bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slow motor neurons resist pathological TDP-43 and mediate motor recovery in the rNLS8 model of amyotrophic lateral sclerosis
Authors: Hur Seong Kwon , Hunter Mandana , Dominique Myrna A. , Farag Madona , Cotton-Samuel Dejania , Khan Tahiyana , Trojanowski John Q. , Spiller Krista J. , Lee Virginia M.-Y. 
Published: May 2022

AbstractIn the intermediate stages of amyotrophic lateral sclerosis (ALS), surviving motor neurons (MNs) that show intrinsic resistance to TDP-43 proteinopathy can partially compensate for the loss of their more disease-susceptible counterparts. Elucidating the mechanisms of this compensation may reveal approaches for attenuating motor impairment in ALS patients. In the rNLS8 mouse model of ALS-like pathology driven by doxycycline-regulated neuronal expression of human TDP-43 lacking a nuclear localization signal (hTDP-43ΔNLS), slow MNs are more resistant to disease than fast-fatigable (FF) MNs and can mediate recovery following transgene suppression. In the present study, we used a viral tracing strategy to show that these disease-resistant slow MNs sprout to reinnervate motor endplates of adjacent muscle fibers vacated by degenerated FF MNs. Moreover, we found that neuromuscular junctions within fast-twitch skeletal muscle (tibialis anterior, TA) reinnervated by SK3-positive slow MNs acquire resistance to axonal dieback when challenged with a second course of hTDP-43ΔNLS pathology. The selective resistance of reinnervated neuromuscular junctions was specifically induced by the unique pattern of reinnervation following TDP-43-induced neurodegeneration, as recovery from unilateral sciatic nerve crush did not produce motor units resistant to subsequent hTDP-43ΔNLS. Using cross-reinnervation and self-reinnervation surgery in which motor axons are disconnected from their target muscle and reconnected to a new muscle, we show that FF MNs remain hTDP-43ΔNLS-susceptible and slow MNs remain resistant, regardless of which muscle fibers they control. Collectively, these findings demonstrate that MN identity dictates the susceptibility of neuromuscular junctions to TDP-43 pathology and slow MNs can drive recovery of motor systems due to their remarkable resilience to TDP-43-driven degeneration. This study highlights a potential pathway for regaining motor function with ALS pathology in the advent of therapies that halt the underlying neurodegenerative process.
Cloth face mask fit and function for children part one: design exploration
Authors: Du Puis Jenny Leigh , Forstenhausler Lauren , Goodge Katarina , Maher Mona , Frey Margaret , Baytar Fatma , Park Huiju 
Published: May 2022

AbstractCommercially available children’s cloth masks range widely in material type and fabric structures, methods of construction, layering, and shape, and there is a lack of sizing systems, anthropometric data or guidelines specifically targeting the fit assessment and design of cloth face masks for children 4-6 years old. To better identify and understand the cloth face mask fit and functional needs of children ages 4-6 years old, the researchers embarked on interdisciplinary in-depth study to investigate commercial market offerings of children’s face masks, identify consumer perspectives, and explore mask design improvements through design research. By triangulating results from survey feedback, commercial market content analysis, and wear trial observations, the researchers were able to identify important design criteria that can be used in the improvement of children’s cloth face mask design: size, comfort, dexterity, movement, and thermal comfort. These criteria were used to iteratively develop new mask prototypes involving a 3D printed head form, traditional sewing and hand patternmaking skills, and the creation of multiple mask versions to explore the design criteria listed above. The designs were interpreted through Bye’s (2010) Problem-Based Design Research (PBDR) framework, which identifies common design research practices in the field on a spectrum and situates PBDR as a process centered on a problem as impetus for design through which artifacts are developed.
Responses of promyelocytic leukemia HL60 cells as an inflammatory cell lineage model to silica microparticles used to coat blood collection tubes
Authors: Masuki Hideo , Uematsu Takashi , Kawabata Hideo , Sato Atsushi , Watanabe Taisuke , Tsujino Tetsuhiro , Nakamura Masayuki , Okubo Masaya , Kawase Tomoyuki 
Published: May 2022

Abstract
Background
The preparation of platelet-rich fibrin (PRF) requires glass blood collection tubes, and thus, the shortage or unavailability of such tubes has driven clinicians to search for suitable substitutes, such as silica-coated plastic tubes. However, we have previously demonstrated the cytotoxicity of silica microparticles (MPs) used in plastic tubes to cultured human periosteal cells. To further establish the effects of silica MPs on inflammation, we examined silica MP-induced changes in a human promyelocytic cell model in vitro.

