bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J. 
Published: April 2024

Abstract
Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive, and limited therapeutic options lead to poor prognosis for patients. HPN328 is a trispecific T cell–activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T-cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models, and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro, concomitant with T-cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T-cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T-cell engagers. HPN328 exhibited linear pharmacokinetics in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3-expressing malignancies.
Prevenção referente às modalidades alternativas de transmissão do Trypanosoma cruzi
Authors: Amato Neto Vicente , Chieffi Pedro Paulo , Nisida Isabelle Vera Vichr , Umezawa Eufrosina Setsu , Sabino Ester Cerdeira , Ruocco Rosa Maria de Souza Aveiro , Lopes Marta Heloisa , Dias João Carlos Pinto 
Published: April 2024

Noventa anos depois da descoberta da doença de Chagas, por Carlos Chagas em conjunto de exemplares investigações científicas que concretizaram os aspectos fundamentais da enfermidade, essa endemia continua, lamentavelmente, ainda proeminente em países latino-americanos, sobretudo em virtude da falta de maiores e melhores providências preventivas por parte de vários setores governamentais. No Brasil tiveram lugar em fase relativamente recente medidas adequadas que tornaram bem menos expressiva a transmissão do Trypanosoma cruri. Almejamos que prossigam e sejam imitadas por outras nações. Convém lembrar, a propósito, que o êxito foi devido à vontade política, à programação elaborada por profissionais competentes e à persistência, não influenciada pelas mudanças de governantes. No Estado de São Paulo, em particular, a transmissão vetorial a seres humanos foi controlada desde o início da década de 80, ocorrendo praticamente o desaparecimento da infestação domiciliar por Triatoma infestans (Souza, AG; Wanderley, D.M.V.; Buralli, G.M.M & Andrade, J.c.R. - Consolidation of the control of Chagas' disease in the State of São Paulo. (Mem. Inst, Oswaldo Cruz, 79 (supl.): 125-132, 1984). Nesse contexto merecem destacada atenção as modalidades alternativas de transmissão do T. cruri, porquanto diante do arrefecimento da veiculação através de triatomíneos elas contribuem efetivamente para o surgimentode novos acometimentos, devendo por isso haver, com rapidez e objetividade, proposição de propostas profiláticas pertinentes. Por isso, o Instituto de Medicina Tropical de São Paulo decidiu promover "Reunião sobre prevenção referente às modalidades alternativas de transmissão do Trypanosoma cruri", com a finalidade de apontar condutas atualmente tidas como recomendáveis, conforme explanações a cargo de alguns convidados capacitados a cooperar efetivamente. Fomos os organizadores do evento, realizado no dia 16 de outubro de 1998 e apoiado pelo Departamento de Higiene e Medicina Tropical da Associação Paulista de Medicina, pela Sociedade Brasileira de Medicina Tropical, pela Sociedade Médica Ítalo-Brasileira e pela Sociedade Paulista de Infectologia. As opiniões emitidas estão nesta coletânea, sempre respaldadas em pontos-de-vista pessoais, justificativas e bibliografia. Representam, se pelo menos suceder valorização do conjunto, contribuição realística para adoção de ações coibitórias a respeito de componentes alternativos, antes erroneamente sob determinados itens rotulados como excepcionais, atuantes na disseminação da doença de Chagas.
Atualização em genética da surdez não-sindrômica
Authors: Braga Maria Cristina C. , Abreu-Silva Ronaldo Serafim , Lezirovitz Karina , Mingroni-Netto Regina C. 
Published: April 2024

A surdez não-sindrômica é uma condição altamente heterogênea, com inúmeros genes de locos diferentes interferindo no desenvolvimento e na fisiologia da audição. Apresentamos uma revisão sobre a genética e biologia molecular do defeito. Estão envolvidos na surdez hereditária não-sindrômica cerca de 30genes autossômicos recessivos e 40 dominantes, 8 genes ligados ao cromossomo X e 5 mutações no DNA mitocondrial. 80% dos casos hereditários de surdez são determinados por mecanismo autossômico recessivo, com predomínio de uma única mutação, 35delG, no gene da Conexina 26, a qual é tida como a principal responsável pela deficiência auditiva neurossensorial congênita. Nos últimos anos, têm sido detectados vários casos de deficiência auditiva associada a mutações do DNA mitocondrial; a principal delas é a mutação A1555G, muitas vezes associada a casos de deficiência auditiva secundária ao uso de antibióticos aminoglicosídeos. Os avanços recentes na biologia molecular da surdez indicam ser justificável a triagem de mutações frequentes na surdez.
Genética do câncer de pulmão
Authors: Capelozzi Vera Luiza 
Published: April 2024

