bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryo-EM structures of human arachidonate 12S-lipoxygenase bound to endogenous and exogenous inhibitors
Authors: Mobbs Jesse I. , Black Katrina A. , Tran Michelle , Burger Wessel A. C. , Venugopal Hariprasad , Holman Theodore R. , Holinstat Michael , Thal David M. , Glukhova Alisa
Published: July 2023

Human 12-lipoxygenase (12-LOX) is a key enzyme involved in platelet activation, and the regulation of its activity has been targeted for the treatment of heparin-induced thrombocytopenia. Despite the clinical importance of 12-LOX, the exact mechanisms by which it affects platelet activation are not fully understood, and the lack of structural information has limited drug discovery efforts. In this study, we used single-particle cryo-electron microscopy to determine high-resolution structures (1.7-2.8 Å) of human 12-LOX. Our results showed that 12-LOX can exist in multiple oligomeric states, from monomer to hexamer, which may affect its catalytic activity and membrane association. We also identified different conformations within the 12-LOX dimer, which likely represent different time points in its catalytic cycle. Furthermore, we identified small molecules bound to 12-LOX. The active site of the 12-LOX tetramer was occupied by an endogenous 12-LOX inhibitor, a long-chain acyl coenzyme A. In addition, we found that the 12-LOX hexamer can simultaneously bind to arachidonic acid and ML355, a selective 12-LOX inhibitor that has passed a phase 1 clinical trial for the treatment of heparin-induced thrombocytopenia and received a fast-track designation by the Food and Drug Administration. Overall, our findings provide novel insights into the assembly of 12-LOX oligomers, their catalytic mechanism, and small molecule binding, paving the way for further drug development targeting the 12-LOX enzyme.
Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy
Authors: La Mura Vincenzo , Bitto Niccolò , Capelli Cecilia , Caputo Camilla , Siboni Simona , Arcudi Sara , Ciavarella Alessandro , Gualtierotti Roberta , Fracanzani Anna Ludovica , Sangiovanni Angelo , Peyvandi Flora
Published: July 2023

Ruling out advanced fibrosis/cirrhosis is mandatory for persons with hemophilia (PWH) who are candidates for gene therapy. However, clinical evaluation and noninvasive tests (NITs) may be inaccurate after hepatitis C virus (HCV) clearance. We conducted a prospective hepatological screening to detect advanced fibrosis/cirrhosis in PWH after HCV clearance. Any risk factor of chronic liver damage was registered by using biochemical data, liver stiffness measurement (LSM), and ultrasound (US). A pre/post-HCV clearance analysis was conducted prospectively in a subgroup of patients who underwent LSM, US, and NITs for fibrosis. We evaluated 119 patients (median age, 53 years; range, 36-87 years) with a previous HCV infection (hemophilia A, n = 108; hemophilia B, n = 11). Ninety-six (81%) presented at least 1 potential risk factor of chronic liver damage. Metabolic risk factors were the most prevalent, with 51 patients (44%) having US steatosis. In 21 patients (18%), clinical, biochemical, liver morphology, and/or LSM were suggestive of advanced fibrosis/cirrhosis. Furthermore, 10 patients (8%) had esophageal varices and 3 (3%) had hepatocellular carcinoma. In 57 patients included in the prospective analysis, LSM and NITs were reduced after HCV clearance (P < .05), but US signs specific of cirrhosis remained unchanged. Overall, 23 of 80 patients (29%) with LSM <10 KPa had at least 1 US sign suggestive of advanced fibrosis/cirrhosis. A similar proportion (18%) was observed for LSM <8 KPa. Overall, risk factors of chronic liver damage are frequent after HCV clearance, but changes in LSM and NITs after clearance may be inaccurate to rule out advanced fibrosis/cirrhosis. A specific diagnostic workup is warranted to evaluate liver health in PWH in the era of gene therapy.
The prevalence of colistin resistance in clinical Stenotrophomonas maltophilia isolates worldwide: a systematic review and meta-analysis
Authors: Delgarm Shams-Abadi Ali , Mohammadian-Hafshejani Abdollah , Paterson David L. , Arash Rezvan , Asadi Farsani Elham , Taji Asieh , Heidari Hamid , Shahini Shams Abadi Milad
Published: July 2023

