bluuebunny/crossref_metadata_2025 huggingface dataset:
One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study
Authors: van Dijk Myrthe J. , Rab Minke A. E. , van Oirschot Brigitte A. , Bos Jennifer , Derichs Cleo , Rijneveld Anita W. , Cnossen Marjon H. , Nur Erfan , Biemond Bart J. , Bartels Marije , Jans Judith J. M. , van Solinge Wouter W. , Schutgens Roger E. G. , van Wijk Richard , van Beers Eduard J.
Published: November 2023

Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD. Here, the 1-year fixed-dose extension period is reported in which 9 of 10 included patients (90%) aged ≥16 years with SCD (HbSS, HbS/β0, or HbS/β+) continued with mitapivat. Mostly mild treatment-emergent adverse events (AEs) (most commonly, transaminase increase and headache) were still reported. Apart from the reported nontreatment-related serious AE (SAE) of a urinary tract infection in the dose-finding period, 1 nontreatment-related SAE occurred in the fixed-dose extension period in a patient who died of massive pulmonary embolism due to COVID-19. Importantly, sustained improvement in Hb level (mean increase, 1.1 ± 0.7 g/dL; P = .0014) was seen, which was accompanied by decreases in markers of hemolysis. In addition, the annualized rate of vaso-occlusive events reduced significantly from a historic baseline of 1.33 ± 1.32 to 0.64 ± 0.87 (P = .0489) when combining the dose-finding period and fixed-dose extension period. Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced. Overall, this study demonstrated 1-year safety and efficacy of treatment with mitapivat in SCD, supporting further evaluation in ongoing phase 2/3 study (RISE UP, NCT05031780). This trial was registered at https://www.clinicaltrialsregister.eu/ as NL8517 and EudraCT 2019-003438-18.
Age of diagnosis for children with chromosome 15q syndromes
Authors: Wheeler Anne C. , Gantz Marie G. , Cope Heidi , Strong Theresa V. , Bohonowych Jessica E. , Moore Amanda , Vogel-Farley Vanessa
Published: November 2023

Objective

The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman syndrome [AS], Prader-Willi syndrome [PWS], and duplication 15q syndrome [Dup15q]).

Methods

Data about the diagnostic process for each condition were contributed by the advocacy organizations. Median and interquartile ranges were calculated for each condition by molecular subtype and year. Comparison tests were run to explore group differences.

Results

The median age of diagnosis was 1.8 years for both AS and Dup15q. PWS was diagnosed significantly younger at a median age of 1 month. Deletion subtypes for both PWS and AS were diagnosed earlier than nondeletion subtypes, and children with isodicentric duplications in Dup15q were diagnosed earlier than those with interstitial duplications.

Conclusion

Understanding variability in the age of diagnosis for chromosome 15 disorders is an important step in reducing the diagnostic odyssey and improving access to interventions for these populations. Results from this study provide a baseline by which to evaluate efforts to reduce the age of diagnosis for individuals with these conditions.
Disentangling the dynamics of energy allocation to develop a proxy for robustness of fattening pigs
Authors: Lenoir Guillaume , Flatres-Grall Loïc , Muñoz-Tamayo Rafael , David Ingrid , Friggens Nicolas C.
Published: November 2023

Background

There is a growing need to improve robustness of fattening pigs, but this trait is difficult to phenotype. Our first objective was to develop a proxy for robustness of fattening pigs by modelling the longitudinal energy allocation coefficient to growth, with the resulting environmental variance of this allocation coefficient considered as a proxy for robustness. The second objective was to estimate its genetic parameters and correlations with traits under selection and with phenotypes that are routinely collected. In total, 5848 pigs from a Pietrain NN paternal line were tested at the AXIOM boar testing station (Azay-sur-Indre, France) from 2015 to 2022. This farm is equipped with an automatic feeding system that records individual weight and feed intake at each visit. We used a dynamic linear regression model to characterize the evolution of the allocation coefficient between the available cumulative net energy, which was estimated from feed intake, and cumulative weight gain during the fattening period. Longitudinal energy allocation coefficients were analysed using a two-step approach to estimate both the genetic variance of the coefficients and the genetic variance in their residual variance, which will be referred to as the log-transformed squared residual (LSR).

