bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive analysis of expression, prognosis and immune infiltration for TIMPs in glioblastoma
Authors: Han Jinkun , Jing Yajun , Han Fubing , Sun Peng
Published: November 2021

Background

Tissue inhibitors of metalloproteinase (TIMP) family proteins are peptidases involved in extracellular matrix (ECM) degradation. Various diseases are related to TIMPs, and the primary reason is that TIMPs can indirectly regulate remodelling of the ECM and cell signalling by regulating matrix metalloproteinase (MMP) activity. However, the link between TIMPs and glioblastoma (GBM) is unclear.

Objective

This study aimed to explore the role of TIMP expression and immune infiltration in GBM.

Methods

Oncomine, GEPIA, OSgbm, LinkedOmics, STRING, GeneMANIA, Enrichr, and TIMER were used to conduct differential expression, prognosis, and immune infiltration analyses of TIMPs in GBM.

Results

All members of the TIMP family had significantly higher expression levels in GBM. High TIMP3 expression correlated with better overall survival (OS) and disease-specific survival (DSS) in GBM patients. TIMP4 was associated with a long OS in GBM patients. We found a positive relationship between TIMP3 and TIMP4, identifying gene sets with similar or opposite expression directions to those in GBM patients. TIMPs and associated genes are mainly associated with extracellular matrix organization and involve proteoglycan pathways in cancer. The expression levels of TIMPs in GBM correlate with the infiltration of various immune cells, including CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells.

Conclusions

Our study inspires new ideas for the role of TIMPs in GBM and provides new directions for multiple treatment modalities, including immunotherapy, in GBM.
Development and validity of the Value-based Stigma Inventory (VASI): a value-sensitive questionnaire for the assessment of mental health stigma
Authors: Rieckhof Sophia , Sander Christian , Speerforck Sven , Prestin Elke , Angermeyer Matthias C. , Schomerus Georg
Published: November 2021

Background

It has been hypothesized that mental illness stigma differs according to what matters most to people, and that this results in value-based differences in stigma within societies. However, there is a lack of stigma measures that account for a broad range of values, including modern and liberal values.

Methods

For the development of the Value-based Stigma Inventory (VASI) a preliminary item-pool of 68 VASI-items was assembled by mental health and stigma experts. For psychometric evaluation, we tested the VASI in an online sample of the general population (n = 4983).

Results

Based on item-characteristics as well as explorative and confirmatory factor analyses, a final version of the VASI was developed, comprising 15 items and 5 subscales. The VASI shows good psychometric properties (item difficulty = 0.34 to 0.67; mean inter-item correlation r = 0.326; Cronbach’s α = 0.879). Medium to high correlations with established stigma scales (SDS, SSMI), medium associations with instruments assessing personal values (PVQ, KSA-3) and small to no associations with a social desirability scale (KSE-G) attest to good convergent and discriminatory validity of the new instrument. Normative values for the VASI subscales are presented.

Conclusions

The developed VASI can be used to assess public stigma of mental illness including personal stigma-relevant value orientations.
Changes in the pattern of suicide attempters visiting the emergency room after COVID-19 pandemic: an observational cross sectional study
Authors: Kang Ji-Hun , Lee Si-Won , Ji Jae-Gu , Yu Jae-Kwang , Jang Yun-Deok , Kim Seong-Ju , Kim Yang-Weon
Published: November 2021

Background

This study aimed to find out the change in the rate and pattern of suicide attempts during severe acute respiratory syndrome COVID-19 pandemic period.

Methods

This study was a retrospective analysis of data collected as a part of an emergency room-based post-suicide management program. The data were collected through interviews and from medical records of suicide attempts, maintained in the emergency room, from January 19 to October 31, 2020, during the “COVID-19 period,” and those who attempted suicide from January 19 to October 31, 2019 “pre-COVID-19 period.” We extracted educational background, marital status, occupation, presence of domestic partner, history of mental illness, alcohol consumption, history of previous suicide attempts; suicide attempt method and location (i.e., at home or a place other than home) at the time of attempt, and whether the attempt was a mass suicide. In addition, we compared patient severity between “COVID-19 period” and “pre-COVID-19 period” using the initial KTAS (South Korean triage and acuity scale) level, consciousness level, and systolic blood pressure. In 2012, KTAS was developed through the Ministry of Health and Welfare’s research project to establish triage system in South Korea.

