bluuebunny/crossref_metadata_2025 huggingface dataset:
Deprescribing research in nursing home residents using routinely collected healthcare data: a conceptual framework
Authors: Thorpe Carolyn , Niznik Joshua , Li Anna
Published: August 2023

Background

Efforts are needed to strengthen evidence and guidance for appropriate deprescribing for older nursing home (NH) residents, who are disproportionately affected by polypharmacy and inappropriate prescribing. Given the challenges of conducting randomized drug withdrawal studies in this population, data from observational studies of routinely collected healthcare data can be used to identify patients who are apparent candidates for deprescribing and evaluate subsequent health outcomes. To improve the design and interpretation of observational studies examining determinants, risks, and benefits of deprescribing specific medications in older NH residents, we sought to propose a conceptual framework of the determinants of deprescribing in older NH residents.

Methods

We conducted a scoping review of observational studies examining patterns and potential determinants of discontinuing or de-intensifying (i.e., reducing) medications for NH residents. We searched PubMed through September 2021 and included studies meeting the following criteria: conducted among adults aged 65 + in the NH setting; (2) observational study designs; (3) discontinuation or de-intensification as the primary outcome with key determinants as independent variables. We conceptualized deprescribing as a behavior through a social-ecological lens, potentially influenced by factors at the intrapersonal, interpersonal, organizational, community, and policy levels.

Results

Our search in PubMed identified 250 potentially relevant studies published through September 2021. A total of 14 studies were identified for inclusion and were subsequently synthesized to identify and group determinants of deprescribing into domains spanning the five core social-ecological levels. Our resulting framework acknowledges that deprescribing is strongly influenced by intrapersonal, patient-level clinical factors that modify the expected benefits and risks of deprescribing, including index condition attributes (e.g., disease severity), attributes of the medication being considered for deprescribing, co-prescribed medications, and prognostic factors. It also incorporates the hierarchical influences of interpersonal differences relating to healthcare providers and family caregivers, NH facility and health system organizational structures, community trends and norms, and finally healthcare policies.

Conclusions

Our proposed framework will serve as a useful tool for future studies seeking to use routinely collected healthcare data sources and observational study designs to evaluate determinants, risks, and benefits of deprescribing for older NH residents.
The utility of syndecan-1 circulating levels as a biomarker in patients with previous or active COVID-19: a systematic review and meta-analysis
Authors: Ghondaghsaz Elina , Khalaji Amirmohammad , Norouzi Mitra , Fraser Douglas D. , Alilou Sanam , Behnoush Amir Hossein
Published: August 2023

Background

With the emergence of coronavirus disease of 2019 (COVID-19), several blood biomarkers have been identified, including the endothelial biomarker syndecan-1, a surface proteoglycan. In the current systematic review and meta-analysis, we aimed to assess the diagnostic and prognostic role of syndecan-1 in COVID-19.

Methods

PubMed, Embase, Scopus, and Web of Science, as international databases, were searched for relevant studies measuring blood syndecan-1 levels in COVID-19 patients, COVID-19 convalescents, and healthy control subjects, in patients with different COVID-19 severities and/or in COVID-19 patients with poor outcomes. Random-effect meta-analysis was performed using STATA to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for the comparison between COVID-19 patients and healthy control subjects or COVID-19 convalescents and controls.

Results

After screening by title/abstract and full text, 17 studies were included in the final review. Meta-analysis of syndecan-1 levels in COVID-19 compared with healthy control subjects revealed that patients with COVID-19 had significantly higher syndecan-1 levels (SMD 1.53, 95% CI 0.66 to 2.41, P < 0.01). In contrast, COVID-19 convalescent patients did not show significant difference with non-convalescents (SMD 0.08, 95% CI -0.63 to 0.78, P = 0.83). Regarding disease severity, two studies reported that more severe forms of the disease were associated with increased syndecan-1 levels. Moreover, patients who died from COVID-19 had higher syndecan-1 levels compared with survivors (SMD 1.22, 95% CI 0.10 to 2.33, P = 0.03).

Conclusion

Circulating syndecan-1 level can be used as a biomarker of endothelial dysfunction in COVID-19, as it was increased in COVID-19 patients and was higher in more severe instances of the disease. Further larger studies are needed to confirm these findings and further enlighten the role of syndecan-1 in clinical settings.
Evaluation of a depression care model for the hill tribes: a family and community-based participatory research
Authors: Singkhorn Onnalin , Hamtanon Pawadee , Moonpanane Katemanee , Pitchalard Khanittha , Sunsern Rachanee , Leaungsomnapa Yosapon , Phokhwang Chananan
Published: August 2023

Background

Even though, there is a particularly high prevalence of depression among individuals from the hill tribes in northern Thailand, they are unable to receive appropriate intervention due to cultural, transportation, communication, and legal barriers. Using community-based participatory research (CBPR), a depression care model was developed for the hill tribe population. The effectiveness of this model was examined using questionnaires, observations, focus groups, and in-depth interviews.

