bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifelong regeneration of cerebellar Purkinje cells after induced cell ablation in zebrafish
Authors: Pose-Méndez Sol , Schramm Paul , Winter Barbara , Meier Jochen C , Ampatzis Konstantinos , Köster Reinhard W
Published: April 2023

Zebrafish have an impressive capacity to regenerate neurons in the central nervous system. However, regeneration of the principal neuron of the evolutionary conserved cerebellum, the Purkinje cell (PC), is believed to be limited to developmental stages based on invasive lesions. In contrast, non-invasive cell type-specific ablation by induced apoptosis closely represents a process of neurodegeneration. We demonstrate that the ablated larval PC population entirely recovers in number, quickly reestablishes electrophysiological properties, and properly integrates into circuits to regulate cerebellum-controlled behavior. PC progenitors are present in larvae and adults, and PC ablation in adult cerebelli results in an impressive PC regeneration of different PC subtypes able to restore behavioral impairments. Interestingly, caudal PCs are more resistant to ablation and regenerate more efficiently, suggesting a rostro-caudal pattern of de- and regeneration properties. These findings demonstrate that the zebrafish cerebellum is able to regenerate functional PCs during all stages of the animal’s life.
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
Authors: Adolf Lea Antje , Müller-Jochim Angelika , Kricks Lara , Puls Jan-Samuel , Lopez Daniel , Grein Fabian , Heilbronner Simon
Published: April 2023

Sufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains [FMMs]) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.
Single cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration
Authors: Celotto Laura , Rost Fabian , Machate Anja , Bläsche Juliane , Dahl Andreas , Weber Anke , Hans Stefan , Brand Michael
Published: April 2023

In the lesioned zebrafish retina, Müller glia produce multipotent retinal progenitors that generate all retinal neurons, replacing lost cell types. To study the molecular mechanisms linking Müller glia reactivity to progenitor production and neuronal differentiation, we used single cell RNA sequencing of Müller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced Müller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of Müller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.
DNA damage signaling in Drosophila macrophages modulates systemic cytokine levels in response to oxidative stress
Authors: Hersperger Fabian , Meyring Tim , Weber Pia , Chhatbar Chintan , Monaco Gianni , Dionne Marc S , Paeschke Katrin , Prinz Marco , Groß Olaf , Classen Anne-Kathrin , Kierdorf Katrin
Published: April 2023

Environmental factors, infection, or injury can cause oxidative stress in diverse tissues and loss of tissue homeostasis. Effective stress response cascades, conserved from invertebrates to mammals, ensure reestablishment of homeostasis and tissue repair. Hemocytes, the Drosophila blood-like cells, rapidly respond to oxidative stress by immune activation. However, the precise signals how they sense oxidative stress and integrate these signals to modulate and balance the response to oxidative stress in the adult fly are ill-defined. Furthermore, hemocyte diversification was not explored yet on oxidative stress. Here, we employed high-throughput single nuclei RNA-sequencing to explore hemocytes and other cell types, such as fat body, during oxidative stress in the adult fly. We identified distinct cellular responder states in plasmatocytes, the Drosophila macrophages, associated with immune response and metabolic activation upon oxidative stress. We further define oxidative stress-induced DNA damage signaling as a key sensor and a rate-limiting step in immune-activated plasmatocytes controlling JNK-mediated release of the pro-inflammatory cytokine unpaired-3. We subsequently tested the role of this specific immune activated cell stage during oxidative stress and found that inhibition of DNA damage signaling in plasmatocytes, as well as JNK or upd3 overactivation, result in a higher susceptibility to oxidative stress. Our findings uncover that a balanced composition and response of hemocyte subclusters is essential for the survival of adult Drosophila on oxidative stress by regulating systemic cytokine levels and cross-talk to other organs, such as the fat body, to control energy mobilization.
Calcium transients trigger switch-like discharge of prostaglandin E2 in an extracellular signal-regulated kinase-dependent manner
Authors: Watabe Tetsuya , Yamahira Shinya , Takakura Kanako , Thumkeo Dean , Narumiya Shuh , Matsuda Michiyuki , Terai Kenta
Published: April 2023

Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin–Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity.
Lack of CCDC146, a ubiquitous centriole and microtubule-associated protein, leads to non-syndromic male infertility in human and mouse
Authors: Muroňová Jana , Kherraf Zine-Eddine , Giordani Elsa , Eckert Simon , Cazin Caroline , Amiri-Yekta Amir , lambert Emeline , Chevalier Geneviève , Martinez Guillaume , Neirijnck Yasmine , Kühne Francoise , Wehrli Lydia , Klena Nikolai , Hamel Virginie , Escoffier Jessica , Guichard Paul , Coutton Charles , Ben Mustapha Selima Fourati , Kharouf Mahmoud , Zouari Raoudha , Thierry-Mieg Nicolas , Nef Serge , Geimer Stefan , Loeuillet Corinne , Ray Pierre , Arnoult Christophe
Published: April 2023

