bluuebunny/crossref_metadata_2025_split huggingface dataset:
A first-in-human phase 1 trial of dose escalating intrathecal (IT) dendritic cells (cDC1s) primed against HER2/HER3 in patients (pts) with leptomeningeal disease (LMD) from triple-negative (TNBC) or HER2+ breast cancer (BC).
Authors: Forsyth Peter A. J. , Gandhi Shipra , Wilcox Jessica , Law Vincent , Mo Qianxing , Chen Zhihua , Ahmed Kamran A. , Piteo Cecily , Evernden Brittany , Pina Yolanda , Boire Adrienne Ann , Kalinski Pawel , Czerniecki Brian J. 
Published: July 2024

TPS2090 Background: Leptomeningeal disease (LMD) is a devastating complication of BC where it occurs in approximately 5% of pts and has a dismal prognosis. The CSF of pts with LMD have an innate (PMID:34035069), but not adaptive, immune response (bioRxiv 2023.03.17.533041; doi: https://doi.org/10.1101/2023.03.17.533041) that is insufficient to combat LMD. We used IT cDC1 to elicit an adaptive response in murine LMD and found that IT cDC1s were safe, induced a Th1 response, cured most HER2+ LMD, and prevented LMD recurrence (PMCID: 9354231). This Th1 response was CD4+ > CD8+ T cell dependent and produced marked B cell infiltration in the CSF. Mechanistic studies are in progress. These cDC1s have been shown to induce Th1 responses to HER2 and HER3 tumors and prolong survival in preclinical models (PMID: 35710296; PMID: 34785506). And there are several trials of cDC1s in BC patients that are ongoing (NCT03384914, NCT03387553, NCT05504707, NCT05325632, NCT04348747, NCT05378464). On the basis of our murine studies we hypothesized testing cDC1 therapy in pts that a RP2D would be found and the CSF following cDC1 therapy would be remodeled to have a Th1 adaptive immunological profile. Methods: This is a phase I single-arm, non-randomized dose escalation multicenter study to establish 1) the safety of IT cDC1s in pts with LMD, and 2) associations between clinical outcomes & translational CSF studies such as scRNAseq and cytokine/chemokine arrays. Eligibility includes TNBC or HER+ LMD pts, prior pCSpRT/WBRT, ECOG PS ≤2, cytologic or MRI diagnosis of LMD, normal marrow and organ function, life expectancy of ≥ 8 weeks, and an Ommaya reservoir in place. Exclusions included other treatments to treat LMD ≤ 2 wks or < five ½ lives, > 8mg of DXM/D or equivalent, pregnancy or immunodeficiency syndromes were excluded. IT cDC1s were administered once a week x 12 wks at one of 4 dose levels (1 X 106 – 5 X 107 cDC1s) until PD, DLT or withdrawal during those 12 wks. Primary Endpoints was to 1) determine the safety and DLTs, and 2) association between various clinical endpoints and immune profiles in the CSF. We used the Bayesian Optimal Interval (BOIN) design to find the MTD. Response was measured using RANO-LM (PMID: 30715514). DLTs were defined as ≥ gr. 3 not due to LMD & didn’t respond to medical intervention/CSF removal ≤ 96 hrs. Final pre & post cDC1 treatment cyto-, chemokine profiles and cellular/tumor profiles (scRNAseq) will be determined and associations between these and clinical endpoints will be determined. As of 01 30 2024 the 1st cohort closed with three pts (1 TNBC, 2 HER2+ pts)at the dose of 1 X 106 cDC1s. Clinical trial information: NCT05809752 .
Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function
Authors: Vella Max , Mohan Sneha , Christie Hannah , Bailey Kent R , Cobelli Claudio , Dalla Man Chiara , Matveyenko Aleksey , Egan Aoife M , Vella Adrian 
Published: July 2024

Abstract

Context
Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.

Objective
To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes.

Design
The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.

Setting
The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.

Participants
Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank.

Intervention
Two-hour, 7-sample OGTT.

Main Outcome Measures
Fasting, nadir, and integrated glucagon concentrations.

Results
One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.