Results

The analysis of the number of suicide attempts during “pre-COVID-19 period” and “ COVID-19 period” showed that the number of suicide attempts during “COVID-19 period” (n = 440) increased compared to the “pre-COVID-19 period” (n = 400). Moreover, the method of suicide attempts during “COVID-19 period” included overdose of drugs such as hypnotics, antipsychotics, and pesticides that were already possessed by the patient increased compared to the “pre-COVID-19 period” (P < 0.05). At the time of the visit to the emergency room, high KTAS level, low level of consciousness, and low systolic blood pressure, were observed, which were significantly different between “COVID-19 period” and “pre-COVID-19 period” (P < 0.05).

Conclusion

With the worldwide COVID-19 virus spread, suicide rate and suicide attempts at home have significantly increased. In addition, patient severity was higher in the “COVID-19 period” than that in the “pre-COVID-19 period.” The increasing suicide attempt rate should be controlled by cooperation between the emergency room and regional organizations.
Effectiveness of the German disease management programs: quasi-experimental analyses assessing the population-level health impact
Authors: Burns Jacob , Kurz Christoph , Laxy Michael
Published: November 2021

Background

In 2002–2003 disease management programs (DMPs) for type 2 diabetes and coronary heart disease were introduced in Germany to improve the management of these conditions. Today around 6 million Germans aged 56 and older are enrolled in one of the DMPs; however, their effect on health remains unclear.

Methods

We estimated the impact of German DMPs on circulatory and all-cause mortality using a synthetic control study. Specifically, using routinely available data, we compared pre and post-intervention trends in mortality of individuals aged 56 and older for 1998–2014 in Germany to trends in other European countries.

Results

Average circulatory and all-cause mortality in Germany and the synthetic control was 1.63 and 3.24 deaths per 100 persons. Independent of model choice, circulatory and all-cause mortality decreased non-significantly less in Germany than in the synthetic control; for the model with a 3 year time lag, for example, by 0.12 (95%-CI: − 0.20; 0.44) and 0.22 (95%-CI: − 0.40; 0.66) deaths per 100 persons, respectively. Further main analyses, as well as sensitivity and subgroup analyses supported these results.

Conclusions

We observed no effect on circulatory or all-cause mortality at the population-level. However, confidence intervals were wide, meaning we could not reject the possibility of a positive effect. Given the substantial costs for administration and operation of the programs, further comparative effectiveness research is needed to clarify the value of German DMPs for type 2 diabetes and CHD.
Lifetime commercial heterosexual behavior among HIV negative elderly men from rural Chengdu, China: a modified knowledge-attitude-practice perspective
Authors: Yang Yi , Deng Hua , He Huan , Fan Shuang Feng , Li Yuan , Wu Xia , Li Na , Xi Jing , Xu Jing , Xiao Jie , Liao Rui Ping , Xiao Wei
Published: November 2021

Background

China is facing big challenges to achieve the “90–90-90 targets”. The HIV prevalence of elderly (≥50 years) men have been steadily increasing in China, mainly through the sexual transmission route, but sexual behaviors of them are far from well-studied. In 2019, elderly men accounted for 59.2% of HIV/AIDS cases in Sichuan, China.

Methods

The research design is a cross-sectional study. Face-to-face interviews were conducted among 795 HIV negative elderly men from rural Chengdu, capital City of Sichuan. Bivariate and multivariate logistic regression models were applied to examine factors associated with commercial heterosexual behavior from a modified Knowledge-Attitude-Practice (KAP) perspective.

Results

129 (16.23%) respondents admitted high-risk sexual behaviors, including 11.07% commercial heterosexual behavior, 6.16% extramarital, 2.89% casual and 0.25% homosexual behavior, and no one used condom consistently. 427(68.43%) had ever gotten HIV-related Health Education (HRHE), mainly through mass media (70.49%). The HIV-related knowledge awareness rate was only 31.41%. Migration history (AOR =2.46,95% CI = 1.02–5.91), age(≥60 vs. 50–59, OR = 0.41, 95% CI = 0.19–0.91), receiving HRHE from mass media (OR = 0.37, 95%CI = 0.16–0.85), marital status (married vs. never married, OR = 0.04, 95%CI = 0–0.52), and undecided (AOR =0.02, 95%CI = 0.01–0.09) and objection (AOR =0.04, 95%CI = 0.01–0.1) attitude toward commercial sex were related to lifetime commercial heterosexual behavior.

