bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary care professionals’ perspectives on tailoring buprenorphine training for rural practice
Authors: Fenstemaker Cheyenne , Abrams Elizabeth A. , Obringer Benjamin , King Katherine , Dhanani Lindsay Y. , Franz Berkeley
Published: March 2024

Purpose

Buprenorphine is a highly effective medication for opioid use disorder (OUD) that remains substantially underutilized by primary care professionals (PCPs). This is particularly true in rural communities, which have fewer prescribers and significant access disparities. The Drug Enforcement Administration removed the X‐waiver requirement in December 2022, yet many rural clinicians still report barriers to prescribing buprenorphine. In this study, we examined rural PCPs’ experiences with buprenorphine to identify tailored training strategies for rural practice.

Methods

Physicians, nurse practitioners, and physician associates practicing in rural Ohio counties were recruited through contacts at statewide health associations and health professions training programs. Twenty‐three PCPs were interviewed about their perspectives on prescribing buprenorphine, including their training history.

Findings

PCPs self‐reported being motivated to respond to OUD. However, they also reported that current training efforts failed to equip them with the knowledge and resources needed to prescribe effectively, and that urban‐focused training often alienated rural clinicians. Participants suggested tailoring training content to rural settings, using rural trainers, and bolstering confidence in navigating rural‐specific barriers, such as resource deficits and acute opioid fatigue.

Conclusion

Our study found that current training on buprenorphine prescribing is inadequate for meeting the needs of rural PCPs. Tailored buprenorphine training is needed to improve accessibility and acceptability, and to better support the clinical workforce in communities disproportionately impacted by the opioid epidemic.
Personalising circadian hygiene educational initiatives aimed at university students—“He who has ears to hear, let him hear”
Authors: Giusti Gianluca , Domenie Esther D. , Zarantonello Lisa , Mangini Chiara , Ferrari Paolo , Costa Rodolfo , Montagnese Sara
Published: March 2024

The aim of the present study was to characterise “early drop‐outs” (n = 3185) out of a group of university students (n = 7766) engaged in an ongoing circadian education initiative, to evaluate its efficacy and direct its developments. The initiative is aimed at improving sleep timing/quality through one of two sets of circadian hygiene advice covering the timing of sleep, meals, exercise and light exposure, and it has already been shown to have a positive effect on sleep timing. This second, interim analysis confirmed the high prevalence of disturbed night sleep and social jetlag amongst students at Padova University. Three‐thousand, one‐hundred and eighty‐five (41.0%) students were early drop‐outs. These were more commonly males (46.4 versus 37.6%; χ2 = 58, p < 0.0001), had later sleep–wake habits, more daytime sleepiness and worse night sleep quality. Chronotype distribution was also different, with a slight but significantly higher proportion of extremely evening/evening types amongst early drop‐outs (χ2 = 10, p < 0.05). These results suggest that the more evening the student, the lower their likelihood of choosing/being able to follow circadian advice.
A multidisciplinary approach to identifying and managing heterotopic gastric inlet patches
Authors: Ayres L. , Perring S. , Nouraei S. A. R.
Published: March 2024

Introduction

Gastric inlet patches are often incidental, but can also be a treatable cause of laryngo‐esophageal symptoms.

Methods

We retrospectively reviewed all patients whose gastric inlet patches were diagnosed following assessment for laryngopharyngeal and swallowing symptoms. Improvement following Argon Plasma Coagulation (APC) was assessed using Minimum Clinically‐Important Difference methodology combining voice, throat, and swallowing domains. Correlations between APC response and measures of reflux and mucosal barrier integrity, measured during 24‐h pH‐impedance manometry, were obtained. Proximal and Distal Mean Nocturnal Baseline Impedance (MNBI) values were separately calculated and the novel variable of Mucosal Impedance Gradient was derived as [((Distal MNBI‐Proximal MNBI)/((Distal MNBI + Proximal MMBI)/2)) x 100].

Key Results

Inlet patches were detected in 57 of 651 patients who had Transnasal Panendoscopy (8.7 ± 2.2%). There were 34 males. Mean age was 58 years. Mean duration of symptoms was 2 years. The commonest symptoms were hoarseness (n = 33), throat symptoms (n = 24), and dysphagia (n = 21), respectively. APC was used to ablate patches in 34 patients. Treatment response was 71% at a mean followup of 5.5 months. MIG > − 25% predicted response to APC, with area under the receiver operating characteristic curve of 0.875 (Sensitivity = 81%; Specificity = 100%; p < 0.0001).