Genetic mutations are a recurrent cause of male infertility. Multiple morphological abnormalities of the flagellum (MMAF) syndrome is a heterogeneous genetic disease, with which more than 50 genes have been linked. Nevertheless, for 50% of patients with this condition, no genetic cause is identified. From a study of a cohort of 167 MMAF patients, pathogenic bi-allelic mutations were identified in the
CCDC146
gene in two patients. This gene encodes a poorly characterized centrosomal protein which we studied in detail here. First, protein localization was studied in two cell lines. We confirmed the centrosomal localization in somatic cells and showed that the protein also presents multiple microtubule-related localizations during mitotic division, suggesting that it is a microtubule-associated protein (MAP). To better understand the function of the protein at the sperm level, and the molecular pathogenesis of infertility associated with
CCDC146
mutations, two genetically modified mouse models were created: a
Ccdc146
knock-out (KO) and a knock-in (KI) expressing a HA-tagged CCDC146 protein. KO male mice were completely infertile, and sperm exhibited a phenotype identical to our two MMAF patient’s phenotype with
CCDC146
mutations. No other pathology was observed, and the animals were viable. CCDC146 expression starts during late spermiogenesis, at the time of flagellum biogenesis. In the spermatozoon, the protein is conserved but is not localized to centrioles, unlike in somatic cells, rather it is present in the axoneme at the level of microtubule doublets. Expansion microscopy associated with the use of the detergent sarkosyl to solubilize microtubule doublets, provided evidence that the protein could be a microtubule inner protein (MIP). At the subcellular level, the absence of CCDC146 affected the formation, localization and morphology of all microtubule-based organelles such as the manchette, the head–tail coupling apparatus (HTCA), and the axoneme. Through this study, we have characterized a new genetic cause of infertility, identified a new factor in the formation and/or structure of the sperm axoneme, and demonstrated that the CCDC146 protein plays several cellular roles, depending on the cell type and the stages in the cell cycle.
A tRNA modification in Mycobacterium tuberculosis facilitates optimal intracellular growth
Authors: Tomasi Francesca G. , Kimura Satoshi , Rubin Eric J. , Waldor Matthew K.
Published: April 2023

Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen,
Mycobacterium tuberculosis
(
Mtb
), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA of
Mtb
, using tRNA sequencing (tRNA-seq) and genome-mining. Homology searches identified 18 candidate tRNA modifying enzymes that are predicted to create 13 tRNA modifications across all tRNA species. Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion of
Mtb
genes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species. Furthermore, the absence of
mnmA
attenuated
Mtb
growth in macrophages, suggesting that MnmA-dependent tRNA uridine sulfation contributes to
Mtb
intracellular growth. Our results lay the foundation for unveiling the roles of tRNA modifications in
Mtb
pathogenesis and developing new therapeutics against tuberculosis.
Second Book Launch and Creative Bilingual Workshop “Follow Your Heart. The School for Multipotentialites”
Authors: Poto Margherita Paola , Murray Emily Margaret , Russo Valentina , Green Jorinde
Published: April 2023

The overall aim of this report is to document the experience gained during the second book launch and the second experience of a creative and emotional education bilingual workshop on the book Follow Your Heart: the school for multipotentialites. Continuing along the lines of the first book launch and the co-created scientific workshop in Shepton Mallet, UK, in February 2023, the authors of the book, in collaboration with the teacher Jorinde Green (LaLa Land, Torino), organized a second event targeting primary-school aged children and their families to join for an afternoon of Follow Your Heart-inspired activities, storytelling, and collaborative work on ecological and emotional education in the Space Habitat, in via Le Chiuse 66, Torino. Building off the first book launch in the UK, which was hosted by the educational farm The Good Life Projects, this second event was held in a community center and project called “Habitat” and brought together 18 children (ages 4 to 9) and their parents and/or guardians. The proceeds from the event, which were collected through book sales, were donated to Windsor Hill Wood and to Space Habitat (our host) itself, to support educational spaces that promote quality education for all. In continuity with the previous report, this report aims to share the key lessons learned from the event and promote further discussion within the field of emotional and ecological education, in line with the project ECO_CARE.
Effectiveness of real-time classroom interactive competition on academic performance: a systematic review and meta-analysis
Authors: Jurado-Castro Jose Manuel , Vargas-Molina Salvador , Gómez-Urquiza Jose L. , Benítez-Porres Javier
Published: April 2023

