bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timelines for returning to physical activity following pediatric spinal surgery: recommendations from the literature and preliminary data
Authors: Willson Leanne R. , Klootwyk Madeline , Rogers Laura G. , Shearer Kathleen , Southon Sarah , Sasseville Christina 
Published: April 2021

Abstract
Objective
Participation in physical activity and sports is known to have positive implications for physical health, and for social and emotional wellbeing of children. Following corrective spinal surgery for scoliosis, the timeline for the return to activities and sports varies from surgeon to surgeon and from location to location, and return to activities can be limited due to pain, fear, and decreased flexibility. It is critical that patients know best-practice guidelines, and it is equally critical that medical professionals know whether their patients are following those guidelines. This paper includes a summary of recommendations published in the literature, and a pilot study to address a gap in the literature on determining how long, post-surgery, adolescents with idiopathic scoliosis waited before returning to various self-care and physical activities, and what factors influenced return to activities. We used a mixed-method approach that involved two phases: a questionnaire (n = 8), and subsequent interviews of some participants (n = 3). Participants were ages 14–17 (M = 15.4) and had had posterior instrumentation and fusion for scoliosis in the past 2 years.

Results
Some patients were cautious about return to activities, either because of emotional or medical reasons. However, in many instances, participants returned to physical activities earlier than was recommended, primarily for emotional and social reasons.
Combined immune checkpoint blockade and radiotherapy induces durable remission in relapsed natural killer/T-cell lymphoma: a case report and review of the literature
Authors: McGehee Elizabeth , Patel Hetalkumari , Pearson Caroline , Clements Keri , Jaso Jesse Manuel , Chen Weina , Callan Alexandra , Desai Neil , Ramakrishnan Geethakumari Praveen 
Published: April 2021

Abstract
Background
Extranodal natural killer/T-cell lymphoma is a rare, aggressive non-Hodgkin lymphoma that is treated upfront mostly with L-asparaginase containing regimens. Relapsed extranodal natural killer/T-cell lymphoma is associated with a poor prognosis, and there is no established standard of care.

Case presentation
We report the case of a 72 year-old white male with a distant extranasal relapse of extranodal natural killer/T-cell lymphoma that has been managed successfully with a combination of radiation and immune checkpoint blockade with pembrolizumab. Pseudoprogression with new skin and bone lesions on positron emission tomography imaging was encountered during this Caucasian patient’s immunotherapy and was successfully managed with supportive care and continuation of immune checkpoint blockade.

Conclusions
The patient has been in complete clinical, radiologic, and molecular remission for close to 3 years and has not had any immune-related adverse effects. Pseudoprogression is a clinical challenge that can be encountered while patients are treated with immunotherapy, and astute clinical acumen is needed for accurate management. We believe this is the longest duration of response to immune checkpoint blockade in relapsed extranodal natural killer/T-cell lymphoma reported to date in literature. There is a strong biologic rationale in combining radiation with immunotherapy. The optimal timing, dose, and duration of radiation combined with immunotherapy in extranodal natural killer/T-cell lymphoma need to be prospectively evaluated.
Filamentous tangles with nemaline rods in MYH2 myopathy: a novel phenotype
Authors: Madigan Nicolas N. , Polzin Michael J. , Cui Gaofeng , Liewluck Teerin , Alsharabati Mohammad H. , Klein Christopher J. , Windebank Anthony J. , Mer Georges , Milone Margherita 
Published: April 2021

