bluuebunny/crossref_metadata_2025_split huggingface dataset:
rTMS combined with CBT as a next step in antidepressant non-responders: a study protocol for a randomized comparison with current antidepressant treatment approaches
Authors: Dalhuisen Iris , Smit Filip , Spijker Jan , van Oostrom Iris , van Exel Eric , van Mierlo Hans , de Waardt Dieuwertje , Arns Martijn , Tendolkar Indira , van Eijndhoven Philip 
Published: February 2022

Abstract
Background
Major depressive disorder (MDD) is one of the most common psychiatric disorders, however, current treatment options are insufficiently effective for about 35% of patients, resulting in treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neuromodulation that is effective in treating TRD. Not much is known about the comparative efficacy of rTMS and other treatments and their timing within the treatment algorithm, making it difficult for the treating physician to establish when rTMS is best offered as a treatment option. This study aims to investigate the (cost-)effectiveness of rTMS (in combination with cognitive behavioral therapy (CBT) and continued antidepressant medication), compared to the next step in the treatment algorithm. This will be done in a sample of patients with treatment resistant non-psychotic unipolar depression.

Methods
In this pragmatic multicenter randomized controlled trial 132 patients with MDD are randomized to either rTMS or the next pharmacological step within the current treatment protocol (a switch to a tricyclic antidepressant or augmentation with lithium or a second-generation antipsychotic). Both groups also receive CBT. The trial consists of 8 weeks of unblinded treatment followed by follow-up of the cohort at four and 6 months. A subgroup of patients (n = 92) will have an extended follow-up at nine and 12 months to assess effect decay or retention. We expect that rTMS is more (cost-)effective than medication in reducing depressive symptoms in patients with TRD. We will also explore the effects of both treatments on symptoms associated with depression, e.g. anhedonia and rumination, as well as the effect of expectations regarding the treatments on its effectiveness.

Discussion
The present trial aims to inform clinical decision making about whether rTMS should be considered as a treatment option in patients with TRD. The results may improve treatment outcomes in patients with TRD and may facilitate adoption of rTMS in the treatment algorithm for depression and its implementation in clinical practice.

Trial registration
This trial is registered within the Netherlands Trial Register (code: NL7628, date: March 29th 2019).
Work environment risk factors causing day-to-day stress in occupational settings: a systematic review
Authors: Lukan Junoš , Bolliger Larissa , Pauwels Nele S. , Luštrek Mitja , Bacquer Dirk De , Clays Els 
Published: February 2022

Abstract
Background
While chronic workplace stress is known to be associated with health-related outcomes like mental and cardiovascular diseases, research about day-to-day occupational stress is limited. This systematic review includes studies assessing stress exposures as work environment risk factors and stress outcomes, measured via self-perceived questionnaires and physiological stress detection. These measures needed to be assessed repeatedly or continuously via Ecological Momentary Assessment (EMA) or similar methods carried out in real-world work environments, to be included in this review. The objective was to identify work environment risk factors causing day-to-day stress.

Methods
The search strategies were applied in seven databases resulting in 11833 records after deduplication, of which 41 studies were included in a qualitative synthesis. Associations were evaluated by correlational analyses.

Results
The most commonly measured work environment risk factor was work intensity, while stress was most often framed as an affective response. Measures from these two dimensions were also most frequently correlated with each other and most of their correlation coefficients were statistically significant, making work intensity a major risk factor for day-to-day workplace stress.

Conclusions
This review reveals a diversity in methodological approaches in data collection and data analysis. More studies combining self-perceived stress exposures and outcomes with physiological measures are warranted.
Physical activity and carotid atherosclerosis risk reduction in population with high risk for cardiovascular diseases: a cross-sectional study
Authors: Chen Lulu , Bi Yuan , Su Jian , Cui Lan , Han Renqiang , Tao Ran , Zhou Jinyi , Wu Ming , Qin Yu 
Published: February 2022

