bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-seq–based miRNA signature as an independent predictor of relapse in pediatric B-cell acute lymphoblastic leukemia
Authors: Kubota Hirohito , Ueno Hiroo , Tasaka Keiji , Isobe Tomoya , Saida Satoshi , Kato Itaru , Umeda Katsutsugu , Hiwatari Mitsuteru , Hasegawa Daiichiro , Imamura Toshihiko , Kakiuchi Nobuyuki , Nannya Yasuhito , Ogawa Seishi , Hiramatsu Hidefumi , Takita Junko
Published: December 2023

Aberrant micro-RNA (miRNA) expression profiles have been associated with disease progression and clinical outcome in pediatric cancers. However, few studies have analyzed genome-wide dysregulation of miRNAs and messenger RNAs (mRNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To identify novel prognostic factors, we comprehensively investigated miRNA and mRNA sequencing (miRNA-seq and mRNA-seq) data in pediatric BCP-ALL samples with poor outcome. We analyzed 180 patients, including 43 matched pairs at diagnosis and relapse. Consensus clustering of miRNA expression data revealed a distinct profile characterized by mainly downregulation of miRNAs (referred to as an miR-low cluster [MLC]). The MLC profile was not associated with any known genetic subgroups. Intriguingly, patients classified as MLC had significantly shorter event-free survival (median 21 vs 33 months; log-rank P = 3 ×10−5). Furthermore, this poor prognosis was retained even in hyperdiploid ALL. This poor prognostic MLC profiling was confirmed in the validation cohort. Notably, non-MLC profiling at diagnosis (n = 9 of 23; Fisher exact test, P = .039) often changed into MLC profiling at relapse for the same patient. Integrated analysis of miRNA-seq and mRNA-seq data revealed that the transcriptional profile of MLC was characterized by enrichment of MYC target and oxidative phosphorylation genes, reduced intron retention, and low expression of DICER1. Thus, our miRNA-mRNA integration approach yielded a truly unbiased molecular stratification of pediatric BCP-ALL cases based on a novel prognostic miRNA signature, which may lead to better clinical outcomes.
Reflecting real-world patients with mesothelioma in research: an interim report of baseline characteristics from the ASSESS-meso cohort
Authors: Conway Ruairi J.H. , Smith Natalie , Cooper William , Lynch Geraldine , Patole Sonia , Symonds Jenny , Edey Anthony , Maskell Nick A. , Bibby Anna C. ,   on behalf of the ASSESS-meso Collaborative group
Published: December 2023

Objective

Mesothelioma varies in clinical phenotype and survival. Clinical trials are unavoidably affected by selection bias, reducing generalisability. ASSESS-meso is a UK, multicentre, prospective, mesothelioma cohort study (ISRCTN61861764). This pre-specified interim analysis, conducted when recruitment reached 25% of target, summarised participant characteristics and evaluated external validity through comparison with real-world and clinical trial cohorts.

Methods

The study took place at 14 hospitals across the UK. People diagnosed with mesothelioma, at any anatomical site, were eligible. Clinical, radiological and biochemical data were collected at enrolment. In this interim report, the external validity of the cohort was investigated through comparison of baseline demographic data with populations included in the 2020 UK National Mesothelioma Audit (real-world cohort), and CHECKMATE-743 and MAPS trials (clinical trial cohorts).

Results

244 patients were enrolled between 7 April 2017 and 1 March 2022. The cohort was predominantly male (195 out of 244; 80%) with a median age of 74 years. Pleural disease and epithelioid subtypes were most prevalent. ASSESS-meso participants were more similar to the real-world population with regard to age, performance status, disease site and stage than the clinical trial population. ASSESS-meso participants were more likely to be formally staged and less likely to have undifferentiated histology compared with the real-world cohort, possibly reflecting high rates of discussion of ASSESS-meso participants at regional mesothelioma multidisciplinary team meetings. As expected, poorer performance status, non-epithelioid histology and neutrophil–lymphocyte ratio were associated with shorter survival in the adjusted analysis.

Conclusion

ASSESS-meso is representative of the UK mesothelioma population. Future outputs from the cohort will help characterise different mesothelioma phenotypes with high external validity.
Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis
Authors: Guillen-Guio Beatriz , Paynton Megan L. , Allen Richard J. , Chin Daniel P.W. , Donoghue Lauren J. , Stockwell Amy , Leavy Olivia C. , Hernandez-Beeftink Tamara , Reynolds Carl , Cullinan Paul , Martinez Fernando , Booth Helen L. , Fahy William A. , Hall Ian P. , Hart Simon P. , Hill Mike R. , Hirani Nik , Hubbard Richard B. , McAnulty Robin J. , Millar Ann B. , Navaratnam Vidya , Oballa Eunice , Parfrey Helen , Saini Gauri , Sayers Ian , Tobin Martin D. , Whyte Moira K.B. , Adegunsoye Ayodeji , Kaminski Naftali , Ma Shwu-Fan , Strek Mary E. , Zhang Yingze , Fingerlin Tasha E. , Molina-Molina Maria , Neighbors Margaret , Sheng X. Rebecca , Oldham Justin M. , Maher Toby M. , Molyneaux Philip L. , Flores Carlos , Noth Imre , Schwartz David A. , Yaspan Brian L. , Jenkins R. Gisli , Wain Louise V. , Hollox Edward J.
Published: December 2023

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of theHLA-DQB1gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.

