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Nature Medicine Jun 2024Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However,...
Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .
PubMed: 38942993
DOI: 10.1038/s41591-024-03110-7 -
Scientific Reports Jun 2024Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We...
Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. F, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.
Topics: Animals; Goats; Ethiopia; Genome; Phylogeny; Stress, Physiological; Genetic Variation
PubMed: 38942813
DOI: 10.1038/s41598-024-65303-x -
Scientific Data Jun 2024Time-course transcriptome expression data were constructed for four parts of the silk gland (anterior, middle, and posterior parts of the middle silk gland, along with...
Time-course transcriptome expression data were constructed for four parts of the silk gland (anterior, middle, and posterior parts of the middle silk gland, along with the posterior silk gland) in the domestic silkworm, Bombyx mori, from days 0 to 7 of the last-instar larvae. For sample preparation, silk glands were extracted from one female and one male larva every 24 hours accurately after the fourth ecdysis. The reliability of these transcriptome data was confirmed by comparing the transcripts per million (TPM) values of the silk gene and quantitative reverse transcription PCR results. Hierarchical cluster analysis results supported the reliability of transcriptome data. These data are likely to contribute to the progress in molecular biology and genetic research using B. mori, such as elucidating the mechanism underlying the massive production of silk proteins, conducting entomological research using a meta-analysis as a model for lepidopteran insect species, and exploring medical research using B. mori as a model for disease species by utilising transcriptome data.
Topics: Bombyx; Animals; Larva; Transcriptome; Female; Male; Silk
PubMed: 38942767
DOI: 10.1038/s41597-024-03560-1 -
Scientific Reports Jun 2024HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was...
Determinants of hemoglobin level and time to default from Highly Active Antiretroviral Therapy (HAART) for adult clients living with HIV under treatment; a retrospective cohort study design.
HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was conducted to investigate the joint predictors of hemoglobin level and time to default from treatment for adult clients living with HIV/AIDS under HAART at the University of Gondar Comprehensive and Specialized Hospital, North-west Ethiopia. The study was conducted using a retrospective cohort design from the medical records of 403 randomly selected adult clients living with HIV whose follow-ups were from September 2015 to March 2022. Hemoglobin level was projected using Sahli's acid-hematin method. Hence, the hemoglobin tube was filled with N/10 hydrochloric acid up to 2 g % marking and the graduated tube was placed in Sahli's hemoglobin meter. The blood samples were collected using the finger-pick method, considering 22 G disposable needles. The health staff did this. From a total of 403 adult patients living with HIV/AIDS included in the current study, about 44.2% defaulted from therapy. The overall mean and median estimated survival time of adult clients under study were 44.3 and 42 months respectively. The patient's lymphocyte count (AHR = 0.7498, 95% CI: (0.7411: 0.7587), p-value < 0.01), The weight of adult patients living with HIV/AIDS (AHR = 0.9741, 95% CI: (0.9736: 0.9747), p-value = 0.012), sex of adult clients (AHR = 0.6019, 95% CI: (0.5979, 0.6059), p-value < 0.01), WHO stages III compared to Stage I (AHR = 1.4073, 95% CI: (1.3262, 1.5078), p-value < 0.01), poor adherence level (AHR = 0.2796, 95% CI: (0.2082, 0.3705) and p-value < 0.01), bedridden patients (AHR = 1.5346, 95% CI: (1.4199, 1.6495), p-value = 0.008), and opportunistic infections (AHR = 0.2237, 95% CI: (0.0248, 0.4740), p-value = 0.004) had significant effect on both hemoglobin level and time to default from treatment. Similarly, other co-morbidity conditions, disclosure status of the HIV disease, and tobacco and alcohol addiction had a significant effect on the variables of interest. The estimate of the association parameter in the slope value of Hgb level and time default was negative, indicating that the Hgb level increased as the hazard of defaulting from treatment decreased. A patient with abnormal BMI like underweight, overweight, or obese was negatively associated with the risk of anemia (lower hemoglobin level). As a recommendation, more attention should be given to those patients with abnormal BMI, patients with other co-morbidity conditions, patients with opportunistic infections, and low lymphocytes, and bedridden and ambulatory patients. Health-related education should be given to adult clients living with HIV/AIDS to be good adherents for medical treatment.
Topics: Humans; Male; Adult; Female; Retrospective Studies; HIV Infections; Antiretroviral Therapy, Highly Active; Hemoglobins; Middle Aged; Ethiopia; Young Adult; Anti-HIV Agents; Undertreatment
PubMed: 38942753
DOI: 10.1038/s41598-024-62952-w -
NPJ Breast Cancer Jun 2024Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. To improve...
Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. To improve reproducibility, the International Immuno-oncology Working Group recently released recommendations for the computational assessment of TILs that build on visual scoring guidelines. However, existing resources do not adequately address these recommendations due to the lack of annotation datasets that enable joint, panoptic segmentation of tissue regions and cells. Moreover, existing deep-learning methods focus entirely on either tissue segmentation or cell nuclei detection, which complicates the process of TILs assessment by necessitating the use of multiple models and reconciling inconsistent predictions. We introduce PanopTILs, a region and cell-level annotation dataset containing 814,886 nuclei from 151 patients, openly accessible at: sites.google.com/view/panoptils . Using PanopTILs we developed MuTILs, a neural network optimized for assessing TILs in accordance with clinical recommendations. MuTILs is a concept bottleneck model designed to be interpretable and to encourage sensible predictions at multiple resolutions. Using a rigorous internal-external cross-validation procedure, MuTILs achieves an AUROC of 0.93 for lymphocyte detection and a DICE coefficient of 0.81 for tumor-associated stroma segmentation. Our computational score closely matched visual scores from 2 pathologists (Spearman R = 0.58-0.61, p < 0.001). Moreover, computational TILs scores had a higher prognostic value than visual scores, independent of TNM stage and patient age. In conclusion, we introduce a comprehensive open data resource and a modeling approach for detailed mapping of the breast tumor microenvironment.
