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127 Pembrolizumab Monotherapy for Locally Advanced or Metastatic Non–Small-Cell Lung Cancer (NSCLC): 10-Year Outcomes From Clinical Trials
No full textClosed-loop control and experimental study of rotor vibration considering track constraints
No full textTo address issues such as excessive 1/rev low-frequency vibration of the rotor and track split caused by blade dissimilarity， a closed-loop vibration control algorithm for rotors based on blade track constraints was developed. Firstly， a rotor aeroelastic coupling model with flexible blades was established， with parameters set to simulate the dissimilarity of blades in engineering applications， thereby generating track split phenomena and vibration imbalance characteristics. Secondly， taking the harmonic components of rotor vibration as the control objective， the collective pitch variation of individual blades as the control input， and the track difference as the constraint condition， a set of constrained optimization problems was constructed to solve for the optimal control inputs. Then， through numerical simulations， the control algorithm without track constraints was compared， and the results demonstrate that introducing track constraints not only significantly reduced the amplitude of low-frequency vibrations but also confined the track difference within a specified range， verifying the effectiveness of the constrained control algorithm. Finally， further experimental validation was conducted by establishing a rotor system test platform， adapting the control algorithm into a Simulink model， and integrating corresponding hardware devices to build a software-hardware architecture. Execution of the control algorithm under different flight conditions shows that vibrations were reduced by over 60% in all cases， with track differences constrained near the set value and achieving a maximum reduction of 73%
Obstructive sleep apnea severity, Alzheimer's disease plasma markers, and CSF brain amyloidosis and tau pathology
No full textINTRODUCTIONWe examined obstructive sleep apnea (OSA) severity's association with Alzheimer's disease (AD) plasma biomarkers, independent or synergistic with cerebrospinal fluid (CSF) amyloid, and as a proof of concept, whether plasma amyloid beta (Aβ)42/Aβ40 with OSA severity improves detection of amyloidosis and tau pathology.METHODSIn 120 cognitively normal older adults (70 with CSF data) from New York University sleep and aging studies (2013–2021), OSA severity was measured using apnea/hypopnea index with 4% desaturation; plasma Aβ40, Aβ42, tau, and neurofilament light chain (NfL) via single molecule array; CSF amyloid and tau via enzyme-linked immunosorbent assay. Associations evaluated adjusted correlations and generalized models; receiver operating characteristic analyses evaluated diagnostic accuracy.RESULTSOSA severity correlated with plasma Aβ40 (r = 0.21), Aβ42 (r = 0.26), and Aβ42/Aβ40 (r = 0.20). Plasma tau and NfL associations depended on CSF–Aβ42. OSA severity with Aβ42/Aβ40 improved CSF amyloidosis (area under the curve [AUC] = 0.78) and tau pathology (AUC = 0.71) detection.DISCUSSIONOSA severity relates to elevated plasma Aβ and, with CSF amyloid, to tau/NfL. Combined plasma and OSA measures aid non-invasive AD associations’ detection.HighlightsObstructive sleep apnea (OSA) is associated with plasma amyloid beta (Aβ)40, Aβ42, and Aβ42/Aβ40.OSA in synergism with brain amyloid levels is associated with plasma tau and neurofilament light chain.Combined with plasma Aβ42/Aβ40, OSA enhances brain amyloidosis and tau pathology detection
Endometrial immune cell profile at the time of frozen embryo transfer as prognostic indicator of live birth
No full textIntroduction: Endometrial receptivity is essential for implantation in both natural and ART cycles, yet the cellular and molecular environment of the endometrium during this window remains poorly characterized. While cytokines affecting implantation have been studied, data on immune cell subtypes in the endometrium are limited. The objective of this study was to determine the association between endometrial immune cell profile at the time of transfer and live birth in patients undergoing frozen embryo transfer (FET) using the index cycle.Methods: This exploratory prospective observational cohort study (IRB#20190139) included 48 patients undergoing a hormone replacement FET cycle between May 2022 and May 2024. After ultrasound-guided FET, the catheter tip was rinsed in IMDM + 10% FBS, centrifuged, and stained for CD45, CD3, CD19, CD4, CD8, γδ TCR, CD25, CD127, CD66b, CD14, CD16, and CD56. The primary outcome was live birth. Secondary outcomes included miscarriage, biochemical pregnancy, and ectopic pregnancy.Results: Elective single embryo transfer was performed for all the patients. There were 24 live births (50%), four miscarriages (8.3%), and three biochemical pregnancies (6.3%). There was no significant difference in demographics of patients that had a live birth compared to those who did not achieve implantation. There was an increased percentage of γδ T cells in the group of live birth compared to non-pregnant group (p=0.019). In contrast, an increased percentage of neutrophils (CD66b+) was noted in patients that did not achieve implantation (p<0.003). Importantly, we found receiver operating characteristic (ROC) curve area under the curve (AUC) of 0.72 with 95% confidence interval (CI) 0.5504 to 0.8989 for γδ T cells and AUC is 0.75 (95% CI 0.5681 to 0.9319) for CD66b+ cells, confirming the overall ability of these two tests to discriminate between patients who will achieve a live birth vs. ones who will have failed implantation.Discussion: Our findings suggest that the uterine immune environment during FET may be associated with implantation outcomes. Characterization of endometrial immune cell profiles could provide insights into biological factors linked to implantation and live birth, although their clinical utility remains to be determined. To our knowledge, this study is among the first to describe associations between immune cell profiles assessed during the index FET cycle and subsequent IVF outcomes, supporting a potential role for endometrial immune composition in pregnancy success
High-dose influenza vaccine augments serological and cellular immunity of older people with HIV
No full textHigh-dose influenza vaccine, containing four times more antigen than standard-dose, is recommended for people aged ≥ 65 years, but there is a knowledge gap surrounding its effect in people with HIV (PWH), who remain more vulnerable to serious influenza infections than people without HIV (PWoH) despite virological suppression. The primary goal of this study was to assess whether high-dose improves antibody responses in PWH, with a particular focus on older PWH.
