bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and design of a multi‐center, prospective randomized controlled trial on the effects of sacubitril–valsartan versus enalapril on left ventricular remodeling in ST‐elevation myocardial infarction: The PERI‐STEMI study
Authors: Diao Kaiyue , Wang Duolao , Chen Zhongxiu , Wu Xi , Ma Min , Zhu Ye , Zhang Li , Wang Hua , Wang Mian , He Sen , Li Chen , Deng Qiao , Yan Ting , Wu Tao , Tang Lu , Huang Baotao , Sun Jiayu , He Yong 
Published: October 2021

AbstractBackgroundAngiotensin receptor neprilysin inhibitor (ARNI) sacubitril‐valsartan has been recommended as one of the first‐line therapies in heart failure with reduced ejection fraction. However, whether ARNI could benefit patients with ST‐segment elevation myocardial infarction (STEMI) by improving left ventricular (LV) remodeling remains unknown. The primary objective of the PERI‐STEMI trial is to assess whether sacubitril‐valsartan is more effective in preventing adverse LV remodeling for patients with STEMI than enalapril.HypothesisWe hypothesize that sacubitril/valsartan is superior to enalapril in preventing adverse LV remodeling evaluated by cardiovascular magnetic resonance imaging at the 6‐month follow‐up.MethodsPERI‐STEMI is an investigator‐initiated, prospective, multi‐center, randomized, open‐label, superiority trial with blinded evaluation of outcomes. A total of 376 first‐time STEMI patients with primary percutaneous coronary intervention (PPCI) within 12 h after symptom onset will be randomized to sacubitril‐valsartan or enalapril treatment. All the patients will receive a baseline cardiovascular magnetic resonance (CMR) examination at 4–7 days post‐PPCI. The primary endpoint is the change of indexed LV mass at the 6‐month follow‐up CMR.ResultsEnrollment of the first patient is planned in November 2021. Recruitment is anticipated to last for 12–18 months and patients will be followed for 5 years after randomization. The study is expected to complete in June 2027.ConclusionsThe results of the PERI‐STEMI trial are expected to provide CMR evidence on whether ARNI could benefit patients with STEMI, so as to facilitate the strategy of CMR‐based risk stratification and therapy selection for these patients. PERI‐STEMI is registered at ClinicalTrials.gov (NCT04912167).
JASPER: Phase 2 trial of first‐line niraparib plus pembrolizumab in patients with advanced non–small cell lung cancer
Authors: Ramalingam Suresh S. , Thara Eddie , Awad Mark M. , Dowlati Afshin , Haque Basir , Stinchcombe Thomas E. , Dy Grace K. , Spigel David R. , Lu Sharon , Iyer Singh Nithya , Tang Yongqiang , Teslenko Iryna , Iannotti Nicholas 
Published: October 2021

BackgroundPoly(ADP‐ribose) polymerase (PARP) inhibitors may synergize with programmed cell death receptor‐1 (PD‐1) inhibitors to enhance adaptive and innate antitumor immune responses. In the phase 2 JASPER study (NCT03308942), the PARP inhibitor niraparib was evaluated in combination with the PD‐1 inhibitor pembrolizumab in patients with metastatic and/or locally advanced non–small cell lung cancer (NSCLC).MethodsPatients whose tumors had programmed cell death ligand 1 (PD‐L1) tumor proportion scores (TPS) ≥50% (cohort 1) or 1%‐49% (cohort 2) received first‐line niraparib (200 mg once daily) plus pembrolizumab (200 mg every 3 weeks). The primary end point was investigator‐assessed objective response rate (ORR). Secondary end points included duration of response (DoR), progression‐free survival (PFS), overall survival (OS), safety, and pharmacokinetics.ResultsThirty‐eight patients were enrolled in cohorts 1 and 2. In cohort 1, ORR (95% confidence interval [CI]) was 56.3% (9 of 16 patients; 29.9%‐80.2%); 2 of 16 patients had complete responses and 7 of 16 had partial responses (PRs). In cohort 2, ORR was 20.0% (5.7%‐43.7%) with 4 of 20 PRs. In cohorts 1 and 2, the median DoR was 19.7 months (95% CI, 4.2 months to not estimable [NE]) and 9.4 months (95% CI, 4.2 months to NE), the median PFS was 8.4 months (95% CI, 3.9‐22.1 months) and 4.2 months (95% CI, 2.0‐6.2 months), and the median OS was NE (95% CI, 6.0 months to NE) and 7.7 months (95% CI, 4.0‐12.5 months), respectively. Grade ≥3 treatment‐emergent adverse events occurred in 88.2% and 85.7% of patients in cohorts 1 and 2, respectively. Safety was consistent with known profiles of single‐agent niraparib and pembrolizumab.ConclusionsNiraparib plus pembrolizumab showed clinical activity in patients with advanced and/or metastatic NSCLC.Lay Summary

The JASPER clinical trial studied a new combination treatment for advanced or metastatic non–small cell lung cancer (NSCLC).

