bluuebunny/crossref_metadata_2025 huggingface dataset:
East‒West genetic differentiation across the Indo-Burma hotspot: evidence from two closely related dioecious figs
Authors: Huang Jian-Feng , Li Shu-Qiong , Xu Rui , Peng Yan-Qiong
Published: June 2023

Background

Understanding biodiversity patterns and their underlying mechanisms is of interest to ecologists, biogeographers and conservationists and is critically important for conservation efforts. The Indo-Burma hotspot features high species diversity and endemism, yet it also faces significant threats and biodiversity losses; however, few studies have explored the genetic structure and underlying mechanisms of Indo-Burmese species. Here, we conducted a comparative phylogeographic analysis of two closely related dioeciousFicusspecies,F. hispidaandF. heterostyla, based on wide and intensive population sampling across Indo-Burma ranges, using chloroplast (psbA-trnH, trnS-trnG) and nuclear microsatellite (nSSR) markers, as well as ecological niche modeling.

Results

The results indicated large numbers of population-specific cpDNA haplotypes and nSSR alleles in the two species.F. hispidashowed slightly higher chloroplast diversity but lower nuclear diversity thanF. heterostyla. Low-altitude mountainous areas of northern Indo-Burma were revealed to have high genetic diversity and high habitat suitability, suggesting potential climate refugia and conservation priority areas. Strong phylogeographic structure and a marked east‒west differentiation pattern were observed in both species, due to the interactions between biotic and abiotic factors. Interspecific dissimilarities at fine-scale genetic structure and asynchronized historical dynamics of east‒west differentiation between species were also detected, which were attributed to different species-specific traits.

Conclusions

We confirm hypothesized predictions that interactions between biotic and abiotic factors largely determine the patterns of genetic diversity and phylogeographic structure of Indo-Burmese plants. The east‒west genetic differentiation pattern observed in two targeted figs can be generalized to some other Indo-Burmese plants. The results and findings of this work will contribute to the conservation of Indo-Burmese biodiversity and facilitate targeted conservation efforts for different species.
Efficacy of initial caspofungin plus trimethoprim/sulfamethoxazole for severe PCP in patients without human immunodeficiency virus infection
Authors: Qi Hui , Dong Danjiang , Liu Ning , Xu Ying , Qi Mengzhi , Gu Qin
Published: June 2023

Background

The number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients.

Methods

A retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups.

Results

A total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy.

Conclusions

For non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.
Nomogram for predicting survival in patients with advanced hepatocellular carcinoma treated with PD-1 inhibitors: incorporating pre-treatment and post-treatment clinical parameters
Authors: Jia Guhe , Qiu Lupeng , Zheng Hongye , Qin Boyu , Sun Zhuoya , Shao Yangyang , Yang Zizhong , Shao Jiakang , Zhou Yuxin , Jiao Shunchang
Published: June 2023

Background

Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications.

Methods

We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed.

Results

The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), hemoglobin (Hb) at 6-week (p = 0.042), neutrophil-to-lymphocyte ratio (NLR) at 6-week (p < 0.001), system immune inflammation index (SII) at 6-week (p = 0.125) as predictors of PFS, and alpha fetoprotein (AFP) (p = 0.035), platelet-to-lymphocyte ratio (PLR) (p = 0.012), Hb at 6-week (p = 0.010) and NLR at 6-week (p = 0.020) as predictors of OS. Furthermore, the results suggest that the OS and PFS nomogram model were in agreement with actual observations.

Conclusion

Biomarkers in peripheral blood can predict the prognosis of patients with aHCC treated with anti-PD-1 antibody. The development of nomogram models can help us to screen potential patients who can benefit from immunotherapy.
Improving eye care quality through brief verbal intervention on optometry service provider by using unannounced standardized patient with refractive error: study protocol for a randomized controlled trial
Authors: Liang Huijuan , Li Jiaqi , Zhang Nan , Wu Fang , Chen Xiaoshan , Luo Huanyuan , He Wenjun , Liu Siyuan , Kang Ting , Zhang Ruotong , Liu Yujie , Huang Zizhen , Zhang Lanping , Zhao Qing , Lv Sensen , Li Chunping , Xie Yunyun , Xu Dong
Published: June 2023

Background

Improper refractive correction can be harmful to eye health, aggravating the burden of vision impairment. During most optometry clinical consultations, practitioner-patient interactions play a key role. Maybe it is feasible for patients themselves to do something to get high-quality optometry. But the present empirical research on the quality improvement of eye care needs to be strengthened. The study aims to test the effect of the brief verbal intervention (BVI) through patients on the quality of optometry service.