Results

The LSR trait, which could be interpreted as an indicator of the response of the animal to perturbations/stress, showed a low heritability (0.05 ± 0.01), a high favourable genetic correlation with average daily growth (− 0.71 ± 0.06), and unfavourable genetic correlations with feed conversion ratio (− 0.76 ± 0.06) and residual feed intake (− 0.83 ± 0.06). Segmentation of the population in four classes using estimated breeding values for LSR showed that animals with the lowest estimated breeding values were those with the worst values for phenotypic proxies of robustness, which were assessed using records routinely collected on farm.

Conclusions

Results of this study show that selection for robustness, based on estimated breeding values for environmental variance of the allocation coefficients to growth, can be considered in breeding programs for fattening pigs.
ScLSTM: single-cell type detection by siamese recurrent network and hierarchical clustering
Authors: Jiang Hanjing , Huang Yabing , Li Qianpeng , Feng Boyuan
Published: November 2023

Motivation

Categorizing cells into distinct types can shed light on biological tissue functions and interactions, and uncover specific mechanisms under pathological conditions. Since gene expression throughout a population of cells is averaged out by conventional sequencing techniques, it is challenging to distinguish between different cell types. The accumulation of single-cell RNA sequencing (scRNA-seq) data provides the foundation for a more precise classification of cell types. It is crucial building a high-accuracy clustering approach to categorize cell types since the imbalance of cell types and differences in the distribution of scRNA-seq data affect single-cell clustering and visualization outcomes.

Result

To achieve single-cell type detection, we propose a meta-learning-based single-cell clustering model called ScLSTM. Specifically, ScLSTM transforms the single-cell type detection problem into a hierarchical classification problem based on feature extraction by the siamese long-short term memory (LSTM) network. The similarity matrix derived from the improved sigmoid kernel is mapped to the siamese LSTM feature space to analyze the differences between cells. ScLSTM demonstrated superior classification performance on 8 scRNA-seq data sets of different platforms, species, and tissues. Further quantitative analysis and visualization of the human breast cancer data set validated the superiority and capability of ScLSTM in recognizing cell types.
A newly identified glycosyltransferase AsRCOM provides resistance to purple curl leaf disease in agave
Authors: Lu Zhiwei , Hou Xiaowan , Ke Zhi , Zhang Yanmei , Yang ZiPing , Zhou Wenzhao
Published: November 2023

Background

Purple curl leaf disease brings a significant threat to the development of agave industry, the underlying mechanism of disease-resistant Agave sisalana. hybrid 11648 (A. H11648R) is still unknown.

Results

To excavate the crucial disease-resistant genes against purple curl leaf disease, we performed an RNA-seq analysis for A.H11648R and A.H11648 during different stages of purple curl leaf disease. The DEGs (differentially expressed genes) were mainly enriched in linolenic acid metabolism, starch and sucrose mechanism, phenylpropanoid biosynthesis, hypersensitive response (HR) and systemic acquired resistance. Further analysis suggested that eight candidate genes (4’OMT2, ACLY, NCS1, GTE10, SMO2, FLS2, SQE1 and RCOM) identified by WGCNA (weighted gene co-expression network analysis) may mediate the resistance to agave purple curl disease by participating the biosynthesis of benzylisoquinoline alkaloids, steroid, sterols and flavonoids, and the regulation of plant innate immunity and systemic acquired resistance. After qPCR verification, we found that AsRCOM, coding a glycosyltransferase and relevant to the regulation of plant innate immunity and systemic acquired resistance, may be the most critical disease-resistant gene. Finally, the overexpression of AsRCOM gene in agave could significantly enhance the resistance to purple curl disease with abundant reactive oxygen species (ROS) accumulations.

Conclusions

Integrative RNA-seq analysis found that HR may be an important pathway affecting the resistance to purple curl leaf disease in agave, and identified glycosyltransferase AsRCOM as the crucial gene that could significantly enhance the resistance to purple curl leaf disease in agave, with obvious ROS accumulations.
Causal effects of genetically vitamins and sepsis risk: a two-sample Mendelian randomization study
Authors: Lou Chen , Meng Zhizhen , Shi Yiyi , Zheng Rui , Pan Jingye , Qian Songzan
Published: November 2023

Background

In recent years, observational studies have been conducted to investigate the potential impact of vitamins on sepsis. However, many of these studies have produced inconsistent results. Our Mendelian randomization (MR) study aims to evaluate the causality between vitamins and sepsis from a genetic perspective.

