Real-world use of pemigatinib for the treatment of cholangiocarcinoma in the US.

BACKGROUND: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA) in the FIGHT-202 trial. However, limited real-world evidence exists on treatment patterns and outcomes in this setting. PATIENTS AND METHODS: Patient characteristics, treatment patterns, and outcomes of US adults who received pemigatinib for unresectable, locally advanced or metastatic CCA were collected via retrospective physician-abstracted chart review. Results were summarized using descriptive statistics. RESULTS: Data from 120 patients (49.2% male; 55.0% White; 19.2% Hispanic; median age at initial pemigatinib prescription, 64.5 years) were collected from 18 physicians/practices. At the time of prescribing, 90.0% of patients had metastatic disease. FGFR2 testing was completed for 92.5% of patients; of those, all but one (result unknown) tested positive, and 95.5% were tested using next-generation sequencing. Pemigatinib was prescribed as second- and third-line therapy among 94.2% and 5.8% of patients, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycles (87.5% of patients). Among 60 patients (50.0% of the full cohort) who discontinued pemigatinib during the 6.5-month median study follow-up period, 68.3% discontinued due to disease progression. The median real-world progression-free survival (rwPFS) from the date of pemigatinib initiation was 7.4 months (95% CI: 6.4-8.6), and the real-world overall response rate (rwORR) was 59.2% (95% CI: 50.0%-68.4%). CONCLUSION: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under real-world conditions. Findings support the clinical benefit of pemigatinib demonstrated in FIGHT-202.

Increased expression of metabolism and lysosome-associated genes in a C. elegans dpy-7 cuticle furrow mutant.

The collagen-based epidermal 'cuticle' of Caenorhabditis elegans functions as an extracellular sensor for damage that regulates genes promoting osmotic balance, innate immunity, and detoxification. Prior studies demonstrate that SKN-1 , an ortholog of the mammalian Nrf transcription factors, activates core detoxification genes downstream from cuticle damage. Prior RNAseq data suggested that expression of five genes with functions in redox balance, ATP homeostasis, and lysosome function ( gst-15 , gst-24 , cyts-1 , argk-1 , and mfsd-8.4 ) were increased in a cuticle collagen mutant; this study employed RT-qPCR to verify this observation and to test the role of SKN-1 . Activation of all five genes was verified in dpy-7 mutants, but none were reduced by skn-1 (RNAi) suggesting parallel or distinct regulatory mechanisms.

Age-dependent changes in phagocytic activity: in vivo response of mouse pulmonary antigen presenting cells to direct lung delivery of charged PEGDA nanoparticles.

BACKGROUND: Current needle-based vaccination for respiratory viruses is ineffective at producing sufficient, long-lasting local immunity in the elderly. Direct pulmonary delivery to the resident local pulmonary immune cells can create long-term mucosal responses. However, criteria for drug vehicle design rules that can overcome age-specific changes in immune cell functions have yet to be established. RESULTS: Here, in vivo charge-based nanoparticle (NP) uptake was compared in mice of two age groups (2- and 16-months) within the four notable pulmonary antigen presenting cell (APC) populations: alveolar macrophages (AM), interstitial macrophages (IM), CD103+ dendritic cells (DCs), and CD11b+ DCs. Both macrophage populations exhibited preferential uptake of anionic nanoparticles but showed inverse rates of phagocytosis between the AM and IM populations across age. DC populations demonstrated preferential uptake of cationic nanoparticles, which remarkably did not significantly change in the aged group. Further characterization of cell phenotypes post-NP internalization demonstrated unique surface marker expression and activation levels for each APC population, showcasing heightened DC inflammatory response to NP delivery in the aged group. CONCLUSION: The age of mice demonstrated significant preferences in the charge-based NP uptake in APCs that differed greatly between macrophages and DCs. Carefully balance of the targeting and activation of specific types of pulmonary APCs will be critical to produce efficient, age-based vaccines for the growing elderly population.

Concurrent multiple cerebral cavernous malformations and cauda equina paraganglioma: illustrative case.