Methods

We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case–control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10−4and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reportedHLA-DQB1association in the subset of studies independent of the original report.

Results

The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. TheHLA-DQB1association was not replicated in the independent IPF studies.

Conclusion

Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.
Amyloid-β and caspase-1 are indicators of sepsis and organ injury
Authors: Tuckey Amanda N. , Brandon Arcole , Eslaamizaad Yasaman , Siddiqui Waqar , Nawaz Talha , Clarke Christopher , Sutherland Erica , Williams Veronica , Spadafora Domenico , Barrington Robert A. , Alvarez Diego F. , Mulekar Madhuri S. , Simmons Jon D. , Fouty Brian W. , Audia Jonathon P.
Published: December 2023

Background

Sepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post-discharge. The present study identifies a novel regulatory relationship between amyloid-β (Aβ) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes.

Methods

Medical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1 and Aβ levels were measured. Data were compared against indices of multiorgan injury and other clinical parameters. Additionally, recombinant proteins were testedin vitroto examine the effect of caspase-1 on a functional hallmark of Aβ, namely aggregation.

Results

Plasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (area under the receiver operating characteristic curve=0.7080). Plasma caspase-1 and the Aβ isoform Aβx-40 showed a significant positive correlation and Aβx-40 associated with organ injury. Additionally, Aβ plasma levels continued to rise from time of ICU admission to 7 days post-admission.In silico, Aβ harbours a predicted caspase-1 cleavage site, andin vitrostudies demonstrated that caspase-1 cleaved Aβ to inhibit its auto-aggregation, suggesting a novel regulatory relationship.

Conclusions

Aβx-40 and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aβx-40 has emerged as a potential culprit in the ensuing development of post-ICU syndrome.
Realization of collimated specific profiles in rotation-symmetrical beam shaping system with divergent light source
Authors: Tsai Cheng-Mu , Yu Tzu-Chen , Han Pin , Fang Yi-Chin
Published: December 2023

A simple numerical method is proposed for the design of two aspherical surfaces, each comprising multiple segmented refractive planes, for generating a collimated beam with a specific irradiance profile in a beam shaping system with a divergent light source. However, in real-world manufacturing, this performance improvement is obtained at the expense of a greater cost and complexity. Accordingly, a second algorithm is proposed which maximizes the number of rays passing through the central regions of the refractive planes in the second aspherical surface and hence minimizes the total number of segments required to achieve the same beam shaping performance. The feasibility of the proposed method is demonstrated through the design of two aspherical lenses for generating collimated output beams with ring- and triangle-like irradiance profiles, respectively. The experimental results show that the beam profiles are in close agreement with the desired irradiance distributions. In general, the results indicate that the proposed method provides a versatile and efficient approach for achieving the desired collimated profile in beam forming systems with a divergent light source.
Bilateral adrenal infarction and insufficiency associated with antiphospholipid syndrome and surgery: a case report
Authors: Iijima Yoshihito , Ishikawa Masahito , Motono Nozomu , Uramoto Hidetaka
Published: December 2023

Background

Antiphospholipid syndrome causes systemic arterial and venous thromboses due to the presence of antiphospholipid antibodies. Adrenal insufficiency is a rare complication of antiphospholipid syndrome that may result in fatal outcomes if left untreated. Therefore, we report adrenal insufficiency as a rare complication of bilateral adrenal infarction associated with antiphospholipid syndrome and trauma surgery.

Case presentation

A 64-year-old male patient underwent surgery for a left traumatic hemothorax. He concurrently had antiphospholipid syndrome and was receiving warfarin. Postoperatively, the patient complained of severe lumbar back pain despite resuming anticoagulation therapy, and he experienced paralytic ileus and shock. Abdominal contrast-enhanced computed tomography revealed adrenal swelling and increased surrounding retroperitoneal adipose tissue density. Diffusion-weighted abdominal magnetic resonance imaging showed high-intensity areas in the bilateral adrenal glands. Cortisol and adrenocorticotropic hormone levels were 3.30 μg/dL and 185.1 pg/dL, respectively. Subsequently, the patient was diagnosed with bilateral adrenal infarction and acute adrenal insufficiency, and hydrocortisone was immediately administered. Adrenal insufficiency improved gradually, and the patient was discharged after initiating steroid replacement therapy.

