bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of reporting quality of cohort studies using real-world data based on RECORD: systematic review
Authors: Zhao Ran , Zhang Wen , Zhang ZeDan , He Chang , Xu Rong , Tang XuDong , Wang Bin
Published: June 2023

Objective

Real-world data (RWD) and real-world evidence (RWE) have been paid more and more attention in recent years. We aimed to evaluate the reporting quality of cohort studies using real-world data (RWD) published between 2013 and 2021 and analyze the possible factors.

Methods

We conducted a comprehensive search in Medline and Embase through the OVID interface for cohort studies published from 2013 to 2021 on April 29, 2022. Studies aimed at comparing the effectiveness or safety of exposure factors in the real-world setting were included. The evaluation was based on the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. Agreement for inclusion and evaluation was calculated using Cohen’s kappa. Pearson chi-square test or Fisher’s exact test and Mann-Whitney U test were used to analyze the possible factors, including the release of RECORD, journal IFs, and article citations. Bonferroni’s correction was conducted for multiple comparisons. Interrupted time series analysis was performed to display the changes in report quality over time.

Results

187 articles were finally included. The mean ± SD of the percentage of adequately reported items in the 187 articles was 44.7 ± 14.3 with a range of 11.1–87%. Of 23 items, the adequate reporting rate of 10 items reached 50%, and the reporting rate of some vital items was inadequate. After Bonferroni’s correction, the reporting of only one item significantly improved after the release of RECORD and there was no significant improvement in the overall report quality. For interrupted time series analysis, there were no significant changes in the slope (p = 0.42) and level (p = 0.12) of adequate reporting rate. The journal IFs and citations were respectively related to 2 areas and the former significantly higher in high-reporting quality articles.

Conclusion

The endorsement of the RECORD cheklist was generally inadequate in cohort studies using RWD and has not improved in recent years. We encourage researchers to endorse relevant guidelines when utilizing RWD for research.
Suggestions on the ideal method of conducting community screenings for older adults
Authors: Kouzuki Minoru , Tanaka Nobuto , Miyamoto Madoka , Urakami Katsuya
Published: June 2023

Background/Objectives

Since dementia and frailty lead to a reduced quality of life and risk of needing long-term care in the older adults, we hypothesized that evaluations related to dementia and frailty would be useful and of high interest in screening for the older adults. Therefore, we conducted a community screening incorporating multiple simple evaluations related to dementia and frailty. In addition to various functional evaluations, we investigated interest in tests, thoughts on the disease, and the relationships between subjective (i.e., how one feels about oneself) and objective evaluations (i.e., the results of tests and rating scales). The purpose of this study was to examine the thoughts regarding tests and diseases and the functions that make it difficult to accurately perceive changes by oneself, and to obtain suggestions on the ideal method of community screening for the older adults.

Subjects/Methods

The participants were 86 people aged 65 and over living in Kotoura Town who participated in the community screening, for which we obtained background information and body measurements. We also assessed physical, cognitive and olfactory function, evaluated nutritional status, and we administered a questionnaire (interest in tests, thoughts on dementia and frailty, and a subjective functional evaluation).

Results

Regarding interest in tests, the participants answers were highest for physical, cognitive and olfactory function, in that order (68.6%, 60.5%, and 50.0%, respectively). In the survey on thoughts on dementia and frailty, 47.6% of participants felt that people with dementia were viewed with prejudice, and 47.7% did not know about frailty. Regarding the relationship between subjective and objective evaluations, only the assessment of cognitive function did not show a correlation between both evaluations.