Methods

Participants include people with depression (n = 17) who were chosen based on their mild to moderately severe depression scores on the Patient Health Questionnaire 9-item (PHQ-9 scores of 5–19) and their caregivers (n = 5). The in-depth interview was conducted to distinguish the selected participants into two groups. The first group, the self-help group program, consisted of 12 participants endorsing negative thoughts about themselves and inappropriate problems solving. The second group, the family camp program, had ten participants, including five patients with family-related issues and their family members. Subjects separately participated in either the self-help or the family groups over three weeks. They completed the PHQ-9 at the beginning and end of the intervention. Questionnaires, observations, focus groups, and in-depth interviews were used to evaluate the effectiveness of the model. Content analysis was used to examine the qualitative data. Wilcoxon signed-rank test was used to analyze the changes in the severity of depression before and after participation in the intervention.

Results

The depression scores on the PHQ-9 of 12 participants improved significantly (11.92 ± 1.08vs.3.08 ± 0.51;p = 0.002) following participation in the self-help group. Increased self-esteem and improved interpersonal relationships were reported by participants in the self-help group program during interviews. There was no significant difference in the depression scores of 10 participating in the family camp program (6.00 ± 3.83 to 5.30 ± 3.56;p = 0.161).

Conclusion

A model for depression care was tested in a hill tribe community, and its effectiveness was clearly observed. The developed model can be applied to other hill tribe communities in northern Thailand to improve depression care.
Autoimmune diabetes mellitus after COVID-19 vaccination in adult population: a systematic review of case reports
Authors: Alsudais Ali S , Alkanani Raghad S , Fathi Abdulaziz B , Almuntashiri Saleh S , Jamjoom Jafar N , Alzhrani Mustafa A , Althubaiti Alaa , Radi Suhaib
Published: August 2023

Background

Autoimmune/type 1 diabetes mellitus (T1DM) is a recently described rare occurrence following the administration of adjuvants such as coronavirus disease 2019 (COVID-19) vaccines. This systematic review aimed to review all available literature on the potential association between COVID-19 vaccines and T1DM.

Methods

The Directory of Open Access Journals, MEDLINE, Google Scholar, and Scopus were systematically searched for all published studies from inception to July 2022. Articles reporting T1DM development within 8 weeks of administration of COVID-19 vaccine were included. Two reviewers independently performed the risk of bias assessment following the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports.

Results

Eight eligible studies were retrieved, comprising 12 patients diagnosed with T1DM after being vaccinated with a COVID-19 vaccine. Six patients (50%) reported T1DM after receiving the second dose. Five patients (41.7%) presented with diabetic ketoacidosis, of which four presented within the first eight days after vaccination. Five patients (41.7%) had genetic susceptibility, with RNA binding motif protein 45 (RBM45/DRB1) and major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) mutations being prominent.

Interpretation

In this review, we have shown a small number of new-onset diabetes cases coincidently occurring soon after the COVID-19 vaccine, especially in those with genetic susceptibility. Despite being older, these patients had a similar phenotype to T1DM. While there might be a causal relationship between COVID-19 vaccines and T1DM development, this should not influence decisions regarding vaccination since the overall benefit outweighs the risk. Further larger prospective trials are needed to assess causal relationship and to clarify the potential roles of COVID-19 vaccine-derived antigens in autoimmune disease development.

Protocol registration

PROSPERO-CRD42022342093.
Direct and residual antimicrobial effect of 2% chlorhexidine gel, double antibiotic paste and chitosan- chlorhexidine nanoparticles as intracanal medicaments against Enterococcus faecalis and Candida albicans in primary molars: an in-vitro study
Authors: Wassel Mariem , Radwan Mohamed , Elghazawy Reham
Published: August 2023

Background

Thorough disinfection of root canals in primary molars may be complicated by the complex root canal morphology. This in-vitro study aimed to compare direct and residual antimicrobial effect of 2% chlorhexidine (CHX) gel, 500 mg/ml double antibiotic paste (DAP) and chitosan-chlorhexidine nanoparticles (CS-CHX NPs) as intracanal medicaments against Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans) in primary molars.

Methods

Mesial roots of 63 mandibular second primary molars were infected with E. faecalis and C. albicans. Teeth were divided into 9 groups: Ia: (CS-CHX NPs), IIa: (CHX), IIIa: (DAP), IVa: chitosan nanoparticles (CSNPs) in which medicaments were placed for 3 days, groups Ib: (CS-CHX NPs), IIb: CHX, IIIb: (DAP), IVb: (CSNPs) in which medicaments were placed for 7 days, and Group V (control): teeth were infected, irrigated with saline, and sampled 3- and 7-days post-infection. Microbiological samples were obtained after infection, 3, and 7 days after medicament placement and 7 days after medicament removal for both time points. One-way ANOVA, Tukey’s post hoc test and paired t-test were used at p < 0.05.

