bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of previous surgery on scaphoid nonunion reconstruction: a retrospective study of 95 cases
Authors: Diehm Yannick F. , Thomé Julia , Siegwart Laura C. , Bickert Berthold , Kneser Ulrich , Hirche Christoph
Published: June 2022

We retrospectively compared 64 scaphoid reconstructions in cases that had not undergone previous surgery with 31 cases in which previous surgery had been performed. The characteristics of the groups were similar except that there were more smokers in the group without previous surgery and a more frequent use of vascularized bone grafts in the group with previous surgery. At final follow-up, 66 and 65 months, respectively, after reconstruction, union incidence was 89% and 90%. In patients with previous surgery, grip strength was higher but not when expressed in percent of the contralateral hand. There were no differences in pinch strength, active wrist motion, functional scores, carpal height or scapholunate angle. We conclude that repeat surgery to the scaphoid did not seem to be a major risk factor for the overall outcomes, keeping in mind that a vascularized bone graft was more frequently used for secondary reconstructions.

Level of evidence: III
Trends and projections in sexually transmitted infections in people aged 45 years and older in England: analysis of national surveillance data
Authors: Camacho C , Camacho EM , Lee DM
Published: June 2022

Aims:

We describe the epidemiology of sexually transmitted infections (STIs) and HIV in people aged ⩾45 years in England and provide future projections about the burden of STIs in this age group.

Methods:

Analysis of national surveillance data in England from 2014 to 2019 for chlamydia, gonorrhoea, herpes, syphilis, anogenital warts and HIV was carried out. Time trends were assessed by the Poisson regression and reported using incidence rate ratios (IRRs). Two scenarios were modelled to predict the number of new STI diagnoses and associated costs in 2040.

Results:

In 2019, there were 37,692 new STI diagnoses in people ⩾45 years in England. Between 2014 and 2019, there was a significant increase in the rate of new STI diagnoses in men (IRR = 1.05, p = .05) and those aged 45–64 years (IRR = 1.04, p = .05). Absolute numbers of new STI diagnoses in men who have sex with men increased by 76% between 2014 and 2019 (IRR = 1.15, p < .001). In adults aged ⩾50 years, the number of episodes of care for HIV increased over time (age = 50–64 years, IRR = 1.10; age = 65+ years, IRR = 1.13; p <.001). The modelled scenarios predicted an increase in STI diagnoses and costs in older people by 2040.

Conclusion:

STI rates in England are increasing in people aged ⩾45 years. The population is ageing and older people will contribute an increasing burden to STI costs if this trend continues. The reasons for this trend are not fully understood and further longitudinal epidemiological research is needed. Sexual health promotion campaigns and healthcare interventions targeted at older people should be prioritised.
Development of a multiagency protocol to support people with No Recourse to Public Funds in Wolverhampton (UK)
Authors: Reddy SM , Mahmood H
Published: June 2022

Background:

No Recourse to Public Funds (NRPF) status is applied to individuals and families that are subject to immigration control, resulting in them having restricted access to state-funded benefits within England. NRPF is a public health risk as it increases the risk of destitution among vulnerable migrants.

Aims:

The aim of this study was to engage with public and voluntary sector staff within Wolverhampton working with people with a NRPF status to develop and create an easily accessible guide (‘protocol’) to help facilitate identification of appropriate cross-sector interventions and support.

Methods:

Data were collected via an online survey as well as face-to-face semi-structured interviews with local NRPF stakeholders.

Results:

Four themes emerged from the thematic analysis of participant responses: understanding NRPF statuses, varying support requirements, poor communication and awareness of vulnerabilities. Currently, in England, there does not appear to be a standardised localised protocol which can be used to reduce the complexities and confusion encountered by public and voluntary sectors who support people with NRPF status.

Conclusion:

The findings from this study have allowed the Wolverhampton NRPF to create an online information resource that includes training events to raise the awareness of NRPF, as well as the development of a localised multiagency protocol that has better equipped it to support and safeguard people with NRPF.
Agglomerations around natural resources in the hospitality industry: Balancing growth with the Sustainable Development Goals
Authors: Aragón-Correa J Alberto , de la Torre-Ruiz José M , Vidal-Salazar M Dolores
Published: June 2022

Many tourism agglomerations are situated near natural resources, which implies a need to balance business growth with environmental preservation. Our analysis of the location decisions of 295 luxury beach hotels in Spain between 1960 and 2015 reveals two main findings. First, we confirm the positive relationship between the existence of demand-related urbanization services around natural resources and the attractiveness of agglomerations to new entrants. Second, we find that an agglomeration’s attractiveness negatively affects the density of firms in the agglomeration if that attractiveness hinders firms’ access to the same natural resources. Our results contribute to the strategy literature on agglomerations and provide a better understanding of how the tourism industry can work toward achieving the sustainable development goals (SDGs).