Conclusion
The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.
The effectiveness of ketamine in medication of treatment-resistant depression - review
Authors: Brzozowska Patrycja , Bulska Klaudia , Sławek Konrad , Piela Andrzej , Piotrowski Jan , Hądzlik Izabela , Biały-Karbowniczek Julia , Nowińska Bianka , Łuczak Blanka , Słychan Katarzyna 
Published: July 2024

In spite of the variety of antidepressant drugs available for treating depressive disorder, treatment resistant depression (TRD) is still prevalent among the population.
Despite being used mainly in anesthesia, and mostly phased out by more modern anesthetics, ketamine shows potential when it comes to depressive disorder treatment.
We've set out to investigate the the relevant body of work to determine the efficacy of ketamine usage in patients with TRD.

Research shows that usage of ketamine used in patients with TRD leads to mood elevation, better cognitive functions, sleep and appetite. Moreover, ketamine is shown to decrease suicidal thoughts and shows potential in acute actions in emergency situations, especially with its faster effects when compared to traditional antidepressants. Some research show significant reduction in suicidal thoughts after just one infusion of ketamine.
Clinicians have developed intranasal, subcutaneous, intramuscular and oral ways of administering ketamine, which, though less bioavailable, when compered to intravenous use, are much more convenient and less expensive for the patients. All those ways of administering the drug have their upsides and downsides, and theres still debate on which is best.
Ketamine shows promise in patients with TRD. Some studies show that up to 70% of people with TRD response to ketamine, which might show efficacy of ketamine usage in those patients

State of knowledge:
Despite extensive research in the field of depression treatment, there's considerable lack of comprehensive reviews of efficacy of ketamine usage in cases where traditional ways of treating depression have failed. In the face of increasing number cases of treatment resistant depression worldwide, this paper aims to gather research papers regarding this topic and synthesize it into comprehensive review.
Rockafellian Relaxation and Stochastic Optimization Under Perturbations
Authors: Royset Johannes O. , Chen Louis L. , Eckstrand Eric 
Published: July 2024

In practice, optimization models are often prone to unavoidable inaccuracies because of dubious assumptions and corrupted data. Traditionally, this placed special emphasis on risk-based and robust formulations, and their focus on “conservative” decisions. We develop, in contrast, an “optimistic” framework based on Rockafellian relaxations in which optimization is conducted not only over the original decision space but also jointly with a choice of model perturbation. The framework enables us to address challenging problems with ambiguous probability distributions from the areas of two-stage stochastic optimization without relatively complete recourse, probability functions lacking continuity properties, expectation constraints, and outlier analysis. We are also able to circumvent the fundamental difficulty in stochastic optimization that convergence of distributions fails to guarantee convergence of expectations. The framework centers on the novel concepts of exact and limit-exact Rockafellians, with interpretations of “negative” regularization emerging in certain settings. We illustrate the role of Phi-divergence, examine rates of convergence under changing distributions, and explore extensions to first-order optimality conditions. The main development is free of assumptions about convexity, smoothness, and even continuity of objective functions. Numerical results in the setting of computer vision and text analytics with label noise illustrate the framework. Funding: This work was supported by the Air Force Office of Scientific Research (Mathematical Optimization Program) under the grant: “Optimal Decision Making under Tight Performance Requirements in Adversarial and Uncertain Environments: Insight from Rockafellian Functions.”
Noteworthy record of melanism in Leopardus tigrinus from El Cocuy National Natural Park, Colombia
Authors: Cáceres-Martínez Carlos H. , Zamora-Abrego Joan Gastón , González-Maya José F. 
Published: July 2024