Conclusions

Gastric inlet patches are common and under‐recognized. They can cause protracted pharyngo‐esophageal symptoms. Patch ablation is an effective treatment for carefully selected patients. Optimal patient selection requires multidisciplinary teamwork. Mucosal Impedance Gradient could further refine patient selection.
Anxiety symptoms without depression are associated with cognitive control network (CNN) dysfunction: An fNIRS study
Authors: Zhao Qinqin , Wang Zheng , Yang Caihong , Chen Han , Zhang Yan , Zeb Irum , Wang Pu , Wu Huifen , Xiao Qiang , Xu Fang , Bian Yueran , Xiang Nian , Qiu Min
Published: March 2024

Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects—139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53‐channel guided near‐infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy‐Hb). Correlation analysis between anxiety severity and oxy‐Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy‐Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy‐Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy‐Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.
The need for nonuniform risk acceptability across climate change scenarios
Authors: Nasr Amro , Ivanov Oskar Larsson , Björnsson Ivar , Johansson Jonas
Published: March 2024

Climate change risk assessment studies focus on identifying and analyzing different risks considering several climate change scenarios and on evaluating the cost‐effectiveness of different adaptation measures. However, risk acceptability is often not reflected on in the context of climate change risk studies. Noting that the different climate change scenarios depict drastically contrasting images of the future in terms of population growth, economic development, and changes to life expectancy, this article uses risk acceptance criteria that are based on socioeconomic considerations to highlight the need for nonuniform risk acceptability across climate change scenarios. For this purpose, the optimum implied cost of averting a fatality derived based on the life quality index concept and the value of a quality‐adjusted life year derived based on the time principle of acceptable life risk are assessed in three different climate change scenarios for Sweden. Additionally, an illustrative example that assesses the acceptable probability of failure of a steel rod under axial tension in the different climate change scenarios is presented. It is shown that risk acceptance criteria can vary considerably across the different climate change scenarios (e.g., more than 190% variation in the acceptable probability of failure for Sweden in the considered example). This article demonstrates that the ability of societies to afford risk‐reducing measures may vary considerably across the different climate change scenarios. Hence, it can be concluded that (1) in the context of climate change risk assessments, risk acceptance criteria need to be developed to account for the different climate change scenarios, and (2) these criteria may vary considerably across the different climate change scenarios. Finally, relevant challenges and research needs are also provided.
The three I's of downward income mobility: A directional subgroup decomposable measure
Authors: Bárcena‐Martín Elena , Cantó Olga
Published: March 2024

The Foster‐Greer‐Thorbecke class of indices and the TIP curve have become classical tools to measure poverty. In this paper we adapt these indices and curve to the income mobility literature and measure downward income mobility considering its three dimensions of incidence, intensity, and inequality. This strategy allows us to incorporate reference dependence, loss aversion and diminishing sensitivity, features emphasized as welfare determinants in Prospect Theory. We propose the use of a class of measures and a Three I's of Downward Mobility curve as a useful graphical device in the income growth framework. Based on this curve we can evaluate the degree of regressivity (or progressivity) of income losses. We provide an empirical illustration for Spain in two recent recession periods. Results show that even if for most households the pandemic shock was not as severe as the Great Recession, some sociodemographic groups had a more similar downward mobility experience in both crises.
Diagenetic dolomite in planktonic foraminifera on the Australian Northwest Shelf
Authors: Zhao Song , Grant Katharine M. , Opdyke Bradley N. , Troitzsch Ulrike , Williams Ian S.
Published: March 2024

Planktonic foraminiferal shells are widely used to investigate past oceanographic and climatic variations via their trace elements and stable isotopes. However, these geochemical methods may be compromised by the presence of diagenetic high‐Mg calcite. In this study, dolomite crystals are observed in planktonic foraminifera from International Ocean Discovery Program Site U1464 sediments on the Australian Northwest shelf, a shallow marine environment (<300 m). This study investigates the formation of the dolomite using new scanning electron microscopy, X‐ray diffraction, stable isotope (carbon and oxygen), Mg/Ca and rare earth element data, combined with shipboard geochemistry and available literature. This study finds that foraminiferal dolomite formation was probably associated with early diagenesis, microbial and ageing processes. Two potential diagenetic processes (seafloor diagenesis and post‐depositional diagenesis) are proposed, and both indicate that the favourable redox condition of dolomite formation is low oxygen, which may activate methanogenic catalysis to facilitate dolomite formation. It is postulated that high‐Mg calcite may be the precursor of foraminiferal dolomite in this case, and that dissolution–precipitation may be the ageing process of dolomite formation. In contrast to deeper, more normal pelagic environments, this study shows that the marine environment can facilitate dolomite precipitation by higher fluxes of organic matter to the seafloor.
Just pair‐merge
Authors: Safir Ken
Published: March 2024

