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This community service aims to increase teacher understanding and optimize the implementation of the Learning Management System (LMS) in the blended learning era. The method for implementing this service uses training in the form of webinars with 119 teachers spread across 40 cities in Indonesia. The evaluation instrument for this activity uses a questionnaire, which is analyzed descriptively. The results of this service activity show an increase in teachers' understanding of implementing LMS. The results are evidenced by teachers' increasing knowledge about making LMS an online classroom, especially in providing teaching materials and setting student assignments and exams.

Dalam dunia pendidikan saat ini, website sekolah merupakan suatu alat yang sangat penting dalam memberikan segala informasi kepada masyarakat seperti profil sekolah, prestasi, kegiatan akademik, alumni dan sebagainya. Objek penelitian dalam penelitian ini adalah Sekolah Menengah Atas berbasis Islam Al Irsyad yang berada di Surabaya, dimana telah memiliki website namun belum maksimal dalam penggunaannya sehari-hari karena jumlah pengunjung masih sedikit, tampilan dan fungsi-fungsi fitur dalam website kurang dapat dipahami pengguna. Berdasarkan hasil pengujian usability testing terlihat bahwa dua indikator yakni learnability dan memorability memiliki nilai yang rendah. Oleh sebab itu, tujuan studi ini adalah perancangan ulang desain website sekolah agar mudah diingat dan digunakan pengguna. Metode yang digunakan adalah User Centered Design karena selalu mengikutsertakan penggunanya dalam proses perancangan. Hasil penelitian menunjukkan total rata-rata keseluruhan indikator usability adalah 3.37, hal ini menunjukkan bahwa redesign website sekolah yang diuji berada pada rentang sangat baik, untuk indikator learnability dan memorability sendiri terjadi peningkatan yang signifikan. Kontribusi utama penelitian ini adalah penggunaan usability testing menjadi langkah awal evaluasi kegunaan website untuk meningkatkan antarmuka pengguna.

The process of ranking requirements in software development is made up of various criteria and numerous stakeholders, which are properly selected for the effective prioritisation of software requirements. These requirements have encountered several challenges, including lack of scalability, complexity of pairwise comparisons and biases due to the cognitive load on stakeholders. Therefore, this research aimed to investigate and find solutions to improve the software prioritisation process using the Reprocolla model. The model was built by weighing the criteria in terms of benefits, opportunities, costs, and risks (BOCR) classification, which were then calculated using the fuzzy analytic hierarchy process (FAHP) method. Furthermore, the selection of alternatives was computed using the fuzzy technique for order preference using the similarity to an ideal solution (FTOPSIS) method. The success of Reprocolla was evaluated using seven datasets based on real projects and compared with the two existing methods for prioritising requirements, FAHP and FTOPSIS. The experiment results used inferential and descriptive statistics approaches with three indicators: accuracy, time consumption, and ease of use. Based on the three indicators mentioned above, the inferential statistics showed no significant difference between the perspectives of clients and developers. Whereas, descriptive statistics found that Reprocolla is more accurate, consumes less time, and has the highest ease of use percentage. The result showed that as stakeholders’ satisfaction level increases, the software development process becomes more accurate, thereby leading to a decrease in time consumption and a rise in ease of usage. The result also showed that the development of the Reprocolla tool, a collaboration between humans and machines, enhanced the effectiveness of the requirements prioritisation process.

Fumigation website is a website owned by PT. Prana Argentum which is used as a platform for disseminating information related to pest control. However, based on interviews with company owners, there are some drawbacks such as the appearance of the website is not very user friendly, the information provided is difficult to find. This is also supported by the results of the UEQ pre-survey of website users, where the results of the 6 UEQ scale get the "bad" criterion, which means the low usability value of the website. This study aims to determine the suitability of the company's website in improving customer experience. To overcome the display problems on the website, a solution is needed, namely redesigning the UI/UX design using the double diamond methodology and usability testing along with UEQ. The result of this research is a redesign of the UI/UX design by adding new features such as a price quote feature, an appointment feature, and a transaction feature. To improve the customer experience, researchers also pay attention to the use of colors, fonts, language styles, to user-friendly navigation flows. In this study, two types of tests were carried out, namely usability testing with the Maze tools and UEQ testing. The usability testing results obtained a usability score of 87 which can be said to be good in terms of its usability value. Based on the results of the UEQ test, it is known that there is an increase in the mean value on all UEQ scales. It is proved that the highest mean value is on the perspicuity scale of 2.09 points and the lowest value is on the novelty scale with a value of 1.53 points. the results of the UI/UX website design of PT. Prana Argentum Corporation is classified as good, proper, and acceptable to users.

This research aims to analyze the application of discovery learning to physics learning during the COVID-19 pandemic. This research method is a study of literature and journals, as many as ten journals that can be accounted for related to the application of discovery learning research models to physics learning during the COVID-19 pandemic in Indonesia. The study was analyzed using qualitative descriptive analysis with paper review technique. It was concluded that: 1) The application of the discovery learning model to physics learning during the COVID-19 pandemic can improve student understanding, students’ critical thinking ability, and mastery of student concepts. 2) The use of online learning tools and discovery learning-based e-modules can improve students’ mastery of concepts in physics learning during the COVID-19 pandemic. 3) The advantages of the discovery learning model in physics learning during the COVID-19 pandemic are that it can improve cognitive abilities and form students’ disciplined and positive attitudes. 4) The flexibility of the discovery learning model in physics learning during the COVID-19 pandemic is that students have difficulty understanding the material, and teachers find it difficult to present the material, so the application of the discovery learning model in physics learning during the COVID-19 pandemic in Indonesia is not all effective.

