bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making the match and breaking it: values, perceptions, and obstacles of trainees applying into physician-scientist training programs
Authors: Pepin M. E. , Kamal Y. , Reisman B. J. , Rockman M. E. , Waller J. P. 
Published: October 2023

Abstract
Background
Replenishing the physician-scientist workforce constitutes a central mission of medical education, but the loss of qualified trainees to non-academic positions remains an ongoing threat. Among the barriers facing physician-scientists today is the game-like model of U.S. medical residency matching through the National Research Matching Program (NRPM), which applies several assumptions regarding the comparability of applicant qualifications, cohort size, and the institutional breadth of applicants’ training needs.

Methods
The current report therefore summarizes the survey-based views and experiences of physician-scientist trainees obtained following the 2021–2022 application cycle for research-oriented residency programs, or physician-scientist training programs (PSTPs). From among this small cohort of applicants, we obtained survey-based feedback of 27 PSTP applicants across 17 U.S. medical universities, among whom 85% (23/27) matched into a PSTP.

Results
Among these PSTP applicants, 25/27 (93%) recognized “scientific community” as the most important feature of a postgraduate training program, with applicants identifying as female placing a higher value on the program’s infrastructure of personal and/or family support. Most (18/27) respondents found “waiting for interviews” as the most stressful phase of their application cycle, and roughly half of all respondents encountered at least one NRMP policy violation through post-interview communication. Specifically, 93% (25/27) respondents were contacted by at least one PSTP following interviews, and 1/3 of them admitted to feeling pressured into sharing their ranking preferences.

Conclusion
We highlight many previously unrecognized priorities among applicants to PSTPs, which include fostering community among its trainees and reinforcing structured mentoring. We uncover an inconsistency among PSTPs regarding the post-interview process, which represents an opportunity to better support applicants seeking to gauge programs according to their clinical, scientific, and academic interests as physician-scientists, while still adhering to NRMP policies.
The role of trust in the implementation and uptake of COVID-19 response measures: a qualitative study of health professionals’ experiences in Tanzania
Authors: Metta Emmy , Shayo Elizabeth H. , Ngalesoni Frida , Kalolo Albino , Nyamuryekung’e Kasusu , Mboya Innocent B. , Ndumwa Harrieth P. , Njiro Belinda J. , Amour Maryam A. 
Published: October 2023

Abstract
Background
Even though trust is placed at the central point in ensuring proper functioning of the health systems, studies remain scant on how it affects both the implementation and uptake of COVID-19 response measures in low- and middle-income countries such as Tanzania. This study, therefore, explored the role of trust in the implementation and uptake of recommended COVID-19 response measures including vaccines from the perspective of health professionals in Tanzania.

Methods
This cross-sectional qualitative study was implemented in four of Tanzania’s thirty-one regions. Qualitative data was collected through 26 in-depth interviews held with regional and district disease outbreak response teams, district cold chain co-ordinators and health facility in-charges. In addition, five focus group discussions and seven group interviews were conducted with healthcare workers from the lower-level health facilities. Thematic analysis was conducted and applied the trust constructs.

Results
Interpersonal trust and health system trust emerged as two major themes in the study. Interpersonal trust was reported to stem from lack of transparency that instigated fear, worries, and confusion regarding the implementation and uptake of the recommended response measures. The distrust was mainly between health professionals in health facilities and those assigned to isolation centres as well as between patients and community members. On the other hand, the health system trust was shaped by mixed feelings regarding COVID-19 vaccine national decisions, and conflicting messages from national officials, politicians and religious leaders on COVID-19 responses, safety, and effectiveness of the vaccines. Questions surrounding the short duration of clinical trials, indeterminate post-vaccination protection duration, impotence-linked beliefs, freemasonry notion and unclear vaccinated cards information are other reported contributory factors to mistrust in the health system. However, after a comprehensive health education and experience in COVID-19 vaccination administration most professionals affirmed the effectiveness of the vaccines in limiting infections and its severe consequences.

