bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review
Authors: Migliorini Filippo , Eschweiler Jörg , Spiezia Filippo , van de Wall Bryan J. M. , Knobe Matthias , Tingart Markus , Maffulli Nicola 
Published: June 2021

Abstract
Background
Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up.

Methods
This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells).

Results
Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12–60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06).

Conclusion
Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up.

Level of evidence
II, systematic review of prospective studies.
Saving lives through life-threatening measures? The COVID-19 paradox of infection prevention in long-term care facilities
Authors: Thiel Ansgar , Altmeier Dorothee , Frahsa Annika , Eschweiler Gerhard W. , Nieß Andreas , Sudeck Gorden ,   on behalf of the BaSAlt study team
Published: June 2021

AbstractThe current SARS Cov-2 infection control measures have paradoxical effects. On the one hand, the lockdown measures help to protect vulnerable populations in particular. On the other hand, these measures inevitably have the effect that those who are to be protected not only become socially isolated and are exposed to enormous psychological stress, but also break down physically due to inactivity. Thus, the activation that is omitted in the lockdown is not compensated by external reference groups, which also indicates that important conditions for healthy ageing are not given in long-term care facilities.
Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium
Authors: Schwartz Lauren , Caixàs Assumpta , Dimitropoulos Anastasia , Dykens Elisabeth , Duis Jessica , Einfeld Stewart , Gallagher Louise , Holland Anthony , Rice Lauren , Roof Elizabeth , Salehi Parisa , Strong Theresa , Taylor Bonnie , Woodcock Kate 
Published: June 2021

AbstractPrader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC “Behavior Outcomes Working Group” sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.
The impact of diabetes and osteoarthritis on the occurrence of stroke, acute myocardial infarction, and heart failure among older adults with non-valvular atrial fibrillation in Hawaii: a retrospective observational cohort study
Authors: Matsunaga Masako , Chen John J. , Jijiwa Mayumi , Lim Eunjung 
Published: June 2021

Abstract
Background
To date, little is known about cardiovascular disease risks among older adults with non-valvular atrial fibrillation by their association with diabetes and osteoarthritis status, based on longitudinal data with substantial amounts of non-white individuals. The objective of this study was to examine the risks for three cardiovascular diseases: stroke, acute myocardial infarction (AMI), and heart failure (HF), by diabetes and osteoarthritis status among older adults with non-valvular atrial fibrillation in Hawaii.

Methods
We conducted a retrospective observational cohort study for older adults (65 years and older) with non-valvular atrial fibrillation using the Hawaii Medicare data 2009–2017. Their risks for the three cardiovascular diseases by diabetes and osteoarthritis status (diabetes, osteoarthritis, diabetes and osteoarthritis, and without diabetes and osteoarthritis) were examined by multivariable Cox proportional hazard regression models.

Results
The analysis included 19,588 beneficiaries followed up for a maximum of 3288 days (diabetes: n = 4659, osteoarthritis: n = 1978, diabetes and osteoarthritis: n = 1230, without diabetes and osteoarthritis: n = 11,721). Among them, those diagnosed with the cardiovascular diseases were identified (stroke: diabetes n = 837, osteoarthritis n = 315, diabetes and osteoarthritis n = 184, without diabetes and osteoarthritis n = 1630)(AMI: diabetes n = 438, osteoarthritis n = 128, diabetes and osteoarthritis n = 118, without diabetes and osteoarthritis n = 603)(HF: diabetes n = 2254, osteoarthritis n = 764, diabetes and osteoarthritis n = 581, without diabetes and osteoarthritis n = 4272). After adjusting for age, sex, race/ethnicity, and other potential confounders, those with diabetes and osteoarthritis had higher risks for HF (hazard ratio: 1.21 95% confidence interval: 1.10–1.33) than those without diabetes and osteoarthritis. They also had higher risks than those with osteoarthritis for HF. Those with diabetes had higher risks for all three cardiovascular diseases than the other three groups.