Two structure‐building operations are currently posited in minimalist theory: an operation forming sets (set merge), and an operation forming ordered pairs (pair‐merge). I argue that pair‐merge is sufficient to generate syntactic relations, so set merge, also called simple merge, should be eliminated from syntactic theory on grounds of simplicity. This conclusion requires reevaluating the relationship between structure‐building and labeling of constituents for the expression of syntactic relations, because labeling plays a crucial role in this comparison of theories according to the simplicity metric. An existing labeling hypothesis, specifically Chomsky's Labeling Algorithm, is shown not to have any advantage claimed for it by comparison with the just pair‐merge hypothesis proposed here. An advantage of the only pair‐merge hypothesis is that it provides a more principled origin for the inherent asymmetry in the c‐command relation that does not follow from a theory that includes set merge.
Blood meal analysis reveals sources of tick‐borne pathogens and differences in host utilization of juvenile Ixodes ricinus across urban and sylvatic habitats
Authors: Sormunen Jani Jukka , Mänttäri Jesse , Vesterinen Eero Juhani , Klemola Tero
Published: March 2024

Aims

Urban green spaces are locations of maximal human activity, forming areas of enhanced risk for tick‐borne disease (TBD) transmission. Being also limited in spatial scale, green spaces form prime targets for control schemes aiming to reduce TBD risk. However, for effective control, the key species maintaining local tick and tick‐borne pathogen (TBP) populations must be identified. To determine how patterns of host utilization vary spatially, we utilized blood meal analysis to study the contributions of voles, shrews, squirrels, leporids and cervids towards blood meals and the acquisition of TBPs of juvenile Ixodes ricinus in urban and sylvatic areas in Finland.

Methods and Results

A total of 1084 nymphs were collected from the capital city of Finland, Helsinki and from a sylvatic island in southwestern Finland, and subjected to qPCR analysis to identify DNA remnants of the previous host. We found significant differences in host contributions between urban and sylvatic environments. Specifically, squirrels and leporids were more common hosts in urban habitats, whereas cervids and voles were more common in sylvatic habitats. In addition to providing 18.4% of larval blood meals in urban habitats, red squirrels were identified as the source of 28.6% (n = 48) of Borrelia afzelii detections and 58.1% (n = 18) of Borrelia burgdorferi sensu stricto detections, indicating an important role for local enzootic cycles.

Conclusions

Our study highlights that the key hosts maintaining tick and TBP populations may be different in urban and sylvatic habitats. Likewise, hosts generally perceived as important for upkeep may have limited importance in urban environments. Consequently, targeting control schemes based on off‐site data of host importance may lead to suboptimal results.
Lanthanide transport in angstrom-scale MoS
2
-based two-dimensional channels
Authors: Wang Mingzhan , Xiong Qinsi , Wang Maoyu , Lewis Nicholas H. C. , Ying Dongchen , Yan Gangbin , Hoenig Eli , Han Yu , Lee One-Sun , Peng Guiming , Zhou Hua , Schatz George C. , Liu Chong
Published: March 2024

Rare earth elements (REEs), critical to modern industry, are difficult to separate and purify, given their similar physicochemical properties originating from the lanthanide contraction. Here, we systematically study the transport of lanthanide ions (Ln
3+
) in artificially confined angstrom-scale two-dimensional channels using MoS
2
-based building blocks in an aqueous environment. The results show that the uptake and permeability of Ln
3+
assume a well-defined volcano shape peaked at Sm
3+
. This transport behavior is rooted from the tradeoff between the barrier for dehydration and the strength of interactions of lanthanide ions in the confinement channels, reminiscent of the Sabatier principle. Molecular dynamics simulations reveal that Sm
3+
, with moderate hydration free energy and intermediate affinity for channel interaction, exhibit the smallest dehydration degree, consequently resulting in the highest permeability. Our work not only highlights the distinct mass transport properties under extreme confinement but also demonstrates the potential of dialing confinement dimension and chemistry for greener REEs separation.
Coactivator condensation drives cardiovascular cell lineage specification
Authors: Gan Peiheng , Eppert Mikayla , De La Cruz Nancy , Lyons Heankel , Shah Akansha M. , Veettil Reshma T. , Chen Kenian , Pradhan Prashant , Bezprozvannaya Svetlana , Xu Lin , Liu Ning , Olson Eric N. , Sabari Benjamin R.
Published: March 2024

