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Abstract Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin‐oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.

Most students who enter a community college never finish. In fact, "fewer than four of every ten complete any type of degree or certificate within six years" (Bailey et al., 2015). One reason for low success rates is the lack of high-quality, frequent feedback provided to students. Feedback has been shown to improve student learning and success. The purpose of this systematic literature review was to understand the root causes for the lack of productive, consistent feedback. To this end, traditional peer-reviewed research, public scholarship sources, and faculty perspectives were included in this literature review. One cause identified was the lack of comprehensive faculty training in pedagogy in general and in how to provide high-quality feedback specifically. Another reason was lack of time. Faculty who teach in community colleges typically have heavy teaching loads, along with service and other responsibilities that make it difficult to provide regular, high-quality feedback to students. Finally, many students have a negative perception of feedback and therefore, often ignore it. When students do not use feedback, faculty can determine that providing feedback is not a good use of their time. There is ample evidence in the literature that supporting faculty to provide high-quality feedback is effective for promoting students' academic success.

Objetivo: Avaliação de dados de encaminhamento de adolescentes portadores de doença falciforme (DF) para o ambulatório de adultos em um serviço único da cidade de São Paulo. Métodos: Foi realizada avaliação do prontuário eletrônico para coleta de dados de pacientes que completaram 18 anos entre os anos de 2021 a 2024. Em 2023, foi implementado o grupo de WhatsApp para informações sobre encaminhamentos de pacientes entre as equipes da Hematologia Pediátrica e de Adulto. Os dados agrupados em 2 grupos: Grupo 1 (G1): anos de 2021 e 2022 e Grupo 2 (G2): anos de 2023 e 2024. Dados coletados: ano de nascimento, genótipos, data da última consulta na pediatria e data da consulta no ambulatório de adultos. Resultados: Foram avaliados prontuários de 97 pacientes, 56 (58%) do G1 e 41 (42%) do G2, correspondendo a 2,3 pacientes/mês para ambos os grupos; destes 62 (64%) tinham anemia falciforme, 26 (27%) doença SC e 9 (9%) S-beta talassemia. No grupo total foram incluídos pacientes de outros serviços pediátricos (PCTE) (encaminhados via CROSS-Central de Regulação de Ofertas de Serviços de Saúde). No G1, observou-se 10 PCTE, com relação PCTE /internos (PCTI) de 1:5 e no G2 foram 4 PCTE com relação de 1:9. O tempo médio entre encaminhamento e consulta no ambulatório de adultos foi de 3 meses no G1 e no G2. Para PCTE, a mediana de tempo foi de 18 meses (IQ: 6;24) no G1 e 9 meses (IQ: 5;9,5) no G2. Houve diferença significante no tempo de encaminhamento (PCTI x PCTE) apenas no G1 (p < 0,0001). Sete pacientes do G1 abandonaram o tratamento (5 PCTI e 2 PCTE) e um do G2 (PCTI). Discussão: Segundo o Ministério da Saúde, o maior número óbitos em doentes com DF ocorreu na faixa etária de 20-29 anos. Estudos demonstram que o ambulatório de transição previne o abandono de tratamento desses adolescentes. A implementação do grupo de WhatsApp visou uma melhor comunicação entre hematologistas pediátricos e de adultos, mas não houve diferença no tempo de encaminhamento quando comparados G1 e G2, embora no G1 só tenham sido contabilizados pacientes que efetivamente chegaram ao ambulatório de adultos. Por isso, o abandono de tratamento observado no G1 pode ser ainda maior. No G2, devido à implantação do WhatsApp, foi possível busca ativa dos pacientes, diminuindo o abandono. Nos PCTE observou-se maior intervalo entre encaminhamento e consulta, e a pandemia de COVID pode ter contribuído nos achados do G1. Ressalta-se a diferença no número de PCTI e de PCTE: G1: 46 e 10; G2: 37 e 4, respectivamente. Na cidade de São Paulo existem 3 serviços pediátricos que não têm retaguarda para encaminhamento de seus pacientes e é sabido que a oferta de vagas pelos serviços que atendem adultos é restrita, o que nos leva a supor que muitos pacientes se encontram desassistidos. Conclusão: A implantação de um serviço de transição adequado para cada instituição é imprescindível para a diminuição do abandono do tratamento dos adolescentes com DF e, consequentemente, para maior sobrevida. No entanto, são necessárias políticas públicas que garantam que todos os adolescentes terão seu tratamento em serviços especializados em DF.