We conducted a study to assess antibody responses to sequential high- versus standard-dose influenza vaccination in PWH. Young (18-40 years) PWoH (n=55) and PWH (n=37); and older (≥ 60 years) PWoH (n=72) and PWH (n=67) received standard-dose during the 2020-2024 seasons and 123 participants, including 41 older PWH, received high-dose the consecutive season. All PWH were virologically suppressed on ART. Hemagglutination inhibition (HAI) titer and HA-specific IgG were analyzed at 0- to 180-days post-vaccination (dpv); T cell activation-induced responses were assessed by flow cytometry.
All groups mounted significant HAI and IgG responses to all vaccine antigens at 28 dpv, after standard- and high-dose vaccination. Responses to A/H1N1 were lower in magnitude and durability in older PWH compared to young PWoH following standard-dose and were not boosted with high-dose, whereas high-dose enhanced A/H3N2 and B/Victoria IgG, and CD4+ T cell responses to all antigens, in older PWH.
Our data demonstrate partial efficacy of high-dose in augmenting antibody responses of older PWH while highlighting limitations in boosting A/H1N1-specific responses.
gov NCT04487041.
NIH grant (5R01AG068110)
Severe and widespread coral reef damage during the 2014-2017 Global Coral Bleaching Event
No full textOcean warming is increasing the frequency, extent, and severity of tropical-coral bleaching and mortality. During 2014–2017, marine heatwaves caused the Third Global Coral Bleaching Event. We analyze data from 15,066 reef surveys globally during 2014–2017. Across all surveyed reefs, 80% and 35% experienced moderate or greater (affecting >10% of corals) bleaching and mortality, respectively. We assess the global extent of coral bleaching and mortality by applying bleaching response curves calibrated from surveyed reefs to predict bleaching globally, based on comprehensive remote-sensing of heat stress. These models predict that 51% and 15% of the world’s coral reefs suffered moderate or greater bleaching and mortality, respectively, during one or multiple years, surpassing damage from any prior global coral bleaching event. Our findings demonstrate that the impacts of ocean warming on coral reefs are accelerating, with the near certainty that ongoing warming will cause large-scale, possibly irreversible, degradation of these essential ecosystems. With heat stress levels during this event surpassing those observed previously, the National Oceanic and Atmospheric Administration developed more extreme Bleaching Alert levels that are now being used during the ongoing Fourth Global Coral Bleaching Event.
The U.S. National Oceanic and Atmospheric Administration’s (NOAA) CRW program and National Coral Reef Monitoring Program were supported by funding from the NOAA Coral Reef Conservation Program and Ocean Remote Sensing Program. University of Maryland and ReefSense personnel were fully supported by NOAA grant NA19NES4320002 (Cooperative Institute for Satellite Earth System Studies) at the University of Maryland/Earth System Science Interdisciplinary Center, and by the Professional, Scientific, and Technical Services Program (ProTech)-Satellite contract with Global Science & Technology, Inc. SFH was partially supported by Australian Research Council grant DP230102986. Bleaching analysis work by SRC was supported by the Australian Research Council (CE140100020) and the Smithsonian Tropical Research Institute. Part of this work was performed and funded under ST133017CQ0050_1332KP22FNEED0042. Additional funding for data collation and analysis provided by Vulcan Inc. We also acknowledge, with gratitude, the myriad funding sources that supported the collection of data that enabled this analysis. The scientific results and conclusions, as well as any views or opinions expressed herein, are those of the author(s) and do not necessarily reflect the views of NOAA or the Department of Commerce. Figure 4 was inspired by a National Geographic infographic94. We thank J. Moneghetti for assistance with statistical programming. Thank you to the hundreds of individual data collectors from organizations such as Reef Check, CORDIO, ILTER/PELD (Brazil), and NOAA around the world who contributed to this dataset. In particular, we thank the hundreds of volunteers and the following team leaders from almost 30 Reef Check chapters, who organized teams, carried out surveys and provided significant datasets for these analyses: Australia: Jennifer Loder, Jodi Salmod, Bahamas: Lourene Jones, Monique Curtis, Tom McFeely, Brunei: Sheikh Al-Idrus Nikman, Colombia: Phanor Montoya, Egypt: Nina Milton, Mohammad Kotb, Moshira Hassan, Florida: Nikole Ordway, France (Pacific): Jean Pascale Quod, Matthieu Petit, Denis Schneider, Harold Cambert, France (Atlantic): Remi Garnier, Mathilde Facon, Grenada: Katlyn Treiber-Vajda, Haiti: Erika Pierre Louis, Indonesia: Delphine