bluuebunny/crossref_metadata_2025_split huggingface dataset:
ImpACT+, a coping intervention to improve clinical outcomes for women living with HIV and sexual trauma in South Africa: study protocol for a randomized controlled trial
Authors: Sikkema K. J. , Rabie S. , King A. , Watt M. H. , Mulawa M. I. , Andersen L. S. , Wilson P. A. , Marais A. , Ndwandwa E. , Majokweni S. , Orrell C. , Joska J. A. 
Published: August 2022

Abstract
Background
Addressing sexual trauma in the context of HIV care is essential to improve clinical outcomes and mental health among women in South Africa. Women living with HIV (WLH) report disproportionately high levels of sexual trauma and have higher rates of posttraumatic stress disorder. Adherence to antiretroviral therapy (ART) may be difficult for traumatized women, as sexual trauma compounds the stress associated with managing HIV and is often comorbid with other mental health disorders, further compromising care engagement and adherence. ART initiation represents a unique window of opportunity for intervention to enhance motivation, increase care engagement, and address the negative effects of trauma on avoidant coping behaviors. Mental health interventions delivered by non-specialists in low- and middle-income countries have potential to treat depression, trauma, and effects of intimate partner violence among WLH. This study will examine the effectiveness of Improving AIDS Care after Trauma (ImpACT +), a task-shared, trauma-focused coping intervention, to promote viral suppression among WLH initiating ART in a South African clinic setting.

Methods
This study will be conducted in Khayelitsha, a peri-urban settlement situated near Cape Town, South Africa. Using a hybrid type 1 effectiveness-implementation design, we will randomize 350 WLH initiating ART to the ImpACT + experimental condition or the control condition (three weekly sessions of adapted problem-solving therapy) to examine the effectiveness of ImpACT + on viral suppression, ART adherence, and the degree to which mental health outcomes mediate intervention effects. ImpACT + participants will receive six once-a-week coping intervention sessions and six monthly maintenance sessions over the follow-up period. We will conduct mental health and bio-behavioral assessments at baseline, 4, 8, and 12 months, with care engagement data extracted from medical records. We will explore scalability using the Consolidated Framework for Implementation Research (CFIR).

Discussion
This trial is expected to yield important new information on psychologically informed intervention models that benefit the mental health and clinical outcomes of WLH with histories of sexual trauma. The proposed ImpACT + intervention, with its focus on building coping skills to address traumatic stress and engagement in HIV care and treatment, could have widespread impact on the health and wellbeing of individuals and communities in sub-Saharan Africa.

Trial registration
Clinicaltrials.gov NCT04793217. Retrospectively registered on 11 March 2021.
Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system
Authors: Dwivedi Garima , Flaman Lisa , Alaybeyoglu Begum , Struglics André , Frank Eliot H. , Chubinskya Susan , Trippel Stephen B. , Rosen Vicki , Cirit Murat , Grodzinsky Alan J. 
Published: August 2022

Abstract
Background
Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease.

Methods
Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin’s grade 0–2, 23–83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile.

Results
Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified.

Conclusion
CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.
Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway
Authors: Zhao Zhijian , Liu Yang , Lu Yingjie , Hou Mingzhuang , Shen Xu , Yang Huilin , Shi Qin , Zhang Yijian , He Fan , Zhu Xuesong 
Published: August 2022

AbstractBackgroundUncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components.Gingko bilobais a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown.MethodsIn our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), fromGingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored.ResultsIn interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it.ConclusionsThese results demonstrated that BB extracted fromGingko bilobaregulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as ade novotherapeutic insight for OA.Graphical AbstractSchematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herbGingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.
Validity of an algorithm for determining sleep/wake states using FS-760 in school-aged children
Authors: Enomoto Minori , Kitamura Shingo , Nakazaki Kyoko 
Published: August 2022