Abstract SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

ABSTRACT Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant intestinal epithelium. RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell, and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex vivo model to advance studies of infant-specific diseases and drug discovery for this population.IMPORTANCETissue or biopsy stem cell-derived human intestinal enteroids are increasingly recognized as physiologically relevant models of the human gastrointestinal epithelium. While enteroids from adults and fetal tissues have been extensively used for studying many infectious and non-infectious diseases, there are few reports on enteroids from infants. We show that infant enteroids exhibit both transcriptomic and morphological differences compared to adult cultures. They also differ in functional responses to barrier disruption and innate immune responses to infection, suggesting that infant and adult enteroids are distinct model systems. Considering the dramatic changes in body composition and physiology that begin during infancy, tools that appropriately reflect intestinal development and diseases are critical. Infant enteroids exhibit key features of the infant gastrointestinal epithelium. This study is significant in establishing infant enteroids as age-appropriate models for infant intestinal physiology, infant-specific diseases, and responses to pathogens.

Abstract Climate impacts increasingly unfold in interlinked systems of people, nature, and infrastructure. The cascading consequences are revealing sometimes surprising connections across sectors and regions, and prospects for climate responses also depend on complex, difficult‐to‐understand interactions. In this commentary, we build on the innovations of the United States Fifth National Climate Assessment to suggest a framework for understanding and responding to complex climate challenges. This approach involves: (a) integration of disciplines and expertise to understand how intersectionality shapes complex climate impacts and the wide‐ranging effects of climate responses, (b) collaborations among diverse knowledge holders to improve responses and better encompass intersectionality, and (c) sustained experimentation with and learning about governance approaches capable of handling the complexity of climate change. Together, these three pillars underscore that usability of climate‐relevant knowledge requires transdisciplinary coordination of research and practice. We outline actionable steps for climate research to incorporate intersectionality, integration, and innovative governance, as is increasingly necessary for confronting climate complexity and sustaining equitable, ideally vibrant climate futures.

This article describes the development of a theatre- and design-based Performance Lecture whose goal is to develop reflexivity around the theme of longevity and innovation in secondary and university level students. Theatre is an art form that aims at developing self-reflection and reflexivity in both audiences and participants, opening the door to reflective learning which, if combined with critical design and design fiction, offers an effective medium for addressing many dimensions of Responsible Innovation (RI). The workshop involves the presentation of a fictional “near-future” product, a drink called "Longevity". The drink contains nanobots that once ingested can be directed (with an app) to stimulate the body to produce certain compounds, allowing the user to control different properties in their blood “in flow”. This innovative use of technology offers more bodily efficiency, leading to a longer life. This methodology was primarily developed during the A Society for All Ages. Longevity-driven design Masters course at Milan Polytechnic (2022-23) and the Interaction Design and Service Design Masters courses at Milan Domus Academy (2023), and is grounded in grassroots approaches to Responsible Innovation.

This paper investigates the use of stance linguistic features in accounting Ph.D. theses in a Nigerian university. We adopted a mixed-methods approach by combining a textual analysis of the theses and explored the context of writing of the participants similar to Swale's textography approach. We compiled three corpora: Bayero University corpus of six accounting Ph.D. theses (BUK corpus); a United Kingdom corpus of six accounting PhD theses (UK corpus) and a corpus of eleven journal articles of accounting (JAA corpus). The results of textual analysis indicate that there is a higher frequency of hedges in all the three corpora than other stance features, followed by boosters, then attitudinal markers, and explicit self-mention features. One striking finding from the BUK corpus is that the authors are rarely used self-mention features compared to authors from other two corpora. However, the result of the chi-square indicates that the differences among the three corpora's use of stance features are insignificant. The contextual data suggests that non-teaching of English for specific purposes and the traditional practices of Bayero University might be some of the possible factors that constrained authors' use of stance linguistic features. We recommend introduction of teaching English for specific purposes on postgraduate programmes in Nigerian universities.