Conclusions

From the viewpoint of the participants’ degree of interest in and the need for accurate evaluations through objective examination, the findings suggest that the assessment of physical and cognitive function may be beneficial as a screening tool for older adults. Objective evaluation is essential, particularly for assessing cognitive function. However, approximately half the participants believed people with dementia were viewed with prejudice and did not know about frailty, which may lead to barriers to testing and low interest. The importance of increasing the participation rate in community screening through disease-related educational activities was suggested.
Bacterial findings in patients referred to hospital for the treatment of acute tonsillitis with or without peritonsillar phlegmon
Authors: Andersen Camilla , Greve Thomas , Reinholdt Kasper Basse , Kjaerulff Ann Marlene Gram , Udholm Nichlas , Khalid Vesal , Madzak Adnan , Duez Christophe , Münch Henrik , Pauli Søren , Danstrup Christian Sander , Petersen Niels Krintel , Klug Tejs Ehlers
Published: June 2023

Background

The vast majority of patients with acute tonsillitis (AT) are managed in general practice. However, occasionally patients are referred to hospital for specialized management because of aggravated symptoms and/or findings suggestive of peritonsillar involvement. No prospective studies have been conducted aiming to investigate the prevalent and significant microorganisms in this highly selected group of patients. We aimed to describe the microbiological findings of acute tonsillitis with or without peritonsillar phlegmon (PP) in patients referred for hospital treatment and to point out potential pathogens using the following principles to suggest pathogenic significance: (1) higher prevalence in patients compared to healthy controls, (2) higher abundance in patients compared to controls, and (3) higher prevalence at time of infection compared to time of follow up.

Methods

Meticulous and comprehensive cultures were performed on tonsillar swabs from 64 patients with AT with (n = 25) or without (n = 39) PP and 55 healthy controls, who were prospectively enrolled at two Danish Ear-Nose-Throat Departments between June 2016 and December 2019.

Results

Streptococcus pyogenes was significantly more prevalent in patients (27%) compared to controls (4%) (p < 0.001). Higher abundance was found in patients compared to controls for Fusobacterium necrophorum (mean 2.4 vs. 1.4, p = 0.017) and S. pyogenes (mean 3.1 vs. 2.0, p = 0.045) in semi-quantitative cultures. S. pyogenes, Streptococcus dysgalactiae, and Prevotella species were significantly more prevalent at time of infection compared to follow up (p = 0.016, p = 0.016, and p = 0.039, respectively). A number of species were detected significantly less frequently in patients compared to controls and the mean number of species was significantly lower in patients compared to controls (6.5 vs. 8.3, p < 0.001).

Conclusions

Disregarding Prevotella spp. because of the prevalence in healthy controls (100%), our findings suggest that S. pyogenes, F. necrophorum, and S. dysgalactiae are significant pathogens in severe AT with or without PP. In addition, infections were associated with reduced diversity (dysbacteriosis).

Trial registration

The study is registered in the ClinicalTrials.gov protocol database (# 52,683). The study was approved by the Ethical Committee at Aarhus County (# 1-10-72-71-16) and by the Danish Data Protection Agency (# 1-16-02-65-16).
Effect of hydrogen/oxygen therapy for ordinary COVID-19 patients: a propensity-score matched case-control study
Authors: Zeng Yingying , Guan Weijie , Wang Kai , Jie Zhijun , Zou Xu , Tan Xiaoping , Li Xinyu , Chen Xiaohua , Ren Xiaoting , Jiang Junhong , Zheng Zeguang , Shi Jindong , Zhong Nanshan
Published: June 2023

Background

Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates.

Methods

This retrospective, propensity-score matched (PSM) case–control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed.

Results

Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25–2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9–15) versus the oxygen group (13 days; 95% CI, 11–20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days).

Conclusion

This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.
TACE sequential MWA guided by cone-beam computed tomography in the treatment of small hepatocellular carcinoma under the hepatic dome
Authors: Li Zhaonan , Xu Kaihao , Zhou Xueliang , Jiao Dechao , Han Xinwei
Published: June 2023

Purpose

An assessment is being conducted to determine the safety and effectiveness of using Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) sequentially to treat small hepatocellular carcinomas (HCCs) located in the hepatic dome.

Materials and methods

Fifty-three patients with small HCCs in the hepatic dome who underwent TACE combined with simultaneous CBCT-guided MWA were studied. Inclusion criteria were a single HCCs ≤ 5.0 cm or a maximum of three. The safety and interventional-related complications were monitored, and local tumor progression (LTP), overall survival (OS), and prognostic factors for LTP/OS were evaluated.