Results

CS-CHX NPs had the highest anticandidal effect which was comparable to CHX and significantly higher than other medicaments (p < 0.001) at both time points. CS-CHX NPs had the highest effect against E. faecalis which was comparable to DAP and significantly higher than other medicaments (p < 0.001) at 3 days. All medicaments showed similar effect against E. faecalis after 7 days. The 7-days placement significantly increased the antimicrobial effect against both micro-organisms in all groups, except CS-CHX NPs which showed an insignificant increase. CS-CHX NPs showed the highest residual effect against both micro-organisms that increased with 7-days placement.

Conclusion

CSNPs and CHX combination showed a synergistic effect against both micro-organisms. CS-CHX NPs displayed a higher effect at a shorter period compared to other medicaments, yet its residual effect was higher with 7-days placement.
Photocrosslinkable gelatin-treated dentin matrix hydrogel as a novel pulp capping agent for dentin regeneration: I. synthesis, characterizations and grafting optimization
Authors: Sedek Eman M. , Kamoun Elbadawy A. , El-Deeb Nehal M. , Abdelkader Sally , Fahmy Amal E. , Nouh Samir R. , Khalil Nesma Mohamed
Published: August 2023

Background

In recent years, treated dentin matrix (TDM) has been introduced as a bioactive hydrogel for dentin regeneration in DPC. However, no study has introduced TDM as a photocrosslinkable hydrogel with a natural photoinitiating system. Therefore, the present study aimed to explore the synthesis, characterizations and grafting optimization of injectable gelatin- glycidyl methacrylate (GMA)/TDM hydrogels as a novel photocrosslinkable pulp capping agent for dentin regeneration.

Methods

G-GMA/TDM hydrogel was photocrosslinked using a new two-component photoinitiating system composed of riboflavin as a photoinitiator under visible light and glycine as a first time coinitiator with riboflavin. The grafting reaction conditions of G-GMA/TDM e.g. GMA concentration and reaction time were optimized. The kinetic parameters e.g. grafting efficiency (GE) and grafting percentage (GP%) were calculated to optimize the grafting reaction, while yield (%) was determined to monitor the formation of the hydrogel. Moreover, G-GMA/TDM hydrogels were characterized by swelling ratio, degradation degree, and cytotoxicity. The instrumental characterizations e.g. FTIR, 1H-NMR, SEM and TGA, were investigated for verifying the grafting reaction. Statistical analysis was performed using F test (ANOVA) and Post Hoc Test (P = 0.05).

Results

The grafting reaction dramatically increased with an increase of both GMA concentration and reaction time. It was realized that the swelling degree and degradation rate of G-GMA/TDM hydrogels were significantly reduced by increasing the GMA concentration and prolonging the reaction time. When compared to the safe low and moderate GMA content hydrogels (0.048, 0.097 M) and shorter reaction times (6, 12, 24 h), G-GMA/TDM with high GMA contents (0.195, 0.391 M) and a prolonged reaction time (48 h) demonstrated cytotoxic effects against cells using the MTT assay. Also, the morphological surface of G-GMA/TDM freeze-dried gels was found more compacted, smooth and uniform due to the grafting process. Significant thermal stability was noticed due to the grafting reaction of G-GMA/TDM throughout the TGA results.

Conclusions

G-GMA/TDM composite hydrogel formed by the riboflavin/glycine photoinitiating system is a potential bioactive and biocompatible system for in-situ crosslinking the activated-light pulp capping agent for dentin regeneration.
Effect of mouthwashes on the force decay of polymeric ligature chains used for dental purposes: a systematic review and meta-analysis
Authors: Castelló Carolina Andrés , Zamora-Martínez Natalia , Paredes-Gallardo Vanessa , Tarazona-Álvarez Beatriz
Published: August 2023

Background

External factors such as the daily use of antimicrobial mouthwashes to maintain oral hygiene and to reduce the microbial activity can contribute to alter the mechanical properties of the elastomeric chains used during orthodontic treatments, causing loss of effectiveness. This systematic review and a meta-analysis assessed the rate of force decay and degradation of the polymeric chains depending on the type of mouthwash.

Methods

A systematic search of the literature were there was an exposure of orthodontic elastomeric chains to certain mouthwashes was conducted in the electronic databases of PubMed, Cochrane Library (CENTRAL), Scopus, EMBASE and Web of Science, as well as grey literature (Opengrey). No limit was placed on publication year and research was done up to June 2022. Based on inclusion/ exclusion criteria, data were extracted by two independent reviewers. For the quantitative analysis, studies were analysed with a mixed-effect (random effect) meta-regression model, with beta coefficients and R [2] values. I [2] index and Q and Egger tests were used to find heterogeneity among studies.