Methods

Our MR study was designed following the STROBE-MR guidelines. Genetic instrumental variables for vitamins including folate, vitamin B12, B6, A (Retinol), C, D, and K were obtained from previous genome-wide association studies (GWAS) and MR studies. Five different sepsis severity levels were included in the analysis. The genetic instrumental variables were screened for potential confounders using PhenoScanner V2. MR analysis was performed using MR-egger, inverse-variance weighted multiplicative random effects (IVW-RE), inverse-variance weighted multiplicative fixed-effects (IVW-FE), and wald ratio methods to assess the relationship between vitamins and sepsis. Sensitivity analysis was performed using the MR-egger_intercept method, and the MR-PRESSO package and Cochran’s Q test were used to evaluate the heterogeneity of the instrumental variables.

Results

Our MR study found no statistically significant association between vitamins and sepsis risk, regardless of the type of vitamin (P-value > 0.05). The odds ratios (ORs) for folate, vitamin B6, vitamin B12, vitamin A, vitamin D, vitamin K, and vitamin C were 1.164 (95% CI: 0.895–1.514), 0.987 (95% CI: 0.969–1.005), 0.975 (95% CI: 0.914–1.041), 0.993 (95% CI: 0.797–1.238), 0.861 (95% CI: 0.522–1.42), 0.955 (95% CI: 0.86–1.059), and 1.049 (95% CI: 0.911–1.208), respectively. Similar results were observed in subgroups of different sepsis severity levels.

Conclusions

Our MR study found no evidence of a causal association between vitamins and sepsis risk from a genetic perspective. Further randomized controlled trials are necessary to confirm these results.
A study of adverse maternal-foetal outcomes in nephrotic syndrome combined with preeclampsia
Authors: Li Dong , Zhang Minyi , Xu Shuxiu , Bian Ziwei , Huang Xiaoli , Hu Guifang , Li Jing
Published: November 2023

Background

Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with similar symptoms such as high proteinuria and bilateral lower limb oedema. In this study, we compared the maternal–foetal outcomes of pregnant women with preeclampsia in a population with nephrotic syndrome and explored the factors that contribute to the corresponding outcomes and disease development.

Methods

A total of 90 pregnant women were included in this study, of whom 30 had nephrotic syndrome and were diagnosed with preeclampsia during pregnancy, and 60 had nephrotic syndrome alone. Descriptive statistical analyses of baseline data were performed to analyse the effect of combined preeclampsia on maternal and foetal pregnancy outcomes using unadjusted and adjusted logistic regression models.

Results

In this study, the baseline data of the two study populations demonstrated no differences except for the history of caesarean section and 24-h proteinuria results, which were significantly different (P < 0.05). The risk of preterm birth in the nephrotic syndrome with preeclampsia group was 8.25 (95% CI:3.041–22.084 P < 0.05); for a low birth weight, the risk was 6.00 (95% CI:2.302–15.638 P < 0.05); for foetal distress,the risk was 5.667 (95% CI:2.070–15.514 P < 0.05); and the risk of foetal birth restriction was 7.429 (95% CI: 2.642–20.885 P < 0.05). A risk-based analysis of adverse maternal outcomes yielded a risk of miscarriage of 2.200 (95% CI: 0.584–8.291; P > 0.05). After adjusting the model for each outcome, significant risks of preterm labour, foetal birth restriction, and low birth weight were revealed (P < 0.05).

Conclusion

Combined preeclampsia has a significantly higher risk of adverse pregnancy outcomes for the foetus.Therefore, the prevention and control of eclampsia in pregnant women should be improved to ensure maternal and neonatal health.
Are the sensorimotor control capabilities of the hands the factors influencing hand function in people with schizophrenia?
Authors: Lai Yu-Jen , Lin Yu-Chen , Hsu Chieh-Hsiang , Tseng Huai-Hsuan , Lee Chia-Ning , Huang Pai-Chuan , Hsu Hsiu-Yun , Kuo Li-Chieh
Published: November 2023

Background

Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands.

Methods

Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman’s rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function.

Results

The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT.

Conclusions

The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function.