BACKGROUND: Cauda equina neuroendocrine tumors (CENETs), previously known as cauda equina paragangliomas, and multiple cerebral cavernous malformations (CCMs) are uncommon conditions affecting the central nervous system. To the authors' knowledge, they have not been reported in the same patient. OBSERVATIONS: The authors present the case of a 45-year-old male with CENET and concurrent incidental MRI findings of multiple CCMs. Familial CCMs are associated with mutations in the KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) genes. Peripheral paragangliomas have been associated with mutations in succinate dehydrogenase (SDHx), RET (multiple endocrine neoplasia 2), VHL (von Hippel-Lindau syndrome), and NF1 (neurofibromatosis type 1) genes. Except for a single case, cauda equina paragangliomas have not been associated with any underlying genetic mutations. LESSONS: It is unclear whether the co-occurrence of these two rare conditions in the same patient is coincidental or suggests a possible shared pathogenesis. https://thejns.org/doi/10.3171/CASE24102.

Advancing common bean (Phaseolus vulgaris L.) disease detection with YOLO driven deep learning to enhance agricultural AI.

Common beans (CB), a vital source for high protein content, plays a crucial role in ensuring both nutrition and economic stability in diverse communities, particularly in Africa and Latin America. However, CB cultivation poses a significant threat to diseases that can drastically reduce yield and quality. Detecting these diseases solely based on visual symptoms is challenging, due to the variability across different pathogens and similar symptoms caused by distinct pathogens, further complicating the detection process. Traditional methods relying solely on farmers' ability to detect diseases is inadequate, and while engaging expert pathologists and advanced laboratories is necessary, it can also be resource intensive. To address this challenge, we present a AI-driven system for rapid and cost-effective CB disease detection, leveraging state-of-the-art deep learning and object detection technologies. We utilized an extensive image dataset collected from disease hotspots in Africa and Colombia, focusing on five major diseases: Angular Leaf Spot (ALS), Common Bacterial Blight (CBB), Common Bean Mosaic Virus (CBMV), Bean Rust, and Anthracnose, covering both leaf and pod samples in real-field settings. However, pod images are only available for Angular Leaf Spot disease. The study employed data augmentation techniques and annotation at both whole and micro levels for comprehensive analysis. To train the model, we utilized three advanced YOLO architectures: YOLOv7, YOLOv8, and YOLO-NAS. Particularly for whole leaf annotations, the YOLO-NAS model achieves the highest mAP value of up to 97.9% and a recall of 98.8%, indicating superior detection accuracy. In contrast, for whole pod disease detection, YOLOv7 and YOLOv8 outperformed YOLO-NAS, with mAP values exceeding 95% and 93% recall. However, micro annotation consistently yields lower performance than whole annotation across all disease classes and plant parts, as examined by all YOLO models, highlighting an unexpected discrepancy in detection accuracy. Furthermore, we successfully deployed YOLO-NAS annotation models into an Android app, validating their effectiveness on unseen data from disease hotspots with high classification accuracy (90%). This accomplishment showcases the integration of deep learning into our production pipeline, a process known as DLOps. This innovative approach significantly reduces diagnosis time, enabling farmers to take prompt management interventions. The potential benefits extend beyond rapid diagnosis serving as an early warning system to enhance common bean productivity and quality.

IgLON5-IgG: Innocent Bystander or Perpetrator?

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.

JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans.

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (KD: 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC50: 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC50: 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases.

Effects of Academic Detailing, Panel Management and Mailed Multi-Target Stool-DNA Testing on Colorectal Cancer Screening.

INTRODUCTION: Academic detailing, patient-panel management, and mailed, stool-based testing have each been utilized to increase colorectal cancer (CRC) screening in rural clinics. The effectiveness of combining these interventions to increase CRC screening during COVID-19 restrictions was unclear. METHODS: We explored the effects of a multi-component intervention including academic detailing, active patient panel management, and mailed MT-sDNA testing on colorectal cancer screening in our rural family medicine clinic. Baseline interventions included EMR-based provider alerts and mailed patient reminders. Our intervention (March-May 2020) and follow-up periods (June-August 2020) coincided with the initial COVID-19 surge, giving us the opportunity to observe the effects of our intervention during COVID-19 restrictions. RESULTS: A total of 407 patients were eligible and overdue for colorectal cancer screening. Our clinic's CRC screening rate increased significantly after intervention (69.7%) as compared with before (64.3%) (P = <0.01; 95%CI = 5.39-5.4). Our clinic's CRC screening rates increased significantly during the initial 3 months of the COVID-19 surge (67.8%) compared with the same period the prior year. (62.3%) (P = .003; 95%CI = 3.4-7.6). Our CRC screening rates increased after intervention (69.7%) compared with our regional health system (67%) (P = <0.01; 95%CI = 2.6-2.77). Our weekly stool-based CRC screening increased (94% increase) compared with other health systems nationally (61 to 83% decrease). DISCUSSION: A multi-component intervention, including academic detailing, panel management, and mailed MT-sDNA testing, can lead to significant increases in CRC screening in a rural family medicine clinic, empowering providers to maintain an effective CRC screening outreach during COVID-19 related restrictions.

Geographical origin identification of mandarin fruits by analyzing fingerprint signatures based on multielemental composition.

Given rising traders and consumers concerns, the global food industry is increasingly demanding authentic and traceable products. Consequently, there is a heightened focus on verifying geographical authenticity as food quality assurance. In this work, we assessed pattern recognition approaches based on elemental predictors to discern the provenance of mandarin juices from three distinct citrus-producing zones located in the Northeast region of Argentina. A total of 202 samples originating from two cultivars were prepared through microwave-assisted acid digestion and analyzed by microwave plasma atomic emission spectroscopy (MP-AES). Later, we applied linear discriminant analysis (LDA), k-nearest neighbor (k-NN), support vector machine (SVM), and random forest (RF) to the element data obtained. SVM accomplished the best classification performance with a 95.1% success rate, for which it was selected for citrus samples authentication. The proposed method highlights the capability of mineral profiles in accurately identifying the genuine origin of mandarin juices. By implementing this model in the food supply chain, it can prevent mislabeling fraud, thereby contributing to consumer protection.

Intervención educativa para la prevención de la escabiosis dirigida a representantes de preescolares de 5-6 años / Educational intervention for the prevention of scabiosis Aimed at representatives of preschoolers of 5-6 years / Intervenção educativa para a prevenção da escabiose dirigida a representantes de crianças pré-escolares de 5 a 6 anos

INTRODUCCIÓN: la escabiosis constituye un problema de salud pública en especial en los niños, es una infestación cutánea, altamente pruriginosa y contagiosa endémica en países en vías de desarrollo, afecta a todos los grupos socioeconómicos y a todas las edades es causa la alta morbilidad OBJETIVO: determinar la información sobre prevención de escabiosis que poseen los representantes de preescolares de 5-6 años de la comunidad de la Peña posterior a una intervención educativa MATERIALES Y MÉTODOS: investigación cuasi experimental de pre test y post test de las intervenciones educativas. El universo estuvo conformado por 143 representantes de preescolares, la muestra intencionada fue de 86 personas, el instrumento fue un cuestionario conformado por ítems de respuestas dicotómicas que se administró a los representantes antes de la intervención educativa y posterior a la misma. RESULTADOS: antes de la intervención existía muy baja información acerca de la prevención de la escabiosis lo que representaba el 67.4 %. Posterior a la misma se incrementa el número de representantes que mejoran su nivel de información hasta llegar a 73.2%. CONCLUSIÓN: El desarrollo y aplicación de la intervención educativa logro elevar los conocimientos sobre que es la escabiosis identificar cuáles son los factores de riesgo.

INTRODUCTION: scabies is a public health problem, especially in children. It is a highly pruritic and contagious skin infestation endemic in developing countries. It affects all socioeconomic groups and causes high morbidity at all ages. OBJECTIVE: to determine the information on the prevention of scabies that the representatives of preschool children aged 5-6 years from the Peña community have after an educational intervention. MATERIALS AND METHODS: quasiexperimental pre-test and post-test research of educational interventions. The universe was made up of 143 preschool representatives, the intended sample was 86 people, and the instrument was a questionnaire made up of items of dichotomous responses that were administered to the representatives before and after the educational intervention. RESULTS: before the intervention, there was very little information about the prevention of scabies, which represented 67.4%. After the same, the number of representatives that improve their level of information increases to 73.2%. CONCLUSION: the development and application of the educational intervention managed to raise the knowledge about what scabies is, to identify which are the risk factors.

INTRODUÇÃO: a escabiose constitui um problema de saúde pública principalmente em crianças, é uma infestação cutânea altamente pruriginosa e contagiosa, endêmica em países em desenvolvimento, afeta todos os grupos socioeconômicos e é causa de alta morbidade em todas as idades OBJETIVO: determinar as informações sobre prevenção de sarna que os representantes de crianças pré-escolares de 5-6 anos da comunidade La Peña têm após uma intervenção educativa MATERIAIS E MÉTODOS: pesquisa quase experimental de pré-teste e pós-teste de intervenções educativas. O universo foi constituído por 143 representantes da pré-escola, a amostra pretendida foi de 86 pessoas, o instrumento foi um questionário composto por itens de resposta dicotómicos que foi aplicado aos representantes antes e após a intervenção educativa. RESULTADOS: antes da intervenção havia muito pouca informação sobre a prevenção da escabiose, o que representava 67,4%. Depois disso, o número de representantes que melhoraram seu nível de informação aumentou para 73,2%. CONCLUSÃO: o desenvolvimento e aplicação da intervenção educativa foi capaz de aumentar o conhecimento sobre o que é sarna para identificar quais são os fatores de risco.