Results

A total of 178 potentially eligible studies were identified, of which 14 were eventually included in the qualitative analysis and 14 in the quantitative meta-analysis. The meta-analysis showed that all the mouthwashes were associated with a greater force decay than the control groups. After 7 days (p = 0.005) significant differences were found among the different mouthwashes, with those containing alcohol having significantly higher impact on the force decay than those containing chlorhexidine 0.2%, sodium fluoride or Persica. However, at 24 h (p = 0.200), 14 days (p = 0.076), 21 days (p = 0.120) and 28 days (p = 0.778) no statistically significant differences among the different mouthwashes were found, although those containing alcohol presented a strong tendency.

Conclusion

Although mouthwashes tend to increase the speed of force decay of elastomeric chains, especially those containing alcohol, clorhexidine 0.2% can be a good alternative due to its low impact on the force decay and its ability to maintain low microbial activity. More in vitro and in vivo studies comparing different manufacturers and other agents should be performed.
Management of encounters related to subfertility and infertility in Australian general practice: a focus on Aboriginal and Torres Strait Islander females
Authors: Gilbert E , Rumbold A. , Campbell S. , Boyle J. A. , Grzeskowiak L.
Published: August 2023

Objective

To investigate the management of subfertility and infertility among Aboriginal and Torres Strait Islander females attending Australian general practice.

Methods

Cross-sectional study of 1,258,581 women (18–49 years) attending general practice between January 2011 and June 2019, utilising data from NPS MedicineWise MedicineInsight, a national general practice database in Australia.

Results

The prevalence of subfertility/infertility encounters was lower for Aboriginal and Torres Strait Islander females (12.37 per 1,000) than for non-Indigenous females (16.62 per 1,000). Aboriginal and Torres Strait Islander females with a subfertility/infertility encounter were younger and more likely to live outside Major cities and in areas of socioeconomic disadvantage than non-Indigenous females. Rates of prescribed infertility medications were not different between groups, however Aboriginal and Torres Strait Islander females were more likely to receive a pelvic ultrasound (24.30% vs. 19.90%); tests for luteinizing hormone (31.89% vs. 25.65%); testosterone (14.93% vs. 9.96%) and; glycated haemoglobin (HbA1c) (6.32% vs. 3.41%),but less likely to receive an anti-müllerian hormone test (2.78% vs. 7.04%).

Conclusions

Lower encounter rates for infertility/subfertility among Aboriginal and Torres Strait Islander peoples may indicate access issues, preferred use of Aboriginal community-controlled health centres or younger average age at first birth and thus less age-related infertility.

Implications for public health

Future efforts should focus on maximising the inclusiveness of infertility surveillance. There is also a need for further research into the experiences of and preferences for infertility care and associated barriers among Aboriginal and Torres Strait Islander people.
Pathways to medical abortion self-use (MASU): results from a cross-sectional survey of women’s experiences in Kenya and Uganda
Authors: Ouma Ogol Japheth , Ngoga Edward O. , Odongo Isaac , Sigu Biko Steve , Akol Angela
Published: August 2023

Background

In Kenya and Uganda, unsafe abortions are a leading cause of maternal mortality. The new WHO policy guidelines on the safe termination of pregnancies up to 9 weeks lack information on women’s experiences with self-administered medical abortion (MA), impeding the development of interventions to increase MA use. This study aimed to comprehend women’s experiences with MA in Kenyan and Ugandan pharmacies.

Methods

A cross-sectional mixed-methods survey utilized data from medical registers in 71 purposefully identified pharmacies and clinics dispensing MA drugs between September and October 2021. Forty women who were MA users participated in focus group discussions. The main outcome variables were: sources of MA information, costs of MA services, complications from MA, pain management, follow-up rates, and use of post-MA contraception. Quantitative data were analyzed using Stata 15, while qualitative thematic analysis was conducted using Dedoose qualitative analysis software.

Results

73.6% of 2,366 women got an MA, both in Kenya (79%) and Uganda (21%). Most (59.1%) were walk-in clients. Kenya had significantly more women referred for MA (49.9%) than Uganda (10.1%) (p 0.05). Friends and family members were the main sources of MA information. The median cost of MA was USD 18 (IQR 10–60.5) in Kenya and USD 4.2 (IQR 2–12) in Uganda. Most MA clients received pain management (89.6%), were followed up (81%), and received post-MA contraception (97.6%). Qualitative results indicated a lack of medicines, high costs of MA, complications, stigma, and inadequate training of providers as barriers to MA use.