Results

The procedures were successfully accomplished in all patients. According to Common Terminology Criteria for Adverse Events (CTCAE), adverse reactions and complications are mainly Grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated). Liver and kidney function and alpha-fetoprotein (AFP) levels remained within a reasonable range after 4 weeks of treatment (both p < 0.001). The mean LTP was 44.406 months (95% CI: 39.429, 49.383) and the mean OS rate was 55.157 months (95% CI: 52.559, 57.754). The combination treatment achieved 1-, 3-, and 5-year LTP rates of 92.5%, 69.6%, and 34.5%, respectively; and 1-, 3-, and 5-year OS rates of 100.0%, 88.4%, and 70.2%, respectively. Results from both univariate and multivariate Cox regression analyses showed that the tumor diameter (< 3 cm) and the distance to the hepatic dome (≥ 5 mm, < 10 mm) had a significant impact on the patient’s LTP and OS, and were related to better survival.

Conclusion

CBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of HCCs located under the hepatic dome.
Nutritional rickets presenting with developmental regression: a rare presentation of rickets
Authors: Pieridou Chariklia , Uday Suma
Published: June 2023

Rickets is a disorder of defective mineralisation of the growth plate. Vitamin D deficiency remains the leading cause of nutritional rickets worldwide.

We present the case of a 3.5-year-old breastfed boy who presented with dental abscess when a history of developmental regression was noted. Clinical assessment revealed hypotonia, poor growth and stunting. Biochemistry identified hypocalcaemia (1.63mmol/L, [normal range (NR) 2.2-2.7mmol/L]), severe vitamin D deficiency (25hydroxyvitamin D 5.3nmol/L, [NR > 50nmol/L]) with secondary hyperparathyroidism (Parathormone 159pmol/L, [NR 1.6-7.5pmol/L]) and rickets on radiographs. Growth failure screening suggested hypopituitarism with central hypothyroidism and low IGF1 at baseline, however, dynamic tests confirmed normal axis. Management included nasogastric nutritional rehabilitation, cholecalciferol and calcium supplementation and physiotherapy. A good biochemical response in all parameters was observed within 3 weeks and reversal of developmental regression by 3 months from treatment. Developmental regression as a presentation of nutritional rickets is rare and requires a high index of suspicion.
Internalised stigma among people with mental illness in Africa, pooled effect estimates and subgroup analysis on each domain: systematic review and meta-analysis
Authors: Alemu Wondale Getinet , Due Clemence , Muir-Cochrane Eimear , Mwanri Lillian , Ziersch Anna
Published: June 2023

Background

Internalisation of stigma occurs when people with a stigmatised attribute, such as a mental illness, supress negative but accepted societal attitudes. However, as far as is known, there is no comprehensive picture of the prevalence of and factors associated with, internalised stigma among people living with mental illness in Africa. This systematic review and meta-analysis provide new knowledge by examining the evidence on the prevalence of internalised stigma and associated factors among people living with mental illness in Africa.

Methods

Using the population, intervention, comparison, outcome, and type of study (PICOT) approach, PubMed, Scopus, MEDLINE, PsycINFO, CINAHL, ScienceDirect, and Google Scholar were searched using a structured search comprising terms associated with mental health, mental illness, internalised stigma, and a list of all African countries. To evaluate paper quality, the Joanna Briggs Institute Quality Appraisal Checklist was used. Subgroup analysis with country and diagnosis was tested using a random-effect model, and bias was checked using a funnel plot and an inspection of Egger’s regression test. A p-value, OR and 95% CI was used to demonstrate an association.