Conclusion
Participants indicated limited trust at both interpersonal and health system levels aggravated by lack of transparency, unclear and conflicting messages on COVID-19 infections and response measures. Enforced transparency on pandemics alongside standardised messages from the reliable sources is crucial in enhancing trust in implementation and uptake of the recommended response measures.
Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status
Authors: Poohadsuan Jirarat , O’Doherty George A. , Owattanapanich Weerapat , Kungwankiattichai Smith , Rojanasakul Yon , Issaragrisil Surapol , Luanpitpong Sudjit 
Published: October 2023

Abstract
Background
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by an accumulation of immature leukemic myeloblasts initiating from leukemic stem cells (LSCs)—the subpopulation that is also considered the root cause of chemotherapy resistance. Repurposing cardiac glycosides to treat cancers has gained increasing attention and supporting evidence, but how cardiac glycosides effectively target LSCs, e.g., whether it involves cell differentiation, remains largely unexplored.

Methods
Digoxin, a user-designed digitoxigenin-α-L-rhamnoside (D6-MA), and ouabain were tested against various human AML-derived cells with different maturation phenotypes. Herein, we established two study models to specifically determine the effects of cardiac glycosides on LSC death and differentiation—one allowed change in dynamics of LSCs and leukemic progenitor cells (LPCs), while another maintained their undifferentiated status. Regulatory mechanisms underlying cardiac glycoside-induced cytotoxicity were investigated and linked to cell cycle distribution and apoptotic machinery.

Results
Primitive AML cells containing CD34+ LSCs/LPCs were very responsive to nanomolar concentrations of cardiac glycosides, with ouabain showing the greatest efficiency. Ouabain preferentially induces caspase-dependent apoptosis in LSCs, independent of its cell differentiation status, as evidenced by (i) the tremendous induction of apoptosis by ouabain in AML cells that acquired less than 15% differentiation and (ii) the higher rate of apoptosis in enriched LSCs than in LPCs. We sorted LSCs and LPCs according to their cell cycle distribution into G0/G1, S, and G2/M cells and revealed that G0/G1 cells in LSCs, which was its major subpopulation, were the top ouabain responders, indicating that the difference in ouabain sensitivity between LSCs and LPCs involved both distinct cell cycle distribution and intrinsic apoptosis regulatory mechanisms. Further, Mcl-1 and c-Myc, which were differentially expressed in LSCs and LPCs, were found to be the key apoptosis mediators that determined ouabain sensitivity in AML cells. Ouabain induces a more rapid loss of Mcl-1 and c-Myc in LSCs than in LPCs via the mechanisms that in part involve an inhibition of Mcl-1 protein synthesis and an induction of c-Myc degradation.

Conclusions
Our data provide new insight for repurposing cardiac glycosides for the treatment of relapsed/refractory AML through targeting LSCs via distinct cell cycle and apoptosis machinery.
Comparing the CFIR-ERIC matching tool recommendations to real-world strategy effectiveness data: a mixed-methods study in the Veterans Health Administration
Authors: Yakovchenko Vera , Lamorte Carolyn , Chinman Matthew J. , Goodrich David E. , Gibson Sandra , Park Angela , Bajaj Jasmohan S. , McCurdy Heather , Morgan Timothy R. , Rogal Shari S. 
Published: October 2023

Abstract
Background
Practical and feasible methods for matching implementation strategies to diagnosed barriers of evidence-based interventions in real-world contexts are lacking. This evaluation compared actual implementation strategies applied with those recommended by an expert opinion-based tool to improve guideline-concordant cirrhosis care in a Veterans Health Administration national learning collaborative effort.

Methods
This convergent parallel mixed-methods study aimed to (1) identify pre-implementation Consolidated Framework for Implementation Research (CFIR) barriers to cirrhosis care through focus groups with frontline providers, (2) generate 20 recommended strategies using focus group identified barriers entered into the CFIR-Expert Recommendations for Implementing Change (ERIC) Implementation Strategy Matching Tool, (3) survey providers over two consecutive years on the actual use of 73 ERIC strategies and determine strategy effectiveness, (4) compare actual versus recommended strategy use, and (5) compare actual versus expected barriers by reverse applying the CFIR-ERIC Matching Tool.

