bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Pertinence and Determinants of Potential Drug–Drug Interactions in Chronic Kidney Disease Patients: A Cross-sectional Study
Authors: Khanna Janvi , Kumar Siddharth , Mehta Sudhir , Chaudhary Jasmine , Jain Akash
Published: April 2024

Background: Chronic kidney disease (CKD) is one of the major health issues effecting around 15% of world population, and its further complications has raised the need of polypharmacy for management. But this polypharmacy also upsurges the risk of potential drug-drug interactions (pDDIs) in CKD patients, which may further be responsible for increased morbidity and mortality. Objective: The main objective is therefore to evaluate the distribution, severity, causes, associated drug interactions, and clinical relevance of determination of pDDIs in CKD patients. Methods: Medical files of CKD patients examined at nephrology department, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, between December 2022 and May 2023 were cross-sectionally assessed for this study. Medscape drug interaction checker was used to study patient profiles for pDDIs, and suggestive measures to minimize those pDDIs were studied using DDInter to ensure better clinical decision-making and patient safety. IBM SPSS (version 24) was utilized for statistical analysis. Results: The data reveal that 74.5% of the 200 medical files being evaluated had 839 pDDIs in total, out of which nearly 78.3% of patients had moderate, 15.6% had minor, and 6.07% had serious interactions. The potential adverse outcomes of pDDIs included an irregular heartbeat, hypokalemia, central nervous system (CNS) adverse effects, hypoglycemia, and a decline in therapeutic efficacy. The prevalence of pDDIs was discovered to be substantially correlated with age ≥60 years, (odds ratio [OR] = 0.65; 95% CI = 0.4-0.9; P = 0.040), length of stay ≥10 days (OR = 4.0; 95% CI = 1.29-6.1; P = 0.016), and number of prescribed drugs ≥10 (OR = 5.5; 95% CI = 2.45-10.69; P = 0.004). Conclusion: Patients with CKD have a high incidence of pDDIs (mainly mild to moderate). Older age, duration of hospital stays, and polypharmacy all raise the risk of pDDIs. Healthcare professionals (physicians and clinical pharmacist) should use drug interaction checker software programs like Medscape and DDInter to acquire knowledge about different pDDIS and their alternative measures so that the associated adverse drug reactions (ADRs) can be controlled and rational drug combination can be prescribed for management of CKD ensuring better patient care.
Impacts of longitudinal water curtain cooling system on transcriptome-related immunity in ducks
Authors: Hu Qian , Zhang Tao , He Hua , Pu Fajun , Zhang Rongping , Li Liang , Hu Jiwei , Bai Lili , Han Chunchun , Wang Jiwen , Liu Hehe
Published: April 2024

Background

The closed poultry houses integrated with a longitudinal water curtain cooling system (LWCCS) are widely used in modern poultry production. This study showed the variations in environmental conditions in closed houses integrated with a longitudinal water curtain cooling system. We evaluated the influence of different environmental conditions on duck growth performance and the transcriptome changes of immune organs, including the bursa of Fabricius and the spleen.

Result

This study investigated the slaughter indicators and immune organ transcriptomes of 52-day-old Cherry Valley ducks by analyzing the LWCC at different locations (water curtain end, middle position, and fan cooling end). The results showed that the cooling effect of the LWCCS was more evident from 10:00 a.m. -14:00. And from the water curtain end to the fan cooling end, the hourly average temperature differently decreased by 0.310℃, 0.450℃, 0.480℃, 0.520℃, and 0.410℃, respectively (P < 0.05). The daily and hourly average relative humidity decreased from the water curtain end to the fan cooling end, dropping by 7.500% and 8.200%, respectively (P < 0.01). We also observed differences in production performance, such as dressing weight, half-eviscerated weight, skin fat rate, and percentage of abdominal fat (P < 0.01), which may have been caused by environmental conditions. RNA-sequencing (RNA-seq) revealed 211 and 279 differentially expressed genes (DEGs) in the ducks’ bursa of Fabricius and spleen compared between the water curtain end and fan cooling end, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the two organs showed the DEGs were mainly enriched in cytokine-cytokine receptor interaction, integral component of membrane, Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway, etc. Our results implied that full-closed poultry houses integrated with LWCCS could potentially alter micro-environments (water curtain vs. fan cooling), resulting in ducks experiencing various stressful situations that eventually affect their immunity and production performance.