Clinical Trail Registration

ClinicalTrials.gov, identifier NCT04941677, 28/06/2021.
Smart phone addiction and its mental health risks among university students in Jordan: a cross-sectional study
Authors: Abuhamdah Sawsan M A , Naser Abdallah Y
Published: November 2023

Background

Addiction to smart phones is classified clinically as behavioral addiction resulted from an excessive problematic usage of smart phones that effect the daily life of the users. Therefore, this study aims to explore the prevalence of smart phone addiction, its associated psychological distress risk, and its associated predictors among university students in Jordan.

Methods

Between November 2022 and January 2023, a cross-sectional online survey study was conducted in Jordan. In this study, we used previously developed questionnaire instruments, the psychological Distress scale of Kessler and the Smartphone Addiction Scale. A score of 30 was used to identify the dummy variable in the binary logistic regression analysis to identify predictors of severe psychological distress, and smartphone addiction score of 38.7 was used to to identify predictors of smartphone addiction.

Results

A total of 2337 university students participated in this study. The mean psychological distress score for the study participants was 30.0 (SD: 8.9). More than half of the study participants (59.1%) had a psychological distress score of 30 and above, which indicates a severe mental disorder state. More than half of the study participants (56.7%) had a smartphone addiction score of 30 and above, which reflects a smartphone addiction state. Females, divorced, those who feel that their mental abilities have been negatively affected by the use of smart phones, those who feel that using smartphones has affected their sleep and made it harder to fall asleep, and those feel that everything requires effort and fatigue, and they do not want to do any activity that requires effort were more likely to have severe psychological distress compared to others (p < 0.05). Females, those who feel that using smartphones has affected their sleep and made it harder to fall asleep, and those feel that everything requires effort and fatigue, and they do not want to do any activity that requires effort were more likely to be smartphone addicted compared to others (p < 0.05).

Conclusion

Mental diseases are a major public health concern in Jordan, especially among university students. Females, those who thought smartphone usage hurt their mental capacities, and those who had trouble sleeping and fatigue were more likely to develop serious psychological discomfort and smartphone addiction. Smartphones are indispensable, but excessive use can lead to addiction and harm university students’ mental health.
Influence of social deprivation on morbidity and all-cause mortality of cardiometabolic multi-morbidity: a cohort analysis of the UK Biobank cohort
Authors: Jiang Zhou , Zhang Shuo , Zeng Ping , Wang Ting
Published: November 2023

Background

The relation of social deprivation with single cardiometabolic disease (CMD) was widely investigated, whereas the association with cardiometabolic multi-morbidity (CMM), defined as experiencing more than two CMDs during the lifetime, is poorly understood.

Methods

We analyzed 345,417 UK Biobank participants without any CMDs at recruitment to study the relation between social deprivation and four CMDs including type II diabetes (T2D), coronary artery disease (CAD), stroke and hypertension. Social deprivation was measured by Townsend deprivation index (TDI), and CMM was defined as occurrence of two or more of the above four diseases. Multivariable Cox models were performed to estimate hazard ratios (HRs) per one standard deviation (SD) change and in quartile (Q1-Q4, with Q1 as reference), as well as 95% confidence intervals (95% CIs).

Results

During the follow up, 68,338 participants developed at least one CMD (median follow up of 13.2 years), 16,225 further developed CMM (median follow up of 13.4 years), and 18,876 ultimately died from all causes (median follow up of 13.4 years). Compared to Q1 of TDI (lowest deprivation), the multivariable adjusted HR (95%CIs) of Q4 (highest deprivation) among participants free of any CMDs was 1.23 (1.20 ~ 1.26) for developing one CMD, 1.42 (1.35 ~ 1.48) for developing CMM, and 1.34 (1.27 ~ 1.41) for all-cause mortality. Among participants with one CMD, the adjusted HR (95%CIs) of Q4 was 1.30 (1.27 ~ 1.33) for developing CMM and 1.34 (1.27 ~ 1.41) for all-cause mortality, with HR (95%CIs) = 1.11 (1.06 ~ 1.16) for T2D patients, 1.07 (1.03 ~ 1.11) for CAD patients, 1.07 (1.00 ~ 1.15) for stroke patients, and 1.24 (1.21 ~ 1.28) for hypertension patients. Among participants with CMM, TDI was also related to the risk of all-cause mortality (HR of Q4 = 1.35, 95%CIs 1.28 ~ 1.43).

