bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the management of chronic pain, opioid use, and opioid use disorder in older adults: study protocol for I-COPE study
Authors: Kagarmanova Ainur , Sparkman Heather , Laiteerapong Neda , Thompson Katherine , Rosul Linda , Lazar Danielle , Staab Erin , Wan Wen , Kass Amanda , Ari Mim 
Published: July 2022

Abstract
Background
Older adults with chronic pain, opioid use, and opioid use disorder (OUD) present complex management decisions in primary care. Clinical tools are needed to improve care delivery. This study protocol describes the planned implementation and evaluation of I-COPE (Improving Chicago Older Adult Opioid and Pain Management through Patient-centered Clinical Decision Support and Project ECHO®) to improve care for this population.

Methods
This study uses a pragmatic, expanding cohort stepped-wedge design to assess the outcomes. The study will be implemented in 35 clinical sites across metropolitan Chicago for patients aged ≥ 65 with chronic pain, opioid use, or OUD who receive primary care at one of the clinics. I-COPE includes the integration of patient-reported data on symptoms and preferences, clinical decision support tools, and a shared decision-making tool into routine primary care for more effective management of chronic pain, opioid prescribing, and OUD in older adults. Primary care providers will be trained through web-based videos and an optional Project ECHO® course, entitled “Pain Management and OUD in Older Adults.” The RE-AIM framework will be used to assess the I-COPE implementation. Effectiveness outcomes will include an increased variety of recommended pain treatments, decreased prescriptions of higher-risk pain treatments, and decreased patient pain scores. All outcomes will be evaluated 6 and 12 months after implementation. PCPs participating in Project ECHO® will be evaluated on changes in knowledge, attitudes, and self-efficacy using pre- and post-course surveys.

Discussion
This study will provide evidence about the effectiveness of collecting patient-reported data on symptoms and treatment preferences and providing clinical decision support and shared decision-making tools to improve management for older adults with chronic pain, opioid use, and OUD.

Trial registration

ClinicalTrials.gov NCT04878562.
An intervention to reduce stigma and improve management of depression, risk of suicide/self-harm and other significant emotional or medically unexplained complaints among adolescents living in urban slums: protocol for the ARTEMIS project
Authors: Yatirajula Sandhya Kanaka , Kallakuri Sudha , Paslawar Srilatha , Mukherjee Ankita , Bhattacharya Amritendu , Chatterjee Susmita , Sagar Rajesh , Kumar Ashok , Lempp Heidi , Raman Usha , Singh Renu , Essue Beverley , Billot Laurent , Peiris David , Norton Robyn , Thornicroft Graham , Maulik Pallab K. 
Published: July 2022

Abstract
Background
There are around 250 million adolescents in India. Adolescents are vulnerable to common mental disorders with depression and self-harm accounting for a major share of the burden of death and disability in this age group. Around 20% of children and adolescents are diagnosed with/ or live with a disabling mental illness. A national survey has found that suicide is the third leading cause of death among adolescents in India. The authors hypothesise that an intervention involving an anti-stigma campaign co-created by adolescents themselves, and a mobile technology-based electronic decision support system will help reduce stigma, depression, and suicide risk and improve mental health for high-risk adolescents living in urban slums in India.

Methods
The intervention will be implemented as a cluster randomised control trial in 30 slum clusters in each of the cities of Vijayawada and New Delhi in India. Adolescents aged 10 to 19 years will be screened for depression and suicide ideation using the Patient Health Questionnaire (PHQ-9). Two evaluation cohorts will be derived—a high-risk cohort with an elevated PHQ-9 score ≥ 10 and/or a positive response (score ≥ 2) to the suicide risk question on the PHQ-9, and a non-high-risk cohort comprising an equal number of adolescents not at elevated risk based on these scores.

Discussion
The key elements that ARTEMIS will focus on are increasing awareness among adolescents and the slum community on these mental health conditions as well as strengthening the skills of existing primary healthcare workers and promoting task sharing. The findings from this study will provide evidence to governments about strategies with potential for addressing the gaps in providing care for adolescents living in urban slums and experiencing depression, other significant emotional or medically unexplained complaints or increased suicide risk/self-harm and should have relevance not only for India but also for other low- and middle-income countries.