Pembrolizumab, a drug approved for NSCLC, was given with niraparib.

Previous research showed that these 2 drugs together might work better than either drug alone.

This study found that more than half of patients with high levels of a tumor marker responded to the combination, and one‐fifth of patients with lower levels of the marker responded.

The types of side effects from the combination were similar to side effects from both drugs alone.

These results support more research on this combination.
Exposed bone in patients with head and neck cancer treated with radiation therapy: An analysis of the Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad)
Authors: Treister Nathaniel S. , Brennan Michael T. , Sollecito Thomas P. , Schmidt Brian L. , Patton Lauren L. , Mitchell Rebecca , Haddad Robert I. , Tishler Roy B. , Lin Alexander , Shadick Ryann , Hodges James S. , Lalla Rajesh V. 
Published: October 2021

BackgroundPatients with head and neck cancer (HNC) treated with radiation therapy (RT) are at risk for jaw osteoradionecrosis (ORN), which is largely characterized by the presence of exposed necrotic bone. This report describes the incidence and clinical course of and risk factors for exposed intraoral bone in the multicenter Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad) cohort.MethodsParticipants were evaluated before RT and at 6, 12, 18, and 24 months after RT. Exposed bone was characterized by location, sequestrum formation, and other associated features. The radiation dose to the affected area was determined, and the history of treatment for exposed bone was recorded.ResultsThe study enrolled 572 participants; 35 (6.1%) were diagnosed with incident exposed bone at 6 (47% of reports), 12 (24%), 18 (20%), and 24 months (8%), with 60% being sequestrum and with 7 cases (20%) persisting for >6 months. The average maximum RT dose to the affected area of exposed bone was 5456 cGy (SD, 1768 cGy); the most frequent associated primary RT sites were the oropharynx (42.9%) and oral cavity (31.4%), and 76% of episodes occurred in the mandible. The diagnosis of ORN was confirmed in 18 participants for an incidence rate of 3.1% (18 of 572). Risk factors included pre‐RT extractions (P = .008), a higher RT dose (P = .039), and tobacco use (P = .048).ConclusionsThe 2‐year incidence of exposed bone in the OraRad cohort was 6.1%; the incidence of confirmed ORN was 3.1%. Exposed bone after RT for HNC is relatively uncommon and, in most cases, is a short‐term complication, not a recurring or persistent one.
Selective Mild Oxidation of Anilines into Nitroarenes by Catalytic Activation of Mesoporous Frameworks Linked with Gold‐Loaded Mn3O4 Nanoparticles
Authors: Daikopoulou Vassiliki , Skliri Euaggelia , Koutsouroubi Eirini D. , Armatas Gerasimos S. , Lykakis Ioannis N. 
Published: October 2021

AbstractThis work reports the synthesis and catalytic application of mesoporous Au‐loaded Mn3O4 nanoparticle assemblies (MNAs) with different Au contents, i. e., 0.2, 0.5 and 1 wt %, towards the selective oxidation of anilines into the corresponding nitroarenes. Among common oxidants, as well as several supported gold nanoparticle platforms, Au/Mn3O4 MNAs containing 0.5 wt % Au with an average particle size of 3–4 nm show the best catalytic performance in the presence of tert‐butyl hydroperoxide (TBHP) as a mild oxidant. In all cases, the corresponding nitroarenes were isolated in high to excellent yields (85–97 %) and selectivity (>98 %) from acetonitrile or greener solvents, such as ethyl acetate, after simple flash chromatography purification. The 0.5 % Au/Mn3O4 catalyst can be isolated and reused four times without a significant loss of its activity and can be applied successfully to a lab‐scale reaction of p‐toluidine (1 mmol) leading to the p‐nitrotulene in 83 % yield. The presence of AuNPs on the Mn3O4 surface enhances the catalytic activity for the formation of the desired nitroarene. A reasonable mechanism was proposed including the plausible formation of two intermediates, the corresponding N‐aryl hydroxylamine and the nitrosoarene.
Controlling Metal Halide Perovskite Crystal Growth via Microcontact Printed Hydrophobic‐Hydrophilic Templates
Authors: Gebremichael Zekarias Teklu , Alam Shahidul , Cefarin Nicola , Pozzato Alessandro , Yohannes Teketel , Schubert Ulrich S. , Hoppe Harald , Tormen Massimo 
Published: October 2021