In recent years, different tools have been introduced into the educational landscape to promote active participation and interaction between students and teachers through personal response systems. The evolution of this methodology has allowed students to participate in real-time by answering questions posed. Previous reviews on the effectiveness of real-time classroom interactive competition (RCIC) on academic performance have been performed; however, this research was based only on Kahoot, without considering other RCIC tools or programs. In addition, the RCIC effectiveness at different educational levels and its effect according to the duration of the intervention has not been meta-analytically analyzed until to date. The aim of this meta-analysis was to analyze the RCIC effectiveness in improving academic performance. A search focused on studies from the educational field published from 2010 until September 2022 was performed. Experimental studies with objective and valid data (scores based on tests or exams) were included. From a total of 397 studies considered potentially eligible, 23 studies met the inclusion criteria. The sample was n = 1,877 for the experimental group and n = 1,765 for the control group with an academic improvement in favor to experimental group (MD 7.34; CI [5.31–9.43]; p < 0.001). There was also significant improvement in academic performance when analyzing different educational levels and different tools. In addition, both short-term interventions (two weeks or less in duration) and long-term (from two weeks to one year in duration) were effective. Therefore, RCIC interventions seem to be an effective strategy to improve academic performance.
Tone in UNICEF Press Releases in the Global Settings: A Contrastive Analysis
Authors: Domingo Nikko
Published: April 2023

Tone sets the readers' mood in which the writers confide their writing styles which can convey much of the cultural background of the community to where they belong. In the world's preceding advancement, the tone in a text has limited literature in the field. This motivated the researcher to look at the press release as it is the new face of public relations. The nature of the study is on Intercultural rhetoric (IR)/Contrastive Rhetoric (CR), the study of written discourse between and among individuals with different cultural backgrounds. The study used quantitative and qualitative approaches as they complement the richness of the study. The gathered press release headlines of UNICEF written by authors from varied discourse communities, namely the Philippines, Thailand, and the United States of America, had gone through content analysis and discovered the ingenuity and inspiration in their word selection in writing headlines. The headlines from the Philippines are analyzed for having a committed tone and logical and analytical attitude. Interestingly, press releases from Thailand have a committed tone as well. On the other hand, press releases from the USA have a neutral tone.
Spending Behavior of Non-Teaching Personnel in Private Higher Educational Institutions in Albay Province
Authors: Llona Feb Marie
Published: April 2023

Spending behavior is disbursing money in response to an action, an environment, or a person to satisfy needs and wants. Employees provide their services in exchange for payment, which may take the form of wages or salary. The aim of this study was to determine the spending behavior of non-teaching personnel in private higher educational institutions in Albay and how they are going to improve their spending behavior. This study used mixed methods, qualitative and quantitative research designs, and utilizing a survey questionnaire which has three parts, to gather the necessary data and information needed for this study. Using the statistical tool frequency count and percentage distribution, Likert scale, and ranking. The analyzed data revealed that the respondents "often" spend on their necessities and "seldom" when it comes to their leisure. However, there are problems encountered by the respondents along with their spending practices that resulted in not having a budget plan. Employees should always keep track of their expenses to ensure proper spending. As a result, they will become more aware of their finances, which will make it easier for them to alter their spending habits by being able to track where their money is going. Employees should be aware of the significance of their financial decisions. They will have a better chance of being financially secure if they have the right knowledge in handling finances.
Lived Experiences of the Graduate School Professors in Albay amidst Covid-19 Pandemic
Authors: Notario Jeorge
Published: April 2023

Everyone affects by the COVID-19 pandemic. The pandemic would have a vastly different impact on each professor. This study aimed to analyze the lived experiences of graduate school professors in private higher education institutions in the second district of Albay and the challenges experienced during the Covid-19 pandemic. Primarily, this research investigated the experiences brought by the shift to different modes of delivery of education from the traditional face-to-face. This study used qualitative and quantitative research designs interview guide, and a survey questionnaire to obtain necessary data and information. The study found that the majority of professors encountered the same challenges encountered power interruption and low internet connection. The study concludes that the respondents can effectively manage their time and pace because of a new way of instruction on the use of the internet. In regards to and in line with the findings, the professors experienced more negative reactions about internet connectivity and technical difficulties, thus hindering them from fully benefiting from the new learning. Professors should be reflective and adaptable in terms of Instructional delivery, learning environment, time management, and student assessment. They may have had to learn how to use different technological tools through the internet and ensure that it can be delivered effectively online.
Development of Online General Chemistry Teaching Materials Integrated with HOTS-Based Media Using the ADDIE Model
Authors: Purba Jamalum , Panggabean Freddy Tua Musa , Widarma Adi , Sutiani Ani
Published: April 2023

The 21st century education system prioritizes students to have critical, creative, collaborative thinking skills and communication skills, including higher-order thinking skills. This study aims to develop online teaching materials for HOTS-based integrated General Chemistry courses using the ADDIE model to improve students' higher order thinking skills. This development research resulted in HOTS-based integrated online teaching materials that were feasible and effective in improving students' higher order thinking skills. Through the HOTS-based media integrated online teaching materials produced, students are required and trained to be able to think critically, creatively, analytically towards existing information and data and have the ability to solve problems.
Benchmark Evaluation & Proposed Electrical Architecture for a 12V BSG Vehicle
Authors: Mishra Priyamvad , Varma K. Phaneendra
Published: April 2023