Conclusions
Variation in cardiovascular disease risks for older adults with non-valvular atrial fibrillation in Hawaii exists with diabetes and osteoarthritis status.
Depletion of EREG enhances the osteo/dentinogenic differentiation ability of dental pulp stem cells via the p38 MAPK and Erk pathways in an inflammatory microenvironment
Authors: Ran Ran , Yang Haoqing , Cao Yangyang , Yan Wanhao , Jin Luyuan , Zheng Ying 
Published: June 2021

Abstract
Background
Epiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Whether EREG can stimulate the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) in inflammatory environment is not clear. The purpose of the present study is to investigate the role of EREG on the osteo/dentinogenic differentiation ability of DPSCs in inflammatory environment.

Methods
DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) were used to knock down EREG expression in DPSCs. Recombinant human EREG (rhEREG) protein was used in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real-time RT-PCR were performed to detect osteo/dentinogenic differentiation markers and related signalling pathways under normal and inflammatory conditions.

Results
EREG depletion promoted the ALP activity and mineralization ability of DPSCs. The expression of BSP, DMP-1, and DSPP was also enhanced. Moreover, 50 ng/mL rhEREG treatment decreased the osteo/dentinogenic differentiation potential of DPSCs, while treatment with 10 ng/mL TNF-α for 4 h increased the expression of EREG in DPSCs. Conversely, EREG knockdown rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanistic studies showed that EREG depletion activated the p38 MAPK and Erk signalling pathways in DPSCs under normal and inflammatory conditions.

Conclusions
Our results demonstrated that EREG could inhibit the osteo/dentinogenic differentiation potential of DPSCs via the p38 MAPK and Erk signalling pathways. Under inflammatory environment, EREG depletion enhanced osteo/dentinogenic differentiation potential of DPSCs by improving the expression of p-p38 MAPK and p-Erk.
Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital
Authors: O’Shea Michael Patrick , Kennedy Cormac , Relihan Eileen , Harkin Kieran , Hennessy Martina , Barry Michael 
Published: June 2021

Abstract
Background
Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings.

Methods
Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis.

Results
Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error.

Conclusion
This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.
The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome
Authors: Foth S. , Meller S. , Kenward H. , Elliott J. , Pelligand L. , Volk H. A. 
Published: June 2021

Abstract
Background
Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders.

Methods
Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed.

Results
All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999).

Conclusions
The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.
Droplet digital PCR allows vector copy number assessment and monitoring of experimental CAR T cells in murine xenograft models or approved CD19 CAR T cell-treated patients
Authors: Haderbache Rafik , Warda Walid , Hervouet Eric , da Rocha Mathieu Neto , Trad Rim , Allain Vincent , Nicod Clementine , Thieblemeont Catherine , Boissel Nicolas , Varlet Pauline , Agha Ibrahim Yakoub , Bouquet Lucie , Guiot Melanie , Venet Fabienne , Sujobert Pierre , Roussel Xavier , Rouzaire Paul-Oliver , Caillot Denis , Casasnovas Olivier , Bories Jean Christophe , Bachy Emmanuel , Caillat-Zucman Sophie , Deschamps Marina , Ferrand Christophe 
Published: June 2021

Abstract
Background
Genetically engineered chimeric antigen receptor (CAR) T lymphocytes are promising therapeutic tools for cancer. Four CAR T cell drugs, including tisagenlecleucel (tisa-cel) and axicabtagene-ciloleucel (axi-cel), all targeting CD19, are currently approved for treating B cell malignancies. Flow cytometry (FC) remains the standard for monitoring CAR T cells using a recombinant biotinylated target protein. Nevertheless, there is a need for additional tools, and the challenge is to develop an easy, relevant, highly sensitive, reproducible, and inexpensive detection method. Molecular tools can meet this need to specifically monitor long-term persistent CAR T cells.