JEL CLASSIFICATION: L83, M13, M14, Q50, Q26, R30
Effect of Decompression Craniectomy on Survival and Functional Outcome in Patients with COVID-19 and Malignant Infarct: A Retrospective Cohort Study and Review of Literature
Authors: Sudheer Pachipala , Gomathy Saranya B. , Agarwal Ayush , Vishnu Venugopalan Y. , Pandit Awadh K. , Deepti Vibha , Bhatia Rohit , Srivastava Padma M. V.
Published: June 2022

Background and objective

Amongst the varied neurological manifestations of COVID-19 infection, stroke is one of the common complications. A large portion of patients had large vessel occlusion (LVO) which increases the risk of malignant cerebral infarction requiring decompressive craniectomy. The impact of COVID-19, however, on decompressive craniectomy is not well described. Through this study, we aim to study the impact of decompressive craniectomy in COVID-19 patients presented to our tertiary care hospital.

Material and methods

Data of all acute ischemic stroke patients who tested COVID positive during the study period was collected. From among them, patients requiring decompressive craniectomy were included. The demographic, clinico-radiological parameters related to stroke, treatment received, outcome and complications were noted. In addition, data from all case reports and case series published on patients with COVID-19, who had developed ischemic stroke and underwent decompression craniectomy was collected and systematically reviewed.

Results

Twenty-seven stroke patients tested positive for COVID-19 infection, out of whom five patients underwent decompression hemicraniectomy in view of neurologic deterioration. The review of literature yielded 453 abstracts. After reading the full text of 69 articles, 12 studies on 15 patients finally met our inclusion criteria and were included in the systematic review. The mortality rate was 40% among stroke patients requiring decompressive craniectomy in COVID-19 patients. The mortality rate and functional outcomes of this cohort are comparable to the pre-pandemic period.

Conclusion

Decompressive craniectomy is a life-saving procedure in COVID-19 patients with malignant infarctions similar to patients in the pre-COVID-19 era.
Predictors of sleep disordered breathing in children with Down syndrome: a systematic review and meta-analysis
Authors: Hanna Nardin , Hanna Youstina , Blinder Henrietta , Bokhaut Julia , Katz Sherri L.
Published: June 2022

Children with Down syndrome are at increased risk of sleep disordered breathing (SDB). SDB is associated with significant morbidity including neurocognitive impairment, cardiometabolic disease and systemic inflammation. The identification of clinical markers that may predict SDB is critical in facilitating early diagnosis and treatment, and ultimately, preventing morbidity. The objective of this systematic review was to identify predictors of SDB in patients with Down syndrome. A search was conducted using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Cumulative Index to Nursing and Allied Health Literature. A meta-analysis was performed according to the Meta-analyses of Observational Studies in Epidemiology checklist. Our review of the literature identified inconsistent associations between a variety of variables and SDB in children with Down syndrome, although the quality of evidence was poor. Meta-analysis of age and sex identified that children with OSA were older than those without OSA, and there was a similar risk of OSA in males and females, although risk favoured males. Currently, the American Academy of Pediatrics guidelines recommend that children with Down syndrome undergo polysomnography by the age of 4 years. Our review supports the recommendation for routine screening of children with Down syndrome. However, results from our meta-analysis suggest a need for longitudinal screening to diagnose children who may develop SDB as they get older.
Impact of 5HydroxyMethylCytosine (5hmC) on reverse/direct association of cell-cycle, apoptosis, and extracellular matrix pathways in gastrointestinal cancers
Authors: Moravveji Sayyed Sajjad , Khoshbakht Samane , Mokhtari Majid , Salimi Mahdieh , Lanjanian Hossein , Nematzadeh Sajjad , Torkamanian-Afshar Mahsa , Masoudi-Nejad Ali
Published: June 2022

Background

Aberrant levels of 5-hydroxymethylcytosine (5-hmC) can lead to cancer progression. Identification of 5-hmC-related biological pathways in cancer studies can produce better understanding of gastrointestinal (GI) cancers.

We conducted a network-based analysis on 5-hmC levels extracted from circulating free DNAs (cfDNA) in GI cancers including colon, gastric, and pancreatic cancers, and from healthy donors. The co-5-hmC network was reconstructed using the weighted-gene co-expression network method. The cancer-related modules/subnetworks were detected. Preservation of three detected 5-hmC-related modules was assessed in an external dataset. The 5-hmC-related modules were functionally enriched, and biological pathways were identified. The relationship between modules was assessed using the Pearson correlation coefficient (p-value < 0.05). An elastic network classifier was used to assess the potential of the 5-hmC modules in distinguishing cancer patients from healthy individuals. To assess the efficiency of the model, the Area Under the Curve (AUC) was computed using five-fold cross-validation in an external dataset.

Results

The main biological pathways were the cell cycle, apoptosis, and extracellular matrix (ECM) organization. Direct association between the cell cycle and apoptosis, inverse association between apoptosis and ECM organization, and inverse association between the cell cycle and ECM organization were detected for the 5-hmC modules in GI cancers. An AUC of 92% (0.73–1.00) was observed for the predictive model including 11 genes.