During development, cells make switch-like decisions to activate new gene programs specifying cell lineage. The mechanisms underlying these decisive choices remain unclear. Here, we show that the cardiovascular transcriptional coactivator myocardin (MYOCD) activates cell identity genes by concentration-dependent and switch-like formation of transcriptional condensates. MYOCD forms such condensates and activates cell identity genes at critical concentration thresholds achieved during smooth muscle cell and cardiomyocyte differentiation. The carboxyl-terminal disordered region of MYOCD is necessary and sufficient for condensate formation. Disrupting this region’s ability to form condensates disrupts gene activation and smooth muscle cell reprogramming. Rescuing condensate formation by replacing this region with disordered regions from functionally unrelated proteins rescues gene activation and smooth muscle cell reprogramming. Our findings demonstrate that MYOCD condensate formation is required for gene activation during cardiovascular differentiation. We propose that the formation of transcriptional condensates at critical concentrations of cell type–specific regulators provides a molecular switch underlying the activation of key cell identity genes during development.
Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis
Authors: von Mässenhausen Anne , Schlecht Marlena Nastassja , Beer Kristina , Maremonti Francesca , Tonnus Wulf , Belavgeni Alexia , Gavali Shubhangi , Flade Karolin , Riley Joel S. , Zamora Gonzalez Nadia , Brucker Anne , Becker Jorunn Naila , Tmava Mirela , Meyer Claudia , Peitzsch Mirko , Hugo Christian , Gembardt Florian , Angeli Jose Pedro Friedmann , Bornstein Stefan R. , Tait Stephen W. G. , Linkermann Andreas
Published: March 2024

Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed. In contrast, MAVS mediated a noncanonical signal resulting in a prominent increase in mitochondrial ROS levels, and increase in the BACH1/pNRF2 transcription factor ratio and GPX4 up-regulation, which was associated with a 50% decrease in intracellular glutathione levels. We conclude that siRNAs commonly sensitize to ferroptosis and may severely compromise the conclusions drawn from silencing approaches in biomedical research. Finally, as ferroptosis contributes to a variety of pathophysiological processes, we cannot exclude side effects in human siRNA-based therapeutical concepts that should be clinically tested.
Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3
Authors: Li Jinze , Zhao Ding , Zhang Tao , Xiong Haoyang , Hu Mingyang , Liu Hongmei , Zhao Feiyu , Sun Xiaodi , Fan Peng , Qian Yuqiang , Wang Di , Lai Liangxue , Sui Tingting , Li Zhanjun
Published: March 2024

Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the
Sry
gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively. In conclusion, dCas9-controlled CRISPR/Cas3-mediated precise large-fragment deletion provides an approach for establishing animal models by chromosome elimination. This method also holds promise as a potential therapeutic strategy for treating fragment mutations or human aneuploidy diseases that involve additional chromosomes.
Gut bacteria–derived serotonin promotes immune tolerance in early life
Authors: Sanidad Katherine Z. , Rager Stephanie L. , Carrow Hannah C. , Ananthanarayanan Aparna , Callaghan Ryann , Hart Lucy R. , Li Tingting , Ravisankar Purnima , Brown Julia A. , Amir Mohammed , Jin Jenny C. , Savage Alexandria Rose , Luo Ryan , Rowdo Florencia Mardorsky , Martin M. Laura , Silver Randi B. , Guo Chun-Jun , Krumsiek Jan , Inohara Naohiro , Zeng Melody Y.
Published: March 2024

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell–mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Interesting case of regional left ventricular hypertrophy
Authors: Elsaid Ahmad , Egdell Robin , Singh Vikram , Russell Stuart
Published: March 2024

This is an account of an interesting case with an unusual cardiac presentation. He is a man in his 60s who presented with chest tightness to the accident and emergency unit. The initial thoughts were of acute coronary syndrome or acute aortic syndrome. The initial set of investigations was non-conclusive. His echocardiogram which was done during hospital admission showed asymmetric hypertrophy of the heart muscle. It was prudent to assess that new finding with an MRI scan. The patient presented to the hospital twice during the investigation and was treated for a lower respiratory tract infection. The MRI report showed an interventricular mass lesion extending to the right ventricular free wall with angiosarcoma being high up in the differential diagnosis. Going through the heart team discussion, the decision was to go for a transcatheter biopsy. The biopsy showed B-cell lymphoma. The treatment started and interestingly with satisfactory results.
Congenital brain tumour in a neonate: a therapeutic challenge
Authors: Mude Praneetha , Pradhan Monalisa , Tiwari Anuj , Parida Tapas Kanti , Nayak Manoj Kumar , Sekar Arun Kumar , Purkait Suvendu , Devi Usha
Published: March 2024