Methods
Based on 2 experimental CAR T cell constructs, IL-1RAP and CS1, we designed 2 quantitative digital droplet (ddPCR) PCR assays. By targeting the 4.1BB/CD3z (28BBz) or 28/CD3z (28z) junction area, we demonstrated that PCR assays can be applied to approved CD19 CAR T drugs. Both 28z and 28BBz ddPCR assays allow determination of the average vector copy number (VCN) per cell. We confirmed that the VCN is dependent on the multiplicity of infection and verified that the VCN of our experimental or GMP-like IL-1RAP CAR T cells met the requirement (< 5 VCN/cell) for delivery to the clinical department, similar to approved axi-cel or tisa-cel drugs.

Results
28BBz and 28z ddPCR assays applied to 2 tumoral (acute myeloid leukemia (AML) or multiple myeloma (MM) xenograft humanized NSG mouse models allowed us to quantify the early expansion (up to day 30) of CAR T cells after injection. Interestingly, following initial expansion, when circulating CAR T cells were challenged with the tumor, we noted a second expansion phase. Investigation of the bone marrow, spleen and lung showed that CAR T cells disseminated more within these tissues in mice previously injected with leukemic cell lines. Finally, circulating CAR T cell ddPCR monitoring of R/R acute lymphoid leukemia or diffuse large B cell lymphoma (n = 10 for tisa-cel and n = 7 for axi-cel) patients treated with both approved CAR T cells allowed detection of early expansion, which was highly correlated with FC, as well as long-term persistence (up to 450 days), while FC failed to detect these events.

Conclusion
Overall, we designed and validated 2 ddPCR assays allowing routine or preclinical monitoring of early- and long-term circulating approved or experimental CAR T cells, including our own IL-1RAP CAR T cells, which will be evaluated in an upcoming phase I clinical trial.
A review of research-supported group treatments for drug use disorders
Authors: López Gabriela , Orchowski Lindsay M. , Reddy Madhavi K. , Nargiso Jessica , Johnson Jennifer E. 
Published: June 2021

AbstractThis paper reviews methodologically rigorous studies examining group treatments for interview-diagnosed drug use disorders. A total of 50 studies reporting on the efficacy of group drug use disorder treatments for adults met inclusion criteria. Studies examining group treatment for cocaine, methamphetamine, marijuana, opioid, mixed substance, and substance use disorder with co-occurring psychiatric conditions are discussed. The current review showed that cognitive behavioral therapy (CBT) group therapy and contingency management (CM) groups appear to be more effective at reducing cocaine use than treatment as usual (TAU) groups. CM also appeared to be effective at reducing methamphetamine use relative to standard group treatment. Relapse prevention support groups, motivational interviewing, and social support groups were all effective at reducing marijuana use relative to a delayed treatment control. Group therapy or group CBT plus pharmacotherapy are more effective at decreasing opioid use than pharmacotherapy alone. An HIV harm reduction program has also been shown to be effective for reducing illicit opioid use. Effective treatments for mixed substance use disorder include group CBT, CM, and women’s recovery group. Behavioral skills group, group behavioral therapy plus CM, Seeking Safety, Dialectical behavior therapy groups, and CM were more effective at decreasing substance use and psychiatric symptoms relative to TAU, but group psychoeducation and group CBT were not. Given how often group formats are utilized to treat drug use disorders, the present review underscores the need to understand the extent to which evidence-based group therapies for drug use disorders are applied in treatment settings.
Pivoting in the pandemic: a qualitative study of child and adolescent psychiatrists in the times of COVID-19
Authors: DiGiovanni Madeline , Weller Indigo , Martin Andrés 
Published: June 2021

Abstract
Objectives
We examined the personal and professional impacts of the COVID-19 pandemic on the development, practice, and shifting values of child and adolescent psychiatrists (CAP), in order to inform how the field may move forward post-pandemic.