Conclusion

The intricate association between biological pathways of identified modules may reveal the hidden significance of 5-hmC in GI cancers. The identified predictive model and new biomarkers may be beneficial in cancer detection and precision medicine using liquid biopsy in the early stages.
Transcriptome analysis of SerpinB2-deficient breast tumors provides insight into deciphering SerpinB2-mediated roles in breast cancer progression
Authors: Piao Yin Ji , Kim Hoe Suk , Han Wonshik , Moon Woo Kyung
Published: June 2022

Background

SerpinB2 is highly expressed in immune and tumor cells and is involved in multiple biological functions, including cell survival and remodeling for disease progression. This study prepared SerpinB2-deficient mice and analyzed the differentially expressed genes (DEGs) to determine if loss of this protein delays mammary tumor progression.

Results

A total of 305 DEGs (75 upregulated and 230 downregulated; > 1.5-fold difference,P < 0.05) were identified in SB2−/−;PyMT tumors compared with PyMT tumors. The DEGs were mainly involved in immune and inflammatory responses related to T cell differentiation, IFN-γ production, and lymphocyte chemotaxis based on 61 enriched GO terms, hierarchical clustering, KEGG pathways, and a functionally grouped annotation network. The significantly changed DEGs (Anxa3, Ccl17, Cxcl13, Cxcr3, IFN-γ, Nr4a1, and Sema3a) annotated with at least two GO categories in SB2−/−;PyMT tumors was validated by qRT-PCR.

Conclusions

SerpinB2 deficiency alters the expression of multiple genes in mammary tumors, which might cause a delay in PyMT-induced mammary tumor progression.
Predictors of patient safety activities among registered nurses and nurse aides in long-term care facilities: cross-sectional study
Authors: Lee Youran , Cho Eunhee
Published: June 2022

Background

In Korea, nurse aides (NAs) are legally permitted as substitutes for registered nurses (RNs) in long-term care (LTC) facilities, even though they have very different levels of education and qualification standards. Many studies in hospitals have shown better hospital nurse staffing, more educated nurses, and improved nurse work environments have been associated with lower hospital mortality and length of stay. There is research showing that a higher percentage of RNs with a bachelor’s degree corresponded to lower incidence rates of pressure ulcers in Korean LTC facilities. This study aimed to explore the factors that influence patient safety activities of the RNs and NAs working in LTC facilities and to identify the relationship between patient safety culture (PSC) and patient safety activities.

Methods

This study is a descriptive cross-sectional survey. The study participants were conveniently collected from 88 RNs and 71 NAs who worked at 33 LTC facilities for more than three months. The patient safety activities tool was developed by the researchers for residents of LTC facilities based on the tools developed by Park et al. (2012) for hospital nurses and the patient safety goals of the Joint Commission. The questionnaires were collected by email or mobile application and kept confidential. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficients, and multiple regression analysis.

Results

The mean scores of PSC and patient safety activities were 4.03 ± 0.51 points and 4.29 ± 0.49 points out of 5, respectively. There was significant correlation between PSC and patient safety activities (r = .23, p = .004). Factors influencing patient safety activities among RNs and NAs in LTC facilities were RNs (β = .377, p < .001), organizational system of PSC (β = .314, p < .010), and work shift type (fixed night shift, on-call, 24-h shift) (β = -.264, p = .004), which explained about 36.0% of total variance (F = 5.69, p < .001).

Conclusion

The findings indicate that it is necessary to mandate RNs instead of NAs to enhance residents’ safety in LTC facilities. Additionally, the importance of an organizational safety system and effective working shift types to prevent residents’ safety accidents in LTC facilities is indicated.
Circulating lymphocyte subsets are prognostic factors in patients with nasopharyngeal carcinoma
Authors: Zhu Jing , Fang Ruhua , Pan Zhiwen , Qian Xu
Published: June 2022

Background

Nasopharyngeal carcinoma (NPC) is a geographically and racially variable disease that has a high incidence in Southeast China. According to previous studies on tumor immunity, we compared multiple clinical parameters and blood indexes with outcomes regarding to Epstein-Barr virus (EBV) status in NPC patients.

Methods

According to the EBV load at diagnosis, 220 NPC patients who received concurrent chemoradiotherapy (CRT) were divided into two groups: EBV DNA ≥ 1500 copies/mL and EBV DNA < 1500 copies/mL, respectively. We compared clinical parameters with peripheral blood mononuclear cells, lymphocyte subsets and biochemical indexes. We also analyzed distant metastases and the overall survival rate regarding to these characteristics.

Results

In most cases, the two groups showed the same trends. Most blood indexes were decreased during CRT and the decrease of the absolute count was more significant than the percentage. Patients with younger age showed the higher CD3+ and CD3 + CD8+ percentages. Patients whose EBV DNA ≥ 1500 copies/mL showed a higher N classification than those with EBV DNA < 1500 copies/mL at first diagnosis. Within patients with EBV DNA ≥ 1500 copies/mL, a higher CD3 + CD8+ percentage or lower CD3-CD56+ percentage had better OS rates, and the CD3 + CD8+ percentage was an independent prognostic factor by multivariate survival analyses.