AbstractThe MYH2 gene encodes the skeletal muscle myosin heavy chain IIA (MyHC-IIA) isoform, which is expressed in the fast twitch type 2A fibers. Autosomal dominant or recessive pathogenic variants in MYH2 lead to congenital myopathy clinically featured by ophthalmoparesis and predominantly proximal weakness. MYH2-myopathy is pathologically characterized by loss and atrophy of type 2A fibers. Additional myopathological abnormalities have included rimmed vacuoles containing small p62 positive inclusions, 15–20 nm tubulofilaments, minicores and dystrophic changes. We report an adult patient with late-pediatric onset MYH2-myopathy caused by two heterozygous pathogenic variants: c.3331C>T, p.Gln1111* predicted to result in truncation of the proximal tail region of MyHC-IIA, and c.1546T>G, p.Phe516Val, affecting a highly conserved amino acid within the highly conserved catalytic motor head relay loop. This missense variant is predicted to result in a less compact loop domain and in turn could affect the protein affinity state. The patient’s genotype is accompanied by a novel myopathological phenotype characterized by centralized large myofilamentous tangles associated with clusters of nemaline rods, and ring fibers, in addition to the previously reported rimmed vacuoles, paucity and atrophy of type 2A fibers. Electron microscopy demonstrated wide areas of disorganized myofibrils which were oriented in various planes of direction and entrapped multiple nemaline rods, as corresponding to the large tangles with rods seen on light microscopy. Nemaline rods were rarely observed also in nuclei. We speculate that the mutated MyHC-IIA may influence myofibril disorganization. While nemaline rods have been described in myopathies caused by pathogenic variants in genes encoding several sarcomeric proteins, to our knowledge, nemaline rods have not been previously described in MYH2-myopathy.
The effects of tobacco taxation and pricing on the prevalence of smoking in Africa
Authors: Immurana Mustapha , Boachie Micheal Kofi , Iddrisu Abdul-Aziz 
Published: April 2021

AbstractBackgroundTobacco use continues to kill millions of people globally, making it one of the major causes of preventable deaths. Notwithstanding, there has been a very marginal fall in the prevalence of tobacco smoking in Africa. Since taxes (hence prices) are part of the main measures suggested to decrease the demand for tobacco products, this study investigates how tobacco taxation and pricing influence the prevalence of smoking in 24 African countries.MethodsUsing panel data on 24 African countries sourced from the World Health Organization (WHO) and the World Bank databases for the period 2010 to 2016, this study employs the system Generalized Method of Moments (GMM) estimator to investigate the effects of tobacco taxation and pricing on the prevalence of smoking. The system GMM estimator is used due its ability to deal with potential endogeneity of tobacco taxation and pricing: the likelihood that the prevalence of smoking can influence tobacco taxation and pricing which may lead to biased estimates.ResultsTobacco taxation and pricing have negative significant effects on the prevalence of smoking among the selected countries after controlling for growth of Gross Domestic Product (GDP) per capita, urbanization, death rate and net inflows of Foreign Direct Investment (FDI). Specifically, a percentage increase in tobacco price is found to decrease the prevalence of smoking by between 0.11 to 0.14%, while a percentage increase in tobacco tax decreases the prevalence of smoking by between 0.25 to 0.36%, all at 1% level of significance.ConclusionSince tobacco taxation and pricing are found to have negative significant effects on the prevalence of smoking, the implication is that, their use can be intensified by African policy makers towards achieving the WHO Framework Convention on Tobacco Control (FCTC) recommended targets and hence decrease the prevalence of tobacco smoking in Africa. Doing so may therefore help in achieving the Sustainable Development Goal (SDG) 3.5 (prevention and treatment of substance abuse), thereby reducing the colossal number of smoking attributable deaths.
Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men
Authors: van der Spoel Evie , Roelfsema Ferdinand , van Heemst Diana 
Published: April 2021