Methods
We conducted individual semi-structured interviews of child and adolescent psychiatrists (n = 24) practicing in the United States. Participants were selected as a diverse purposive sample of active members of the American Academy of Child and Adolescent Psychiatry (AACAP). We analyzed anonymized transcripts through iterative coding using thematic analysis aided by NVivo software.

Results
We identified three main thematic domains within participants’ response to the pandemic, which have engendered a reevaluation of and a recommitment to the aims of each clinician and the field of CAP more broadly. These domains, paired with representative questions, include: (1) Unsettling, or “who have we been?” (identifying discontents such as daily inefficiencies and intraprofessional loss of trust); (2) Adaptation, or “who are we now?” (exploring affordances and limitations of virtual work, and the evolution of personal and professional identity); and (3) Reimagination, or “who will we become?” (renewing a commitment to psychiatry as advocacy). Even as we identified a collective agreement toward the need for implementing change, just what needs to change, and how that change will be realized, remain contested.

Conclusion
These three thematic domains, augmented by a national confrontation with race and equity, have engendered a field-wide reckoning with known inequities. They have reinvigorated collective responses and calls to action. The divergent mindsets to change and leadership have provided an aperture for what values and practices the field might instill in its next generation of practitioners.
USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells
Authors: Liao Yuning , Shao Zhenlong , Liu Yuan , Xia Xiaohong , Deng Yuanfei , Yu Cuifu , Sun Wenshuang , Kong Weiyao , He Xiaoyue , Liu Fang , Guo Zhiqiang , Chen Guoxing , Tang Daolin , Gan Huoye , Liu Jinbao , Huang Hongbiao 
Published: June 2021

AbstractBackgroundHepatocellular carcinoma (HCC) remains a medical challenge due to its high proliferation and metastasis. Although deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation, their pathological roles in HCC have not been fully elucidated.MethodsBy using biomass spectrometry, co-immunoprecipitation, western blotting and immunofluorescence assays, we identify ribosomal protein S16 (RPS16) as a key substrate of ubiquitin-specific peptidase 1 (USP1). The role of USP1-RPS16 axis in the progression of HCC was evaluated in cell cultures, in xenograft mouse models, and in clinical observations.ResultsWe show that USP1 interacts with RPS16. The depletion of USP1 increases the level of K48-linked ubiquitinated-RPS16, leading to proteasome-dependent RPS16 degradation. In contrast, overexpression of USP1-WT instead of USP1-C90A (DUB inactivation mutant) reduces the level of K48-linked ubiquitinated RPS16, thereby stabilizing RPS16. Consequently, USP1 depletion mimics RPS16 deficiency with respect to the inhibition of growth and metastasis, whereas transfection-enforced re-expression of RPS16 restores oncogenic-like activity in USP1-deficient HCC cells. Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients.ConclusionsThese findings reveal a previously unrecognized role for the activation of USP1-RPS16 pathway in driving HCC, which may be further developed as a novel strategy for cancer treatment.
A rare ovarian hilus cell tumour accompanying bilateral serous cystadenomas: report of a case
Authors: Malakzai Haider Ali , Abdul-Ghafar Jamshid , Ibrahimkhil Abdul Sami , Haidary Ahmed Maseh 
Published: June 2021

Abstract
Background
Hilus cell tumours is considered an uncommon branch of androgen producing neoplasms that accounts for < 5% of all ovarian tumours. They are mostly benign and have characteristic gross and microscopic features. Here we present the first case of a hilus cell tumour in association with bilateral serous cystadenomas.

Case presentation
A 65-year-old lady with no symptoms of virilization, presented with postmenopausal dysfunctional uterine bleeding and radiological investigations revealing bilateral ovarian cysts that required a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Gross and microscopic evaluation confirmed the diagnosis of hilus cell tumour associated with bilateral serous cystadenomas.

Conclusions
This was the first case of hilus cell tumour in association with bilateral serous cystadenomas of the ovaries. Although, majority of hilus cell tumours that have been reported in the literature were benign, further studies are required to determine the behavior of the disease.