Conclusions

The timing of postoperative anticoagulant therapy initiation remains controversial. Therefore, adrenal insufficiency due to adrenal infarction should be monitored while anticoagulant therapy is discontinued in patients with antiphospholipid syndrome.
Efficacy of acupuncture for psychogenic erectile dysfunction: a randomized, sham-controlled trial
Authors: Wang Hao , Lei Xulu , Ma Dongyue , Zhao Ziwei , Wang Anmin , Du Guanchao , Zhang Jiwei , Wang Fu , Guo Jun
Published: December 2023

Background

Psychogenic erectile dysfunction (pED) is a common sexual dysfunction often accompanied by psychosomatic factors. Its treatment includes oral medications, psychotherapy, and behavioral therapy. Acupuncture’s effect on erectile function in pED patients remains to be investigated. This randomized study evaluated the effects of acupuncture and sham acupuncture in pED patients. Altogether, 66 men with pED were randomized to the acupuncture (n = 33) or sham acupuncture group (n = 33). Both groups have a 6-week treatment with 18 sessions. Primary outcome was the International Index of Erectile Function-5 (IIEF-5) at 6 weeks. Secondary outcomes were IIEF-5 (weeks 2, 4, and 10), erection hardness score (EHS), sexual encounter profile-2 (SEP-2), SEP-3, self-rating anxiety scale (SAS), and self-rating depression scale (SDS).

Results

Among the 66 participants, 64 completed the outcome measurements at week 10. Both acupuncture and sham acupuncture groups had improved IIEF-5 and EHS and decreased SAS and SDS post-treatment (p < 0.05). The acupuncture group had significantly better improvement in IIEF-5, EHS, and SEP-3 and significantly reduced SAS and SDS than the sham acupuncture group (p < 0.05). The improvement in SEP-2 post-treatment was not significantly different between the two groups (p > 0.05). There were no serious adverse events.

Conclusions

The 6-week acupuncture treatment significantly improved the erectile capacity and psychosomatic status of pED patients.

Trial registration

ChiCTR2200064345 (Chinese Clinical Trial Registry) (https://www.chictr.org.cn/showproj.html?proj=174873).
Adult zebrafish infected by clinically isolated Klebsiella pneumoniae with different virulence showed increased intestinal inflammation and disturbed intestinal microbial biodiversity
Authors: Wang Xu , Li Ting , Zhou Lu , Tu Fan , Rui Xiaohong , Xu Ze , Liu Jun , Cao Futao
Published: December 2023

Background

Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae.

Methods

In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested.

Results

Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1β (Il-1β), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria.

Conclusions

Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.
Interventions to reduce falls among dialysis patients: a systematic review
Authors: Gute Lelise , Zimbudzi Edward
Published: December 2023

Introduction

Despite all available evidence regarding increased morbidity and mortality among dialysis patients due to falls and their complications, and an increase in risk factors for falls, relatively little attention has been focused on evidence-based interventions that can reduce falls. We evaluated the effectiveness of fall prevention interventions among dialysis patients.

Methods

We searched Ovid-Medline, Ovid-Embase, PubMed, Cumulated Index to Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials (Central) from inception to 19 July 2023 for studies that evaluated the effectiveness of fall prevention interventions among dialysis patients. The search, screening and extraction of data followed standardised processes and the methodological quality of studies was independently assessed by two reviewers. Data was analysed using a narrative synthesis approach.

Results

Of the 18 studies that had full text review, five were eligible. Three studies were performed in the USA and one each in UK and Japan. Four studies were conducted in outpatient hemodialysis centres and one in a hospital-based nephrology unit. Reported sample sizes ranged from 51 to 96 participants per study with a follow-up period of 3 to 35 months. There was moderate-quality evidence that exercises reduce the rate of falls compared to usual care and low to moderate quality of evidence that multifactorial falls prevention interventions reduce the rate of falls. However, treatment effects could not be quantitatively estimated for all interventions due to substantial heterogeneity of included studies.

Conclusions

This systematic review reflects that there is insufficient evidence regarding falls prevention strategies specific to dialysis patients. Available data based on low to moderate quality studies, suggest that among dialysis patients, exercises may reduce falls and the effectiveness of multifactorial interventions such as staff and patient education still need to be explored using high-quality prospective studies.
A multivariable model of ultrasound and clinicopathological features for predicting axillary nodal burden of breast cancer: potential to prevent unnecessary axillary lymph node dissection
Authors: Yang Lei , Gu Yifan , Wang Bing , Sun Ming , Zhang Lei , Shi Lei , Wang Yanfei , Zhang Zheng , Yin Yifei
Published: December 2023

Background

To develop a clinical model for predicting high axillary nodal burden in patients with early breast cancer by integrating ultrasound (US) and clinicopathological features.

