bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural mechanisms for VMAT2 inhibition by tetrabenazine
Authors: Dalton Michael P , Cheng Mary Hongying , Bahar Ivet , Coleman Jonathan A
Published: October 2023

The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson’s disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2’s importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information. Here, we report a 3.1 Å resolution cryo-electron microscopy (cryo-EM) structure of VMAT2 complexed with tetrabenazine (TBZ), a non-competitive inhibitor used in the treatment of Huntington’s chorea. We find TBZ interacts with residues in a central binding site, locking VMAT2 in an occluded conformation and providing a mechanistic basis for non-competitive inhibition. We further identify residues critical for cytosolic and lumenal gating, including a cluster of hydrophobic residues which are involved in a lumenal gating strategy. Our structure also highlights three distinct polar networks that may determine VMAT2 conformational dynamics and play a role in proton transduction. The structure elucidates mechanisms of VMAT2 inhibition and transport, providing insights into VMAT2 architecture, function, and the design of small-molecule therapeutics.
A revised terminology for male genitalia in Hymenoptera (Insecta), with a special emphasis on Ichneumonoidea
Authors: Dal Pos Davide , Mikó István , Talamas Elijah J. , Vilhelmsen Lars , Sharanowski Barbara J.
Published: October 2023

Applying consistent terminology for morphological traits across different taxa is a highly pertinent task in the study of morphology and evolution. Different terminologies for the same traits can generate bias in phylogeny and prevent correct homology assessments. This situation is exacerbated in the male genitalia of Hymenoptera, and specifically in Ichneumonoidea, in which the terminology is not standardized and has not been fully aligned with the rest of Hymenoptera. In the current contribution, we review the terms used to describe the skeletal features of the male genitalia in Hymenoptera, and provide a list of authors associated with previously used terminology. We propose a unified terminology for the male genitalia that can be utilized across the order and a list of recommended terms. Further, we review and discuss the genital musculature for the superfamily Ichneumonoidea based on previous literature and novel observations and align the terms used for muscles across the literature.
Bicycle balance assist system reduces roll and steering motion for young and older bicyclists during real-life safety challenges
Authors: Alizadehsaravi Leila , Moore Jason K.
Published: October 2023

Bicycles are more difficult to control at low speeds due to the vehicle’s unstable low-speed dynamics. This issue might be exacerbated by factors such as aging, disturbances, and multi-tasking. To address this issue, we developed a prototype ‘balance assist system’ with Royal Dutch Gazelle and Bosch eBike Systems at Delft University of Technology, which includes an electric motor capable of providing additional steering torque. We implemented a speed-adaptive feedback controller to generate the additional steering torque to that of the rider. We conducted a study with 18 older and 14 younger cyclists to first examine the effect of aging, disturbances, and multi-tasking on cycling at lower forward speeds, and evaluate the effectiveness of the system in improving the stability of the rider-bicycle system while facing these challenges. The study consisted of two scenarios: a single-task scenario where participants rode the bicycle on a marked narrow straight-line track, and a multi-task scenario where participants performed a shoulder check task and followed visual cues while tracking the straight-line. We introduced handlebar disturbances using the steer motor in half of the trials in both scenarios. All trials were repeated with and without the balance assist system. We calculated the bicycle mean magnitude of roll and steering rate—as indicators of bicycle balance control and required steering actions, respectively—and the rider’s mean magnitude of lean rate with respect to the ground to investigate the effect of the balance assist system on rider’s lateral motion. Our results showed that aging, disturbances, and multi-tasking increased the roll rate, and the balance assist system was able to significantly reduce it. The effect size of the balance assist system in reducing the roll rate across all conditions was found to be larger in older cyclists, indicating a more substantial impact compared to younger cyclists. Disturbances and multi-tasking increased the steering rate, which was successfully reduced by the balance assist system. Aging did not significantly affect the steering rate. The rider’s lean rate was not significantly affected by age, disturbances, or the balance assist, indicating that the upper body plays a minor role when riders have good steering control authority. Overall, our findings suggest that lateral motion and required steering action can be affected by age, multi-tasking, and handlebar disturbances which can endanger cyclists’ safety, and the balance assist system has the potential to improve cycling safety and reduce the incidence of single-actor crashes. Further investigation on riders’ contribution to control actions is required.
El metro como inductor de urbanidad a partir de la extensión de la línea 2 del Metro en San Bernardo, Santiago, Chile
Authors:   , Suitt Riquelme Karhynn Joseline
Published: October 2023

La presente investigación pone especial atención en cómo la periferia de la ciudad ha sido abandonada por parte del estado y sus políticas, en especial, la comuna de San Bernardo que se encuentra al final sur de la línea 2, que se ha visto como receptora de viviendas sociales y planes MINVU, pero sin el abastecimiento correcto o el diseño urbano necesario, que actualmente continúa siendo receptor de actividad agrícola y una constante urbanización, transformándose en un territorio difuso de lo urbano y rural, mientras que se conforma por hitos geográficos como cerros islas y el río Maipo y, cuenta con un recorrido de tren de la empresa EFE. La accesibilidad dispar, la disminución en la calidad de vida de sus habitantes y el desabastecimiento de equipamientos, infraestructuras y servicios, da paso a generar una intervención proyectual, de carácter multiescalar en donde la comuna de San Bernardo se transforme en un articulador tanto de forma interna como con el resto de la ciudad, conectando sus hitos geográficos, generando un nuevo micro centro, aportando servicios públicos, comercio, vivienda, entre otros, aumentando la calidad de vida y accesibilidad de sus habitantes y dando valor a una zona vulnerable y estigmatizada.
El valor de la sustentabilidad para Ilko: Un plan de comunicación estratégica
Authors:   , Fernández Peña María Antonieta
Published: October 2023