Conclusions and recommendations

Communities are a valuable information resource for MA, but only if they have access to the right information. A relatively weak health referral system in Uganda highlights the importance of pharmacies and clinicians collaborating to support clients’ abortion needs and contraceptive use after medical abortion (MA). Low client follow-up rates show how important it is to make sure pharmacy technicians know how to give MA correctly. Finally, it is crucial to strengthen the supply chain for MA products in order to eliminate cost barriers to access.
Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK
Authors: Henderson Alasdair D. , Adesanya Elizabeth , Mulick Amy , Matthewman Julian , Vu Nhung , Davies Firoza , Smith Catherine H. , Hayes Joseph , Mansfield Kathryn E. , Langan Sinéad M.
Published: August 2023

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997–2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13–1.16], psoriasis 1.17 [1.15–1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1–1.12], psoriasis 1.21 [1.19–1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.
Coat color affects the resilience against heat stress impacts on testicular hemodynamics, reproductive hormones, and semen quality in Baladi goats
Authors: El-Sherbiny Hossam R. , Hashem Nesrein M. , Abdelnaby Elshymaa A.
Published: August 2023

Drastic climatic changes threaten animal productivity and prolificacy, whose adaptability is governed by its pheno- and genotypic traits. This study was aimed at investigating the effect of coat color on the adaptability of goat bucks under heat stress conditions from the perspectives of testicular blood flow (TBF) and biometry, reproductive hormones, and semen quality. Twenty bucks (Capra hircus) bearing different coat colors were selected from a large flock and divided into four equal groups (n = 5 each) as follows: black coat (BC; 100% black), brown coat (BrC; 100% dark brown), white coat (WC; 100% white), white-black coat (WBC; 50–60% white). Bucks were examined for TBF [Doppler ultrasonography and serum nitric oxide (NO)], testosterone (T) and luteinizing hormone (LH), seminal plasma oxidative biomarkers [catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA)], and sperm traits percentages [progressive motility (PM), viability (SV), normal morphology (NM), and sperm concentration (SC) once a week for seven consecutive weeks (W1-W7) in the summer season (temperature humidity index = 88.4–92.2). Specifically, at W3-W7, darker bucks (BC and BrC) testicular volume, testicular colored area, T, NO, CAT, TAC, PM, SV, NM, and SC (W7 only) differed significantly (P < 0.05) by decrease than the lighter ones (WC and WBC). Both Doppler indices and serum MDA concentrations were elevated (P < 0.05) at W3-W7 in the BC and BrC bucks compared to WC and WBC groups. In conclusion, bucks with lighter coats were more resistant to the negative effects of HS on TBF, seminal oxidative biomarkers, and semen quality.
Food insecurity and unmet healthcare needs in South Korea
Authors: Choe Hwi , Pak Tae-Young
Published: August 2023

Background

Food insecurity is a significant risk factor for chronic and infectious diseases. It is also a barrier to accessing healthcare because food insecurity tends to co-occur with other socioeconomic disadvantages. The objective of this study is to examine whether food insecure individuals in South Korea can access desired level of healthcare when needed.

Methods

This repeated cross-sectional study used data from the 2013–2015 and 2019–2021 waves of the Korean National Health and Nutrition Examination Survey. Multivariable logistic regression models were used to examine the association between household food insecurity and two indicators of unmet healthcare needs - any experience of forgoing medical service and the reasons for unmet needs (problems with availability, acceptability, and accessibility). Covariates indicating predisposing, enabling, and need factors were included in the regression analyses.

Results

Of the 19,394 participants aged 19–64 years, 4.5% were moderately food insecure, 0.9% were severely food insecure, and 9.3% reported unmet healthcare needs. In the adjusted model, moderate food insecurity (OR, 1.47; 95% CI, 1.19–1.82) and severe food insecurity (OR, 3.32; 95% CI, 2.27–4.85) were associated with higher odds of unmet healthcare needs in a dose-graded manner. These associations were largely due to the increased odds of accessibility-related unmet needs among participants with moderate (OR, 2.31; 95% CI, 1.68–3.19) and severe food insecurity (OR, 6.15; 95% CI, 3.91–9.68).

Conclusions

Food insecurity was associated with higher odds of unmet healthcare needs among Korean adults. Competing life demands may have a cumulative impact on health over the short and long term. Efforts to address trade-offs between healthcare needs and food insecurity may improve the health and well-being of marginalized populations.
Increased age, bilirubin, international normalized ratio, and creatinine score to triglyceride ratio are associated with alcohol-associated primary liver carcinoma: a single-centered retrospective study
Authors: Jia Xiaoqing , Li Rong , Zhang Xiaoting , Zhou Tao , Sun Dalong , Yang Na , Luo Zheng
Published: August 2023

Background

This study analyzed the clinical features and biomarkers of alcohol-associated liver disease (ALD) to investigate the diagnostic value of age, bilirubin, international normalized ratio (INR), and creatinine (ABIC) score to triglyceride (TG) ratio (ABIC/TG) in ALD-associated primary liver carcinoma (PLC).