El melanismo es el exceso de la pigmentación oscura que cubre parcial o totalmente el cuerpo de un animal. La presencia de individuos melánicos es relativamente común en varias de las especies de felinos. El objetivo de esta nota es reportar el segundo caso de melanismo en Leopardus tigrinus en vida libre para Colombia. Para el país solo existe un registro publicado para el departamento de Caldas. Entre junio de 2012 y marzo de 2020 se colocaron 158 estaciones simples de fototrampeo, en 5 áreas protegidas en la Cordillera Oriental de Colombia. Después de casi 8 años de monitoreo y con un esfuerzo de muestreo de 60,704 noches/trampa, registramos un individuo melánico de L. tigrinus, en el Parque Nacional Natural El Cocuy. Hasta ahora, la presencia de individuos de L. tigrinus melánicos se ha registrado principalmente en Brasil (aunque una vez se aclare su taxonomía pueda corresponder a una especie diferente). Para Colombia se cuenta con un registro documentado a más de 350 km de distancia del nuestro (departamento de Boyacá). Se considera que este fenómeno puede ser una respuesta adaptativa de las especies a presiones evolutivas del ambiente, y ha sido propuesta como una estrategia de segregación de nicho; sin embargo, dada la rareza de este fenotipo en el área de estudio, y en general a lo largo de su distribución, es necesario recabar mayor evidencia que pueda potencialmente explicar las fuerzas selectivas que favorecen o limitan este tipo de expresión fenotípica.
Predation of Sumichrast's vesper rat Nyctomys sumichrasti by the lizard Basiliscus plumifrons
Authors: Alvarado Randy , Mora José Manuel 
Published: July 2024

En Costa Rica hay 33 especies de Cricetidae, incluida Nyctomys sumichrasti, una rata relativamente poco común. En Costa Rica, habita principalmente en el dosel y rara vez se le ve debido a sus hábitos nocturnos y arbóreos. En México, se le ha observado tanto en las copas de los árboles como en el suelo en medio de vegetación densa y árboles. Durante una caminata en Selva Verde Lodge en el norte de Costa Rica, observamos un evento de depredación. Tomamos fotos desde aproximadamente 5 m para no perturbar al depredador. Identificamos al depredador en el lugar y luego confirmamos la identificación de la presa al comparar nuestras fotos con otras imágenes, guías de campo y claves taxonómicas. El 19 de marzo de 2023 a las 17:28 hr, observamos a una hembra adulta de basilisco verde (Basiliscus plumifrons) que depredó y consumió una Nyctomys sumichrasti. El basilisco persiguió a la rata por el suelo, la agarró con sus mandíbulas, la mató y luego la engulló. Todo el proceso duró aproximadamente 40 minutos. Nyctomys sumichrasti visita edificios en Selva Verde lodge donde siempre hay basiliscos. Estos son diurnos, mientras que N. sumichrasti es nocturna, pero pueden coincidir en actividad y ubicación. Recientemente, un basilisco verde hembra capturó una lagartija nocturna, y semanas antes, un macho de la misma especie consumió una cría de iguana verde en la misma área.
New records of small mammals in the diet of the buff-fronted owl, Aegolius harrisii and the black-and-white owl, Strix nigrolineata, along with a review of mammal prey of owls in Colombia
Authors: Marín-Giraldo Valentina , Chaves-Castaño Sarah , Mejía-Fontecha Ingrith Y. , Velásquez-Guarín Daniela , Mejía-Egas Ofelia , López-Ordoñez Juan Pablo , Ramírez-Chaves Héctor E. 
Published: July 2024

La dieta de los búhos y lechuzas de Colombia ha sido escasamente estudiada. El consumo de murciélagos y otros pequeños mamíferos ha sido registrado para Aegolius harrisii y Strix nigrolineata en otros países de Centro y Sudamérica; sin embargo, no había información sobre el tema para Colombia. Presentamos nuevas observaciones de la depredación de mamíferos por búhos en Colombia y una breve revisión de registros históricos. Reportamos el intento de consumo de un murciélago del género Platyrrhinus por parte del búho bicolor (Aegolius harrisii) y la presencia de murciélagos (Dermanura y Rhogeessa) y musarañas (Cryptotis) en una egagrópila del búho carinegro (Strix nigrolineata), en los Andes de Colombia. La revisión de la literatura y datos de colecciones biológicas arrojó un total de al menos 30 especies de mamíferos que han sido registradas en la dieta de 8 especies adicionales de búhos en el país. Los roedores son las presas con mayor número de reportes, que incluyen taxa de bosques, áreas urbanas y periurbanas. Esta información puede ser útil para estudios posteriores sobre los posibles efectos de la pérdida del hábitat en el consumo de mamíferos por búhos y su papel como controladores de hospederos de agentes zoonóticos.
Scavenging insects found on a carcass of the endangered Galápagos sea lion Zalophus wollebaeki
Authors: Román Andrea C. , Chicaiza-Herrera Janna , Betancourt-Cargua Lenyn , Pinto C. Miguel 
Published: July 2024