Conclusions

We revealed that people living with high deprived conditions would suffer from higher hazard of CMD, CMM and all-cause mortality.
Improving global health security through implementation of the National Action Plan for Health Security in Sierra Leone, 2018–2021: lessons from the field
Authors: Njuguna Charles , Vandi Mohamed , Singh Tushar , Njeru Ian , Githuku Jane , Gachari Wilson , Musoke Robert , Caulker Victor , Bunting-Graden Joseph , Mahar Michael , Brown Sydney Morgan , Bah Mohamed Alpha , Idriss Mo-Bashir , Talisuna Ambrose , Chamla Dick , Yoti Zabulon , Sreedharan Rajesh , Suryantoro Ludy , Gueye Abdou Salam , Chungong Stella
Published: November 2023

Background

All countries are required to implement International Health Regulations (IHR) through development and implementation of multi-year National Action Plans for Health Security (NAPHS). IHR implementation requires annual operational planning which involves several tools such as NAPHS, State Party Annual Report (SPAR), Joint External Evaluation (JEE) and WHO IHR Benchmarks tool. Sierra Leone has successfully improved IHR capacities across the years through successful annual operational planning using the above tools. We conducted a study to document and share the country’s unique approach to implementation of NAPHS.

Methods

This was an observational study where the process of implementing and monitoring NAPHS in Sierra Leone was observed at the national level from 2018 to 2021. Data was obtained through review and analysis of NAPHS annual operational plans, quarterly review reports and annual IHR assessment reports. Available data was supplemented by information from key informants. Qualitative data was captured as notes and analysed for various themes while quantitative data was analyzed mainly for means and proportions.

Results

The overall national IHR Joint External Evaluation self-assessment score for human health improved from 44% in 2018 to 51% in 2019 and 57% in 2020. The score for the animal sector improved from 32% in 2018 to 43% in 2019 and 52% in 2020. A new JEE tool with new indicators was used in 2021 and the score for both human and animal sectors declined slightly to 51%. Key enablers of success included strong political commitment, whole-of-government approach, annual assessments using JEE tool, annual operational planning using WHO IHR Benchmarks tool and real time online monitoring of progress. Key challenges included disruption created by COVID-19 response, poor health infrastructure, low funding and inadequate health workforce.

Conclusion

IHR annual operational planning and implementation using evidence-based data and tools can facilitate strengthening of IHR capacity and should be encouraged.
Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11
Authors: Wang Dexin , Fang Yu , Lin Liang , Long Wensuo , Wang Lei , Yu Liwei , Deng Huaiming , Wang Dan
Published: November 2023

Background

Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA.

Methods

An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis.

Results

The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model.

Conclusions

Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA.
Reflective learning conversations model for simulation debriefing: a co-design process and development innovation
Authors: Almomani Emad , Sullivan Jacqueline , Saadeh Omar , Mustafa Emad , Pattison Natalie , Alinier Guillaume
Published: November 2023

Background

Health practitioners must be equipped with effective clinical reasoning skills to make appropriate, safe clinical decisions and avoid practice errors. Under-developed clinical reasoning skills have the potential to threaten patient safety and delay care or treatment, particularly in critical and acute care settings. Simulation-based education which incorporates post-simulation reflective learning conversations as a debriefing method is used to develop clinical reasoning skills while patient safety is maintained. However, due to the multidimensional nature of clinical reasoning, the potential risk of cognitive overload, and the varying use of analytic (hypothetical-deductive) and non-analytic (intuitive) clinical reasoning processes amongst senior and junior simulation participants, it is important to consider experience, competence, flow and amount of information, and case complexity related factors to optimize clinical reasoning while attending group- based post-simulation reflective learning conversations as a debriefing method. We aim to describe the development of a post-simulation reflective learning conversations model in which a number of contributing factors to achieve clinical reasoning optimization were addressed.

Methods

A Co-design working group (N = 18) of doctors, nurses, researchers, educators, and patients’ representatives collaboratively worked through consecutive workshops to co-design a post-simulation reflective learning conversations model to be used for simulation debriefing. The co-design working group established the model through a theoretical and conceptual-driven process and multiphasic expert reviews. Concurrent integration of appreciative inquiry, plus/delta, and Bloom’s Taxonomy methods were considered to optimize simulation participants’ clinical reasoning while attending simulation activities. The face and content validity of the model were established using the Content Validity Index CVI and Content Validity Ratio CVR methods.

