bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of processing method and severity for hybrid fall rye on dry matter intake, ruminal fermentation, and apparent total tract nutrient digestibility in ruminally cannulated beef heifers
Authors: Pereira Murillo C.S. , Johnson Jordan A. , Brattain Rebecca S. , Wehrle Herman , Penner Gregory B. 
Published: July 2022

This study compared dry-rolled and tempered hybrid rye when processed to a coarse or fine severity on dry matter intake (DMI), ruminal fermentation, and apparent total tract nutrient digestibility for beef cattle. Eight ruminally cannulated Simmental heifers (327 ± 33.1 kg, mean ± SD) were used in a replicated 4 × 4 Latin square (21-day periods with 16 days for adaptation and 5 d collection) balanced for carry-over effects with a 2 × 2 factorial arrangement of treatments. Feeding tempered rye increased ( P = 0.01) DMI when compared to dry-rolled rye, but there was no effect of processing severity. Cattle fed dry-rolled rye had a greater ( P = 0.04) area that pH was <5.5 when compared to those fed tempered rye. Feeding dry-rolled rye increased dry matter digestibility ( P = 0.02) and crude protein digestibility ( P = 0.01) when compared to tempered rye, and there was a greater effect to increase total tract starch digestibility with increasing severity of processing for tempering than for dry rolling (interaction, P = 0.03). In conclusion, tempered hybrid rye processed to a fine severity may result in similar total tract starch digestibility to dry-rolled hybrid rye without the marked reductions in DMI and ruminal pH.
Coverage-Based Debloating for Java Bytecode
Authors: Soto-Valero César , Durieux Thomas , Harrand Nicolas , Baudry Benoit 
Published: July 2022

Software bloat is code that is packaged in an application but is actually not necessary to run the application. The presence of software bloat is an issue for security, performance, and for maintenance. In this article, we introduce a novel technique for debloating, which we call coverage-based debloating. We implement the technique for one single language: Java bytecode. We leverage a combination of state-of-the-art Java bytecode coverage tools to precisely capture what parts of a project and its dependencies are used when running with a specific workload. Then, we automatically remove the parts that are not covered, in order to generate a debloated version of the project. We succeed to debloat 211 library versions from a dataset of 94 unique open-source Java libraries. The debloated versions are syntactically correct and preserve their original behaviour according to the workload. Our results indicate that 68.3% of the libraries’ bytecode and 20.3% of their total dependencies can be removed through coverage-based debloating.
For the first time in the literature on software debloating, we assess the utility of debloated libraries with respect to client applications that reuse them. We select 988 client projects that either have a direct reference to the debloated library in their source code or which test suite covers at least one class of the libraries that we debloat. Our results show that 81.5% of the clients, with at least one test that uses the library, successfully compile and pass their test suite when the original library is replaced by its debloated version.
A Cross-Sectional Study on the Application of IS in Perioperative Pulmonary Function Training in Spine and Orthopedics
Authors: Qiu Ting , Li Yong , Zhang Jingjing , Hou Xuanzhu , Wu Yuqi , Xu Yan , Chen Wenyue , Rui Jingjing , Yang Jin , Qian Jing 
Published: July 2022

Background. The incentive spirometer (IS) is a mechanical device that promotes lung expansion and can be used to prevent and treat postoperative pulmonary complications. In this study, the preventive effect of pulmonary function training with IS on the improvement of pulmonary function and pulmonary complications was observed. Methods. From May 2019 to April 2021, 69 scoliosis patients with impaired moderate and severe lung function were divided into the traditional pulmonary training group (n = 32) and IS-enhanced pulmonary training group (n = 35). The patient underwent lung function testing after admission and one week after the start of training and chest CT on the third day after surgery. Results. The average age was 13.47 and 15.66, respectively (

p

= 0.223). The Cobb angles were 83.84 and 83.97 (

p

= 0.756), respectively, and no statistical difference between the parameters of lung function was detected. After 1 week of respiratory function training, significant improvement in lung function testing parameters including VC%, FVC%, FEV1%, FEV1/FVC, FEV1/VC, and MVV% was found in both groups. Analysis of covariance showed more significant improvement in IS-enhanced group compared to the conventional training group (

p

< 0.05). The incidence of postoperative pulmonary atelectasis was lower in IS-enhanced group than in traditional groups (2.9% vs. 21.9%,