Results

The pooled prevalence of internalised stigma was 29.05% (25.42,32.68: I2 = 59.0%, p ≤ 0.001). In the subgroup analysis by country, Ethiopia had the highest prevalence of internalised stigma at 31.80(27.76,35.84: I2 = 25.6%, p ≤ 0.208), followed by Egypt at 31.26(13.15,49.36: I2 = 81.6%, p ≤ 0.02), and Nigeria at 24.31(17.94,30.67: I2 = 62.8%, p ≤ 0.02). Based on domains of internalised stigma, pooled prevalence was stigma resistance: 37.07%, alienation: 35.85%, experience of discrimination: 31.61%, social withdrawal: 30.81% and stereotype: 26.10%. Experiencing psychotic symptoms (1.42(0.45,2.38)), single marital status (2.78(1.49,4.06)), suicidal ideation (2.32(1.14,3.49)), drug nonadherence (1.5(-0.84,4.00)), poor social support (6.69(3.53,9.85)), being unemployed (2.68(1.71,3.65)), and being unable to read and write (3.56(2.26,4.85)) were identified as risk factors for internalised stigma.

Conclusions

Internalised stigma is common among people suffering from mental illnesses in Africa. This review determined that 29% of the sample population had elevated internalised stigma scores, and there were variations by country. People experiencing mental illness who have a single marital status, suicidal behaviours, poor social support, unemployed and have poor literacy levels were at a higher risk of internalised stigma. The finding points to populations that require support to address internalised stigma and improve the mental health outcomes.
Development of nomogram for predicting major complications in patients with esophageal cancer in the early postoperative period
Authors: Mijiti Maimaiti , Li Dan , Yan Rui , Yuan Tingting , Shen Guimei , Zhao Dan
Published: June 2023

Purpose

To investigate the predictive value of the Prognostic Nutrition Index (PNI) in major complications after esophagectomy for esophageal cancer and to develop a Nomogram risk prediction model.

Method

The clinical data of 386 patients who underwent radical esophageal cancer surgery from May 2019 to March 2022 were retrospectively analyzed. Logistic regression analysis was performed to screen independent risk factors associated with major postoperative complications. A nomogram risk prediction model for major postoperative complications was developed based on the predictors, and the clinical utility of the model was assessed by decision curve analysis(DCA).

Result

In this study logistic univariate regression analysis found that age, preoperative radiotherapy, American Society of Anesthesiologists physical status (ASA score), length of surgery, and PNI may be associated with the development of major postoperative complications. logistic multifactorial analysis showed that the above risk factors were independent risk factors for the development of major postoperative complications in esophageal cancer. Nomogram was developed by incorporating the above risk factors with ASA classification. The calibration curves showed that the model had a good agreement. The decision curves showed that the model has good clinical application.

Conclusion

Individualized nomograms based on PNI combined with clinical indicators can be used to predict major complications in the early postoperative period and help to enhance perioperative management.
Dentist-reported differences in services provided to patients with public vs. private dental insurance
Authors: Reynolds Julie , Ingleshwar Aparna , Nwachukwu Pamela , McKernan Susan , Damiano Peter
Published: June 2023

Introduction

Variation in dentists’ provision of types of dental services based on patients’ insurance may impact population access to comprehensive care. The aim of this study was to describe differences in the types of services provided to adult patients with Medicaid versus private insurance among private practice general dentists.

Methods

The data source was a 2019 survey of private practice dentists in Iowa, and the study sample included general dentists with current or recent participation in Iowa’s Medicaid program for adults (n = 264). Bivariate analyses were used to compare differences in the types of services provided to privately insured and publicly insured patients.

Results

Dentists reported the greatest differences in services provided to patients with public versus private insurance for prosthodontic procedures, including complete dentures, removable partial dentures, and crown and bridge services. Endodontic services were the least frequently provided category of services provided by dentists for both patient groups. Patterns were generally similar among both urban and rural providers.

Conclusion

Access to dental care for Medicaid members should be evaluated not only on the proportion of dentists who see new Medicaid patients but also on the types of services dentists provide to this population.
Collagen turnover is associated with cardiovascular autonomic and peripheral neuropathy in type 1 diabetes: novel pathophysiological mechanism?
Authors: Hansen Christian S. , Rasmussen Daniel G. K. , Hansen Tine W. , Nielsen Signe Holm , Theilade Simone , Karsdal Morten A. , Genovese Federica , Rossing Peter
Published: June 2023

Background

Diabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D).

Methods

In a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry. Symmetrical vibration sensation threshold above 25 V constituted DSPN.

Results

Participants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio > 2 for CAN and > 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations.