Conclusions

CRT caused an overall decrease of blood cells in NPC patients. Among all the blood indexes, the CD3 + CD8+ percentage showed a correlation with age and was an independent prognostic factor in patients with EBV DNA ≥ 1500 copies/mL at first diagnosis, which is worthy for further large cohort study.
Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer
Authors: Li Jian-Di , Farah Abdirahman Ahmed , Huang Zhi-Guang , Zhai Gao-Qiang , Wang Rui-Gong , Liu Jia-Lin , Wang Qin-Jie , Zhang Guan-Lan , Lei Zi-Long , Dang Yi-Wu , Li Sheng-Hua
Published: June 2022

Background

Pituitary tumor transforming gene-1 (PTTG1) transcription factor is identified as carcinogenic and associated with tumor invasiveness, but its role in bladder cancer (BLCA) remains obscure. This research is intended to analyze the aberrant expression and clinical significance of PTTG1 in BLCA, explore the relationship between PTTG1 and tumor microenvironment characteristics and predict its potential transcriptional activity in BLCA tissue.

Methods

We compared the expression discrepancy of PTTG1 mRNA in BLCA and normal bladder tissue, using the BLCA transcriptomic datasets from GEO, ArrayExpress, TCGA, and GTEx. In-house immunohistochemical staining was implemented to determine the PTTG1 protein intensity. The prognostic value of PTTG1 was evaluated using the Kaplan-Meier Plotter. CRISPR screen data was utilized to estimate the effect PTTG1 interference has on BLCA cell lines. We predicted the abundance of the immune cells in the BLCA tumor microenvironment using the microenvironment cell populations-counter and ESTIMATE algorithms. Single-cell RNA sequencing data was applied to identify the major cell types in BLCA, and the dynamics of BLCA progression were revealed using pseudotime analysis. PTTG1 target genes were predicted by CistromeDB.

Results

The elevated expression level of PTTG1 was confirmed in 1037 BLCA samples compared with 127 non-BLCA samples, with a standardized mean difference value of 1.04. Higher PTTG1 expression status exhibited a poorer BLCA prognosis. Moreover, the PTTG1 Chronos genetic effect scores were negative, indicating that PTTG1 silence may inhibit the proliferation and survival of BLCA cells. With PTTG1 mRNA expression level increasing, higher natural killer, cytotoxic lymphocyte, and monocyte lineage cell infiltration levels were observed. A total of four candidate targets containing CHEK2, OCIAD2, UBE2L3, and ZNF367 were determined ultimately.

Conclusions

PTTG1 mRNA over-expression may become a potential biomarker for BLCA prognosis. Additionally, PTTG1 may correlate with the BLCA tumor microenvironment and exert transcriptional activity by targeting CHEK2, OCIAD2, UBE2L3, and ZNF367 in BLCA tissue.
Prognostic analysis of E2F transcription factors E2F1 and E2F3 in four independent pediatric neuroblastoma cohorts
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu , Zhang Ji
Published: June 2022

Background

Previously, we had analyzed the prognosis of E2F transcription factors across adult tumor types. However, the expressions and prognosis of E2F transcription factors in pediatric neuroblastoma have not yet been fully studied.

Methods

The prognosis of E2F transcription factors was determined in four independent pediatric neuroblastoma cohorts from Therapeutically Applicable Research to Generate Effective Treatments (TARGET), Gene Expression Omnibus (GEO) and European ArrayExpres datasets using Kaplan–Meier and cox regression analysis.

Results

E2F regulated gene set was associated with the event free survival and the overall survival of neuroblastoma. E2F1 and E2F3 were prognostic factors in all four independent pediatric neuroblastoma cohorts. Over-expressions of E2F1 or E2F3 were correlated with the shorted event free survival and overall survival of neuroblastoma. Expression levels of E2F1 and E2F3 were higher in neuroblastoma patients with MYCN amplification or age at diagnosis ≥ 18 months. Moreover, the prognostic significance of E2F1 or E2F3 in neuroblastoma was independent of MYCN amplification and age of diagnosis. Combinations of E2F1, E2F3 with MYCN amplification or age of diagnosis achieved better prognosis of neuroblastoma. Identification of 234 genes were associated with E2F1 and E2F3 expressions in neuroblastoma and those genes were significantly enriched in cell cycle signaling pathway. Also, higher scores of cell cycle signaling pathway were correlated with the adverse prognosis of neuroblastoma.

Conclusions

E2F transcription factors E2F1 and E2F3 were prognostic makers of neuroblastoma.
Effectiveness of a healthcare-based mobile intervention on sedentary patterns, physical activity, mental well-being and clinical and productivity outcomes in office employees with type 2 diabetes: study protocol for a randomized controlled trial
Authors: Alòs Francesc , Colomer Mª. Àngels , Martin-Cantera Carlos , Solís-Muñoz Montserrat , Bort-Roig Judit , Saigi I. , Chirveches-Pérez E. , Solà-Gonfaus Mercè , Molina-Aragonés Josep Maria , Puig-Ribera Anna
Published: June 2022

Background

Prolonged sedentary time is associated with an increased incidence of chronic disease including type 2 diabetes mellitus (DM2). Given that occupational sedentary time contributes significantly to the total amount of daily sedentariness, incorporating programmes to reduce occupational sedentary time in patients with chronic disease would allow for physical, mental and productivity benefits. The aim of this study is to evaluate the short-, medium- and long-term effectiveness of a mHealth programme for sitting less and moving more at work on habitual and occupational sedentary behaviour and physical activity in office staff with DM2. Secondary aims. To evaluate the effectiveness on glycaemic control and lipid profile at 6- and 12-month follow-up; anthropometric profile, blood pressure, mental well-being and work-related post-intervention outcomes at 3, 6 and 12 months.