Virutex Ilko nace en 1945, fundada por el alemán Herbert Munzer quién migró desde Alemania hasta Cerrillos, donde emplazó la primera fábrica de la empresa. Esta organización se compone de tres marcas: Virutex, especialista en artículos de aseo y limpieza del hogar; Ilko, productos de cocina; e Impeke; limpieza y desinfección. En la organización trabajan 1.500 colaboradores y están presentes en Argentina, Perú, México, Colombia y Asia. Ilko, como marca, nace en 1970 y es pionera en la producción local de utensilios no eléctricos para la cocina. Tras recibir el mandato y analizar el contexto en el que se inserta la organización, desarrollamos una metodología de trabajo que permitió detectar el problema comunicacional de Ilko, a través de levantamiento de información y análisis de datos. En el sondeo se utilizaron técnicas de recolección de información como entrevistas de fuentes primarias (8) y documentos de fuentes secundarias. En cuanto al análisis de datos, se utilizan FODA (Organización), PESTAL (Entorno) y la Matriz de Stakeholders. Como diagnóstico concluimos que la organización no está comunicando su estrategia de sustentabilidad ni las acciones sustentables que realiza, y para esto, elaboramos un plan de comunicación estratégica.
Conectad@s al cuidado: ciclo de jornadas de formación en convivencia digital para docentes de quinto y sexto básico en la comuna de Melipilla
Authors:   , Fernández Flández Gustavo Misael
Published: October 2023

El plan de acción "Conectad@s al cuidado" surge como una propuesta que apela al empoderamiento docente ante los desafíos que implica el actual escenario digital para niños, niñas y adolescentes. Su relevancia radica en el rol mediador que cumple hoy en día el profesorado en la gestión de la convivencia digital y la prevención temprana de conflictos en entornos digitales.
Diseño de un plan de acción para la prevención del abandono escolar en estudiantes jóvenes y adultos. Estudio de caso: CEIA Liceo de Adultos Pucará de Chena de San Bernardo
Authors:   , Ávila Muñoz Juan Marcelo
Published: October 2023

Este proyecto aborda el problema de retención escolar en un establecimiento educacional para jóvenes y adultos, dificultad que se refleja en sus datos de eficiencia interna. Su objetivo principal es la elaboración de un plan de acción, diseñado a partir de información extraída desde parte de la propia comunidad educativa, en conjunto con literatura sobre esta temática. Esta herramienta, además se focaliza en la relevancia del liderazgo que le compete al Inspector General en particular, debido a la importancia de su rol y función en esta dificultad de gestión escolar. El proyecto, se desarrolla a modo de estudio de caso en un liceo bajo administración Municipal, en donde se aplicaron instrumentos de recolección de tipo cualitativo, como entrevistas al equipo de gestión y encuesta en los funcionarios del establecimiento para la obtención de información. Como resultado del trabajo, se obtendría una herramienta coherente al contexto de su modalidad, que tendría como meta principal la retención escolar y la eficiencia interna. Además, buscaría impactar positivamente en la buena convivencia dentro de la comunidad escolar, planteando que la prevención del abandono escolar es de tipo multifactorial, reivindicando a la Inspectoría General, quien ha sido cuestionada por su gestión en este problema.
Characterization of metabolic interactions between bacteria of the intestinal microbiome during the utilization of dietary fibers
Authors:   , Vega Sagardía Marco Antonio
Published: October 2023

El microbioma intestinal es una comunidad de microorganismos anaeróbicos. Esta composición puede ser modulada por la ingesta de alimentos ricos en fibras dietéticas, como prebióticos, que son polisacáridos complejos no modificados en el intestino delgado. Estos son fermentados selectivamente por bacterias intestinales, otorgando un beneficio a la salud del huésped. Dentro de estas fibras se incluye la inulina, y el xilano. La inulina es un fructano que es encontrado en cebollas y achicorias. Por otra parte, xilano es un polisacárido complejo de unidades de xilosa con cadenas laterales sustituidas, encontrado en las paredes celulares de las plantas como el maíz. Además, en el microbioma intestinal, existen interacciones bacterianas positivas (cross-feeding), o negativas (competencia) mediadas por el consumo de estas fibras. En este estudio se evaluaron interacciones bacterianas de diferentes cepas del microbioma intestinal de Lactobacillus, Bifidobacterium, Bacteroides, and Phocaeicola mientras consumen inulina o xilano. Ensayos bidireccionales en xilano mostraron que Bifidobacterium longum PT4 aumentó su crecimiento en presencia de Bacteroides ovatus HM222. Los análisis proteómicos indicaron que B. ovatus sintetizó enzimas que degradan xilano, como β-xilanasa, arabinosidasa, y xilosidasa. En presencia de B. ovatus, B. longum PT4 aumentó la producción de enzimas para consumir xilooligosacáridos, como α-L-arabinosidasa, L-arabinosa isomerasa, xilulosa quinasa, xilosa isomerasa y transportadores de azúcar. Por otra parte, ensayos bidireccionales en inulina mostraron un predominio de la competencia por esta fibra por parte de Lacticaseibacillus paracasei M38, cuando interactuó con otras cepas intestinales comensales (Ligilactobacillus ruminis PT16, B. longum PT4 y Bacteroides fragilis HM714) que se vieron desfavorecidas. Los estudios proteómicos destacaron el aumento en cocultivos de las enzimas que degradan la inulina, como la β-fructosidasa, el sistema de transporte PTS D-fructosa y ABC. Posibles características fenotípicas de L. paracasei le dieron una ventaja adaptativa en condiciones adversas. Los resultados confirman la complejidad de las interacciones metabólicas intestinales, las que pueden ser positivas o negativas dependiendo de las cepas involucradas.
Síntesis de compositos de nanocelulosa y nanopartículas de LiFePO4 para su aplicación como material catódico de baterías de ion litio
Authors:   , Kroff Cortez Macarena Alicia
Published: October 2023