El lobo marino (Zalophus wollebaeki) es una especie endémica de las Galápagos. Cadáveres de lobos marinos de las Galápagos se encuentran con frecuencia en las playas, pero poco se conoce sobre sus descomponedores. El objetivo del presente trabajo es reportar una muestra de insectos encontrados sobre un cadáver de lobo marino. En noviembre de 2022 se halló un cuerpo de Z. wollebaeki en el islote Caamaño del que se recolectaron e identificaron pupas y adultos de insectos carroñeros. Se encontraron 2 especies de escarabajos y 1 de mosca. Los especímenes fueron identificados como: Phaleria manicata (Coleoptera: Tenebrionidae), Dermestes ater (Coleoptera: Dermestidae) y Galopagomyia inoa (Diptera: Sarcophagidae). Phaleria manicata y G. inoa se reportan por primera vez en el cuerpo de un lobo marino. En las Galápagos, los insectos carroñeros y el papel que desempeñan en el proceso de descomposición son poco conocidos. Por lo tanto, más estudios se deben focalizar en comprender el papel ecológico de las comunidades de descomponedores en los distintos ecosistemas de las Islas Galápagos.
Felis catus preying on a Megasorex gigas, an endemic and threatened shrew from México
Authors: Ortega-Álvarez Rubén , Guevara Lázaro 
Published: July 2024

Los gatos (Felis catus) han proliferado de forma dramática, generando un serio problema de conservación mundial. En regiones tropicales y megadiversas, su impacto sobre la vida silvestre ha sido pobremente documentado. El objetivo de esta nota fue reportar la captura de una musaraña presuntamente cazada por un gato en Colima, México. En enero 30, 2022, le quitamos una musaraña a un gato en el Centro Universitario de Gestión Ambiental (CEUGEA). Detectamos inicialmente al gato a 25 m mientras jugaba con una presa. Nos aproximamos y lo espantamos para examinar la musaraña, la cual estaba fresca y presentaba una herida en uno de sus flancos. Tras una revisión minuciosa del espécimen, se identificó como musaraña gigante mexicana, Megasorex gigas, con base en características externas y craneales. Megasorex es un género monotípico endémico del oeste de México. Está considerada como Amenazada por el gobierno mexicano y se le considera rara. Los gatos han sido observados cazando la fauna de CEUGEA, mientras que los reportes de gatos depredando musarañas han sido históricamente típicos en países de zonas templadas. En regiones tropicales, las anécdotas de gatos llevando musarañas a casas no son desconocidas. Sin embargo, no existe un registro preciso ni formal de estos eventos que permita documentar el impacto de estos depredadores sobre las musarañas. Esperamos que esta nota contribuya a iniciar la sistematización de los registros asociados a la depredación de musarañas por gatos para mejorar la comprensión del efecto de especies exóticas invasoras sobre la fauna nativa de países megadiversos.
New records of Neotropical otter, Lontra annectens, in Arroyo Romerillos and Santa Catarina River, Acaxochitlán, Hidalgo, México
Authors: Hernández-Silva Dante Alfredo , Pérez-Gracida Luis David , Berges-Cervera Paul Jafet , Morales-González Beatriz , Vázquez-Maldonado Laura Elena , Gallo-Reynoso Juan Pablo 
Published: July 2024

