines) including 141,377 participants (18–93 years) which were followed-up regarding mortality for 8.6 years (range 3.0–13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models.

Results
The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56–3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15–4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty).

Conclusions
In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.
Factors Affecting the Adoption of Electronic Data Reporting and Outcomes Among Selected Central Cancer Registries of the National Program of Cancer Registries
Authors: Tangka Florence K. L. , Edwards Patrick , Pordell Paran , Wilson Reda , Blumenthal Wendy , Jones Sandy F. , Jones Madeleine , Beizer Jenny , Bernacet Amarilys , Cole-Beebe Maggie , Subramanian Sujha 
Published: August 2021

PURPOSE The CDC's National Program of Cancer Registries has expanded the use of electronic reporting to collect more timely information on newly diagnosed cancers. The adoption, implementation, and use of electronic reporting vary significantly among central cancer registries. We identify factors affecting the adoption of electronic reporting among these registries. METHODS Directors and data managers of nine National Program of Cancer Registries took part in separate 1-hour telephone interviews in early 2019. Directors were asked about their registry's key data quality goals; staffing, resources, and tools used to aid processes; their definition and self-perception of electronic reporting adoption; key helpers and challenges; and cost and sustainability implications for adoption of electronic reporting. Data managers were asked about specific data collection processes, software applications, electronic reporting adoption and self-perception, information technology infrastructure, and helpers and challenges to data collection and processing, data quality, and sustainability of approach. RESULTS Larger registries identified organizational capacity and technical expertise as key aides. Other help for implementing electronic reporting processes came from partnerships, funding availability, management support, legislation, and access to an interstate data exchange. Common challenges among lower adopters included lack of capacity at both registry and data source levels, insufficient staffing, and a lack of information technology or technical support. Other challenges consisted of automation and interoperability of software, volume of cases received, state political environment, and quality of data received. CONCLUSION Feedback from the formative evaluation yielded several useful solutions that can guide implementation of electronic reporting and help refine the technical assistance provided to registries. Our findings may help guide future process and economic evaluations of electronic reporting and identify best practices to strengthen registry operations.
Pigment pattern morphospace ofDaniofishes: evolutionary diversification and mutational effects
Authors: McCluskey Braedan M. , Liang Yipeng , Lewis Victor M. , Patterson Larissa B. , Parichy David M. 
Published: August 2021

ABSTRACTMolecular and cellular mechanisms underlying variation in adult form remain largely unknown. Adult pigment patterns of fishes in the genus Danio, which includes zebrafish, Danio rerio, consist of horizontal stripes, vertical bars, spots and uniform patterns, and provide an outstanding opportunity to identify causes of species level variation in a neural crest derived trait. Understanding pigment pattern variation requires quantitative approaches to assess phenotypes, yet such methods have been mostly lacking for pigment patterns. We introduce metrics derived from information theory that describe patterns and pattern variation in Danio fishes. We find that these metrics used singly and in multivariate combinations are suitable for distinguishing general pattern types, and can reveal even subtle phenotypic differences attributable to mutations. Our study provides new tools for analyzing pigment pattern in Danio and potentially other groups, and sets the stage for future analyses of pattern morphospace and its mechanistic underpinnings.