Materials and methods

Data were collected from 410 participants with ALD, and the epidemiological and clinical records of 266 participants were analyzed. Participants were divided into ALD-without-PLC and ALD-associated-PLC groups. Relationships between clinical characteristics, biomarkers and ALD-associated PLC were estimated. Serum lipid levels and liver function were compared between ALD patients without PLC and patients with ALD-associated PLC. Scoring systems were calculated to investigate ALD severity. The robustness of the relationship was analyzed by the receiver operating characteristic (ROC) curve.

Results

Age and dyslipidemia were more strongly associated with ALD-associated PLC than with ALD-without PLC, with AORs of 2.39 and 0.25, respectively, with P less than 0.05. Drinking time and average daily intake, ABIC score, and ABIC/TG ratio were significantly higher in the ALD-associated-PLC group than in the ALD-without-PLC group. The AUC for the ABIC/TG ratio predicting the incidence of PLC was 0.80 (P < 0.01), which was higher than that of the ABIC and TG scores alone; additionally, the specificity and Youden index for the ABIC/TG ratio were also higher, and the cutoff value was 6.99.

Conclusions

In ALD patients, age, drinking time, and average daily intake were risk factors for PLC. Drinking time, average daily intake, TG and ABIC score have diagnostic value for ALD-associated PLC. The ABIC/TG ratio had a higher AUC value and Youden index than the ABIC score and TG level.
Treatment regimens, patient reported outcomes and health-related quality of life in children with moderate and severe hemophilia A in China: using real-world data
Authors: Zhang Luying , Zhang Peng , Chen Wen
Published: August 2023

Background

Prophylaxis therapy for children with moderate and severe hemophilia A (HA) is the optimal treatment regimen. The real-world treatment regimens, patient-reported outcomes, and health-related quality of life (HRQoL) in children with moderate and severe HA in China are less known.

Objective

This study aimed to describe real-world treatment regimens and evaluate the association of treatment regimens with comprehensive patient-reported outcomes including bleeds, chronic pain, target joints, disability, and HRQoL in children under 18 years old with HA in China.

Methods

Real-world data of a nationwide online cross-sectional survey in 2021 and patients’ coagulation factor utilization data from self-management records from 2020 to 2021 were merged. 373 eligible children were included and categorized by treatment regimens according to the Chinese guideline: on-demand, short-term prophylaxis, and long-term prophylaxis treatment.

Results

Currently, in China, 4.8% of children with HA are receiving full-dose long-term prophylaxis treatment. Prophylaxis treatment was a significant positive predictor of better patient-reported outcomes and HRQoL. For children with prophylaxis treatment, there were significantly fewer annual bleeds (p < 0.001), lower frequency of chronic pain(p < 0.001), and higher health utility scores(p < 0.01) and EQ-VAS scores(p < 0.05) than children with on-demand treatment.

Conclusion

Accessible long-term prophylaxis treatment should be promoted for children with moderate and severe HA in China and regular monitoring of their outcomes and HRQoL should be carried out.
VPS35 and α-Synuclein fail to interact to modulate neurodegeneration in rodent models of Parkinson’s disease
Authors: Chen Xi , Tsika Elpida , Levine Nathan , Moore Darren J.
Published: August 2023

Background

Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene cause late-onset, autosomal dominant Parkinson’s disease (PD), with a single missense mutation (Asp620Asn, D620N) known to segregate with disease in families with PD. The VPS35 gene encodes a core component of the retromer complex, involved in the endosomal sorting and recycling of transmembrane cargo proteins. VPS35-linked PD is clinically indistinguishable from sporadic PD, although it is not yet known whether VPS35-PD brains exhibit α-synuclein-positive brainstem Lewy pathology that is characteristic of sporadic cases. Prior studies have suggested a functional interaction between VPS35 and the PD-linked gene product α-synuclein in lower organisms, where VPS35 deletion enhances α-synuclein-induced toxicity. In mice, VPS35 overexpression is reported to rescue hippocampal neuronal loss in human α-synuclein transgenic mice, potentially suggesting a retromer deficiency in these mice.

Methods

Here, we employ multiple well-established genetic rodent models to explore a functional or pathological interaction between VPS35 and α-synuclein in vivo.

Results

We find that endogenous α-synuclein is dispensable for nigrostriatal pathway dopaminergic neurodegeneration induced by the viral-mediated delivery of human D620N VPS35 in mice, suggesting that α-synuclein does not operate downstream of VPS35. We next evaluated retromer levels in affected brain regions from human A53T-α-synuclein transgenic mice, but find normal levels of the core subunits VPS35, VPS26 or VPS29. We further find that heterozygous VPS35 deletion fails to alter the lethal neurodegenerative phenotype of these A53T-α-synuclein transgenic mice, suggesting the absence of retromer deficiency in this PD model. Finally, we explored the neuroprotective capacity of increasing VPS35 expression in a viral-based human wild-type α-synuclein rat model of PD. However, we find that the overexpression of wild-type VPS35 is not sufficient for protection against α-synuclein-induced nigral dopaminergic neurodegeneration, α-synuclein pathology and reactive gliosis.

