bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of coronary computed tomography angiography stenosis score for coronary stenosis
Authors: Xiong Qing-feng , Fu Xiao-rong , Ku Lei-zhi , Zhou Di , Guo Sheng-peng , Zhang Wen-sheng
Published: February 2024

Background

Coronary computed tomography angiography stenosis score (CCTA-SS) is a proposed diagnosis score that considers the plaque characteristics, myocardial function, and the diameter reduction rate of the lesions. This study aimed to evaluate the diagnostic performance of the CCTA-SS in seeking coronary artery disease (CAD).

Methods

The 228 patients with suspected CAD who underwent CCTA and invasive coronary angiography (ICA) procedures were under examination. The diagnostic performance was evaluated with the receiver operating curve (ROC) for CCTA-SS in detecting CAD (defined as a diameter reduction of ≥ 50%) and severe CAD (defined as a diameter reduction of ≥ 70%).

Results

The area under ROC (AUC) of CCTA-SS was 0.909 (95% CI: 0.864–0.943), which was significantly higher than that of CCTA (AUC: 0.826; 95% CI: 0.771–0.873; P = 0.0352) in diagnosing of CAD with a threshold of 50%. The optimal cutoff point of CCTA-SS was 51% with a sensitivity of 90.66%, specificity of 95.65%, positive predictive value of 98.80%, negative predictive value of 72.13%, and accuracy of 91.67%, whereas the optimal cutoff point of CCTA was 55%, and the corresponding values were 87.36%, 93.48%, 98.15%, 65.15%, and 88.60%, respectively. With a threshold of 70%, the performance of CCTA-SS with an AUC of 0.927 (95% CI: 0.885–0.957) was significantly higher than that of CCTA with an AUC of 0.521 (95% CI: 0.454–0.587) (P < 0.0001).

Conclusions

CCTA-SS significantly improved the diagnostic accuracy of coronary stenosis, including CAD and severe CAD, compared with CCTA.
Quality-of-life measures and their psychometric properties used in African chronic kidney disease populations: a systematic review using COSMIN methodology
Authors: Faye Moustapha , Manneville Florian , Faye Adama , Frimat Luc , Guillemin Francis
Published: February 2024

Background

If any benefit is to be derived from the use of the health-related quality of life (HRQoL) questionnaires in chronic kidney disease (CKD) patients, they should be validated and culturally adapted to the target population. We aimed to critically appraise the psychometric properties of HRQoL questionnaires used in African populations with CKD.

Methods

Web of Science, Embase, PubMed and PsycINFO databases were searched. Psychometric validation studies of HRQoL questionnaires reporting at least one psychometric property of the COSMIN checklist in CKD African population, published up to October 16, 2023 were included and independently assessed for methodological quality and level of measurement properties by using the COSMIN methodology.

Results

From 1163 articles, 5 full-text were included. Only the Kidney Disease Quality-of-Life questionnaire was translated and cross-culturally adapted for studies of patients with CKD. Internal consistency was of doubtful quality in 4 studies and very good in 1. Its measurement was sufficient in 1 study and insufficient in 4. Test–retest reliability was of doubtful quality in 4 studies. Its measurement was sufficient in 3 studies and insufficient in 1. Structural validity was of inadequate quality in 1 study and very good quality in 1. Its measurement was sufficient in both. Construct validity was of inadequate quality in all studies. Their measurement was insufficient in 4 studies and sufficient in 1.

Conclusions

This review highlighted that only one HRQoL questionnaire used in studies of African populations with CKD underwent a small number of cultural adaptations and psychometric validations, generally of poor methodological quality. HRQoL validation studies in African CKD populations are needed to better take advantage of the benefits in patient care, population health management, and research.
Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study
Authors: Liu Hui , Wu Dan , Chen Zhi-bin , Xiao Qian , Cheng Ji-wei , Xie Xiao-yan , Qu Dong-xiao , Tao Jie , Wang Wei-zhong , Peng Yi-feng , Li Guo-yi , Weng Ying-feng
Published: February 2024

Objectives

Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images.

Methods

We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed.

Results

After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001).