AbstractBackgroundDecreased physical activity had been reported to be a common causal and modifiable risk factor for major vascular events. However, the relationship of physical activity and sedentary leisure time with carotid atherosclerosis in population with high risk for cardiovascular diseases (CVDs) is still inconclusive. We aimed to evaluate the association of physical activity and sedentary leisure time with the risk of carotid atherosclerosis, and investigate any possible effect modifiers in population with high risk for CVDs.MethodsThe study population was drawn from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project-Jiangsu project, which is a population-based screening project that included permanent residents aged 35-75 years from 6 surveillance cities in Jiangsu Province. Linear regression models were used to evaluate the association of physical activity and sedentary leisure time with carotid intima-media thickness (CIMT). The risks of abnormal carotid artery and carotid plaque (CP) were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression.ResultsOverall, a total of 10,920 participants were enrolled in the final analysis. There was a significant inverse association of physical activity level with CIMT (per SD increase: β=-0.0103; 95%CI: -0.0154, -0.0053). The risk of abnormal carotid artery and CP decreased significantly with the increase of physical activity level (per SD increase: OR=0.908, 95%CI: 0.869-0.948; OR=0.900, 95%CI: 0.857-0.945, respectively). When physical activity level was categorized as quartiles, a significantly lower risk of abnormal carotid artery and CP was found in quartiles 2-4 with quartile 1 as reference (P<0.05 for all). Furthermore, the inverse association were stronger in participants with age ≥60 years (vs. <60 years,Pinteraction<0.001 for both). However, there were no significant association of sedentary leisure time with CIMT, abnormal carotid artery and CP.ConclusionsIn population with high risk for CVDs, physical activity was inversely associated with CIMT, abnormal carotid artery and CP, particularly among the elders. Sedentary leisure time was not associated with them. These results suggested that physical activity is important for carotid vascular health, and perhaps especially in elder population.
STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life
Authors: Witte Jan A. , Braunstahl Gert-Jan , Blox Wouter J. B. , van ’t Westeinde Susan C. , in ’t Veen Johannes C. C. M. , Kappen Jasper H. , van Rossum Elisabeth F. C. 
Published: February 2022

Abstract
Background
Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of ‘false-negative’ T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits.

Methods
The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17–75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal.

Discussion
This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients.
Trial registration Netherlands Trial Register, NL8759, registered 2020–07-06, https://www.trialregister.nl/trial/8759.
Protocol version and date: version 2.1, 20 November 2020.
miR-140-3p is a potential differential biomarker in benign phyllodes tumors and fibroadenoma of the breast
Authors: Li Qiang , Liu Yao , Bai Jiajia , Zhao Song , Wang Yawen , Shabbir Arzoo , Zhang Kai , Jiang Fan , Zhu Jiang , Ma Rong , Wang Jianli 
Published: February 2022

Abstract
Background
Benign phyllodes tumor (BPT) and fibroadenoma (FA) have some difficulties in differential diagnosis. BPT is often misdiagnosed as FA during the first operation and is not diagnosed until postoperative recurrence and reoperation. The intent of this research was to find and validate microRNAs (miRNAs) with significant differential expression between BPT and FA as novel potential differential biomarkers.

Methods
Tissue specimens from three BPT patients and three FA patients were selected to detect the expression of miRNAs by miRNA-Seq technique. Primary cells were extracted and cultured from fresh BPT and FA tissues by tissue-block culture. The expression of differentially expressed miRNA (DEmiRNA) was further verified by quantitative real-time polymerase chain reaction (qRT-PCR) in twelve BPT and eleven FA patient specimens as well as primary cells. Data with a P value < 0.05 were considered statistically significant.

Results
The miRNA-Seq results showed totally six DEmiRNA were identified, consisting of two downregulated genes and four upregulated genes in BPT. Further validation by qRT-PCR manifest that miR-140-3p was downregulated by approximately 70% in BPT.

Conclusion
miR-140-3p could become potential differential biomarker for BPT and FA.
Standup comedy principles and the personal monologue to explore interpersonal bias: experiential learning in a health disparities course
Authors: Chin Marshall H. , Aburmishan Mona M. , Zhu Mengqi 
Published: February 2022

Abstract
Background
Interpersonal biases between clinicians and patients contribute to disparities in health care and outcomes by race, ethnicity, and socioeconomic status. We used standup comedy principles and exercises to help medical students recognize how others perceive them and how they perceive others, and engage in difficult discussions around implicit biases and interpersonal racism.

Methods
90 min Zoom workshop with 40 first-year medical students in urban medical school. Intervention consisted of three exercises: Naming icebreaker, Rant and Rave (communicate strong perspective clearly), and Personal Monologue about how others perceive you and how you perceive yourself. Discussion debriefed the personal monologue exercise. Likert scale questions on post-session survey evaluated workshop overall, whether workshop increased skills, and safety of learning environment. Open-ended questions included what trainees liked about the module, what could be improved, and what impact the module had on them?