While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000–2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.
Metabolic-GWAS provides insights into genetic architecture of seed metabolome in buckwheat
Authors: Zargar Sajad Majeed , Manzoor Madhiya , Bhat Basharat , Wani Amir Bashir , Sofi Parvaze Ahmad , Sudan Jebi , Ebinezer Leonard Barnabas , Dall’Acqua Stefano , Peron Gregorio , Masi Antonio
Published: July 2023

Background

Buckwheat (Fagopyrum spp.), belonging to the Polygonaceae family, is an ancient pseudo-cereal with high nutritional and nutraceutical properties. Buckwheat proteins are gluten-free and show balanced amino acid and micronutrient profiles, with higher content of health-promoting bioactive flavonoids that make it a golden crop of the future. Plant metabolome is increasingly gaining importance as a crucial component to understand the connection between plant physiology and environment and as a potential link between the genome and phenome. However, the genetic architecture governing the metabolome and thus, the phenome is not well understood. Here, we aim to obtain a deeper insight into the genetic architecture of seed metabolome in buckwheat by integrating high throughput metabolomics and genotyping-by-sequencing applying an array of bioinformatics tools for data analysis.

Results

High throughput metabolomic analysis identified 24 metabolites in seed endosperm of 130 diverse buckwheat genotypes. The genotyping-by-sequencing (GBS) of these genotypes revealed 3,728,028 SNPs. The Genome Association and Prediction Integrated Tool (GAPIT) assisted in the identification of 27 SNPs/QTLs linked to 18 metabolites. Candidate genes were identified near 100 Kb of QTLs, providing insights into several metabolic and biosynthetic pathways.

Conclusions

We established the metabolome inventory of 130 germplasm lines of buckwheat, identified QTLs through marker trait association and positions of potential candidate genes. This will pave the way for future dissection of complex economic traits in buckwheat.
Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury
Authors: Smith Joshua D. , Mentz Graciela , Leis Aleda M. , Yuan Yuan , Stucken Chaz L. , Chinn Steven B. , Casper Keith A. , Malloy Kelly M. , Shuman Andrew G. , McLean Scott A. , Rosko Andrew J. , Prince Mark E. P. , Tremper Kevin K. , Spector Matthew E. , Schechtman Samuel A.
Published: July 2023

Background

Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection.

Methods

This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 – 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth’s estimation given low prevalence of the primary outcome.

Results

Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 – 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 – 5.51, p = 0.26).

Conclusions

In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.
Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma
Authors: Zhang Zhen , Gao Wenhui , Liu Zhuo , Yu Shuxian , Jian Huiying , Hou Zongwei , Zeng Puhua
Published: July 2023

Background

N6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear.

Methods

The related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups.

Results

The m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC.

Conclusion

A comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments.
Influence of COVID-19 on the notification of drug-resistant pulmonary tuberculosis cases
Authors: Orfão Nathalia Halax , Andrade Rubia Laine de Paula , Ruffino-Netto Antônio , da Silva Leila Wiedmann Florentino , Villa Tereza Cristina Scatena , Seifert Marva Lynn , Zilly Adriana , Arcoverde Marcos Augusto Moraes , Hoare Ismael , Izurieta Ricardo , da Silva-Sobrinho Reinaldo Antônio
Published: July 2023

Background

To analyze the influence of the COVID-19 pandemic on the process of diagnosis and monitoring of drug-resistant pulmonary tuberculosis (TB) cases reported in the state of Paraná, Brazil, from 2015 to 2020.

Methods

Ecological study with quantitative approach. This study was based on diagnosed cases of pulmonary TB reported in the Notifiable Disease Information System in residents of Paraná; as well as through the number of confirmed cases of COVID-19 in the state epidemiological bulletin for the year 2020. The study data were analyzed using descriptive statistics.

Results

It was found that, although the number of reported pulmonary TB cases (drug-resistant and general) increased between 2015 and 2019, there was a drop in notification in 2020, the first year of the COVID-19 pandemic. The notification of TB cases was also influenced monthly during the year according to the increase in the number of COVID-19 cases. For cases of drug-resistant pulmonary TB, the provision of diagnostic tests and Directly Observed Treatment decreased by more than half in 2020, especially when compared to 2019.

Conclusions

In view of these findings, the influence of COVID-19 on the diagnosis and monitoring of drug-resistant and general pulmonary TB cases is evident, showing that the pandemic has compromised the advances of recent decades in achieving the goals established for its eradication by 2035.
Non-contrast CT-based radiomics nomogram of pericoronary adipose tissue for predicting haemodynamically significant coronary stenosis in patients with type 2 diabetes
Authors: Chen Can , Chen Meng , Tao Qing , Hu Su , Hu Chunhong
Published: July 2023

Background

Type 2 diabetes mellitus (T2DM) patients have a higher incidence of coronary artery disease than the general population. The aim of this study was to develop a radiomics nomogram of pericoronary adipose tissue (PCAT) based on non-contrast CT to predict haemodynamically significant coronary stenosis in T2DM patients.