Conclusions

Results show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D.
Genetic susceptibility to airway inflammation and exposure to short-term outdoor air pollution
Authors: Bouma Femke , Nyberg Fredrik , Olin Anna-Carin , Carlsen Hanne Krage
Published: June 2023

Background

Air pollution is a large environmental health hazard whose exposure and health effects are unequally distributed among individuals. This is, at least in part, due to gene-environment interactions, but few studies exist. Thus, the current study aimed to explore genetic susceptibility to airway inflammation from short-term air pollution exposure through mechanisms of gene-environment interaction involving the SFTPA, GST and NOS genes.

Methods

Five thousand seven hundred two adults were included. The outcome measure was fraction of exhaled nitric oxide (FeNO), at 50 and 270 ml/s. Exposures were ozone (O3), particulate matter < 10 µm (PM10), and nitrogen dioxide (NO2) 3, 24, or 120-h prior to FeNO measurement. In the SFTPA, GST and NOS genes, 24 single nucleotide polymorphisms (SNPs) were analyzed for interaction effects. The data were analyzed using quantile regression in both single-and multipollutant models.

Results

Significant interactions between SNPs and air pollution were found for six SNPs (p < 0.05): rs4253527 (SFTPA1) with O3 and NOx, rs2266637 (GSTT1) with NO2, rs4795051 (NOS2) with PM10, NO2 and NOx, rs4796017 (NOS2) with PM10, rs2248814 (NOS2) with PM10 and rs7830 (NOS3) with NO2. The marginal effects on FeNO for three of these SNPs were significant (per increase of 10 µg/m3):rs4253527 (SFTPA1) with O3 (β: 0.155, 95%CI: 0.013–0.297), rs4795051 (NOS2) with PM10 (β: 0.073, 95%CI: 0.00–0.147 (single pollutant), β: 0.081, 95%CI: 0.004–0.159 (multipollutant)) and NO2 (β: -0.084, 95%CI: -0.147; -0.020 (3 h), β: -0.188, 95%CI: -0.359; -0.018 (120 h)) and rs4796017 (NOS2) with PM10 (β: 0.396, 95%CI: 0.003–0.790).

Conclusions

Increased inflammatory response from air pollution exposure was observed among subjects with polymorphisms in SFTPA1, GSTT1, and NOS genes, where O3 interacted with SFTPA1 and PM10 and NO2/NOx with the GSTT1 and NOS genes. This provides a basis for the further exploration of biological mechanisms as well as the identification of individuals susceptible to the effects of outdoor air pollution.
Association between atherogenic index of plasma and prehypertension or hypertension among normoglycemia subjects in a Japan population: a cross-sectional study
Authors: Tan Mingjuan , Zhang Yongliang , Jin Ling , Wang Youli , Cui Weiwei , Nasifu Lubanga , He Bangshun
Published: June 2023

Objective

The atherogenic index of plasma (AIP), consisting of triglycerides and high-density lipoprotein cholesterol, is applied to estimate the cardiovascular disease risk. The evidence regarding the association between AIP and prehypertension or hypertension remains inconclusive. This study was conducted to investigate the association of AIP and prehypertension or hypertension in normoglycemic subjects in Japan.

Methods

In the present cross-sectional study, 15,453 normoglycemic participants aged 18 years or older in Gifu, Japan, were evaluated. The selected participants were separated into four groups in the light of AIP quartiles, ranging from the lowest quartile (Q1) to the highest quartile (Q4). And the association between AIP and prehypertension or hypertension was explored with multivariate logistic regression by gradually adjusting model.

Results

Among the 15,453 participants, aged of 43.7 ± 8.9 years, and of whom 45.5% were females, the prevalence rates of prehypertension or hypertension were 27.68% (4,278) and 6.23% (962) respectively. In multivariate logistic regression analyses, participants in the highest AIP quartile had an increase risk in prehypertension and hypertension, compared with participants the lowest one, the odds ratios (OR) were 1.15 (95%CI: 1.00–1.13, P = 0.045) for prehypertension and 1.54 (95%CI:1.16–2.04, P = 0.003) for hypertension after adjusting confounders. In subgroup analyses, the high risk of hypertension was also observed for female participants in the highest AIP quartile (Q4) (OR = 2.19, 95%CI: 1.37–3.49, P = 0.001), especially between the ages of 40 and 60 years (OR = 2.20, 95%CI: 1.24–3.88, P = 0.007).