Methods and materials

Patients with breast cancer who underwent preoperative US examination and breast surgery at the Affiliated Hospital of Nantong University (centre 1, n = 250) and at the Affiliated Hospital of Jiangsu University (centre 2, n = 97) between January 2012 and December 2016 and between January 2020 and March 2022, respectively, were deemed eligible for this study (n = 347). According to the number of lymph node (LN) metastasis based on pathology, patients were divided into two groups: limited nodal burden (0–2 metastatic LNs) and heavy nodal burden (≥ 3 metastatic LNs). In addition, US features combined with clinicopathological variables were compared between these two groups. Univariate and multivariate logistic regression analysis were conducted to identify the most valuable variables for predicting ≥ 3 LNs in breast cancer. A nomogram was then developed based on these independent factors.

Results

Univariate logistic regression analysis revealed that the cortical thickness (p < 0.001), longitudinal to transverse ratio (p = 0.001), absence of hilum (p < 0.001), T stage (p = 0.002) and Ki-67 (p = 0.039) were significantly associated with heavy nodal burden. In the multivariate logistic regression analysis, cortical thickness (p = 0.001), absence of hilum (p = 0.042) and T stage (p = 0.012) were considered independent predictors of high-burden node. The area under curve (AUC) of the nomogram was 0.749.

Conclusion

Our model based on US variables and clinicopathological characteristics demonstrates that can help select patients with ≥ 3 LNs, which can in turn be helpful to predict high axillary nodal burden in early breast cancer patients and prevent unnecessary axillary lymph node dissection.
The roles of the general practitioner and sexual health centre in HIV testing: comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study
Authors: Twisk Denise E. , Meima Abraham , Richardus Jan Hendrik , van Sighem Ard , Rokx Casper , den Hollander Jan G. , Götz Hannelore M.
Published: December 2023

Background

Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence.

Methods

Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence.

Results

The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds.

Conclusions

GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.
Common domains of nurses’ competencies in public health emergencies: a scoping review
Authors: Guo Xue-E. , Bian Li-Fang , Li Yan , Li Chun-Yan , Lin Yu
Published: December 2023

Background

A public health emergency can cause large numbers of deaths in a short period, with devastating social, economic and health consequences. Nurses are the main healthcare providers during such emergencies, and their competencies affect the control and outcomes of the situation. Studies on nurses’ competencies in public health emergencies vary between countries and healthcare systems. Therefore, we conducted a scoping review to identify the common domains of nurses’ competencies in public health emergencies worldwide.

Methods

We searched the PubMed, CINHAL, Scopus, Web of Science, Science Direct, Embase, Cochrane Library, WanFang and ECRI databases from their inception to 2023. All published articles on nurses’ competencies in public health emergencies that were published in English and Chinese were included. We mainly analyzed and synthesized nurses’ competencies, assessment instruments and the training described in the included studies.

Results

A total of 27 competency domains were identified following an analysis and summary. The most frequently cited domains were communication skills, self-protection skills, basic knowledge of a public health emergency, laws and ethics and the capacity for organizational collaboration. The Disaster Preparedness Evaluation Tool and the Emergency Preparedness Information Questionnaire were the most commonly used tools for assessing competencies. Most training was conducted online and the content that was covered varied by country.

Conclusions

Given the significant roles and responsibilities of nurses in public health emergencies, knowing the domains of their competencies is essential to evaluating, developing, and conducting clinical training.
Knowledge and dispensing practice of community pharmacists towards antipsychotic medicines in a Nigerian metropolitan city – a cross-sectional study
Authors: Olasupo Joseph , Taiwo Faith , Aje Akinniyi , Fakeye Titilayo O.
Published: December 2023

Background

Antipsychotic drugs are prescription-only-medications which require valid prescriptions before it can be obtained from a pharmacy. On the other hand, community pharmacists in developing countries have sometimes been implicated in over-the-counter dispensing of prescription-only-medications.

Objective

This study investigated the accessibility of antipsychotic drugs without prescriptions from community pharmacies, and the factors responsible for the over-the-counter dispensing of antipsychotics by community pharmacists.

Methods

An exploratory cross-sectional mixed method survey design using pretested structured questionnaires among 119 community pharmacists, simulated patients in 119 community pharmacies, and one-on-one in-depth interview among eleven (11) community pharmacist-owners/superintendent pharmacists were utilized for data collection. The knowledge of the pharmacists on antipsychotics including classification, side effects, and dispensing practices were explored. Qualitative data was analyzed with thematic analysis, while quantitative data was analyzed using descriptive statistics.