With the progression of various mobile technologies, mobile applications have tremendously increased, especially during the Covid-19 pandemic, and such applications have been exploited much in teaching and learning. This study explores the educational potential of using mobile applications in English language teaching (ELT) or Mobile Assisted Language Teaching (MALT). A critical review of the research in mobile applications in English language teaching is explored in this study, specifically from the published papers since 2015. Initially 131 articles were selected from ScienceDirect, SAGE, IEEEXplore, and Google Scholar. However, only 13 articles matched the inclusion criteria. These articles were analyzed and reviewed using the following categories: the role of mobile technology, pedagogical practices, research methodologies, the context of usage, and outcomes. The research found that mobile technologies in teaching language are increasing, and it is expected to rise in the future. In addition, teachers use different technologies to enhance English language teaching in the settings of inside and outside classrooms. During the COVID-19 pandemic, schools have closed indefinitely. This unexpected situation has forced students to stay at home, and online learning seems to grow exponentially. Thus, through this research review, significant educational outcomes are identified for future investigation practices.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Cancer is a global health challenge with rising incidence and mortality rates, posing significant concerns. The World Health Organization reports cancer as a leading cause of death worldwide, contributing to nearly one in six deaths. Cancer pathogenesis involves disruptions in cellular signaling pathways, resulting in uncontrolled cell growth and metastasis. Among emerging players in cancer biology, Transient Receptor Potential (TRP) channels, notably TRPV1, have garnered attention due to their altered expression in cancer cells and roles in tumorigenesis and progression. TRPV1, also known as the capsaicin receptor, is pivotal in cancer cell death and pain mediation, offering promise as a therapeutic target. Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death. Additionally, TRPV1 is implicated in cancer-induced pain and chemo-sensitivity, with upregulation observed in sensory neurons innervating oral cancers. Also, when capsaicin, a compound from chili peppers, interacts with TRPV1, it elicits a “hot” sensation and influences cancer processes through calcium influx. Understanding TRPV1’s multifaceted roles in cancer may lead to novel therapeutic strategies for managing cancer-related symptoms and improving patient outcomes. The current review elucidates the comprehensive role of capsaicin in cancer therapy, particularly through the TRPV1 channel, highlighting its effects in various cells via different signaling pathways and discussing its limitations.

Over the last several decades, graduate students from engineering courses have faced a challenge of regular rejections in the work market despite their outstanding academic qualifications. In response to this challenge, many universities across the globe have introduced in their curricula the English for Specific Purposes (ESP) courses tailored to the need of engineering students. The present study evaluated the effectiveness of the ESP course for engineering students introduced at Dhofar University in Oman. The study participants were first- and second-year undergraduates from the Faculty of Engineering. The participants responded to a 26-item survey that addressed the course content and the changes in the students' English language proficiency. The results demonstrated that taking the ESP course had a positive impact on the course content, participants' vocabulary and grammar, as well as on their specific English language skills. The limitations of the study include a relatively small sample of participants and the self-reporting bias inherent in the use of a self-report methodology. Therefore, further research using more objective measures to evaluate the effectiveness and impact of ESP courses on English proficiency of engineering students would be needed.

Abstract The acute water and electricity shortages in Gaza necessitate comprehensive solutions that recognize the interconnected nature of these vital resources. This article presents pragmatic solutions to align supply with fundamental needs in both domains, offering viable pathways for achieving strategic water‐energy security in Gaza. Baseline data reveals a deficit in the current water supply, falling below the international minimum of 100 L per capita per day, while the reported 137–189 MW per day electricity supply significantly lags behind the estimated 390 MW per day peak demand. To meet projected 2024 residential, commercial, and industrial demands, this study proposes actionable measures including expanding wastewater treatment to enable over 150 MCM per year tertiary effluents for agricultural reuse and adopting energy‐efficient forward osmosis‐reverse osmosis and osmotically assisted reverse osmosis desalination methods to increase potable water supply to 150 MCM per year. Electricity supply strategies include scaling renewable capacity towards 110 MW per day, exploring regional cooperation to unlock over 360 MW of power per day, and potentially recovering up to 60 MW per day through system efficiencies. These recommendations aim to prevent exacerbated scarcity and alleviate hardships in Gaza.

BackgroundHydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. ObjectiveThe goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. MethodsRecruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. ResultsTotal enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P

PurposeThis study aimed to identify determinants influencing the utilization of early intervention services among young children with sickle cell disease (SCD) based on perspectives from medical and early intervention providers.Design and methodsEarly intervention and medical providers from the catchment area surrounding St. Jude Children's Research Hospital and Washington University were recruited (20 total providers). Interviews were completed over the phone and audio recorded. All interviews were transcribed verbatim, coded, and analyzed using inductive thematic analysis.ResultsThree overarching themes were identified from both groups: Awareness (e.g., lack of awareness about the EI system and SCD), Access (e.g., difficulties accessing services), and Communication (e.g., limited communication between medical and early intervention providers, and between providers and families). Although these three themes were shared by medical and early intervention providers, the differing perspectives of each produced subthemes unique to the two professional fields.ConclusionsEarly intervention services can limit the neurodevelopmental deficits experienced by young children with SCD; however, most children with SCD do not receive these services. The perspectives of early intervention and medical providers highlight several potential solutions to increase early intervention utilization among young children with SCD.