A term neonate with history of ventriculomegaly in the fetal period was diagnosed with a central nervous system tumour after radiological investigations. It was confirmed as an immature teratoma after histopathological examination. He underwent left frontal craniotomy with tumour excision. Intraoperatively, massive haemorrhage (venous bleed) occurred due to the high vascularity of the tumour and led to haemodynamic instability. A massive transfusion protocol was initiated. Despite multiple transfusions and shock management, he succumbed at 2 weeks of life. This case report highlights the importance of antenatal diagnosis and fetal MRI in prognostication and also the possible role of neoadjuvant chemotherapy in reducing tumour vascularity and, hence, bleeding.
Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study
Authors: Pignon Baptiste , Matta Joane , Wiernik Emmanuel , Toussaint Anne , Loewe Bernd , Robineau Olivier , Carrat Fabrice , Severi Gianluca , Touvier Mathilde , Gouraud Clement , Ouazana Vedrines Charles , Pitron Victor , Ranque Brigitte , Hoertel Nicolas , Kab Sofiane , Goldberg Marcel , Zins Marie , Lemogne Cédric
Published: March 2024

Background

Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions.

Objective

This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6–10 months later.

Methods

A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome.

Findings

At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up.

Conclusions

The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline.

Clinical implications

Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.
Deep learning model to predict lupus nephritis renal flare based on dynamic multivariable time-series data
Authors: Huang Siwan , Chen Yinghua , Song Yanan , Wu Kaiyuan , Chen Tiange , Zhang Yuan , Jia Wenxiao , Zhang Hai-Tao , Liang Dan-Dan , Yang Jing , Zeng Cai-Hong , Li Xiang , Liu Zhi-Hong
Published: March 2024

Objectives

To develop an interpretable deep learning model of lupus nephritis (LN) relapse prediction based on dynamic multivariable time-series data.

Design

A single-centre, retrospective cohort study in China.

Setting

A Chinese central tertiary hospital.

Participants

The cohort study consisted of 1694 LN patients who had been registered in the Nanjing Glomerulonephritis Registry at the National Clinical Research Center of Kidney Diseases, Jinling Hospital from January 1985 to December 2010.

Methods

We developed a deep learning algorithm to predict LN relapse that consists of 59 features, including demographic, clinical, immunological, pathological and therapeutic characteristics that were collected for baseline analysis. A total of 32 227 data points were collected by the sliding window method and randomly divided into training (80%), validation (10%) and testing sets (10%). We developed a deep learning algorithm-based interpretable multivariable long short-term memory model for LN relapse risk prediction considering censored time-series data based on a cohort of 1694 LN patients. A mixture attention mechanism was deployed to capture variable interactions at different time points for estimating the temporal importance of the variables. Model performance was assessed according to C-index (concordance index).

Results

The median follow-up time since remission was 4.1 (IQR, 1.7–6.7) years. The interpretable deep learning model based on dynamic multivariable time-series data achieved the best performance, with a C-index of 0.897, among models using only variables at the point of remission or time-variant variables. The importance of urinary protein, serum albumin and serum C3 showed time dependency in the model, that is, their contributions to the risk prediction increased over time.

Conclusions

Deep learning algorithms can effectively learn through time-series data to develop a predictive model for LN relapse. The model provides accurate predictions of LN relapse for different renal disease stages, which could be used in clinical practice to guide physicians on the management of LN patients.
Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China
Authors: Huang Li , Zou Jun , Zhang Yuxin , Gu Jiaowei , Wu Jianlong , Zhang Che
Published: March 2024

Introduction

Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS.

Methods and analysis

We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient’s efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples.

Ethics and dissemination

The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/).

Trial registration number

ISRCTN62094626.
Early predictors of bacterial pneumonia infection in children with congenital heart disease after cardiopulmonary bypass: a single-centre retrospective study
Authors: Wang Qingfeng , Liu Hui , Zou Liang , Cun Yueshuang , Shu Yaqin , Patel Nishant , Yu Di , Mo Xuming
Published: March 2024

Objectives

The objective of this study was to evaluate the early predictors of bacterial pneumonia infection in children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB).

Design

Retrospective study.

Setting

A freestanding tertiary paediatric hospital in China.

Participants

Patients admitted to the hospital due to CHD who underwent open-heart surgery.