Polyhydroxyalkanoate (PHA) is a microbial storage polymer that is naturally produced by certain bacteria. This is the first study on the ability of this particular species Massilia haematophila to synthesize a PHA copolymer containing 3-hydroxyvalerate (3HV) monomer. Using the statistical design on Massilia haematophila UMTKB-2, this study highlights the optimization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), P(3HB-co-3HV), copolymer production for shaken-flask cultivation. Moreover, the mechanical and thermal features of the polymers were determined. The production of P(3HB-co-3HV) by Massilia haematophila UMTKB-2 using optimal conditions provided by response surface methodology (RSM) yielded 5.0 g/l of P(3HB-co-7 mol% 3HV), which was higher than the value obtained from unoptimized conditions such as 4.40 g/l of P(3HB-co-4mol% 3HV). This result showed a 14% increase in copolymer concentration and a two-fold increase in 3HV composition. In this study, the P(3HB-co-3HV) synthesized was determined as a block copolymer and its thermal properties were better than P(3HB). Using RSM, the optimization conditions were successfully obtained for this bacterium, and this result is a starting platform for additional studies of a larger scaled PHA production from Massilia haematophila UMTKB-2 using bioreactors.

Spinal cord injury (SCI) results in the development of chronic pain syndromes that can persist indefinitely and cause reductions in quality of life. Treatment of chronic pain after SCI remains extremely challenging; thus, an important research goal is to determine whether early treatments can attenuate the subsequent development of pain conditions. The current study examined the hypothesis that early administration of the microglial-inhibiting drug minocycline could ameliorate the development of pain after SCI. Adult male Sprague-Dawley rats underwent SCI at the ninth thoracic spinal segment and received either vehicle or minocycline treatment for 5 days postinjury. Time course studies revealed that over 4 weeks post- SCI, microglial activation in vehicle-treated animals was progressively increased. Minocycline treatment resulted in reduction, but not prevention, of microglial activation over time. Electrophysiological experiments showed that early minocycline administration attenuated the development of chronic hyperresponsiveness of lumbar dorsal horn neurons. Similarly, behavioral assessment showed that minocycline also resulted in increased pain thresholds. These results suggest that inhibition of early neuroimmune events can have a powerful impact on the development of long-term pain phenomena following SCI and support the conclusion that modulation of microglial signaling may provide a new therapeutic strategy for patients suffering from post-SCI pain. [ABSTRACT FROM AUTHOR]

Abstract Background Substitute decision-makers are integral to the care of dying patients and make many healthcare decisions for patients. Unfortunately, conflict between physicians and surrogate decision-makers is not uncommon in end-of-life care and this could contribute to a “bad death” experience for the patient and family. We aim to describe Canadian family physicians’ experiences of conflict with substitute decision-makers of dying patients to identify factors that may facilitate or hinder the end-of-life decision-making process. This insight will help determine how to best manage these complex situations, ultimately improving the overall care of dying patients. Methods Grounded Theory methodology was used with semi-structured interviews of family physicians in Edmonton, Canada, who experienced conflict with substitute decision-makers of dying patients. Purposeful sampling included maximum variation and theoretical sampling strategies. Interviews were audio-taped, and transcribed verbatim. Transcripts, field notes and memos were coded using the constant-comparative method to identify key concepts until saturation was achieved and a theoretical framework emerged. Results Eleven family physicians with a range of 3 to 40 years in clinical practice participated. The family physicians expressed a desire to achieve a “good death” and described their role in positively influencing the experience of death. Finding Common Ground to Achieve a “Good Death” for the Patient emerged as an important process which includes 1) Building Mutual Trust and Rapport through identifying key players and delivering manageable amounts of information, 2) Understanding One Another through active listening and ultimately, and 3) Making Informed, Shared Decisions. Facilitators and barriers to achieving Common Ground were identified. Barriers were linked to conflict. The inability to resolve an overt conflict may lead to an impasse at any point. A process for Resolving an Impasse is described. Conclusions A novel framework for developing Common Ground to manage conflicts during end-of-life decision-making discussions may assist in achieving a “good death”. These results could aid in educating physicians, learners, and the public on how to achieve productive collaborative relationships during end-of-life decision-making for dying patients, and ultimately improve their deaths.