Conclusions

The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.
Experiences of breastfeeding peer counseling among women with low incomes in the US: a qualitative evaluation
Authors: Rhodes Elizabeth C. , Zahid Mahrukh , Abuwala Nafeesa , Damio Grace , LaPlant Helen Wilde , Crummett Carrianne , Surprenant Rebecca , Pérez-Escamilla Rafael
Published: February 2024

Background

Person-centered breastfeeding counseling is a key but often overlooked aspect of high-quality services. We explored women’s experiences of the Breastfeeding Heritage and Pride™ program, an evidence-based breastfeeding peer counseling program serving women with low incomes in the United States.

Methods

This study was conducted through an equitable community-clinical-academic partnership and guided by the World Health Organization (WHO) quality of care framework for maternal and newborn health, which highlights three domains of positive experiences of care: effective communication; respect and dignity; and emotional support. In-depth interviews were conducted with a purposive sample of women participating in the Breastfeeding Heritage and Pride™ program. Women were asked to describe their experiences with the program including examples of when good quality counseling was or was not provided. Each interview was conducted in English or Spanish, audio-recorded, and transcribed verbatim. Data were analyzed using reflexive thematic analysis. Once themes were generated, they were organized according to the three care experience domains in the WHO quality of care framework.

Results

Twenty-eight in-depth interviews were conducted with a racially/ethnically and socio-economically diverse sample of women. Three themes described effective communication practices of peer counselors: tailoring communication to meet women’s individual needs; offering comprehensive and honest information about infant feeding; and being timely, proactive, and responsive in all communications across the maternity care continuum. Two themes captured why women felt respected. First, peer counselors were respectful in their interactions with women; they were courteous, patient, and non-judgmental and respected women’s infant feeding decisions. Second, peer counselors showed genuine interest in the well-being of women and their families, beyond breastfeeding. The key theme related to emotional support explored ways in which peer counselors offered encouragement to women, namely by affirming women’s efforts to breastfeed and by providing reassurance that alleviated their worries about breastfeeding. These positive experiences of counseling were appreciated by women.

Conclusions

Women described having and valuing positive experiences in their interactions with peer counselors. Efforts to expand access to high-quality, person-centered breastfeeding counseling should, as part of quality assurance, include women’s feedback on their experiences of these services.
A case report of single umbilical artery combined with fetal bladder exstrophy in singleton pregnancy and related literature review
Authors: Zhan Jun , Jia Fenglin , Gao Qianqian , Xiao Xue
Published: February 2024

Background

According to prenatal ultrasonographic studies, single umbilical artery may be present alone or in association with other fetal abnormalities. So far, the exact pathogenesis of bladder exstrophy is unclear. Some scholars believe that bladder exstrophy and cloacal exstrophy should be regarded as a disease spectrum to explore their pathogenesis. If bladder exstrophy and cloacal exstrophy are regarded as the same disease spectrum, then we can speculate that the single umbilical artery should have the probability of being accompanied by bladder exstrophy at the same time.

Case presentation

For the first time, we report a rare case of fetal bladder exstrophy with single umbilical artery in single pregnancy. This patient underwent targeted color Doppler ultrasound at 26 weeks of pregnancy which first suspected bladder exstrophy with single umbilical artery and fetal MRI for diagnosis at 38 + 3 weeks of pregnancy which confirmed the suspicion. After the diagnosis was confirmed, the patient was scheduled for a multidisciplinary discussion. Ultimately the patient opted for induced fetal demise at 38 + 5 weeks of pregnancy and the physical appearance of the fetal demise affirmed previous ultrasound and MRI examination results.

Conclusions

Our report is the first finding of single umbilical artery combined with bladder exstrophy in a singleton pregnancy. Accordingly, our case enhances the evidence that cloacal exstrophy and bladder exstrophy should be treated as the same disease spectrum. In addition, we conducted a literature review on the diagnostic progress of single umbilical artery combined with bladder exstrophy, hoping to provide useful references for the diagnosis of this disease.
Adapting a complex violence prevention intervention: a case study of the Good School Toolkit in Uganda
Authors: Grundlingh Heidi , Kyegombe Nambusi , Namy Sophie , Nakuti Janet , Laruni Yvonne , Nanyunja Barbrah , Muluusi Hassan , Nakiboneka Mastula , Mukuwa Aggrey , Tanton Clare , Knight Louise , Naker Dipak , Devries Karen
Published: February 2024

Background

Adaptation is a key strategy to extend the reach of evidence-based interventions to prevent violence in new populations, but there is a dearth of practical case examples. The Good School Toolkit was developed by Ugandan NGO Raising Voices for use in primary schools (GST-P). We describe our systematic approach to adapting the GST-P for use in secondary schools in Uganda, and reflect on the utility of the process as well as limitations of existing adaptation frameworks.