Conclusion

In this study, our results indicated that uneven distributions of longitudinal environmental factors caused by LWCCS would affect the dressed weight, breast muscle weight, skin fat rate, and other product performance. Moreover, the expression of immune-related genes in the spleen and bursa of ducks could be affected by the LWCCS. This provides a new reference to optimize the use of LWCCS in conjunction with close duck houses in practical production.
Haplotype-resolved genome of Mimosa bimucronata revealed insights into leaf movement and nitrogen fixation
Authors: Jia Haifeng , Lin Jishan , Lin Zhicong , Wang Yibin , Xu Liangwei , Ding Wenjie , Ming Ray
Published: April 2024

Background

Mimosa bimucronata originates from tropical America and exhibits distinctive leaf movement characterized by a relative slow speed. Additionally, this species possesses the ability to fix nitrogen. Despite these intriguing traits, comprehensive studies have been hindered by the lack of genomic resources for M. bimucronata.

Results

To unravel the intricacies of leaf movement and nitrogen fixation, we successfully assembled a high-quality, haplotype-resolved, reference genome at the chromosome level, spanning 648 Mb and anchored in 13 pseudochromosomes. A total of 32,146 protein-coding genes were annotated. In particular, haplotype A was annotated with 31,035 protein-coding genes, and haplotype B with 31,440 protein-coding genes. Structural variations (SVs) and allele specific expression (ASE) analyses uncovered the potential role of structural variants in leaf movement and nitrogen fixation in M. bimucronata. Two whole-genome duplication (WGD) events were detected, that occurred ~ 2.9 and ~ 73.5 million years ago. Transcriptome and co-expression network analyses revealed the involvement of aquaporins (AQPs) and Ca2+-related ion channel genes in leaf movement. Moreover, we also identified nodulation-related genes and analyzed the structure and evolution of the key gene NIN in the process of symbiotic nitrogen fixation (SNF).

Conclusion

The detailed comparative genomic and transcriptomic analyses provided insights into the mechanisms governing leaf movement and nitrogen fixation in M. bimucronata. This research yielded genomic resources and provided an important reference for functional genomic studies of M. bimucronata and other legume species.
Combined sensory, volatilome and transcriptome analyses identify a limonene terpene synthase as a major contributor to the characteristic aroma of a Coffea arabica L. specialty coffee
Authors: Marie Lison , Breitler Jean-Christophe , Bamogo Pingdwende Kader Aziz , Bordeaux Mélanie , Lacombe Séverine , Rios Maëlle , Lebrun Marc , Boulanger Renaud , Lefort Eveline , Nakamura Sunao , Motoyoshi Yudai , Mieulet Delphine , Campa Claudine , Legendre Laurent , Bertrand Benoît
Published: April 2024

Background

The fruity aromatic bouquet of coffee has attracted recent interest to differentiate high value market produce as specialty coffee. Although the volatile compounds present in green and roasted coffee beans have been extensively described, no study has yet linked varietal molecular differences to the greater abundance of specific substances and support the aroma specificity of specialty coffees.

Results

This study compared four Arabica genotypes including one, Geisha Especial, suggested to generate specialty coffee. Formal sensory evaluations of coffee beverages stressed the importance of coffee genotype in aroma perception and that Geisha Especial-made coffee stood out by having fine fruity, and floral, aromas and a more balanced acidity. Comparative SPME–GC–MS analyses of green and roasted bean volatile compounds indicated that those of Geisha Especial differed by having greater amounts of limonene and 3-methylbutanoic acid in agreement with the coffee cup aroma perception. A search for gene ontology differences of ripening beans transcriptomes of the four varieties revealed that they differed by metabolic processes linked to terpene biosynthesis due to the greater gene expression of prenyl-pyrophosphate biosynthetic genes and terpene synthases. Only one terpene synthase (CaTPS10-like) had an expression pattern that paralleled limonene loss during the final stage of berry ripening and limonene content in the studied four varieties beans. Its functional expression in tobacco leaves confirmed its functioning as a limonene synthase.