Methods

The study enrolled 215 T2DM patients who underwent non-contrast CT and coronary computed tomography angiography (CCTA). CCTA derived fractional flow reserve (FFRCT) ≤ 0.80 was defined as hemodynamically significant stenosis.1691 radiomics features were extracted from PCAT on non-contrast CT. Minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to select useful radiomics features to construct Radscore. Logistic regression was applied to select significant factors among Radscore, fat attenuation index (FAI) and coronary artery calcium score (CACS) to construct radiomics nomogram.

Results

Radscore [odds ratio (OR) = 2.84; P < 0.001] and CACS (OR = 1.00; P = 0.023) were identified as independent predictors to construct the radiomics nomogram. The radiomics nomogram showed excellent performance [training cohort: area under the curve (AUC) = 0.81; 95% CI: 0.76–0.86; validation cohort: AUC = 0.83; 95%CI: 0.76–0.90] to predict haemodynamically significant coronary stenosis in patients with T2DM. Decision curve analysis demonstrated high clinical value of the radiomics nomogram.

Conclusion

The non-contrast CT-based radiomics nomogram of PCAT could effectively predict haemodynamically significant coronary stenosis in patients with T2DM, which might be a potential noninvasive tool for screening of high-risk patients.
Association of age-related declined renal function and osteoporosis based on trabecular bone score in Bushehr Elderly Health (BEH) program
Authors: Mahmudpour Mehdi , Homayoun Narges , Nabipour Iraj , Kalantar Hormozi Mohammad Reza , boushehri Saeid Najafpour , Larijani Bagher , Ostovar Afshin , Amini Azam , Marzban Maryam
Published: July 2023

Purpose

Osteoporosis is a systemic disease characterized by decreased bone strength and an increased risk of fracture in old age. Age and pathologic renal failure are independent risk factors for osteoporosis. However, it is not determined whether age-related decreased renal function, in the context of senescence, can be considered as an independent risk factor for osteoporosis. Therefore, this study was conducted to evaluate the effect of senescence-induced renal failure on bone quality and trabecular bone score.

Methods

This study used a cross-sectional design and was carried out based on data collected during the Bushehr Elderly Health (BEH) program, Phase II. A total of 2,125 elderly participants aged over 60 years old entered the study after meeting the inclusion criteria and providing informed consent. They underwent examinations for weight, height, abdominal and hip circumference, as well as blood pressure measurement. All participants also underwent DXA to assess bone mass density (BMD). Trabecular bone score (TBS) was calculated using the DXA apparatus software output. Univariate and adjusted multivariate linear regression analyses were used to evaluate the associations.

Results

In the univariate linear regression analysis, there was a direct correlation between age-related renal failure and TBS (β = 0.038, p < 0.0001), neck of femur BMD (β = 0.047, p < 0.0001), and lumbar BMD (β = 0.055, p < 0.0001). However, after adjusting for BMI, age, sex, smoking, and physical activity, no significant association was observed for these variables.

Conclusion

It is hypothesized that age-related renal failure cannot be considered as an independent risk factor for osteoporosis in elderly individuals aged over 60 years old.
A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer
Authors: Nadal Ernest , Saleh Mansoor , Aix Santiago Ponce , Ochoa-de-Olza Maria , Patel Sandip Pravin , Antonia Scott , Zhao Yumin , Gueorguieva Ivelina , Man Michael , Estrem Shawn T. , Liu Jiangang , Avsar Emin , Lin Wen Hong , Benhadji Karim A. , Gandhi Leena , Guba Susan C. , Diaz Inmaculada Ales
Published: July 2023

Background

In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.

Methods

Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.

Results

This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.

Conclusions

The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.

Trial registration

Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).
Changes in health-related rehabilitation trajectories following a major Norwegian welfare reform
Authors: Wittlund Sina , Lorentzen Thomas
Published: July 2023

Background

In this study we investigated the health-related rehabilitation trajectories of young Norwegian adults between 2004–2019. The study period is interesting because it overlaps with an extensive welfare system reform that occurred in Norway between 2006–2011. In parallel with the reform there was a substantial increase in health-related welfare dependency among young people due to mental health conditions.