Conclusions

Higher AIP is significantly and positively associated with the risk of prehypertension or hypertension in normoglycemic subjects in Gifu, Japan, which was more pronounced in the female population, especially between the years of 40 and 60.
Association between fatty liver index and blood coagulation markers: a population-based study
Authors: Iglesias Morcillo Maximilian , Freuer Dennis , Peters Anette , Heier Margit , Teupser Daniel , Meisinger Christine , Linseisen Jakob
Published: June 2023

Background

Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.

Methods

After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.

Results

In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.

Conclusion

In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.
Health-related quality of life in children with developmental coordination disorder: a systematic review
Authors: Weber Meyene Duque , Draghi Tatiane Targino Gomes , Rohr Liz Araújo , Cavalcante Neto Jorge Lopes , Tudella Eloisa
Published: June 2023

The aims of this study were (1) to synthesize evidence of the general health-related quality of life in children with DCD compared to their typically developing peers, and (2) to verify which domains of HRQOL are more compromised in children with DCD. A systematic search was carried out to identify cross-sectional studies that evaluated self-perception and/or the parent's perception of the HRQOL in children with and without DCD as an outcome. The methodological quality of the studies was assessed, and the effect size calculated. Initial searches in the databases identified 1092 articles. Of these, six were included. Most of the articles (5/6) included noted that children with DCD show a significantly lower HRQOL than their typically developing peers. Regarding the most compromised HRQOL domains, the results are heterogeneous. Most studies (3/6) had moderate methodological quality, and two studies were classified as high methodological quality. Effect sizes ranged from low to high.
Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice
Authors: Liu Cheng , Zhou Ying , Gao Huihui , Zhang Zeping , Zhou Yu , Xu Zifeng , Zhang Chenhong , Xu Zhen , Zheng Huajun , Ma Yan-Qing
Published: June 2023

Objective and design

An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event.

Subjects

Mice under different treatments were used in this study.

Methods and treatment

We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined.

Results

Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT.

Conclusion

These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT.
Gauging innovation and health impact from biomedical research: survey results and interviews with recipients of EU-funding in the fields of Alzheimer’s disease, breast cancer and prostate cancer
Authors: Pistollato Francesca , Campia Ivana , Daskalopoulos Evangelos P. , Bernasconi Camilla , Desaintes Christian , Di Virgilio Sergio , Kyriakopoulou Christina , Whelan Maurice , Deceuninck Pierre
Published: June 2023

Biomedical research on Alzheimer’s disease (AD), breast cancer (BC) and prostate cancer (PC) has globally improved our understanding of the etiopathological mechanisms underlying the onset of these diseases, often with the goal to identify associated genetic and environmental risk factors and develop new medicines. However, the prevalence of these diseases and failure rate in drug development remain high. Being able to retrospectively monitor the major scientific breakthroughs and impact of such investment endeavors is important to re-address funding strategies if and when needed. The EU has supported research into those diseases via its successive framework programmes for research, technological development and innovation. The European Commission (EC) has already undertaken several activities to monitor research impact. As an additional contribution, the EC Joint Research Centre (JRC) launched in 2020 a survey addressed to former and current participants of EU-funded research projects in the fields of AD, BC and PC, with the aim to understand how EU-funded research has contributed to scientific innovation and societal impact, and how the selection of the experimental models may have underpinned the advances made. Further feedback was also gathered through in-depth interviews with some selected survey participants representative of the diverse pre-clinical models used in the EU-funded projects. A comprehensive analysis of survey replies, complemented with the information derived from the interviews, has recently been published in a Synopsis report. Here we discuss the main findings of this analysis and propose a set of priority actions that could be considered to help improving the translation of scientific innovation of biomedical research into societal impact.
A comprehensive insight into the correlation between ncRNAs and the Wnt/β-catenin signalling pathway in gastric cancer pathogenesis
Authors: Akhavanfar Roozbeh , Shafagh Seyyed-Ghavam , Mohammadpour Behnood , Farahmand Yalda , Lotfalizadeh Mohammad Hassan , Kookli Keihan , Adili Ali , Siri Goli , Eshagh Hosseini Seyed Mahmoud
Published: June 2023