Methods

This study will take unannounced standardized patient (USP) with refractive error as the core research tool, both in measurement and intervention. The USP case and the checklist will be developed through a standard protocol and assessed for validity and reliability before its full use. USP will be trained to provide standardized responses during optical visits and receive baseline refraction by the skilled study optometrist who will be recruited within each site. A multi-arm parallel-group randomized trial will be used, with one common control and three intervention groups. The study will be performed in four cities, Guangzhou and three cities in Inner Mongolia, China. A total of 480 optometry service providers (OSPs) will be stratified and randomly selected and divided into four groups. The common control group will receive USP usual visits (without intervention), and three intervention groups will separately receive USP visits with three kinds of BVI on the patient side. A detailed outcome evaluation will include the optometry accuracy, optometry process, patient satisfaction, cost information and service time. Descriptive analysis will be performed for the survey results, and the difference in outcomes between interventions and control providers will be compared and statistically tested using generalized linear models (GLMs).

Discussion

This research will help policymakers understand the current situation and influencing factors of refractive error care quality, and then implement precise policies; at the same time, explore short and easy interventions for patients to improve the quality of optometry service.

Trial registration

Chinese Clinical Trial Registry ChiCTR2200062819. Registered on August 19, 2022.
Comparison of the morphological characteristics of the choroidal sublayer between idiopathic macular holes and epiretinal membranes with automatic analysis
Authors: Zhang Shijie , Li Junmeng , Zhang Wenbo , Zhang Yanzhen , Gu Xiaopeng , Zhang Yadi
Published: June 2023

Purpose

To compare the choroidal sublayer morphologic features between idiopathic macular hole (IMH) and idiopathic epiretinal membrane (iERM) on spectral-domain optical coherent tomography (SD-OCT) using an automatic segmentation model.

Methods

Thirty-three patients with idiopathic IMHs and 44 with iERMs who underwent vitrectomies were involved. The enhanced depth imaging mode of SD-OCT was used to obtain the B-scan image after single line scanning of the macular fovea. The choroidal sublayer automatic analysis model divides the choroidal into the choroidal large vessel layer, the middle vessel layer and the small vessel layer (LVCL, MVCL and SVCL, respectively) and calculates the choroidal thickness (overall, LVCL, MVCL and SVCL) and vascular index (overall, LVCL, MVCL and SVCL). The morphological characteristics of the choroidal sublayer in the ERM eyes and the IMH eyes were compared.

Results

The mean choroidal thickness in the macular centre of the IMH eyes was significantly thinner than that of the ERM eyes (206.35 ± 81.72 vs. 273.33 ± 82.31 μm; P < 0.001). The analysis of the choroidal sublayer showed that the MVCL and SVCL macular centres and 0.5–1.5 mm of the nasal and temporal macula were significantly thinner in the IMH eyes than in the ERM eyes (P < 0.05), and there was a difference in the macular centre of the LVCL between the two groups (P < 0.05). In contrast, the choroidal vascular index of the macular centre in the IMH eyes was significantly higher than that in iERM eyes (0.2480 ± 0.0536 vs. 0.2120 ± 0.0616; P < 0.05). There was no significant difference in the CVI of other parts of the macula, the LVCL or MVCL between the two groups.

Conclusion

The choroidal thickness of the IMH eyes was significantly thinner than that of the iERM eyes, which was mainly observed in 3 mm of the macular centre and the MVCL and SVCL layers of the choroid. The choroidal vascular index of the IMH eyes was higher than that of the iERM eyes. These findings suggest that the choroid may be involved in the pathogenesis of IMH and iERM.
Cataract surgery in neovascular AMD: impact on visual acuity and disease activity
Authors: Tang Hin Yan , Rosén Mats , Granstam Elisabet
Published: June 2023

Background

Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD.

Methods

Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority.

Results

In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF.