To better understand this group, we addressed three questions: 1) what were the most typical health-related rehabilitation trajectories for young Norwegians aged 23–27 between 2004–2019, 2) did the trajectories and composition of health-related benefit recipients change overtime and 3) in parallel with the welfare reform, do we see improved labour market outcomes in our study population?

Methods

Using high-quality Norwegian registry data, we established four cohorts of Norwegian health-related rehabilitation benefit recipients aged 23–27 in either 2004 (cohort 1), 2008 (cohort 2), 2011 (cohort 3) or 2014 (cohort 4). The follow-up period for each cohort was six years. We used sequence and cluster analyses to identify typical health-related rehabilitation trajectories. In addition, descriptive statistics and multinomial logistic regression were used to scrutinise the relationship between trajectory types, sociodemographic characteristics and cohort membership.

Results

The majority follow trajectories consisting of welfare dependency, unemployment and unstable, low-income work. Both the trajectories and composition of the study population changed across cohorts. Over the observation period there was a 1) three-fold increase in the proportion following a trajectory ending in permanent disability benefits, 2) nine-fold increase in the proportion following trajectories characterised by long periods of health-related rehabilitation, 3) five-fold decrease in the share following unemployment occupational handicap trajectories 4) 6.9% increase in the proportion of early school leavers and 5) 8.9% decrease in the share with disabled parents.

Conclusion

Our study population is a vulnerable group with suboptimal mental health, functioning and employment outcomes. In conjunction with the welfare reform, we witnessed a significant drop in use of work-related benefits, accompanied by a substantial increase in uptake of health-related rehabilitation- and disability benefits. Thus, it appears that rather than improving employment outcomes, welfare policy changes have created a new problem by steering a greater proportion into disability benefits.
Mental health impact of cuts to local government spending on cultural, environmental and planning services in England: a longitudinal ecological study
Authors: Fahy Katie , Alexiou Alexandros , Daras Konstantinos , Mason Kate , Bennett Davara , Taylor-Robinson David , Barr Ben
Published: July 2023

Background

Over the past decade, there have been significant and unequal cuts to local authority (LA) budgets, across England. Cultural, environmental and planning (CEP) budgets have been cut by 17% between 2011 and 2019. This funding supports services such as parks, leisure centres, community development and libraries, all of which have potential to influence population mental health. We therefore investigated whether cuts to CEP services have affected mental health outcomes and the extent to which they have contributed to mental health inequalities between areas.

Methods

Using fixed effects regression applied to longitudinal LA-level panel data in England, we assessed whether trends in CEP spend were associated with trends in mental health outcomes, between 2011 and 2019. The exposure was CEP spend and the primary outcome was the LA-average Small Area Mental Health Index (SAMHI). Additionally, we considered subcategories of CEP spend as secondary exposures, and antidepressant prescription rate and self-reported anxiety levels as secondary outcomes, both aggregated to LA-level. We adjusted all models for confounders and conducted subgroup analysis to examine differential mental health effects of spending cuts based on the level of area deprivation.

Results

The average decrease in CEP spend of 15% over the period was associated with a 0.036 (95% CI: 0.005, 0.067) increase in SAMHI score, indicating worsening mental health. Amongst subcategories of CEP spending, cuts to planning and development services impacted mental health trends the most, with a 15% reduction in spend associated with a 0.018 (95% CI: 0.005, 0.031) increase in the SAMHI score. The association between cuts in CEP and deteriorating mental health was greater in more affluent areas.

Conclusion

Cuts to spending on cultural, environmental, planning and development services were associated with worsening population mental health in England. Impacts were driven by cuts to planning and development services in particular. Reinvesting in these services may contribute to improved public mental health.
Standardization and learning curve in laparoscopic hernia repair: experience of a high-volume center
Authors: Brucchi Francesco , Ferraina Federica , Masci Emilia , Ferrara Davide , Bottero Luca , Faillace Giuseppe G.
Published: July 2023

Purpose

Groin hernias are a common condition that can be treated with various surgical techniques, including open surgery and laparoscopic approaches. Laparoscopic surgery has several advantages but its use is limited due to the complexity of the posterior inguinal region and the need for advanced laparoscopic skills. This paper presents a standardized and systematic approach to trans-abdominal pre-peritoneal (TAPP) groin hernioplasty, which is useful for training young surgeons.