Introduction/backgroundPhosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer.Methods/materialsPatients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p

Abstract Background This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. Methods Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. Results A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. Conclusions Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED.

Abstract A computationally efficient dehomogenization technique was developed based on a bioinspired diffusion-based pattern generation algorithm to convert an orientation field into explicit large-scale fluid flow channel structures. Due to the transient nature of diffusion and reaction, most diffusion-based pattern generation models were solved in both time and space. In this work, we remove the temporal dependency and directly solve a steady-state equation. The steady-state Swift-Hohenberg model was selected due to its simplistic form as a single variable equation and intuitive parameter setting for pattern geometry control. Through comparison studies, we demonstrated that the steady-state model can produce statistically equivalent solutions to the transient model with potential computational speedup. This work marks an early foray into the use of steady-state pattern generation models for rapid dehomogenization in multiphysics engineering design applications. To highlight the benefits of this approach, the steady-state model was used to dehomogenize optimized orientation fields for the design of microreactor flow structures involving hundreds of microchannels in combination with a porous gas diffusion layer. A homogenization-based multi-objective optimization routine was used to produce a multi-objective Pareto set that explored the trade-offs between flow resistance and reactant distribution variability. In total, the diffusion-based dehomogenization method enabled the generation of 200 unique and distinctly different microreactor flow channel designs. The proposed dehomogenization approach permits comprehensive exploration of numerous bioinspired solutions capturing the full complexity of the optimization and Swift-Hohenberg design space.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19–induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24− cells among CD19+ B cells (termed ‘plasmablasts’ for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Hydrogen selenide (H2Se) is an emerging biomolecule of interest with similar properties to that of other gaseous signaling molecules (i.e., gasotransmitters that include nitric oxide, carbon monoxide, and hydrogen sulfide). H2Se is enzymatically generated in humans where it serves as a key metabolic intermediate in the production of selenoproteins and other selenium-containing biomolecules. However, beyond its participation in biosynthetic pathways, its involvement in cellular signaling or other biological mechanisms remains unclear. To uncover its true biological significance, H2Se-specific chemical tools capable of functioning under physiological conditions are required but lacking in comparison to those that exist for other gasotransmitters. Recently, researchers have begun to fill this unmet need by developing new H2Se-releasing compounds, along with pioneering methods for selenide detection and quantification. In combination, the chemical tools highlighted in this review have the potential to spark groundbreaking explorations into the chemical biology of H2Se, which may lead to its branding as the fourth official gasotransmitter.

Overexposure to antibiotics originating in wastewater has profound environmental and health implications. Conventional treatment methods are not fully effective in removing certain antibiotics, such as the commonly used antibiotic, tetracycline, leading to its accumulation in water catchments. Alternative antibiotic removal strategies are garnering attention, including sonocatalytic oxidative processes. In this work, we investigated the degradation of tetracycline using a combination of TiO2 fractured nanoshells (TFNs) and an advanced sonochemical reactor design. The study encompassed an examination of multiple process parameters to understand their effects on the degradation of tetracycline. These included tetracycline adsorption on TFNs, reaction time, initial tetracycline concentration, solvent pH, acoustic pressure amplitude, number of acoustic cycles, catalyst dosage, TFNs' reusability, and the impact of adjuvants such as light and H2O2. Though TFNs adsorbed tetracycline, the addition of ultrasound was able to degrade tetracycline completely (with 100% degradation) within six minutes. Under the optimal operating conditions, the proposed sonocatalytic system consumed 80% less energy compared to the values reported in recently published sonocatalytic research. It also had the lowest CO2 footprint when compared to the other sono-/photo-based technologies. This study suggests that optimizing the reaction system and operating the reaction under low power and at a lower duty cycle are effective in achieving efficient cavitation for sonocatalytic reactions.