AbstractBackgroundActigraphy is a method used for determining sleep (S)/wakefulness (W) by actigraph, a device equipped with a built-in accelerometer and an algorithm validated for each device. The S/W determination algorithm for the waist-worn actigraph FS-760 has been formulated for adults. However, the algorithm for children has not been established. The purpose of this study was to formulate an algorithm for discriminating S/W in school-aged children using FS-760 and to evaluate its validity. We further tested the generalizability of existing algorithm for adults by applying it to the children’s activity data and then examined factors associated with adult algorithm agreement rates by multiple regression analysis using combined adult and children data.MethodsSixty-five, healthy, school-aged children (aged 6 to 15 years) were recruited and randomly assigned to two groups: A (n= 33) and B (n= 32). They underwent 8-h polysomnography (PSG) and wore FS-760 simultaneously to obtain activity data. To determine the central epoch of the sleep/wake states (𝑥), a five-order linear discriminant analysis was conducted using the activity intensity of group A for five epochs (𝑥−2, 𝑥−1, 𝑥, 𝑥+1, 𝑥+2; 10 min) and evaluate its accuracy with the activity of group B. To reveal the factors associated with adult algorithm agreement rate, we integrated the activity, age, sleep efficiency of 15 adults (aged 20 to 39 years) and those of 65 children for multiple regression analysis.ResultsThe mean agreement rate of the developed algorithm was 91.0%, with a mean sensitivity (true sleep detection rate) of 93.0% and a mean specificity (true wakefulness detection rate) of 63.9%. The agreement rate of the adult algorithm applied to children’s activity was significantly lower (81.8%) than that of the children algorithm. Multiple regression analysis showed that the agreement rates calculated by the adult algorithm were significantly related to mean activity of the 𝑥 epoch in NREM and REM sleep as well as age and sleep efficiency.ConclusionsThe S/W states in school-aged children can be reliably assessed using the developed algorithm for waist-worn actigraph FS-760. Since the accuracy of the adult algorithms decreased when applied it to children which have different activity levels during sleep, the establishment and validation of population-specific S/W algorithms should be required.
The effect of aging on the repeated-dose liver micronucleus assay using diethylnitrosamine
Authors: Satomoto Kensuke , Suzuki Isamu , Mita Koji , Wakita Atsushi , Yamagata Hiroshi , Mitsumoto Tatsuya , Hamada Shuichi 
Published: August 2022

AbstractBackgroundThe repeated-dose liver micronucleus (RDLMN) assay has been well-developed and applied because of its simplicity and the ease of integration into general toxicity studies which is the preferred method from the 3R’s point of view. In this assay, we observed micronucleated hepatocytes which accumulated during a rather long-term dosing period. When considering integration into general toxicity studies, the effects of age of the animals used in the micronucleus assay becomes a major issue. The effect of age on the micronucleus induction rate has been reported in bone marrow micronucleus assays, and it is considered that the decrease in cell proliferation rate due to aging is the cause of the decrease in sensitivity. A decrease in sensitivity due to aging was also reported in a liver micronucleus assay using clofibrate and the cause is considered to be a decrease in hepatocyte proliferation activity due to aging. However, no actual decrease in hepatocyte proliferation rate due to aging has been reported. In addition, there are no reports, so far, on whether similar effects of aging appear when other substances were administered. To investigate the effects of aging in the RDLMN assay, this study focused on the effects of 14-day repeated administration of DEN, a well-known genotoxic hepatocarcinogen with the hepatocyte toxicity which should cause an elevation of cell proliferation rate as a reflective regeneration.ResultsThe liver micronuclei induced by DEN were equivalent between the two age groups (i.e., six and eight weeks of age at the start of dosing). In the histopathological examination for the liver, single cell necrosis, karyomegaly, and increased mitosis were observed in the hepatocytes, and the frequency and severity were increased dose-dependently. Ki-67 immunohistochemical analysis which can detect all cells in the cell cycle other than those in the G0 phase revealed dose-dependent increase of cell proliferation activity, and the difference between ages was not observed.ConclusionThe effect of aging on the RDLMN assay could not be recognized when DEN was administered for 14 days in rats. Meanwhile, it was supported by the histopathological examination and Ki-67 immunohistochemical analysis that such an effect of aging was masked by the compensatory hepatocyte proliferation which was induced by the hepatocyte toxicity of DEN.
Treating mental stress in elite footballers using a stigma-free psychological approach: the Power Threat Meaning Framework
Authors: James Ian Andrew , Morris Simon , Johnston Allan , Glover Danny 
Published: August 2022

SUMMARYThere are many pressures on elite footballers. They work in a meritocracy, where only the best are selected and play at the highest levels. From the moment they enter an academy to their retirement there is a fear of deselection and rejection. Elite players need to contend with criticisms from fans and via social media; team and management dynamics can be stressful. Fears of injury are major concerns. In addition, the players are likely to face everyday difficulties experienced by the rest of society, such as relationship, family and financial problems. There is a great deal of stigma associated with mental health problems in footballers, hence approaches are required that are destigmatising. This article presents two frameworks conceptualising stress in footballers: the Power Threat Meaning Framework, which describes stress in non-diagnostic terms; and the Yerkes–Dodson curve, which describes how stress can affect footballers’ mental and physical performances on the pitch. Both frameworks can combine to enable therapists to understand players’ distress and its impact and to guide towards appropriate treatments, as we show in a fictitious case study.
Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial
Authors: Byng Richard , Kirkpatrick Tim , Lennox Charlotte , Warren Fiona C. , Anderson Rob , Brand Sarah Louise , Callaghan Lynne , Carroll Lauren , Durcan Graham , Gill Laura , Goodier Sara , Graham Jonathan , Greer Rebecca , Haddad Mark , Harris Tirril , Henley William , Hunter Rachael , Leonard Sarah , Maguire Mike , Michie Susan , Owens Christabel , Pearson Mark , Quinn Cath , Rybczynska-Bunt Sarah , Stevenson Caroline , Stewart Amy , Stirzaker Alex , Todd Roxanne , Walter Florian , Weston Lauren , Wright Nat , Taylor Rod S. , Shaw Jenny 
Published: August 2022