La demanda por vehículos eléctricos ha aumentado debido principalmente a las limitaciones de emisión de CO2. En consecuencia, se ha incrementado la demanda de baterías de ion litio también, ya que es la tecnología que sustenta los vehículos eléctricos. En este ámbito, el cátodo de fosfato de hierro y litio (LFP) es un candidato prometedor para las nuevas generaciones de estas baterías debido a su bajo costo, estabilidad térmica y compatibilidad ambiental. Sin embargo, posee poca conductividad eléctrica y una lenta difusión del ion litio, lo que disminuye su capacidad en la práctica y limita su uso. Debido a esto, distintas metodologías han sido propuestas para mejorar el desempeño de LFP, donde la reducción del tamaño de partícula y la formación de compositos con materiales conductores son los más utilizados. En este proyecto se plantea realizar la síntesis hidrotermal asistida por microondas de nanopartículas de LFP en presencia de nanocelulosa, dado que esta puede actuar como agente reductor del hierro y ser la fuente de carbono para la realización posterior del composito LFP/C. Los parámetros determinantes de la síntesis hidrotermal planeada son el pH con el agente reductor externo añadido, como también la temperatura y tiempo de reacción. En la condición de síntesis propuesta (150°C por 30 min) añadir nanocelulosa (NC) de cualquiera de los tipos ayuda a disminuir los tamaños de partícula promedios observados, además de mejorar las intensidades de la cara cristalina responsable de la difusión del litio (020). Sin embargo al realizar un ciclado del cátodo por 10 ciclos a una velocidad baja, comienzan a aparecer otras especies de hierro +3 o 0, lo que representa una baja en el desempeño del LFP. Cuando se estudia el recubrimiento de la partícula de LFP con el uso de la nanocelulosa fibrilar (NCF) se observan pocos recubrimientos con porcentajes cercanos a los 12,6% o menores. El composito con 22,8% de carbón es el que presenta el mayor recubrimiento de las partículas de LFP y por ende, mejor respuesta electroquímica. Sin embargo, se continúan observando partículas de tamaño y recubrimiento heterogéneo. Por lo que, el mejoramiento de estos parámetros ayudaría a obtener capacidades cercanas a la teórica. Utilizando la síntesis hidrotermal asistida por microondas es posible obtener un composito LFP/C con una mejora en el desempeño electroquímica del cátodo conseguido a diferencia del obtenido sin utilizar NC en su síntesis, e incluso al compuesto LFP-comercial. Por lo que la síntesis propuesta tiene un potencial uso como realización de este cátodo para futuras generaciones de cátodos para baterías de ion lito.
Effects of aquatic and step aerobic exercises on flexibility parameters in sedentary women
Authors: Türkmen İrem , Çağlar Esin Çağla
Published: October 2023

The aim of this study was to investigate the effects of aquatic and step aerobic exercises on flexibility parameters in sedentary individuals. A total of n=45 sedentary women between the ages of 25-50 years, n=15 for aquatic exercise, n=15 for step aerobic exercise and n=15 for control group, who came to municipal sports centres, participated in this study. All measurements were taken before and after 8 weeks of aquatic and step aerobic exercises. In our study, after measuring body weight, body mass index, fat percentage, lean body mass, chest circumference, waist circumference, hip circumference, thigh circumference, sit-lie flexibility, hand flexibility at waist, hand flexibility at neck, planter flex right, planter flex left, dorsi flex right, dorsi flex left were measured respectively. For statistical analyses, paired t-test was used for dependent group comparisons for continuous variables and Wilcoxon test was used for non-normally distributed data. In comparisons of numerical variables between more than two independent groups, one-way analysis of variance (ANOVA) was used for normally distributed data and Kruskal-Wallis test for non-normally distributed data. After ANOVA and Kruskal-Wallis test, Tukey or Mann Whitney U post-hoc multiple comparison tests with Bonferroni correction were used to determine the groups in which the difference originated. When the in-group comparisons of aquatic exercise were evaluated, the pre-test and post-test values of sit-lie flexibility, flexibility at hand waist, flexibility at hand neck, planter flexion right, planter flexion left, dorsi flex right, dorsi flex left variables were statistically significantly different (P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, respectively). In step aerobic exercise, the pre-test and post-test values of sit-lie flexibility, flexibility at hand waist, flexibility at hand neck, planter flexion right, planter flexion left, dorsi flex right, dorsi flex left variables were statistically significantly different (respectively; P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001, P< 0.001).
Examination of the job satisfaction and occupational burnout of physical education teachers based on certain variables according to the type of school they work in
Authors: Köroğlu Yaşar , Sitti Samet
Published: October 2023

The present study aims to scientifically reveal the effect of job satisfaction and professional burnout levels of physical education teachers working in private and public schools. A total of 120 physical education teachers, 61 male and 59 female, participated in the study. The job satisfaction scale, a demographic information form and the Maslach Burnout Inventory (MBI) were used to assess the demographic data of the physical education teachers. Frequency distributions were utilized in the evaluation of demographic data. Since the data were normally distributed, the data were presented in the form of mean and standard deviation. The difference between the groups and demographic variables was analyzed using independent t-test and one-way ANOVA. When there was a difference in more than two variables, the post-hoc Tukey HSD test was used to determine which of the variables contained the difference. Correlation analysis was performed to determine the correlations between the variables. It was determined that there was no significant difference between the demographic variables of the physical education teachers and their job satisfaction and professional burnout levels. While there is a low degree of correlation between occupational burnout and job satisfaction, there is a strong relationship between occupational burnout and its sub-dimensions. There was a weak and moderate relationship between occupational burnout and its sub-dimensions and job satisfaction. In conclusion, it can be stated that physical education teachers enjoy their jobs whether in private or public schools and their working environment can be improved by providing the necessary facilities and support.
An Innovative Approach in the Fabrication of a Hollow Vaginal Stent Using Ice in a Gender Dysphoria Patient: A Case Report
Authors: Khubchandani Sheetal Rameshlal , Bhoyar Anjali , Sathe Seema , Kanojiya Ekta , Pathak Ankita
Published: October 2023

Gender dysphoria is the term used for individuals who are unhappy with their assigned gender at birth. They experience a strong desire to have the body of the opposite gender or to be socially recognised as a person of the opposite gender. Gender dysphoria can occur in both genders, but it is more prevalent in males, ranging from 0.005% to 0.014%. In females, the prevalence rate is lower, ranging from 0.002% to 0.003%. This case report highlights the prosthetic management of a 31 years old male patient with gender dysphoria after undergoing surgical intervention to remove male genitalia and create a neovagina. The patient underwent multiple surgeries to fulfill their gender transition desires. The patient initially visited the Department of Prosthodontics before vaginoplasty, where a custom-made hollow vaginal stent was planned and fabricated using a novel technique. In addition to prosthetic treatment, the patient also required hormonal therapies and psychological counseling, both of which were provided.
Multi Detector Computed Tomography and Ultrasound Evaluation of Neck Masses with Pathological Correlation
Authors: Charan Kumar Ashok , Shyam S.  , Parthasarathy K. R.  , Vaishnavi R. S.  , Prerana A. T.  , Shahab Qadir B.  , Kumar Ajay , Sachin T. D.  , Gowda Preetham
Published: October 2023

Introduction: Neck imaging has always been a diagnostic challenge. High-resolution sonography being inexpensive and safe has become the initial investigation of choice for neck pathologies; it provides information regarding the origin and extent of the lesion. Computed tomography (CT) has a unique capacity for displaying soft tissue, bone and airway details and provides critical anatomical information about lesions involving the neck. This study aims to determine the role of USG and CT in neck masses for pre-operative characterization based on location, extent, morphological characteristics and enhancement pattern and to compare USG and CT findings with histopathological diagnosis.

Material and Methods: A total number of 60 adult patients with suspected neck masses were studied in the department of Radiodiagnosis, SSIMS&RC, Davanagere and inputs from Dr. B. R. Ambedkar Medical College, Bengaluru over a period of 24 months. Ultrasound was done using GE Voluson E6 machine & Contrast enhanced CT was done using GE Revolution Multidetector CT scan machine. Post processing techniques (like volume rendered techniques) were applied wherever useful.

Results: The findings on USG and CT were conclusive in nearly 90% of cases. Enhancement patterns and presence/absence of bony invasion were found to be more specific in differentiating benign/malignant nature.

Conclusion: High-resolution sonography can be used as the first-line modality for evaluating cervical soft tissue masses, it helps the clinicians to characterize the lesion. Multi-detector computed tomography is a sensitive diagnostic tool for diagnosing neck masses and differentiating between benign and malignant lesions with high accuracy. The extent of pathology with local/ contiguous spread predicted by CT examination was conclusive. The overall findings suggest that MDCT and Ultrasound, when used in conjunction with pathological correlation, can be effective tools for accurately characterizing and diagnosing the neck masses.
Acoustic Properties of Stretchable Liquid Metal‐Elastomer Composites for Matching Layers in Wearable Ultrasonic Transducer Arrays
Authors: Krings Ethan J. , Hage Benjamin D. , Truong Sequoia L. , Reeser Kiersten A. , Fox Eli L. , Snyder Matthew G. , Walker Quentin , Bashford Gregory R. , Markvicka Eric J.
Published: October 2023

Ultrasound is a safe, noninvasive diagnostic technique used to measure internal structures such as tissues, organs, and arterial and venous blood flow. Skin‐mounted wearable ultrasound devices can enable long‐term continuous monitoring of patients to provide solutions to critical healthcare needs. However, stretchable ultrasound devices that are composed of ultrasonic transducers embedded in an elastomer matrix are incompatible with existing rigid acoustic matching layers, leading to reduced energy transmission and reduced imaging resolution. Here, a systematic study of soft composites with liquid metal (LM) fillers dispersed in elastomers reveals key strategies to tune the acoustic impedance of soft materials. Experiments supported by theoretical models demonstrate that the increase in acoustic impedance is primarily driven by the increase in density with negligible changes to the speed of sound through the material. By controlling the volume loading and particle size of the LM fillers, a material is created that achieves a high acoustic impedance 4.8 Mrayl, (> 440% increase over the polymer matrix) with low modulus (< 1 MPa) and high stretchability (> 100% strain). When the device is mechanically strained, a small decrease is observed in acoustic impedance (< 15%) with negligible decrease in sound transmittance and impact on attenuation for all droplet sizes. The stretchable acoustic matching layer is then integrated with a wearable ultrasound device and the ability to measure motion is demonstrated using a phantom model as is performed in Doppler ultrasound.
Tunable Fabrication of MAPbX3 Triangular‐Micro‐Wires Array for Constructing High Sensitivity Photodetector
Authors: Xu Xiuzhen , Xiong Yuting , Liu Wenfei , Hao Dandan , Ji Zhenkai , Zhan Yiqiang , Huang Jia , Xu Xiaobin
Published: October 2023

Organic‐inorganic hybrid perovskite (MAPbX3) is known having excellent photoelectric properties. Compared to polycrystalline films, perovskite micro/nanowires can provide improved optoelectronic properties, mechanical flexibility, and adaptability due to higher crystallinity. However, their economical, scalable, and controllable fabrication remains a challenge. In this work, the authors report a facile way to fabricate high‐quality MAPbX3 triangular‐micro‐wires (TMWs). The Si/SiO2 substrate with triangular‐micro‐trenches (TMTs) array serves as the template for the growth of MAPbX3 TMWs array through blade coating. The MAPbX3 TMW first nucleated at the trench bottom, which facilitating the nanowire growth with high crystallinity. In addition, the size and periodicity of TMTs array can be independently controlled, providing potential for scale‐up device applications. The photodetectors fabricated with these MAPbI3 TMWs show excellent responsivity of (144.5 ± 2.1) A/W and specific detectivity of (2.7 ± 0.02) × 1011 Jones under weak light (0.5 µW cm−2). Their photoresponse to pulsed light is stable and reproducible, with rise and decay times of 7.5 and 6.0 ms, respectively. Finally, with the demonstration of the image sensor application, MAPbX3 TMWs array is anticipated to be suitable for large‐area, high‐performance integrated optoelectronics.
Stability Investigations on a Pt@HGS Catalyst as a Model Material for Fuel Cell Applications: The Role of the Local pH
Authors: Gunnarson Alexander , Quast Thomas , Dieckhöfer Stefan , Pfänder Norbert , Schüth Ferdi , Schuhmann Wolfgang
Published: October 2023

Increasing the resistance of catalysts against electrochemical degradation is one of the key requirements for the wider use of Proton Exchange Membrane Fuel Cells (PEMFCs). Here, we study the degradation of one entity of a highly stable catalyst, Pt@HGS, on a nanoelectrode under accelerated mass transport conditions. We find that the catalyst degrades more rapidly than expected based on previous ensemble measurements. Corroborated by identical location transmission electron microscopy and catalyst layer experiments, we deduce that locally different pH values are likely the reason for this difference in stability. Ultimately, this work provides insights into the actual conditions present in a PEMFC and raises questions about the applicability of accelerated stress tests usually performed to evaluate catalyst stability, particularly when they are performed in half‐cell setups under inert gas.
The osteology of the Late Triassic reptile Scleromochlus taylori from μCT data
Authors: Foffa Davide , Nesbitt Sterling J. , Butler Richard J. , Brusatte Stephen L. , Walsh Stig , Fraser Nicholas C. , Barrett Paul M.
Published: October 2023