Methods

Multicentre randomized controlled trial. A sample size of 220 patients will be randomly allocated into a control (n = 110) or intervention group (n = 110), with post-intervention follow-ups at 6 and 12 months. Health professionals from Spanish Primary Health Care units will randomly invite patients (18–65 years of age) diagnosed with DM2, who have sedentary office desk-based jobs. The control group will receive usual healthcare and information on the health benefits of sitting less and moving more. The intervention group will receive, through a smartphone app and website, strategies and real-time feedback for 13 weeks to change occupational sedentary behaviour. Variables: (1) Subjective and objective habitual and occupational sedentary behaviour and physical activity (Workforce Sitting Questionnaire, Brief Physical Activity Assessment Tool, activPAL3TM); 2) Glucose, HbA1c; 3) Weight, height, waist circumference; 4) Total, HDL and LDL cholesterol, triglycerides; (5) Systolic, diastolic blood pressure; (6) Mental well-being (Warwick-Edinburgh Mental Well-being); (7) Presenteeism (Work Limitations Questionnaire); (8) Impact of work on employees´ health, sickness absence (6th European Working Conditions Survey); (9) Job-related mental strain (Job Content Questionnaire). Differences between groups pre- and post- intervention on the average value of the variables will be analysed.

Discussion

If the mHealth intervention is effective in reducing sedentary time and increasing physical activity in office employees with DM2, health professionals would have a low-cost tool for the control of patients with chronic disease.

Trial Registration

ClinicalTrials.gov NCT04092738. Registered September 17, 2019.
Non-age-related gait kinematics and kinetics in the elderly
Authors: Liang Yuanhao , Xu Tinghan , Qi Shichen , Cao Xiang , Yeung Eric Hiu Kwong , Hu Yong
Published: June 2022

Background

The change of gait kinematics and kinetics along aging were reported to indicate age-related gait patterns. However, few studies focus on non-age-related gait analysis. This study aims to explore the non-age-related gait kinematics and kinetics by comparing gait analysis outcomes among the healthy elderly and young subjects.

Methods

Gait analysis at self-paced was conducted on 12 healthy young subjects and 8 healthy elderly subjects. Kinematic and kinetic features of ankle, knee and hip joints were analyzed and compared in two groups. The degree of variation between the young and elderly in each kinematic or kinetic feature was calculated from pattern distance and percentage of significant difference. The k-means clustering and Elbow Method were applied to select and validate non-age-related features. The average waveforms with standard deviation were plotted for the comparison of the results.

Results

A total of five kinematic and five kinetic features were analyzed on ankle, knee and hip joints in healthy young and elderly groups. The degrees of variation in ankle moment, knee angle, hip flexion angle, and hip adduction moment were 0.1074, 0.1593, 0.1407, and 0.1593, respectively. The turning point was where the k value equals two. The clustering centers were 0.1417 and 0.3691, and the two critical values closest to the cutoff were 0.1593 and 0.3037. The average waveforms of the kinematic or kinetic features mentioned above were highly overlapped with a minor standard deviation between the healthy young and elderly but showed larger variations between the healthy and abnormal.

Conclusions

The cluster with a minor degree of variation in kinematic and kinetic features between the young and elderly were identified as non-age-related, including ankle moment, knee angle, hip flexion angle, and hip adduction moment. Non-age-related gait kinematics and kinetics are essential indicators for gait with normal function, which is essential in the evaluation of mobility and functional ability of the elderly, and data fusion of the assistant device.
A novel sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular join
Authors: Zhang Yadi , Xing Baorui , Hou Xiuxiu , Li Yunmei
Published: June 2022

Purpose

The aim of this study was to explore the efficacy of sternoclavicular hook plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint.

Methods

Between October 2016 and December 2020, 16 cases (9 male and 7 female patient, with a mean age of (42 ± 10) years) of proximal clavicle fracture with dislocation of sternoclavicular joint were included in the study. Injured side, injury mechanism, time to surgery, Complications and duration of follow-up were recorded. The outcomes were evaluated with radiographic assessment, American Shoulder and Elbow Surgeons’ Form (ASES). All the patients were evaluated on postoperative 3rd, 6th, and 12th months.

Results

According to the ASES scoring system, the average score was 49 ± 4 (preoperative score), 87 ± 5 (3 months follow-up), 88 ± 3 (6 months follow-up) and 91 ± 3 (12 months follow-up). Statistics differences was showed between preoperative and 3,6,12 months follow-up score of ASES score (p < 0.001). The postoperative physical function was better than the preoperative function. Internal fixation failure and fracture non-union complications in two patients.