Conclusion

Collectively, our data suggest a limited interaction of VPS35 and α-synuclein in neurodegenerative models of PD, and do not provide support for their interaction within a common pathophysiological pathway.
miR-203 drives breast cancer cell differentiation
Authors: Martínez-Illescas Nuria G. , Leal Silvia , González Patricia , Graña-Castro Osvaldo , Muñoz-Oliveira Juan José , Cortés-Peña Alfonso , Gómez-Gil María , Vega Zaira , Neva Verónica , Romero Andrea , Quintela-Fandino Miguel , Ciruelos Eva , Sanz Consuelo , Aragón Sofía , Sotolongo Leisy , Jiménez Sara , Caleiras Eduardo , Mulero Francisca , Sánchez Cristina , Malumbres Marcos , Salazar-Roa María
Published: August 2023

A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.
Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning
Authors: Horlacher Marc , Wagner Nils , Moyon Lambert , Kuret Klara , Goedert Nicolas , Salvatore Marco , Ule Jernej , Gagneur Julien , Winther Ole , Marsico Annalisa
Published: August 2023

We present RBPNet, a novel deep learning method, which predicts CLIP-seq crosslink count distribution from RNA sequence at single-nucleotide resolution. By training on up to a million regions, RBPNet achieves high generalization on eCLIP, iCLIP and miCLIP assays, outperforming state-of-the-art classifiers. RBPNet performs bias correction by modeling the raw signal as a mixture of the protein-specific and background signal. Through model interrogation via Integrated Gradients, RBPNet identifies predictive sub-sequences that correspond to known and novel binding motifs and enables variant-impact scoring via in silico mutagenesis. Together, RBPNet improves imputation of protein-RNA interactions, as well as mechanistic interpretation of predictions.
The detection and management of attempted fraud during an online randomised trial
Authors: Willis Thomas A. , Wright-Hughes Alexandra , Skinner Clare , Farrin Amanda J. , Hartley Suzanne , Walwyn Rebecca , Weller Ana , Althaf Mohamed , Wilson Stephanie , Gale Chris P. , Foy Robbie
Published: August 2023

Background

Online studies offer an efficient method of recruiting participants and collecting data. Whilst delivering an online randomised trial, we detected unusual recruitment activity. We describe our approach to detecting and managing suspected fraud and share lessons for researchers.

Methods

Our trial investigated the single and combined effects of different ways of presenting clinical audit and feedback. Clinicians and managers who received feedback from one of five United Kingdom national clinical audit programmes were emailed invitations that contained a link to the trial website. After providing consent and selecting their relevant audit, participants were randomised automatically to different feedback versions. Immediately after viewing their assigned feedback, participants completed a questionnaire and could request a financial voucher by entering an email address. Email addresses were not linked to trial data to preserve participant anonymity. We actively monitored participant numbers, questionnaire completions, and voucher claims.

Results

Following a rapid increase in trial participation, we identified 268 new voucher claims from three email addresses that we had reason to believe were linked. Further scrutiny revealed duplicate trial completions and voucher requests from 24 email addresses. We immediately suspended the trial, improved security measures, and went on to successfully complete the study.

We found a peak in questionnaires completed in less than 20 seconds during a likely contamination period. Given that study and personal data were not linked, we could not directly identify the trial data from the 268 duplicate entries within the 603 randomisations occurring during the same period. We therefore excluded all 603 randomisations from the primary analysis, which was consequently based on 638 randomisations. A sensitivity analysis, including all 961 randomisations over the entire study except for questionnaire completions of less than 20 seconds, found only minor differences from the primary analysis.

Conclusion

Online studies offering incentives for participation are at risk of attempted fraud. Systematic monitoring and analysis can help detect such activity. Measures to protect study integrity include linking participant identifiers to study data, balancing study security and ease of participation, and safeguarding the allocation of participant incentives.