AbstractHerein, a simple, low‐cost, solution‐processed, and parallel fabrication method to form metal halide perovskite (MHP) poly and single‐crystalline films confined in ordered micrometer‐sized domains is reported. A cross‐linked polydimethylsiloxane (PDMS) stamp featuring 25 µm side squares is used to pattern their substrates. The substrate is microcontact printed on the PDMS inked with self‐assembled monolayers (SAMs) of alkanethiol to form a molecular template, resulting in hydrophilic (gold) and hydrophobic (alkanethiol) domains. The subsequent deposition of lead bromide (PbBr2) and methylammonium bromide (MABr) precursor solutions on the pre‐patterned substrate resulted in poly and single‐crystalline films of methylammonium lead bromide (MAPbBr3) confined to the hydrophilic domains. Two deposition methods: drop‐casting and two‐step spin‐coating are systematically investigated to find well confined and large‐sized single‐crystal MAPbBr3. Casting proves to be more effective than two‐step spin‐coating to achieve better confinement of MAPbBr3. The patterning process is monitored in dependence of the a) deposition methods used to b) precisely control the MAPbBr3 crystal growth in a pre‐defined site which leads to c) grow poly and single‐crystals in a periodic arrangement. Their nondestructive and less energy processable fabrication method will have its own contribution in transferring patterns to desired substrates that enables them to fabricate different types of MHP optoelectronic devices and integrated electronic systems with more complex architectures.
A high step‐up DC–DC converter with active switched LC‐network and voltage‐lift circuit: Topology, operating principle, and implementation
Authors: Dastgiri Armineh , Hosseinpour Majid , Sedaghati Farzad , Mousavi‐Aghdam Seyed Reza 
Published: October 2021

AbstractTo meet the higher DC link voltage requirement in distributed energy resources (DERs) such as fuel cells (FCs), wind turbines (WTs), and photovoltaic (PV) systems, DC–DC converters are applied. A voltage‐lift (VL) circuit‐based transformer‐less active switched LC‐network (ASLC) converter with a high‐voltage gain is proposed in this paper. Compared to a similar reference converter, the voltage gain of the proposed converter increases efficiently by adding one extra capacitor and diode. The operation of the converter in continuous current mode (CCM) and discontinuous current mode (DCM), the analysis of the steady‐state condition, and comparative analysis with some similar converters are discussed. Moreover, the parasitic elements are assumed to calculate the DC‐voltage gain and the efficiency of the converter accurately. The performance of the proposed step‐up converter is simulated in the PSIM software. A prototype circuit rating of about 20/280 V, 200 W of converter model is designed, and its performance is validated. The experimental outcomes clarify the feasibility of the proposed converter.
TIGIT blockade enhances NK cell activity against autologous HIV‐1‐infected CD4+ T cells
Authors: Holder Kayla A , Burt Kimberley , Grant Michael D 
Published: October 2021

AbstractObjectivesDuring chronic human immunodeficiency virus (HIV)‐1 infection, inhibitory molecules upregulated on lymphocytes contribute to effector cell dysfunction and immune exhaustion. People living with HIV (PLWH) are at greater risk for age‐related morbidities, an issue magnified by human cytomegalovirus (CMV) coinfection. As CMV infection modifies natural killer (NK) cell properties and NK cells contribute to protection against HIV‐1 infection, we considered the role of T‐cell immunoreceptor with immunoglobulin and intracellular tyrosine inhibitory motif domains (TIGIT) in NK cell‐based HIV‐1 immunotherapy and elimination strategies.MethodsWe measured TIGIT expression on immune cell subsets of 95 PLWH and assessed its impact on NK cell function, including elimination of autologous CD4+ T cells infected through reactivation of endogenous HIV‐1.ResultsTIGIT was expressed on CD4+ T cells, CD8+ T cells and NK cells from PLWH. Although TIGIT levels on T cells correlated with HIV‐1 disease progression, the extent of TIGIT expression on NK cells more closely paralleled adaptation to CMV. TIGIT interacts with its predominant ligand, poliovirus receptor (PVR), to inhibit effector cell functions. Circulating CD4+ T cells from PLWH more frequently expressed PVR than HIV‐seronegative controls, and PVR expression was enriched in CD4+ T cells replicating HIV‐1 ex vivo. Treatment with anti‐TIGIT monoclonal antibodies increased NK cell HIV‐1‐specific antibody‐dependent cytotoxicity in vitro and ex vivo.ConclusionBlocking TIGIT may be an effective strategy to invigorate antibody‐dependent NK cell activity against HIV‐1 activated in cellular reservoirs for cure or treatment strategies.
Community modeling reveals the importance of elevation and land cover in shaping migratory bird abundance in the Andes
Authors: Céspedes Arias Laura N. , Wilson Scott , Bayly Nicholas J. 
Published: October 2021