Results
Seventeen (42.5%) students responded to survey. Six respondents identified as white, 4 as Asian, 1 as Black, 1 as multiracial, and 5 did not identify. Seventy-six percent rated the module as “very good” or “excellent”, and 94% would recommend the module to others. Most respondents reported the workshop helped them become better listeners (75%) and more observant (82%). Eighty-three percent reported the training could help them take better care of patients with lived experiences different than their own. All respondents believed the learning environment was safe, and 94% reported that instructors created an atmosphere in which they could take risks. Thirty-six percent felt stressed. Students reported the workshop helped them recognize their own identities, others’ perceptions, and bidirectional biases, and inspired them to strive for more accurate, authentic interactions with patients.

Conclusions
Standup comedy principles show promise for engaging students in meaningful, safe discussions about perceptions and interpersonal biases rooted in their own personal experiences and those of their classmates.
Developing a patient-centered community-based model for management of multi-drug resistant tuberculosis in Uganda: a discrete choice experiment
Authors: Makabayi-Mugabe Rita , Musaazi Joseph , Zawedde-Muyanja Stella , Kizito Enock , Namwanje Hellen , Aleu Philip , Charlet Danielle , Freitas Lopez Debora B. , Brightman Haley , Turyahabwe Stavia , Nkolo Abel 
Published: February 2022

Abstract
Background
The advent of all-oral regimens for the management of multi-drug resistant tuberculosis (MDR-TB) makes the implementation of community-based directly observed therapy (CB-DOT) a possibility for this group of patients. We set out to determine patient preferences for different attributes of a community-based model for the management of MDR-TB in Uganda.

Methods
The study was conducted at five tertiary referral hospitals. We used a parallel convergent mixed methods study design. To collect quantitative data, we conducted a discrete choice experiment (DCE) with three different attributes of community-based care (DOT provider, location of care, and type of support) combined into eight choice sets, each with two options and an opt-out. We elicited patient reasons for selection of each choice set using qualitative methods. We fitted a mixed logit choice model to determine patient preferences for different attributes of community-based care and estimated the relative importance of each attribute using the range method. and used deductive thematic analysis to understand the reasons for the choices made.

Results
From December 2019 to January 2020, we interviewed 103 patients with MDR-TB. We found that all the three attributes considered were important predicators of choice. The relative importance of each attribute was as follows; the type of additional support (relative importance 36.2%), the location of treatment delivery (33.5%), and the type of DOT provider (30.3%). Participants significantly valued treatment delivered by community health workers (CHWs) or expert clients over that delivered by a family member, treatment delivered at home over that delivered at the workplace, and monthly travel vouchers as the form of additional support over phone call or SMS reminders. Subgroup analyses showed significant differences in preference across HIV status, age groups and duration on MDR-TB treatment, but not across gender.
The preferred model consisted of a CHW giving DOT at home and travel vouchers to enable attendance of monthly clinic follow-up visits to tertiary referral hospitals for treatment monitoring. Qualitative interviews revealed that patients perceived CHWs as knowledgeable and able to offer psychosocial support. Patients also preferred to take medication at home to save both time and money and lower the risk of facing TB stigma.

Conclusion
People with MDR-TB prefer to be supported to take their medicine at home by a member of their community. The effectiveness of this model of care is being further evaluated.
Development of a prognostic pyroptosis-related gene signature for head and neck squamous cell carcinoma patient
Authors: Zhu Weiwen , Zhang Jiayi , Wang Mengyao , Zhai Rundong , Xu Yanbin , Wang Jie , Wang Mengqi , Zhang Hang , Liu Laikui 
Published: February 2022

Abstract
Objective
Head and neck squamous cell carcinoma (HNSCC) is a major threat to public health. Pyroptosis is a form of inflammatory programmed cell death that is still incompletely understood. The role of pyroptotic cell death in HNSCC remains to be fully defined. As such, the present study was developed to explore the potential prognostic utility of a pyroptosis-related gene (PRG) signature in HNSCC.

Methods
PRG expression patterns and the associated mutational landscape in HNSCC were analyzed, after which a 6-gene prognostic model was constructed through least absolute shrinkage and selection operator (LASSO) and Cox regression analyses using the TCGA dataset, followed by validation with two GEO datasets (GSE41643 and GSE65858). The relative expression of the genes in the prognostic model was assessed via RT-qPCR in tumor and paired adjacent normal tissue samples from a 32-patient cohort. Potential predictors of patient outcomes associated with this 6-gene model were identified through topological degree analyses of a protein–protein interaction network. Moreover, the prognostic value of NLRP3 as a predictor of HNSCC patient prognosis was established through immunohistochemical (IHC) analyses of samples from 176 HNSCC patients. Lastly, in vitro studies were performed to further demonstrate the relevance of NLRP3 in the context of HNSCC development.