Methods
Human promyelocytic HL60 cells were used either without chemical induction or after differentiation induced using phorbol myristate acetate (PMA) or dimethyl sulfoxide. HL60 cells, osteoblastic MG63, and Balb/c mouse cells were treated with silica MPs, and their surface ultrastructure and numbers were examined using a scanning electron microscope and an automated cell counter, respectively. Differentiation markers, such as acid phosphatase, non-specific esterase, and CD11b, were visualized by cytochemical and immunofluorescent staining, and superoxide dismutase (SOD) activity was quantified.

Results
Regardless of SOD activity, silica cytotoxicity was observed in MG63 and Balb/c cells. At sub-toxic doses, silica MPs slightly or moderately upregulated the differentiation markers of the control, PMA-induced monocytic, and dimethyl sulfoxide-induced granulocytic HL60 cells. Although SOD activity was the highest (P < 0.05) in PMA-induced cells, a silica-induced reduction in cell adhesion was observed only in those cells (P < 0.05).

Conclusions
Silica MP contamination of PRF preparations can potentially exacerbate inflammation at implantation sites. Consequently, unless biomedical advantages can be identified, silica-coated plastic blood collection tubes should not be routinely used for PRF preparations.
Developing guideline-based key performance indicators for recurrent miscarriage care: lessons from a multi-stage consensus process with a diverse stakeholder group
Authors: Hennessy Marita , Linehan Laura , Dennehy Rebecca , Devane Declan , Rice Rachel , Meaney Sarah , O’Donoghue Keelin 
Published: May 2022

Abstract
Background
Standardised care pathways tailored to women/couples who experience recurrent miscarriage are needed; however, clinical practice is inconsistent and poorly organised. In this paper, we outline our processes and experiences of developing guideline-based key performance indicators (KPIs) for recurrent miscarriage care with a diverse stakeholder group which will be used to evaluate national services. To date, such exercises have generally only involved clinicians, with the need for greater stakeholder involvement highlighted.

Methods
Our study involved six stages: (i) identification and synthesis of recommendations for recurrent miscarriage care through a systematic review of clinical practice guidelines; (ii) a two-round modified e-Delphi survey with stakeholders to develop consensus on recommendations and outcomes; (iii) four virtual meetings to develop this consensus further; (iv) development of a list of candidate KPIs; (v) survey to achieve consensus on the final suite of KPIs and a (vi) virtual meeting to agree on the final set of KPIs. Through participatory methods, participants provided feedback on the process of KPI development.

Results
From an initial list of 373 recommendations and 14 outcomes, 110 indicators were prioritised for inclusion in the final suite of KPIs: (i) structure of care (n = 20); (ii) counselling and supportive care (n = 7); (iii) investigations (n = 30); treatment (n = 34); outcomes (n = 19). Participants’ feedback on the process comprised three main themes: accessibility, richness in diversity, streamlining the development process.

Conclusions
It is important and feasible to develop guideline-based KPIs with a diverse stakeholder group. One hundred and ten KPIs were prioritised for inclusion in a suite of guideline-based KPIs for recurrent miscarriage care. Insights into our experiences may help others undertaking similar projects, particularly those undertaken in the absence of a clinical guideline and/or involving a range of stakeholders.
Agreement between older adult patient and caregiver proxy symptom reports
Authors: Kroenke Kurt , Stump Timothy E. , Monahan Patrick O. 
Published: May 2022

Abstract
Background
Proxy report is essential for patients unable to complete patient-reported outcome (PRO) measures themselves and potentially beneficial when the caregiver perspective can complement patient report. In this study, we examine agreement between self-report by older adults and proxy report by their caregivers when completing PROs for pain, anxiety, depression, and other symptoms/impairments.

Methods
Four PROs were administered by telephone to older adults and their caregivers followed by re-administration within 24 h in a random subgroup. The PROs included the PHQ-9 depression, GAD-7 anxiety, PEG pain, and SymTrak multi-dimensional symptom and functional status scales.

Results
The sample consisted of 576 older adult and caregiver participants (188 patient-caregiver dyads, 200 patients without identified caregiver). The four measures had good internal (Cronbach’s alpha, 0.76 to 0.92) and test–retest (ICC, 0.63 to 0.92) reliability whether completed by patients or caregivers. Total score and item-level means were relatively similar for both patient and caregiver reports. Agreement for total score as measured by intraclass correlation coefficient (ICC) was better for SymTrak-23 (0.48) and pain (0.58) than for anxiety (0.28) and depression (0.25). Multinomial modeling showed higher (worse) patient-reported scale scores were associated with caregiver underreporting, whereas higher caregiver task difficulty was associated with overreporting.