Trial status
Protocol version – V7, 20 Dec 2021
Recruitment start date: tentatively after 15th July 2022
Recruitment end date: tentatively 14th July 2023 (1 year after the trial start date)

Trial registration
The trial has been registered in the Clinical Trial Registry India, which is included in the WHO list of Registries (https://www.who.int/clinical-trials-registry-platform/network/primary-registries) Reference No. CTRI/2022/02/040307. Registered on 18 February 2022.
The tentative start date of participant recruitment for the trial will begin after 15th July 2022.
Metabolic control by the microbiome
Authors: Cox Timothy O. , Lundgren Patrick , Nath Kirti , Thaiss Christoph A. 
Published: July 2022

AbstractThe interaction between the metabolic activities of the intestinal microbiome and its host forms an important part of health. The basis of this interaction is in part mediated by the release of microbially-derived metabolites that enter the circulation. These products of microbial metabolism thereby interface with the immune, metabolic, or nervous systems of the host to influence physiology. Here, we review the interactions between the metabolic activities of the microbiome and the systemic metabolism of the host. The concept that the endocrine system includes more than just the eukaryotic host component enables the rational design of exogenous interventions that shape human metabolism. An improved mechanistic understanding of the metabolic microbiome-host interaction may therefore pioneer actionable microbiota-based diagnostics or therapeutics that allow the control of host systemic metabolism via the microbiome.
Tenogenic induction of human adipose-derived stem cells by soluble tendon extracellular matrix: composition and transcriptomic analyses
Authors: Rao Ying , Zhu Chenxian , Suen Hoi Ching , Huang Shuting , Liao Jinyue , Ker Dai Fei Elmer , Tuan Rocky S. , Wang Dan 
Published: July 2022

Abstract
Background
Tendon healing is clinically challenging largely due to its inferior regenerative capacity. We have previously prepared a soluble, DNA-free, urea-extracted bovine tendon-derived extracellular matrix (tECM) that exhibits strong pro-tenogenic bioactivity on human adipose-derived stem cells (hASCs). In this study, we aimed to elucidate the mechanism of tECM bioactivity via characterization of tECM protein composition and comparison of transcriptomic profiles of hASC cultures treated with tECM versus collagen type I (Col1) as a control ECM component.

Methods
The protein composition of tECM was characterized by SDS-PAGE, hydroxyproline assay, and proteomics analysis. To investigate tECM pro-tenogenic bioactivity and mechanism of action, differentiation of tECM-treated hASC cultures was compared to serum control medium or Col1-treated groups, as assessed via immunofluorescence for tenogenic markers and RNA Sequencing (RNA-Seq).

Results
Urea-extracted tECM yielded consistent protein composition, including collagens (20% w/w) and at least 17 non-collagenous proteins (< 100 kDa) based on MS analysis. Compared to current literature, tECM included key tendon ECM components that are functionally involved in tendon regeneration, as well as those that are involved in similar principal Gene Ontology (GO) functions (ECM-receptor interaction and collagen formation) and signaling pathways (ECM-receptor interaction and focal adhesion). When used as a cell culture supplement, tECM enhanced hASC proliferation and tenogenic differentiation compared to the Col1 and FBS treatment groups based on immunostaining of tenogenesis-associated markers. Furthermore, RNA-Seq analysis revealed a total of 584 genes differentially expressed among the three culture groups. Specifically, Col1-treated hASCs predominantly exhibited expression of genes and pathways related to ECM-associated processes, while tECM-treated hASCs expressed a mixture of ECM- and cell activity-associated processes, which may explain in part the enhanced proliferation and tenogenic differentiation of tECM-treated hASCs.

Conclusions
Our findings showed that urea-extracted tECM contained 20% w/w collagens and is significantly enriched with other non-collagenous tendon ECM components. Compared to Col1 treatment, tECM supplementation enhanced hASC proliferation and tenogenic differentiation as well as induced distinct gene expression profiles. These findings provide insights into the potential mechanism of the pro-tenogenic bioactivity of tECM and support the development of future tECM-based approaches for tendon repair.
Combatting the effect of image reconstruction settings on lymphoma [18F]FDG PET metabolic tumor volume assessment using various segmentation methods
Authors: Ferrández Maria C. , Eertink Jakoba J. , Golla Sandeep S. V. , Wiegers Sanne E. , Zwezerijnen Gerben J. C. , Pieplenbosch Simone , Zijlstra Josée M. , Boellaard Ronald 
Published: July 2022

Abstract
Background
[18F]FDG PET-based metabolic tumor volume (MTV) is a promising prognostic marker for lymphoma patients. The aim of this study is to assess the sensitivity of several MTV segmentation methods to variations in image reconstruction methods and the ability of ComBat to improve MTV reproducibility.