Methods

We adapted the GST-P in four phases, which included: I) clarifying the logic model and core intervention components using a streamlined process; II) conducting formative research (cross-sectional survey, focus groups, etc.) to understand the new population; III) selecting and preparing new intervention components and modifying existing intervention components; and IV) pretesting new intervention components with teachers and students in Uganda.

Results

We identified core components using a logic model. Formative research showed results largely in line with our apriori hypotheses. Teacher violence remained highly prevalent in secondary versus primary schools (> 65% of secondary students reported past year exposure), while peer violence significantly increased (secondary = 52% vs. primary girls = 40%, P < 0.001; secondary = 54% vs. primary boys = 44%, P = 0.009) in secondary versus primary schools. Significantly more secondary girls (51%) than secondary boys (45%) reported past year dating/intimate partner violence (P = 0.03). Inequitable, gendered educational practices emerged as a salient theme, perceived to heighten female students’ vulnerability to violence. In light of these findings, we made several adjustments to the adapted intervention. We strengthened existing teacher and peer violence intervention components. We also developed, pretested and revised new program components to prevent dating violence and promote ‘gender fairness in schools’. Finally, original activities were modified to support engagement with school administration and promote increased student agency in secondary schools.

Conclusions

Based on our experience, it was difficult to apply mechanistic models to clarify the intervention logic of the GST-P, a complex multicomponent intervention, and simpler methods may be sufficient. Our team had high levels of contextual knowledge before the adaptation, and formative research to understand the new target population provided only limited additional insight. In similar situations, a simplified approach to mapping the core intervention components, qualitative research to understand the new target population, and pre-testing of new intervention components may be the most informative elements of systematic adaptation processes.
Magnitude of early relaparotomy and its outcome among patients who underwent laparotomy in a tertiary hospital in Eastern Ethiopia: a cross- sectional study
Authors: Amentie Eyobel , Beyene Badhaasaa , Sisay Mekonnen , Zelka Muluwas Amentie , Nigussie Shambel
Published: February 2024

Introduction

Several studies conducted worldwide revealed the magnitude of early relaparotomy and its outcome among patients undergoing laparotomy. However, there was very little evidence on the magnitude of early relaparotomy and its outcome among patients who underwent laparotomy in Ethiopia, especially in the study area.

Objective

this study aimed to the assess magnitude of early relaparotomy and its outcome among patients who underwent laparotomy in a Tertiary Hospital in Eastern Ethiopia.

Methods

A retrospective cross-sectional study was conducted. All patients who underwent laparotomy during the data retrieval period were included. Data were collected using a data abstraction checklist from patients’ medical records. The collected data were entered, cleaned, and analyzed by using SPSS version 23. Descriptives statistics were generated where by continuous variables were summarized into means and standard deviation and categorical variables were summarized as the frequency with proportions.

Result

The magnitude of relaparotomy was 6.8%. Among 82 patients included in the final analysis, 53 (64.6%) were males and the mean (± SD) age of patients was 33.32 ± 16.63 years. The major indications for relaparotomy were intra-abdominal collection (26.8%) and anastomotic leak (24.4%). Among 82 patients who underwent relaparotomy, 52(63.4%) were developed post relaparotomy complications, and 30(36.6%) patients died.

Conclusion

The magnitude of early relaparotomy was 6.8%. The magnitude of in-hospital mortality was high in comparison to earlier study findings from developing countries. About three fourth of patients who underwent relaparotomy were developed postoperative complications.
Preservation of the pulmonary branches of the vagus nerve during three-dimensional thoracoscopic radical resection of lung cancer: a retrospective study
Authors: Huang Wencong , Yang Jiantian , Chen Huiwen , Li Peijian , Wei Wei
Published: February 2024

Background

In this study, we investigated the effect of preservation of the pulmonary branches of the vagus nerve during systematic dissection of mediastinal lymph nodes, when performing radical resection of lung cancer, on the postoperative complication rate.