BackgroundMany male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse.AimsThis study aims to evaluate whether the Engager intervention improves mental health outcomes following release.MethodThe design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3–5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT).ResultsIn total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI –1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact.ConclusionsEngager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.
Disparities in Oral Cancer Stage at Presentation in a High HIV Prevalence Setting In Sub-Saharan Africa
Authors: Motlokwa Precious K. , Tsima Billy M. , Martei Yehoda M. , Ralefala Tlotlo , Galebole Faith , Stephens-Shields Alisa J. , Grover Surbhi , Gross Robert 
Published: August 2022

PURPOSEOral cancer is the sixth most common cancer worldwide and is the seventh most common in Botswana. Lack of improvement in oral cancer survival despite the availability of multiple treatment options may be due to the high prevalence of advanced stage at presentation. We identified risk factors for presenting with oral cancer at an advanced stage to facilitate interventions to reduce mortality from oral cancers.METHODSA retrospective cohort analysis was conducted among individuals with biopsy-confirmed oral cancer at Princess Marina Hospital in Gaborone, Botswana, between 2010 and 2020. Data collected included age at diagnosis, sex, place of residence, HIV status, oral cancer stage, and oral subsite. Multivariable analyses were controlled for age, sex, district of residence, and oral subsite.RESULTSOf the 218 records analyzed, 79% were male, 58% were HIV-positive, the median age was 56 years (interquartile range: 47-63), and 67% presented with advanced-stage disease. Cancers from hidden oral sites were more likely to present at an advanced stage with an adjusted odds ratio (OR) of 2.98 (95% CI, 1.29 to 6.89; P = .01). Residence in socioeconomically disadvantaged districts was associated with higher likelihood (OR, 2.36; 95% CI, 1.28 to 4.39; P = .01) of advanced stage presentation compared with other districts. HIV infection was not associated with risk of advanced lesion presentation (OR, 1; 95% CI, 0.61 to 1.61; P = .97).CONCLUSIONHidden oral cancer sites and residence in districts with limited access to care were risk factors for advanced oral cancer at the time of diagnosis in Botswana. These findings support a need to increase efforts to improve access to care and increase oral cancer awareness to decrease the burden of advanced oral cancer.
Patient, Family, and Clinician Perspectives on Location of Death for Adolescents and Young Adults With Cancer
Authors: Odejide Oreofe O. , Fisher Lauren , Kushi Lawrence H. , Chao Chun R. , Vega Brenda , Rodrigues Gilda , Josephs Isabel , Brock Katharine E. , Buchanan Susan , Casperson Mallory , Cooper Robert M. , Fasciano Karen M. , Kolevska Tatjana , Lakin Joshua R. , Lefebvre Anna , Schwartz Corey M. , Shalman Dov M. , Wall Catherine B. , Wiener Lori , Altschuler Andrea , Mack Jennifer W. 
Published: August 2022

PURPOSE:Adolescents and young adults (AYAs) with cancer have high rates of hospital deaths. It is not clear if this reflects their preferences or barriers to dying at home.METHODS:Between December 2018 and January 2021, we conducted in-depth interviews with AYAs (age 12-39 years) with stage IV or recurrent cancer, family caregivers including bereaved caregivers, and clinicians of AYAs with cancer. Patients were asked about their priorities for care including location of death, caregivers were asked what was most important in the care of their AYA family member, and clinicians were asked to reflect on priorities identified through caring for AYAs. Directed content analysis was applied to interview data, and themes regarding location of death were developed.RESULTS:Eighty individuals (23 AYAs, 28 caregivers, and 29 clinicians) participated in interviews. Most AYAs and caregivers preferred a home death. However, some AYAs and caregivers opted for a hospital death to alleviate caregiver burden or protect siblings from the perceived trauma of witnessing a home death. Lack of adequate services to manage intractable symptoms at home and insufficient caregiver support led some AYAs/caregivers to opt for hospital death despite a preference for home death. Participants acknowledged the value of hospice while also pointing out its limitations in attaining a home death.CONCLUSION:Although most AYAs prefer to die at home, this preference is not always achieved. Robust home-based services for effective symptom management and caregiver support are needed to close the gap between preferred and actual location of death for AYAs.
Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis
Authors: Sullivan Brittany G. , Lo Angelina , Yu Jingjing , Gonda Amber , Dehkordi-Vakil Farideh , Dayyani Farshid , Senthil Maheswari 
Published: August 2022

Abstract
Introduction
Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier.

Methods
We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360TM). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.

Results
Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n = 61; visceral metastases: n = 138; other metastases: n = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p < 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%; p < 0.01). In a subset of patients (n = 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue.

Conclusions
PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.