Results

A Post-simulation reflective learning conversations model was developed and piloted. The model was supported with worked examples and scripted guidance. The face and content validity of the model were evaluated and confirmed.

Conclusions

The newly co-designed model was established in consideration to different simulation participants’ seniority and competence, flow and amount of information, and simulation case complexity. These factors were considered to optimize clinical reasoning while attending group-based simulation activities.
Academic climate and psychopathological symptomatology in Spanish medical students
Authors: Esquerda Montse , Garcia-Estañ Joaquín , Ruiz-Rosales Albert , Garcia-Abajo J. Miguel , Millan Jesus
Published: November 2023

Introduction

Medical Education studies suggest that medical students experience depression, anxiety and psychopathological symptomatology in a proportion higher than in the rest of the population. In the present study, we aimed to conduct a nationwide analysis to describe student’s perceptions of Educational Climate in Spanish medical schools, and its relationship with psychopathological symptomatology.

Methods

The study was carried out in 2022 in all 44 medical schools in Spain, and analyses the academic climate, and psychopathological symptomatology among medical students (n = 4374). To measure these variables, we used the Dundee Ready Education Environment Measure (DREEM) for academic climate, and the SA-45 (Symptom Assessment-45 Questionnaire was used to assess psychopathological symptomatology.

Results

The mean DREEM global score was low, 95.8 (SD 22.6). Worse perception of the academic climate has been found in females (t -2.21, p 0.027), in students of the clinical academic years (t 16.9, p < 0.001), and public medical schools ( t 15.6, p < 0.001).

The SA45 general index score was high (p90) in 25.6% of participants. In respect of gender, female students presented higher levels of SA45 general index score, depression, interpersonal sensitivity, somatization, anxiety, obsession-compulsion, and phobic anxiety symptoms.

Higher DREEM global and subscale scores corresponded to a higher SA-45 global index score and higher SA-45 subscale scores.

Conclusions

Our study suggests a correlation between a poor perception of academic climate, increased depression, anxiety, and other psychopathological symptoms, with a pattern that varies between different faculties. The perception of academic climate varied between medical schools, as did the psychopathological symptoms scores. Our finding suggests the prevalence of these variables in medical students is, at least in part, attributable to factors directly related to the learning atmosphere.
Vaccination practices of pediatric oncologists from eight states
Authors: van Thiel Berghuijs Karely M. , Kaddas Heydon K. , Warner Echo L. , Fair Douglas B. , Fluchel Mark , Knackstedt Elizabeth D. , Verma Anupam , Kepka Deanna , Green Adam L. , Smitherman Andrew B. , Draper Lauren , Johnson Rebecca H. , Kirchhoff Anne C.
Published: November 2023

Background

Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors.

Methods

We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2.

Results

Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists.

Conclusions

Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.
Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer
Authors: Razi Niayesh , Li Weizhong , Ignacio Maxinne A. , Loube Jeffrey M. , Agostino Eva L. , Zhu Xiaoping , Scull Margaret A. , DeStefano Jeffrey J.
Published: November 2023

Background

SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2.

Methods

Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo.

Results

We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects.

Conclusions

Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.
A multi-task deep learning model for EGFR genotyping prediction and GTV segmentation of brain metastasis
Authors: Zhou Zichun , Wang Min , Zhao Rubin , Shao Yan , Xing Ligang , Qiu Qingtao , Yin Yong
Published: November 2023

Background

The precise prediction of epidermal growth factor receptor (EGFR) mutation status and gross tumor volume (GTV) segmentation are crucial goals in computer-aided lung adenocarcinoma brain metastasis diagnosis. However, these two tasks present continuous difficulties due to the nonuniform intensity distributions, ambiguous boundaries, and variable shapes of brain metastasis (BM) in MR images.The existing approaches for tackling these challenges mainly rely on single-task algorithms, which overlook the interdependence between these two tasks.