Conclusions

High-risk sexual behaviors are common among elderly men from rural areas in Chengdu. Receiving HRHE from mass media and undecided and objection attitude toward commercial sex prevent elderly from being involving in commercial heterosexual behavior. According to the results, health facilities should continue to conduct systematic interventions, paying more attention to 50–59 years old group. Sex and condom use need to be talked in public. Working with mass media, health facilities give elderly men education not only focusing on HIV/AIDS, but also on knowledge and skills of condom use.
Global trends and predictors of face mask usage during the COVID-19 pandemic
Authors: Badillo-Goicoechea Elena , Chang Ting-Hsuan , Kim Esther , LaRocca Sarah , Morris Katherine , Deng Xiaoyi , Chiu Samantha , Bradford Adrianne , Garcia Andres , Kern Christoph , Cobb Curtiss , Kreuter Frauke , Stuart Elizabeth A.
Published: November 2021

Background

Guidelines and recommendations from public health authorities related to face masks have been essential in containing the COVID-19 pandemic. We assessed the prevalence and correlates of mask usage during the pandemic.

Methods

We examined a total of 13,723,810 responses to a daily cross-sectional online survey in 38 countries of people who completed from April 23, 2020 to October 31, 2020 and reported having been in public at least once during the last 7 days. The outcome was individual face mask usage in public settings, and the predictors were country fixed effects, country-level mask policy stringency, calendar time, individual sociodemographic factors, and health prevention behaviors. Associations were modeled using survey-weighted multivariable logistic regression.

Results

Mask-wearing varied over time and across the 38 countries. While some countries consistently showed high prevalence throughout, in other countries mask usage increased gradually, and a few other countries remained at low prevalence. Controlling for time and country fixed effects, sociodemographic factors (older age, female gender, education, urbanicity) and stricter mask-related policies were significantly associated with higher mask usage in public settings. Crucially, social behaviors considered risky in the context of the pandemic (going out to large events, restaurants, shopping centers, and socializing outside of the household) were associated with lower mask use.

Conclusion

The decision to wear a face mask in public settings is significantly associated with sociodemographic factors, risky social behaviors, and mask policies. This has important implications for health prevention policies and messaging, including the potential need for more targeted policy and messaging design.
Humerus trochlear angle (HTa)—a possible alternative for Baumann angle in the reduction of supracondylar humerus fractures
Authors: Chen Gang , Cui Lu , Shi Jiaqi , Zhang Peng , Li Jun , Wang Zijian , Song Jun , Wang Bangjun
Published: November 2021

Background

The supracondylar humerus fractures are the most common fracture in children’s elbows. Generally, close reduction and percutaneous pinning can provide satisfactory outcomes after adequate reduction. Baumann angle is commonly used to evaluate reduction quality, however, it may fail to assess reduction well when the elbow is in flexion and/or when the patient is young. We conducted this study to evaluate the potential value of the humerus trochlear angle (HTa) for the reduction evaluation and compare it with the Baumann angle.

Methods

We retrospectively reviewed supracondylar humerus fractures in our trauma center from 2016 to 2019. Patients were grouped as followed: in the HTa group, an arthrogram was used to evaluate the HTa angle and reduction (HTa, defined by the intersection of the axis of the humerus shaft and the tangent of the articular surface of the trochlear); In the Baumann group, the Baumann angle was used to assess the reduction. Baumann angle ratio (BA of injured side/BA of contralateral side) was calculated to evaluate the reduction quality between groups. Flynn’s grading criteria were utilized to evaluate both function and cosmetic outcomes in two groups during the follow-up. Operation time, fluoroscopy shots, complications and Flynn’s grading scores were compared between groups.