This case report describes the anesthetic, surgical, and postoperative management of scapulohumeral arthrodesis in a juvenile reindeer with severe lameness due to a chronic proximal humeral fracture and scapulohumeral luxation. The reindeer was managed with prolonged stall confinement and physical therapy and 9 months postoperatively was walking and bearing weight equally when standing. This case demonstrates that comparative techniques from other veterinary species coupled with considerations for reindeer anesthesia can be successful in restoring functional soundness after scapulohumeral arthrodesis.

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

IntroductionThe Sickle Cell Data Collection Program (SCDC) is a multi-state initiative utilizing multiple data sources to estimate population prevalence of Sickle Cell Disease (SCD) with the goal of improving quality of life and health outcomes among those affected. SCDC in Tennessee operates as a multi-site, interdisciplinary team using multiple sources of data to learn more about SCD in Tennessee.MethodsThis analysis characterizes the number, demographics, and proximity to specialty care of individuals living with SCD in Tennessee who have been covered by Medicaid or identified by newborn screening. We compared demographic patterns of individuals with SCD living in rural areas with those living in urban areas, as well as those living in counties contributing more than 50 individuals to the cohort, respectively, to demographic patterns of individuals with SCD in the rest of the state, using Chi-Square or Fisher’s exact tests.ResultsFindings show that overall, 66.1% of all SCD patients identified through newborn screening were residents of Davidson and Shelby counties at the time of birth, and 81.8% of those identified through Medicaid claims lived in Davidson, Hamilton, Knox, Madison, Montgomery, Rutherford, or Shelby County. In total, 8.6% of the cohort lived in rural settings and 91.4% in urban settings. Of the 95 counties in Tennessee, 75 (78.9%) had at least 1 to 40 residents with SCD, yet of these 75 counties, less than half had a hematology/oncology trained provider practicing within them.DiscussionThis analysis brings us closer to understanding how many people with SCD live in rural areas of Tennessee and the challenges they face in seeking the care needed to adequately manage their disease. Acute healthcare utilization remains highest in the young adulthood years. This analysis provides insight into how healthcare utilization patterns among individuals with SCD vary by age group and over time.

Smoking increases lipid levels, including triglycerides, leading to increased cardiovascular disease risk. We performed a meta-analysis to quantify the effects of smoking and smoking cessation on triglyceride levels. The PubMed and Scopus databases were searched to identify studies reporting either triglyceride levels in smokers and non-smokers or the effects of smoking cessation on triglyceride levels. Fixed- and random-effects models were used to perform the analyses when three or more studies/comparisons were available. We identified 169 and 21 studies evaluating the effects of smoking and smoking cessation, respectively, on triglyceride levels. Triglyceride levels were 0.50 mmol/L (95% confidence interval: 0.49–0.50 mmol/L) higher in smokers than non-smokers, but the effect differed widely across studies. No statistically significant effect was observed on triglyceride levels between baseline and 6 weeks (mean difference [MD] = 0.02 [−0.09, 0.12] mmol/L), 2 months (MD = 0.03 [−0.21, 0.27] mmol/L), 3 months (MD = 0.08 [−0.03, 0.21] mmol/L), or 1 year (MD = 0.04 [−0.06, 0.14] mmol/L) after quitting. However, a slightly significant decrease in triglyceride levels was observed at 1 month after cessation (MD = −0.15 [−0.15, −0.01] mmol/L). The results of this meta-analysis provide a basis for understanding the effects of smoking and smoking cessation on triglyceride levels, which could have important implications for public health.

Introduction Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV prevention. Animal and human studies have demonstrated that bnAbs which neutralise HIV can prevent infection. The optimal plasma antibody concentrations to confer protection against HIV infection in humans is under intense study. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 012C trial will evaluate extended safety and pharmacokinetics of CAP256V2LS and VRC07-523LS among young HIV-negative South African and Zambian women. The study design also allows for an evaluation of a signal of HIV prevention efficacy.Methods and analysis CAPRISA 012 is a series of trials with three distinct protocols. The completed CAPRISA 012A and 012B phase 1 trials provided critical data for the CAPRISA 012C trial, which is divided into parts A and B. In part A, 90 participants were randomised to receive both CAP256V2LS and VRC07-523LS at 20 mg/kg or placebo, subcutaneously every 16 or 24 weeks. Part B will enrol 900 participants in South Africa and Zambia who will be randomised in a 1:1 ratio and receive an initial loading dose of 1.2 g of CAP256V2LS and VRC07-523LS or placebo followed by 600 mg of CAP256V2LS and 1.2 g of VRC07-523LS or placebo subcutaneously every 6 months. Safety will be assessed by frequency and severity of reactogenicity and other related adverse events. Pharmacokinetics of both antibodies will be measured in systemic and mucosal compartments over time, while participants will be monitored for breakthrough HIV infections.Ethics and dissemination of study findings The University of KwaZulu-Natal Biomedical Research Ethics Committee and South African Health Products Regulatory Authority have approved the trial (BREC/00002492/2021, SAHPRA20210317). Results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number PACTR202112683307570.

