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81.
Dylan A. Levy Jaimin J. Patel Shaun A. Nguyen W. Nicholas Jungbauer David M. Neskey Ezra E. W. Cohen Chrystal M. Paulos John A. Kaczmar Hannah M. Knochelmann Terry A. Day 《世界耳鼻咽喉头颈外科杂志(英文)》2022,8(3):177
BackgroundPD‐1 and PD‐L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).MethodsSystematic review and meta‐analysis of PD‐1 and PD‐L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression‐free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment‐related adverse events (TRAEs).ResultsEleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18–90). The total mOS was 7.97 months (range: 6.0–16.5). Mean mPFS for all studies was 2.84 months (range: 1.9–6.5). PD‐1 inhibitors had a lower rate of RECIST Progressive Disease than PD‐L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29–49.06 vs. 56.79%, 95% CI: 49.18–64.19, P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8–65.6) did not differ.ConclusionsMeta‐analysis shows the efficacy of PD‐1 and PD‐L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD‐1 and PD‐L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted. 相似文献
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Laura Oggianu Giorgio Di Dato Giorgina Mangano Maria Teresa Rosignoli Savannah McFeely Alice Ban Ke Hannah M. Jones Alessandro Comandini 《CTS Clinical and Translational Science》2022,15(6):1417
Trazodone is approved for the treatment of major depressive disorders, marketed as immediate release (IR), prolonged release, and once a day (OAD) formulation. The different formulations allow different administration schedules and may be useful to facilitate patients’ compliance to the antidepressant treatment. A previously verified physiologically‐based pharmacokinetic model based on in vitro and in vivo information on trazodone pharmacokinetics was applied, aiming at predicting brain receptor occupancy (RO) after single and repeated dosing of the IR formulation and repeated dosing of the OAD formulation in healthy subjects. Receptors included in the simulations were selected using static calculations of RO based on the maximum unbound brain concentration (Cmax,brain,u) of trazodone for each formulation and dosing scheme, resulting in 16 receptors being simulated. Seven receptors were simulated for the IR low dose formulation (30 mg), with similar t onset and duration of coverage (range: 0.09–0.25 h and 2.1–>24 h, respectively) as well as RO (range: 0.64–0.92) predicted between day 1 and day 7 of dosing. The 16 receptors evaluated for the OAD formulation (300 mg) showed high RO (range: 0.97–0.84 for the receptors also covered by the IR formulation and 0.73–0.48 for the remaining) correlating with affinity and similar duration of time above the target threshold to the IR formulation (range: 2–>24 h). The dose‐dependent receptor coverage supports the multimodal activity of trazodone, which may further contribute to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
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Andrew Berry Janet Browne 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(30)
Evolution by natural selection is an explicitly genetic theory. Darwin recognized that a working theory of inheritance was central to his theory and spent much of his scientific life seeking one. The seeds of his attempt to fill this gap, his “provisional hypothesis” of pangenesis, appear in his notebooks when he was first formulating his evolutionary ideas. Darwin, in short, desperately needed Mendel. In this paper, we set Mendel’s work in the context of experimental biology and animal/plant breeding of the period and review both the well-known story of possible contact between Mendel and Darwin and the actual contact between their ideas after their deaths. Mendel’s contributions to evolutionary biology were fortuitous. Regardless, it is Mendel’s work that completed Darwin’s theory. The modern theory based on the marriage between Mendel’s and Darwin’s ideas as forged most comprehensively by R. A. Fisher is both Darwin’s achievement and Mendel’s. 相似文献
86.
John Monro Suman Mishra Halina Stoklosinski Kerry Bentley-Hewitt Duncan Hedderley Hannah Dinnan Sheridan Martell 《Nutrients》2022,14(15)
Non-sugar components of kiwifruit reduce the amplitude of the glycaemic response to co-consumed cereal starch. We determined the relative contribution of different non-sugar kiwifruit components to this anti-glycaemic effect. Healthy participants (n = 9) ingested equal carbohydrate meals containing 20 g starch as wheat biscuit (WB, 30 g), and the sugar equivalent of two kiwifruit (KFsug, 20.4 g), either intrinsic or added as glucose, fructose and sucrose (2:2:1). The meals were WB+KFsug (control, no non-sugar kiwifruit components), WB + whole kiwifruit pulp (WB+KF), WB + neutralised kiwifruit pulp (WB+KFneut), WB + low-fibre kiwifruit juice (WB+KFjuice) and WB+KFsug + kiwifruit organic acids (WB+KFsug+OA). All meals were spiked with 100 mg sodium [1-13C] acetate to measure intestinal absorption. Each participant ingested all meals in random order. Blood glucose and breath 13CO2 were measured at ingestion and at 15 min intervals up to 180 min. Compared with WB+KFsug, whole kiwifruit pulp (WB+KF) almost halved glycaemic response amplitude (p < 0.001), reduced incremental area under the blood glucose response curve (iAUC) at 30 min (peak) by 50% (p < 0.001), and averted late postprandial hypoglycaemia. All other treatments suppressed response amplitude half as much as whole kiwifruit and averted acute hypoglycaemia, with little effect on iAUC. Effects on 13CO2 exhalation paralleled effects on blood glucose (R2 = 0.97). Dietary fibre and organic acids contributed equally to the anti-glycaemic effect of kiwifruit by reducing intestinal absorption rate. Kiwifruit flesh effectively attenuates glycaemic response in carbohydrate exchange, as it contains fructose, dietary fibre and organic acids. 相似文献
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Austin M. Looney Hannah K. Day Spencer M. Comfort Stiles T. Donaldson Steven B. Cohen 《Current reviews in musculoskeletal medicine》2023,16(3):103
Purpose of ReviewTo assess the current literature surrounding the treatment and rehabilitation strategies surrounding proximal hamstring rupture injuries, along with comparative return to sport and patient-reported outcomes.Recent FindingsA high degree of variability exists in protective and rehabilitation strategies after both operative and non-operative proximal hamstring rupture management. Acceptable outcomes after both operative and non-operative management have been observed but may vary greatly with injury chronicity, severity, and surgical technique.SummaryThe high complication rates observed after surgical treatment, along with poor functional outcomes that may occur in the setting of non-operative treatment or delayed surgery, highlight the importance of early injury evaluation and careful patient selection. Further high-quality research elucidating clearer indications for early operative management and an optimized and standardized rehabilitation protocols may improve outcomes and return to sport experience and metrics for individuals sustaining proximal hamstring ruptures. 相似文献
89.
90.
Joshua M. Wong Hannah R. Volkman Laura E. Adams Carene Oliveras García Alma Martinez-Quiones Janice Perez-Padilla Jorge Bertrn-Pasarell Diego Sainz de la Pea Rafael Tosado-Acevedo Gilberto A. Santiago Jorge L. Muoz-Jordn Brenda C. Torres-Velsquez Olga Lorenzi Liliana Snchez-Gonzlez Vanessa Rivera-Amill Gabriela Paz-Bailey 《The American journal of tropical medicine and hygiene》2023,108(1):107