Methods
Fifty-six lesions were segmented from baseline [18F]FDG PET scans of 19 lymphoma patients. For each scan, EARL1 and EARL2 standards and locally clinically preferred reconstruction protocols were applied. Lesions were delineated using 9 semiautomatic segmentation methods: fixed threshold based on standardized uptake value (SUV), (SUV = 4, SUV = 2.5), relative threshold (41% of SUVmax [41M], 50% of SUVpeak [A50P]), majority vote-based methods that select voxels detected by at least 2 (MV2) and 3 (MV3) out of the latter 4 methods, Nestle thresholding, and methods that identify the optimal method based on SUVmax (L2A, L2B). MTVs from EARL2 and locally clinically preferred reconstructions were compared to those from EARL1. Finally, different versions of ComBat were explored to harmonize the data.

Results
MTVs from the SUV4.0 method were least sensitive to the use of different reconstructions (MTV ratio: median = 1.01, interquartile range = [0.96–1.10]). After ComBat harmonization, an improved agreement of MTVs among different reconstructions was found for most segmentation methods. The regular implementation of ComBat (‘Regular ComBat’) using non-transformed distributions resulted in less accurate and precise MTV alignments than a version using log-transformed datasets (‘Log-transformed ComBat’).

Conclusion
MTV depends on both segmentation method and reconstruction methods. ComBat reduces reconstruction dependent MTV variability, especially when log-transformation is used to account for the non-normal distribution of MTVs.
Scoring system and a simple nomogram for predicting radioiodine refractory differentiated thyroid cancer: a retrospective study
Authors: Liu Ye , Wang Yuhua , Zhang Wanchun 
Published: July 2022

Abstract
Background
Differentiated thyroid carcinoma (DTC) originates from abnormal follicular cells and accounts for approximately 90–95% of thyroid malignancies. The diagnosis of radioiodine refractory DTC (RR-DTC) is based on clinical evolution and iodine uptake characteristics rather than pathological characteristics. Thus, it takes a long time to become apparent, and the definition of RR-DTC covers multiple aspects. We aimed to analyze the clinical and molecular imaging characteristics of patients with RR-DTC and identify independent predictors to develop an RR-DTC scoring system and a simple nomogram for predicting the probability of RR-DTC. We reviewed the data of 404 patients with metastatic DTC who underwent both post-RAI WB therapy scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Data on the clinical features and molecular characteristics of RR-DTC and non-RR-DTC cases were obtained from medical records. We screened for predictors using univariate analyses, obtained independent predictors through multivariate analyses, and then established a scoring system and a simple nomogram for predicting RR-DTC according to the corresponding odds ratio (OR) values.

Results
Diagnosis at age ≥ 48 years (OR, 1.037; 95% confidence interval [CI], 1.007–1.069), recurrence between the operation and iodine-131 treatment (OR, 7.362; 95% CI 2.388–22.698), uptake of 18F-FDG (OR, 39.534; 95% CI 18.590–84.076), and the metastasis site (OR, 4.365; 95% CI 1.593–11.965) were highly independently associated with RR-DTC. We established a scoring system for predicting RR-DTC, showing that the area under the receiver operating characteristic curve (AUC) with a cutoff value of 10 points (AUC = 0.898) had a higher discernibility than any other single independent predictor. The risk factors of RR-DTC in nomogram modeling include diagnosis at age ≥ 48 years, recurrence between the operation and iodine-131 treatment, uptake of 18F-FDG, and the site of metastasis. The concordance index (c-Index) of the nomogram was 0.9.