Hyperreflexia associated with spasticity is a prevalent neurological condition characterized by excessive and exaggerated reflex responses to stimuli. Hyperreflexia can be caused by several diseases including multiple sclerosis, stroke and spinal cord injury (SCI). Although we have previously identified the contribution of the RAC1-PAK1 pathway underlying spinal hyperreflexia with SCI-induced spasticity, a feasible druggable target has not been validated. To assess the utility of targeting PAK1 to attenuate H-reflex hyperexcitability, we administered Romidepsin, a clinically available PAK1 inhibitor, in Thy1-YFP reporter mice. We performed longitudinal EMG studies with a study design that allowed us to assess pathological H-reflex changes and drug intervention effects over time, before and after contusive SCI. As expected, our results show a significant loss of rate-dependent depression - an indication of hyperreflexia and spasticity - 1 month following SCI as compared with baseline, uninjured controls (or before injury). Romidepsin treatment reduced signs of hyperreflexia in comparison with control cohorts and in pre- and post-drug intervention in SCI animals. Neuroanatomical study further confirmed drug response, as romidepsin treatment also reduced the presence of SCI-induced dendritic spine dysgenesis on α-motor neurons. Taken together, our findings extend previous work demonstrating the utility of targeting PAK1 activity in SCI-induced spasticity and support the novel use of romidepsin as an effective tool for managing spasticity. KEY POINTS: PAK1 plays a role in contributing to the development of spinal cord injury (SCI)-induced spasticity by contributing to dendritic spine dysgenesis. In this study, we explored the preclinical utility of inhibiting PAK1 to reduce spasticity and dendritic spine dysgenesis in an SCI mouse model. Romidepsin is a PAK1 inhibitor approved in the US in 2009 for the treatment of cutaneous T-cell lymphoma. Here we show that romidepsin treatment after SCI reduced SCI-induced H-reflex hyperexcitability and abnormal α-motor neuron spine morphology. This study provides compelling evidence that romidepsin may be a promising therapeutic approach for attenuating SCI-induced spasticity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Introduction: Childhood cancer survivors (CCS) are at risk of experiencing psychological distress years after completing cancer treatments. We aimed to assess the prevalence and associated risk factors affecting psychological distress and health-related quality of life (HRQOL) among CCS in Singapore, and compare with their siblings without a history of or existing cancer as control., Method: We recruited 143 young adult CCS aged ≥18 years attending survivorship clinics at KK Women's and Children's Hospital in Singapore who were in remission for ≥5 years and treatment-free for ≥2 years, and 57 siblings. CCS and siblings were matched at a 1:1 ratio based on sociodemographic factors yielding 46 pairs for comparison. Among CCS participants, 79 (55.2%) were male, 86 (60.1%) had leukaemia, 29 (20.3%) had solid tumours, 15 (10.5%) had lymphoma and 13 (9.1%) had brain tumours. All participants completed the Brief Symptom Inventory-18 (BSI-18) and Medical Outcomes Short Form-36 (MOS SF-36) questionnaires from August 2021 to July 2022., Results: There were 35 (24.5%) CCS who reported psychological distress in the BSI-18 Global Severity Index. Five (3.5%) and 31 (21.7%) CCS reported low HRQOL in the physical and mental composite scores, respectively. Mean scores between CCS and their siblings were not statistically significant across all domains of the BSI-18 and MOS SF-36. Associated risk factors for psychological distress and low HRQOL among CCS were history of psychiatric illness after cancer diagnosis and mood affected by the COVID-19 pandemic., Conclusion: CCS reported significant psychological distress and low HRQOL although they were not statistically different from their siblings. A holistic and risk factor-centric follow-up programme can aid early detection and mitigation of psychological late effects for CCS and their families.

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Neuropathic pain is a debilitating form of pain arising from injury or disease of the nervous system that affects millions of people worldwide. Despite its prevalence, the underlying mechanisms of neuropathic pain are still not fully understood. Dendritic spines are small protrusions on the surface of neurons that play an important role in synaptic transmission. Recent studies have shown that dendritic spines reorganize in the superficial and deeper laminae of the spinal cord dorsal horn with the development of neuropathic pain in multiple models of disease or injury. Given the importance of dendritic spines in synaptic transmission, it is possible that studying dendritic spines could lead to new therapeutic approaches for managing intractable pain. In this review article, we highlight the emergent role of dendritic spines in neuropathic pain, as well as discuss the potential for studying dendritic spines for the development of new therapeutics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants., Methods: In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7-12 months of age., Results: Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs . 96.9%), clinical relapse (19.5 vs . 14.3%), or retreatment (12.6 vs . 10.1%) (all p  > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs . 2.1%; p  = 0.464) and 10 times (0.5 vs . 0%; p  = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity., Conclusions: PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment., Impact and Implications: In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants., Competing Interests: MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, and Roche, and is an advisory board member of and/or received research funding from AbbVie, Aligos Therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, and Roche. WKS received speaker’s fees from AstraZeneca; is an advisory board member of and received speaker’s fees from Abbott; received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer, and Ribo Life Science; and is an advisory board member of and received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Authors.)

Spasticity is a hyperexcitability disorder that adversely impacts functional recovery and rehabilitative efforts after spinal cord injury (SCI). The loss of evoked rate-dependent depression (RDD) of the monosynaptic H-reflex is indicative of hyperreflexia, a physiological sign of spasticity. Given the intimate relationship between astrocytes and neurons, that is, the tripartite synapse, we hypothesized that astrocytes might have a significant role in post-injury hyperreflexia and plasticity of neighboring neuronal synaptic dendritic spines. Here, we investigated the effect of selective Rac1KO in astrocytes (i.e., adult male and female mice, transgenic cre-flox system) on SCI-induced spasticity. Three weeks after a mild contusion SCI, control Rac1 wt animals displayed a loss of H-reflex RDD, that is, hyperreflexia. In contrast, transgenic animals with astrocytic Rac1KO demonstrated near-normal H-reflex RDD similar to pre-injury levels. Reduced hyperreflexia in astrocytic Rac1KO animals was accompanied by a loss of thin-shaped dendritic spine density on α-motor neurons in the ventral horn. In SCI-Rac1 wt animals, as expected, we observed the development of dendritic spine dysgenesis on α-motor neurons associated with spasticity. As compared with WT animals, SCI animals with astrocytic Rac1KO expressed increased levels of the glial-specific glutamate transporter, glutamate transporter-1 in the ventral spinal cord, potentially enhancing glutamate clearance from the synaptic cleft and reducing hyperreflexia in astrocytic Rac1KO animals. Taken together, our findings show for the first time that Rac1 activity in astrocytes can contribute to hyperreflexia underlying spasticity following SCI. These results reveal an opportunity to target cell-specific molecular regulators of H-reflex excitability to manage spasticity after SCI. Significance Statement Spinal cord injury leads to stretch reflex hyperexcitability, which underlies the clinical symptom of spasticity. This study shows for the first time that astrocytic Rac1 contributes to the development of hyperreflexia after SCI. Specifically, astrocytic Rac1KO reduced SCI-related H-reflex hyperexcitability, decreased dendritic spine dysgenesis on α-motor neurons, and elevated the expression of the astrocytic glutamate transporter-1 (GLT-1). Overall, this study supports a distinct role for astrocytic Rac1 signaling within the spinal reflex circuit and the development of SCI-related spasticity., (Copyright © 2023 the authors.)