Results

Majority of the community pharmacists (87.4%) showed good knowledge of antipsychotics as it relates to the different classes and the side effects peculiar to each class. Antipsychotic medications were dispensed by 85 (71.4%) of community pharmacists without a prescription. One-on-one in-depth interview sessions with community pharmacist owners/superintendent pharmacists demonstrated that community pharmacists are knowledgeable about antipsychotics and their side effects. Reasons given for dispensing this class of drugs without prescription included emergencies, and knowledge of the person as being on the drugs long-term. About 4% pharmacists were adamant on dispensing only with prescription.

Conclusion

Community pharmacists in Ibadan metropolis readily dispense antipsychotics without valid prescriptions despite having an optimal knowledge about the negative implications of doing so. This could be due to weak legislation and regulation of drug laws. There is a need for more stringent regulations as well as adequate sensitization about the negative effects of inappropriate dispensing of prescription-only-medications.
Maternal sevoflurane exposure increases the epilepsy susceptibility of adolescent offspring by interrupting interneuron development
Authors: Liang Xinyue , Jiang Ming , Xu Hao , Tang Tianxiang , Shi Xiangpeng , Dong Yi , Xiao Lei , Xie Yunli , Fang Fang , Cang Jing
Published: December 2023

Background

Exposure to general anesthesia influences neuronal functions during brain development. Recently, interneurons were found to be involved in developmental neurotoxicity by anesthetic exposure. But the underlying mechanism and long-term consequences remain elusive.

Methods

Pregnant mice received 2.5% sevoflurane for 6-h on gestational day 14.5. Pentylenetetrazole (PTZ)-induced seizure, anxiety- and depression-like behavior tests were performed in 30- and 60-day-old male offspring. Cortical interneurons were labeled using Rosa26-EYFP/-; Nkx2.1-Cre mice. Immunofluorescence and electrophysiology were performed to determine the cortical interneuron properties. Q-PCR and in situ hybridization (ISH) were performed for the potential mechanism, and the finding was further validated by in utero electroporation (IUE).

Results

In this study, we found that maternal sevoflurane exposure increased epilepsy susceptibility by using pentylenetetrazole (PTZ) induced-kindling models and enhanced anxiety- and depression-like behaviors in adolescent offspring. After sevoflurane exposure, the highly ordered cortical interneuron migration was disrupted in the fetal cortex. In addition, the resting membrane potentials of fast-spiking interneurons in the sevoflurane-treated group were more hyperpolarized in adolescence accompanied by an increase in inhibitory synapses. Both q-PCR and ISH indicated that CXCL12/CXCR4 signaling pathway downregulation might be a potential mechanism under sevoflurane developmental neurotoxicity which was further confirmed by IUE and behavioral tests. Although the above effects were obvious in adolescence, they did not persist into adulthood.

Conclusions

Our findings demonstrate that maternal anesthesia impairs interneuron migration through the CXCL12/CXCR4 signaling pathway, and influences the interneuron properties, leading to the increased epilepsy susceptibility in adolescent offspring. Our study provides a novel perspective on the developmental neurotoxicity of the mechanistic link between maternal use of general anesthesia and increased susceptibility to epilepsy.
The stories about racism and health: the development of a framework for racism narratives in medical literature using a computational grounded theory approach
Authors: Figueroa Caroline A. , Manalo-Pedro Erin , Pola Swetha , Darwish Sajia , Sachdeva Pratik , Guerrero Christian , von Vacano Claudia , Jha Maithili , De Maio Fernando , Kennedy Chris J.
Published: December 2023

Introduction

The scientific study of racism as a root cause of health inequities has been hampered by the policies and practices of medical journals. Monitoring the discourse around racism and health inequities (i.e., racism narratives) in scientific publications is a critical aspect of understanding, confronting, and ultimately dismantling racism in medicine. A conceptual framework and multi-level construct is needed to evaluate the changes in the prevalence and composition of racism over time and across journals.

Objective

To develop a framework for classifying racism narratives in scientific medical journals.

Methods

We constructed an initial set of racism narratives based on an exploratory literature search. Using a computational grounded theory approach, we analyzed a targeted sample of 31 articles in four top medical journals which mentioned the word ‘racism’. We compiled and evaluated 80 excerpts of text that illustrate racism narratives. Two coders grouped and ordered the excerpts, iteratively revising and refining racism narratives.

Results

We developed a qualitative framework of racism narratives, ordered on an anti-racism spectrum from impeding anti-racism to strong anti-racism, consisting of 4 broad categories and 12 granular modalities for classifying racism narratives. The broad narratives were “dismissal,” “person-level,” “societal,” and “actionable.” Granular modalities further specified how race-related health differences were related to racism (e.g., natural, aberrant, or structurally modifiable). We curated a “reference set” of example sentences to empirically ground each label.

Conclusion

We demonstrated racism narratives of dismissal, person-level, societal, and actionable explanations within influential medical articles. Our framework can help clinicians, researchers, and educators gain insight into which narratives have been used to describe the causes of racial and ethnic health inequities, and to evaluate medical literature more critically. This work is a first step towards monitoring racism narratives over time, which can more clearly expose the limits of how the medical community has come to understand the root causes of health inequities. This is a fundamental aspect of medicine’s long-term trajectory towards racial justice and health equity.
Platelets as delivery vehicles for targeted enrichment of NO· to cerebral glioma for magnetic resonance imaging
Authors: Ding Yuchen , Ge Min , Zhang Chao , Yu Juncheng , Xia Donglin , He Jian , Jia Zhongzheng
Published: December 2023

Using a magnetic resonance imaging (MRI) contrast agent, MRI has made substantial contributions to glioma diagnosis. Metal-free MRI agents, such as the nano free radical nitric oxide (NO·) micelle, can overcome the inherent toxicity of metal-based agents in certain patient populations. However, the low spatial resolution of nano NO· micelle in MRI limits its clinical development. In this study, we pretreated platelets (PLTs) and loaded them with nano NO· micelles to synthesize NO·@PLT, which can overcome the low contrast and poor in vivo stability of nitroxide-based MRI contrast agents. The PLTs can serve as potential drug carriers for targeting and delivering nano NO· micelles to gliomas and thus increase the contrast in T1-weighted imaging (T1WI) of MRI. This drug carrier system uses the unique tumor-targeting ability of PLTs and takes advantage of the high signal presentation of steady nano NO· micelles in T1WI, thereby ultimately achieving signal amplification of glioma in T1WI. With the effect of PLTs-tumor cell adhesion, NO·@PLT has per-nitroxide transverse relativities of approximately 2-fold greater than those of free NO· particles. These features allow a sufficient NO·@PLT concentration to accumulate in murine subcutaneous glioma tumors up from 5 min to 2.5 h (optimum at 1.5 h) after systemic administration. This results in MRI contrast comparable to that of metal-based agents. This study established a promising metal-free MRI contrast agent, NO·@PLT, for glioma diagnosis, because it has superior spatial resolution owing to its high glioma-targeting ability and has significant translational implications in the clinic.
Differences in buprenorphine prescribing readiness among primary care professionals with and without X-waiver training in the US
Authors: Franz Berkeley , Dhanani Lindsay Y. , Hall O. Trent , Brook Daniel L. , Simon Janet E. , Miller William C.
Published: December 2023

Background

Medications for opioid use disorder (OUD) are effective at preventing overdose and infectious disease but are vastly under-prescribed in the US. For decades, prescribers faced additional training and regulation to prescribe buprenorphine which stigmatized the medication and lessened support for a harm reduction approach to treating opioid use disorder. The Drug Enforcement Administration removed the X-waiver requirement for prescribing buprenorphine in late 2022, which removed stigma and lessened important barriers to prescribing but also left training at the discretion of individual organizations. Our study aimed to assess differences in knowledge, confidence, and stigma regarding buprenorphine between those who went through the X-waiver training and those who did not, among practicing primary care providers (PCPs).

Methods

We assessed buprenorphine prescribing readiness among primary care aligned outpatient providers in Ohio, USA. Using survey data, we conducted bivariate and regression analyses predicting primary prescribing outcomes. Primary outcomes measured knowledge of and confidence in buprenorphine, as well as perceived adequacy of one’s training. Secondary outcomes were attitudes toward patients with OUD, including bias toward OUD patients, stress when working with them, and empathy toward them. Participants (n = 403) included physicians, nurse practitioners, and physician assistants practicing in primary care aligned disciplines.

Results

Survey data showed that PCPs who received X-waiver training were more likely to understand and have confidence in the mechanism of buprenorphine, and consider their training on treating OUD to be adequate. PCPs with an X-waiver showed more empathy, less negative bias, and experienced less stress when working with patients with OUD.

Conclusion

Removing restrictive policies for prescribing buprenorphine is an important step to expanding access and reducing the stigma associated with opioid use disorder treatment. Yet, our findings suggest that the training received alongside regulation may be important for improving prescribing confidence and reducing stigma. Strategies to increase buprenorphine prescribing are unlikely to be effective without also expanding access to prescribing support for primary care providers across the career course.
Macrophage polarization in inflammatory bowel disease
Authors: Zhang Kun , Guo Jing , Yan Wenlong , Xu Lingfen
Published: December 2023

The growing prevalence of inflammatory bowel disease (IBD) has encouraged research efforts, which have contributed to gradual improvements in our understanding of IBD diagnosis and therapeutic approaches. The pathogenesis of IBD has not been fully elucidated; however, the combined actions of environmental, genetic, immune factors, and microbial organisms are believed to cause IBD. In the innate immune system, macrophages play important roles in maintaining intestinal health and in the development of IBD. Macrophages can be polarized from M0 into several phenotypes, among which M1 and M2 play critical roles in IBD development and the repair of intestinal homeostasis and damage. Certain macrophage-related IBD studies already exist; however, the functions of each phenotype have not been fully elucidated. As technology develops, understanding the link between macrophages and IBD has increased, including the growing knowledge of the developmental origins of intestinal macrophages and their performance of comprehensive functions. This review describes macrophage polarization in IBD from the perspectives of macrophage development and polarization, macrophage changes in homeostasis and IBD, metabolic changes, and the mechanisms of macrophage polarization in IBD. The discussion of these topics provides new insights into immunotherapy strategies for IBD.
Outpatient screening for anxiety and depression symptoms in adolescents with type 1 diabetes - a cross-sectional survey
Authors: Reinauer Christina , Tittel Sascha R. , Müller-Stierlin Annabel , Baumeister Harald , Warschburger Petra , Klauser Katharina , Minden Kirsten , Staab Doris , Gohlke Bettina , Horlebein Bettina , Schwab Karl Otfried , Meißner Thomas , Holl Reinhard W.
Published: December 2023

Background

The daily demands of type 1 diabetes management may jeopardize adolescents’ mental health. We aimed to assess anxiety and depression symptoms by broad-scale, tablet-based outpatient screening in adolescents with type 1 diabetes in Germany.

Methods

Adolescent patients with type 1 diabetes mellitus (n = 2,394; mean age 15.4 y [SD 2.0]; 50.7% male) were screened for anxiety (GAD-7) and depression symptoms (PHQ-9) by self-report questionnaires and linked to clinical data from the DPV patient registry. Logistic regression was used to estimate the contribution of clinical parameters to positive screening results.

Results

Altogether, 30.2% showed a positive screening (score ≥ 7 in either test), and 11.3% reported suicidal ideations or self-harm. Patients with anxiety and depression symptoms were older (15.7 y [CI 15.5–15.8] vs. 15.3 y [CI 15.2–15.4]; p < 0.0001), had higher HbA1c levels (7.9% [CI 7.8-8.0] (63 mmol/mol) vs. 7.5% [CI 7.4–7.5] (58 mmol/mol); p < 0.0001), and had higher hospitalization rates. Females (adjusted odds ratio (aOR) 2.66 [CI 2.21–3.19]; p < 0.0001), patients > 15 years (aOR 1.40 [1.16–1.68]; p < 0.001), who were overweight (aOR 1.40 [CI 1.14–1.71]; p = 0.001), with HbA1c > 9% (> 75 mmol/mol; aOR 2.58 [1.83–3.64]; each p < 0.0001), with a migration background (aOR 1.46 [CI 1.17–1.81]; p < 0.001), or smoking (aOR 2.72 [CI 1.41–5.23]; p = 0.003) had a higher risk. Regular exercise was a significant protective factor (aOR 0.65 [CI 0.51–0.82]; p < 0.001). Advanced diabetes technologies did not influence screening outcomes.

Conclusions

Electronic mental health screening was implemented in 42 centers in parallel, and outcomes showed an association with clinical parameters from sociodemographic, lifestyle, and diabetes-related data. It should be integrated into holistic patient counseling, enabling early recognition of mild mental health symptoms for preventive measures. Females were disproportionally adversely affected. The use of advanced diabetes technologies did not yet reduce the odds of anxiety and depression symptoms in this cross-sectional assessment.
The cost-utility of an intervention for children and adolescents with a parent having a mental illness in the framework of the German health and social care system: a health economic evaluation of a randomized controlled trial
Authors: Waldmann Tamara , Schaible Jochen , Stiawa Maja , Becker Thomas , Wegscheider Karl , Adema Bonnie , Wiegand-Grefe Silke , Kilian Reinhold
Published: December 2023

Background

Children of families with a parent with a mental illness have an increased risk of developing social and mental health problems resulting in decreased quality of life. Therefore, children and adolescents living in families with a parent with mental illness are regarded as a target group for preventive interventions. To date, only a few economic evaluation studies for interventions directed at preventing the intergenerational transmission of mental health problems exist. In this investigation we estimated the cost utility of an intervention for the support of children and adolescents with a parent having a mental illness from the perspective of the German health and social care system.