AbstractThe tropical Andes are characterized by extreme topographic and climatic complexity, which has likely contributed to their outstanding current species diversity, composed of many range‐restricted species. However, little is known about how the distribution and abundance of highly mobile organisms, like long‐distance migratory birds, varies across different land covers, elevations, and climatic conditions within the Andes. We conducted 1,606 distance‐sampling point counts across the Colombian Andes, spanning elevations from 253 to 3,708 m, a range of precipitation regimes and representative land covers. We then employed a novel application of a multispecies hierarchical modeling approach to evaluate how elevation, local land cover, aboveground woody biomass, cloud cover, precipitation, and seasonality in precipitation shape the abundance of the migratory land bird community in the Andes. We detected 1,824 individuals of 29 species of migratory land birds, six of which were considered incidental in our study region. We modeled the abundance of the remaining 23 species, while considering observer and time of day effects on detectability. We found that both elevation and land cover had an overriding influence on the abundance of migratory species across the Andes, with strong evidence for a mid‐elevation peak in abundance, and species‐specific responses to both variables. As a community, migratory birds had the highest mean abundance in shade coffee plantations, secondary forest, and mature forest. Aboveground woody biomass did not affect the abundance of all species as a group, but a few showed strong responses to this variable. Contrary to predictions of a positive correlation between abundance and precipitation, we found no evidence for community‐level responses to precipitation, aside for a weak tendency for birds to select areas with intermediate levels of precipitation. This novel use of a multispecies model sheds new light on the mechanisms shaping the winter distribution of migratory birds and highlights the importance of elevation and land cover types over climatic variables in the context of the Colombian Andes.
Diving deeper into the underlying white shark behaviors at Guadalupe Island, Mexico
Authors: Aquino‐Baleytó Marc , Leos‐Barajas Vianey , Adam Timo , Hoyos‐Padilla Mauricio , Santana‐Morales Omar , Galván‐Magaña Felipe , González‐Armas Rogelio , Lowe Christopher G. , Ketchum James T. , Villalobos Héctor 
Published: October 2021

Abstract

Fine‐scale movement patterns are driven by both biotic (hunting, physiological needs) and abiotic (environmental conditions) factors. The energy balance governs all movement‐related strategic decisions.

Marine environments can be better understood by considering the vertical component. From 24 acoustic trackings of 10 white sharks in Guadalupe Island, this study linked, for the first time, horizontal and vertical movement data and inferred six different behavioral states along with movement states, through the use of hidden Markov models, which allowed to draw a comprehensive picture of white shark behavior.

Traveling was the most frequent state of behavior for white sharks, carried out mainly at night and twilight. In contrast, area‐restricted searching was the least used, occurring primarily in daylight hours.

Time of day, distance to shore, total shark length, and, to a lesser extent, tide phase affected behavioral states. Chumming activity reversed, in the short term and in a nonpermanent way, the behavioral pattern to a general diel vertical pattern.
Different responses of soil respiration to environmental factors across forest stages in a Southeast Asian forest
Authors: Rodtassana Chadtip , Unawong Weerapong , Yaemphum Siriphong , Chanthorn Wirong , Chawchai Sakonvan , Nathalang Anuttara , Brockelman Warren Y. , Tor‐ngern Pantana 
Published: October 2021