Results
Eighteen semi-structured focus groups were conducted with 197 providers representing 95 VA sites to identify barriers to quality improvement, including cirrhosis care complexity, clarity of national goals, and local leadership support. The CFIR-ERIC Matching Tool recommended strategies such as assessing for readiness and needs, promoting adaptability, building local groups, preparing champions, and working with opinion leaders and early adopters. Subsequent strategy surveys found that sites used the top 20 “recommended” strategies no more frequently than other strategies. However, 14 (70%) of the top recommended strategies were significantly positively associated with cirrhosis care compared to 48% of actual strategies. Reverse CFIR-ERIC matching found that the strategies most used in the first year corresponded to the following barriers: opinion leaders, access to knowledge and information, and resources. The strategies most frequently employed in the second year addressed barriers such as champions, cosmopolitanism, readiness for implementation, relative priority, and patient needs and resources. Strategies used in both years were those that addressed adaptability, trialability, and compatibility.

Conclusions
This study is among the first to empirically evaluate the relationship between CFIR-ERIC Matching Tool recommended strategies and actual strategy selection and effectiveness in the real world. We found closer connections between recommended strategies and strategy effectiveness compared to strategy frequency, suggesting validity of barrier identification, and application of the expert-informed tool.
Altered expression of proteins involved in metabolism in LGMDR1 muscle is lost in cell culture conditions
Authors: Rico Anabel , Valls Andrea , Guembelzu Garazi , Azpitarte Margarita , Aiastui Ana , Zufiria Mónica , Jaka Oihane , López de Munain Adolfo , Sáenz Amets 
Published: October 2023

Abstract
Background
Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy due to mutations in the CAPN3 gene. While the pathophysiology of this disease has not been clearly established yet, Wnt and mTOR signaling pathways impairment in LGMDR1 muscles has been reported.

Results
A reduction in Akt phosphorylation ratio and upregulated expression of proteins implicated in glycolysis (HK-II) and in fructose and lactate transport (GLUT5 and MCT1) in LGMDR1 muscle was observed. In vitro analysis to establish mitochondrial and glycolytic functions of primary cultures were performed, however, no differences between control and patients were observed. Additionally, gene expression analysis showed a lack of correlation between primary myoblasts/myotubes and LGMDR1 muscle while skin fibroblasts and CD56− cells showed a slightly better correlation with muscle. FRZB gene was upregulated in all the analyzed cell types (except in myoblasts).

Conclusions
Proteins implicated in metabolism are deregulated in LGMDR1 patients’ muscle. Obtained results evidence the limited usefulness of primary myoblasts/myotubes for LGMDR1 gene expression and metabolic studies. However, since FRZB is the only gene that showed upregulation in all the analyzed cell types it is suggested its role as a key regulator of the pathophysiology of the LGMDR1 muscle fiber. The Wnt signaling pathway inactivation, secondary to FRZB upregulation, and GLUT5 overexpression may participate in the impaired adipogenesis in LGMD1R patients.
Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal
Authors: Ando Yukio , Waddington-Cruz Marcia , Sekijima Yoshiki , Koike Haruki , Ueda Mitsuharu , Konishi Hiroaki , Ishii Tomonori , Coelho Teresa 
Published: October 2023

AbstractHereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients’ genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients’ nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region.
Mental health treatment programs for children and young people in secure settings: A systematic review
Authors: Schutte Valerie , Danseco Evangeline , Lucente Gabrielle , Sundar Purnima 
Published: October 2023