Methods

To comprehensively address these challenges, we propose a multi-task deep learning model that simultaneously enables GTV segmentation and EGFR subtype classification. Specifically, a multi-scale self-attention encoder that consists of a convolutional self-attention module is designed to extract the shared spatial and global information for a GTV segmentation decoder and an EGFR genotype classifier. Then, a hybrid CNN-Transformer classifier consisting of a convolutional block and a Transformer block is designed to combine the global and local information. Furthermore, the task correlation and heterogeneity issues are solved with a multi-task loss function, aiming to balance the above two tasks by incorporating segmentation and classification loss functions with learnable weights.

Results

The experimental results demonstrate that our proposed model achieves excellent performance, surpassing that of single-task learning approaches. Our proposed model achieves a mean Dice score of 0.89 for GTV segmentation and an EGFR genotyping accuracy of 0.88 on an internal testing set, and attains an accuracy of 0.81 in the EGFR genotype prediction task and an average Dice score of 0.85 in the GTV segmentation task on the external testing set. This shows that our proposed method has outstanding performance and generalization.

Conclusion

With the introduction of an efficient feature extraction module, a hybrid CNN-Transformer classifier, and a multi-task loss function, the proposed multi-task deep learning network significantly enhances the performance achieved in both GTV segmentation and EGFR genotyping tasks. Thus, the model can serve as a noninvasive tool for facilitating clinical treatment.
Does osteotomizing the lower border of the mandible affect the lingual split pattern in a sagittal split ramus osteotomy?
Authors: Al-Dawoody Alah Dawood , Hamad Shehab Ahmed , Kheder Khrwatany Khurshid A. , Saleem Twana Hoshyar
Published: November 2023

Aim

The purpose of this study was to evaluate the effect of adding a fourth osteotomy at the lower border of the mandible on the lingual cortical fracture pattern in bilateral sagittal split ramus osteotomies.

Patients and methods

The sample of the study consisted of 20 patients (12 male and 8 female, with a mean age of 26.79 ± 7.12 years) with mandibular deformities who needed bilateral sagittal split ramus osteotomy. One side underwent a traditional sagittal split ramus osteotomy, and the procedure was modified on the other side by adding a 1 cm horizontal osteotomy at the lower border of the mandible, just distal to the caudal end of the vertical buccal osteotomy cut. A 3D CBCT was used to identify the split pattern.

Results

In the total sample, 40% of the lingual splits ran vertically toward the lower border of the mandible (LSS1), 20% of the splits passed horizontally to the posterior border of the mandible (LSS2), 32.5% of the splits took place along the inferior alveolar canal (LSS3), and 7.5% of the splits were unfavourable fractures (LSS4). On the inferior border osteotomy sides, the distribution of LSS1, LSS2, LSS3, and LSS4 was 10 (25%), 6 (15%), 4 (10%), and 0 (00), respectively. Their distribution on the sides without inferior border osteotomy was 6 (15%), 8 (20%), 13 (32.5%), and 3 (7.5%), respectively. Statistical analysis revealed a significant difference between the two groups (p < 0.05).

Conclusion

Inferior border osteotomy tends to direct the lingual split fracture line toward the lower and posterior borders of the mandible and minimizes bad splits; however, further studies are needed to confirm our findings.
Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study
Authors: Zhang Xuejie , Jia Ruoyu , Zheng Zhifang , Jiang Luhua , Xu Yizhou , Raj Ashok , Sun Dong
Published: November 2023

Background

Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs).

Methods

This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60–100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency.

Results

Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, − 20.09 ng/mL; 95% CI, − 30.26 to − 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, − 7.87 nmol/L; 95% CI, − 12.11 to − 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study.

Conclusions

Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients.

Trial registration: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

Graphical abstract
Indonesian secular vs. Madrasah schools: assessing the discrepancy in English reading and listening tests
Authors: Nawas Abu , Darmawan I Gusti Ngurah , Maadad Nina
Published: November 2023