Scleromochlus taylori is one of the most enigmatic members of the herpetofauna from the Lossiemouth Sandstone Formation (Upper Triassic) of Elgin (Moray, Scotland). For many years it was thought to be closely related to pterosaurs and dinosaurs, but the anatomy of this animal is difficult to interpret because of the notoriously poor preservation of the six available specimens, which comprise void space in the sandstone after the bones were destroyed by diagenesis. Historically, these fossils have been studied using physical molds, which provide only incomplete, and potentially distorted, information. Due to these uncertainties, interpretations of the anatomy, phylogenetic relationships, and paleobiology of Scleromochlus taylori have remained contentious. Here, we use microcomputed tomographic (μCT) techniques to redescribe and illustrate the osteology of Scleromochlus in detail, building upon a short redescription of keystone features of the anatomy that we recently published. We digitally visualize, describe, and figure previously inaccessible—and thus unaltered—portions of its skeleton, as well as providing new observations on the exposed parts of each specimen. This work reveals many novel features of the skull, mandible, trunk, tail, girdles, forelimb, and hindlimb (particularly of the manus, femur, and pes), demonstrating that historic molding techniques failed, in some cases, to accurately capture the anatomy of Scleromochlus. Our review sheds light on some of the most controversial aspects of Scleromochlus morphology showing that this taxon retains plesiomorphic features of Avemetatarsalia in the postcranial skeleton, alongside a suite of synapomorphies diagnostic of pterosauromorphs (the broad clade of pterosaurs and taxa more closely related to them than dinosaurs), particularly one subgroup, the lagerpetids. Consistent with recent work, our updated phylogenetic analyses (Maximum Parsimony and Bayesian Inference) demonstrate that Scleromochlus taylori is an avemetatarsalian archosaur that is recovered firmly in an early diverging position within Pterosauromorpha, as a member of Lagerpetidae, thus shedding important information on the origin of pterosaurs, the first group of vertebrates to evolve powered flight.
Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors
Authors: Anjali  , Kamboj Payal , Alam Ozair , Patel Harun , Ahmad Iqrar , Ahmad Syed Sufian , Amir Mohd.
Published: October 2023

A new series of quinoxaline derivatives possessing the hydrazone moiety were designed, synthesized, and screened for in‐vitro anti‐inflammatory activity by the bovine serum albumin (BSA) denaturation technique, and for antioxidant activity, by the (2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay. The synthesized compounds were also tested for p38α mitogen‐activated protein (MAP) kinase inhibition. The in‐vivo anti‐inflammatory activity was assessed by the carrageenan‐induced rat paw edema inhibition method. All the compounds (4a–n) exhibited moderate to high in‐vitro anti‐inflammatory activity. Compound 4a displayed the highest inhibitory activity in the BSA assay (83.42%) in comparison to the standard drug diclofenac sodium (82.90%), while 4d exhibited comparable activity (81.87%). The DPPH assay revealed that compounds 4a and 4d have free radical scavenging potential (74.70% and 74.34%, respectively) comparable to the standard butylated hydroxyanisole (74.09%). Furthermore, the p38α MAP kinase inhibition assay demonstrated that compound 4a is highly selective against p38α MAP kinase (IC50 = 0.042) in comparison to the standard SB203580 (IC50 = 0.044). The five most active compounds (4a–4d and 4f) with good in‐vitro profiles were selected for in‐vivo anti‐inflammatory studies. Compounds 4a and 4d were found to display the highest activity (83.61% and 82.92% inhibition, respectively) in comparison to the standard drug diclofenac sodium (82.65% inhibition). These compounds (4a and 4d) also exhibited better ulcerogenic and lipid peroxidation profiles than diclofenac sodium. The molecular docking and molecular dynamics simulation studies were also performed and found to be in agreement with the p38α MAP kinase inhibitory activity.
A 2D Nano‐architecture (NPSMC@Ir−Ru@rGO) Derived from Graphene Enfolded Polyphosphazene Nanospheres Decorated Ir−Ru Metals (PZS@Ir−Ru@GO) towards Bifunctional Water Splitting
Authors: Akram Raheel , Arif Muhammad , Arshad Anila , Zhang Shuangkun , Liu Wei , Wu Zhanpeng , Zhang Teng
Published: October 2023

A leap‐forward approach has been successfully devised to synthesize a novel hierarchical binary metal modified heteroatom doped 2D micro‐/mesporous carbon‐graphene nanostructure (NPSMC@Ir−Ru@rGO) for overall water splitting application. To investigate the role of decorating metals, different electrolcatalysts like NPSMC, NPSMC@rGO, NPSMC@Ir@rGO, and NPSMC@Ru@rGO were also synthesized and structural changes were compared and investigated by physiochemical techniques. All of the samples have shown electrocatalytic activities attributed to the presence of heteroatom (N, P, S) doped micro‐/mesoporous carbonaceous matrix, amorphous carbon in the coexistence of graphitic lattice carbons, presence of active metal NPs (Ir and/‐or Ru), an even distribution of active sites, and graphene 2D interconnected channels to promote electron transfer ability, respectively. However, the Ir−Ru metal codeped nanocatalyst (NPCMS@Ir−Ru@rGO) is proved to be an excellent electrocatalyst based on the synergistic role of Ir−Ru metals that necessitates the low overpotentials of 181 mV and 318 mV to convey a current density of 10 mA cm−2 towards the electroctalytic application of HER and OER, respectively. Furthermore, exhibiting the corresponding Tafel slopes (132 and 70 mV dec−1) in an alkaline medium. This work is anticipated to open up new avenues for the development of promising electrocatalysts based on active metals modified heteroatom doped carbon nanomaterials for energy applications.
A simple and rapid external standard calibration HPLC method for determination of lumefantrine in dried blood spot samples from malaria patients in Botswana
Authors: Brooks Blondie O. , Paganotti Giacomo Maria , Massele Amos , Sepako Enoch , Adiukwu Paul , Sichilongo Kwenga Festus
Published: October 2023