The SARS-CoV-2 pandemic resulted in approximately 7 million deaths and impacted 767 million individuals globally, primarily through infections. Acknowledging the impactful influence of sedentary behaviors, particularly exacerbated by COVID-19 restrictions, a substantial body of research has emerged, utilizing wearable sensor technologies to assess these behaviors. This comprehensive review aims to establish a framework encompassing recent studies concerning wearable sensor applications to measure sedentary behavior parameters during the COVID-19 pandemic, spanning December 2019 to December 2022. After examining 582 articles, 7 were selected for inclusion. While most studies displayed effective reporting standards and adept use of wearable device data for their specific research aims, our inquiry revealed deficiencies in apparatus accuracy documentation and study methodology harmonization. Despite methodological variations, diverse metrics, and the absence of thorough device accuracy assessments, integrating wearables within the pandemic context offers a promising avenue for objective measurements and strategies against sedentary behaviors.

Spasticity is a chronic neurological complication associated with spinal cord injury (SCI), characterized by increased muscle tone and stiffness. A physiological sign of spasticity is hyperreflexia, evident by the loss of evoked rate-dependent depression (RDD) in the H-reflex. Although previous work has shown that SCI-induced astrogliosis contributes to hyperexcitability disorders, including neuropathic pain and spasticity, it is unclear how reactive astrocytes can modulate synaptic transmission within the injured spinal cord. To study astrocytes' role in post-SCI hyperreflexia, we examined glutamate transporter-1 (GLT-1) and postsynaptic density protein 95 (PSD-95) proteins in astrocytes and neurons, respectively, within the ventral horn (lamina IX) below the level of injury (spinal segment L4-5). The close juxtaposition of GLT-1 and PSD-95 markers is a molecular correlate of tripartite synapses and is thought to be a key element in the astrocyte-induced plasticity of neuronal synapses. Our study compared animals with and without SCI-induced hyperreflexia and spasticity and investigated potential synaptic abnormalities associated with astrocyte involvement. As expected, 4 wk after SCI, we observed a loss in evoked H-reflex RDD in hindlimb electromyogram recordings, i.e., hyperreflexia, in contrast to uninjured sham. Importantly, our main findings show a significant increase in the presence of GLT-1-PSD-95 tripartite synapses in the ventral spinal cord motor regions of animals exhibiting SCI-induced hyperreflexia. Taken together, our study suggests the involvement of astrocyte-neuron synaptic complexes in the plasticity-driven progression of chronic spasticity. NEW & NOTEWORTHY The role of astrocytes in H-reflex hyperexcitability following SCI remains understudied. Our findings establish a relationship between GLT-1 expression, its proximity to neuronal PSD-95 in the spinal cord ventral horn, and the loss of H-reflex RDD, i.e., hyperreflexia. Our findings provide a new perspective on synaptic alterations and the development of SCI-related spasticity.

Detection of viable viruses in the air is critical in order to determine the level of risk associated with the airborne diffusion of viruses. Different methods have been developed for the isolation, purification, and detection of viable airborne viruses, but they require an extensive processing time and often present limitations including low physical efficiency (i.e., the amount of collected viruses), low biological efficiency (i.e., the number of viable viruses), or a combination of all. To mitigate such limitations, we have employed an efficient technique based on the magnetic levitation (Maglev) technique with a paramagnetic solution and successfully identified distinct variations in levitation and density characteristics among bacteria ( Escherichia coli ), phages (MS2), and human viruses (SARS-CoV-2 and influenza H1N1). Notably, the Maglev approach enabled a significant enrichment of viable airborne viruses in air samples. Furthermore, the enriched viruses obtained through Maglev exhibited high purity, rendering them suitable for direct utilization in subsequent analyses such as reverse transcription-polymerase chain reaction (RT-PCR) or colorimetric assays. The system is portable, easy to use, and cost-efficient and can potentially provide proactive surveillance data for monitoring future outbreaks of airborne infectious diseases and allow for the induction of various preventative and mitigative measures.

Purpose: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m 2 of anthracyclines., Patients and Methods: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m 2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts., Results: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively ( P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% ( P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively ( P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004)., Conclusion: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.

Asparaginase is a critical component of therapy for childhood acute lymphoblastic leukemia (ALL), but it is commonly associated with allergy, which results in morbidity and poorer outcomes. The underlying basis of this allergy is undoubtedly immune-mediated, but the exact components of T-cell immunity have yet to be characterized. We performed longitudinal TCR sequencing of 180 bone marrow samples from 67 children with B-ALL treated as part of the Ma-Spore-ALL-2010 trial, and we evaluated the associations of TCR profile with asparaginase hypersensitivity, with functional validation of asparaginase activity in a separate cohort of 113 children. We found that a more diverse and dynamically changing TCR repertoire was associated with increased risk of clinical hypersensitivity and decreased L-asp activity. Allergic patients had a higher proportion of infrequent clonotypes, as well as a significantly lower degree of shared clonotypes amongst the cohort. Allergic patients also had significantly higher longitudinal variability of clonotypes across timepoints, where a higher dissimilarity between diagnosis and week 5 represented an 8.1-fold increased risk of an allergic event. After an allergy had occurred, there was shaping and convergence of the TCR repertoire towards a common antigen. Understanding the immunological basis of T-cell responses in allergy lays the groundwork for developing predictive biomarkers or strategies to mediate this common toxicity in childhood ALL.

In Kendo, there is no consensus as to which hand should produce more pressure when attacking the opponent with the bamboo sword, let alone how to teach the pressure distribution during coaching. There is the theory that a Kendo attack can be divided into five phases, which has not entered the coaching practice, either. The aim of this study was to measure the grip pressure during Kendo attacks, investigate the pressure distribution between the two hands, and find evidence for the existence of the alleged five attack phases. We instrumented a bamboo sword with grip pressure sensors and investigated the grip pressure in 23 participants. In all attack targets and in both hands, the pressure across all attack phases was significantly different. In general, the left-hand pressure was consistently and significantly higher than the right-hand one, across all five attack phases, for the hand, head, and flank attack targets. The surprising exception was the throat target with only two attack phases, the strike phase of which showed a greater pressure in the right hand. Across all participants, the left-hand pressure was greater in 60.22-100% in any phase of the four attack targets, except for the strike phase of the throat target. Through these results, we could verify the effect of the teaching customs in Kendo, as well as provide first-time evidence of the existence of the five attack phases.

Background: When a country introduces different COVID-19 control measures over time, it is important to identify the specific measure that was effective and therefore responsible for "flattening the curve". This information helps policymakers find the right decision and saves the economy by avoiding severe yet ineffective measures., Objective: This paper aims to fill the literature gap by investigating two regions that introduced two or three consecutive measures during the second COVID-19 wave, namely Austria and Victoria., Method: We calculated the first derivative (acceleration) of the filtered daily case data and identified the date of the start and end of the acceleration's major downturn (effective phase) relative to the date when the control measures were introduced (Austria: soft/hard lockdowns; Victoria: stages 3/4 lockdowns, mask order)., Results: In Austria, the effective phase started 5 days after the introduction of the soft lockdown and ended at the start of the hard lockdown. In Victoria, the effective phase started 19 days after the introduction of the stage 3 lockdown, 5 days after the introduction of the mask order, and ended 6 days after the start of the stage 4 lockdown., Conclusion: Considering that the effect of control measures is expected the earliest one serial interval after their introduction, the control measure responsible for "flattening the curve" was the soft lockdown in Austria and the mask mandate in Victoria. The severe lockdowns in both regions were ineffective., (© 2022. The Author(s).)

Aim: Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening infection risk prediction model that would allow remote rapid triage of patients to reduce time to first dose of antibiotics and sepsis-related mortality., Methods: A retrospective analysis of 2068 fever episodes during ALL therapy was used for model building and subsequent internal validation., Results: Three hundred and seventy-seven patients were treated for ALL in two institutions with comparable critical and supportive care resources. A total of 55 patients accounted for 71 admissions to the critical care unit for sepsis that led to eight septic deaths during a 16-year study period. A retrospective analysis of risk factors for sepsis enabled us to build a model focused on 13 variables that discriminated admissions requiring critical care well: area under the receiver operating characteristic curve of .82; 95% CI .76-.87, p<.001, and Brier score of .033. Significant univariate predictors included neutropenia, presence of symptoms of abdominal pain, diarrhea, fever during induction or steroid-based phases, and the lack of any localizing source of infection at time of presentation., Conclusion: We have developed a risk prediction model that can reliably identify ALL patients undergoing treatment who are at a higher risk of life-threatening sepsis. Clinical applicability can potentially be extended to low-middle income settings, and its utility should be further studied in real-world settings., (© 2022 John Wiley & Sons Australia, Ltd.)

Objective: This pilot study aimed to determine the proportions, level of knowledge, anxiety and confidence of foreign domestic workers (FDWs) who were involved in supporting the healthcare needs of older persons with long-term non-communicable diseases., Design: The pilot study used a cross-sectional and descriptive design.FDWs who accompanied the older adults attending a primary healthcare setting in Singapore. 100 eligible FDWs' demographic data, knowledge and confidence level of caregiving in food preparation, medication supervision, exercise, blood pressure (BP), blood glucose (BG) monitoring and anxiety level assessed by the Generalised Anxiety Disorder-7 scale were recorded. Descriptive statistics were performed and presented. Items on confidence were regrouped into two groups of 'very' versus 'no/a little/moderate'. Knowledge scores and caregiving tasks were assessed with items on confidence using Mann-Whitney U test and χ 2 test, respectively., Results: The FDWs were from Indonesia (60%), Philippines (23%) and Myanmar (14%). Their mean age was 33 years with an average of 5.8 years working experience; 62% self-reported previous caregiver training for elderly. The mean age of care-recipients was 81 years. Knowledge of FDWs on BP and BG monitoring was low (<50% answered correctly). Among the 55 FDWs who were required to perform BP monitoring, 45.5% lack confidence. Similarly, 40% of the 30 FDWs were not confident in performing BG monitoring. Those with very high confidence levels had higher knowledge on BP and BG monitoring. Of those who were involved in medication supervision (n=86), 36% lacked confidence. The majority of the FDWs (96%) were not affected by anxiety in managing these healthcare tasks for older persons., Conclusion: More than half of the FDWs supported healthcare needs of older persons but they had inadequate knowledge and lacked confidence in performing the healthcare-related tasks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Racial and ethnic disparities persist in the incidence and treatment outcomes of childhood acute lymphoblastic leukemia (ALL). However, there is a paucity of data describing the genetic basis of these disparities, especially in association with modern ALL molecular taxonomy and in the context of contemporary treatment regimens., Objective: To evaluate the association of genetic ancestry with childhood ALL molecular subtypes and outcomes of modern ALL therapy., Design, Setting, and Participants: This multinational, multicenter genetic association study was conducted from March 1, 2000, to November 20, 2020, among 2428 children and adolescents with ALL enrolled in frontline trials from the United States, South East Asia (Singapore and Malaysia), and Latin America (Guatemala), representing diverse populations of European, African, Native American, East Asian, and South Asian descent. Statistical analysis was conducted from February 3, 2020, to April 19, 2021., Main Outcomes and Measures: Molecular subtypes of ALL and genetic ancestry were comprehensively characterized by performing RNA sequencing. Associations of genetic ancestries with ALL molecular subtypes and treatment outcomes were then evaluated., Results: Among the participants in the study, 1340 of 2318 (57.8%) were male, and the mean (SD) age was 7.8 (5.3) years. Of 21 ALL subtypes identified, 8 were associated with ancestry. East Asian ancestry was positively associated with the frequency of somatic DUX4 (odds ratio [OR], 1.30 [95% CI, 1.16-1.45]; P < .001) and ZNF384 (OR, 1.40 [95% CI, 1.18-1.66]; P < .001) gene rearrangements and negatively associated with BCR-ABL1-like ALL (OR, 0.79 [95% CI, 0.66-0.92]; P = .002) and T-cell ALL (OR, 0.80 [95% CI, 0.71-0.90]; P < .001). By contrast, occurrence of CRLF2 rearrangements was associated with Native American ancestry (OR, 1.48 [95% CI, 1.29-1.69]; P < .001). When the percentage of Native American ancestry increased, ETV6-RUNX1 fusion became less frequent (OR, 0.80 [95% CI, 0.70-0.91]; P < .001), with the opposite trend observed for ETV6-RUNX1-like ALL. There was a marked preponderance of T-cell ALL in children of African descent compared with those with a high percentage of Native American ancestry (African: OR, 1.22 [95% CI, 1.07-1.37]; P = .003; Native American: OR, 0.53 [95% CI, 0.40-0.67]; P < .001). African ancestry was also positively associated with the prevalence of TCF3-PBX1 (OR, 1.49 [95% CI, 1.25-1.76]; P < .001) and negatively associated with DUX4 rearrangements (OR, 0.70 [95% CI, 0.48-0.93]; P = .01) and hyperdiploidy (OR, 0.77 [95% CI, 0.68-0.86]; P < .001). African and Native American ancestries as continuous variables were both associated with poorer event-free survival (for every 25% increase in ancestry: hazard ratio [HR], 1.2; 95% CI, 1.1-1.4; P = .001 for African ancestry; HR, 1.3; 95% CI, 1.0-1.6; P = .04 for Native American ancestry) and overall survival (for every 25% increase in ancestry: HR, 1.2; 95% CI, 1.1-1.5; P = .01 for African ancestry; HR, 1.4; 95% CI, 1.0-1.8; P = .03 for Native American ancestry). Even after adjusting for biological subtypes and clinical features, Native American and African ancestries remained associated with poor prognosis., Conclusions and Relevance: This study suggests that ALL molecular subtypes and prognosis are associated with genetic ancestry, potentially pointing to a genetic basis for some of the racial and ethnic disparities in ALL. Therefore, molecular subtype-driven treatment individualization is needed to help address racial and ethnic gaps in outcomes.