AbstractSoil respiration (SR) in forests contributes significant carbon dioxide emissions from terrestrial ecosystems and is highly sensitive to environmental changes, including soil temperature, soil moisture, microbial community, surface litter, and vegetation type. Indeed, a small change in SR may have large impacts on the global carbon balance, further influencing feedbacks to climate change. Thus, detailed characterization of SR responses to changes in environmental conditions is needed to accurately estimate carbon dioxide emissions from forest ecosystems. However, data for such analyses are still limited, especially in tropical forests of Southeast Asia where various stages of forest succession exist due to previous land‐use changes. In this study, we measured SR and some environmental factors including soil temperature (ST), soil moisture (SM), and organic matter content (OM) in three successional tropical forests in both wet and dry periods. We also analyzed the relationships between SR and these environmental variables. Results showed that SR was higher in the wet period and in older forests. Although no response of SR to ST was found in younger forest stages, SR of the old‐growth forest significantly responded to ST, plausibly due to the nonuniform forest structure, including gaps, that resulted in a wide range of ST. Across forest stages, SM was the limiting factor for SR in the wet period, whereas SR significantly varied with OM in the dry period. Overall, our results indicated that the responses of SR to environmental factors varied temporally and across forest succession. Nevertheless, these findings are still preliminary and call for detailed investigations on SR and its variations with environmental factors in Southeast Asian tropical forests where patches of successional stages dominate.
Creating community: a peer‐led, adaptable postdoc program to build transferable career skills and overcome isolation
Authors: Fork Megan L. , Anderson Elsa C. , Castellanos Adrian A. , Fischhoff Ilya R. , Matsler A. Marissa , Nieman Chelsey L. , Oleksy Isabella A. , Wong Michelle Y. 
Published: October 2021

AbstractPostdoctoral positions provide critical opportunities for early‐career ecologists to build transferable skills, knowledge, and networks that will prepare them for professional success. However, these positions often come with personal and professional challenges such as stress, isolation, and lack of agency. Here, we describe a peer‐led postdoc program we created to maximize benefits and minimize challenges while preparing ourselves for a wide range of possible future careers using our training and expertise in ecology. We also give recommendations for other postdocs and early‐career scientists in ecology and across science, technology, engineering, and mathematics fields seeking to build a similar program.
Atlantic bluefin tuna spawn early to avoid metabolic meltdown in larvae
Authors: Fiksen Øyvind , Reglero Patricia 
Published: October 2021

AbstractTo predict shifts in phenology and distribution of organisms we need to understand how survival through early life stages depends on environmental conditions. Here, we present a mechanistic model of development, feeding and bioenergetics of early life stages in bluefin tuna and predict the optimal time of the year for them to be born. We find that the availability of prey, particularly nauplii, is sufficient for fast growth in tuna larvae while temperature is moderate during midsummer, but not when temperatures increase later in summer. High temperatures benefit egg and yolk‐sac stages, but the metabolic needs of feeding larvae are hard to sustain during the warmest periods. Heatwaves, such as the one in 2003, increase larval survival potential, but shorten the viable part of the season for the larvae. Atlantic bluefin tuna is a large, highly migratory marine top predator that spawns while temperatures are rising, but before the heat leads to a metabolic meltdown in larvae. This means that food resources modulate how temperature change shifts optimal phenology.
Single‐Site and Cooperative Bond Activation Reactions with Ylide‐Functionalized Tetrylenes: A Computational Study
Authors: Steinert Henning , Löffler Julian , Gessner Viktoria H. 
Published: October 2021

AbstractDue to their transition metal‐like behavior divalent group 14 compounds bear huge potential for their application in bond activation reactions and catalysis. Here we report on detailed computational studies on the use of ylide‐substituted tetrylenes in the activation of dihydrogen and phenol. A series of acyclic and cyclic ylidyltetrylenes featuring various α‐substituents with different σ‐ and π‐donating capabilities have been investigated which demonstrate that particularly π‐accepting boryl groups lead to beneficial properties and low barriers for single‐site activation reactions, above all in the case of silylenes. In contrast, for the thermodynamically more stable germylenes and stannylenes an alternative mechanism involving the active participation of the ylide ligand in the E−H bond (E=H or PhO) activation process by addition across the element carbon linkage was found to be energetically favored. Furthermore, the boryl substituted tetrylenes allowed for a further activation pathway involving the active participation of the boron element bond. These cooperative mechanisms are especially attractive for the heavier cyclic ylidyltetrylenes in which the loss of the protonated ylide group is prevented due to the cyclic framework. Overall, the present studies suggest that cyclic ylide‐substituted germylenes and stannylenes bear huge potential for cooperative bond activations at mild conditions which should be experimentally addressed in the future.