Conclusion

Our study indicates that open reduction and sternoclavicular hook plate fixation for the treatment of traumatic sternoclavicular fracture is a safe, relatively straightforward surgical procedure that can lead to satisfactory outcomes.
Role for autophagy-related markers Beclin-1 and LC3 in endometriosis
Authors: Kong Zhiwei , Yao Tingting
Published: June 2022

Background

Endometriosis is a common and challenging disease in women of childbearing age with high personal and social costs. Many molecular differences between ectopic and eutopic endometrium present difficulties in the development of new drug therapies and therapies. Autophagy is a response to stress and has recently been studied in human cancers. Two important autophagy genes, Beclin-1 and LC3, have been reported in several human cancers. However, the reports of Beclin-1 and LC3 in endometriosis are limited and controversial.

Methods

In this study, we investigated the expression of Beclin-1 and LC3 by Immunohistochemistry.

Results

We found their downregulation in endometriosis. We also found these two autophagy gene expression are negatively correlated with the stage of endometriosis.

Conclusions

Decreased expression of Beclin-1 and LC3 may be related to the occurrence and development of endometriosis.
Effects of obesity on CC16 and their potential role in overweight/obese asthma
Authors: Goudarzi Houman , Kimura Hirokazu , Kimura Hiroki , Makita Hironi , Matsumoto Munehiro , Takei Nozomu , Shimizu Kaoruko , Suzuki Masaru , Watanabe Taku , Kikuchi Eiki , Ohira Hiroshi , Tsujino Ichizo , Sakakibara-Konishi Jun , Shinagawa Naofumi , Shijubo Noriharu , Sato Hirokazu , Shigehara Katsunori , Kaga Kichizo , Hida Yasuhiro , Murakami Soichi , Ebihara Yuma , Nakamura Akinobu , Miyoshi Hideaki , Hirano Satoshi , Hizawa Nobuyuki , Atsumi Tatsuya , Huang Shau-ku , Ito Yoichi M. , Nishimura Masaharu , Konno Satoshi
Published: June 2022

Introduction

Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures.

Methods

Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures.

Results

BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI’s association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001).

Conclusions

We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer
Authors: Wu Mengting , Qiu Qiongzi , Zhou Qing , Li Jia , Yang Juze , Zheng Chengcai , Luo Aoran , Li Xufan , Zhang Honghe , Cheng Xiaodong , Lu Weiguo , Liu Pengyuan , Lu Bingjian , Lu Yan
Published: June 2022

Background

CircRNAs are a novel class of evolutionarily conserved noncoding RNA molecules that form covalently closed continuous loop structures without 5′ caps and 3′ poly(A) tails. Accumulating evidence suggests that circRNAs play important regulatory roles in cancer and are promising biomarkers for cancer diagnosis and prognosis, as well as targets for cancer therapy. In this study, we identify and explore the role of a novel circRNA, circFBXO7, in ovarian cancer.

Methods

rRNA-depleted RNA-sequencing was performed to identify differentially expressed circRNAs between ovarian cancerous and normal tissues. qRT-PCR and single-molecule RNA in-situ hybridization was used to quantify circFBXO7 expression in tumor tissues. The association of circFBXO7 expression with patient prognosis was evaluated by Kaplan–Meier survival analysis. The biological function of circFBXO7 was also investigated using loss-of-function and gain-of-function assays in vivo and in vitro. Luciferase reporter and TOP/FOP-Flash reporter assays were then conducted together with RNA immunoprecipitation and western blot to assess the circFBXO7/miR-96-5p/MTSS1/Wnt/β-catenin axis.

Results

circFBXO7 was downregulated in ovarian cancer which was associated with poor prognosis. Biologically, circFBXO7 overexpression significantly suppressed ovarian cancer cell proliferation, migration, and invasion in vitro, and inhibited tumor growth and metastasis in vivo, whereas its knockdown exerted an opposite role. Mechanistically, circFBXO7 functioned as a competing endogenous RNA for miR-96-5p to regulate the expression of MTSS1. Consequently, downregulation of MTSS1 led to excessive accumulation of β-catenin and increased phosphorylation of GSK3β, leading to the translocation of β-catenin to the nucleus, thereby activating the Wnt/β-catenin signaling pathway and ultimately promoting ovarian cancer progression.

Conclusions

Our findings indicate that circFBXO7 acts as a bone fide tumor suppressor in ovarian cancer and that the circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt/β-catenin signaling pathway which may provide a promising target for ovarian cancer therapy.
Pathways to improve health information systems in Ethiopia: current maturity status and implications
Authors: Biru Amanuel , Birhan Dawit , Melkamu Gemechis , Gebeyehu Abebaw , Omer Afrah Mohammedsanni
Published: June 2022

Background

To achieve national and international strategic goals, countries are advised to assess the maturity status of their health information systems (HIS), including business continuity and interoperability. This work aims to determine the existing maturity status of the Ethiopian HIS, set HIS improvement goals, and inform a path towards an improved national HIS by the end of 2024.

Methods

This assessment was a collaborative and transparent process that was carried out with the engagement of all key stakeholders through consultation. We used the Stages of Continuous Improvement (SOCI) tool to guide the assessment to measure the maturity level of the Ethiopian HIS in five core domains, 13 components and 39 subcomponents and to guide future plans.