A simple external calibration liquid chromatography‐diode array detector method was developed, validated, and applied for the determination of lumefantrine (Lum) in dried blood spot (DBS) samples collected from malaria patients in Botswana. The samples were validated in accordance with the United States Food and Drug Administration guidelines for bioanalytical methods after sample preparation using solid–liquid extraction. Separation was achieved using an XTerra C18 column (50 × 4.6 mm, 5 μm), and a binary solvent system of acetonitrile and water adjusted to pH 2.3 was used as the mobile phase. The validated method was applied for the determination of Lum in DBS samples collected from malaria patients infected with Plasmodium falciparum in Botswana. The calibration curve was linear between 0.5 and 12 μg/mL with a coefficient of determination (R2) of 0.9996. The limit of detection and the lower limit of quantification were 0.5 and 1.4 μg/mL, respectively. The efficiency of extraction measured as percentage recovery ranged between 84.2% and 107.8% at the three quality control (QC) levels, that is, low QC, mid QC, and high QC. In conclusion, data suggest that the method is suitable for the determination of trace Lum in biofluids and can also be used for therapeutic drug monitoring and pharmacokinetic profiling.
Development and validation of an LC–MS/MS method for the determination of AZD7648 in rat plasma: Application to a pharmacokinetic study
Authors: Fang Xun , Lu Qi , Han Jichun
Published: October 2023

AZD7648 is a potent DNA‐PK inhibitor that is being developed for the treatment of ovarian cancer. The study aimed to develop a simple and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to determine the concentration of AZD7648 in rat. AZD7648 was extracted from plasma by acetonitrile‐mediated protein precipitation. The quantification was performed on a Thermo Vantage TSQ mass spectrometer with ibrutinib as an internal standard. A Waters Acquity UPLC BEH C18 column combined with 0.1% aqueous formic acid and acetonitrile was employed for chromatographic separation. The precursor‐to‐product ion transitions were m/z 421.2 > 337.2 and m/z 441.2 > 138.1 for AZD7648 and internal standard, respectively. This method was successfully validated according to the US Food and Drug Administration guidance. The calibration curve was linear over the concentration range of 0.5–1,000 ng/ml with correlation coefficient >0.999. The precision expressed as the coefficient of variation was <8.09%, while the accuracy expressed as relative error ranged from −10.00 to 9.08%. The mean recovery was >94.49%. AZD7648 was stable in rat plasma after storage under certain conditions. The validated method was demonstrated to be selective, sensitive and reliable, and has been successfully applied to the pharmacokinetic study of AZD7648 in rat plasma after oral and intravenous administration (1 mg/kg).
Detailed Phytochemical Evaluation of a Locally Endemic Species (Campanula baskilensis) by LC‐MS/MS and Its In‐Depth Antioxidant and Enzyme Inhibitory Activities
Authors: Yilmaz Mustafa Abdullah , Cakir Oğuz , Izol Ebubekir , Tarhan Abbas , Behcet Lutfi , Zengin Gokhan
Published: October 2023

The importance of bioactive plant species in the scientific world is increasing day by day. The relationship between health and traditional‐modern life, promotes the creation of new value‐added natural products. This is the first research to conduct a bioactivity and chemical composition analysis of Campanula baskilensis species, which belongs to the medicinally important genus Campanula L (Campanulaceae). The aim of the current study is to quantitatively investigate the phytochemical contents of aerial and root parts of different C. baskilensis extracts (ethanol, methanol, and water) by LC‐MS/MS and to evaluate their total phenolic and flavonoid contents, antioxidant and enzyme inhibitory activities. Remarkably, LC‐MS/MS results revealed that, high amounts of quinic acid (53.6 mg/g aerial‐MeOH extract), fumaric acid (6.3 mg/g aerial‐H2O extract, 2.5 mg/g root‐H2O extract), protocatechuic acid (11.4 mg/g aerial‐H2O extract), vanillic acid (1.4 mg/g aerial‐EtOH extract), quercetin‐3‐O‐rutinoside (rutin) (2.3 mg/g aerial‐EtOH extract), hesperetin 7‐rutinoside (hesperidin) (2.0 mg/g aerial‐EtOH extract), kaempferol‐3‐O‐rutinoside (nicotiflorin) (5.5 mg/g aerial‐EtOH extract) were detected in the extracts of the species. Considering the bioactivity tests performed on C. baskilensis extracts, aerial‐H2O extract showed significant activity in all antioxidant assays. However, ethanol extracts of root and aerial parts exhibited the highest activities in all enzyme inhibitory tests.
Chemical Constituents of the Deep‐sea Gammarid Shrimp‐Derived Fungus Penicillium citrinum XIA‐16
Authors: Yu Hao‐Yu , Li Yan , Zhang Meng , Zou Zheng‐Biao , Hao You‐Jia , Xie Ming‐Min , Li Li‐Sheng , Meng Da‐Li , Yang Xian‐Wen
Published: October 2023

One new alkaloid, (S)‐2‐acetamido‐4‐(2‐(methylamino)phenyl)‐4‐oxobutanoic acid (1), was isolated from the deep‐sea‐derived Penicillium citrinum XIA‐16, together with 25 known compounds including ten polyketones (2–11), eight alkaloids (12–19), six steroids (20–25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR‐ESI‐MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3‐induced ferroptosis (EC50=2.0 μM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 μM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.
A rare case of Burkitt's lymphoma of the breast in a 19‐year‐old male: Case report
Authors: Kato Ronald , Solomon Kibudde
Published: October 2023

Key Clinical Message

Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body, which include jaw, facial bones, retroperitoneum, and abdominal viscera, it is worth noting that breast involvement is extremely rare in Burkitt's lymphoma and has not been documented.

Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body including breast. This sarcoma is identified as a rapidly fatal malignant lymphoma syndrome and 50% of all malignant tumors in children. However, breast involvement has not been documented. A 19‐year‐old male presented to our emergency department with a left breast swelling for 2 months associated with drenching night sweats, weight loss and evening fevers. Physical examination revealed a mass measuring approximately 15 × 16 × 15 cm in the widest dimension, skin hyperpigmentation, no nipple discolorations, discharges, and non‐tender on palpation. Biopsy was done, and the histology report revealed sheets of monomorphic medium lymphocytes with a high mitotic rate and frequent apoptotic bodies showing a starry‐sky appearance. The immunohistochemistry report revealed positive staining for Ki‐67, CD‐20, and CD‐10 tumor markers and CD45 on flow cytometry. The patient was started on aggressive hydration, rasubricase administration, CODOX‐M/IVAC regimen 6 cycles, and G‐CSF and registered significant reduction in the size of the mass. Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body. It commonly involves the jaw, facial bones, retroperitoneum, and abdominal viscera. The disease typically affects young patients in areas of high incidence, such as the jaw, whereas visceral involvement is more common in older patients in low‐incidence areas. It is worth noting that breast involvement is extremely rare in Burkitt's lymphoma.
Structural Optimization of Antimycobacterial Azaaurones Towards Improved Solubility and Metabolic Stability
Authors: Campaniço André , Harjivan Shrika G. , Freitas Elisabete , Serafini Marco , Gaspar M. Manuela , Capela Rita , Gomes Pedro , Jordaan Audrey , Madureira Ana M. , André Vânia , Silva Andreia B. , Duarte M. Teresa , Portugal Isabel , Perdigão João , Moreira Rui , Warner Digby F. , Lopes Francisca
Published: October 2023

While N‐acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), their low metabolic stability remains an unaddressed liability. We now report a study designed to improve the metabolic stability and solubility of the azaaurone scaffold and to identify the structural requirements for antimycobacterial activity. Replacing the N‐acetyl moiety for a N‐carbamoyl group led to analogues with sub‐ and nanomolar potencies against M. tuberculosis H37Rv, as well as equipotent against drug‐susceptible and drug‐resistant M. tuberculosis isolates. The new N‐carbamoyl azaaurones exhibited improved microsomal stability, compared to their N‐acetylated counterparts, with several compounds displaying moderate to high kinetic solubility. The frequency of spontaneous resistance to azaaurones was observed to be in the range of 10−8, a value that is comparable to current TB drugs in the market. Overall, these results reveal that azaaurones are amenable to structural modifications to improve metabolic and solubility liabilities, and highlight their potential as antimycobacterial agents.
Treosulfan Exposure Predicts Thalassemia‐Free Survival in Patients with Beta Thalassemia Major Undergoing Allogeneic Hematopoietic Cell Transplantation
Authors: Pai Aswin Anand , Mohanan Ezhilpavai , Panetta John C. , Kulkarni Uday P. , Illangeswaran Raveen Stephen Stallon , Balakrishnan Balaji , Jayaraman Agila , Edison Eunice S. , Lakshmi Kavitha M. , Devasia Anup J. , Fouzia Nambiathayil Aboobacker , Korula Anu , Abraham Aby , George Biju , Srivastava Alok , Mathews Vikram , Standing Joseph F. , Balasubramanian Poonkuzhali
Published: October 2023

A toxicity‐reduced conditioning regimen with treosulfan, fludarabine, and thiotepa in patients with high‐risk β‐thalassemia major has significantly improved hematopoietic stem cell transplantation (HCT) outcomes. However, complications resulting from regimen‐related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose–exposure‐response relationship of treosulfan and its active metabolite S, S‐EBDM, in a uniform cohort of patients with β‐thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of treosulfan is feasible. Plasma treosulfan/S, S‐EBDM levels were measured in 77 patients using a validated liquid chromatography with tandem mass spectrometry method, and the pharmacokinetic parameters were estimated using nlmixr2. The influence of treosulfan and S, S‐EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1‐year overall survival (OS), and thalassemia‐free survival (TFS) were assessed. We observed that treosulfan exposure was lower in patients with graft rejection than those without (1,655 vs. 2,037 mg•h/L, P = 0.07). Pharmacodynamic modeling analysis to identify therapeutic cutoff revealed that treosulfan exposure ≥1,660 mg•hour/L was significantly associated with better 1‐year TFS (97% vs. 81%, P = 0.02) and a trend to better 1‐year OS (90% vs. 69%, P = 0.07). Further, multivariate analysis adjusting for known pre‐HCT risk factors also revealed treosulfan exposure <1,660 mg•h/L (hazard ratio (HR) = 3.23; 95% confidence interval (CI) = 1.12–9.34; P = 0.03) and GSTA1*B variant genotype (HR = 3.75; 95% CI = 1.04–13.47; P = 0.04) to be independent predictors for inferior 1‐year TFS. We conclude that lower treosulfan exposure increases the risk of graft rejection and early transplant‐related mortality affecting TFS. As no RRTs were observed with increasing treosulfan exposure, TDM‐based dose adjustment could be feasible and beneficial.