This paper makes an effort to define an optimal electrical architecture for a 12V BSG system for a mid- sized diesel engine, with the help of functional validation tests and specific test cases developed by the authors. The first few sections of the paper explain various modes of a 12V BSG hybrid operations namely-ESS, torque assist and recuperation on a reference vehicle. Set of test cases have been developed to explain 12V BSG behavior as a DC motor during ESS and torque- assist mode of operation and as a 3-phase generator during regenerative coasting mode. In the final section, an optimized electrical architecture of 12V BSG system is proposed for mid-sized diesel engine with manual transmission, based on objective measurement of test cases and a Pugh Comparison matrix of various feasible architectures.
Otimização da desidratação osmótica da mangaba (Hancornia speciosa) como alternativa para a sua preservação
Authors: De Souza Michael Ruan Silveira , Da Silva Larissa de Sousa , Chaves Rosane Patrícia Ferreira , Pombo Joseane Cristina Pinheiro , Moraes Jaqueline de Fátima Cabral , Souza Tammy Sara Oliveira Iuco , Cardoso Raiane Vieira , De Araújo Adriano Lucena
Published: April 2023

A mangaba (Hancornia speciosa) é um fruto característico da região Nordeste do Brasil e apresenta excelentes atributos sensoriais e nutritivos, sendo também utilizado na industrialização, sob a forma de doces, geleias, compotas, vinho, vinagre, suco e sorvete. Esta pesquisa objetiva otimizar o processo de desidratação osmótica (DO) da mangaba ao analisar a influência de diferentes concentrações de solução osmótica (C) em diferentes períodos de imersão (T) do fruto, sobre as respostas perda de água (PA) e ganho de sólidos (GS), a fim de estabelecer condições ótimas para a melhor conservação do fruto.  Para o desenvolvimento da pesquisa, os frutos foram adquiridos no estádio de maturação maduro de um fornecedor local da região de Salvaterra (Pará) e transportados para o Laboratório de Tecnologia de Alimentos (UEPA – Campus Salvaterra), onde se iniciaram os procedimentos de desidratação osmótica. A relação amostra/solução foi de 1 g do fruto para cada 5 mL da solução osmótica, sendo a umidade determinada antes e após o processo. Para avaliar os efeitos das variáveis independentes (C e T), foi utilizado um delineamento composto central rotacional (DCCR) do tipo 22, totalizando 11 ensaios experimentais. As análises estatísticas dos coeficientes de regressão e a análise de variância (ANOVA) foram utilizados para avaliar o grau de ajuste dos modelos propostos aos dados experimentais. As superfícies de respostas apontaram que maiores concentrações de solução osmótica (C) e maiores tempos de imersão (T) favoreceram as maiores PA e GS no fruto. Os resultados obtidos para a otimização simultânea das respostas definiu como condições ótimas para o processo: C = 56 % e T = 55,18 min, visando a maximização da PA e minimização do GS.
Segurança em megaeventos: o olhar de torcedores sobre a copa do mundo de 2018
Authors: Medeiros Tiago Aquiles Ribeiro , Pinto Rafaela Caetano
Published: April 2023

Este trabalho versa sobre segurança em megaeventos esportivos. O objetivo geral do estudo é analisar a segurança da Copa do Mundo de 2018 sob a ótica do torcedor presente nos estádios e evento paralelo oficial (FAN FEST). A coleta de dados desta pesquisa qualitativa deu-se por um grupo focal realizado com torcedores residentes em Brasília-DF que estiveram na Rússia para assistir aos jogos da Copa do Mundo de 2018 a fim de compreender as questões formuladas no problema e nos objetivos da pesquisa. As respostas foram analisadas seguindo o método de análise de conteúdo (Bardin, 2011). A pesquisa revelou que os torcedores consideraram a segurança como um dos pontos positivos na Copa do Mundo de 2018. Os participantes também afirmaram terem se sentido seguros nos locais de competição e nas cidades-sede por onde passaram. Os torcedores ainda identificaram riscos e analisaram medidas de segurança adotadas no referido megaevento esportivo.
Hyer-Ulam-Stability of Generalized Quadratic Functional Equation in Random Normed Spaces
Authors: Devi Sushma
Published: April 2023

The purpose of this paper to propose a finite variable generalized quadratic functional equation with solution. Also investigate Hyers Ulam stability in Random normed space by direct method.
After a Texas Judge Invalidated the ACA’s No-Cost Mandate for Common Preventive Care Under Private Insurance, What Can Patients Expect?
Authors: Rubin Rita
Published: April 2023

This Medical News article discusses a recent court ruling that invalidated the Affordable Care Act’s requirement for privately insured patients to have no out-of-pocket costs for certain preventive services and drugs.
Immune Checkpoint Inhibitors and Long-term Survival of Patients With Metastatic Urothelial Cancer
Authors: Zhu Alec , Garcia Jorge Alberto , Faltas Bishoy , Grivas Petros , Barata Pedro , Shoag Jonathan E.
Published: April 2023

This cohort study uses published clinical trial data to assess long-term survival of patients with metastatic urothelial carcinoma who are treated with immune checkpoint inhibitors.
Risk of Recall Associated With Modifications to High-risk Medical Devices Approved Through US Food and Drug Administration Supplements
Authors: Dubin Jonathan R. , Enriquez Jonathan R. , Cheng An-Lin , Campbell Hunter , Cil Akin
Published: April 2023

Importance

High-risk medical devices approved by the US Food and Drug Administration (FDA) can undergo modifications to their original premarket approval (PMA) via 1 of 5 types of supplements. Only panel track supplements (approximately 1%) require clinical data for approval. The association between device modifications and risk to patient safety has not previously been analyzed.