Conclusion

Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.
The difference between shorter- versus longer-term psychotherapy for adult mental health disorders: a systematic review with meta-analysis
Authors: Juul Sophie , Jakobsen Janus Christian , Jørgensen Caroline Kamp , Poulsen Stig , Sørensen Per , Simonsen Sebastian
Published: June 2023

Background

The optimal psychotherapy duration for mental health disorders is unclear. Our aim was to assess the beneficial and harmful effects of shorter- versus longer-term psychotherapy for adult mental health disorders.

Method

We searched relevant databases and websites for published and unpublished randomised clinical trials assessing different durations of the same psychotherapy type before June 27, 2022. Our methodology was based on Cochrane and an eight-step procedure. Primary outcomes were quality of life, serious adverse events, and symptom severity. Secondary outcomes were suicide or suicide-attempts, self-harm, and level of functioning.

Results

We included 19 trials randomising 3,447 participants. All trials were at high risk of bias. Three single trials met the required information size needed to confirm or reject realistic intervention effects. One single trial showed no evidence of a difference between 6 versus 12 months dialectical behavioral therapy for borderline personality when assessing quality of life, symptom severity, and level of functioning. One single trial showed evidence of a beneficial effect of adding booster sessions to 8 and 12 weeks of internet-based cognitive behavioral therapy for depression and anxiety when assessing symptom severity and level of functioning. One single trial showed no evidence of a difference between 20 weeks versus 3 years of psychodynamic psychotherapy for mood- or anxiety disorders when assessing symptom severity and level of functioning. It was only possible to conduct two pre-planned meta-analyses. Meta-analysis showed no evidence of a difference between shorter- and longer-term cognitive behavioural therapy for anxiety disorders on anxiety symptoms at end of treatment (SMD: 0.08; 95% CI: -0.47 to 0.63; p = 0.77; I2 = 73%; four trials; very low certainty). Meta-analysis showed no evidence of a difference between shorter and longer-term psychodynamic psychotherapy for mood- and anxiety disorders on level of functioning (SMD 0.16; 95% CI -0.08 to 0.40; p = 0.20; I2 = 21%; two trials; very low certainty).

Conclusions

The evidence for shorter versus longer-term psychotherapy for adult mental health disorders is currently unclear. We only identified 19 randomised clinical trials. More trials at low risk of bias and at low risk of random errors assessing participants at different levels of psychopathological severity are urgently needed.

Systematic review registration

PROSPERO CRD42019128535.
In search of environmental risk factors for obsessive-compulsive disorder: study protocol for the OCDTWIN project
Authors: Mataix-Cols David , Fernández de la Cruz Lorena , De Schipper Elles , Kuja-Halkola Ralf , Bulik Cynthia M. , Crowley James J. , Neufeld Janina , Rück Christian , Tammimies Kristiina , Lichtenstein Paul , Bölte Sven , Beucke Jan C.
Published: June 2023

Background

The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at least as important and should be a priority because some of them may be amenable to prevention or early intervention strategies. Genetically informative studies, particularly those employing the discordant monozygotic (MZ) twin design, are ideally suited to study environmental risk factors. This protocol paper describes the study rationale, aims, and methods of OCDTWIN, an open cohort of MZ twin pairs who are discordant for the diagnosis of OCD.

Methods

OCDTWIN has two broad aims. In Aim 1, we are recruiting MZ twin pairs from across Sweden, conducting thorough clinical assessments, and building a biobank of biological specimens, including blood, saliva, urine, stool, hair, nails, and multimodal brain imaging. A wealth of early life exposures (e.g., perinatal variables, health-related information, psychosocial stressors) are available through linkage with the nationwide registers and the Swedish Twin Registry. Blood spots stored in the Swedish phenylketonuria (PKU) biobank will be available to extract DNA, proteins, and metabolites, providing an invaluable source of biomaterial taken at birth. In Aim 2, we will perform within-pair comparisons of discordant MZ twins, which will allow us to isolate unique environmental risk factors that are in the causal pathway to OCD, while strictly controlling for genetic and early shared environmental influences. To date (May 2023), 43 pairs of twins (21 discordant for OCD) have been recruited.

Discussion

OCDTWIN hopes to generate unique insights into environmental risk factors that are in the causal pathway to OCD, some of which have the potential of being actionable targets.
Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases
Authors: Wang Yuting , Wang Jiaxi , Yan Zhanfeng , Liu Siming , Xu Wenlong
Published: June 2023

Background

RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics.

Methods

We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication.

Results

In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids.