Results

A total of 57 patients with an average age of 4.62 years and follow-up duration of 21.49 ± 5.40 months were included in the analysis. The gender and age distributions were similar in the two groups. Fluoroscopy shots in the HTa group were significantly less than in Baumann group (16.17 ± 0.73 vs. 21.85 ± 0.78, p < 0.0001), and operation time were also less in HTa group (45.78 ± 1.96 min vs. 62.21 ± 1.58 min, p < 0.0001). Baumann ratio showed no significant difference between the two groups (1.002 ± 0.023 in the Baumann group and 1.01 ± 0.023 in HTa group, p < 0.0001). Length of hospitalization, complications, and Flynn’s grading scores were similar between groups. The HTa angle was positively correlated with Baumann angle in the HTa group (R-value is 0.71 and P = 0.0002).

Conclusions

There was no significant difference in reduction quality and Flynn’s scores between HTa and Baumann groups. Furthermore, HTa was associated with shorter operation time and less radiation exposure in this investigation. Therefore, HTa may be a convenient and reliable parameter that could guide the reduction of supracondylar humerus fractures, especially for young children.
Manual handling of heavy loads and low back pain among different occupational groups: results of the 2018 BIBB/BAuA employment survey
Authors: Sauter Martha , Barthelme Julia , Müller Charlotte , Liebers Falk
Published: November 2021

Background

In Germany and other European countries, many occupations still involve manual handling of loads (MHL), an activity that puts the musculoskeletal system at risk of low back pain (LBP). This study aims to describe the current prevalence of MHL in different occupational groups stratified by gender in Germany, the association between MHL and LBP and the adjusted prevalence of LBP in different respond-categories of MHL.

Methods

Data was collected in telephone interviews conducted as part of the 2018 BIBB/BAuA Employment Survey, which covers work-related topics like working conditions, education, health status and job satisfaction. The analyses were limited to full-time workers (> 35 h/week) aged between 15 and 67. The frequency of MHL was analysed descriptively. BLOSSFELD classification was used to group the participants in occupational categories. The analysis of the association between MHL and the prevalence of LBP over the last 12 months was based on robust log-linear Poisson regression that results in prevalence ratios (PR). The main regression model was adjusted for gender, age, working hours, and working conditions. Adjusted estimates for the prevalence of LBP were calculated based on regression analysis.

Results

The sample consists of n = 14,331 participants (men: n = 8828, 61.6%; women: n = 5503, 38.4%; median age 49 years). Of these, 52.8% say they were exposed to MHL at work. MHL is most common in agricultural occupations, skilled and unskilled occupations. In the regression model, participants who said they were “often” exposed to MHL reported more frequently LBP than those participants who said they were “never” exposed to MHL. The PR as estimate for the association is 1.41 (95%CI [1.32; 1.49]). Postestimation of the prevalence of LBP began with 47.3% (95%CI [43.8%; 51.1%]) for participants who said they were “never” exposed to MHL and rose to 66.5% (95%CI [62.4%; 71.0%]) for participants who indicated they were “often” exposed to MHL.

Conclusions

The 2018 BIBB/BAuA Employment Survey emphasizes that MHL is still common in the German workforce and shows a significant association to LBP. Prevention policies for avoiding MHL remain vital.
Effects of aging on the histology and biochemistry of rat tendon healing
Authors: Lai Fan , Tang Hong , Wang Jingjing , Lu Kang , Bian Xuting , Wang Yunjiao , Shi Youxing , Guo Yupeng , He Gang , Zhou Mei , Zhang Xuan , Zhou Binghua , Zhang Jiqiang , Chen Wan , Tang Kanglai
Published: November 2021

Introduction

Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing.

Method

A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes.

Results

The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation.

Conclusions

Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.
Relationship of footwear comfort, selected size, and lower leg overuse injuries among infantry soldiers
Authors: Nesterovica Darja , Vaivads Normunds , Stepens Ainars
Published: November 2021

Background

High rates of musculoskeletal injuries such as plantar fasciitis and stress fractures have been observed among physically active military personnel. During service time, infantry soldiers use issued boots daily that should fit well and provide comfort to prevent injuries and decrease lower extremity pain effectively. The association of military boot comfort with overuse injuries remains unclear. This study investigates the relationship between the chosen military boot size, perceived boot comfort and lower leg overuse injury.