During the past decades, gastric cancer (GC) has emerged as one of the most frequent malignancies with a growing rate of prevalence around the world. Despite considerable advances in therapeutic methods, the prognosis and management of patients with gastric cancer (GC) continue to be poor. As one of the candidate molecular targets in the treatment of many types of cancer, the Wnt/β-catenin pathway includes a family of proteins that have important functions in adult tissue homeostasis and embryonic development. The aberrant regulation of Wnt/β-catenin signaling is strongly correlated with the initiation and development of numerous cancers, including GC. Therefore, Wnt/β-catenin signaling has been identified as one of the main targets for extending therapeutic approaches for GC patients. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, are important components of epigenetic mechanisms in gene regulation. They play vital roles in various molecular and cellular processes and regulate many signaling pathways, such as Wnt/β-catenin pathways. Insights into these regulatory molecules involved in GC development may lead to the identification of potential targets for overcoming the limitations of current therapeutic approaches. Consequently, this review aimed to provide a comprehensive overview of ncRNAs interactions involved in Wnt/β-catenin pathway function in GC with diagnostic and therapeutic perspectives.
Implementation of elementary school physical education quantity and quality law through school district audit, feedback, and coaching
Authors: Thompson Hannah R. , Madsen Kristine A. , Zamek Maya , McKenzie Thomas L. , Dzewaltowski David A.
Published: June 2023

Background

To address low state physical education (PE) quantity and quality law implementation in elementary schools, the New York City Department of Education (NYCDOE) delivered a multilevel intervention (PE Works; 2015-2019), which included a district-led audit of school PE-law implementation, feedback, and coaching with principals. Using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) implementation science framework, we assessed the primary multilevel drivers of success for this approach in increasing adherence to PE quantity and quality law.

Methods

We conducted in-depth, semi-structured interviews with district-level personnel (n=17), elementary school administrators (n=18), and PE teachers (n=6) in 2020-21.

Results

Interview results suggested several key RE-AIM drivers of successful PE law implementation. Reach: Ensure higher-need schools receive the necessary initial support to improve PE and later focus on lower-need schools. Effectiveness: Provide support tailored to school needs, not penalties, to improve PE. Adoption: Increase the priority of PE at both district and school levels (e.g., audit and feedback, themselves, appear to elevate PE’s priority). Streamline data collection and feedback reports; collecting/reporting too much information is burdensome and leads to lack of focus. Involve qualified (i.e., skilled in both school administration and PE programming/pedagogy) district-level personnel to work collaboratively with schools. Implementation: Build strong, trusting district-school relationships. Maintenance: Provide ongoing district-level support to schools and involve parents to advocate for quality PE.

Conclusions

PE audits, feedback, and coaching (PEAFC) can guide schools in establishing long-term plans for successfully implementing PE-related law. Future research should examine the impact of PEAFC elsewhere (e.g., secondary schools, other districts).
ST6GALNAC4 promotes hepatocellular carcinogenesis by inducing abnormal glycosylation
Authors: Man Da , Jiang Yifan , Zhang Deguo , Wu Jingjing , Ding Bo , Liu Hanqing , Xu Guangming , Lu Jiahua , Ru Junnan , Tong Rongliang , Zheng Shusheng , Chen Diyu , Wu Jian
Published: June 2023