Conclusions

Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.
Clinical and epidemiological characteristics of 369 patients with pelvic fractures in Eastern Zhejiang Province of China: a retrospective study
Authors: Dai Jiao , He Junhong , Ying Ying , Huang Dichao , Feng Leling
Published: June 2023

Background

Data on the epidemiological characteristics and prognostic factors of patients with pelvic fractures are lacking, particularly in China. This study aimed to summarise the clinical and epidemiological characteristics of patients with pelvic fractures in eastern Zhejiang Province, China, and to identify risk factors for poor prognosis.

Methods

The clinical data of 369 patients with pelvic fractures admitted to the Ningbo No. 6 Hospital between September 2020 and September 2021 were retrospectively analysed. Data on the demographic characteristics; fracture classification; injury time, cause, and site; treatment plan; and prognosis were collected using the Picture Archiving and Communication System and the Hospital Information System. Differences in constituent proportions were analysed using the chi-square test. Logistic regression analysis was used to identify factors affecting patient prognosis. Statistical significance was set at p ≤ 0.05.

Results

Among the 369 patients, there were 206 men and 163 women, at a ratio of 1.26:1, and the average age was 53.64 ± 0.78 years. More than 50% of patients were aged 41–65 years. The average length of hospital stay was 18.88 ± 1.78 days. The three most common causes of pelvic fractures were traffic accidents (51.2%), falls from height (31.44%), and flat-ground falls (14.09%). There were significant differences in the distribution of the three causes of injury depending on age (p < 0.001), sex (p < 0.001), and occupation (p < 0.0001). Most patients were manual workers (48.8%). Furthermore, most patients (n = 262, 71.0%) underwent surgical treatment for pelvic fractures. Postoperative complications occurred in 26 patients (7.05%), and infection was the main complication (73.08%). Age (p = 0.013), occupation (p = 0.034), cause of injury (p = 0.022), treatment options (p = 0.001), and complications (p < 0.0001) were independent factors affecting the prognosis of patients with pelvic fractures. One death (0.027%) occurred, which was due to severe blood loss.

Conclusions

Age, occupation, cause of injury, treatment options and complications were factors affecting patient prognosis. In addition, changes in blood flow and prevention of infection warrant attention.
Cinacalcet increases renal calcium excretion in PTHrP-mediated hypercalcemia: a case report
Authors: Faiq Samya , Lavelle Kristen , Hu Tina , Shoback Dolores , Ku Gregory
Published: June 2023

Background

In the acute setting, PTH-independent hypercalcemia is typically treated with anti-resorptive agents such as zoledronic acid or denosumab. When these agents are no longer able to control hypercalcemia, several case reports have shown the utility of cinacalcet. However, it is not known if cinacalcet can be effective in patients naïve to anti-resorptive therapy or how cinacalcet ameliorates the hypercalcemia.

Case presentation

A 47-year-old male with a history of alcohol-induced cirrhosis was admitted for left cheek bleeding and swelling from an infiltrative squamous cell carcinoma of the oral cavity. On admission, he was found to have an elevated albumin-corrected serum calcium of 13.6 mg/dL, a serum phosphorus of 2.2 mg/dL and an intact PTH of 6 pg/mL (normal 18–90) with a PTHrP of 8.1 pmol/L (normal < 4.3), consistent with PTHrP-dependent hypercalcemia. Aggressive intravenous saline hydration and subcutaneous salmon calcitonin were initiated, but his serum calcium remained elevated. Given tooth extractions scheduled for the next day and possible irradiation to the jaw in the near future, alternatives to antiresorptive therapy were sought. Cinacalcet was initiated at 30 mg twice daily then increased to 60 mg twice daily the following day. The albumin-corrected serum calcium level decreased from 13.2 to 10.9 mg/dL within 48 h. The fractional excretion of calcium increased from 3.7 to 7.0%.

Conclusions

This case demonstrates the utility of cinacalcet for the treatment of PTHrP-mediated hypercalcemia without prior anti-resorptive therapy via increased renal clearance of calcium.
Effect of cleaning materials on microtensile bond strength of resin composite to primary dentin contaminated with root canal sealers
Authors: Çakir Asu
Published: June 2023

Background

There have been no studies on the bond strength of adhesives with dentin surfaces contaminated with root canal sealers in primary teeth without underlying permanent teeth germs. This study investigated the cleaning materials used for primary tooth dentin contaminated with root canal sealers. The aim was to increase the success rate of root canal treatment in pedodontics clinics and retain the teeth for longer.

Methods

The occlusal enamel layer was removed, followed by the application of root canal sealers (AH Plus or MTA Fillapex) to the dentin and cleaning using different irrigation solutions (saline, NaOCl, and ethanol). The specimens were restored using a self-etch adhesive and composite. Sticks with a thickness of approximately 1 mm were obtained from each sample, and the bond strengths were measured using a microtensile testing device. The interfacial morphology of the bonded space was evaluated using scanning electron microscopy.

Results

The control and AH Plus saline groups had the highest bond strengths. The groups cleaned using ethanol had the lowest bond strengths (p < 0.01).

Conclusion

Cleaning the dentin with saline-soaked cotton pellets provided the best bond strengths. Therefore, saline is the most effective material for removing both epoxy resin- and calcium silicate-based root canal sealers from the access cavity.
The association between how medical students were selected and their perceived stress levels in Year-1 of medical school
Authors: Broks Vera M.A. , Stegers-Jager Karen M. , Fikrat-Wevers Suzanne , Van den Broek Walter. W. , Woltman Andrea M.
Published: June 2023

Background

The prevalence of medical students’ mental distress is high. While schools apply various methods to select a well-performing and diverse student population, little is known about the association between different selection methods and the well-being of these students during medical school. The present retrospective multi-cohort study assessed whether students selected by high grades, assessment, or weighted lottery showed different stress perception levels in Year-1 of medical school.

Methods

Of 1144 Dutch Year-1 medical students, 650 (57%) of the cohorts 2013, 2014, and 2018 who were selected by high grades, assessment, or weighted lottery completed a stress perception questionnaire (PSS-14). A multilevel regression analysis assessed the association between selection method (independent variable) and stress perception levels (dependent variable) while controlling for gender and cohort. In a post-hoc analysis, academic performance (optimal vs. non-optimal) was included in the multilevel model.

Results

Students selected by assessment (B = 2.25, p < .01, effect size (ES) = small) or weighted lottery (B = 3.95, p < .01, ES = medium) had higher stress perception levels than students selected by high grades. Extending the regression model with optimal academic performance (B=-4.38, p < .001, ES = medium), eliminated the statistically significant difference in stress perception between assessment and high grades and reduced the difference between weighted lottery and high grades from 3.95 to 2.45 (B = 2.45, p < .05, ES = small).

Conclusions

Selection methods intended to create a diverse student population – assessment and lottery - are associated with higher stress perception levels in Year-1 of medical school. These findings offer medical schools insights into fulfilling their responsibility to take care of their students’ well-being.
Strategies for specialty training of healthcare professionals in low-resource settings: a systematic review on evidence from stroke care
Authors: Habibi Junaid , Bosch Jackie , Bidulka Patrick , Belson Sarah , DePaul Vincent , Gandhi Dorcas , Kumurenzi Anne , Melifonwu Rita , Pandian Jeyaraj , Langhorne Peter , Solomon John M. , Dawar Dimple , Carroll Sandra , Urimubenshi Gerard , Kaddumukasa Martin , Hamilton Leah
Published: June 2023

Background

The greatest mortality and disability from stroke occurs in low- and middle-income countries. A significant barrier to implementation of best stroke care practices in these settings is limited availability of specialized healthcare training. We conducted a systematic review to determine the most effective methods for the provision of speciality stroke care education for hospital-based healthcare professionals in low-resource settings.

Methods

We followed the PRISMA guidelines for systematic reviews and searched PubMed, Web of Science and Scopus for original clinical research articles that described or evaluated stroke care education for hospital-based healthcare professionals in low-resource settings. Two reviewers screened titles/abstracts and then full text articles. Three reviewers critically appraised the articles selected for inclusion.

Results

A total of 1,182 articles were identified and eight were eligible for inclusion in this review; three were randomized controlled trials, four were non-randomized studies, and one was a descriptive study. Most studies used several approaches to education. A “train-the-trainer” approach to education was found to have the most positive clinical outcomes (lower overall complications, lengths of stay in hospital, and clinical vascular events). When used for quality improvement, the “train-the-trainer” approach increased patient reception of eligible performance measures. When technology was used to provide stroke education there was an increased frequency in diagnosis of stroke and use of antithrombotic treatment, reduced door-to-needle times, and increased support for decision making in medication prescription was reported. Task-shifting workshops for non-neurologists improved knowledge of stroke and patient care. Multidimensional education demonstrated an overall care quality improvement and increased prescriptions for evidence-based therapies, although, there were no significant differences in secondary prevention efforts, stroke reoccurrence or mortality rates.

Conclusions

The “train the trainer” approach is likely the most effective strategy for specialist stroke education, while technology is also useful if resources are available to support its development and use. If resources are limited, basic knowledge education should be considered at a minimum and multidimensional training may not be as beneficial. Research into communities of practice, led by those in similar settings, may be helpful to develop educational initiatives with relevance to local contexts.
The development of a Cancer Pain Belief Modification Program for patients with oral cancer in China: a feasibility study
Authors: Wang Rongna , Zheng Xiaoyan , Su Xixi , Huang Xiuyu , Liu Huangju , Guo Yulai , Gao Ji
Published: June 2023

Background

Acceptance-based pain management interventions have been receiving growing attention in cancer pain care. This study aimed to develop a cancer pain management program based on belief modification to improve the cancer pain experience of Chinese oral cancer survivors and to explore the acceptability and preliminary outcomes of the Cancer Pain Belief Modification Program (CPBMP).

Methods

A mixed-methods approach was applied to develop and revise the program. The CPBMP was developed and revised using the Delphi technique, and its further improvement was explored with a one-group pre- and post-trial designed with a sample of 16 Chinese oral cancer survivors, and semi-structured interviews. Research instruments included Numeric Rating Scale (NRS), Chinese version of Illness Perception Questionnaire-Revised for Cancer Pain (IPQ-CaCP), and the University of Washington Quality of Life assessment scale (UW-QOL). Descriptive statistics, t-test, and Mann–Whitney U test were used to analyse the data. The semi-structured questions were analysed using content analysis.

Results

The six-module CPBMP was endorsed by most experts and patients. The expert authority coefficient value was 0.75 in the first round of the Delphi survey and 0.78 in the second round. The “pain intense”, “negative pain beliefs” scores of pre- and post-testing decreased from 5.63 ± 0.48 to 0.81 ± 0.54 (t = -3.746, p < 0.001); from 140.63 ± 9.02 to 52.75 ± 7.27 (Z = 12.406, p < 0.001); and the “positive pain beliefs”, “quality of life” scores increased from 55.13 ± 4.54 to 66.00 ± 4.70 (Z = -6.983, p < 0.001); from 66.97 ± 15.01 to 86.69 ± 8.42 (Z = 7.283, p < 0.001). The qualitative data also indicated that CPBMP was well acceptable.

Conclusion

Our study showed the acceptability and preliminary outcomes of CPBMP patients. CPBMP improves the pain experience of Chinese oral cancer patients and provides a reference for cancer pain management in the future.

Trial registration

The feasibility study has already been registered on the Chinese Clinical Trial Registry (ChiCTR) (www.chictr.org.cn) in 11/09/2021. (ChiCTR2100051065).
Individual and contextual level enablers and barriers determining electronic community health information system implementation in northwest Ethiopia
Authors: Hailemariam Tesfahun , Atnafu Asmamaw , Gezie Lemma Derseh , Kaasbøll Jens Johan , Klein Jörn , Tilahun Binyam
Published: June 2023

Background

The government of Ethiopia has envisioned digitalizing primary healthcare units through the electronic community health information system (eCHIS) program as a re-engineering strategy aiming to improve healthcare data quality, use, and service provision. The eCHIS is intended as a community-wide initiative to integrate lower health structure with higher administrative health and service delivery unit with the ultimate goal of improving community health. However, the success or failure of the program depends on the level of identifying enablers and barriers of the implementation. Therefore, this study aimed to explore individual and contextual-level enablers and barriers determining eCHIS implementation.

Method

We conducted an exploratory study to determine the enablers and barriers to successfully implementing eCHIS in rural Wogera district, northwest Ethiopia. In-depth interviews and key informant interviews were applied at participants from multiple sites. A thematic content analysis was conducted based on the key themes reported. We applied the five components of consolidated framework for implementation research to interpret the findings.

Results

First, based on the intervention's characteristics, implementers valued the eCHIS program. However, its implementation was impacted by the heavy workload, limited or absent network and electricity. Outer-setting challenges were staff turnover, presence of competing projects, and lack of incentive mechanisms. In terms of the inner setting, lack of institutionalization and ownership were mentioned as barriers to the implementation. Resource allocation, community mobilization, leaders’ engagement, and availability of help desk need emphasis for a better achievement. With regard to characteristics of the individuals, limited digital literacy, older age, lack of peer-to-peer support, and limited self-expectancy posed challenges to the implementation. Finally, the importance of mentoring and engaging community and religious leaders, volunteers, having defined plan and regular meetings were identified elements of the implementation process and need emphasis.

Conclusion

The findings underlined the potential enablers and barriers of eCHIS program for quality health data generation, use, and service provision and highlighted areas that require emphasis for further scale-up. The success and sustainability of the eCHIS require ongoing government commitment, sufficient resource allocation, institutionalization, capacity building, communication, planning, monitoring, and evaluation.
Reduced folate carrier 1 is present in retinal microvessels and crucial for the inner blood retinal barrier integrity
Authors: Gurler Gokce , Belder Nevin , Beker Mustafa Caglar , Sever-Bahcekapili Melike , Uruk Gokhan , Kilic Ertugrul , Yemisci Muge
Published: June 2023

Background

Reduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known.

Methods

We used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-h by applying FeCl3 to central retinal artery. We used RT-qPCR and Western blotting to determine RFC1. Endothelium (CD31), pericytes (PDGFR-beta, CD13, NG2), tight-junctions (Occludin, Claudin-5 and ZO-1), main basal membrane protein (Collagen-4), endogenous IgG and RFC1 were determined immunohistochemically.

Results

Our analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia.

Conclusion

In conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia–immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas.
Fixation techniques in lower extremity correction osteotomies and fractures in mild-to-severe osteogenesis imperfecta patients: evaluation of the results and complications
Authors: Emet Abdulsamet , Yilmaz Engin Turkay , Danisman Murat , Aksoy Cemalettin , Yilmaz Guney
Published: June 2023

Introduction

Osteogenesis imperfecta is a genetic disorder leading to multiple fractures and deformities. Intramedullary rods have been used in the surgical treatment of osteogenesis imperfecta for decades. Complication rates reported by current techniques have been high. This study aimed to examine the results of intramedullary fixation combined with plate and screw technique in patients with osteogenesis imperfecta compared to isolated intramedullary fixation.

Methods

Between 2006 and 2020, forty patients who had surgical treatment for deformities or fractures of the femur, tibia or both with at least two years of follow-up after surgery were included in the study. Patients were divided into groups according to fixation methods. Group 1 was intramedullary fixation only (Titanium Elastic Nail [TEN], Rush Pin, and Fassier-Duval Rod), and Group 2 was intramedullary fixation combined with plate and screws. Medical records and follow-up radiographs were reviewed to evaluate healing and callus formation, types of complications and infection rates.

Results

The total number of operated lower extremities of these forty patients was 61 (45 femur and 16 tibia). The mean age of the patients was 9.3 ± 4.6 years. Mean follow-up duration of the patients was 4.4 ± 1.7 years. Thirty-seven (61%) were in Group 1, and 24 (39%) were in Group 2. There was no statistically significant difference in callus formation time between Group 1 and Group 2 (p = 0.67). Complications occurred in 21 of 61 surgeries. While 17 of these complications were in Group 1, 4 were in Group 2 (p = 0.01).

Conclusion

Intramedullary fixation combined with the plate and screw technique in children with osteogenesis imperfecta is successful considering the complications and revision requirements.
Progress in quality control, detection techniques, speciation and risk assessment of heavy metals in marine traditional Chinese medicine
Authors: Guo Yuan-sheng , Zuo Tian-tian , Chen An-zhen , Wang Zhao , Jin Hong-yu , Wei Feng , Li Ping , Ma Shuang-cheng
Published: June 2023

Marine traditional Chinese medicines (MTCMs) hold a significant place in the rich cultural heritage in China. It plays an irreplaceable role in addressing human diseases and serves as a crucial pillar for the development of China's marine economy. However, the rapid pace of industrialization has raised concerns about the safety of MTCM, particularly in relation to heavy metal pollution. Heavy metal pollution poses a significant threat to the development of MTCM and human health, necessitating the need for detection analysis and risk assessment of heavy metals in MTCM. In this paper, the current research status, pollution situation, detection and analysis technology, removal technology and risk assessment of heavy metals in MTCM are discussed, and the establishment of a pollution detection database and a comprehensive quality and safety supervision system for MTCM is proposed. These measures aim to enhance understanding of heavy metals and harmful elements in MTCM. It is expected to provide a valuable reference for the control of heavy metals and harmful elements in MTCM, as well as the sustainable development and application of MTCM.
Shared genetic risk loci between Alzheimer’s disease and related dementias, Parkinson’s disease, and amyotrophic lateral sclerosis
Authors: Wainberg Michael , Andrews Shea J. , Tripathy Shreejoy J.
Published: June 2023

Background

Genome-wide association studies (GWAS) have indicated moderate genetic overlap between Alzheimer’s disease (AD) and related dementias (ADRD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), neurodegenerative disorders traditionally considered etiologically distinct. However, the specific genetic variants and loci underlying this overlap remain almost entirely unknown.

Methods

We leveraged state-of-the-art GWAS for ADRD, PD, and ALS. For each pair of disorders, we examined each of the GWAS hits for one disorder and tested whether they were also significant for the other disorder, applying Bonferroni correction for the number of variants tested. This approach rigorously controls the family-wise error rate for both disorders, analogously to genome-wide significance.

Results

Eleven loci with GWAS hits for one disorder were also associated with one or both of the other disorders: one with all three disorders (the MAPT/KANSL1 locus), five with ADRD and PD (near LCORL, CLU, SETD1A/KAT8, WWOX, and GRN), three with ADRD and ALS (near GPX3, HS3ST5/HDAC2/MARCKS, and TSPOAP1), and two with PD and ALS (near GAK/TMEM175 and NEK1). Two of these loci (LCORL and NEK1) were associated with an increased risk of one disorder but decreased risk of another. Colocalization analysis supported a shared causal variant between ADRD and PD at the CLU, WWOX, and LCORL loci, between ADRD and ALS at the TSPOAP1 locus, and between PD and ALS at the NEK1 and GAK/TMEM175 loci. To address the concern that ADRD is an imperfect proxy for AD and that the ADRD and PD GWAS have overlapping participants (nearly all of which are from the UK Biobank), we confirmed that all our ADRD associations had nearly identical odds ratios in an AD GWAS that excluded the UK Biobank, and all but one remained nominally significant (p < 0.05) for AD.

Conclusions

In one of the most comprehensive investigations to date of pleiotropy between neurodegenerative disorders, we identify eleven genetic risk loci shared among ADRD, PD, and ALS. These loci support lysosomal/autophagic dysfunction (GAK/TMEM175, GRN, KANSL1), neuroinflammation/immunity (TSPOAP1), oxidative stress (GPX3, KANSL1), and the DNA damage response (NEK1) as transdiagnostic processes underlying multiple neurodegenerative disorders.
Anesthesia in patients with Brugada syndrome: two case reports
Authors: Hsu Che-Hao , Lin Shin-Hong , Chang Li-Yen
Published: June 2023

Background

Brugada syndrome is a rare disease. It causes sudden cardiac arrest, which is a serious life-threatening event. Sudden cardiac death mostly results from coronary artery disease. However, patients with Brugada syndrome show normal cardiac anatomy and no evidence of ischemia or electrolyte imbalance. Anesthesia in patients with Brugada syndrome is challenging due to its unpredictable nature, and is worth our attention.

Case presentation

We report two cases of Brugada syndrome during anesthesia. In case one, a 31-year-old Filipino laborer was scheduled for laparoscopic appendectomy. The patient denied any preexisting cardiac disease. The preoperative vital signs were stable, with mild fever of 37.9 °C. The operation was smooth. During the emergence period, the patient suffered from sudden onset of ventricular tachycardia. After resuscitation, the cardiac rhythm returned to normal. Later, he was confirmed to have a genetic trait of Brugada syndrome. In case two, a young Taiwanese patient with pre-diagnosed Brugada syndrome underwent an operation. The perioperative precautions were taken to prevent the occurrence of ventricular arrhythmia. The surgery was uneventful.

Conclusions

Brugada syndrome, although rare, has the highest incidence in South East Asian healthy young males. It brings attention to possible fatal cardiac arrhythmia in this population. Careful preoperative evaluation and perioperative management can help reduce the harmful outcome of the disease and prevent any untoward events.