Robbe, Gianfranco Rossi, Meike Huhn, Andrew Taylor, Nyoman Sugiarto, Iran: Mohammad Ghavasi, Japan: Yasuaki Miamoto, J Harukawa, Satoshi Nojima, Megumu Tsuchikawa, Maldives: Jean-Luc Solandt, Matthias Hammer, Catherine Edsell (Biosphere Expeditions), Malaysia: Julian Hyde, Sue Yee Chen, Alvin Chelliah, Netherlands Antilles: Marjo van den Brulck, Oman: Jean-Luc Solandt, Matthias Hammer, Catherine Edsell (Biosphere Expeditions), Philippines: Vanessa Vergara, Carina Escudero, Xavier Verdadero, Analies Andringa, Scott Countryman, Colin Lock, Puerto Rico: Joel Melendez, Carolina Aragones, St Kitts/Nevis: James Hewlett, Sao Tome/Principe: An Bollen, Thailand: Nathan Cook, Suchana Chavanich, Timor-Leste: Jenny House, Tobago: Lanya Fanovich, Taiwan: Kah-Leng Cherh; and Healthy Reefs for Healthy People Initiative country coordinators who organized teams, carried out surveys and provided significant datasets for these analyses: Belize: Nicole Craig, Guatemala: Ana Giró Petersen. We are grateful for the work of myriad other scientists and non-scientists who contributed data used herein. We acknowledge the Traditional Custodians of coral regions across the tropics from which datasets used here were collected and recognize these First Nations peoples as among the world’s earliest reef scientists
Evaluation of Readability in Patient Education Materials for Primary Hyperparathyroidism
No full textPatient education is essential for effective medical care. Although over half of patients search for health information online, most educational materials exceed the recommended sixth-grade reading level. Parathyroid disease is common yet often underdiagnosed. This study evaluates the readability of online patient resources for parathyroid disorders. A review of 100 online educational materials related to parathyroid disorders was performed. Using three validated instruments: Flesch Reading Ease, Simplified Measure of Gobbledygook, and Gunning Fog Index scores, reading grade level was calculated and Spearman correlations performed to evaluate associations between instruments. 59 sources were included. Majority of materials were from academic/research (36%), followed by general information/overviews (20%), government/institutional (14%), cancer-specific organizations (12%), professional societies (12%) and children's health (5%). No patient materials were written at the appropriate grade level. Materials were > 12th grade reading level in 59% of sources (FRE = 71%, SMOG = 34%, GFI = 71%). There were strong, positive correlations between the three reading instruments. Readable educational materials facilitate effective healthcare literacy and empower patients to participate in shared decision-making, which is especially important given the complex diagnostic and therapeutic considerations for parathyroid disorders. This study demonstrates a significant ongoing disparity. Future efforts should focus on developing patient materials at the recommended reading level.</p
" Comparative Prognostic Accuracy of Model for End-Stage Liver Disease Scores and the Freiburg Index of Post-TIPS Survival in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt for Ascites or Gastroesophageal Bleeding: A Meta-Analysis of Time-Specific Mortality"
No full textThis meta-analysis compares the prognostic accuracy of Model for End-Stage Liver Disease-based scores (MELD) and the Freiburg Index of Post-TIPS Survival (FIPS) for predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) for ascites or gastroesophageal bleeding (GEB) and examines the sources of heterogeneity.
The study followed PRISMA guidelines and searched major biomedical databases for retrospective studies reporting area under the curve (AUC) based mortality prediction.
This meta-analysis included 11 studies (5,180 patients). In ascites, pooled AUCs for 90-day mortality were 0.703 (95% CI: 0.606-0.800) for MELD (6 studies) and 0.699 (95% CI: 0.570-0.828) for MELD-Na (5 studies). FIPS (2 studies) and MELD 3.0 (1 study) showed good performance: AUCs of 0.821 (95% CI: 0.656-0.985), and 0.790 (95% CI: 0.689-0.873), respectively. Subgroup differences were not significant (p=0.412). In GEB, MELD (6 studies), MELD-Na (5 studies), and MELD 3.0 (2 studies) yielded AUCs of 0.827 (95% CI: 0.740-0.914), 0.781 (95% CI: 0.689-0.873), and 0.797 (95% CI: 0.641-0.953), respectively. FIPS (4 studies) showed lower performance (AUC = 0.689; 95% CI: 0.580-0.797), with no statistically significant subgroup differences (p = 0.274).
The discriminatory performance of MELD-based scores varies according to the underlying indication for TIPS. In patients treated for GEB, MELD, MELD-Na, and MELD 3.0 showed good discriminatory capacity for early mortality (30-90 days). In contrast, in patients undergoing TIPS for ascites, MELD and MELD-Na showed only fair accuracy, with some improvement observed for MELD 3.0