Objective

To determine the association between PMA supplements and the risk of any device recall and high-risk (class 1) recall.

Design, Setting, and Participants

In this cohort study, the FDA database was queried for original devices approved via PMA from January 1, 2008, through December 31, 2019. Supplement and recall data were obtained for these devices from January 1, 2008, through December 31, 2021, giving a minimum 2-year follow-up after initial approval. Data were analyzed from July 6 to August 6, 2022. Retrospective, time-to-event analysis investigated the association between the number and type of supplements and risk of recall.

Exposures

Supplements submitted by manufacturers for FDA approval to modify devices.

Main Outcomes and Measures

A mixed-effects Cox proportional hazards regression model with frailty terms was used, modeling device recall as an outcome variable during the observation period. A second model was performed for class 1 (high-risk) recall. Explanatory variables are the number of supplements, number of panel track supplements, and cardiovascular devices. Multivariable analysis was performed to identify independent risk factors for recall with hazard ratios (HRs) as the main end point.

Results

A total of 373 original PMA devices with 10 776 associated supplements were included in the analysis. A median 2.5 (IQR, 1.2-5.0) supplements per device were approved annually. Cardiovascular devices contributed 138 supplements (37.0%), followed by microbiology with 45 (12.1%). No other specialty contributed more than 10%. Multivariable analysis demonstrated that each increase of 1 supplement per year was associated with increased risk of recall (HR, 1.28 [95% CI, 1.15-1.44]; P < .001). For class 1 recall, increased number of supplements (HR, 1.32 [95% CI, 1.06-1.64]; P = .01) and cardiovascular vsnoncardiovascular classification of devices (HR, 3.51 [95% CI, 1.15-10.72]; P = .03) were significantly associated with an increased risk of recall.

Conclusions and Relevance

The findings of this cohort study suggest that PMA supplements are associated with an approximately 30% increased risk of any recall and class 1 recall. The FDA processes for approving modifications to high-risk medical devices should be reevaluated to optimize patient safety and public health.
Evaluation of Preferred Language and Timing of COVID-19 Vaccine Uptake and Disease Outcomes
Authors: Quadri Nasreen S. , Knowlton Greg , Vazquez Benitez Gabriela , Ehresmann Kirsten R. , LaFrance Amy B. , DeFor Terese A. , Smith M. Kumi , Mann Erin M. , Alpern Jonathan D. , Stauffer William M.
Published: April 2023

Importance

Beyond traditional race and ethnicity demographic characteristics, additional discrete data variables are needed for informed health interventions in the US.

Objective

To examine whether COVID-19 vaccine uptake patterns and associated disease outcomes differ among language preference groups.

Design, Setting, and Participants

A cohort study of 851 410 individuals aged 18 years or older in a large multispecialty health system in Minnesota and western Wisconsin was conducted between December 15, 2020, and March 31, 2022.

Exposure

Self-identified language preference and limited English proficiency (LEP) as measured by interpreter need were used to create subgroups using US census categories and attention to capture languages known to represent refugee groups.

Main Outcomes and Measures

The primary outcome was COVID-19 vaccination uptake rates and time to first vaccine. Secondary outcomes were rates of COVID-19–associated hospitalization and death.

Results

Most of the 851 410 participants (women, 493 910 [58.0%]; median age, 29 [IQR, 35-64] years) were US-born English speakers; 7.5% were born in other countries, 4.0% had a language preference other than English (LPOE), and 3.0% indicated LEP as measured by interpreter need. Marked temporal clusters were observed for COVID-19 vaccination uptake, hospitalizations, and deaths associated with primary series vaccine eligibility, booster availability, and COVID-19 variants. Delayed first-dose vaccine was observed with LPOE (hazard ratio [HR], 0.83; 95% CI, 0.82-0.84) and interpreter need (HR, 0.81; 95% CI, 0.80-0.82) compared with those with English language preference and proficiency. Patients with LPOE were approximately twice as likely to be hospitalized (rate ratio [RR], 1.85; 95% CI, 1.63-2.08) or die (RR, 2.13; 95% CI, 1.65-2.69). Patients with LEP experienced even higher rates of hospitalization (RR, 1.98; 95% CI, 1.73-2.25) and COVID-19–associated death (RR, 2.32; 95% CI, 1.79-2.95). Outcomes varied for individual language preference groups.