The greater emphasis on the significance and difference in English performance between the school types has mainly been investigated across Asian countries. However, not much is known about what language skills differentiate their overall language achievement. Using a quantitative study with comparative analysis, this study measured the reading and listening skills of 1319 Indonesian students who were selected using a stratified sample design and grouped them into secular (Sekolah, n = 726) and Islamic (Madrasah, n = 593) groups. The samples were selected from 9205 of the total population of secondary school students, in Bone Regency, South Sulawesi Indonesia. The three-way ANOVA results showed a significant difference (p < 0.05) in reading and listening subskills between the groups. Highly significant results of Madrasah students in reading and listening subskills indicate they are better at constructing what text means in a variety of contexts, as a literary experience in reading texts and obtaining general and specific information from listening tests compared to those attending secular schools. Poor performance of boys and students who enrolled in public secular schools may become the main explanation for achievement gaps across the groups. The main and interaction effects of the school system, sectors, and gender on the tested subskills were also explained in this study. Additionally, the result of the DIF test confirmed that the equity of the tested items between them was supported.
Development and internal validation of a model predicting patient-reported shoulder function after arthroscopic rotator cuff repair in a Swiss setting
Authors: Stojanov Thomas , Aghlmandi Soheila , Müller Andreas Marc , Scheibel Markus , Flury Matthias , Audigé Laurent
Published: November 2023

Background

Prediction models for outcomes after orthopedic surgery provide patients with evidence-based postoperative outcome expectations. Our objectives were (1) to identify prognostic factors associated with the postoperative shoulder function outcome (the Oxford Shoulder Score (OSS)) and (2) to develop and validate a prediction model for postoperative OSS.

Methods

Patients undergoing arthroscopic rotator cuff repair (ARCR) were prospectively documented at a Swiss orthopedic tertiary care center. The first primary ARCR in adult patients with a partial or complete rotator cuff tear were included between October 2013 and June 2021. Thirty-two potential prognostic factors were used for prediction model development. Two sets of factors identified using the knowledge from three experienced surgeons (Set 1) and Bayesian projection predictive variable selection (Set 2) were compared in terms of model performance using R squared and root-mean-squared error (RMSE) across 45 multiple imputed data sets using chained equations and complete case data.

Results

Multiple imputation using data from 1510 patients was performed. Set 2 retained the following factors: American Society of Anesthesiologists (ASA) classification, baseline level of depression and anxiety, baseline OSS, operation duration, tear severity, and biceps status and treatment. Apparent model performance was R-squared = 0.174 and RMSE = 7.514, dropping to R-squared = 0.156, and RMSE = 7.603 after correction for optimism.

Conclusion

A prediction model for patients undergoing ARCR was developed using solely baseline and operative data in order to provide patients and surgeons with individualized expectations for postoperative shoulder function outcomes. Yet, model performance should be improved before being used in clinical routine.
Evidence-based Egyptian clinical practice guidelines: for the prevention and management of iron deficiency and iron deficiency anemia in infants, children and adolescents
Authors: Mokhtar Galila , Youssef Ahmed , Abdel Baky Ashraf , El Khashab Ehab Khairy , Raafat Enas , Youssry Ilham , Ragab Iman , Sherief Laila , Fathy Manar Mohamed , Hesham Mervat Abdallah , Salah Nouran Yousef , Afifi Rasha AbdelRaouf AbdelAziz , Shalaby Sherein Abdelhamid , Habib Sonia Adolf , Omar Tarek , El Gendy Yasmin Gamal
Published: November 2023

Background

Iron deficiency (ID) is the most common nutritional disorder affecting all age groups. Infants and young children are vulnerable to anemia especially iron deficiency anemia (IDA), which represents a public health problem with defined impacts on the health of communities. IDA, however, is a preventable and treatable condition; therefore, early diagnosis represents the cornerstone in protection from its adverse consequences and combating its contributing factors. Several international guidelines for the management of ID/IDA are available, however national guidelines that can be implemented and suits our local needs are lacking.

Objective

To adapt the pre-existing high-quality practice guidelines for the screening, prevention and management of ID/IDA in different pediatric age groups, to be available for the national use by general practitioners, pediatricians, and other health care professionals.

Results

The adaptation group for this guideline included key leaders from different Egyptian institutions. The panel used the ADAPTE methodology for adaptation of guidelines. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of detection, identification of infants, children, and adolescents at high risk of developing ID/IDA, proper management, and prevention. The final version of the adapted clinical practice guideline has been made after thorough review of an external review panel and was guided by their official recommendations and modifications. Implementation tools included algorithms, tables, and flow charts to aid decision making in practice, as well as patient-directed information in the Arabic language.

Conclusions

This adapted guideline serves as a tool for the screening, prevention and management of ID/IDA in different pediatric age groups.