Ground state nuclei usually have compact geometries. However, there have been theoretical predictions that excited nuclei can take on more extended shapes such as toroids or bubbles. There have been many attempts to identify signatures of such shapes in experimental data. One signature, both predicted by theory and reported in experimental data, is narrow resonances at high excitation energy in peripheral intermediate-energy heavy-ion collisions. This potential evidence for toroidal states was reported in the alpha particle disassembly of 28Si after collision with a 12C target at 35 MeV/nucleon. The prior work was limited by angular resolution and statistical uncertainties. The present work aims to measure the excitation energy distribution for these disassembly events with improved angular resolution and reduced statistical uncertainty using the Forward Array Using Silicon Technology (FAUST). FAUST is equipped with resistive dual-axis duo-lateral (DADL) position-sensitive silicon detectors capable of sub-millimeter position resolution. The measured excitation energy distributions of 7-α disassembly events showed no strong evidence for highly excited states at the cross section and widths suggested by previous experiment.

The central regions of the Milky Way constitute a unique laboratory for a wide swath of astrophysical studies; consequently, the inner ∼400 pc have been the target of numerous large surveys at all accessible wavelengths. In this paper, we present a catalog of sources at 25 and 37 μ m located within all of the regions observed with the SOFIA/FORCAST instrument in the inner ∼200 pc of the Galaxy. The majority of the observations were obtained as part of the SOFIA Cycle 7 Galactic Center Legacy program survey, which was designed to complement the Spitzer/MIPS 24 μ m catalog in regions saturated in the MIPS observations. Due to the wide variety of source types captured by our observations at 25 and 37 μ m, we do not limit the FORCAST source catalog to unresolved point sources, or treat all sources as if they are pointlike sources. The catalog includes all detectable sources in the regions, resulting in a catalog of 950 sources, including point sources, compact sources, and extended sources. We also provide the user with metrics to discriminate between the source types.

We present the detection of a magnetized dust ring (M0.8–0.2) in the central molecular zone (CMZ) of the Galactic center. The results presented in this paper utilize the first data release of the Far-Infrared Polarimetric Large Area CMZ Emission (FIREPLACE) survey (i.e., Paper I of this series). The FIREPLACE survey is a 214 μ m polarimetric survey of the Galactic center using the SOFIA/HAWC+ telescope. The M0.8–0.2 ring is a region of gas and dust that has a circular morphology with a central depression. The dust polarization in the M0.8–0.2 ring implies a curved magnetic field that traces the ring-like structure of the cloud. We posit an interpretation in which an expanding shell compresses and concentrates the ambient gas and magnetic field. We argue that this compression results in strengthening of the magnetic field, as we infer from the observations toward the interior of the ring.

We present the first data release of the Far-Infrared Polarimetric Large Area CMZ Exploration (FIREPLACE) survey. The survey was taken using the 214 μ m band of the HAWC+ instrument with the SOFIA telescope (19.″6 resolution; 0.7 pc). In this first data release we present dust polarization observations covering a ∼0.°5 region of the Galactic center’s central molecular zone (CMZ), approximately centered on the Sgr B2 complex. We detect ∼25,000 Nyquist-sampled polarization pseudovectors, after applying the standard SOFIA cuts for minimum signal-to-noise ratios in fractional polarization and total intensity of three and 200, respectively. Analysis of the magnetic field orientation suggests a bimodal distribution in the field direction. This bimodal distribution shows enhancements in the distribution of field directions for orientations parallel and perpendicular to the Galactic plane, which are suggestive of a CMZ magnetic field configuration with polodial and torodial components. Furthermore, a detailed analysis of individual clouds included in our survey (i.e., Sgr B2, Sgr B2-NW, Sgr B2-Halo, Sgr B1, and Cloud E/F) shows they have fractional polarization values of 1%–10% at 214 μ m, with most of the emission having values