Hepatocellular carcinoma (HCC) is one of the most lethal tumor types worldwide. Glycosylation has shown promise in the study of tumor mechanisms and treatment. The glycosylation status of HCC and the underlying molecular mechanisms are still not fully elucidated. Using bioinformatic analysis we obtained a more comprehensive characterization of glycosylation of HCC. Our analysis presented that high glycosylation levels might correlate with tumor progression and poor prognosis. Subsequent Experiments identified key molecular mechanisms for ST6GALNAC4 promoting malignant progression by inducing abnormal glycosylation. We confirmed the contribution of ST6GALNAC4 to proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies revealed that ST6GALNAC4 may be induced abnormal TGFBR2 glycosylation, resulting in the higher protein levels of TGFBR2 and TGF$$\beta$$βpathway increased activation. Our study also provided a further understand of immunosuppressive function of ST6GALNAC4 through T antigen-galectin3+ TAMs axis. This study has provided one such possibility that galectin3 inhibitors might be an acceptable treatment choice for HCC patients with high T antigen expression.
Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study
Authors: Möller Ingrid , Rodas Gil , Villalón Jose María , Rodas Jose A. , Angulo Francisco , Martínez Nina , Vergés Josep
Published: June 2023

Background

Specialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients.

Methods

This randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18–68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments.

Results

Patients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported.

Conclusions

These findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation.

Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849
Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice
Authors: Alves da Costa Filipa , Cardoso Borges Fábio , Ramos Adriana , Mayer Alexandra , Brito Claudia , Ramos Catarina , Bernardo Catarina , Cossito Mariane , Furtado Cláudia , Ferreira Arlindo R. , Martins-Branco Diogo , da Costa Miranda Ana , Lourenço António
Published: June 2023

Background

New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2.

Methods

A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan–Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used.

Results

There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7–35.2) and median duration of treatment was 17.5 months (IQR: 7.8–29.1). Median PFS was 19.5 months (95%CI 14.2–24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2–75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5–50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4–28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4–36.0). TPF was 19.8 months (95%CI 14.2–24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0–29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%).

Conclusions

Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.
Stem-loop structures control mRNA processing of the cellulosomal cip-cel operon in Ruminiclostridium cellulolyticum
Authors: Wang Na , Li Ping , Cheng Ying , Song Houhui , Xu Chenggang
Published: June 2023

Background

Anaerobic, mesophilic, and cellulolytic Ruminiclostridium cellulolyticum produces an efficient cellulolytic extracellular complex named cellulosome, which consist of a non-catalytic multi-functional integrating subunit, organizing the various catalytic subunits into the complex. Main components of cellulosome were encoded by the cip-cel operon in R. cellulolyticum, and their stoichiometry is controlled by the mechanism of selective RNA processing and stabilization, which allows to confer each processed RNA portion from the cip-cel mRNA on different fates due to their stability and resolve the potential contradiction between the equimolar stoichiometry of transcripts with a within a transcription unit and the non-equimolar stoichiometry of subunits.

Results

In this work, RNA processing events were found to occur at six intergenic regions (IRs) harboring stem-loop structures in cip-cel operon. These stem-loops not only stabilize processed transcripts at their both ends, but also act as cleavage signals specifically recognized by endoribonucleases. We further demonstrated that cleavage sites were often located downstream or 3′ end of their associated stem-loops that could be classified into two types, with distinct GC-rich stems being required for RNA cleavage. However, the cleavage site in IR4 was found to be located upstream of the stem-loop, as determined by the bottom AT-pair region of this stem-loop, together with its upstream structure. Thus, our findings reveal the structural requirements for processing of cip-cel transcripts, which can be potentially used to control the stoichiometry of gene expression in an operon.

Conclusions

Our findings reveal that stem-loop structures acting as RNA cleavage signals not only can be recognized by endoribonucleases and determine the location of cleavage sites but also determine the stoichiometry of their flanking processed transcripts by controlling stability in cip-cel operon. These features represent a complexed regulation of cellulosome in the post-transcriptional level, which can be exploited for designing synthetic elements to control gene expression.
Peripheral neuropathy secondary to a ‘domino’ liver transplant: a case report
Authors: Ball Harriet A. , Stevens James , Gillmore Julian D.
Published: June 2023

Background

Peripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR).

Case presentation

We describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a ‘domino’ liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel “gene silencing” therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins.

Conclusions

This represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated.