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The need to develop wearable devices for personal health monitoring, diagnostics, and therapy has inspired the production of innovative on-demand, customizable technologies. Several of these technologies enable printing of raw electronic materials directly onto biological organs and tissues. However, few of them have been thoroughly investigated for biocompatibility of the raw materials on the cellular, tissue, and organ levels or with different cell types. In addition, highly accurate multiday in vivo monitoring using such on-demand, in situ fabricated devices has yet to be done. Presented herein is the first fully biocompatible, on-skin fabricated electronics for multiple cell types and tissues that can capture electrophysiological signals with high fidelity. While also demonstrating improved mechanical and electrical properties, the drawn-on-skin ink retains its properties under various writing conditions, which minimizes the variation in electrical performance. Furthermore, the drawn-on-skin ink shows excellent biocompatibility with cardiomyocytes, neurons, mice skin tissue, and human skin. The high signal-to-noise ratios of the electrophysiological signals recorded with the DoS sensor over multiple days demonstrate its potential for personalized, long-term, and accurate electrophysiological health monitoring.

Fencing, often referred to as a physical game of chess, is an organized sport involving the use of a sword, epee, foil, or saber for attack and defense according to set movements and rules. Fencing, one of the first nine sports included in the first Olympic Games in 1896, has a long history. This paper has systematically reviewed literature and evaluated the role of fencing in the empowerment of women through a combination of qualitative and quantitative research methods including first-hand observation, interviews, archival analysis, and secondary statistical data collection. It has attempted to narrow the empirical gap by exploring the gender perspective of fencing as a sport. It reveals that due to historical, social and cultural bias, financial constraints, as well as a lack of leadership, women's involvement in fencing had been limited throughout fencing's history. Since the 2nd half of the 19th century, fencing has witnessed tremendous strides in breaking the barriers influenced by the changing society propelled by a long history of feminist and civil rights activists who took a blend of the consciousness-raising and organizing approach and the pragmatic approach. Women's fencing shows a history of breaking barriers, and with the enacting of Title IX to eliminate gender discrimination in sports and education it is the most significant turning point. Title IX has not only broadened and deepened the scope and participation of women in fencing but also made fencing an enabler and driver to enhance women's grit and leadership, leading to the empowerment of women in society. The paper develops a framework to highlight the linkage between Title IX, women's fencing, and empowerment. The impact of Title IX on women with fencing as an enabler and drivers is farreaching. It has widened the scope of women in fencing by reaching the general public and deepened the scope of women's fencing by raising the visibility of this women's sport in national and international arenas. Keywords: Discrimination against women, Women's fencing, Barriers, Title IX, Empowerment of women, Qualitative and quantitative research, women in sports, Introduction 'Sport has the power to change the world. It has the power to inspire. It has the power to unite people in a way that little else does. It [...]

There is growing evidence to suggest that lifestyle initiatives promote brain health and reduce dementia risk. However, there is comparatively limited research focused on lifestyle interventions among people living with dementia. Most recent systematic reviews of lifestyle interventions among people living with dementia centre on the impact of exercise on cognition; yet, functional abilities and quality of life are most consistently prioritized by people living with dementia, care partners, and healthcare professionals. There is insufficient evidence to inform guidelines on effective lifestyle interventions, programs, resources, and policies for people living with dementia. To address this knowledge gap, the objective of this study is to perform a systematic review to understand the impact of lifestyle interventions among people living with dementia. The specific research questions are: "What is the effectiveness of physical activity interventions on improving functional abilities and quality of life among community-dwelling people living with dementia?", "What is the effectiveness of healthy eating/nutrition on improving nutritional status or quality of life among community-dwelling people living with dementia?" and "Does the effectiveness of interventions vary depending on the components (single or multi), setting (in-home or community centre, geography), program structure, mode of delivery, dosage, and participant characteristics (sex/gender, ethno-cultural or language group, race, dementia type)?" The results from this review will inform recommendations of lifestyle interventions and their delivery among people living with dementia in the community. Trial registration: Systematic review registration PROSPERO #CRD42024509408. [ABSTRACT FROM AUTHOR]

In Fig. 3c of this Letter, the the effects of CRISPR-Cas9-mediated deletion of NR3C1, TXNIP and CNR2 in patient-derived B-lineage leukaemia cells were shown. For curves depicting NR3C1 (left graph), data s for TXNIP (middle graph) were inadvertently plotted. This figure has been corrected online, and the original Fig. 3c is shown as Supplementary Information to this Amendment for transparency. The error does not affect the conclusions of the Letter. In addition, Source Data files have been added for the Figs. 1-4 and Extended Data Figs. 1-10 of the original Letter.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.

Protein engineering often targets binding pockets or active sites which are enriched in epistasis--nonadditive interactions between amino acid substitutions--and where the combined effects of multiple single substitutions are difficult to predict. Few existing sequence-fitness datasets capture epistasis at large scale, especially for enzyme catalysis, limiting the development and assessment of model-guided enzyme engineering approaches. We present here a combinatorially complete, 160,000-variant fitness landscape across four residues in the active site of an enzyme. Assaying the native reaction of a thermostable ß-subunit of tryptophan synthase (TrpB) in a nonnative environment yielded a landscape characterized by significant epistasis and many local optima. These effects prevent simulated directed evolution approaches from efficiently reaching the global optimum. There is nonetheless wide variability in the effectiveness of different directed evolution approaches, which together provide experimental benchmarks for computational and machine learning workflows. The most-fit TrpB variants contain a substitution that is nearly absent in natural TrpB sequences--a result that conservation-based predictions would not capture. Thus, although fitness prediction using evolutionary data can enrich in more-active variants, these approaches struggle to identify and differentiate among the most-active variants, even for this near-native function. Overall, this work presents a large-scale testing ground for model-guided enzyme engineering and suggests that efficient navigation of epistatic fitness landscapes can be improved by advances in both machine learning and physical modeling. [ABSTRACT FROM AUTHOR]

Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1(+)) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1(Neg)) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1(+) cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.

Trauma is the leading non-obstetric cause of maternal and fetal mortality and affects an estimated 5–7% of all pregnancies. Pregnant women, thankfully, are a small subset of patients presenting in the trauma bay, but they do have distinctive physiologic and anatomic changes. These increase the risk of certain traumatic injuries, and the gravid uterus can both be the primary site of injury and mask other injuries. The primary focus of the initial management of the pregnant trauma patient should be that of maternal stabilization and treatment since it directly affects the fetal outcome. Diagnostic imaging plays a pivotal role in initial traumatic injury assessment and should not deviate from normal routine in the pregnant patient. Radiographs and focused assessment with sonography in the trauma bay will direct the use of contrast-enhanced computed tomography (CT), which remains the cornerstone to evaluate the potential presence of further management-altering injuries. A thorough understanding of its risks and benefits is paramount, especially in the pregnant patient. However, like any other trauma patient, if evaluation for injury with CT is indicated, it should not be denied to a pregnant trauma patient due to fear of radiation exposure. [ABSTRACT FROM AUTHOR]

Cancer health disparities persist across the cancer care continuum despite decades of effort to eliminate them. Among the strategies currently used to address these disparities are multi-institution research initiatives that engage multiple stakeholders and change efforts. Endemic to the theory of change of such programs is the idea that collaboration—across institutions, research disciplines, and academic ranks—is necessary to improve outcomes. Despite this emphasis on collaboration, however, it is not often a focus of evaluation for these programs and others like them. In this paper we describe a method for evaluating collaboration within the Meharry-Vanderbilt-Tennessee State University Cancer Partnership using network analysis. Specifically, we used network analysis of co-authorship on academic publications to visualize the growth and patterns of scientific collaboration across partnership institutions, research disciplines, and academic ranks over time. We presented the results of the network analysis to internal and external advisory groups, creating the opportunity to discuss partnership collaboration, celebrate successes, and identify opportunities for improvement. We propose that basic network analysis of existing data along with network visualizations can foster conversation and feedback and are simple and effective ways to evaluate collaboration initiatives. [ABSTRACT FROM AUTHOR]

Based on a business student survey, this article explores students' experiences, perceptions, attitudes, and motivation toward learning business information literacy (IL) skills. The survey received 413 responses and investigated topics including most encountered research tasks, use of research tools, most experienced feelings, self-rated research competencies, perceived research importance, interest to learn more, research scenarios, challenges, preferred learning settings and learning modes, motivational factors, the time commitment for learning, and preferred quality of a learning module. Incorporating students' suggestions on improving their IL skills, the article proposes to create six dynamic learning opportunities for students and shares ideas for realizing these opportunities through collaboration, integration, and experimentation. [ABSTRACT FROM AUTHOR]

Luminescence imaging is widely used to identify spatial defects and extract key electrical parameters of photovoltaic devices. To reliably identify defects, high‐quality images are desirable; however, acquiring such images implies a higher cost or lower throughput as they require better imaging systems or longer exposure times. This study proposes a deep learning‐based method to effectively diminish the noise in luminescence images, thereby enhancing their quality for inspection and analysis. The proposed method eliminates the requirement for extra hardware expenses or longer exposure times, making it a cost‐effective solution for image enhancement. This approach significantly improves image quality by >30% and >39% in terms of the peak signal‐to‐noise ratio and the structural similarity index, respectively, outperforming state‐of‐the‐art classical denoising algorithms. [ABSTRACT FROM AUTHOR]

Background Most countries have formally adopted the World Health Organization's 2015 recommendation of universal HIV treatment ('treat all'). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. Methods and findings We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI -2.9 to 3.8; p = 0.804) and Uganda (-4.2 pp, 95% CI -9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16-24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. Conclusions Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation., Author(s): Olga Tymejczyk 1,2,*, Ellen Brazier 1,2, Constantin T. Yiannoutsos 3, Michael Vinikoor 4,5, Monique van Lettow 6,7, Fred Nalugoda 8, Mark Urassa 9, Jean d'Amour Sinayobye 10, Peter F. [...]

Whole-body exposure to high-energy particle radiation remains an unmitigated hazard to human health in space. Ongoing experiments at the NASA Space Radiation Laboratory and elsewhere repeatedly show persistent changes in brain function long after exposure to simulations of this unique radiation environment, although, as is also the case with proton radiotherapy sequelae, how this occurs and especially how it interacts with common comorbidities is not well-understood. Here, we report modest differential changes in behavior and brain pathology between male and female Alzheimer's-like and wildtype littermate mice 7–8 months after exposure to 0, 0.5, or 2 Gy of 1 GeV proton radiation. The mice were examined with a battery of behavior tests and assayed for amyloid beta pathology, synaptic markers, microbleeds, microglial reactivity, and plasma cytokines. In general, the Alzheimer's model mice were more prone than their wildtype littermates to radiation-induced behavior changes, and hippocampal staining for amyloid beta pathology and microglial activation in these mice revealed a dose-dependent reduction in males but not in females. In summary, radiation-induced, long-term changes in behavior and pathology, although modest, appear specific to both sex and the underlying disease state. [ABSTRACT FROM AUTHOR]