Methods

The paper provides a detailed, step-by-step description of the TAPP based on evidence from literature, anatomical knowledge, and the authors’ experience spanning over 30 years. The sample includes 487 hernia repair procedures, with 319 surgeries performed by experienced surgeons and 168 surgeries performed by young surgeons in training. The authors performed a descriptive analysis of their data to provide an overview of the volume of laparoscopic hernioplasty performed.

Results

The analysis of the data shows a low complication rate of 0.41% (2/487) and a low recurrence rate of 0.41% (2/487). The median duration of the surgery was 55 min, while the median operation time for surgeons in training was 93 min, specifically 83 min for unilateral hernia and 115 min for bilateral hernia.

Conclusions

The TAPP procedure appears, to date, comparable to the open inguinal approach in terms of recurrence, postoperative pain and speed of postoperative recovery. In this paper, the authors challenge the belief that TAPP is not suitable for surgeons in training. They advocate for a training pathway that involves gradually building surgical skills and expertise. This approach requires approximately 100 procedures to achieve proficiency.
Presence of Candida and its associated factors in participants attending oral cancer screening in the lower northeastern area of Thailand
Authors: Deeiam Krongkan , Pankam Jintana , Sresumatchai Vanvisa , Visedketkan Patama , Jindavech Warut , Rungraungrayabkul Dulyapong , Pimolbutr Kununya , Klongnoi Boworn , Khovidhunkit Siribang-on Piboonniyom
Published: July 2023

Background

Certain evidence indicated high prevalence of Candida in oral potentially malignant disorders (OPMDs) and oral cancer (OC). This study was aimed to investigate the presence of Candida and its associated factors in participants who attended the oral cancer screening program in the lower northeastern districts of Thailand.

Methods

Convenient participants residing in the lower northeastern districts of Thailand who attended the oral cancer screening were enrolled. A questionnaire retrieving demographic characteristics, risk factors of oral cancer, and risk of having Candida was completed. Oral examination was performed by oral medicine specialists or oral surgeons. The participants were categorized into 4 groups according to their clinical diagnosis, namely normal oral mucosa (NOM), OPMDs/OC, non-OPMDs/OC and clinically suspected oral candidiasis (CSOC). Stimulated saliva flow rate was measured. Dip-slide test was performed in each participant to evaluate the presence of Candida. The levels of Candida were categorized into high and low levels according to the score received from the dip-slide test. Factors associated with high levels of Candida were identified using multivariate logistic regression analysis.

Results

A total of 577 participants were recruited. High levels of Candida were found in 31.3%, 24.7%, 25.9% and 18.1% in the OPMDs/OC, the non-OPMDs/OC, the CSOC and the NOM groups, respectively. According to multivariate logistic regression analysis, age above 60 years, female gender, betel quid chewing habit, use of denture, hyposalivation, and being in the CSOC group were found to be significantly associated with high levels of Candida.

Conclusion

Higher number of participants in the OPMDs/OC group was found to have high levels of Candida. Increasing age, female gender, betel quid chewing habit, use of denture, hyposalivation and having CSOC lesions were associated with high levels of Candida.
The impacts of altruism levels on the job preferences of medical students: a cross-sectional study in China
Authors: Zhang Yue , Lin Xing , Li Xing , Han Youli
Published: July 2023

Background

Rational allocation of human resources for health is crucial for ensuring public welfare and equitable access to health services. Understanding medical students’ job preferences could help develop effective strategies for the recruitment and retention of the health workforce. Most studies explore the relationship between extrinsic incentives and job choices through discrete choice experiments (DCEs). Little attention has been paid to the influence of intrinsic altruism on job choice. This study aimed to explore the heterogeneous preferences of medical students with different levels of altruism regarding extrinsic job attributes.

Methods

We conducted an online survey with 925 medical students from six hospitals in Beijing from July to September 2021. The survey combined job-choice scenarios through DCEs and a simulation of a laboratory experiment on medical decision-making behavior. Behavioral data were used to quantify altruism levels by estimating altruistic parameters based on a utility function. We fit mixed logit models to estimate the effects of altruism on job preference.

Results

All attribute levels had the expected effect on job preferences, among which monthly income (importance weight was 30.46%, 95% CI 29.25%-31.67%) and work location (importance weight was 22.39%, 95% CI 21.14%–23.64%) were the most salient factors. The mean altruistic parameter was 0.84 (s.d. 0.19), indicating that medical students’ altruism was generally high. The subgroup analysis showed that individuals with higher altruism levels had a greater preference for non-financial incentives such as an excellent work environment, sufficient training and career development opportunities, and a light workload. The change in the rate of the uptake of a rural position by individuals with lower levels of altruism is sensitive to changes in financial incentives.