Conclusions and Relevance

In this study, delayed time to first-dose vaccine was associated with increased COVID-19 hospitalization and death rates for specific LPOE and LEP groups. The findings suggest that data collection of language preference and interpreter need provides actionable health intervention information. Standardized system-level data collection, including at a national level, may improve efficient identification of social groups with disproportionate health disparities and provide key information on improving health equity in the US.
Another Effort to Get People With Mental Illness Experiencing Homelessness Off the Streets—A Sound Idea?
Authors: Hogan Michael F.
Published: April 2023

This Viewpoint assesses the plan to use police officers to arrange hospitalization of people with mental illness experiencing homelessness in New York City and suggests improvements and alternatives.
Effort-Cost Decision-making Among Individuals With Schizophrenia
Authors: Blouzard Elodie , Pouchon Arnaud , Polosan Mircea , Bastin Julien , Dondé Clément
Published: April 2023

Importance

Motivational impairments in schizophrenia are by definition associated with poor outcome. It is postulated that the reduction of goal-directed behavior arises from abnormal trade-offs between rewards and efforts.

Objective

To examine whether schizophrenia is associated with impairments in effort-cost decision-making.

Data Sources

For this systematic review and meta-analysis, the PubMed, ScienceDirect, PsycINFO, Embase, and ClinicalTrials.gov databases were searched from inception to July 2022 for studies that investigated effort-cost decision-making in schizophrenia. Search terms included effort, cost, and schizophrenia.

Study Selection

Consensual criteria for inclusion were peer-reviewed studies published in English that used a computerized effort-cost decision-making behavioral paradigm and compared individuals with schizophrenia with control individuals.

Data Extraction and Synthesis

The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used for abstracting data. Data were extracted independently by 2 authors and then pooled using random-effects sizes and bayesian approaches.

Main Outcomes and Measures

The main outcomes were performance on effort-cost decision-making tasks requiring an effort-reward trade-off, measured by Hedges g effect size. Effects of moderators were tested with meta-regressions and subgroup analyses.

Results

Twenty studies involving 1503 participants were included: 837 individuals with schizophrenia (541 [64.6%] male; mean [SD] age, 35.89 [6.70] years) and 666 control individuals without schizophrenia (360 [54.1%] male; mean [SD] age, 34.16 [5.92] years). Participants with schizophrenia had significantly reduced willingness to expend effort for rewards compared with controls (k = 20; effect size, 0.43; 95% CI, 0.30-0.56; P < .001; I2 = 33.1%; Q test P = .08). The magnitude of the deficit was significantly greater for high-reward trials. The severity of negative symptoms was negatively associated with effort-cost decision-making (k = 8; effect size, −0.33; 95% CI, −0.50 to −0.15; P < .001), while participants with a high number of negative symptoms had a significantly larger impairment in effort-cost decision-making (k = 5; effect size, 0.47; 95% CI, 0.10-0.84; P = .01).

Conclusions and Relevance

In this systematic review and meta-analysis, schizophrenia was associated with deficits in effort allocation as indexed by effort-cost decision-making tasks. Understanding the cognitive and neurobiological mechanisms driving effort allocation impairments may assist in developing novel interventions.
Association of Year of Surgery and Carotid Stenting Outcomes in High-risk Patients, 2015-2021
Authors: Stonko David P. , Bose Sanuja , McDermott Katherine , Keegan Alana , Morrison Jonathan J. , Hicks Caitlin W.
Published: April 2023

This cohort study quantifies the yearly trends and outcomes of transcarotid artery revascularization vs transfemoral carotid artery stenting among high-risk patients from 2015 to 2021.
Self‐configuring nnU‐Net for automatic delineation of the organs at risk and target in high‐dose rate cervical brachytherapy, a low/middle‐income country's experience
Authors: Duprez Didier , Trauernicht Christoph , Simonds Hannah , Williams O'Brian
Published: April 2023

Background

The high‐dose rate (HDR) brachytherapy treatment planning workflow for cervical cancer is a labor‐intensive, time‐consuming, and expertise‐driven process. These issues are amplified in low/middle‐income countries with large deficits in experienced healthcare professionals. Automation has the ability to substantially reduce bottlenecks in the planning process but often require a high level of expertise to develop.

Purpose

To implement the out of the box self‐configuring nnU‐Net package for the auto‐segmentation of the organs at risk (OARs) and high‐risk CTV (HR CTV) for Ring‐Tandem (R‐T) HDR cervical brachytherapy treatment planning.

Methods

The computed tomography (CT) scans of 100 previously treated patients were used to train and test three different nnU‐Net configurations (2D, 3DFR, and 3DCasc). The performance of the models was evaluated by calculating the Sørensen‐dice similarity coefficient, Hausdorff distance (HD), 95th percentile Hausdorff distance, mean surface distance (MSD), and precision score for 20 test patients. The dosimetric accuracy between the manual and predicted contours was assessed by looking at the various dose volume histogram (DVH) parameters and volume differences. Three different radiation oncologists (ROs) scored the predicted bladder, rectum, and HR CTV contours generated by the best performing model. The manual contouring, prediction, and editing times were recorded.