Results
Differentially expressed PRGs were able to readily differentiate between HNSCC tumors and normal tissues. Risk scores derived from the 6-gene PRG model were independent predictors of HNSCC patient prognosis, and genes that were differentially expressed between low- and high-risk groups were associated with tumor immunity. RT-qPCR assays also showed the potential protective role of NLRP3 in HNSCC patients. IHC analyses further supported the value of NLRP3 as a predictor of HNSCC patient outcomes. Invasion and migration assays demonstrated the potential role of NLRP3 in the inhibition of HNSCC development.

Conclusions
Overall, these results highlight a novel prognostic gene signature that offers value in the context of HNSCC patient evaluation, although additional research will be essential to elucidate the mechanisms linking these PRGs to HNSCC outcomes.
Economic evaluation of severe malaria in children under 14 years in Zambia
Authors: Mtalimanja Michael , Abasse Kassim Said , Mtalimanja James Lamon , Yuan Xu Zheng , Wenwen Du , Xu Wei 
Published: February 2022

Abstract
Introduction
Malaria exerts a significant economic burden on health care providers and households and our study attempts to make claims on the cost effectiveness of artesunate against quinine in patients under 14 years of age in Zambia. Also, to find the average total costs involved in the treatment of severe malaria in children and their impact on household expenditure.

Methods
Cost-effectiveness analysis of severe malaria treatment was conducted from a healthcare provider perspective using a Markov model. Standard costing was performed for the identification, measurement and assessment phases with data from quantification reports for anti-malaria commodities as these documents provides drug procurement costs from suppliers and freight costs. Average and incremental cost-effectiveness ratio were estimated and uncertainties were assessed through probabilistic sensitivity analysis.

Results
In Zambia severe malaria in children has been shown to account for over 45% of the total monthly curative healthcare costs incurred by households compared to the mean per capita monthly income. The cost of treating severe malaria depleted 7.67% of the monthly average household income. According, to the cost effectiveness analysis the of artesunate with quinine the ICER was $105 per death averted.

Conclusion
The use of artesunate over quinine in the treatment of severe malaria in children under 14 years is a highly cost-effective strategy for the healthcare provider in Zambia.
Sex-specific differences in plasma lipid profiles are associated with Gulf War Illness
Authors: Oberlin Sarah , Nkiliza Aurore , Parks Megan , Evans James E. , Klimas Nancy , Keegan Andrew P. , Sullivan Kimberly , Krengel Maxine H. , Mullan Michael , Crawford Fiona , Abdullah Laila 
Published: February 2022

Abstract
Background
Nearly 250,000 veterans from the 1990–1991 Gulf War have Gulf War Illness (GWI), a condition with heterogeneous pathobiology that remains difficult to diagnose. As such, availability of blood biomarkers that reflect the underlying biology of GWI would help clinicians provide appropriate care to ill veterans. In this study, we measured blood lipids to examine the influence of sex on the association between blood lipids and GWI diagnosis.

Methods
Plasma lipid extracts from GWI (n = 100) and control (n = 45) participants were subjected to reversed-phase nano-flow liquid chromatography-mass spectrometry analysis.

Results
An influence of sex and GWI case status on plasma neutral lipid and phospholipid species was observed. Among male participants, triglycerides, diglycerides, and phosphatidylcholines were increased while cholesterol esters were decreased in GWI cases compared to controls. In female participants, ceramides were increased in GWI cases compared to controls. Among male participants, unsaturated triglycerides, phosphatidylcholine and diglycerides were increased while unsaturated cholesterol esters were lower in GWI cases compared to controls. The ratio of arachidonic acid- to docosahexaenoic acid-containing triglyceride species was increased in female and male GWI cases as compared to their sex-matched controls.

Conclusion
Differential modulation of neutral lipids and ratios of arachidonic acid to docosahexaenoic acid in male veterans with GWI suggest metabolic dysfunction and inflammation. Increases in ceramides among female veterans with GWI also suggest activation of inflammatory pathways. Future research should characterize how these lipids and their associated pathways relate to GWI pathology to identify biomarkers of the disorder.