Methods

We randomly assigned a total of 214 families with 337 children and adolescents to the intervention (INT) group (108/170) or the control (TAU) group (106/167). Families in the intervention group received on average eight intervention sessions (50–90 min) over 6 months. We estimated total cost of illness by means of the Children and Adolescent Mental Health Service Receipt Inventory (CAMHSRI) over 24 months. For the estimation of Quality-Adjusted Live Years (QALYs) we applied the KIDSCREEN-10. For estimating the incremental cost-utility of the intervention compared to treatment as usual we used the net-benefit approach.

Results

We estimated the annual cost of illness amounting to € 3784.59 (SD € 8581.11) in the TAU group and € 3264.44 (SD € 9431.89) in the INT group. The annual cost difference between INT and TAU was € − 516.14 (SE 1124.95) which was not significant (p ≤ 0.05). We estimated the average QALY to be 0.759 (SD 0.073) in the TAU group and 0.763 (SD 0.072). The QALY difference between INT and TAU was 0.0037 (SE 0.0092) which was not significant (p ≤ 0.05). The incremental cost utility ratio (ICUR) indicated that the gain of one additional year in full health by means of the intervention was associated with the saving of € 139.49. However, the stochastic insecurity of the ICUR did not allow a unique decision about the cost-utility of the intervention.

Conclusions

More information on the economic value of the intervention for families with a parent with mental illness in comparison to treatment as usual in Germany is needed.

Trial registration: ClinicalTrials.gov, identifier NCT02308462; German Clinical Trials Register: DRKS00006806.
Characteristics and clinical evaluation of X chromosome translocations
Authors: Huang Ning , Zhou Jihui , Lu Wan , Luo Laipeng , Yuan Huizhen , Pan Lu , Ding Shujun , Yang Bicheng , Liu Yanqiu
Published: December 2023

Background

Individuals with X chromosomal translocations, variable phenotypes, and a high risk of live birth defects are of interest for scientific study. These characteristics are related to differential breakpoints and various types of chromosomal abnormalities. To investigate the effects of X chromosome translocation on clinical phenotype, a retrospective analysis of clinical data for patients with X chromosome translocation was conducted. Karyotype analysis plus endocrine evaluation was utilized for all the patients. Additional semen analysis and Y chromosome microdeletions were assessed in male patients.

Results

X chromosome translocations were detected in ten cases, including seven females and three males. Infantile uterus and no ovaries were detected in case 1 (FSH: 114 IU/L, LH: 30.90 mIU/mL, E2: < 5.00 pg/ml), and the karyotype was confirmed as 46,X,t(X;22)(q25;q11.2) in case 1. Infantile uterus and small ovaries were both visible in two cases (FSH: 34.80 IU/L, LH: 17.06 mIU/mL, E2: 15.37 pg/ml in case 2; FISH: 6.60 IU/L, LH: 1.69 mIU/mL, E2: 23.70 pg/ml in case 3). The karyotype was detected as 46,X,t(X;8)(q13;q11.2) in case 2 and 46,X,der(X)t(X;5)(q21;q31) in case 3. Normal reproductive hormone levels and fertility abilities were found for cases 4, 6 and 7. The karyotype were detected as 46,X,t(X;5)(p22.3;q22) in case 4 and 46,X,der(X)t(X;Y)(p22.3;q11.2) in cases 6 and 7. These patients exhibited unremarkable clinical manifestations but experienced a history of abnormal chromosomal pregnancy. Normal phenotype and a complex reciprocal translocation as 46,X,t(X;14;4)(q24;q22;q33) were observed in case 5 with a history of spontaneous abortions. In the three male patients, multiple semen analyses confirmed the absence of sperm. Y chromosome microdeletion and hormonal analyses were normal. The karyotypes were detected as 46,Y,t(X;8)(q26;q22), 46,Y,t(X;1)(q26;q23), 46,Y,t(X;3)(q26;p24), respectively.

Conclusions

Our study provides insights into individuals with X chromosome translocations. The clinical phenotypes are variable and unpredictable due to differences in breakpoints and X chromosome inactivation (XCI) patterns. Our results suggest that physicians should focus on the characteristics of the X chromosome translocations and provide personalized clinical evaluations in genetic counselling.
ENGEP: advancing spatial transcriptomics with accurate unmeasured gene expression prediction
Authors: Yang Shi-Tong , Zhang Xiao-Fei
Published: December 2023

Imaging-based spatial transcriptomics techniques provide valuable spatial and gene expression information at single-cell resolution. However, their current capability is restricted to profiling a limited number of genes per sample, resulting in most of the transcriptome remaining unmeasured. To overcome this challenge, we develop ENGEP, an ensemble learning-based tool that predicts unmeasured gene expression in spatial transcriptomics data by using multiple single-cell RNA sequencing datasets as references. ENGEP outperforms current state-of-the-art tools and brings biological insight by accurately predicting unmeasured genes. ENGEP has exceptional efficiency in terms of runtime and memory usage, making it scalable for analyzing large datasets.