Spasticity is a disabling characteristic of neurological disorders, described by a velocity-dependent increase in muscle tone during passive stretch. During the last few years, many studies have been carried out to assess spasticity using wearable IMU (inertial measurements unit) sensors. This review aims to provide an updated framework of the current research on IMUs wearable sensors in people living with spasticity in recent studies published between 2017 and 2021. A total of 322 articles were screened, then finally 10 articles were selected. Results show the lack of homogenization of study procedures and missing apparatus information in some studies. Still, most studies performed adequately on measures of reporting and found that IMUs wearable data was successful in their respective purposes and goals. As IMUs estimate translational and rotational body motions, we believe there is a strong potential for these applications to estimate velocity-dependent exaggeration of stretch reflexes and spasticity-related characteristics in spasticity. This review also proposes new directions of research that should be challenged by larger study groups and could be of interest to both researchers as well as clinicians. The use of IMUs to evaluate spasticity is a promising avenue to provide an objective measurement as compared to non-instrumented traditional assessments.

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.

Background: Gait symmetry is used to measure pathological gait but is usually applied to unilateral pathology. This study aims to investigate bilateral impairment using existing and new gait symmetry methods., Methods: 15 healthy volunteers and 14 people with diabetes and distal symmetrical polyneuropathy participated in this study. Three temporal parameters (combined step, stance phase and double stance), expressed as a percentage, were extracted for comparing gait symmetry between healthy volunteers and patients using in-shoe measurements (Pedar-X). Three indices were calculated, including the widely used Symmetry Index; the well-established Variability Index; and the newly developed Laterality Index, that calculates how well distributed a condition is across both legs., Findings: In all three parameters, Symmetry and Variability Index proved to be significantly greater in the diabetic cohort (p-values range < 0.001-0.0226). The Laterality Index was significantly greater in the diabetic cohort for the stance and double stance phases (p-values 0.03 and < 0.001), but not for the combined step (p-value 0.3953). In both cohorts, Laterality Index <1 (fractional laterality) was associated with small Symmetry Index data, whereas in large Symmetry Index data, the Laterality Index was 1 (unilateral condition)., Interpretations: Gait symmetry and variability are useful tools for quantifying locomotion and the effects of aging and diseases. We have shown the ability of these two indices in differentiating two extreme groups of individuals. For cases with small Symmetry Index, the current method of using an arbitrary value is not ideal. The newly developed Laterality Index can be used to decide on the cut-off between symmetrical and asymmetrical gait., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Smoking is a health hazard. Current smoking cessation measures such as behavioral change counselling by trained professionals, nicotine replacement therapy and medications have limited success. Smoking intensity is assessed using a portable device to measure the smokers' exhaled breath carbon monoxide (eCO) level. A systematic review suggests the potential of serious gaming to increase smoking quit rate. However, the related studies were unable to explain and determine the effect gamification on smoking cessation. A handy personalized eCO measurement device linked to a smart-phone applications (app) has been developed (integrated STEADES-2 system). This novel system incorporates app-based video and print learning resources, authentication function and gamification using the eCO data as game element. Trained multidisciplinary healthcare professionals access the STEADES-2 data to monitor smoking status and support smokers via asynchronous virtual coaching. The pilot randomized controlled trial will enroll 20 smokers to use the STEADES-2 system (intervention group) and another 20 to the existing smoking cessation programme (control group) in primary care. The primary feasibility outcomes will include the recruitment response rate, the smokers' usability of the STEADES-2 system, their self eCO monitoring, frequencies of participation in the serious games and interactions with their virtual coaches. Their smoking literacy, utility and experience of the STEADES-2 system are other outcomes. Smokers in both groups will be compared on their cigarette abstinence as secondary outcome based on eCO levels and urine cotinine test (primary outcomes after 12 weeks). The results will be disseminated via conferences and publications., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. N. C. Tan reports funding by the Clinician Innovator Development Award by the National Medical Research Council of Singapore (grant number MOH-CIA18Nov-0002), related to the current work, and support from SingHealth Polyclinics for participation in the International Shared Decision Making Conference in Quebec, Canada, in July 2019., (© 2021 Tan N. C. et al.)

Purpose: Complete upfront resection of pediatric gastrointestinal lymphomas is recommended over biopsy whenever feasible, but either approach may have adverse sequelae. We sought to compare gastrointestinal and oncological outcomes of pediatric gastrointestinal lymphomas who underwent attempted upfront resection or biopsy of the presenting bowel mass., Methods: We retrospectively reviewed charts of children with gastrointestinal lymphomas treated on LMB89 and LMB96 protocols from 2000 to 2019 who underwent upfront gastrointestinal surgery, and compared resection and biopsy groups., Results: Of 33 children with abdominal lymphomas, 20 had upfront gastrointestinal surgery-10 each had resection or biopsy. Patients with attempted upfront resections had fewer postoperative gastrointestinal complications compared to biopsies (10% vs. 60%, p = 0.057), but longer time to chemotherapy initiation (median 11.5 vs. 4.5 days, p < 0.001). Three resection patients were surgically down-staged. Second surgeries were required in 30% and 40% of resected and biopsied patients, respectively, at median 4.6 months. Survival was similar in both groups, but better in patients on LMB96 protocol and stage II/III disease., Conclusions: Children with upfront attempted resection had low rates of surgical down-staging, greater delay in chemotherapy initiation, but fewer gastrointestinal complications and subsequent surgeries than biopsies. Survival was similar regardless of upfront surgery, likely reflecting beneficial effects of newer protocols.

Introduction: Transfusion-dependent thalassaemia is associated with complications related to iron overload from frequent red cell transfusions which affect quality of life. We collected data on the clinical outcomes, complications, socioeconomic status and health-related quality of life (HRQoL) of transfusion-dependent thalassaemia patients in Singapore, and analysed the associations between clinical and socioeconomic factors with development of transfusion-related complications and HRQoL scores., Materials and Methods: This was a cross-sectional study of transfusion-dependent thalassaemia patients treated at four major public hospitals in Singapore. Clinical information was obtained from retrospective reviews of medical records. Socioeconomic data and patient-reported compliance to iron chelators were obtained from prospective interviews of patients or caregivers using a questionnaire. A validated, disease-specific HRQoL instrument, the TranQOL, was administered to patients and caregivers during a routine clinic or transfusion visit., Results: Liver iron loading was the most common transfusion-related complication and occurred in 79% of patients. Cardiac iron loading was noted in 28.3% and endocrine complications were present in 34.2%. Liver iron loading was significantly associated with higher mean ferritin level. Cardiac iron loading was significantly associated with increasing age, higher mean ferritin level and type of iron chelator. Endocrine complications were associated with increasing age, higher mean ferritin level, type of iron chelator and poorer patient-reported compliance to iron chelators. The lowest TranQOL scores were reported by caregiver parents of patients aged less than 18 years. Lower TranQOL scores were significantly associated with increasing age, especially in the 31-50 age cohort, and with reception of social assistance., Conclusion: The main morbidities noted in transfusion-dependent thalassaemia patients in Singapore are from complications associated with iron loading. The cohort of older thalassaemia patients aged 31-50 experienced significantly higher rates of cardiac iron loading, endocrine complications and lower TranQOL scores compared to younger age cohorts., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 16-year-old boy with severe hemophilia B and minimal bleeding manifestations in his early childhood presented with gastrointestinal bleeding at 11 years of age. Following administration of prothrombin complex concentrate, he developed peripheral venous thrombosis and cerebral sinovenous thrombosis, posing a management dilemma. His cerebral sinovenous thrombosis resolved spontaneously, proving watchful waiting to be a useful strategy. He developed spontaneous intracranial bleed at 14 years of age for which he was treated with factor IX concentrate and commenced on prophylaxis. We discuss the factors contributing to genotype-phenotype dissonance in severe hemophilia and considerations before commencing prophylaxis in such cases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A major complication with spinal cord injury (SCI) is the development of spasticity, a clinical symptom of hyperexcitability within the spinal H-reflex pathway. We have previously demonstrated a common structural motif of dendritic spine dysgenesis associated with hyperexcitability disorders after injury or disease insults to the CNS. Here, we used an adeno-associated viral (AAV)-mediated Cre-Lox system to knockout Rac1 protein expression in motor neurons after SCI. Three weeks after AAV9-Cre delivery into the soleus/gastrocnemius of Rac1-"floxed" adult mice to retrogradely infect spinal alpha-motor neurons, we observed significant restoration of RDD and reduced H-reflex excitability in SCI animals. Additionally, viral-mediated Rac1 knockdown reduced presence of dendritic spine dysgenesis on motor neurons. In control SCI animals without Rac1 knockout, we continued to observe abnormal dendritic spine morphology associated with hyperexcitability disorder, including an increase in mature, mushroom dendritic spines, and an increase in overall spine length and spine head size. Taken together, our results demonstrate that viral-mediated disruption of Rac1 expression in ventral horn motor neurons can mitigate dendritic spine morphological correlates of neuronal hyperexcitability, and reverse hyperreflexia associated with spasticity after SCI. Finally, our findings provide evidence of a putative mechanistic relationship between motor neuron dendritic spine dysgenesis and SCI-induced spasticity.