Hay pocos registros publicados sobre la nutria neotropical (Lontra annectens) para el estado de Hidalgo. Este trabajo amplía el conocimiento de su distribución en el estado. El trabajo de campo consistió en la evaluación de 2 sitios en busca de evidencias de la presencia de la especie: Arroyo Romerillos y Río Santa Catarina. Para la obtención de los registros se hicieron recorridos a pie, a lo largo de ambos caudales; las evidencias indirectas fueron identificadas siguiendo literatura especializada y corroboradas en campo. El primer registro en el Arroyo Romerillos fue una hez encontrada sobre una roca. En el Río Santa Catarina se encontraron 3 registros: el primero la observación de un individuo entrando al agua, el segundo un comedero con restos de acamaya (Procambarus sp.) sobre una roca, el tercero fue una madriguera junto al río con heces de cría. Este trabajo destaca la importancia de continuar con la prospección de la especie por medio de métodos de muestreo directos e indirectos, para conocer aspectos ecológicos del hábitat de las nutrias, además de conocer el estado de conservación de estos cuerpos de agua en el estado de Hidalgo, con la finalidad de aportar información que permita generar estrategias para la conservación de la especie y su hábitat.
Implementation of a high-resolution micro-grating accelerometer using a subdivision interpolation technique
Authors: Peng Haifeng , Tang Jiuhui , Guo Shangzhou , Jin Li , Xie Kunyang , Li Mengwei 
Published: July 2024

This paper proposes a subdivision interpolation technique for
an optical accelerometer based
on diffraction grating interferometry. The diffraction light intensity
curve presents a sine shape with the increase of
the acceleration. To address
the issues of linearization signal processing across the entire range,
a subdivision interpolation circuit is employed, in conjunction with a
90° phase shift and high-precision DC bias-voltage techniques,
converting an analog signal with sinusoidal characteristics from the
photodetector into standard incremental digital signals that vary
linearly over the full range. The novel methodology, to the best of
our knowledge, ensures that its performance is least affected by the
phase imbalance, offset error, and amplitude mismatch induced by
fabrication and alignment errors of the grating, achieving
high-resolution digital signal output. The experiment results reveal
that the optical accelerometer based on grating interferometry
achieved a sensitivity of 85.2 V/g, a resolution of
137.6 µg, as well as a subdivision interpolation factor of 45.
This work provides a significant guide for the development of
high-resolution MOEMS accelerometers in practical applications.
Proximal femoral nail antirotation versus InterTan nail for the treatment of intertrochanteric fractures: A systematic review and meta-analysis
Authors: Liao Chang-sheng , He Fang-zheng , Li Xi-yong , Han Peng-fei 
Published: July 2024

PurposeThis meta-analysis compared the efficacy and safety of Proximal Femoral Nail Antirotation (PFNA) and InterTan Nail in the treatment of intertrochanteric fractures. Given the high incidence of femoral intertrochanteric fractures in the elderly population and its impact on quality of life, choosing the most effective and safest surgical option is crucial. PFNA and InterTan are currently two commonly used techniques, but there is a lack of systematic evaluation comparing their safety and effectiveness. This study aims to fill this knowledge gap through Meta-analysis, providing clinicians with evidence-based treatment recommendations.Materials and methodsA computer search was used to search for published literature on PFNA and InterTan in the treatment of intertrochanteric fractures in PubMed (Medline), Web of Science, Embase, Cochrane Library (CENTRAL), Cinahl, CBM, and CNKI.A total of 853 related literatures were retrieved, and 15 literatures were finally included. Newcastle-Ottawa-Scale and Cochrane systematic review methodologies were used to assess the quality of the literature. Meta-analysis was performed using Review Manager 5.4 software, following data extraction.ResultsThe comparison found that during the surgical treatment of intertrochanteric fractures, the operation time, fluoroscopy time, and blood loss in the PFNA group were significantly shorter than those in the InterTan group, and the difference was statistically significant. In terms of postoperative complication rates, the InterTan group had a significant advantage over the PFNA group. Shaft fracture, varus collapse, cut out, screw migration, and pain of hip and thigh were the most likely to occur in the PFNA group, and the differences were all statistically significant. In terms of postoperative efficacy, the results of the PFNA group and the InterTan group were comparable, and there was no significant differences.ConclusionsWhen selecting surgical techniques for the treatment of femoral intertrochanteric fractures, it is necessary to conduct individualized assessments based on the patient’s overall health status, surgical tolerance, and post-operative recovery needs. For patients who cannot tolerate long-term surgery or are in poor physical condition, PFNA may be more appropriate. While for patients who can tolerate long-term surgery or have more complex conditions, InterTan may be more suitable.