Outcome measures

We retrospectively reviewed and analysed data from 1622 patients with CHD after CPB from June 2018 to December 2020 at the Children’s Hospital of Nanjing Medical University. Enrolled patients were assigned to an infection group or a non-infection group according to the presence of postoperative bacterial pneumonia infection, and the differences in clinical indicators were compared. Potential predictors were analysed by multivariate logistic regression analysis and area under the curve (AUC) analysis.

Results

Among the 376 patients (23.2%) in the infection group, the three most common bacteria wereStreptococcus pneumoniaein 67 patients (17.8%),Escherichia coliin 63 patients (16.8%) andHaemophilus influenzaein 53 patients (14.1%). The infection group exhibited a lower weight (8.0 (6.0–11.5) kg vs 11.0 (7.5–14.5) kg, p<0.001). In the infection group, procalcitonin (PCT) (ng/mL: 4.72 (1.38–9.52) vs 1.28 (0.47–3.74), p<0.001) and C reactive protein (CRP) (mg/L: 21.0 (12.1–32.0) vs 17.0 (10.0–27.0), p<0.001) levels were significantly greater than those in the non-infection group. Binary logistic regression analysis revealed that weight, PCT and CRP were independent risk factors for pulmonary bacterial infection after CPB. The AUCs of weight, PCT, CRP and PCT+CRP for predicting pulmonary bacterial infection after CPB were 0.632 (95% CI 0.600 to 0.664), 0.697 (95% CI 0.667 to 0.727), 0.586 (95% CI 0.554 to 0.618) and 0.694 (95% CI 0.664 to 0.724), respectively, and the cut-off values were ≤10.25 kg, ≥4.25 ng/mL, ≥6.50 mg/L and ≥0.20, respectively. The sensitivities were 69.7%, 54.0%, 93.9% and 70.2%, and the specificities were 53.5%, 77.7%, 19.4% and 59.1%, respectively.

Conclusions

In our study, weight, PCT and CRP were found to be independent predictors of pulmonary bacterial infection after CPB. Moreover, PCT was the most specific predictor, and CRP was the most sensitive independent predictor that might be beneficial for the early diagnosis of pulmonary bacterial infection after CPB in patients with CHD.
How to facilitate NHS professionals to recognise and use skills gained from global health engagement when back in the UK workforce? A participatory action research project to design, pilot and evaluate a series of online leadership workshops
Authors: Spowart Lucy , Inman Alice C , Hardy Louise J , Dillon Michael J
Published: March 2024

Objectives

Leadership knowledge and skills are known to be developed by health professionals during global health experiences overseas. However, volunteers struggle to recognise and use these new skills on return to their workplace. A series of bespoke leadership workshops were designed, delivered and evaluated by leadership experts to help enhance the transferability of leadership skills back to the UK National Health Service.

Design

A mixed-methods participatory action research methodology was employed to explore the impact of the workshops. This approach lends itself to a complex, situated project involving multiple partners. Quantitative and qualitative descriptive data were collected via online survey (n=29 participants) and focus groups (n=18 focus groups) and thematically analysed.

Setting

The authors delivered the tailored leadership workshops online to globally engaged National Health Service (NHS) healthcare professionals based in England who had all worked overseas within the past 5 years.

Participants

29 participants attended: 11 medical doctors; 6 nurses/midwives; 10 allied health professionals; 1 NHS manager and 1 student nurse (who was also working as a healthcare assistant).

Results

Participants were able to network both during the large group discussions and while in smaller breakout groups. Data highlighted the substantial benefits obtained from this networking, with 91% of participants reporting it enriched their learning experience, particularly within a multi-disciplinary context, and by having the time and space for facilitated reflection on leadership. Furthermore, 78% agreed that they learned new skills for influencing changebeyondtheir position and 76% reported they could maximise the impact of this change for themselvesandtheir employer. Participants also reported the development of systems and ethical leadership knowledge that they felt they could transfer to their NHS roles.

Conclusions

This study extends explorations of global health experiences by moving beyond the skills gained while working in low-income and middle-income countries. The innovative online leadership workshops gave agency to individuals to recognise and use the skills gained from global health placements on return to the NHS.
Can ChatGPT pass the MRCP (UK) written examinations? Analysis of performance and errors using a clinical decision-reasoning framework
Authors: Maitland Amy , Fowkes Ross , Maitland Stuart
Published: March 2024

Objective

Large language models (LLMs) such as ChatGPT are being developed for use in research, medical education and clinical decision systems. However, as their usage increases, LLMs face ongoing regulatory concerns. This study aims to analyse ChatGPT’s performance on a postgraduate examination to identify areas of strength and weakness, which may provide further insight into their role in healthcare.