AbstractBackgroundWhile there are mental health treatment programs for children and young people in secure settings (i.e., secure treatment programs) in many countries, there is a lack of transparency and consistency across these that causes confusion for stakeholders and challenges for the design and delivery of high-quality, evidence-based programs. This systematic review addresses two questions: What do mental health treatment programs for children and young people in secure community settings look like across jurisdictions? What is the evidence underlying the various components of these programs?MethodsTwelve databases were searched in November 2021: CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, Scopus, Science Direct, Academic Search Complete, Psychology and Behavioral Sciences Collection, Google Scholar, OpenDOAR, and GreyLit.org. To be included, publications had to be empirical literature or a report on mental health treatment within a secure setting for people under the age of 25; contain pre-identified keywords; be based on a research or evaluation study conducted since 2000; and be assessed as low risk of bias using an adaptation of the Critical Appraisal Skills Programme qualitative research checklist. The systematic review included 63 publications. Data were collected and analyzed in NVivo qualitative software using a coding framework.ResultsThere are secure treatment programs in Australia, Belgium, Canada, New Zealand, the Netherlands, England and Wales, Scotland, and the United States. Although there are inconsistencies across programs in terms of the systems in which they are embedded, client profiles, treatments provided, and lengths of stays, most share commonalities in their governance, definitions, designs, and intended outcomes.ConclusionsThe commonalities across secure treatment programs appear to stem from them being designed around a need for treatment that includes a mental disorder, symptom severity and salience involving significant risk of harm to self and/or others, and a proportionality of the risks and benefits of treatment. Most share a common logic; however, the evidence suggested that this logic may not to lead to sustained outcomes. Policymakers, service providers, and researchers could use the offered recommendations to ensure the provision of high-quality secure treatment programming to children and young people with serious and complex mental health needs.
The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
Authors: van der Pol Ymke , Moldovan Norbert , Ramaker Jip , Bootsma Sanne , Lenos Kristiaan J. , Vermeulen Louis , Sandhu Shahneen , Bahce Idris , Pegtel D. Michiel , Wong Stephen Q. , Dawson Sarah-Jane , Chandrananda Dineika , Mouliere Florent 
Published: October 2023

Abstract
Background
Existing methods to detect tumor signal in liquid biopsy have focused on the analysis of nuclear cell-free DNA (cfDNA). However, non-nuclear cfDNA and in particular mitochondrial DNA (mtDNA) has been understudied. We hypothesize that an increase in mtDNA in plasma could reflect the presence of cancer, and that leveraging cell-free mtDNA could enhance cancer detection.

Results
We survey 203 healthy and 664 cancer plasma samples from three collection centers covering 12 cancer types with whole genome sequencing to catalogue the plasma mtDNA fraction. The mtDNA fraction is increased in individuals with cholangiocarcinoma, colorectal, liver, pancreatic, or prostate cancer, in comparison to that in healthy individuals. We detect almost no increase of mtDNA fraction in individuals with other cancer types. The mtDNA fraction in plasma correlates with the cfDNA tumor fraction as determined by somatic mutations and/or copy number aberrations. However, the mtDNA fraction is also elevated in a fraction of patients without an apparent increase in tumor-derived cfDNA. A predictive model integrating mtDNA and copy number analysis increases the area under the curve (AUC) from 0.73 when using copy number alterations alone to an AUC of 0.81.

Conclusions
The mtDNA signal retrieved by whole genome sequencing has the potential to boost the detection of cancer when combined with other tumor-derived signals in liquid biopsies.
e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence
Authors: Mitchell E. J. , Appelbe D. , Bravery A. , Culliford L. , Evans H. , Farrin A. J. , Gillies K. , Hood K. , Love S. B. , Sydes M. R. , Williamson P. R. , Wakefield N. ,   as part of the e-Consent collaborative group
Published: October 2023

Abstract
Background
During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods
A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April–June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results
Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion
e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.
Tailored interventions to improve adherence to medication in elderly patients with Parkinson’s disease: a study protocol for a randomized controlled trial (AdhCare)
Authors: Mendorf Sarah , Teschner Ulrike , Lehmann Thomas , Prell Tino , Mühlhammer Hannah Maria 
Published: October 2023

Abstract
Background
Nonadherence to medication is a major issue in patients with chronic disorders such as Parkinson’s disease (PD). Many interventions for increasing adherence have been tested, and these have shown weak-to-moderate efficiency. Although the best methods to improve adherence remain unclear, it is reasonable to use tailored interventions instead of the “one-size-fits-all” approach.

Methods
A randomized, controlled, triple-blinded trial in elderly patients with PD is conducted to test the efficacy of AdhCare, a tailored intervention to enhance adherence compared with that achieved with routine care (64 participants per arm). Motor function, quality of life, and adherence measures will be assessed at baseline and at 3 and 6 months of follow-up. The type of intervention depends on the main personal reason for nonadherence (e.g., forgetting to take the medication or poor knowledge about the medication).

Discussion
The results of this study will provide valuable information for health professionals and policymakers on the effectiveness of tailored interventions in elderly patients with PD.

Trial registration
German Clinical Trials Register DRKS00023655. Registered on 24 February 2021. Last update on 22 March 2023.