Recommendations for the response against COVID-19 in migratory contexts under a closed border: The case of Colombia / Recomendaciones para la respuesta contra la COVID-19 en contextos migratorios bajo una frontera cerrada: el caso de Colombia

Despite the positive response of Colombia's health system to the arrival of Venezuelan migrants, the new challenges that accompany the COVID-19 pandemic have triggered a closed-borders response that runs the risk of encouraging a negative view of migrants and increasing their health risks. This manuscript discusses the recommendations that could be proposed in the case of a country with limited resources such as Colombia to respond to the needs of the Venezuelan mixed migrant flows.

A pesar de la respuesta positiva del sistema de salud de Colombia a la llegada de migrantes venezolanos, los nuevos desafíos que acompañan la pandemia de COVID-19 han desencadenado una respuesta de fronteras cerradas, con lo que se corre el riesgo de alentar una visión negativa de los migrantes e incrementar sus riesgos en salud. Este manuscrito discute las recomendaciones que podrían proponerse en el caso de un país con recursos limitados, como Colombia, para responder a las necesidades de una población vulnerable como la conformada por los flujos de migrantes mixtos venezolanos.

Indicadores de gobernanza para el desarrollo de estrategias binacionales deprotección social en la salud de los migrantes / Governance indicators for the development of bi-national strategies on social protection for the health of immigrants

Este artículo presenta resultados de un estudio cuyo principal objetivo fue identificar los actores clave, sus roles, coaliciones y los espacios de interacción para el desarrollo de protección social en la salud de los migrantes. Se identificaron 10 categorías de actores clave para estrategias de salud para emigrantes, así como metas de política y estrategias binacionales de salud con diferentes niveles de factibilidad y efectividad. Un seguro público binacional de salud para emigrantes indocumentados es factible pero requiere una gran inversión y movilización de recursos públicos. Para ello se deberán desarrollar nuevas iniciativas dirigidas a resolver los problemas de equidad y acceso en la salud de los migrantes.

Improving access to health care for undocumented immigrants in the United States / Mejor acceso a la atención en salud para inmigrantes indocumentados en los Estados Unidos

Objective. To identify policies that increase access to health care for undocumented Mexican immigrants. Materials and methods. Four focus groups (n=34 participants) were conducted with uninsured Mexican immigrants in Los Angeles, California. The feasibility and desirability of different policy proposals for increasing access were discussed by each group. Results. Respondents raised significant problems with policies including binational health insurance, expanded employer-provided health insurance, and telemedicine. The only solution with a consensus that the change would be feasible, result in improved access, and they had confidence in was expanded access to community health centers (CHC's). Conclusions. Given the limited access to most specialists at CHC's and the continued barriers to hospital care for those without health insurance, the most effective way of improving the complete range of health services to undocumented immigrants is through immigration reform that will bring these workers under the other health care reform provisions.

Objetivo. Identificar políticas para mejorar el acceso a la salud en migrantes indocumentados mexicanos en los Estados Unidos. Material y métodos. Se realizaron cuatro grupos focales (34 participantes) con migrantes mexicanos sin seguro médico residentes de Los Ángeles, California. Se discutieron la factibilidad y pertinencia de varias propuestas de políticas de mejora en el acceso. Resultados. Los participantes identificaron limitaciones profundas con propuestas como seguro binacional de salud, expansión de seguro por medio de trabajo y programas de telemedicina. La única con consenso de factibilidad, accesibilidad y pertinencia fue el crecimiento de la red de centros a la atención de salud comunitaria (CHC por sus siglas en ingles). Conclusiones. Dado la escasez de especialistas en CHC y las barreras para acudir a hospitales cuando no cuentan con seguro médico en EUA, la manera más eficaz para mejorar acceso para migrantes indocumentados es por medio de una reforma de las leyes de migración.