Design

We evaluated the performance of ChatGPT 4 (24 May 2023 version) on official MRCP (Membership of the Royal College of Physicians) parts 1 and 2 written examination practice questions. Statistical analysis was performed using Python. Spearman rank correlation assessed the relationship between the probability of correctly answering a question and two variables: question difficulty and question length. Incorrectly answered questions were analysed further using a clinical reasoning framework to assess the errors made.

Setting

Online using ChatGPT web interface.

Primary and secondary outcome measures

Primary outcome was the score (percentage questions correct) in the MRCP postgraduate written examinations. Secondary outcomes were qualitative categorisation of errors using a clinical decision-making framework.

Results

ChatGPT achieved accuracy rates of 86.3% (part 1) and 70.3% (part 2). Weak but significant correlations were found between ChatGPT’s accuracy and both just-passing rates in part 2 (r=0.34, p=0.0001) and question length in part 1 (r=−0.19, p=0.008). Eight types of error were identified, with the most frequent being factual errors, context errors and omission errors.

Conclusion

ChatGPT performance greatly exceeded the passing mark for both exams. Multiple choice examinations provide a benchmark for LLM performance which is comparable to human demonstrations of knowledge, while also highlighting the errors LLMs make. Understanding the reasons behind ChatGPT’s errors allows us to develop strategies to prevent them in medical devices that incorporate LLM technology.
Do smoking abstinence periods among pregnant smokers improve birth weight? A secondary analysis of a randomised, controlled trial
Authors: Berlin Ivan , Goldzahl Leontine , Jusot Florence , Berlin Noemi
Published: March 2024

Objectives

Maternal smoking during pregnancy is associated with low birth weight (LBW). Reduction of cigarette consumption does not seem to improve birth weight but it is not known whether implementation of periods of smoking abstinence improves it. We assessed whether the number of 7-day periods of smoking abstinence during pregnancy may help reduce the number of newborns with LBW.

Design and setting

Secondary analysis of a randomised, controlled, multicentre, smoking cessation trial among pregnant smokers.

Participants

Pregnant women were included at <18 weeks of gestational age and assessed at face-to-face, monthly visits. Data of 407 singleton live births were analysed.

Primary outcome measure

Newborns with low birth weight.

Results

40 and 367 newborns were born with and without LBW, respectively. Adjusted for all available confounders, 3 or more periods of at least 7 days’ smoking abstinence during pregnancy was associated with reduced likelihood of LBW compared with no abstinence periods (OR = 0.124, 95% CI 0.03 to 0.53, p = 0.005). Reduction of smoking intensity by at least 50% was not associated with birth weight.

Conclusion

Aiming for several periods of smoking abstinence among pregnant smokers unable to remain continuously abstinent from smoking may be a better strategy to improve birth weight than reducing cigarette consumption.

Trial registration number

ClinicalTrials.govNCT02606227.
Exploration of Latina/Hispanic women’s experiences living with non-alcoholic fatty liver disease: a qualitative study with patients in Houston
Authors: Heredia Natalia I , Mendoza Duque Erika , Ayieko Sylvia , Averyt Amelia , McNeill Lorna H , Hwang Jessica P , Fernandez Maria E
Published: March 2024

Objectives

A deeper understanding of the lived experiences of Hispanic patients with non-alcoholic fatty liver disease (NAFLD) can help guide the development of behavioural programmes that facilitate NAFLD management. This paper explores Hispanic women’s experiences living with NAFLD.

Design, setting, participants

We collected brief sociodemographic questionnaires and conducted in-depth interviews with 12 low-income (all had household income ≤USD$55 000 per year) Hispanic women with NAFLD from the Houston area. Transcripts were audio-recorded and transcribed. We developed a coding scheme and used thematic analysis to identify emergent themes, supported by Atlas.ti.

Results

Participants identified physicians as their main information source on NAFLD but also consulted the internet, family, friends and peers. Many were still left wanting more information. Participants identified family history, sedentary lifestyles, poor diet and comorbid conditions as causes for their NAFLD. Participants also reported emotional distress after diagnosis. Participants experienced both successes and challenges in making lifestyle changes in nutrition and physical activity. Some participants received desired social support in managing NAFLD, although there were conflicting feelings about spousal support.