Methods

During the cross-sectional study, 227 (males, n = 213; females, n = 14) active-duty infantry soldiers at a mean age of 29.5 years old, and with an average service time of 7.2 years were assessed for a history of overuse injury, footprint length, appropriate shoe size, and footwear comfort. Males with a history of overuse injury (n = 32) and non-injured age-matched controls (n = 34) were selected for detailed testing and establishing the possible relationship between footwear comfort and lower leg overuse injury.

Results

No relationship was found between footwear comfort and a history of lower leg overuse injury. N = 38 (57.6%) of study subjects were wearing an inappropriate shoe size daily. Inappropriate shoe size usage affected footwear comfort ratings significantly.

Conclusions

Study results showed that improper boot size was significantly related to comfort ratings but was not associated with a history of lower leg overuse injury.
Preliminary outcomes of the combination of demineralized bone matrix and platelet Rich plasma in the treatment of long bone non-unions
Authors: Nie Wei , Wang Zhaojun , Cao Jiaqing , Wang Wei , Guo Yanjie , Zhang Chi , Jia Weitao , Li Xiaolin
Published: November 2021

Background

A variety of bone graft substitutes have been introduced into the treatment of bone non-unions. However, clinical outcomes from current evidences are various and conflicting. This study aimed to present the preliminary outcomes of a treatment protocol in which the combination of demineralized bone matrix (DBM) and platelet rich plasma (PRP) was used as a bone graft substitute for long bone non-unions.

Methods

Data of this retrospective study were reviewed and collected from a consecutive case series involving 43 patients who presented with a long bone non-union and were treated in our department from October 2018 to May 2019. The combination of DMB and PRP was applied as a bone defect filler in 16 patients, whilst the other 27 patients were treated with iliac bone autografting. Patients’ demographics, postoperative complications and the result of bone union were compared and evaluated.

Results

The demographic data between the two groups were comparable. No significant difference was found with regard to the incidence of postoperative complications. No graft rejection, heterotopic ossification or other complications were noted. The distribution of bony healing time was rather scattered but did not differ significantly between the groups (7.533 ± 3.357 months vs. 6.625 ± 2.516 months; P=0.341). Union was identified radiographically in 15 of 16 patients in the DBM+PRP group and in 24 of 27 patients in autograft group.

Conclusions

The present study identified that low incidence of postoperative complications and satisfactory bony healing rate could be achieved in the treatment of long bone non-unions augmented with the combination of DBM and PRP. Although these findings might indicate the promising future of this treatment protocol, larger and higher quality studies should also be executed to assess its routine use.
Suppression of the hypothalamic-pituitary-thyroid axis is associated with the severity of prognosis in hospitalized patients with COVID-19
Authors: Zheng Juan , Cui Zhenhai , Shi Ningjie , Tian Shenghua , Chen Ting , Zhong Xueyu , Qiu Kangli , Zhang Jiaoyue , Zeng Tianshu , Chen Lulu , Li Huiqing
Published: November 2021

Background

The outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19).

Methods

In this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status.

Results

Among 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07–105.7), 23.1 (95% CI 5.75–92.8), and 4.04 (95% CI 0.69–23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56–5.05), 4.68 (95% CI 1.76–12.4), and 2.63 (95% CI 1.09–6.36) respectively.

Conclusions

Our study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.
A better understanding of the association between maternal perception of foetal movements and late stillbirth—findings from an individual participant data meta-analysis
Authors: Thompson John M. D. , Wilson Jessica , Bradford Billie F. , Li Minglan , Cronin Robin S. , Gordon Adrienne , Raynes-Greenow Camille H. , Stacey Tomasina , Cullling Vicki M. , Askie Lisa M. , O’Brien Louise M. , Mitchell Edwin A. , McCowan Lesley M. E. , Heazell Alexander E. P.
Published: November 2021

Background

Late stillbirth continues to affect 3–4/1000 pregnancies in high-resource settings, with even higher rates in low-resource settings. Reduced foetal movements are frequently reported by women prior to foetal death, but there remains a poor understanding of the reasons and how to deal with this symptom clinically, particularly during the preterm phase of gestation. We aimed to determine which women are at the greatest odds of stillbirth in relation to the maternal report of foetal movements in late pregnancy (≥ 28 weeks’ gestation).