Factores de riesgo relacionado con la mortalidad en la cirugía multivalvular / Fatores de risco relacionados à mortalidade na cirurgia multivalvar / Risk factors related to multivalve surgey mortality

Las enfermedades cardiovasculares son las que afectan en mayor grado a los países desarrollados y a los países en vía de desarrollo. Cuba no está exenta de esto, y las enfermedades cardiovasculares son la primera causa de muerte en nuestro medio y, dentro de ellas, las lesiones valvulares siguensiendo una enfermedad cardiaca frecuente. Se realizó un estudio descriptivo y retrospectivo en 128 pacientes operados de 2 o más válvulas cardíacas en el Servicio de Cirugía Cardiovascular del Hospital Hermanos Ameijeiras, de enero del 2006 a diciembre del 2010. Se evaluaron las variables preoperatorias, transoperatorias y postoperatorias y su relación con la mortalidad. Predominóel sexo femenino y las edades entre 40 y 59 años. Todos los pacientes se encontraban en clase funcional III y IV. El 50% de los casos presentó el antecedente de fiebre reumática. La afectación valvular predominante fue mitro-aórtica, así como la doble sustitución valvular el procedimientoquirúrgico más realizado. La mortalidad global en este quinquenio de los pacientes operados de válvulas en nuestro servicio fue del 5,9%. Sin embargo en el subgrupo específico de operaciones realizadas sobre varias válvulas fue del 14,8 %, constatándose una asociación significativa de esta variable con: la presencia de fiebre reumática, el hecho de pertenecer a la clase funcional IV, tiempos de CEC por encima de 211 minutos y tiempo de paro anóxico superior a 150 minutos. La presencia de complicaciones como arritmias, anemia y trastornos de la coagulación, del tipo respiratorias, las complicaciones renales y la reintervención quirúrgica mostraron asociación significativa con la mortalidad...

As doenças cardiovasculares são as mais comuns nos países desenvolvidos e nos países em via de desenvolvimento. Cuba também não está isenta e as doenças cardiovasculares são a primeiracausa de morte em nosso meio e, como sabemos, as lesões valvares continuam sendo uma doença cardíaca frequente. Realizou-se um estudo descritivo e retrospectivo em 128 pacientes operados de 2 ou mais valvas cardíacas no Serviço de Cirurgia Cardiovascular do Hospital Hermanos Ameijeiras,de janeiro de 2006 a dezembro de 2010. Avaliaram-se as variáveis pré operatórias, transoperatóriase pós operatórias e sua relação com a mortalidade. O predomínio foi do sexo feminino e as idades predominantes foram de 40 a 59 anos. Todos os pacientes se encontravam em classe funcional III e IV. 50% dos casos apresentou febre reumática como antecedente. A valva mais afetada foi amitro-aórtica, e a dupla troca valvar foi o procedimento cirúrgico mais realizado.A mortalidade global dos pacientes operados de válvulas em nosso serviço neste quinquênio, foi de 5,9%, entretanto, no subgrupo específico de operações realizadas sobre várias válvulas, foi de 14,8%, constatando-se uma associação significativa desta variável com a presença de febrereumática, o fato de pertenecer à classe funcional IV, tempos de CEC acima de 211 minutos e tempo de parada anóxica superior a 150 minutos. A presença de complicações como arritmias, anemia e trastornos de coagulação, de tiporespiratórias, as complicações renais e a reintervenção cirúrgica, mostraram associação significativa com a mortalidade...

Cardiovascular diseases affect both developed and developing countries. Cuba is not an exception and cardiovascular diseases are the first cause of death in our country and, in them, valve lesions still continue being a frequent heart disease. A descriptive and retrospective analysis of 128 patients operated of two or more cardiac valves was carried out at the Department of Cardiovascular Surgery at the Hermanos Ameijeiras Hospital from January 2006 to December 2010. Preoperative, intraoperative and postoperative variables were assessed and how they related to mortality. There was a prevalence of the female gender and ages ranged from 40 to 59 years. Allpatients were in functional Class III and IV. 50% of the cases had preexisting rheumatic fever. The predominant valve disease was mitral aortic, and the procedure mostly carried out was double valve replacement. Overall mortality of patients undergoing valve surgery in our Department during these five years was 5.9%. Nevertheless, in the specific subgroup of surgeries of several valves mortality was 14.8%, thus reporting a significant relationship of this variable with: presence of rheumatic fever, belonging to functional Class IV, by-pass time over 211 minutes and time of anoxic arrest over 150minutes. The presence of complications such as arrhythmia, anemia, coagulation, respiratory and renaldisorders and surgical re-interventions were statistically significantly related to mortality...