Conclusions

Medical students’ altruism was generally high, and those with higher altruism paid more attention to non-financial incentives. This suggests that policymakers and hospital managers should further focus on nonfinancial incentives to better motivate altruistic physicians, in addition to appropriate economic incentive when designing recruitment and retention interventions. Medical school administrations could attach importance to the promotion of altruistic values in medical education.
Using the sociotechnical model to conduct a focused usability assessment of a breast reconstruction decision tool
Authors: Foraker Randi , Phommasathit Crystal , Clevenger Kaleigh , Lee Clara , Boateng Jessica , Shareef Napiera , Politi Mary C.
Published: July 2023

Introduction

BREASTChoice is a web-based breast reconstruction decision aid. The previous clinical trial—prior to the adaptation of this refined tool in which we explored usability—measured decision quality, quality of life, patient activation, shared decision making, and treatment choice. The current usability study was designed to elicit patients’ and clinicians’ perspectives on barriers and facilitators for implementing BREASTChoice into the clinical workflow.

Methods

We conducted qualitative interviews with patients and clinicians from two Midwestern medical specialty centers from August 2020 to April 2021. Interviews were first double coded until coders achieved a kappa > 0.8 and percent agreement > 95%, then were coded independently. We used a sociotechnical framework to evaluate BREASTChoice’s implementation and sustainability potential according to end-users, human-computer interaction, and contextual factors.

Results

Twelve clinicians and ten patients completed interviews. Using the sociotechnical framework we determined the following. People Using the Tool: Patients and clinicians agreed that BREASTChoice could help patients make more informed decisions about their reconstruction and prepare better for their first plastic surgery appointment. Workflow and Communications: They felt that BREASTChoice could improve communication and process if the patient could view the tool at home and/or in the waiting room. Clinicians suggested the information from BREASTChoice about patients’ risks and preferences be included in the patient’s chart or the clinician electronic health record (EHR) inbox for accessibility during the consultation. Human Computer Interface: Patients and clinicians stated that the tool contains helpful information, does not require much time for the patient to use, and efficiently fills gaps in knowledge. Although patients found the risk profile information helpful, they reported needing time to read and digest.

Conclusion

BREASTChoice was perceived as highly usable by patients and clinicians and has the potential for sustainability. Future research will implement and test the tool after integrating the stakeholder-suggested changes to its delivery process and content. It is critical to conduct usability assessments such as these prior to decision aid implementation to ensure success of the tool to improve risk communication.
Cross-cultural adaptation and psychometric validation of the Chinese version of career success in nursing scale (CSNS)
Authors: Cui Yuan-Yuan , Zhong Xia , Wen Li-Ying , Chen Xing-Yu , Bai Xing-Hua
Published: July 2023

Objective

To translate the career success in nursing scale (CSNS) into Chinese and evaluate its psychometric properties.

Background

A lower sense of career success seriously affects the enthusiasm of nurses and increases their turnover rate. Therefore, an accurate assessment of the career success level of nurses is necessary. However, China does not have a professional tool for assessing the career success of nurses.

Methods

The stratified sampling method was used to recruit participants from 22 hospitals of different grades in 5 cities in China. A total of 650 and 348 subjects were selected for item analysis and reliability and validity tests, respectively, of the translated initial scale.

Results

The Chinese version of the CSNS (C-CSNS) with 33 items had good psychometric properties. Cronbach’s α was 0.960, split-half reliability was 0.893, and ICC within two weeks was 0.981. Exploratory factor analysis extracted 5 common factors that explained 63.73% of the total variance, and confirmatory factor analysis supported acceptable construct validity.

Conclusion

The C-CSNS has adequate construct validity and excellent psychometric properties and can be used for accurate assessment of nurses’ career success.

Implications for nursing management

A new tool that is more suitable for the Chinese hospital nursing context is available for evaluating Chinese clinical nurses’ career success. Nursing managers can formulate appropriate management strategies according to the evaluation results to assist nurses in career development planning, thereby improving their career success level.
Assessing resource allocation based on workload: a data envelopment analysis study on clinical departments in a class a tertiary public hospital in China
Authors: Hao Xiaoxiong , Han Lei , Zheng Danyang , Jin Xiaozhi , Li Chenguang , Huang Lvshuai , Huang Zhaohui
Published: July 2023

Objective

Today, the development mode of public hospitals in China is turning from expansion to efficiency, and the management mode is turning from extensive to refined. This study aims to evaluate the efficiency of clinical departments in a Chinese class A tertiary public hospital (Hospital M) to analyze the allocation of hospital resources among these departments providing a reference for the hospital management.

Methods

The hospitalization data of inpatients from 32 clinical departments of Hospital M in 2021 are extracted from the hospital information system (HIS), and a dataset containing 38,147 inpatients is got using stratified sampling. Considering the non-homogeneity of clinical departments, the 38,147 patients are clustered using the K-means algorithm based on workload-related data labels including inpatient days, intensive care workload index, nursing workload index, and operation workload index, so that the medical resource consumption of inpatients from non-homogeneous clinical departments can be transformed into the homogeneous workload of medical staff. Taking the numbers of doctors, nurses, and beds as input indicators, and the numbers of inpatients assigned to certain clusters as output indicators, an input-oriented BCC model is built named the workload-based DEA model. Meanwhile, a control DEA model with the number of inpatients and medical revenue as output indicators is built, and the outputs of the two models are compared and analyzed.

Results

Clustering of 38,147 patients into 3 categories is of better interpretability. 14 departments reach DEA efficient in the workload-based DEA model, 10 reach DEA efficient in the control DEA model, and 8 reach DEA efficient in both models. The workload-based DEA model gives a relatively rational judge on the increase of income brought by scale expansion, and evaluates some special departments like Critical Care Medicine Dept., Geriatrics Dept. and Rehabilitation Medicine Dept. more properly, which better adapts to the functional orientation of public hospitals in China.

Conclusion

The design of evaluating the efficiency of non-homogeneous clinical departments with the workload as output proposed in this study is feasible, and provides a new idea to quantify professional medical human resources, which is of practical significance for public hospitals to optimize the layout of resources, to provide real-time guidance on manpower grouping strategies, and to estimate the expected output reasonably.
The EAT-Lancet diet, genetic susceptibility and risk of atrial fibrillation in a population-based cohort
Authors: Zhang Shunming , Stubbendorff Anna , Ericson Ulrika , Wändell Per , Niu Kaijun , Qi Lu , Borné Yan , Sonestedt Emily
Published: July 2023

Background

The EAT-Lancet Commission proposed a global reference diet with both human health benefits and environmental sustainability in 2019. However, evidence regarding the association of such a diet with the risk of atrial fibrillation (AF) is lacking. In addition, whether the genetic risk of AF can modify the effect of diet on AF remains unclear. This study aimed to assess the association of the EAT-Lancet diet with the risk of incident AF and examine the interaction between the EAT-Lancet diet and genetic susceptibility of AF.

Methods

This prospective study included 24,713 Swedish adults who were free of AF, coronary events, and stroke at baseline. Dietary habits were estimated with a modified diet history method, and an EAT-Lancet diet index was constructed to measure the EAT-Lancet reference diet. A weighted genetic risk score was constructed using 134 variants associated with AF. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI).

Results

During a median follow-up of 22.9 years, 4617 (18.7%) participants were diagnosed with AF. The multivariable HR (95% CI) of AF for the highest versus the lowest group for the EAT-Lancet diet index was 0.84 (0.73, 0.98) (P for trend < 0.01). The HR (95% CI) of AF per one SD increment of the EAT-Lancet diet index for high genetic risk was 0.92 (0.87, 0.98) (P for interaction = 0.15).

Conclusions

Greater adherence to the EAT-Lancet diet index was significantly associated with a lower risk of incident AF. Such association tended to be stronger in participants with higher genetic risk, though gene-diet interaction was not significant.
Vertical transmission of porcine circovirus-like virus P1 in BALB/c mice
Authors: Sheng Shaoyang , Guan Lin , Xie Jianping , Xiao Qi , Wen Libin , He Kongwang
Published: July 2023

Background

Porcine circovirus-like virus P1 is the animal virus with the smallest genome discovered so far, and it has become widely distributed in the Chinese mainland in recent years.