Methods

This is an individual participant data meta-analysis of all identified case-control studies of late stillbirth. Studies included in the IPD were two from New Zealand, one from Australia, one from the UK and an internet-based study based out of the USA. There were a total of 851 late stillbirths, and 2257 controls with ongoing pregnancies.

Results

Increasing strength of foetal movements was the most commonly reported (> 60%) pattern by women in late pregnancy, which were associated with a decreased odds of late stillbirth (adjusted odds ratio (aOR) = 0.20, 95% CI 0.15 to 0.27). Compared to no change in strength or frequency women reporting decreased frequency of movements in the last 2 weeks had increased odds of late stillbirth (aOR = 2.33, 95% CI 1.73 to 3.14). Interaction analysis showed increased strength of movements had a greater protective effect and decreased frequency of movements greater odds of late stillbirth at preterm gestations (28–36 weeks’ gestation). Foetal hiccups (aOR = 0.45, 95% CI 0.36 to 0.58) and regular episodes of vigorous movement (aOR = 0.67, 95% CI 0.52 to 0.87) were associated with decreased odds of late stillbirth. A single episode of unusually vigorous movement was associated with increased odds (aOR = 2.86, 95% CI 2.01 to 4.07), which was higher in women at term.

Conclusions

Reduced foetal movements are associated with late stillbirth, with the association strongest at preterm gestations. Foetal hiccups and multiple episodes of vigorous movements are reassuring at all gestations after 28 weeks’ gestation, whereas a single episode of vigorous movement is associated with stillbirth at term.
Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer’s disease
Authors: Jia Longfei , Zhu Min , Yang Jianwei , Pang Yana , Wang Qi , Li Ying , Li Tingting , Li Fangyu , Wang Qigeng , Li Yan , Wei Yiping
Published: November 2021

Background

The most common biomarkers of Alzheimer’s disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB).

Methods

RNA samples were extracted from the participant’s blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity.

Results

In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB.

Conclusions

This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD.
Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014
Authors: Shen Qianqian , Xu Qian , Li Guoju , Ren Lisheng , Zhang Zhenhong , Zhang Yangting , Zhong Zhaoyi , Li Xiaona , Wang Qiuzhen
Published: November 2021

Background

Vitamin D deficiency (VDD) may increase the risk of hypertension in women of childbearing age, who may be exposed to secondhand smoke (SHS) simultaneously. Till now, few studies have investigated the joint effects of VDD and SHS on hypertension in this population. We evaluated whether exposure to SHS modified the association between VDD and hypertension.

Methods

Data from National Health and Nutrition Examination Surveys (NHANES) 2007-2014 were analyzed. Our research subjects were 2826 nonsmoking and nonpregnant women of childbearing age (20-44 years old). Hypertension was defined based either on systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg or on now taking prescribed medicine for hypertension. The directed acyclic graphs (DAG) and the back-door criterion were used to select a minimal sufficient adjustment set of variables (MSAs) that would identify the unconfounded effect of 25(OH)D and hypertension. The interactive effect of VDD and SHS on hypertension was evaluated by using logistic regression models, followed by strata-specific analyses.

Results

The prevalence of VDD in the hypertension group was significantly higher than that in the non-hypertension group (48.2% vs 41.0%, P = 0.008), as well as the exposure rate of SHS (39.1% vs 33.8%, P = 0.017). VDD was independently associated with nearly 50% increased risk of hypertension [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.01, 2.04], while no significant association was observed between SHS and hypertension. However, SHS showed a significant synergistic effect on VDD with a higher aOR of 1.79 (95% CI: 1.14, 2.80) (Pinteraction = 0.011). This synergistic effect was more obvious when stratified by BMI (in overweight women, aOR, 95% CI =4.74, 1.65-13.60 for interaction vs 2.33, 1.01-5.38 for VDD only) and race (in Non-Hispanic Black women, aOR, 95% CI =5.11, 1.58-16.54 for interaction vs 2.69, 1.10-6.62 for VDD only).