Results

The mean DSC, HD, HD95, MSD and precision scores for our best performing model (3DFR) were 0.92/7.5 mm/3.0 mm/ 0.8 mm/0.91 for the bladder, 0.84/13.8 mm/5.3 mm/1.4 mm/0.84 for the rectum, and 0.81/8.5 mm/6.0 mm/2.2 mm/0.80 for the HR CTV. Mean dose differences (D2cc/90%) and volume differences were 0.08 Gy/1.3 cm3 for the bladder, 0.02 Gy/0.7 cm3 for the rectum, and 0.33 Gy/1.5 cm3 for the HR CTV. On average, 65% of the generated contours were clinically acceptable, 33% requiring minor edits, 2% required major edits, and no contours were rejected. Average manual contouring time was 14.0 min, while the average prediction and editing times were 1.6 and 2.1 min, respectively.

Conclusion

Our best performing model (3DFR) provided fast accurate auto generated OARs and HR CTV contours with a large clinical acceptance rate.
Natural history and survival rate of familial amyloidosis with polyneuropathy: A nationwide databank
Authors: Tseng Wei‐Hsiang , Huang Han‐Wei , Li Chia‐Chun , Chang Chin‐Sung , Chan Wing P. , Lin Kong‐Pin , Wu Chih‐Hsing
Published: April 2023

Objective

Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy, a rare autosomal‐dominant disease, has gained attention in recent years owing to treatment improvements. However, epidemiological real‐world mega database of nationwide natural history and survival rates, especially with the specific mutation of Ala97Ser, are limited.

Methods

Taiwan National Health Insurance Research Database contains data from over 23 million individuals; Among them, 175 ATTRv amyloidosis patients validated by rare disease registry were enrolled. Multivariable Cox proportional hazard analyses were applied to investigate the association between baseline characteristics and all‐cause mortality.

Findings

From 2008 to 2020, the annual incidence and prevalence rates of specific mutations (Ala97Ser) leading to ATTRv amyloidosis with polyneuropathy were 0.04–1.14 and 0.04–4.79 per million in Taiwan, respectively. In Taiwan, these patients exhibited male predominance with a mean age at validation of 62.75 years. At the 5th year after validation, patients exhibited a survival rate of approximately 50%, with higher mortality in male patients (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.15–4.31) and patients older at validation (HR: 1.10, 95% CI: 1.06–1.15). The two most common departments in outpatient were neurology and family medicine, and neurology and cardiology in inpatient. The three most common causes of death registered were unspecified amyloidosis (30.6%), organ‐limited amyloidosis (20.9%), and neuropathic heredofamilial amyloidosis (9.7%).

Interpretation

The annual prevalence rate of specific mutation (Ala97Ser)‐dominant ATTRv amyloidosis with polyneuropathy in Taiwan is comparable to the mid‐ to high‐prevalence country level of the research by Schmidt et al. The extraordinarily high mortality, especially among patients older at validation, may reflect the inadequate awareness and the necessity of early intervention with novel disease‐modifying regimens.
MC4R in Central and Peripheral Systems
Authors: Wei Ran , Li Danjie , Jia Sheng , Chen Yuhong , Wang Jiqiu
Published: April 2023

Obesity has emerged as a critical and urgent health burden during the current global pandemic. Among multiple genetic causes, melanocortin receptor‐4 (MC4R), involved in food intake and energy metabolism regulation through various signaling pathways, has been reported to be the lead genetic factor in severe and early onset obesity and hyperphagia disorders. Most previous studies have illustrated the roles of MC4R signaling in energy intake versus expenditure in the central system, while some evidence indicates that MC4R is also expressed in peripheral systems, such as the gut and endocrine organs. However, its physiopathological function remains poorly defined. This review aims to depict the central and peripheral roles of MC4R in energy metabolism and endocrine hormone homeostasis, the diversity of phenotypes, biased downstream signaling caused by distinct MC4R mutations, and current drug development targeting the receptor.
Photofunctional Scope of Fluorescent Dithienylethene Conjugates with Aza‐Heteroaromatic Cations
Authors: Chen‐Wu Jialei , Guzmán‐Ríos David B. , Remón Patricia , González‐Delgado José A. , Martínez‐Martínez Antonio J. , Nájera Francisco , Arteaga Jesús F. , Pischel Uwe
Published: April 2023