AbstractObjectiveTo investigate the relationship between LH and testosterone (T), which characteristics associate with the strength of this relationship, and their interrelationships with GH, TSH, cortisol, and ACTH.DesignHormones were measured in serum samples collected every 10 minutes during 24 hours from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between 2 timeseries for all possible time shifts.ResultsMean (95% CI) maximal correlation was 0.21 (0.10-0.31) at lag time of 60 minutes between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared with men with no cross-correlation, lower fat mass (18.5 [14.9-19.7] vs. 22.3 [18.4-29.4] kg), waist circumference (93.6 [5.7] vs. 103.1 [12.0] cm), high-sensitivity C-reactive protein (0.7 [0.4-1.3] vs. 1.8 [0.8-12.3] mg/L), IL-6 (0.8 [0.6-1.0] vs. 1.2 [0.9-3.0] pg/mL), and 24-hour mean LH (4.3 [2.0] vs. 6.1 [1.5] U/L), and stronger LH-T feedforward synchrony (1.5 [0.3] vs. 1.9 [0.2]). Furthermore, T was positively cross-correlated with TSH (0.32 [0.21-0.43]), cortisol (0.26 [0.19-0.33]), and ACTH (0.26 [0.19-0.32]).ConclusionsLH is followed by T with a delay of 60 minutes in healthy older men. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, LH levels, and LH-T feedforward synchrony. We observed positive correlations between T and TSH, cortisol, and ACTH.
Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway
Authors: Wang Hui , Wang Chengdong , Long Qi , Zhang Yuan , Wang Meiling , Liu Jie , Qi Xufeng , Cai Dongqing , Lu Gang , Sun Jianmin , Yao Yong-Gang , Chan Wood Yee , Chan Wai Yee , Deng Yi , Zhao Hui 
Published: April 2021

ABSTRACT
The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.
A novel injury paradigm in the central nervous system of adult Drosophila: molecular, cellular and functional aspects
Authors: Losada-Pérez María , García-Guillén Nuria , Casas-Tintó Sergio 
Published: April 2021

ABSTRACT
The mammalian central nervous system (CNS) exhibits limited regenerative capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the study of long-term and short-term cellular responses, including those of the CNS and the immune system, and of any implications regarding functional recovery. We demonstrate for the first time that adult Drosophilamelanogaster glial cells undergo spontaneous functional recovery following crush injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here, we validate this model and analyse the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glial cells and macrophages contribute to functional regeneration through mechanisms involving the Jun N-terminal kinase (JNK) pathway and the Drosophila protein Draper (Drpr), characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for functional recovery. Further, we show that the proteins Grindelwald and Drpr in Drosophila glial cells mediate activation of JNK, and that expression of drpr is dependent on JNK activation. Finally, we link neuron-glial communication and the requirement of neuronal vesicular transport to regulation of the JNK pathway and functional recovery.
This article has an associated First Person interview with the first author of the paper.
Counseling at all contacts for postpartum contraceptive use: can paper-based tools help community health workers improve continuity of care? A qualitative study from Ethiopia
Authors: Mossie Muluneh Yigzaw , Pfitzer Anne , Yusuf Yousra , Wondimu China , Bazant Eva , Bansal Vaiddehi , Mackenzie Devon , Sitrin Deborah , Pleah Tsigue 
Published: April 2021

Background: Globally, there has been a resurgence of interest in postpartum family planning (PPFP) to advance reproductive health outcomes. Few programs have systematically utilized all contacts a woman and her baby have with the health system, from pregnancy through the first year postpartum, to promote PPFP. Nested into a larger study covering two districts, this study assessed the use, acceptability, and feasibility of tools for tracking women’s decision-making and use of PPFP in the community health system in Oromia region, Ethiopia. Community-level tracking tools included a modified Integrated Maternal and Child Health (IMCH) card with new PPFP content, and a newly developed tool for pregnant and postpartum women for use by Women Development Armies (WDAs). Proper completion of the tools was monitored during supervision visits. Methods: In-depth interviews and focus group discussions were conducted with health officials, health extension workers, and volunteers. A total of 34 audio-files were transcribed and translated into English, double-coded using MAXQDA, and analyzed using a thematic approach. Results: The results describe how HEWs used the modified IMCH card to track women’s decision making through the continuum of care, to assess pregnancy risk and to strengthen client-provider interaction. Supervision data demonstrated how well HEWs completed the modified IMCH card. The WDA tool was intended to promote PPFP and encourage multiple contacts with facilities from pregnancy to extended postpartum period. HEWs have reservations about the engagement of WDAs and their use of the WDA tool. Conclusions: To conclude, the IMCH card improves counseling practices through the continuum of care and is acceptable and feasible to apply. Some elements have been incorporated into a revised national tool and can serve as example for other low-income countries with similar community health systems. Further study is warranted to determine how to engage WDAs in promoting PPFP.
Addressing implementation considerations when developing universal interventions for speech, language and communication needs in the ordinary classroom: a protocol for a scoping review
Authors: Gallagher Aoife , Murphy Carol-Anne , Fitzgerald Johanna , Law James 
Published: April 2021