Conclusions
We demonstrated that a predictive model based on four factors has a good ability to predict RR-DTC. An index score ≥ 10 points was found to be the optimal index point for predicting RR-DTC. Moreover, this nomogram model has good predictive ability and stability. This model may help establish an active surveillance or appropriate treatment strategy for RR-DTC cases.
New insights into fibrosis from the ECM degradation perspective: the macrophage-MMP-ECM interaction
Authors: Zhao Xiangyu , Chen Jiayin , Sun Hongxiang , Zhang Yao , Zou Duowu 
Published: July 2022

AbstractFibrosis is a pathological feature of a variety of chronic inflammatory diseases that can affect almost all organs, which can cause severe consequences and even lead to death. Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) due to disruption of the balance between ECM production and degradation. Although overabundance of ECM proteins has long been the focus of studies on fibrosis, another facet of the problem—impaired degradation of the ECM—is gaining increasing attention. Matrix metalloproteinase (MMP) and the tissue inhibitor of metalloproteinase (TIMP) system is the main molecular system contributing to ECM degradation, and macrophages are the major regulators of ECM. However, the relationship among macrophages, the MMP/TIMP system and the ECM is not fully understood in the context of fibrosis. Here, we discuss in detail the role played by the ECM in the development of fibrosis and highlight the macrophage-MMP-ECM interaction that is involved in fibrogenesis and may be a potential therapeutic target for fibrosis.
Relevance of the post-COVID syndrome within rehabilitation (PoCoRe): study protocol of a multi-centre study with different specialisations
Authors: Kupferschmitt Alexa , Hinterberger Thilo , Montanari Ida , Gasche Matthias , Hermann Christoph , Jöbges Michael , Kelm Stefan , Sütfels Gerhard , Wagner Andreas , Loew Thomas H. , Köllner Volker 
Published: July 2022

Abstract
Background
In Patients suffering from post-COVID syndrome, in addition to physical limitations, cognitive limitations, fatigue, dyspnea as well as depression and anxiety disorders may also be present. Up to now (as of May 2022), approx. 514 million people worldwide have been infected with SARS-CoV-2, in Germany this affects approx. 25 million. In Germany, 2.5 million people could potentially be affected by post-COVID syndrome. Post-COVID is thus a highly relevant public health issue. So far, there is no specific causal therapy for the post-COVID syndrome, but with multimodal symptom-oriented rehabilitation, the course can be favourably influenced. However, there is no study yet that focuses on patients in different rehabilitation indications and compares the focal symptomatology and coping strategies as well as the patients' benefit per indication.

Methods/design
As first objective, pulmonal, cardiac, neurological, cognitive or/and psychological functional impairments in rehabilitation patients after COVID-19 disease will be described. The second objective is the differentiated review of the specific rehabilitation measures, in the short term and in the longer term for the purpose of future prognoses and optimisation of therapeutic interventions. This prospective, non-randomised, controlled longitudinal study, plus multi-group comparisons will take place in seven rehabilitation clinics of different specialisations: cardiological rehab, pneumological rehab, neurological rehab, psychosomatic rehab. Within 12 months, 1000 cases across all participating centres will be included. Somatic and psychological testing will be conducted at three measurement points: Admission (t0), discharge (t1), 6-montas Catamnesis (t2). The patients receive the usual care according to the respective rehabilitation priorities, adapted to the special challenges of post-COVID symptoms. Patients of the post-COVID outpatient clinic without rehabilitation will be used as a control group.

Discussion
This study will precisely assess the extent to which subclinical neurological or/and psychological impairments are present in post-COVID-19 rehabilitation and the results will help, developing, providing and evaluating appropriate treatment concepts. This may also have relevant implications for the improvement of physical ability and quality of life in post-COVID-19 patients and increase the probability of return to work.

Trial registration Z-2022-1749-8, registered 03. February 2022, https://studienanmeldung.zks-regensburg.de
Accidental duodenal foreign body of toothbrush removed laparoscopically: a case report
Authors: Soga Masahiro , Tanaka Tetsuya , Ueda Takeshi , Kirihataya Yuki , Yamaguchi Yohei , Okura Yasushi , Sawai Masayoshi , Yoshimura Atsushi 
Published: July 2022

Abstract
Background
Foreign body ingestion is a common case in daily medical care, and it usually passes through the entire gastrointestinal tract naturally and is excreted in the feces. However, long and sharp foreign bodies may be difficult to pass naturally due to their shape. Here, we present a rare case of a duodenal foreign body, a toothbrush, that required laparoscopic surgical removal after a failed endoscopic attempt.