Conclusions

Taken together, these data indicate that coffee variety genotypic specificities may influence ripe berry chemotype and final coffee aroma unicity. For the specialty coffee variety Geisha Especial, greater expression of terpene biosynthetic genes including CaTPS10-like, a limonene synthase, resulted in the greater abundance of limonene in green beans, roasted beans and a unique citrus note of the coffee drink.
Anticipatory prescribing of injectable controlled drugs (ICDs) in care homes: a qualitative observational study of staff role, uncertain dying and hospital transfer at the end-of-life
Authors: Teggi Diana , Woodthorpe Kate
Published: April 2024

Background

The anticipatory prescribing of injectable controlled drugs (ICDs) by general practitioners (GPs) to care home residents is common practice and is believed to reduce emergency hospital transfers at the end-of-life. However, evidence about the process of ICD prescribing and how it affects residents’ hospital transfer is limited. The study examined how care home nurses and senior carers (senior staff) describe their role in ICDs prescribing and identify that role to affect residents’ hospital transfers at the end-of-life.

Methods

1,440 h of participant observation in five care homes in England between May 2019 and March 2020. Semi-structured interviews with a range of staff. Interviews (n = 25) and fieldnotes (2,761 handwritten A5 pages) were analysed thematically.

Results

Senior staff request GPs to prescribe ICDs ahead of residents’ expected death and review prescribed ICDs for as long as residents survive. Senior staff use this mechanism to ascertain the clinical appropriateness of withholding potentially life-extending emergency care (which usually led to hospital transfer) and demonstrate safe care provision to GPs certifying the medical cause of death. This enables senior staff to facilitate a care home death for residents experiencing uncertain dying trajectories.

Conclusion

Senior staff use GPs’ prescriptions and reviews of ICDs to pre-empt hospital transfers at the end-of-life. Policy should indicate a clear timeframe for ICD review to make hospital transfer avoidance less reliant on trust between senior staff and GPs. The timeframe should match the period before death allowing GPs to certify death without triggering a Coroner’s referral.
Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia
Authors: Chen Ping-Kang , Cheng Zhong-Yuan , Wang Ya-Lin , Xu Bao-Jun , Yu Zong-Chao , Li Zhao-Xia , Gong Shang-Ao , Zhang Feng-Tao , Qian Long , Cui Wei , Feng You-Zhen , Cai Xiang-Ran
Published: April 2024

Background

To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia.

Methods

A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON,n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment.

Results

The HUA, AP, and AP + EM group MKOSand MKISvalues gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOSand MKISvalues were positively correlated with Masson’s trichrome staining results (r = 0.687,P < 0.001 andr = 0.604,P = 0.001, respectively). The MDOSand FAISwere negatively correlated with Masson’s trichrome staining (r = -626,P < 0.0014 andr = -0.468,P = 0.01, respectively).

Conclusion

DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.
Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study
Authors: Atlani Mahendra , Kumar Ashok , Ahirwar Rajesh , Meenu M. N. , Goel Sudhir K. , Kumari Ravita , Anirudhan Athira , Vallamshetla Saikrishna , Reddy G. Sai Tharun
Published: April 2024

Background

Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India.

Methods

The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test.

Results

CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3–132.7) µg/L compared to CKD 4.5 (0.0–58.8) µg/L and healthy subjects 39.01 (4.8–67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003–1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029–9.818) p < .05).

Conclusion

The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.
Perceptions of diabetes distress during pregnancy in women with type 1 and type 2 diabetes: a qualitative interpretive description study
Authors: Tschirhart Holly , Landeen Janet , Yost Jennifer , Nerenberg Kara A. , Sherifali Diana
Published: April 2024

Background

Diabetes distress is commonly seen in adults with pre-existing diabetes and is associated with worsened glycemic management and self-management practices. While a majority of women report increased stress during pregnancy, it is unknown how women with type 1 or type 2 diabetes experience diabetes distress during this unique and transitional time.

Purpose

This study aimed to understand the experiences and perceptions of diabetes distress in women with pre-existing diabetes during pregnancy.

Methods

A qualitative study using an interpretive description approach was conducted. In-depth, one to one interviewing was used to capture rich descriptions of the pregnancy experience. Nested, stratified, and theoretical sampling was used to recruit 18 participants with type 1 and type 2 diabetes from the quantitative strand of this mixed methods study. Constant comparative analysis was used to inductively analyze the data and develop themes.

Findings

Four themes, each with several subthemes, emerged under the main finding of “Diabetes Distress”: 1) Worry for Baby’s Health – “What’s this going to do to the baby?”’ 2) Feeling Overwhelmed with Diabetes Management—“It just seemed unattainable”; 3) Living with Diabetes – “There’s no way out” and 4) Cycle of Diabetes Distress.