The lung cancer is one of the neoplasms of higher mortality. Biologicaly is the expression of the genetic alterations in the epithelial cells of the aerial ways. It is necessary to study the genetics and the pathology so that let us can arrive the best responses about the treatment, diagnosis and evolution of the disease.
Síndrome de Treacher Collins: aspectos clínicos, genéticos e moleculares
Authors: Passos-Bueno Maria Rita , Splendore Alessandra 
Published: April 2024

A síndrome de Treacher Collins (STC) é um distúrbio do desenvolvimento craniofacial de herança autossômica dominante que afeta cerca de 1 em 50.000 recém-nascidos, sendo que aproximadamente 60% dos casos são resultantes de mutações novas. A grande variabilidade observada no quadro clínico pode dificultar o diagnóstico, principalmente nos casos mais leves. Desde a identificação do gene responsável pela síndrome em 1996, já foram identificados diversos defeitos moleculares que causam a STC, a maioria dosquais são específicos para cada família, o que torna o exame de detecção de mutações bastante trabalhoso. Contudo, nos casos em que há dúvida de diagnóstico, a realização dos testes moleculares é extremamente importante. Apesar dos avanços na caracterização molecular desta doença, ainda não é possível explicar a grande variabilidade clínica observada entre os pacientes, inclusive dentro de uma mesma família. A identificação de fatores que contribuem para determinar a gravidade do quadro clínico será possivelmente omaior desafio no estudo molecular da STC, e certamente trará facilitará o aconselhamento genético para as famílias de afetados.
« C’est plus grave de faire un enfant que de faire une IVG ! ». Redéfinir l’avortement par la physiologie : luttes des sages-femmes pour défendre une juridiction professionnelle controversée
Authors: Borel Myriam 
Published: April 2024

Résumé
En 1975, la loi inscrit l’IVG dans la juridiction de la médecine, investie comme instrument du contrôle social dans la régulation des naissances. La demande d’IVG demeurait pensée comme phénomène relevant de la pathologie. Cependant, une normalisation de cette activité s’opère dans le système de soins avec l’évolution de l’encadrement réglementaire et des techniques de prise en charge. Notamment, les sages-femmes sont enrôlées dans le réagencement des formes de l’action publique en la matière. Leur champ de compétence est élargi. Ces nouvelles définitions de l’expertise médicale en santé sexuelle et reproductive donnent lieu à des délibérations sur les conceptions de la pratique abortive. L’association nationale des sages-femmes orthogénistes (ANSFO) se saisit de cette opportunité pour renforcer la légitimité du groupe professionnel, en opérant un travail cognitif de « physiologisation » de l’IVG.
Early and Late Complications of Mandibulectomy Free Flap Reconstruction: Does the Selective Use of Soft Tissue Only Flaps Reduce Complications?
Authors: McBee Dylan B. , DiLeo Michael J. , Keehn Caroline C. , Huang Andrew T. , Haskins Angela D. , Hernandez David J. 
Published: April 2024

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy. Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, <90 days; and late, >90 days) and the patients’ functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer’s exact test, and 2-sample t tests were used to analyze differences among variables. Results: We analyzed a cohort of 114 consecutive patients with mandibular defects, comprising 57 anterior and 57 posterior defects. Bony free flaps with hardware were used to reconstruct 98% of anterior defects compared to 58% of posterior defects ( P < .001). All soft tissue only flaps did not utilize any hardware during the reconstruction. Anterior defects demonstrated more late complications requiring additional surgery (30% vs 9%, P = .04). A secondary analysis of posterior mandibular reconstructions compared soft tissue only flaps and bony free flaps with hardware and showed equivalent rates of early (12% vs 13%, P > .99) and late (9% vs 8%, P > .99) complications requiring additional surgery while demonstrating a similar return to full oral competence (55% vs 46%, P = .52) and recovery of a 100% oral diet (67% vs 54%, P = .53). Conclusion: Osseous free tissue transfer for segmental mandibular defects remains the gold standard in reconstruction. In our patient cohort, anterior mandibular defects are associated with greater late (>90 day) complications requiring additional surgery. Comparable outcomes may be achieved with soft tissue only versus osseous free flap reconstruction of posterior mandibular defects.
“It Kills Your Soul”: A Mixed Methods Study of Ethical Sensitivity of Critical Care Nurses
Authors: Waterfield Denise , Barnason Susan 
Published: April 2024