Conclusion

Multifaceted programming that improves patient–provider communication, conveys accurate information and enhances social support is needed to support Hispanic women in managing NAFLD.
Role of oesophageal balloon cryoablation in combination with personalised immunotherapy to achieve luminal control in metastatic oesophageal cancer: a case report
Authors: Norton Benjamin Charles , Papaefthymiou Apostolis , Telese Andrea , Duku Margaret , Chaudhry Imran , Murino Alberto , Johnson Gavin , Murray Charles , Haidry Rehan
Published: March 2024

Metastatic oesophageal adenocarcinoma (OAC) is associated with a poor prognosis, but patients with a good performance status may be offered palliative oncological intervention. Oesophageal cryoablation is an emerging therapy for the palliation of malignant dysphagia that can be given over multiple sessions with relatively few side effects. Emerging evidence suggests that cryoablation may provide a synergistic effect with modern immunotherapies as cryonecrosis leads to the release of many tumour-specific autoantigens that induce a systemic antitumour response. We present the case of a 39-year-old man who presented with several months of non-specific upper abdominal pain and heartburn. He was subsequently diagnosed with metastatic OAC and proceeded to self-funded genomic tumour profiling. This enabled initiation of a personalised oncological treatment plan involving immunotherapy and a neoantigen cancer vaccination regimen. To facilitate continued oral intake and avoid the risk of endoscopic stenting, the patient underwent a concurrent programme of oesophageal balloon cryoablation over eight sessions. At 15 months following his diagnosis, he had complete histological remission of luminal disease and a preserved systemic treatment response. In summary, oesophageal cryoablation is an endoscopic option for luminal control among patients undergoing immunotherapy for metastatic OAC. This would provide a synergistic treatment effect and mitigate against the risk of endoscopic stenting.
Implications of conscious AI in primary healthcare
Authors: Ranjbari Dorsai , Abbasgholizadeh Rahimi Samira
Published: March 2024

The conversation about consciousness of artificial intelligence (AI) is an ongoing topic since 1950s. Despite the numerous applications of AI identified in healthcare and primary healthcare, little is known about how a conscious AI would reshape its use in this domain. While there is a wide range of ideas as to whether AI can or cannot possess consciousness, a prevailing theme in all arguments is uncertainty. Given this uncertainty and the high stakes associated with the use of AI in primary healthcare, it is imperative to be prepared for all scenarios including conscious AI systems being used for medical diagnosis, shared decision-making and resource management in the future. This commentary serves as an overview of some of the pertinent evidence supporting the use of AI in primary healthcare and proposes ideas as to how consciousnesses of AI can support or further complicate these applications. Given the scarcity of evidence on the association between consciousness of AI and its current state of use in primary healthcare, our commentary identifies some directions for future research in this area including assessing patients’, healthcare workers’ and policy-makers’ attitudes towards consciousness of AI systems in primary healthcare settings.
Relationship between in-stent restenosis following carotid artery stenting and platelet reactivity to clopidogrel
Authors: Kwon Min-Yong , Lee Sang Hyo , Lee Yongjae , Kim Young Deok , Lee Si Un , Bang Jae Seung , Kwon O-Ki , Oh Chang Wan , Ban Seung Pil
Published: March 2024

Objective

To analyze the relationship between in-stent restenosis (ISR) following carotid artery stenting (CAS) and platelet clopidogrel reactivity confirmed by the P2Y12 reaction unit (PRU) and inhibition rate (IR).

Methods

We retrospectively analyzed 171 patients who underwent CAS with extracranial carotid stenosis from January 2016 to December 2019. Dual antiplatelet therapy with 100 mg aspirin and 75 mg clopidogrel was started ≥5 days before CAS. Clopidogrel resistance was measured with the PRU and IR the day before CAS. The ISR degree was classified into R1, R2, and R3 (moderate to severe luminal stenosis of ≥50% or occlusion) by carotid CT angiography after 24–30 months. The degree of quantitative association between platelet reactivity and ISR R3 was determined by the receiver operating characteristic curve method. The optimal cut-off values of PRU and IR were derived using the maximum Youden index.

Results

There were 33 R3 degrees of ISR (19.3%) and nine ipsilateral ischemic strokes (5.3%). The PRU and IR were different between R1+R2 degrees (176.4±50.1, 27.5±18.7%) and R3 degree (247.5±55.0, 10.3±13.4%) (P<0.001). The areas under the curves of PRU and IR were 0.841 and 0.781, and the optimal cut-off values were 220.0 and 14.5%, respectively. Multivariate logistic regression analysis showed that PRU ≥220 and IR ≤14.5% were significant predictive factors for ISR R3 (P<0.001 and P=0.017, respectively). ISR R3 was independently associated with ipsilateral ischemic stroke after CAS (P=0.012).

Conclusions

High PRU (≥220) and low IR (≤14.5%) are related to ISR R3 following CAS, which may cause ipsilateral ischemic stroke.