Methods

The clinical data for 80 patients who underwent three-dimensional thoracoscopic radical resection of lung cancer in the Department of Thoracic Surgery at Huizhou Municipal Central Hospital between 2020 and 2022 were analyzed. The patients were divided into two groups according to whether the pulmonary branches of the vagus nerve were retained during intraoperative carinal lymph node dissection. The operation time, time until first postoperative defecation, duration for which a chest tube was needed, total chest drainage volume, average pain intensity during the first 5 postoperative days, incidence of postoperative pneumonia, and postoperative length of stay were compared between the two groups.

Results

There was no statistically significant difference in histological staging or in time until first postoperative defecation between the two groups (p > 0.05). However, there were significant differences in operation time, the duration for which a chest tube was needed, total chest drainage volume, average pain intensity during the first 5 postoperative days, white blood cell count and procalcitonin level on postoperative days 1 and 5, and postoperative length of stay between the two groups (p < 0.05).

Conclusion

Preserving the pulmonary branches of the vagus nerve during carinal lymph node dissection when performing three-dimensional thoracoscopic radical resection of lung cancer can reduce the risk of postoperative complications.
Key drivers of hysterectomy among women of reproductive age in three states in India: comparative evidence from NFHS-4 and NFHS-5
Authors: Singh Shri Kant , Chauhan Kirti , Tripathi Vrijesh
Published: February 2024

Purpose

According to the 4th and 5th rounds of National Family Health Survey (NFHS), there is high prevalence of hysterectomies in the three states of Andhra Pradesh Telangana and Bihar. The three said states have more than double the number of hysterectomies taking place than the national average. Our purpose is to analyse whether these rates are increasing, decreasing or have stabilized and their reasons thereof. Such an analyses will help the policy makers in recommending good clinical practices within their states.

Material and methods

We used data from NFHS-4 (2015-16) and NFHS-5 (2019-2021) rounds. We calculated the differences in predicted probabilities for various factors, performed a Fairlie Decomposition analyses to quantify the positive and negative contributors in the prevalence of hysterectomy across the three states over two time points, and assessed the association of various socio-demographic characteristics to hysterectomy through a multilevel logistic regression model.

Results and conclusion

The results show that out of a total of 80,976 eligible respondents from the states under study, 5826 respondents self-reported that they had a hysterectomy done. It was found that older age, living in rural areas, belonging to other backward classes and higher wealth quintile, and higher parity positively contributed to the increased prevalence of hysterectomies in the three states. Higher educational attainment and previous use of family planning methods acted as protective factors. Characteristics at the household level had the highest intra-class correlation value in the prevalence of hysterectomy among women, followed by the Primary Sampling Unit and District levels, indicating high clustering in the prevalence of hysterectomy at the household level in all three states. Heavy menstrual bleeding/pain was the leading cause of hysterectomies in all three states, followed by fibroids/cysts in Andhra Pradesh and Telangana and Uterine disorder/ prolapse in Bihar. Over 80% of hysterectomies took place in the private hospitals.

Recommendations

The study recommends better, more efficient and accountable hysterectomy surveillance to ensure more sustainable woman’s reproductive health services in India. Government should adopt and implement standard regulatory guidelines to prevent provider-driven avoidable hysterectomies. Moreover, we recommend informing primary care professionals about the long-term health effects of hysterectomy and promoting alternate therapies for treating uterine fibroids and heavy bleeding.
“Counteract the gaslighting” – a thematic analysis of open-ended responses about what women survivors of intimate partner sexual violence need from service providers
Authors: Peeren Síofra , McLindon Elizabeth , Tarzia Laura
Published: February 2024

Background

Intimate partner sexual violence (IPSV) is a prevalent but misunderstood form of gender-based violence with significant impacts women’s health and well-being. Research suggests that IPSV has a specific context and unique impacts, but little is known about how to tailor service responses. To address this gap, we explored help-seeking experiences and needs among IPSV survivors after disclosure.

Methods

This study draws on qualitative data from a subsample of women who participated in a cross-sectional survey about the service needs of intimate partner violence survivors. Women who reported IPSV and provided information about IPSV-specific help-seeking needs after disclosure were included in the analysis. Open-ended text responses of 37 IPSV survivors were analysed using thematic analysis.

Results

IPSV was invisible and silenced in service responses. Three themes suggest potential ways forward. In the first theme, ‘Don’t dismiss it’, women needed providers to take their disclosures seriously and listen to the significant impacts of IPSV on their well-being and safety. In the second theme, ’See the bigger picture’, women needed service providers to understand that IPSV fits into broader patterns of abuse, and that psychological abuse and coercive control impacts women’s ability to consent. In the third theme, ‘counteract the gaslighting’, women needed providers to educate them about the continuum of IPSV and help them label IPSV as a form of violence.

Conclusions

Our exploratory findings extend the limited evidence base on IPSV and highlight a need for further in-depth research to explore a tailored approach to supporting IPSV survivors. To avoid contributing to the silencing of IPSV survivors, service responses should recognise the harmful and sexualised nature of IPSV, challenge cultural stereotypes that minimise IPSV, and understand that co-occurring psychological abuse may exacerbate shame and prevent women from articulating the source of their distress.
Prediction of Sjögren’s disease diagnosis using matched electronic dental-health record data
Authors: Mao Jason , Gomez Grace Gomez Felix , Wang Mei , Xu Huiping , Thyvalikakath Thankam P.
Published: February 2024

Background

Sjögren’s disease (SD) is an autoimmune disease that is difficult to diagnose early due to its wide spectrum of clinical symptoms and overlap with other autoimmune diseases. SD potentially presents through early oral manifestations prior to showing symptoms of clinically significant dry eyes or dry mouth. We examined the feasibility of utilizing a linked electronic dental record (EDR) and electronic health record (EHR) dataset to identify factors that could be used to improve early diagnosis prediction of SD in a matched case-control study population.

Methods

EHR data, including demographics, medical diagnoses, medication history, serological test history, and clinical notes, were retrieved from the Indiana Network for Patient Care database and dental procedure data were retrieved from the Indiana University School of Dentistry EDR. We examined EHR and EDR history in the three years prior to SD diagnosis for SD cases and the corresponding period in matched non-SD controls. Two conditional logistic regression (CLR) models were built using Least Absolute Shrinkage and Selection Operator regression. One used only EHR data and the other used both EHR and EDR data. The ability of these models to predict SD diagnosis was assessed using a concordance index designed for CLR.

Results

We identified a sample population of 129 cases and 371 controls with linked EDR-EHR data. EHR factors associated with an increased risk of SD diagnosis were the usage of lubricating throat drugs with an odds ratio (OR) of 14.97 (2.70-83.06), dry mouth (OR = 6.19, 2.14–17.89), pain in joints (OR = 2.54, 1.34–4.76), tear film insufficiency (OR = 27.04, 5.37–136.), and rheumatoid factor testing (OR = 6.97, 1.94–25.12). The addition of EDR data slightly improved model concordance compared to the EHR only model (0.834 versus 0.811). Surgical dental procedures (OR = 2.33, 1.14–4.78) were found to be associated with an increased risk of SD diagnosis while dental diagnostic procedures (OR = 0.45, 0.20–1.01) were associated with decreased risk.

Conclusion

Utilizing EDR data alongside EHR data has the potential to improve prediction models for SD. This could improve the early diagnosis of SD, which is beneficial to slowing or preventing complications of SD.
The AGE-RAGE axis associates with chronic pulmonary diseases and smoking in the Rotterdam study
Authors: Lu Tianqi , Lahousse Lies , Wijnant Sara , Chen Jinluan , Brusselle Guy G. , van Hoek Mandy , Zillikens M. Carola
Published: February 2024

Background

Chronic obstructive pulmonary disease (COPD) and asthma associate with high morbidity and mortality. High levels of advanced glycation end products (AGEs) were found in tissue and plasma of COPD patients but their role in COPD and asthma is unclear.

Methods

In the Rotterdam Study (n = 2577), AGEs (by skin autofluorescence (SAF)), FEV1 and lung diffusing capacity (DLCOc and DLCOc /alveolar volume [VA]) were measured. Associations of SAF with asthma, COPD, GOLD stage, and lung function were analyzed using logistic and linear regression adjusted for covariates, followed by interaction and stratification analyses. sRAGE and EN-RAGE associations with COPD prevalence were analyzed by logistic regression.

Results

SAF associated with COPD prevalence (OR = 1.299 [1.060, 1.591]) but not when adjusted for smoking (OR = 1.106 [0.89, 1.363]). SAF associated with FEV1% predicted (β=-3.384 [-4.877, -1.892]), DLCOc (β=-0.212 [-0.327, -0.097]) and GOLD stage (OR = 4.073, p = 0.001, stage 3&4 versus 1). Stratified, the association between SAF and FEV1%predicted was stronger in COPD (β=-6.362 [-9.055, -3.670]) than non-COPD (β=-1.712 [-3.306, -0.118]). Association of SAF with DLCOc and DLCOc/VA were confined to COPD (β=-0.550 [-0.909, -0.191]; β=-0.065 [-0.117, -0.014] respectively). SAF interacted with former smoking and COPD prevalence for associations with lung function. Lower sRAGE and higher EN-RAGE associated with COPD prevalence (OR = 0.575[0.354, 0.931]; OR = 1.778[1.142, 2.768], respectively).

Conclusions

Associations between SAF, lung function and COPD prevalence were strongly influenced by smoking. SAF associated with COPD severity and its association with lung function was more prominent within COPD. These results fuel further research into interrelations and causality between SAF, smoking and COPD.

Take-home message

Skin AGEs associated with prevalence and severity of COPD and lung function in the general population with a stronger effect in COPD, calling for further research into interrelations and causality between SAF, smoking and COPD.
Large airway T cells in adults with former bronchopulmonary dysplasia
Authors: Gao Jing , Um-Bergström Petra , Pourbazargan Melvin , Berggren-Broström Eva , Li ChuanXing , Merikallio Heta , Kaarteenaho Riitta , Reinke Nichole Stacey , Wheelock Craig E , Melén Erik , Anders Lindén , Wheelock Åsa M , Rassidakis Georgios , Ortiz-Villalon Cristian , Sköld Magnus Carl
Published: February 2024

Background

Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown.

Objective

To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD.

Methods

Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry.

Results

The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1.

Conclusions

The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.
Quantifying microbial robustness in dynamic environments using microfluidic single-cell cultivation
Authors: Blöbaum Luisa , Torello Pianale Luca , Olsson Lisbeth , Grünberger Alexander
Published: February 2024

Background

Microorganisms must respond to changes in their environment. Analysing the robustness of functions (i.e. performance stability) to such dynamic perturbations is of great interest in both laboratory and industrial settings. Recently, a quantification method capable of assessing the robustness of various functions, such as specific growth rate or product yield, across different conditions, time frames, and populations has been developed for microorganisms grown in a 96-well plate. In micro-titer-plates, environmental change is slow and undefined. Dynamic microfluidic single-cell cultivation (dMSCC) enables the precise maintenance and manipulation of microenvironments, while tracking single cells over time using live-cell imaging. Here, we combined dMSCC and a robustness quantification method to a pipeline for assessing performance stability to changes occurring within seconds or minutes.

Results

Saccharomyces cerevisiae CEN.PK113-7D, harbouring a biosensor for intracellular ATP levels, was exposed to glucose feast-starvation cycles, with each condition lasting from 1.5 to 48 min over a 20 h period. A semi-automated image and data analysis pipeline was developed and applied to assess the performance and robustness of various functions at population, subpopulation, and single-cell resolution. We observed a decrease in specific growth rate but an increase in intracellular ATP levels with longer oscillation intervals. Cells subjected to 48 min oscillations exhibited the highest average ATP content, but the lowest stability over time and the highest heterogeneity within the population.

Conclusion

The proposed pipeline enabled the investigation of function stability in dynamic environments, both over time and within populations. The strategy allows for parallelisation and automation, and is easily adaptable to new organisms, biosensors, cultivation conditions, and oscillation frequencies. Insights on the microbial response to changing environments will guide strain development and bioprocess optimisation.

Graphical Abstract
Melanoma biology and treatment: a review of novel regulated cell death-based approaches
Authors: Hsieh Ming-yun , Hsu Sheng-Kai , Liu Tzu-Yu , Wu Chang-Yi , Chiu Chien-Chih
Published: February 2024

The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.
NY-ESO-1-specific T cell receptor-engineered T cells and Tranilast, a TRPV2 antagonist bivalent treatment enhances the killing of esophageal cancer: a dual-targeted cancer therapeutic route
Authors: Amissah Obed Boadi , Chen Wenfang , de Dieu Habimana Jean , Sun Yirong , Lin Lihui , Liu Yujie , Wang Ling , Liu Zhaoming , Mukama Omar , Basnet Rajesh , Liu Hohua , Li Junyi , Ding Xuanyan , Lv Lingshuang , Chen Min , Liang Yalin , Huang Rongqi , Li Zhiyuan
Published: February 2024