Conclusion
When averaged over individuals at the group level, proxy reports of PRO scores by caregivers tend to approximate patient reports. For individual patients, proxy report should be interpreted more cautiously for psychological symptoms as well as when patient-reported symptoms are more severe, or caregiver task difficulty is high.
Maintaining Implementation through Dynamic Adaptations (MIDAS): protocol for a cluster-randomized trial of implementation strategies to optimize and sustain use of evidence-based practices in Veteran Health Administration (VHA) patients
Authors: Damschroder Laura J. , Sussman Jeremy B. , Pfeiffer Paul N. , Kurlander Jacob E. , Freitag Michelle B. , Robinson Claire H. , Spoutz Patrick , Christopher Melissa L.D. , Battar Saraswathy , Dickerson Kimberly , Sedgwick Christopher , Wallace-Lacey Ashleigh G. , Barnes Geoffrey D. , Linsky Amy M. , Ulmer Christi S. , Lowery Julie C. 
Published: May 2022

Abstract
Background
The adoption and sustainment of evidence-based practices (EBPs) is a challenge within many healthcare systems, especially in settings that have already strived but failed to achieve longer-term goals. The Veterans Affairs (VA) Maintaining Implementation through Dynamic Adaptations (MIDAS) Quality Enhancement Research Initiative (QUERI) program was funded as a series of trials to test multi-component implementation strategies to sustain optimal use of three EBPs: (1) a deprescribing approach intended to reduce potentially inappropriate polypharmacy; (2) appropriate dosing and drug selection of direct oral anticoagulants (DOACs); and (3) use of cognitive behavioral therapy as first-line treatment for insomnia before pharmacologic treatment. We describe the design and methods for a harmonized series of cluster-randomized control trials comparing two implementation strategies.

Methods
For each trial, we will recruit 8–12 clinics (24–36 total). All will have access to relevant clinical data to identify patients who may benefit from the target EBP at that clinic and provider. For each trial, clinics will be randomized to one of two implementation strategies to improve the use of the EBPs: (1) individual-level academic detailing (AD) or (2) AD plus the team-based Learn. Engage. Act. Process. (LEAP) quality improvement (QI) learning program. The primary outcomes will be operationalized across the three trials as a patient-level dichotomous response (yes/no) indicating patients with potentially inappropriate medications (PIMs) among those who may benefit from the EBP. This outcome will be computed using month-by-month administrative data. Primary comparison between the two implementation strategies will be analyzed using generalized estimating equations (GEE) with clinic-level monthly (13 to 36 months) percent of PIMs as the dependent variable. Primary comparative endpoint will be at 18 months post-baseline. Each trial will also be analyzed independently.

Discussion
MIDAS QUERI trials will focus on fostering sustained use of EBPs that previously had targeted but incomplete implementation. Our implementation approaches are designed to engage frontline clinicians in a dynamic optimization process that integrates the use of actional clinical data and making incremental changes, designed to be feasible within busy clinical settings.

Trial registration
ClinicalTrials.gov: NCT05065502. Registered October 4, 2021—retrospectively registered.
Best–worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy
Authors: Salloum Ramzi G. , Bishop Jeffrey R. , Elchynski Amanda L. , Smith D. Max , Rowe Elizabeth , Blake Kathryn V. , Limdi Nita A. , Aquilante Christina L. , Bates Jill , Beitelshees Amber L. , Cipriani Amber , Duong Benjamin Q. , Empey Philip E. , Formea Christine M. , Hicks J. Kevin , Mroz Pawel , Oslin David , Pasternak Amy L. , Petry Natasha , Ramsey Laura B. , Schlichte Allyson , Swain Sandra M. , Ward Kristen M. , Wiisanen Kristin , Skaar Todd C. , Van Driest Sara L. , Cavallari Larisa H. , Tuteja Sony 
Published: May 2022

Abstract
Background
Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best–worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use.

Methods
We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites.

Results
Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions.

Conclusions
This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.
Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland
Authors: Poma Anello Marcello , Proietti Agnese , Macerola Elisabetta , Bonuccelli Diana , Conti Marco , Salvetti Alessandra , Dolo Vincenza , Chillà Andrea , Basolo Alessio , Santini Ferruccio , Toniolo Antonio , Basolo Fulvio 
Published: May 2022

Abstract

Context
Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum adrenocorticotropic hormone (ACTH) levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated.

Objective
To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes.

Methods
SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time reverse transcription polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry, and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay.

Results
The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2–positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization, and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus positivity.