p

= 0.043) with no difference in the overall incidence of pulmonary complications (

p

= 0.164) and shorter preoperative and total hospitalization in the IS-enhanced group. Conclusion. Compared to traditional pulmonary function training, IS-enhanced training can significantly accelerate the improvement of pulmonary function testing parameters, shorten the preoperative pulmonary function training time, reduce the incidence of postoperative pulmonary tension complications, and accelerate postoperative rehabilitation.
Association of Tumor Mutational Burden with Efficacy of Pembrolizumab±Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study
Authors: Lee Keun-Wook , Van Cutsem Eric , Bang Yung-Jue , Fuchs Charles S. , Kudaba Iveta , Garrido Marcelo , Chung Hyun Cheol , Lee Jeeyun , Castro Hugo R. , Chao Joseph , Wainberg Zev A. , Cao Z. Alexander , Aurora-Garg Deepti , Kobie Julie , Cristescu Razvan , Bhagia Pooja , Shah Sukrut , Tabernero Josep , Shitara Kohei , Wyrwicz Lucjan 
Published: July 2022

Abstract

Purpose:
This prespecified exploratory analysis evaluated the association between tumor mutational burden (TMB) status and outcomes of first-line pembrolizumab±chemotherapy versus chemotherapy in KEYNOTE-062.

Patients and Methods:
In patients with advanced gastric cancer and evaluable TMB data, we evaluated the association between TMB (continuous variable; square root scale) assessed with FoundationOne CDx and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] using logistic (ORR) and Cox proportional hazards (PFS, OS) regression models. Clinical utility of TMB was assessed using the prespecified cutoff of 10 mut/Mb.

Results:
TMB data were available for 306 of 763 patients (40.1%; pembrolizumab, 107; pembrolizumab+chemotherapy, 100; chemotherapy, 99). TMB was significantly associated with clinical outcomes in patients treated with pembrolizumab and pembrolizumab+chemotherapy (ORR, PFS, and OS; all P &lt; 0.05) but not with chemotherapy (all P &gt; 0.05). The overall prevalence of TMB ≥10 mut/Mb was 16% across treatment groups; 44% of patients who had TMB ≥10 mut/Mb had high microsatellite instability (MSI-H) tumors. Improved clinical outcomes (ORR, PFS, and OS) were observed in pembrolizumab-treated patients (pembrolizumab monotherapy and pembrolizumab+chemotherapy) with TMB ≥10 mut/Mb. When the analysis was limited to the non–MSI-H subgroup, both the positive association between clinical outcomes with pembrolizumab or pembrolizumab+chemotherapy and TMB as a continuous variable and the clinical utility of pembrolizumab (with or without chemotherapy) versus chemotherapy by TMB cutoff were attenuated.

Conclusions:
This exploratory analysis of KEYNOTE-062 suggests an association between TMB and clinical efficacy with first-line pembrolizumab-based therapy in patients with advanced gastric/gastroesophageal junction adenocarcinoma. However, after the exclusion of patients with MSI-H tumors, the clinical utility of TMB was attenuated.
A Cathepsin-Targeted Quenched Activity–Based Probe Facilitates Enhanced Detection of Human Tumors during Resection
Authors: Kennedy Gregory T. , Holt David E. , Azari Feredun S. , Bernstein Elizabeth , Nadeem Bilal , Chang Ashley , Sullivan Neil T. , Segil Alix , Desphande Charuhas , Bensen Eric , Santini John T. , Kucharczuk John C. , Delikatny Edward J. , Bogyo Matthew , Egan A.J. Matthew , Bradley Charles W. , Eruslanov Evgeniy , Lickliter Jason D. , Wright Gavin , Singhal Sunil 
Published: July 2022

Abstract

Purpose:
Fluorescence-guided surgery using tumor-targeted contrast agents has been developed to improve the completeness of oncologic resections. Quenched activity–based probes that fluoresce after covalently binding to tumor-specific enzymes have been proposed to improve specificity, but none have been tested in humans. Here, we report the successful clinical translation of a cathepsin activity–based probe (VGT-309) for fluorescence-guided surgery.