Results

The overall average score of the national HIS maturity was 2.68/5, which is categorized between repeatable (stage 2) and defined (stage 3) maturity levels. The assessment findings revealed that three out of the five HIS maturity domains were at a repeatable stage. Only the leadership and governance and the data quality and use domains were at the defined maturity level. A majority (7/13) of the subcomponents were at the repeatable level of maturity, while four were at the defined level. Policy, legal and regulatory framework and compliance from the leadership and governance domain and interoperability from the data quality and use domain were categorized as having an emerging status. Considering the current HIS maturity status, gaps and strengths identified, ongoing HIS initiatives, existing platforms, and the interest and level of engagement of senior government leadership, this assessment put forward an improvement roadmap for achieving the desired managed stage (4.37) of maturity by the end of 2024.

Conclusions

The findings show that the overall maturity level of the Ethiopian HIS is 2.68, which is between the repeatable and defined maturity stages. Enforcement of policies and legislation, data exchange among systems, and information and communication technology infrastructure business continuity planning are the main challenges of Ethiopian HIS requiring further investment. Strengthened and collaborative effort is critical to reaching the desired goal of “managed” HIS (stage 4) in the country by 2024.
Cardiac involvement in MPS patients: incidence and response to therapy in an Italian multicentre study
Authors: Sestito Simona , Rinninella Giada , Rampazzo Angelica , D’Avanzo Francesca , Zampini Lucia , Santoro Lucia , Gabrielli Orazio , Fiumara Agata , Barone Rita , Volpi Nicola , Scarpa Maurizio , Tomanin Rosella , Concolino Daniela
Published: June 2022

Background

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by the deficit of lysosomal hydrolases involved in the degradation of glycosaminoglycans (GAGs). The course is chronic and progressive, with multisystemic involvement that often leads to cardiovascular disease. We describe the overall incidence and type of cardiac damage in a cohort of Italian MPS patients, and their progression over time, also with reference to treatment efficacy in patients under Enzyme Replacement Therapy (ERT). Moreover, we report a possible association between genetic variants and cardiac phenotype in homozygous and hemizygous patients to understand whether a more aggressive clinical phenotype would predict a greater cardiac damage.

Results

Our findings confirm that cardiac involvement is very common, already at diagnosis, in MPS VI (85.7% of our cohort), and in MPS II (68% of our cohort) followed by MPS I subjects (55% of our cohort). The most frequent heart defect observed in each MPS and at any time-point of evaluation was mitral insufficiency; 37% of our patients had mitral insufficiency already at diagnosis, and 60% at post-ERT follow-up. After at least six years of treatment, we observed in some cases (including 6 MPS II, 2 MPS IV and 2 MPS VI) a total regression or improvement of some signs of the cardiac pathology, including some valve defects, though excluding aortic insufficiency, the only valvulopathy for which no regression was found despite ERT. The general clinical phenotype proved not to be strictly correlated with the cardiac one, in fact in some cases patients with an attenuated phenotype developed more severe heart damage than patients with severe phenotype.

Conclusions

In conclusion, our analysis confirms the wide presence of cardiopathies, at different extent, in the MPS population. Since cardiac pathology is the main cause of death in many MPS subtypes, it is necessary to raise awareness among cardiologists about early cardiac morpho-structural abnormalities. The encouraging data regarding the long-term effects of ERT, also on heart damage, underlines the importance of an early diagnosis and timely start of ERT.
Synaptotagmin 11 scaffolds MKK7–JNK signaling process to promote stem-like molecular subtype gastric cancer oncogenesis
Authors: Kim Bo-Kyung , Kim Da-Mi , Park Hyunkyung , Kim Seon-Kyu , Hwang Mi-Aie , Lee Jungwoon , Kang Mi-Jung , Byun Jae-Eun , Im Joo-Young , Kang Minho , Park Kyung Chan , Yeom Young Il , Kim Seon-Young , Jung Haiyoung , Kweon Dae-Hyuk , Cheong Jae-Ho , Won Misun
Published: June 2022

Background

Identifying biomarkers related to the diagnosis and treatment of gastric cancer (GC) has not made significant progress due to the heterogeneity of tumors. Genes involved in histological classification and genetic correlation studies are essential to develop an appropriate treatment for GC.

Methods

In vitro and in vivo lentiviral shRNA library screening was performed. The expression of Synaptotagmin (SYT11) in the tumor tissues of patients with GC was confirmed by performing Immunohistochemistry, and the correlation between the expression level and the patient’s survival rate was analyzed. Phospho-kinase array was performed to detect Jun N-terminal kinase (JNK) phosphorylation. SYT11, JNK, and MKK7 complex formation was confirmed by western blot and immunoprecipitation assays. We studied the effects of SYT11 on GC proliferation and metastasis, real-time cell image analysis, adhesion assay, invasion assay, spheroid formation, mouse xenograft assay, and liver metastasis.