Conclusion
Our study supports the tropism of SARS-CoV-2 for human pituitary and encourages exploration of pituitary dysfunction after COVID-19.
Comparative analysis of dental pulp stem cells and stem cells from human exfoliated teeth in terms of growth kinetics, immunophenotype, self-renewal and multi lineage differentiation potential for future perspective of calcified tissue regeneration
Authors: Naz Shagufta , Khan Farhan Raza , Khan Irfan , Zohra Raheela Rahmat , Salim Asmat , Mohammed Nuruddin , Ahmad Tashfeen 
Published: May 2022

Background and Objectives: Owing to high proliferation rate, multipotency and self-renewal capability, dental pulp stem cells (DPSC) and stem cells from human exfoliated teeth (SHED) have become stem cell source of choice for cell based regenerative therapies. We aimed to compare DPSC and SHED as stem cell sources with a future use in regeneration of calcified tissue.
Methods: Explant derived human DPSC (n=9) and SHED (n=1) were cryopreserved, thawed and expanded for analysis of population doubling time, colony forming unit assay and efficiency. A growth curve was plotted to determine population doubling time, while colony forming numbers and efficiency was determined at plating cell densities of 5.6, 11.1 and 22.2 / cm2. The isolated cells were characterized for the presence of stem cell markers by immunophenotyping and immunofluorescence staining, and tri-lineage differentiation. Statistical analysis was performed by Pearson correlation, Exponential regression and two way Anova with Tukey test at p<0.05.
Results: DPSC and SHED exhibited spindle shaped fibroblast like morphology. SHED was found superior than DPSC in terms of proliferation and colony forming efficiency. Immunophenotypes showed that DPSC contain 62.6±26.3 %, 90.9±14.8% and 19.8±0.1%, while SHED contain 90.5%, 97.7% and 0.1% positive cells for CD90, CD73 and CD105. DPSC were strongly positive for vimentin, CD29, CD73, while reactivity was moderate to weak against CD44 and CD90. SHED expressed vimentin, CD29, CD105, CD90 and CD44. Both were negative for CD45. Upon induction, both cell types differentiated into bone, fat and cartilage like cells.
Conclusion: Cultured DPSC and SHED were proliferative and exhibited self-renewal property. Both DPSC and SHED expressed stem cell markers and were able to differentiate into bone, fat and cartilage like cells. Thus, these could be a suitable stem cell sources for cell based regenerative therapies.
doi: https://doi.org/10.12669/pjms.38.5.5187
How to cite this:Naz S, Khan FR, Khan I, Zohra RR, Salim A, Mohammed N, et al. Comparative analysis of dental pulp stem cells and stem cells from human exfoliated teeth in terms of growth kinetics, immunophenotype, self-renewal and multi lineage differentiation potential for future perspective of calcified tissue regeneration. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5187
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reliability of hand-held dynamometer in measuring gluteus medius isometric muscle strength in healthy population
Authors: Soomro Rabail Rani , Karimi Hossein , Gillani Syed Amir 
Published: May 2022

Objectives: To determine the inter-rater and intra-rater reliability of the hand-held dynamometer in measuring isometric gluteus medius muscle strength in asymptomatic healthy population.
Methods: It was a cross sectional study conducted at the department of physiotherapy, Sindh Institute of Physical Medicine and Rehabilitation from March 2021 to April 2021. Thirty healthy subjects aged 18 to 25 years of both sexes and no previous or current complaints of hip or knee pain were included through non-probability purposive sampling technique. The strength of the unilateral isometric gluteus medius muscle was measured using a hand-held dynamometer by two raters at the same day and a week later. Pearson Correlation coefficient was calculated to see the relationship of muscle strength measured by each rater within and between day’s sessions. Intra–class correlation was calculated with 95% confidence interval and Standard error of measurements using reliability analysis.
Results: In the present study there were thirty participants studied by two raters, the mean age of participants was 21.53 (SD=±1.40) years, the mean BMI was 24.05 (SD=±1.12) kg/m2 and 70% participants were female and 30% were males. This study showed the mean muscle measurement of participants within days was 12.92 (SD=±0.94), with intra-class correlation ICC (2,2) 0.94 and SEM 0.12 and mean muscle measurement of patients between days was 12.99 (SD=±0.91), with intra-class correlation ICC (2,2) 0.90 and SEM 0.12.
Conclusion: Hand-held dynamometer has shown excellent inter-rater and intra-rater reliability in measuring isometric strength of Gluteus Medius muscle among healthy population. It is convenient to be used in clinical settings and can be a useful outcome tool to assess strength in interventional studies.
doi: https://doi.org/10.12669/pjms.38.5.5207
How to cite this:Soomro RR, Karimi H, Gillani SA. Reliability of hand-held dynamometer in measuring gluteus medius isometric muscle strength in healthy population. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5207
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.