Background

Esophageal cancer (EC) is a global canker notorious for causing high mortality due to its relentless incidence rate, convoluted with unyielding recurrence and metastasis. However, these intricacies of EC are associated with an immoderate expression of NY-ESO-1 antigen, presenting a lifeline for adoptive T cell therapy. We hypothesized that naturally isolated higher-affinity T cell receptors (TCRs) that bind to NY-ESO-1 would allow T lymphocytes to target EC with a pronounced antitumor response efficacy. Also, targeting TRPV2, which is associated with tumorigenesis in EC, creates an avenue for dual-targeted therapy. We exploited the dual-targeting antitumor efficacy against EC.

Methods

We isolated antigen-specific TCRs (asTCRs) from a naive library constructed with TCRs obtained from enriched cytotoxic T lymphocytes. The robustness of our asTCRs and their TCR-T cell derivatives, Tranilast (TRPV2 inhibitor), and their bivalent treatment were evaluated with prospective cross-reactive human-peptide variants and tumor cells.

Results

Our study demonstrated that our naive unenhanced asTCRs and their TCR-Ts perpetuated their cognate HLA-A*02:01/NY-ESO-1(157–165) specificity, killing varying EC cells with higher cytotoxicity compared to the known affinity-enhanced TCR (TCRe) and its wild-type (TCR0) which targets the same NY-ESO-1 antigen. Furthermore, the TCR-Ts and Tranilast bivalent treatment showed superior EC killing compared to any of their monovalent treatments of either TCR-T or Tranilast.

Conclusion

Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.
Deep neural networks for wearable sensor-based activity recognition in Parkinson’s disease: investigating generalizability and model complexity
Authors: Davidashvilly Shelly , Cardei Maria , Hssayeni Murtadha , Chi Christopher , Ghoraani Behnaz
Published: February 2024

Background

The research gap addressed in this study is the applicability of deep neural network (NN) models on wearable sensor data to recognize different activities performed by patients with Parkinson’s Disease (PwPD) and the generalizability of these models to PwPD using labeled healthy data.

Methods

The experiments were carried out utilizing three datasets containing wearable motion sensor readings on common activities of daily living. The collected readings were from two accelerometer sensors. PAMAP2 and MHEALTH are publicly available datasets collected from 10 and 9 healthy, young subjects, respectively. A private dataset of a similar nature collected from 14 PwPD patients was utilized as well. Deep NN models were implemented with varying levels of complexity to investigate the impact of data augmentation, manual axis reorientation, model complexity, and domain adaptation on activity recognition performance.

Results

A moderately complex model trained on the augmented PAMAP2 dataset and adapted to the Parkinson domain using domain adaptation achieved the best activity recognition performance with an accuracy of 73.02%, which was significantly higher than the accuracy of 63% reported in previous studies. The model’s F1 score of 49.79% significantly improved compared to the best cross-testing of 33.66% F1 score with only data augmentation and 2.88% F1 score without data augmentation or domain adaptation.

Conclusion

These findings suggest that deep NN models originating on healthy data have the potential to recognize activities performed by PwPD accurately and that data augmentation and domain adaptation can improve the generalizability of models in the healthy-to-PwPD transfer scenario. The simple/moderately complex architectures tested in this study could generalize better to the PwPD domain when trained on a healthy dataset compared to the most complex architectures used. The findings of this study could contribute to the development of accurate wearable-based activity monitoring solutions for PwPD, improving clinical decision-making and patient outcomes based on patient activity levels.
Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature
Authors: Li Yawei , Su Hang , Liu Kaidong , Zhao Zhangxiang , Wang Yuquan , Chen Bo , Xia Jie , Yuan Huating , Huang De-Shuang , Gu Yunyan
Published: February 2024

Background

TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level.

Methods

Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA).

Results

A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion.

Conclusions

Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.
Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients
Authors: Huang Yongqi , Huang Xiaoliang , Wang Zhen , He Fuhai , Huang Zigui , Chen Chuanbin , Tang Binzhe , Qin Mingjian , Wu Yongzhi , Long Chenyan , Tang Weizhong , Mo Xianwei , Liu Jungang
Published: February 2024

Background

Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status.

Method

A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5–23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora.

Result

There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated.