Results

SYT11 is highly expressed in the stem-like molecular subtype of GC in transcriptome analysis of 527 patients with GC. Moreover, SYT11 is a potential prognostic biomarker for histologically classified diffuse-type GC. SYT11 functions as a scaffold protein, binding both MKK7 and JNK1 signaling molecules that play a role in JNK1 phosphorylation. In turn, JNK activation leads to a signaling cascade resulting in cJun activation and expression of downstream genes angiopoietin-like 2 (ANGPTL2), thrombospondin 4 (THBS4), Vimentin, and junctional adhesion molecule 3 (JAM3), which play a role in epithelial-mesenchymal transition (EMT). SNU484 cells infected with SYT11 shRNA (shSYT11) exhibited reduced spheroid formation, mouse tumor formation, and liver metastasis, suggesting a pro-oncogenic role of SYT11. Furthermore, SYT11-antisense oligonucleotide (ASO) displayed antitumor activity in our mouse xenograft model and was conferred an anti-proliferative effect in SNU484 and MKN1 cells.

Conclusion

SYT11 could be a potential therapeutic target as well as a prognostic biomarker in patients with diffuse-type GC, and SYT11-ASO could be used in therapeutic agent development for stem-like molecular subtype diffuse GC.
Deep oncopanel sequencing reveals within block position-dependent quality degradation in FFPE processed samples
Authors: Zhang Yifan , Blomquist Thomas M. , Kusko Rebecca , Stetson Daniel , Zhang Zhihong , Yin Lihui , Sebra Robert , Gong Binsheng , Lococo Jennifer S. , Mittal Vinay K. , Novoradovskaya Natalia , Yeo Ji-Youn , Dominiak Nicole , Hipp Jennifer , Raymond Amelia , Qiu Fujun , Arib Hanane , Smith Melissa L. , Brock Jay E. , Farkas Daniel H. , Craig Daniel J. , Crawford Erin L. , Li Dan , Morrison Tom , Tom Nikola , Xiao Wenzhong , Yang Mary , Mason Christopher E. , Richmond Todd A. , Jones Wendell , Johann Donald J. , Shi Leming , Tong Weida , Willey James C. , Xu Joshua
Published: June 2022

Background

Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized diploid cell line was used to create FFPE samples with four different pre-tissue processing formalin fixation times. A total of 96 FFPE sections were then distributed to different laboratories for targeted sequencing analysis by four oncopanels, and variants resulting from technical error were identified.

Results

Tissue sections that fail more frequently show low cellularity, lower than recommended library preparation DNA input, or target sequencing depth. Importantly, sections from block surfaces are more likely to show FFPE-specific errors, akin to “edge effects” seen in histology, while the inner samples display no quality degradation related to fixation time.

Conclusions

To assure reliable results, we recommend avoiding the block surface portion and restricting mutation detection to genomic regions of high confidence.
Imipramine and olanzapine block apoE4-catalyzed polymerization of Aβ and show evidence of improving Alzheimer’s disease cognition
Authors: Johnson Noah R. , Wang Athena C.-J. , Coughlan Christina , Sillau Stefan , Lucero Esteban , Viltz Lisa , Markham Neil , Allen Cody , Dhanasekaran A. Ranjitha , Chial Heidi J. , Potter Huntington
Published: June 2022

Background

The apolipoprotein E (APOE) ε4 allele confers the strongest risk for late-onset Alzheimer’s disease (AD) besides age itself, but the mechanisms underlying this risk are debated. One hypothesis supported by evidence from multiple labs is that apoE4 binds to the amyloid-β (Aβ) peptide and catalyzes its polymerization into neurotoxic oligomers and fibrils. Inhibiting this early step in the amyloid cascade may thereby reduce or prevent neurodegeneration and AD.

Methods

Using a design of experiments (DOE) approach, we developed a high-throughput assay to identify inhibitors of apoE4-catalyzed polymerization of Aβ into oligomers and fibrils. We used it to screen the NIH Clinical Collection of small molecule drugs tested previously in human clinical trials. We then evaluated the efficacy and cytotoxicity of the hit compounds in primary neuron models of apoE4-induced Aβ and phosphorylated tau aggregation. Finally, we performed retrospective analyses of the National Alzheimer’s Coordinating Center (NACC) clinical dataset, using Cox regression and Cox proportional hazards models to determine if the use of two FDA-approved hit compounds was associated with better cognitive scores (Mini-Mental State Exam), or improved AD clinical diagnosis, when compared with other medications of the same clinical indication.

Results

Our high-throughput screen identified eight blood-brain barrier (BBB)-permeable hit compounds that reduced apoE4-catalyzed Aβ oligomer and fibril formation in a dose-dependent manner. Five hit compounds were non-toxic toward cultured neurons and also reduced apoE4-promoted Aβ and tau neuropathology in a dose-dependent manner. Three of the five compounds were determined to be specific inhibitors of apoE4, whereas the other two compounds were Aβ or tau aggregation inhibitors. When prescribed to AD patients for their normal clinical indications, two of the apoE4 inhibitors, imipramine and olanzapine, but not other (non-hit) antipsychotic or antidepressant medications, were associated with improvements in cognition and clinical diagnosis, especially among APOE4 carriers.

Conclusions

The critical test of any proposed AD mechanism is whether it leads to effective treatments. Our high-throughput screen identified two promising FDA-approved drugs, imipramine and olanzapine, which have no structural, functional, or clinical similarities other than their shared ability to inhibit apoE4-catalyzed Aβ polymerization, thus identifying this mechanism as an essential contribution of apoE4 to AD.