Background: Understanding the factors that influence the implementation of health interventions in the context of education is essential to improving outcomes for children and young people with speech and language needs (SLCN). Yet implementation considerations have not been adequately addressed when developing interventions for this context. The aim of this paper is to present a protocol for a scoping review of existing implementation frameworks that might guide SLCN intervention research in schools. Methods: In accordance with scoping review guidelines, the study will be conducted in six phases: (1) identification of the research question, (2) identification of potentially relevant studies of Implementation Science frameworks, (3) study screening and selection, (4) charting and extracting data from identified frameworks, (5) collating, summarising and reporting the results and (6) consultation with stakeholders. Two reviewers will conduct the screening and extraction stages independently. Identified frameworks will be collated, and described, and constructs from the IS frameworks will be categorised using domains from the Consolidated Framework for Implementation Research. A draft IS model will be proposed based on the findings of the scoping review. Conclusions: The findings of this review will provide guidance for researchers in addressing implementation considerations when developing universal interventions for SLCN in the ordinary classroom, and ultimately will contribute towards improving outcomes for this vulnerable childhood population.
Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review
Authors: Odhiambo Mercy , Kariuki Symon M. , Newton Charles R. 
Published: April 2021

Background: The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We conducted a systematic review to evaluate the extent of therapeutic drug monitoring (TDM) of ASM in LMIC, including purposes and methods used during monitoring. Methods: A search was conducted on four main databases (PubMed, Psych-Info, CINAHL and Embase), with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Descriptive statistics were used to pool median distribution of TDM across studies. Results: Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform. Conclusions: TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive TDM in LMICs that incorporates dose titration of ASM using pharmacokinetics and pharmacodynamics modelling, for both first generation and second generation ASMs.
Assigning Priorities (or Not) in Service Systems with Nonlinear Waiting Costs
Authors: Ouyang Huiyin , Taník Argon Nilay , Ziya Serhan 
Published: April 2021

For a queueing system with multiple customer types differing in service-time distributions and waiting costs, it is well known that the cµ-rule is optimal if costs for waiting are incurred linearly with time. In this paper, we seek to identify policies that minimize the long-run average cost under nonlinear waiting cost functions within the set of fixed priority policies that only use the type identities of customers independently of the system state. For a single-server queueing system with Poisson arrivals and two or more customer types, we first show that some form of the cµ-rule holds with the caveat that the indices are complex, depending on the arrival rate, higher moments of service time, and proportions of customer types. Under quadratic cost functions, we provide a set of conditions that determine whether to give priority to one type over the other or not to give priority but serve them according to first-come, first-served (FCFS). These conditions lead to useful insights into when strict (and fixed) priority policies should be preferred over FCFS and when they should be avoided. For example, we find that, when traffic is heavy, service times are highly variable, and the customer types are not heterogenous, so then prioritizing one type over the other (especially a proportionally dominant type) would be worse than not assigning any priority. By means of a numerical study, we generate further insights into more specific conditions under which fixed priority policies can be considered as an alternative to FCFS. This paper was accepted by Baris Ata, stochastic models and simulation.
Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks
Authors: Arnold David T. , Donald Charmaine , Lyon Max , Hamilton Fergus W. , Morley Anna J. , Attwood Marie , Dipper Alexandra , Barratt Shaney L. 
Published: April 2021

Introduction
Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up.

Methods
Prospective single centre observational study.

Results
Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml).

Conclusions
The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.