Conclusions

The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.
Enhanced molecular release from elderly bone samples using collagenase I: insights into fatty acid metabolism alterations
Authors: Malvandi Amir Mohammad , Halilaj Esra , Faraldi Martina , Mangiavini Laura , Cristoni Simone , Leoni Valerio , Lombardi Giovanni
Published: February 2024

Background

Bone is a metabolically active tissue containing different cell types acting as endocrine targets and effectors. Further, bone is a dynamic depot for calcium, phosphorous and other essential minerals. The tissue matrix is subjected to a constant turnover in response to mechanical/endocrine stimuli. Bone turnover demands high energy levels, making fatty acids a crucial source for the bone cells. However, the current understanding of bone cell metabolism is poor. This is partly due to bone matrix complexity and difficulty in small molecules extraction from bone samples. This study aimed to evaluate the effect of metabolite sequestering from a protein-dominated matrix to increase the quality and amount of metabolomics data in discovering small molecule patterns in pathological conditions.

Methods

Human bone samples were collected from 65 to 85 years old (the elderly age span) patients who underwent hip replacement surgery. Separated cortical and trabecular bone powders were treated with decalcifying, enzymatic (collagenase I and proteinase K) and solvent-based metabolite extraction protocols. The extracted mixtures were analyzed with the high-resolution mass spectrometry (HRMS). Data analysis was performed with XCMS and MetaboAnalystR packages.

Results

Fast enzymatic treatment of bone samples before solvent addition led to a significantly higher yield of metabolite extraction. Collagenase I and proteinase K rapid digestion showed more effectiveness in cortical and trabecular bone samples, with a significantly higher rate (2.2 folds) for collagenase I. Further analysis showed significant enrichment in pathways like de novo fatty acid biosynthesis, glycosphingolipid metabolism and fatty acid oxidation-peroxisome.

Conclusion

This work presents a novel approach for bone sample preparation for HRMS metabolomics. The disruption of bone matrix conformation at the molecular level helps the molecular release into the extracting solvent and, therefore, can lead to higher quality results and trustable biomarker discovery. Our results showed β-oxidation alteration in the aged bone sample. Future work covering more patients is worthy to identify the effective therapeutics to achieve healthy aging.
A 4D-CBCT correction network based on contrastive learning for dose calculation in lung cancer
Authors: Cao Nannan , Wang Ziyi , Ding Jiangyi , Zhang Heng , Zhang Sai , Gao Liugang , Sun Jiawei , Xie Kai , Ni Xinye
Published: February 2024

Objective

This study aimed to present a deep-learning network called contrastive learning-based cycle generative adversarial networks (CLCGAN) to mitigate streak artifacts and correct the CT value in four-dimensional cone beam computed tomography (4D-CBCT) for dose calculation in lung cancer patients.

Methods

4D-CBCT and 4D computed tomography (CT) of 20 patients with locally advanced non-small cell lung cancer were used to paired train the deep-learning model. The lung tumors were located in the right upper lobe, right lower lobe, left upper lobe, and left lower lobe, or in the mediastinum. Additionally, five patients to create 4D synthetic computed tomography (sCT) for test. Using the 4D-CT as the ground truth, the quality of the 4D-sCT images was evaluated by quantitative and qualitative assessment methods. The correction of CT values was evaluated holistically and locally. To further validate the accuracy of the dose calculations, we compared the dose distributions and calculations of 4D-CBCT and 4D-sCT with those of 4D-CT.

Results

The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) of the 4D-sCT increased from 87% and 22.31 dB to 98% and 29.15 dB, respectively. Compared with cycle consistent generative adversarial networks, CLCGAN enhanced SSIM and PSNR by 1.1% (p < 0.01) and 0.42% (p < 0.01). Furthermore, CLCGAN significantly decreased the absolute mean differences of CT value in lungs, bones, and soft tissues. The dose calculation results revealed a significant improvement in 4D-sCT compared to 4D-CBCT. CLCGAN was the most accurate in dose calculations for left lung (V5Gy), right lung (V5Gy), right lung (V20Gy), PTV (D98%), and spinal cord (D2%), with the relative dose difference were reduced by 6.84%, 3.84%, 1.46%, 0.86%, 3.32% compared to 4D-CBCT.

Conclusions

Based on the satisfactory results obtained in terms of image quality, CT value measurement, it can be concluded that CLCGAN-based corrected 4D-CBCT can be utilized for dose calculation in lung cancer.