Experimental Design:
We optimized the specificity, dosing, and timing of VGT-309 in preclinical models of lung cancer. To evaluate clinical feasibility, we conducted a canine study of VGT-309 during pulmonary tumor resection. We then conducted a randomized, double-blind, dose-escalation study in healthy human volunteers receiving VGT-309 to evaluate safety. Finally, we tested VGT-309 in humans undergoing lung cancer surgery.

Results:
In preclinical models, we found highly specific tumor cell labeling that was blocked by a broad spectrum cathepsin inhibitor. When evaluating VGT-309 for guidance during resection of canine tumors, we found that the probe selectively labeled tumors and demonstrated high tumor-to-background ratio (TBR; range: 2.15–3.71). In the Phase I human study, we found that VGT-309 was safe at all doses studied. In the ongoing Phase II trial, we report two cases in which VGT-309 localized visually occult, non-palpable tumors (TBRs = 2.83 and 7.18) in real time to illustrate its successful clinical translation and potential to improve surgical management.

Conclusions:
This first-in-human study demonstrates the safety and feasibility of VGT-309 to label human pulmonary tumors during resection. These results may be generalizable to other cancers due to cathepsin overexpression in many solid tumors.
In Vivo Syngeneic Tumor Models with Acquired Resistance to Anti–PD-1/PD-L1 Therapies
Authors: Denis Morgane , Grasselly Chloé , Choffour Pierre-Antoine , Wierinckx Anne , Mathé Doriane , Chettab Kamel , Tourette Anne , Talhi Nolan , Bourguignon Aurore , Birzele Fabian , Kress Elsa , Jordheim Lars Petter , Klein Christian , Matera Eva-Laure , Dumontet Charles 
Published: July 2022

Abstract

Antibodies targeting PD-1 and PD-L1 have produced durable responses in a subset of patients with cancer. However, a majority of these patients will ultimately relapse due to acquired resistance. To explore the underlying mechanisms of this secondary resistance, we developed five syngeneic murine tumor variants with acquired resistance to anti–PD-1 and/or PD-L1 antibodies in vivo. Resistant in vivo models were obtained by serial treatment/reimplantation cycles of the MC38 colorectal, MB49 and MBT2 bladder, and RENCA kidney and TyrNras melanoma models. Tumor immune infiltrates were characterized for wild type and resistant tumors using spectral cytometry and their molecular alterations analyzed using RNA sequencing analyses. Alterations in the tumor immune microenvironment were strongly heterogeneous among resistant models, involving select lymphoid and/or myeloid subpopulations. Molecular alterations in resistant models included previously identified pathways as well as novel candidate genes found to be deregulated in several resistant models. Among these, Serpinf1, coding for pigment epithelial-derived factor (PEDF) was further explored in the MC38 and the MBT2 models. Overexpression of Serpinf1 induced resistance to anti–PD-1 antibodies in the MC38 model, whereas knockdown of Serpinf1 sensitized this model as well as the primarily resistant MBT2 model. Serpinf1 overexpression was associated with increased production of free fatty acids and reduced activation of CD8+ cells, while orlistat, a compound that reduces the production of free fatty acids, reversed resistance to anti–PD-1 therapy. Our results suggest that a panel of syngeneic resistant models constitutes a useful tool to model the heterogeneity of resistance mechanisms encountered in the clinic.
Stronger North Atlantic than Tropical Pacific Effects on North Pacific Decadal Prediction
Authors: Lv Zhen , Yang Jun-Chao , Lin Xiaopei , Zhang Yu 
Published: July 2022

Abstract
Sea surface temperature (SST) variability in the North Pacific (NP) has broad impacts on climate, ecology, and fishing, but its decadal prediction remains challenging. Some studies have highlighted the importance of tropical Pacific forcing on NP SST variability, while others suggested a non-negligible role of North Atlantic forcing. The contribution of each region to NP SST decadal prediction needs to be carefully evaluated. Here, we apply linear inverse models (LIMs) to assess decadal prediction skill of observed NP SST (based on predictions averaged over 2–5 and 6–9 years in advance). By using model experiments that restore to observed SST variability, we quantify tropical Pacific and North Atlantic forcing, and find that the latter exhibits stronger contribution than the former to NP SST decadal prediction. Specifically, by removing the North Atlantic forcing (tropical Pacific forcing), the area ratio of the NP region with significant prediction skill reduces from 49% to 29% (43%) for years 2–5 and from 48% to 26% (44%) for years 6–9. Further analyses reveal the possible reason: NP SST decadal prediction is strongly modulated by two leading non-orthogonal patterns of the LIMs with long decay time (although higher-order patterns also play a role for years 2–5); the North Atlantic forcing largely and robustly contributes to the long decay time, while the tropical Pacific forcing plays a secondary role. Our study calls for more efforts on improving the simulation of the Atlantic trans-basin effect for better predicting NP climate.
Development and Evaluation of Ensemble Consensus Precipitation Estimates over High Mountain Asia
Authors: Maina Fadji Z. , Kumar Sujay V. , Dollan Ishrat Jahan , Maggioni Viviana 
Published: July 2022