Conclusions

The findings from this study identify the sources and experiences of diabetes distress during pregnancy in women with pre-existing diabetes. Diabetes distress often presents as cyclical and multifaceted during pregnancy, with elements of fear for the unborn baby, difficulties with diabetes management, and having negative lived experiences of diabetes. Further work is needed to develop appropriate screening tools for pregnancy and interventions to mitigate diabetes distress. Diabetes educators are well-positioned provide emotional support and person-centred self-management education to individuals with diabetes.
Transition of the genital mollicutes from the second to the third trimester of pregnancy and its association with adverse pregnancy outcomes in GDM women: a prospective, single-center cohort study from China
Authors: Xuan Yan , Zhao Jun , Hong Xiang , Yan Tao , Zhang Yue , Zhou Xu , Zhang Junhui , Wang Bei
Published: April 2024

Background

The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied.

Methods

We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes.

Results

Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes.

Conclusion

Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.
Clinical characteristics analysis of pediatric spinal cord injury without radiological abnormality in China: a retrospective study
Authors: Liu Renfeng , Fan Qizhi , He Jingpeng , Wu Xin , Tan Wei , Yan Zuyun , Wang Weiguo , Li Zhiyue , Deng You-Wen
Published: April 2024

Purpose

This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence.

Methods

A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed.

Results

A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications.

Conclusion

SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of “neijuan” is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.
Women’s experiences of attempted suicide in the perinatal period (ASPEN-study) – a qualitative study
Authors: De Backer Kaat , Pali Alexandra , Challacombe Fiona L. , Hildersley Rosanna , Newburn Mary , Silverio Sergio A. , Sandall Jane , Howard Louise M. , Easter Abigail
Published: April 2024

Background

Suicide is a leading cause of maternal death during pregnancy and the year after birth (the perinatal period). While maternal suicide is a relatively rare event with a prevalence of 3.84 per 100,000 live births in the UK [1], the impact of maternal suicide is profound and long-lasting. Many more women will attempt suicide during the perinatal period, with a worldwide estimated prevalence of 680 per 100,000 in pregnancy and 210 per 100,000 in the year after birth [2]. Qualitative research into perinatal suicide attempts is crucial to understand the experiences, motives and the circumstances surrounding these events, but this has largely been unexplored.

Aim

Our study aimed to explore the experiences of women and birthing people who had a perinatal suicide attempt and to understand the context and contributing factors surrounding their perinatal suicide attempt.

Methods

Through iterative feedback from a group of women with lived experience of perinatal mental illness and relevant stakeholders, a qualitative study design was developed. We recruited women and birthing people (N = 11) in the UK who self-reported as having undertaken a suicide attempt. Interviews were conducted virtually, recorded and transcribed. Using NVivo software, a critical realist approach to Thematic Analysis was followed, and themes were developed.

Results

Three key themes were identified that contributed to the perinatal suicide attempt. The first theme ‘Trauma and Adversities’ captures the traumatic events and life adversities with which participants started their pregnancy journeys. The second theme, ‘Disillusionment with Motherhood’ brings together a range of sub-themes highlighting various challenges related to pregnancy, birth and motherhood resulting in a decline in women’s mental health. The third theme, ‘Entrapment and Despair’, presents a range of factors that leads to a significant deterioration of women’s mental health, marked by feelings of failure, hopelessness and losing control.

Conclusions

Feelings of entrapment and despair in women who are struggling with motherhood, alongside a background of traumatic events and life adversities may indicate warning signs of a perinatal suicide. Meaningful enquiry around these factors could lead to timely detection, thus improving care and potentially prevent future maternal suicides.
“This is how I'm going to do it, but this is not how you're going to do it”: the expectation gap between student paramedics and mentors in East and Central Scotland
Authors: Worsfold Megan E. , Jouanny Clare , Hamer Ela , Mohrsen Stian A. , Jadzinski Patryk , Harper Mick
Published: April 2024

Background

The role of paramedics has expanded significantly over the past two decades, requiring advanced skills and education to meet the demands of diverse healthcare settings. In 2021, the academic requirements for paramedics were raised to a bachelor’s degree to align with other registered professions. The limited evidence on effective paramedic practice education necessitates a novel or new examination of unique learning methods, emphasising the need to establish effective learning relationships between mentors and learners to enhance professional respect and support achieving learning outcomes. This study aimed to investigate expectations between student paramedics and their mentors, focusing on the learning dynamics within paramedic education.

Methods

This qualitative study used purposive sampling to recruit participants from two distinct cohorts: student paramedics from the University of Stirling and Practice Educator Mentors from the Scottish Ambulance Service. Focus groups were conducted to illuminate comprehensive insights into participants' expectations regarding practice education and their respective roles in the learning process. Codebook thematic analysis was used to assess the alignment of these expectations.

Results

Findings illustrate important challenges within practice placement across learning paradigms and highlight the attitudes surrounding the integration of higher education and expectations of practice placements. These challenges encompass systemic barriers, including the support provided to mentors as they assume increased responsibilities and barriers that deter qualified staff from initially undertaking this role.

Conclusion

The study aimed to assess expectations between practice educators and students within the paramedic profession in Scotland. The methodology effectively identified key themes from comprehensive data, marking the first primary research in this field. There are disparities in learning styles, expectation measurement, and attitudes toward higher education during practice placements, which could significantly impact the teaching and assessment processes. The findings suggest increased support for practice educators, educational programs addressing challenges of mentorship, and stronger links between higher education institutes and the Scottish Ambulance Service. Further research is needed to understand the extent of the expectation gap, how expectations evolve, and to develop strategies to address disparities.
Improving the ability to discriminate medical multiple-choice questions through the analysis of the competitive examination to assign residency positions in Spain
Authors: Murias Quintana Eduardo , Rodríguez Castro José , Sánchez Lasheras Fernando , Vega Villar Juan , Curbelo García Jose Juan , Cadenas Rodríguez María , Baladrón Romero Jaime
Published: April 2024

Introduction

Psychometrics plays a vital role in evaluating educational research, including the analysis of multiple-choice exams. This study aims to improve the discriminatory ability of the “Médico Interno Residente” (MIR) medical exam in Spain, used to rank candidates for specialized healthcare training, through psychometric analysis.

Methods

We analyzed 2,890 MIR exam questions from 2009 to 2021 (totaling 147,214 exams), categorizing them based on methodology and response type. Evaluation employed classical test theory and item response theory (IRT). Classical test theory determined difficulty and discrimination indices, while IRT assessed the relationship between knowledge levels and question performance.

Results

Question distribution varied across categories and years. Frequently addressed knowledge areas included various medical specialties. Non-image-associated clinical cases were the easiest, while case-based clinical questions exhibited the highest discriminatory capacity, differing significantly from image-based case or negative questions. High-quality questions without images had longer stems but shorter answer choices. Adding images reduced discriminatory power and question difficulty, with image-based questions being easier. Clinical cases with images had shorter stems and longer answer choices.

Conclusions

For improved exam performance, we recommend using a clinical case format followed by direct short-answer questions. Questions should be of low difficulty, providing clear and specific answers based on scientific evidence and avoiding ambiguity. Typical clinical cases with key characteristic features should be presented, excluding uncertain boundaries of medical knowledge. Questions should have lengthy stems and concise answer choices, minimizing speculation. If images are used, they should be typical, clear, consistent with the exam, and presented within clinical cases using clinical semiotics and propaedeutics.
Maturity model for assessing the medical humanities: a Delphi study
Authors: Zhang Xin , Duan Zhiguang
Published: April 2024

Background

Becoming a first-level discipline in China means access to more educational resources. The development of medical humanities in China has been going on for more than 40 years, and some medical schools have set up master’s and doctoral programs in medical humanities. The demand for medical humanities-related knowledge in China is also growing after COVID-19. However, medical humanities is only a second-level discipline and receives limited resources to meet the needs of society. This study aims to establish a system of indicators that can assess whether the medical humanities has a first-level discipline and provide a basis for its upgrading to a first-level.

Methods

A Delphi technique was used, with the panel of expert expressing their views in a series of two questionnaires. A coefficient of variation of less than 0.2 indicates expert agreement.

Result

A total of 25 experts participated in this Delphi study. Consensus was reached on 11 first-grade indices and 48 s-grade indices. The authoritative coefficient(Cr) of the experts was 0.804, which indicates that the experts have a high level of reliability.

Conclusion

This study provides a reliable foundation for the evaluation of medical humanities maturity.
Capturing artificial intelligence applications’ value proposition in healthcare – a qualitative research study
Authors: Hennrich Jasmin , Ritz Eva , Hofmann Peter , Urbach Nils
Published: April 2024

Artificial intelligence (AI) applications pave the way for innovations in the healthcare (HC) industry. However, their adoption in HC organizations is still nascent as organizations often face a fragmented and incomplete picture of how they can capture the value of AI applications on a managerial level. To overcome adoption hurdles, HC organizations would benefit from understanding how they can capture AI applications’ potential.

We conduct a comprehensive systematic literature review and 11 semi-structured expert interviews to identify, systematize, and describe 15 business objectives that translate into six value propositions of AI applications in HC.

Our results demonstrate that AI applications can have several business objectives converging into risk-reduced patient care, advanced patient care, self-management, process acceleration, resource optimization, and knowledge discovery.

We contribute to the literature by extending research on value creation mechanisms of AI to the HC context and guiding HC organizations in evaluating their AI applications or those of the competition on a managerial level, to assess AI investment decisions, and to align their AI application portfolio towards an overarching strategy.
Co-development of a training programme on disability for healthcare workers in Uganda
Authors: Smythe Tracey , Ssemata Andrew Sentoogo , Slivesteri Sande , Mbazzi Femke Bannink , Kuper Hannah
Published: April 2024

Background

Approximately 1.3 billion people worldwide face barriers in accessing inclusive healthcare due to disabilities, leading to worse health outcomes, particularly in low and middle-income countries (LMIC). However, there is a lack of training of healthcare workers about disability, both globally and in Uganda.

Objectives

To use mixed research methods to develop a comprehensive training program with standardisedelements for healthcare workers in Uganda, focusing on improving their knowledge, attitudes, and skills inproviding care for people with disabilities.

Methods

The Medical Research Council (MRC) approach was employed to guide the development of the training intervention. We conducted an umbrella review to gather relevant literature on disability training for healthcare workers. Interviews were conducted with international experts to gain insights and perspectives on the topic. Additionally, interviews were undertaken with people with disabilities and healthcare workers in Uganda to understand their experiences and needs. A participatory workshop was organised involving key stakeholders, to collaboratively design the training material based on the findings from these data sources.

Results

Eight review articles examined training programs for healthcare workers on disability. Training settings ranged from specialised clinical settings to non-clinical settings, and the duration and evaluation methods of the training varied widely. Lectures and didactic methods were commonly used, often combined with other approaches such as case studies and simulations. The impact of the training was assessed through healthcare worker reports on attitudes, knowledge, and self-efficacy. Interviews emphasised the importance of involving people with disabilities in the training and improving communication and understanding between healthcare providers and people with disabilities. Five themes for a training on disability for healthcare workers were generated through the workshop, including responsibilities and rights, communication, informed consent, accommodation, and referral and connection, which were used to guide the development of the curriculum, training materials and training approach.

Conclusion

This study presents a novel approach to develop a training program that aims to enhance healthcare services for people with disabilities in Uganda. The findings offer practical insights for the development of similar programs in LMICs. The effectiveness of the training program will be evaluated through a pilot test, and policy support is crucial for its successful implementation at scale.
CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway
Authors: Tan Hongpei , Liu Jiahao , Li Yanan , Mi Ze , Liu Baiying , Rong Pengfei
Published: April 2024

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it.

Methods

A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein–protein interaction studies and mouse xenograft models.

Results

CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis.

Conclusion

CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.

Graphical Abstract
The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases
Authors: Shi Xiangguang , Chen Yahui , Shi Mengkun , Gao Fei , Huang Lihao , Wang Wei , Wei Dong , Shi Chenyi , Yu Yuexin , Xia Xueyi , Song Nana , Chen Xiaofeng , Distler Jörg H. W. , Lu Chenqi , Chen Jingyu , Wang Jiucun
Published: April 2024

Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids’ biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.
Map-1a regulates Sertoli cell BTB dynamics through the cytoskeletal organization of microtubule and F-actin
Authors: Wang Lingling , Yan Ming , Bu Tiao , Wu Xiaolong , Li Linxi , Silvestrini Bruno , Sun Fei , Cheng C. Yan , Chen Hao
Published: April 2024

Microtubule-associated protein 1a (Map1a) is a microtubule (MT) regulatory protein that binds to the MT protofilaments in mammalian cells to promote MT stabilization. Maps work with MT cleavage proteins and other MT catastrophe-inducing proteins to confer MT dynamics to support changes in the Sertoli cell shape to sustain spermatogenesis. However, no functional studies are found in the literature to probe its role in spermatogenesis. Using an RNAi approach, coupled with the use of toxicant-induced testis (in vivo)- and Sertoli cell (in vitro)-injury models, RNA-Seq analysis, transcriptome profiling, and relevant bioinformatics analysis, immunofluorescence analysis, and pertinent biochemical assays for cytoskeletal organization, we have delineated the functional role of Map1a in Sertoli cells and testes. Map1a was shown to support MT structural organization, and its knockdown (KD) also perturbed the structural organization of actin, vimentin, and septin cytoskeletons as these cytoskeletons are intimately related, working in concert to support spermatogenesis. More importantly, cadmium-induced Sertoli cell injury that perturbed the MT structural organization across the cell cytoplasm was associated with disruptive changes in the distribution of Map1a and a surge in p-p38-MAPK (phosphorylated p38-mitogen-activated protein kinase) expression but not total p38-MAPK. These findings thus support the notion that p-p38-MAPK activation is involved in cadmium-induced Sertoli cell injury. This conclusion was supported by studies using doramapimod, a specific p38-MAPK phosphorylation (activation) inhibitor, which was capable of restoring the cadmium-induced disruptive structural organization of MTs across the Sertoli cell cytoplasm. In summary: this study provides mechanistic insights regarding restoration of toxicant-induced Sertoli cell and testis injury and male infertility.
Specific isoforms of the ubiquitin ligase gene WWP2 are targets of osteoarthritis genetic risk via a differentially methylated DNA sequence
Authors: Roberts Jack B. , Boldvig Olivia L.G. , Aubourg Guillaume , Kanchenapally S. Tanishq , Deehan David J. , Rice Sarah J. , Loughlin John
Published: April 2024

Background

Transitioning from a genetic association signal to an effector gene and a targetable molecular mechanism requires the application of functional fine-mapping tools such as reporter assays and genome editing. In this report, we undertook such studies on the osteoarthritis (OA) risk that is marked by single nucleotide polymorphism (SNP) rs34195470 (A > G). The OA risk-conferring G allele of this SNP associates with increased DNA methylation (DNAm) at two CpG dinucleotides within WWP2. This gene encodes a ubiquitin ligase and is the host gene of microRNA-140 (miR-140). WWP2 and miR-140 are both regulators of TGFβ signaling.

Methods

Nucleic acids were extracted from adult OA (arthroplasty) and foetal cartilage. Samples were genotyped and DNAm quantified by pyrosequencing at the two CpGs plus 14 flanking CpGs. CpGs were tested for transcriptional regulatory effects using a chondrocyte cell line and reporter gene assay. DNAm was altered using epigenetic editing, with the impact on gene expression determined using RT-qPCR. In silico analysis complemented laboratory experiments.

Results

rs34195470 genotype associates with differential methylation at 14 of the 16 CpGs in OA cartilage, forming a methylation quantitative trait locus (mQTL). The mQTL is less pronounced in foetal cartilage (5/16 CpGs). The reporter assay revealed that the CpGs reside within a transcriptional regulator. Epigenetic editing to increase their DNAm resulted in altered expression of the full-length and N-terminal transcript isoforms of WWP2. No changes in expression were observed for the C-terminal isoform of WWP2 or for miR-140.

Conclusions

As far as we are aware, this is the first experimental demonstration of an OA association signal targeting specific transcript isoforms of a gene. The WWP2 isoforms encode proteins with varying substrate specificities for the components of the TGFβ signaling pathway. Future analysis should focus on the substrates regulated by the two WWP2 isoforms that are the targets of this genetic risk.
Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging
Authors: Cantero Jose L. , Atienza Mercedes , Sastre Isabel , Bullido María Jesús
Published: April 2024

Background

Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging, which may contribute to the elucidation of the role of HSV-1 infection as a potential AD risk factor.

Methods

To shed light into this question, serum anti-HSV IgG levels were correlated with18F-Florbetaben-PET binding to Aβ deposits and blood markers of neurodegeneration (pTau181 and neurofilament light chain) in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers.

Results

We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration.

Conclusions

All together, these results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.