A series of dithienylethene (DTE) photoswitches with aza‐heteroaromatic cationic moieties is synthesized. The switches are characterized regarding their photochemical and photophysical properties in acetonitrile and in water. The efficiency of the switching and the photostationary state composition depend on the degree ofπ‐conjugation of the heteroaromatic systems. Thus, DTEs with acridinium‐derived moieties have very low quantum yields for the ring‐closing process, which is in contrast to switches with pyridinium and quinolinium moieties. All switches emit fluorescence in their open forms. The involved electronic transitions are traced back to an integrative picture including the DTE core and the cationic arms. The emission can be fine‐tuned by theπ‐conjugation of the heteroaromatic cations, reaching the red spectral region for DTEs with acridinium moieties. On ring‐closing of the DTEs the fluorescence is not observable anymore. Theoretical calculations point to rather low‐lying energy levels of the highly conjugated ring‐closed DTEs, which would originate near‐infrared emission (> 1200 nm). The latter is predicted to be very weak due to the concurrent non‐radiative deactivation, according to the energy‐gap law. In essence, an ON–OFF fluorescence switching as the result of the electrocyclic ring‐closing reaction is observed.
Fiber Crossbars: An Emerging Architecture of Smart Electronic Textiles
Authors: Zhou Xuhui , Wang Zhe , Xiong Ting , He Bing , Wang Zhixun , Zhang Haozhe , Hu Dongmei , Liu Yanting , Yang Chunlei , Li Qingwen , Chen Ming , Zhang Qichong , Wei Lei
Published: April 2023

Smart wearables have a significant impact on people's daily lives, enabling personalized motion monitoring, realizing the Internet of Things, and even reshaping the next generation of telemedicine systems. Fiber crossbars (FCs), constructed by crossing two fibers, have become an emerging architecture among the accessible structures of state‐of‐the‐art smart electronic textiles. The mechanical, chemical, and electrical interactions between crossing fibers result in extensive functionalities, leading to the significant development of innovative electronic textiles employing FCs as their basic units. This review provides a timely and comprehensive overview of the structure designs, material selections, and assembly techniques of FC‐based devices. The recent advances in FC‐based devices are summarized, including multipurpose sensing, multiple‐mode computing, high‐resolution display, high‐efficient power supply, and large‐scale textile systems. Finally, current challenges, potential solutions, and future perspectives for FC‐based systems are discussed for their further development in scale‐up production and commercial applications.
Two‐Step Sequential Process for Fabricating Graphene Nanosheets Decorated with Copper Halide Nanocrystals and Their Optoelectronic Applications
Authors: Kim Minjin , Le Thanh‐Hai , Lee Jisun , Lee Haney , Kim Changjun , Heo Eunseo , Chang Mincheol , Yun Changhun , Yoon Hyeonseok
Published: April 2023

Nanocrystals of Cs3Cu2I5, a metal halide with promising potential as a perovskite substitute, are successfully grown on graphene nanosheets. An intermediate stage of physically exfoliated graphene nanosheets, concurrent with the formation of copper‐based seeds on graphene surface, is developed, for the first time, allowing for the subsequent growth of Cs3Cu2I5 nanocrystals (CsNCs) to obtain CsNCs‐decorated graphene nanohybrids (CsGNHs). The morphology and properties of the CsGNHs depend on the input amount of graphene nanosheets during the reaction. The photoluminescence intensity of the CsGNHs decreases with increasing graphene content, indicating that graphene facilitates nonradiative energy transfer from the CsNCs in the CsGNHs. The inherent self‐trapping exciton emission of the CsNCs is also affected by the graphene substrate. As the graphene content increases, the emission peaks of the CsGNHs broaden and diminish. The CsGNHs emit a stable solid‐state luminescence with a large Stokes shift (zero self‐absorption) under a high‐energy ultraviolet (UV) light. Consequently, the CsGNHs can act as optoelectronic transducers and selectively generate a turn‐on photocurrent response under specific‐wavelength UV light. Additionally, a new anticounterfeiting strategy is developed using the CsGNHs as a luminescent black ink to fabricate luminescent quick‐response codes with fake pixels.
Chiral Boro‐Phosphate Catalyzed Asymmetric Transfer Hydrogenation of 1‐Enal Substituted 2‐Naphthols: Access to Axially Chiral Styrene‐Type Allylalcohols
Authors: Jiang Hong‐Xin , Han Dan‐Dan , Song Rui‐Ping , Shi Qin , He Xiao‐Fan , Kou Wan‐Qing , Zhao Qi , Shao You‐Dong , Cheng Dao‐Juan
Published: April 2023

Herein, we present a chiral boro‐phosphate catalyzed atroposelective asymmetric transfer hydrogenation method, leading to a family of axially chiral styrene‐type allylalcohols. This dynamic kinetic resolution approach portrays simple procedure, mild conditions and good enantiocontrol (51–95% ee), thus providing an important alternative to assemble the challenging atropisomeric aryl‐acyclic alkene scaffolds.

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Recent Advances in Radical Reactions of Azo Compounds
Authors: Zhou Qin , Gong Xuanming , Yan Guobing
Published: April 2023

Azo compounds have attracted much attention in the past decades, due to their unique properties. Recently, the free radical strategy has been widely applied to the chemical transformations of azobenzenes, dialkyl azodicarboxylates, mainly including hydrogenation and functionalization of N=N double bond, and N‐functionalization reactions via the cleavage of the N=N double bonds. In this review, we systematically summarized these reactions as well as their mechanisms are discussed.

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