PubMed: 38942745
DOI: 10.1038/s41523-024-00663-1 -
Diagnostic and Interventional Imaging Jun 2024Radiology in Canada is advancing through innovations in clinical practices and research methodologies. Recent developments focus on refining evidence-based practice... (Review)
Review
Radiology in Canada is advancing through innovations in clinical practices and research methodologies. Recent developments focus on refining evidence-based practice guidelines, exploring innovative imaging techniques and enhancing diagnostic processes through artificial intelligence. Within the global radiology community, Canadian institutions play an important role by engaging in international collaborations, such as with the American College of Radiology to refine implementation of the Ovarian-Adnexal Reporting and Data System for ultrasound and magnetic resonance imaging. Additionally, researchers have participated in multidisciplinary collaborations to evaluate the performance of artificial intelligence-driven diagnostic tools for chronic liver disease and pediatric brain tumors. Beyond clinical radiology, efforts extend to addressing gender disparities in the field, improving educational practices, and enhancing the environmental sustainability of radiology departments. These advancements highlight Canada's role in the global radiology community, showcasing a commitment to improving patient outcomes and advancing the field through research and innovation. This update underscores the importance of continued collaboration and innovation to address emerging challenges and further enhance the quality and efficacy of radiology practices worldwide.
PubMed: 38942638
DOI: 10.1016/j.diii.2024.06.004 -
Journal of the American Board of Family... Jun 2024Interest is growing in clinic-based programs that screen for and intervene on patients' social risk factors, including housing, food, and transportation. Though several...
BACKGROUND
Interest is growing in clinic-based programs that screen for and intervene on patients' social risk factors, including housing, food, and transportation. Though several studies suggest these programs can positively impact health, few examine the mechanisms underlying these effects. This study explores pathways through which identifying and intervening on social risks can impact families' health.
METHODS
This qualitative study was embedded in a randomized clinical trial that examined the health impacts of participation in a social services navigation program. We conducted semi-structured interviews with 27 English or Spanish-speaking caregivers of pediatric patients who had participated in the navigation program. Interviews were analyzed using thematic analysis.
RESULTS
Caregivers described 3 pathways through which the navigation program affected overall child and/or caregiver health: 1) increasing families' knowledge of and access to social services; 2) helping families connect with health care services; and 3) providing emotional support that reduced caregiver isolation and anxiety. Participants suggested that navigation programs can influence health even when they do not directly impact resource access.
DISCUSSION
Social care programs may impact health through multiple potential pathways. Program impacts seem to be mediated by the extent to which programs increase knowledge of and access to social and health care services and support positive relationships between families and program personnel.
PubMed: 38942446
DOI: 10.3122/jabfm.2023.230232R2 -
International Journal of Spine Surgery Jun 2024We provide a historical and technical perspective on the evolution of Kambin's triangle as a safe working corridor for percutaneous access to the intervertebral disc to...
We provide a historical and technical perspective on the evolution of Kambin's triangle as a safe working corridor for percutaneous access to the intervertebral disc to an anatomically expanded space to accommodate and facilitate open lumbar total joint replacement. The nearly 6-decade progression from intradiscal access in the intact lumbar spine to an enlarged working space following facetectomy to accommodate a transforaminal lumbar interbody fusion, and eventual further expansion via pedicle vertebral body osteotomy to support motion preservation with total joint replacement, represents a unique evolutionary pathway in surgical technique development. For each of these steps in evolution, we detail and provide the historical context of the corresponding surgical modifications required to expand the original anatomical boundaries of Kambin's triangle. It is postulated that the introduction of machine learning technologies coupled with innovations in robotics, materials science, and advanced imaging will further accelerate and refine the adaptation of more complex, precise, and efficacious surgical procedures to treat spinal degeneration via this working corridor.
PubMed: 38942442
DOI: 10.14444/8611 -
BMJ Military Health Jun 2024Soldiers must achieve high-level mission-preparedness to endure extended periods of physical and cognitive activity, with unpredictable recovery, in all environments.... (Review)
Review
Soldiers must achieve high-level mission-preparedness to endure extended periods of physical and cognitive activity, with unpredictable recovery, in all environments. Nutrition provides the foundation for health and performance. Militaries have not maximised the strategic and financial value that considering nutrition as a military capability could deliver. A whole system approach to military nutrition, based on the prepare-perform-recover human capability cycle phases, is presented. Trainee nutrition requirements, through to very-high-readiness forces undertaking arduous roles at reach, must be specifically addressed. Promoting military performance diets in the prepare phase, through practitioner-supported nutrition education and food provision, will ensure mission readiness and mitigate ill health. Delivering nutrition in field settings in the perform phase-through smaller/lighter, nutritionally optimised rations and smart packaging technologies-will improve utility and minimise waste. Strategic dietary supplement use can provide a mission performance-enhancing adjunct to a food-first philosophy. Impact value chain analysis of military nutrition capability investments could support cost-benefit measurement.
PubMed: 38942432
DOI: 10.1136/military-2024-002738 -
Joint Bone Spine Jun 2024
PubMed: 38942355
DOI: 10.1016/j.jbspin.2024.105752