Conclusion

There exist synergistic effects of SHS and VDD on the prevalence of hypertension in American women of childbearing age, with more significant effects in women who were overweight or Non-Hispanic Black. Further studies are warranted to verify this finding in other populations, and the molecular mechanisms underlying the joint effect of SHS and VDD need to be elucidated.
Comparing measurement properties of EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric patients
Authors: Fitriana Titi Sahidah , Purba Fredrick Dermawan , Rahmatika Rina , Muhaimin Riski , Sari Nur Melani , Bonsel Gouke , Stolk Elly , Busschbach Jan J. V.
Published: November 2021

Background

The adult versions EQ-5D-3L and EQ-5D-5L have been extensive compared. This is not the case for the EQ-5D youth versions. The study aim was to compare the measurement properties and responsiveness of EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric patients.

Methods

A sample of patients 8–16 years old with different diseases and a wide range of disease severity was asked to complete EQ-5D-Y-3L, EQ-5D-Y-5L, PedsQL Generic Core Scale, and selected, appropriate disease-specific instruments, three times. EQ-5D-Y-3L and EQ-5D-Y-5L were compared in terms of: feasibility, (re-)distribution properties, discriminatory power, convergent validity, test–retest reliability, and responsiveness.

Results

286 participating patients suffered from one of the following diseases: major beta-thalassemia, haemophilia, acute lymphoblastic leukaemia, acute illness. Missing responses were comparable between versions of the EQ-5D-Y, suggesting comparable feasibility. The number of patients in the best health state (level profile 11111) was equal in both EQ-5D-Y versions. The projection of EQ-5D-Y-3L scores onto EQ-5D-Y-5L for all dimensions showed that the two additional levels in EQ-5D-Y-5L slightly improved the accuracy of patients in reporting their problems, especially if severe. Convergent validity with PedsQL and disease-specific measures showed that the two EQ-5D-Y versions performed about equally. Test–retest reliability (EQ-5D-Y-3L 0.78 vs EQ-5D-Y-5L 0.84), and sensitivity for detecting health changes, were both better in EQ-5D-Y-5L.

Conclusions

Extending the number of levels did not give clear superiority to EQ-5D-Y-5L over EQ-5D-Y-3L based on the criteria assessed in this study. However, increasing the number of levels benefitted EQ-5D-Y performance in the measurement of moderate to severe problems and especially in longitudinal study designs.
Gabapentin and intrathecal morphine combination therapy results in decreased oral narcotic use and more consistent pain scores after posterior spinal fusion for adolescent idiopathic scoliosis
Authors: Li Ying , Swallow Jennylee , Robbins Christopher , Caird Michelle S. , Leis Aleda , Hong Rebecca A.
Published: November 2021

Background

Gabapentin and intravenous patient-controlled analgesia (PCA) can reduce postoperative pain scores, postoperative opioid use, and time to completing physical therapy compared to PCA alone after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Gabapentin combined with intrathecal morphine has not been studied. The primary purpose of this retrospective study was to evaluate whether perioperative gabapentin and intrathecal morphine provide more effective pain control than intrathecal morphine alone after PSF for AIS.

Methods

Patients aged 11 to 18 years who underwent PSF for AIS were identified. Patients who received intrathecal morphine only (ITM group) were matched by age and sex to patients who received intrathecal morphine and perioperative gabapentin (ITM+GABA group). The ITM+GABA group received gabapentin preoperatively and for up to 2 days postoperatively. Both groups received oxycodone and the same non-narcotic adjuvant medications.

Results

Our final study group consisted of 50 patients (25 ITM, 25 ITM+GABA). The ITM+GABA group had significantly lower mean total oxycodone consumption during the hospitalization (0.798 vs 1.036 mg/kg, P<0.015). While the ITM group had a lower mean pain score between midnight and 8 am on POD 1 (2.4 vs 3.7, P=0.026), pain scores were significantly more consistent throughout the postoperative period in ITM+GABA group. The ITM+GABA group experienced less nausea/vomiting (52% vs 84%, P=0.032) and pruritus (44% vs 72%, P=0.045). Time to physical therapy discharge and length of hospital stay were similar.