Aims: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study., Methods: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed., Results: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR 24h levels (P = .03 and P = .04, respectively). The median VCR 24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR 24h (P = .04) than 2677TT., Conclusion: We showed that in childhood B-ALL, the intracellular VCR 24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR 24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype., (© 2020 British Pharmacological Society.)

Purpose: To determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time., Patients and Methods: Sixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia-Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients., Results: Significant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014)., Conclusion: Outcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hard-shell thoracolumbar sacral orthoses (TLSOs) are used for treating idiopathic scoliosis, a deformation of the spine with a sideways curvature. The pressure required inside the TLSO for ideal corrective results remains unclear. Retrofitting TLSOs with commercially available pressure measurement systems is expensive and can only be performed in a laboratory. The aim of this study was to develop a cost-effective but accurate pressure sensor system for TLSOs. The sensor was built from a piezoresistive polymer, placed between two closed-cell foam liners, and evaluated with a material testing machine. Because foams are energy absorbers, the pressure-conductance curve was affected by hysteresis. The sensor was calibrated on a force plate with the transitions from loading to unloading used to establish the calibration curve. The root mean square error was 12% on average within the required pressure range of 0.01-0.13 MPa. The sensor reacted to the changing pressure during breathing and different activities when tested underneath a chest belt at different tensions. The peak pressure reached 0.135 MPa. The sensor was further tested inside the scoliosis brace during different activities. The measured pressure was 0.014-0.124 MPa. The results from this study enable cheaper and mobile systems to be used for clinical studies on the comfort and pressure of braces during daily activities.

Background: The majority of prescriptions for supplemental oxygen are written when patients are discharged to home from the hospital and the evaluation of these patients is inconsistent. Respiratory Therapists receive training in the evaluation and management of patients needing oxygen. The primary goal of the study was to estimate the frequency with which respiratory therapists (RTs) evaluate the need for home oxygen in patients hospitalized for COPD exacerbations before discharge., Methods: An online questionnaire was distributed to RTs in the United States by the American Association for Respiratory Care. RTs were asked to indicate how frequently they evaluate the need for home oxygen on an ordinal scale: Never, Rarely/occasionally, Sometimes, Most of the time, Almost every time, or Every time. Consistent evaluation for home oxygen was defined as performing an evaluation for home oxygen therapy Almost every time or Every time (ie, > 75% of the time). Bivariate and multivariable analyses were assessed using the Fisher exact test and logistic regression models., Results: Of 611 respondents, 490 were eligible for analysis. Fifty-eight percent of RTs reported consistently evaluating patients for home oxygen at rest, whereas 43% reported doing so during activity and 14% during sleep. Consistent evaluation for home oxygen requirements at rest was significantly associated with more years of practice ( P = .03; highest among RTs with ≥ 30 y of practice at 40%), region of practice ( P = .001; highest in the Midwest at 44%), and greater familiarity with criteria for home oxygen ( P < .001; highest among RTs who selected Very familiar with guidelines from the Centers for Medicare and Medicaid Services at 58%). Practice in the Midwest and greater familiarity with criteria for home oxygen was associated with consistent evaluation for home oxygen during activity. Practice in the Midwest (vs Northeast; adjusted odds ratio 2.56, P < .001) and being very familiar with home oxygen criteria (vs not at all familiar; adjusted odds ratio 5.66, P < .001) were independently associated with a higher odds of evaluating for home oxygen at rest and with activity. Only 25% of RTs were involved in making decisions about home oxygen equipment., Conclusions: RTs do not consistently evaluate patients hospitalized for COPD exacerbations for home oxygen prior to discharge, and only a minority of RTs are involved in selecting home oxygen equipment., Competing Interests: Dr Tan has disclosed a relationship with the National Institutes of Health (NIH). Dr Krishnan has disclosed relationships with the NIH, the Patient-Centered Outcomes Research Institute, ResMed, and Regeneron. Dr Vines has disclosed a relationship with Ohio Medical. Dr Prieto-Centurion has disclosed relationships with the NIH and ResMed. Mr Kallstrom is Executive Director of the American Association for Respiratory Care and Publisher of Respiratory Care., (Copyright © 2021 by Daedalus Enterprises.)

Background: The Neurodata Without Borders data standard (NWB) unifies diverse modalities of neurophysiology data in a single format. Integrating NWB with a database unleashes its full potential to promote collaboration, standardize analyses, capitalize on historical data, and ensures data integrity by maintaining process transparency. NWB database technology is the bedrock of analytical systems used by academic leaders including the Allen Institute and the International Brain Laboratory. Here we present the benefits of incorporating NWB design principles in a big data analytics application., New Method: Data standards and databases are the foundation of big data analytics. To demonstrate the benefits of using these systems together, we implemented NWB in Jupyter notebooks using DataJoint to streamline database operations., Results: We demonstrate the utility of combining the NWB with DataJoint in a Jupyter-based electronic lab journal. We convert open-field behavioral data (using X, Y coordinates) to NWB format and process it with a DataJoint pipeline. Additional notebooks demonstrate working NWB files, data sharing, combining data from diverse sources, and retrospective analyses with data query filtering techniques., Comparison With Existing Methods: NWB describes how to structure and store neurophysiology data and is streamlined for research settings. In contrast to other data standards, combining NWB with DataJoint's database interface can dramatically increase data analytical capabilities., Conclusions: The joint use of NWB with DataJoint transforms traditional laboratory datasets and workflows. Our Jupyter notebooks showcase the analytical and collaborative advantages of adopting big data analytics and can be tailored to other modalities by researchers interested in evaluating NWB., (Published by Elsevier B.V.)