Results

In this study, a BALB/c mouse model was used to reveal P1 infection in female reproductive systems and the vertical transmission of the virus. The female reproductive system, including the ovary and uterus, was harvested on day 14 postinfection and examined for pathological lesions. One-day-old mice without colostrum born from infected or uninfected mothers were collected, and P1 virus distribution in the different organs was investigated. During the trials, all the mice showed no clinical symptoms or gross lesions. However, stillbirth did occur in groups infected with the P1 virus. P1 nucleic acid was detected in the heart, liver, spleen, lung, kidney, and brain tissues of 1-day-old mice born from infected mice. Microscopic lesions in P1-infected female mice were characterized by necrosis of the ovarian follicular granulosa cells and abscission, follicular atresia, necrosis of the endometrial epithelial and uterine glandular epithelial cells, and hyperplasia of the squamous endometrial epithelium. The spermatocytes in the seminiferous tubules of the infected male mice were disorderly arranged, and the germ and Sertoli cells were shed, necrotic, and decreased in number. Immunohistochemical results identified P1-positive particles in the nucleus and cytoplasm of cells from the ovary and uterus of female mice.

Conclusions

This study shows that the P1 virus could cause pathological damage to the reproductive system of female mice and could be transmitted vertically.
Carbon nanodots constructed by ginsenosides and their high inhibitory effect on neuroblastoma
Authors: Jiang Yingnan , Xiao Lizhi , Wang Jifeng , Tian Tenghui , Liu Guancheng , Zhao Yu , Guo Jiajuan , Zhang Wei , Wang Jiawen , Chen Changbao , Gao Wenyi , Yang Bai
Published: July 2023

Background

Neuroblastoma is one of the common extracranial tumors in children (infants to 2 years), accounting for 8 ~ 10% of all malignant tumors. Few special drugs have been used for clinical treatment currently.

Results

In this work, herbal extract ginsenosides were used to synthesize fluorescent ginsenosides carbon nanodots via a one-step hydrothermal method. At a low cocultured concentration (50 µg·mL− 1) of ginsenosides carbon nanodots, the inhibition rate and apoptosis rate of SH-SY5Y cells reached ~ 45.00% and ~ 59.66%. The in vivo experiments showed tumor volume and weight of mice in ginsenosides carbon nanodots group were ~ 49.81% and ~ 34.14% to mice in model group. Since ginsenosides were used as sole reactant, ginsenosides carbon nanodots showed low toxicity and good animal response.

Conclusion

Low-cost ginsenosides carbon nanodots as a new type of nanomedicine with good curative effect and little toxicity show application prospects for clinical treatment of neuroblastoma. It is proposed a new design for nanomedicine based on bioactive carbon nanodots, which used natural bioactive molecules as sole source.
NPAideS: a drug-checking study among 3-methylmethcathinone (3-MMC) users
Authors: Willeman Théo , Grundig Nathan , Pochon Christine , Michels David , Charpentier Nicolas , Eysseric-Guérin Hélène , Fouilhé Sam-Lai Nathalie , Stanke-Labesque Françoise , Revol Bruno
Published: July 2023

Background

3-methylmethcathinone (3-MMC) has been available on the European drug market for several years, but an increase in its availability seems to have occurred around 2020, associated with reports of harm and death. We aimed to analyze the composition of the supposed 3-MMC samples purchased and its concordance with the assumed composition of the drug.

Methods

A prospective multicenter (n = 6) study was conducted between February 2021 and September 2021 in Auvergne-Rhone-Alpes, France. The inclusion criteria were: 3-MMC users over 18 years of age in contact with a community-based organization (CBO) called AIDES. Consumption was evaluated with an anonymized questionnaire and samples of 3-MMC powder were analyzed with a combination of qualitative (GC–MS) and quantitative methods (UPLC-MS/MS), to compare the assumed and real compositions of the products purchased.

Results

We studied 45 samples provided by 33 users. The study population was predominantly male (91%), with a median age of 40 years, most were university graduates and regular users of 3-MMC. Intravenous drug use was reported by 15.2% of the population. Most of the users bought their 3-MMC online via the Clear Web. Drug testing was requested by 86% of the users, highlighting the need for this type of harm reduction strategy. The purity of the 3-MMC powder samples tested ranged from 21 to 98%. Other NPS drugs, such as 4-CEC (4-chloroethcathinone), 4-MMC, and 2-fluorodeschloroketamine (2-FDCK), supplied as methoxphenidine (MXP), were also detected.

Conclusion

This prospective study shows that 3-MMC purity and dose vary considerably. It also describes the characteristics of 3-MMC users and their expectations of a drug-checking program. Our data suggest that drug-checking services may be useful in this population. Health associations and laboratories should work together to help increase access to such programs.