Case presentation
A 51-year-old male with intellectual disability presented to our hospital due to fever. Initially, he was diagnosed with aspiration pneumonia by chest X-ray and blood examination. However, abdominal X-ray examination suggested a foreign body, and a computed tomography scan revealed a toothbrush in the duodenum. Therefore, upper gastrointestinal endoscopy was immediately attempted to remove it, but it could not be safely removed because the handle part of the toothbrush seemed deeply embedded in the duodenal mucosa. Therefore, this case was diagnosed as duodenal incarceration of the toothbrush, and it was removed by laparoscopic surgery. The operation was performed safely, and the patient’s postoperative course was good without any complications. The extracted toothbrush was 15 cm in length.

Conclusion
We experienced a rare case of a duodenal foreign body, which was a toothbrush. The duodenal foreign body was safely removed by laparoscopic surgery for the first time.
Completely detached mechanical aortic valve prosthesis stuck to the aortic arch in a patient with Behçet’s disease
Authors: Nagase Haruhiro , Hoashi Takaya , Masuoka Ayumu , Hotoda Kentaro , Toda Koichi , Yoshitake Akihiro , Suzuki Takaaki 
Published: July 2022

Abstract
Background
Although detachment of the implanted valve prosthesis was a well-known complication in patients with Behçet’s disease, complete detachment of an aortic bileaflet valve prosthesis has never been reported.

Case presentation
An 18-year-old boy with Behçet’s disease (HLA-A26 positive) who had previously undergone aortic valve replacement with an 18-mm ATS-Advanced Performance (ATS-AP) valve (ATS Medical, Inc., Minneapolis, MN) at the age of 12 years, presented sudden-onset general fatigue and was emergently transferred to the regional hospital. Chest X-ray showed displacement of the implanted mechanical valve. An echocardiogram revealed mobile valve prosthesis and severe aortic regurgitation. Just before leaving for our hospital for surgical treatment, a completely detached valve prosthesis was floating in the ascending aorta. On arrival, the valve prosthesis was stuck to the transverse arch. Emergent removal of the previous mechanical valve from the aortic arch and redo aortic valve replacement with a 24-mm ATS-AP valve were performed under total circulatory arrest. Infectious endocarditis was denied by histopathological examination. The patient was back to the intensive care unit with extracorporeal membrane oxygenation support, which was successfully decannulated 5 days later.

Conclusions
This was the first report of a patient with Behçet’s disease who encountered a complete detachment of implanted aortic valve prosthesis. The patient could be rescued by emergent surgery.
SAFETEL: a pilot randomised controlled trial to assess the feasibility and acceptability of a safety planning and telephone follow-up intervention to reduce suicidal behaviour
Authors: O’Connor Rory C. , Smillie Susie , McClelland Heather , Lundy Jenna-Marie , Stewart Corinna , Syrett Suzy , Gavigan Marcela , McConnachie Alex , Stanley Bethany , Smith Michael , Brown Gregory K. , Stanley Barbara , Simpson Sharon A. 
Published: July 2022

Abstract
Background
A previous suicide attempt is an important predictor of future suicide. However, there are no evidence-based interventions administered in UK general hospital contexts to reduce suicidal behaviour in patients admitted following a suicide attempt. Consequently, the objective of this pilot randomised controlled trial was to explore whether a safety planning and telephone follow-up intervention (SAFETEL) was feasible and acceptable for individuals treated in hospital following a suicide attempt.

Methods
In this three-phase study with an embedded process evaluation, a safety planning intervention was tailored to the UK context (Phase I), piloted (Phase II, n = 32), and tested in a feasibility randomised controlled trial (Phase III). In Phase III, participants were allocated to either the intervention (n = 80) or control group (n = 40) using telephone randomisation with a 2:1 ratio. The acceptability and feasibility of the trial and intervention procedures were evaluated using both qualitative (interviews and focus groups) and quantitative data. The number of hospital representations of suicidal behaviour was also collected 6 months after study recruitment based on electronic patient records.

Results
Findings indicated that SAFETEL was both acceptable and feasible. Hospital staff reported the intervention fitted and complemented existing services, and patients reported that they favoured the simplicity and person-centred approach of the safety planning intervention.

Conclusions
All progression criteria were met supporting further evaluation of the intervention in a full-scale clinical effectiveness trial.

Trial registration
ISRCT,ISRCTN62181241, 5/5/2017