Background: Critically ill patients often experience distressful and impactful symptoms and conditions that include pain, agitation/sedation, delirium, immobility, and sleep disturbances (PADIS). The presence of PADIS can affect recovery and long-term patient outcomes. An integral part of critical care nursing is PADIS prevention, assessment, and management. Ethical sensitivity of everyday nursing practice related to PADIS is an imperative part of implementing evidence-based care for patients. Objective: The first 2 aims of this study were to determine the measured level of ethical awareness as an attribute of ethical sensitivity among the critical care nurse participants and to explore the ethical sensitivity of critical care nurses related to the implementation of PADIS care. The third aim was to examine how the measured level of ethical awareness and ethical sensitivity exploration results converge, diverge, and/or relate to each other to produce a more complete understanding of PADIS ethical sensitivity by critical care nurses. Methods: This was a convergent parallel mixed methods study (QUAL + quant). Ethical sensitivity was explored by conducting an ethnography of critical care nurses. The participants were 19 critical care nurses who were observed during patient care, interviewed individually, participated in a focus group (QUAL), and were administered the Ethical Awareness Scale (quant). Findings: Despite high levels of individual ethical awareness among nurses, themes of ambiguous beneficence, heedless autonomy, and moral distress were found to be related to PADIS care. Conclusions: More effort is needed to establish moral community, ethical leadership, and individual ethical guidance for nurses to establish patient-centered decision-making and PADIS care.
Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database
Authors: Jiang Ying , Cheng Yusi , Du Zhiqiang , Shen Yuan , Zhou Qin , Ji Yingying , Zhu Haohao 
Published: April 2024

Objective: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. Methods: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. Results: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose ( n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt ( n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin ( n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive ( n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug’s label. Conclusion: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.
Retail investors, COVID and the quality of the New Zealand Stock Exchange
Authors: Gilbert Aaron , Tourani-Rad Alireza 
Published: April 2024

In this article, we investigate the impact of the influx of retail investors during the COVID-19 lockdowns on the New Zealand Stock Exchange on the efficiency of the market. On one hand, these investors bring added liquidity to the market, which generally improves market efficiency, and on the other hand, many of these investors were inexperienced retail traders who are often viewed as noise traders harming market efficiency. This natural experiment allows us to investigate the impact of retail investors. Using a sample of 99 New Zealand Exchange listed companies, we collect intraday price and quote data from 1 January 2019 to 24 March 2021. We compute a range of market quality measures across three categories: trading costs, price efficiency and speed of information incorporation. Our results clearly indicate that the influx of retail investors has reduced market quality; in particular, we observe more price predictability and information being impounded into prices more slowly. JEL Classification: C10, G14, G20
Improving Maternal Health and Birth Outcomes Through FreshRx: A Food-Is-Medicine Intervention
Authors: Ferris Dan , Roll Stephen , Huang Jin , Mathews Katherine , Ragain Trina , Simpson Katie , Jabbari Jason , Gilbert Kourtney , Frank Tyler 
Published: April 2024

Purpose Food insecurity has far-reaching consequences for health and well-being, especially during pregnancy and postpartum periods. This study examines a food-is-medicine approach that aimed to reduce food insecurity, maternal stress, depression, anxiety, preterm labor, and low birthweight. Design Pre-post interventional study of FreshRx: Nourishing Healthy Starts, a pregnancy focused food-is-medicine program led by a local hunger relief organization and obstetrics department. Setting St. Louis, Missouri, a Midwestern U.S. city with higher-than-average infant mortality, low birthweight, and preterm birth rates. Sample Participants (N = 125) recruited from a local obstetrics clinic had pregnancies earlier than 24 weeks gestation; spoke English; and were enrolled in Medicaid. At baseline, 67.0% reported very low food security and none reported high food security, while 34.7% indicated depressive symptoms. Intervention FreshRx included weekly deliveries of fresh food meal kits, nutrition counseling and education, care coordination, and supportive services. Measures 18-Question U.S. Household Food Security Survey, Edinburgh Postnatal Depression Scale, birthweight, gestational age. Analysis Single arm pre-post analysis. Results Average gestational age of 38.2 weeks (n = 84) and birthweight of 6.7 pounds (n = 81) were higher than rates for the general population in the area. For study participants who completed a sixty-day post-partum assessment, 13% (n = 45) indicated maternal depression ( P < .01). Conclusion Food-is-medicine interventions may be an efficient, effective, and equitable tool for improving birth and maternal health outcomes.
Temporarily Reversing Warfarin With Low-Dose 4-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Patients Undergoing an Invasive Procedure
Authors: Stevenson Byron , Roberts A. Joshua , Dager William E. 
Published: April 2024