Trial registration

International Standard Randomised Controlled Trial Number: ISRCTN41584028. Registration date is August 17, 2017.
Metagenomics revealed a correlation of gut phageome with autism spectrum disorder
Authors: Shahin Khashayar , Soleimani-Delfan Abbas , He Zihan , Sansonetti Philippe , Collard Jean-Marc
Published: August 2023

The human gut bacteriome is believed to have pivotal influences on human health and disease while the particular roles associated with the gut phageome have not been fully characterized yet with few exceptions. It is argued that gut microbiota can have a potential role in autism spectrum disorders (ASD). The public microbiota database of ASD and typically developing (TD) Chinese individuals were analyzed for phage protein-coding units (pPCU) to find any link between the phageome and ASD. The gut phageome of ASD individuals showed a wider diversity and higher abundance compared to TD individuals. The ASD phageome was associated with a significant expansion of Caudoviricetes bacteriophages. Phages infecting Bacteroidaceae and prophages encoded within Faecalibacterium were more frequent in ASD than in TD individuals. The expansion and diversification of ASD phageome can influence the bacterial homeostasis by imposing pressure on the bacterial communities. In conclusion, the differences of phages community in in ASD and TD can be used as potential diagnosis biomarkers of ASD. Further investigations are needed to verify the role of gut phage communities in the pathogenesis of ASD.
Monitoring montane-subalpine forest ecotone in the Pyrenees through sequential forest inventories and Landsat imagery
Authors: Aulló-Maestro Isabel , Gómez Cristina , Hernández Laura , Camarero J. Julio , Sánchez-González Mariola , Cañellas Isabel , Vázquez de la Cueva Antonio , Montes Fernando
Published: August 2023

Key message

Abies albaMill.–Pinus uncinataRamond. ecotone dynamics are examined along both altitudinal and protection level gradients by combining field inventories and Landsat data. An upward expansion ofA. albato the subalpine belt is observed in the last decades as a result of stand maturation after logging cessation.

Context

High-mountain forests constitute sensitive locations to monitor the impacts of global change on tree-species composition and ecotone dynamics. In this study, we focus on the Spanish Pyrenees where silver fir (Abies albaMill.) coexists with mountain pine (Pinus uncinataRamond.) forming montane-subalpine ecotones.

Aims

The main goal of this study is to assess the spatiotemporal dynamics of the silver fir–mountain pine ecotone and its underlying driving factors.

Methods

We reconstructed the spatial distribution and dynamics of the species by combining remote sensing imagery and field plot data from 1989 to 2015, employing support vector machine techniques for image classification. Using variance analysis and mixed effects models, we then analyzed the evolution of basal area and replacement index, a measure of relative change in species composition, over time and altitude range. Additionally, we explored their relationship with site factors and protection level (National Park vs. protection buffer zone).

Results

Silver fir has expanded its distribution in both the National Park and the protection buffer zone, whereas mountain pine has remained stable. Both species exhibit increased basal area associated with stand maturation and a higher level of protection. The replacement index indicates a rise in silver fir in the understory on North-facing slopes, attributed to stand densification. These findings are particularly noticeable in the area with the highest level of protection.

Conclusion

The cessation of traditional land uses has led to ongoing stand densification, promoting succession and favoring the increased abundance of silver fir at its uppermost locations, where this species outcompetes mountain pine.
Driving mechanisms of productivity stability vary with selective harvesting intensities in a mixed broad-leaved Korean pine forest
Authors: Geng Yan , Xiang Kehan , Zhang Chunyu , Zhao Xiuhai
Published: August 2023

Key message

We found that the stabilizing mechanisms for forest productivity varied across harvesting intensities in a mixed broad-leaved Korean pine forest. Effects of overyielding at high species richness and species asynchrony occurred only in unharvested and lightly harvested plots, whereas asymmetries between individuals of different size contributed significantly to stabilizing productivity when harvestings became intensive.

Context

Understanding the driving factors of forest ecosystem stability has become increasingly crucial in forest management. However, it remains unclear whether and how the stabilizing mechanisms of forest productivity might be influenced by management practices.

Aims

We related the temporal stability of aboveground biomass productivity to harvesting history. We further tested how three key driving mechanisms of stability might be modulated by selective harvesting intensities.

Methods

Based on a 10-year monitoring (five repeated tree inventories) of a mixed broad-leaved Korean pine forest in Northeastern China recovering from selective harvesting, we examined the relative importance of two diversity-dependent mechanisms (overyielding and species asynchrony) and one size-dependent mechanism (asymmetric growth) for productivity stability across a wide range of intensities (0–73.4% basal area removed).

Results

We found that selective harvesting significantly lowered the productivity stability, species asynchrony, and growth dominance coefficient. Growth dominance coefficient had an overall stronger effect on stability than species richness and asynchrony. Moreover, the strengths of stabilizing mechanisms varied across harvesting intensities: effects of overyielding at high species richness and species asynchrony were detected only in unharvested and lightly harvested plots, whereas the explanatory power of growth dominance coefficient outweighed the diversity-related variables when harvesting became intensive.

Conclusions

We emphasized the importance to consider both diversity- and size-related explanatory variables as potential mechanisms for the temporal stability of forest productivity. In fact, how growth is partitioned among trees of different species as well as sizes may co-determine the response of forest stability to disturbances.