We present infrared aperture-masking interferometry (AMI) observations of newly formed dust from the colliding winds of the massive binary Wolf–Rayet system WR 137 with JWST using the Near Infrared Imager and Slitless Spectrograph (NIRISS). NIRISS AMI observations of WR 137 and a point-spread function calibrator star, HD 228337, were taken using the F380M and F480M filters in 2022 July and August as part of the Director’s Discretionary Early Release Science program #1349. Interferometric observables (squared visibilities and closure phases) from the WR 137 “interferogram” were extracted and calibrated using three independent software tools: ImPlaneIA, AMICAL, and SAMpip. The analysis of the calibrated observables yielded consistent values except for slightly discrepant closure phases measured by ImPlaneIA. Based on all three sets of calibrated observables, images were reconstructed using three independent software tools: BSMEM, IRBis, and SQUEEZE. All reconstructed image combinations generated consistent images in both F380M and F480M filters. The reconstructed images of WR 137 reveal a bright central core with a ∼300 mas linear filament extending to the northwest. A geometric colliding-wind model with dust production constrained to the orbital plane of the binary system and enhanced as the system approaches periapsis provided a general agreement with the interferometric observables and reconstructed images. Based on a colliding-wind dust condensation analysis, we suggest that dust formation within the orbital plane of WR 137 is induced by enhanced equatorial mass loss from the rapidly rotating O9 companion star, whose axis of rotation is aligned with that of the orbit.

During inherited retinal degenerations (IRDs), vision is lost due to photoreceptor cell death; however, a range of optogenetic tools have been shown to restore light responses in animal models. Restored response characteristics vary between tools and the neuronal cell population to which they are delivered: the interplay between these is complex, but targeting upstream neurons (such as retinal bipolar cells) may provide functional benefit by retaining intraretinal signal processing. In this study, our aim was to compare two optogenetic tools: mammalian melanopsin (hOPN4) and microbial red-shifted channelrhodopsin (ReaChR) expressed within two subpopulations of surviving cells in a degenerate retina. Intravitreal adeno-associated viral vectors and mouse models utilising the Cre/lox system restricted expression to populations dominated by bipolar cells or retinal ganglion cells and was compared with non-targeted delivery using the chicken beta actin (CBA) promoter. In summary, we found bipolar-targeted optogenetic tools produced faster kinetics and flatter intensity-response relationships compared with non-targeted or retinal-ganglion-cell-targeted hOPN4. Hence, optogenetic tools of both mammalian and microbial origins show advantages when targeted to bipolar cells. This demonstrates the advantage of bipolar-cell-targeted optogenetics for vision restoration in IRDs. We therefore developed a bipolar-cell-specific gene delivery system employing a compressed promoter with the potential for clinical translation.

Purpose: Proton beam radiotherapy (PBT) has been used for the definitive treatment of localized prostate cancer with low rates of high-grade toxicity and excellent patient-reported quality-of-life metrics. Technological advances such as pencil beam scanning (PBS), Monte Carlo dose calculations, and polyethylene glycol gel rectal spacers have optimized prostate proton therapy. Here, we report the early clinical outcomes of patients treated for localized prostate cancer using modern PBS–PBT with hydrogel rectal spacing and fiducial tracking without the use of endorectal balloons. Materials and Methods: This is a single institutional review of consecutive patients treated with histologically confirmed localized prostate cancer. Prior to treatment, all patients underwent placement of fiducials into the prostate and insertion of a hydrogel rectal spacer. Patients were typically given a prescription dose of 7920 cGy at 180 cGy per fraction using a Monte Carlo dose calculation algorithm. Acute and late toxicity were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 5. Biochemical failure was defined using the Phoenix definition. Results: From July 2018 to April 2020, 33 patients were treated (median age, 75 years). No severe acute toxicities were observed. The most common acute toxicity was urinary frequency. With a median follow-up of 18 months, there were no high-grade genitourinary late toxicities; however, one grade 3 gastrointestinal toxicity was observed. Late erectile dysfunction was common. One treatment failure was observed at 21 months in a patient treated for high-risk prostate cancer. Conclusion: Early clinical outcomes of patients treated with PBS–PBT using Monte Carlo–based planning, fiducial placement, and rectal spacers sans endorectal balloons demonstrate minimal treatment-related toxicity with good oncologic outcomes. Rectal spacer stabilization without the use of endorectal balloons is feasible for the use of PBS– PBT.