Conclusion

Addition of gabapentin resulted in reduced oral opioid consumption and more consistent postoperative pain scores after PSF for AIS. The patients who received intrathecal morphine and gabapentin also experienced a lower rate of nausea/vomiting and pruritus.

Trial registration

All data was collected retrospectively from chart review, with institutional IRB approval. Trial registration is not applicable.
Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
Authors: He Jiehua , Chu Ziqiang , Lai Wei , Lan Qiusheng , Zeng Yujie , Lu Daning , Jin Shaowen , Xu Heyang , Su Pengwei , Yin Dong , Chu Zhonghua , Liu Lu
Published: November 2021

Background

The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification.

Methods

Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver.

Results

We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC.

Conclusions

CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.
STOML2 interacts with PHB through activating MAPK signaling pathway to promote colorectal Cancer proliferation
Authors: Ma Wenhui , Chen Yuehong , Xiong Wenjun , Li Wenyi , Xu Zhuoluo , Wang Ying , Wei Zhigang , Mou Tingyu , Wu Zhaokun , Cheng Mingzhen , Zou Yini , Zhu Yu , Zhou Weijie , Liu Feng , Geng Yan
Published: November 2021

Background

Highly expressed STOML2 has been reported in a variety of cancers, yet few have detailed its function and regulatory mechanism. This research aims to reveal regulatory mechanism of STOML2 and to provide evidence for clinical therapeutics, via exploration of its role in colorectal cancer, and identification of its interacting protein.

Methods

Expression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay screened interacting proteins of STOML2, followed by bioinformatics analysis to predict biological function and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.

Results

STOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, and ERK1/2 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.

Conclusions

This study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.
SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop
Authors: Bian Zehua , Zhou Mingyue , Cui Kaisa , Yang Fan , Cao Yulin , Sun Shengbai , Liu Bingxin , Gong Liang , Li Jiuming , Wang Xue , Li Chaoqun , Yao Surui , Yin Yuan , Huang Shenglin , Fei Bojian , Huang Zhaohui
Published: November 2021

Background

Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear.

Methods

SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC.

Results

Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop.

Conclusions

We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.
A systematic review and meta-analysis of enrollment into ARDS and sepsis trials published between 2009 and 2019 in major journals
Authors: Krutsinger Dustin C. , Yadav Kuldeep N. , Harhay Michael O. , Bartels Karsten , Courtright Katherine R.
Published: November 2021

Background

Enrollment problems are common among randomized controlled trials conducted in the ICU. However, little is known about actual trial enrollment rates and influential factors. We set out to determine the overall enrollment rate in recent randomized controlled trials (RCTs) of patients with acute respiratory distress syndrome (ARDS), acute lung injury (ALI), or sepsis, and which factors influenced enrollment rate.

Methods

We conducted a systematic review by searching Pubmed using predefined terms for ARDS/ALI and sepsis to identify individually RCTs published among the seven highest impact general medicine and seven highest impact critical care journals between 2009 and 2019. Cluster randomized trials were excluded. Data were extracted by two independent reviewers using an electronic database management system. We conducted a random-effects meta-analysis of the eligible trials for the primary outcome of enrollment rate by time and site.

Results

Out of 457 articles identified, 94 trials met inclusion criteria. Trials most commonly evaluated pharmaceutical interventions (53%), were non-industry funded (78%), and required prospective informed consent (81%). The overall mean enrollment rate was 0.83 (95% confidence interval: 0.57–1.21) participants per month per site. Enrollment in ARDS/ALI and sepsis trials were 0.48 (95% CI 0.32–0.70) and 0.98 (95% CI 0.62–1.56) respectively. The enrollment rate was significantly higher for single-center trials (4.86; 95% CI 2.49–9.51) than multicenter trials (0.52; 95% CI 0.41–0.66). Of the 36 trials that enrolled < 95% of the target sample size, 8 (22%) reported slow enrollment as the reason.

Conclusions

In this systematic review and meta-analysis, recent ARDS/ALI and sepsis clinical trials had an overall enrollment rate of less than 1 participant per site per month. Novel approaches to improve critical care trial enrollment efficiency are needed to facilitate the translation of best evidence into practice.