Background: American Association for Thoracic Surgery and The International Society for Heart and Lung Transplantation (AATS/ISHLT) guidelines recommend warfarin in patients with continuous-flow left ventricular assist devices (LVADs) to reduce the risk of device thrombosis and systemic embolization. Left ventricular assist device patients often undergo elective and emergent procedures that require interrupted anticoagulation. Data and experience vary on the optimal strategy to rapidly reverse warfarin in LVAD patients when an emergent procedure is planned. Objective: The purpose of this study was to describe the use of 4-factor prothrombin complex concentrate (PCC4) for warfarin reversal in patients with LVADs undergoing elective and emergent procedures. Methods: This retrospective, single-center, cohort review describes the use of PCC4 in patients with LVADs who require warfarin reversal for elective or emergent procedures. The primary outcome was a composite incidence of pump thrombosis, venous thromboembolism, and ischemic stroke within 30 days of PCC4 administration. Results: In total, 14 patients received 17 administrations of PCC4. One patient received 3 administrations, and 1 other patient received 2 administrations during separate encounters. The median dose was 500 units or 6.6 units/kg (range = 4.2-14.1 units/kg). Of the PCC4 administrations, 82% (14/17) were for low bleed risk procedures and 76% (13/17) were for elective procedures. There were no cases of pump thrombosis, venous thromboembolism, or stroke within 30 days of the procedure. Conclusions and Relevance: Low-dose PCC4 appears to be a safe and effective temporary reversal strategy for patients with LVADs undergoing low-bleed risk elective procedures.
Caffeine and Sleep in Preventing Post-spinal Headache: Which One is More Effective?
Authors: Yayla Ayşegül , Karaman Özlü Zeynep , Uymaz Aras Gülistan 
Published: April 2024

Objective The study aimed to determine the effects of caffeine consumption and sleep on post-spinal headache after spinal anesthesia. Background Post-spinal headache is among the most well-known and common complications of spinal anesthesia. Although caffeine consumption is recommended to prevent headache after spinal anesthesia, caffeine does not prevent headache and causes sleep-related problems. No study in the literature found a correlation between sleep and caffeine consumption after spinal anesthesia and post-spinal headache. Methods The research is a descriptive and cross-sectional study. The study sample comprised 425 patients who underwent elective surgery in a research hospital. The research data were collected by face-to-face interviews between April 2021 and December 2023. The “Sociodemographic and Clinical Characteristics Form,” “Richard-Campbell Sleep Scale,” “Insomnia Severity Index,” and “Visual Analog Scale” were used in data collection. Factors affecting post-spinal headache were determined using binary logistic regression analysis. Results According to the binary logistic regression, the insomnia severity score (OR = 1.234; p < .001), sleep quality score (OR = .992; p < .01), postoperative sleep duration (OR = .619; p < .05), and not consuming coffee (OR = .035; p < .001) are statistically significant predictors of post-spinal headache and explain 57.7% of the variance. A one-unit increase in patients’ insomnia severity increased the probability of experiencing a post-spinal headache by 23.4%. With a one-unit increase in sleep quality, there was an 8% decrease in the probability of experiencing spinal headache, and a 3.81% decrease in the probability of experiencing post-spinal headache with an increase in sleep duration after surgery. The probability of experiencing post-spinal headache was 0.35 times higher in individuals who did not consume caffeine after surgery than in those who consumed it. Conclusion The present study demonstrated that insomnia severity and sleep quality were more effective than caffeine consumption in preventing post-spinal headache. Insomnia and decreased sleep quality may cause a significant burden in developing post-spinal headache in patients and may cause post-spinal headache to be observed more frequently. Therefore, the use of caffeine in preventing or reducing post-spinal headache may adversely affect the duration and quality of sleep and increase the severity of insomnia.