Abstract
Precipitation estimates are highly uncertain in complex regions such as High Mountain Asia (HMA), where ground measurements are very difficult to obtain and atmospheric dynamics poorly understood. Though gridded products derived from satellite-based observations and/or reanalysis can provide temporally and spatially distributed estimates of precipitation, there are significant inconsistencies in these products. As such, to date, there is little agreement in the community on the best and most accurate gridded precipitation product in HMA, which is likely area dependent because of HMA’s strong heterogeneities and complex orography. Targeting these gaps, this article presents the development of a consensus ensemble precipitation product using three gridded precipitation datasets [the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG), the Climate Hazards Group Infrared Precipitation with Station data (CHIRPS), and the ECMWF reanalysis ERA5] with a localized probability matched mean (LPM) approach. We evaluate the performance of the LPM estimate along with a simple ensemble mean (EM) estimate to overcome the differences and disparities of the three selected constituent products on long-term averages and trends in HMA. Our analysis demonstrates that LPM reduces the high biases embedded in the ensemble members and provides more realistic spatial patterns compared to EM. LPM is also a good alternative for merging data products with different spatiotemporal resolutions. By filtering disparities among the individual ensemble members, LPM overcomes the problem of a certain product performing well only in a particular area and provides a consensus estimate with plausible temporal trends.
Prediction of Meso-γ-Scale Local Heavy Rain by Ground-Based Cloud Radar Assimilation with Water Vapor Nudging
Authors: Kato Ryohei , Shimizu Shingo , Ohigashi Tadayasu , Maesaka Takeshi , Shimose Ken-ichi , Iwanami Koyuru 
Published: July 2022

Abstract
Meso-γ-scale (2–20 km) local heavy rain (LHR) can cause fatalities through the sudden rise of rivers and flooding of roads. To help prevent this loss of life, we developed prediction methods for these types of meteorological hazards. We assimilated ground-based cloud radar (Ka-band radar) data that can capture cloud droplets before raindrops form and attempted to predict LHR with a cloud resolving numerical weather prediction (NWP) model. High-temporal (1-min interval) three-dimensional cloud radar data obtained through special observation were assimilated using a water vapor nudging method in the pre-rain stage of an LHR-causing cumulonimbus. While rainfall was not predicted by the NWP model without assimilation, LHR was predicted approximately 20 min after the conclusion of cloud radar data assimilation cycling. Results suggest that NWP with cloud radar data assimilation in the pre-rain stage has great potential for predicting LHR, and can lead to an early evacuation warning and subsequent evacuation of vulnerable populations.

Significance Statement
The development of prediction methods for local (within several kilometers) heavy rain (LHR) is important because LHR events can cause deaths through the sudden rise of rivers and flooding of roads by rapidly developing (≤30 min) rain clouds. This study aims to develop a method for predicting LHR even before it begins to rain, which has been difficult to date. Using a technique called data assimilation, which integrates observation and simulation, we developed a method for assimilating cloud radar observations that can capture cloud droplets before raindrops form. As a result, we succeeded in predicting LHR before rainfall commenced. By extending and applying this research, early evacuation of vulnerable populations during LHR is possible.
Antidepressant utilization patterns and predictors of treatment continuation in pregnant women: A 16-year population-based cohort
Authors: Hung Chun , Chan Joe Kwun Nam , Wong Corine Sau Man , Fung Vivian Shi Cheng , Lee Krystal Chi Kei , Chang Wing Chung 
Published: July 2022

Objective: Existing data on prenatal antidepressant prescribing patterns are mostly derived from Western countries, with limited research assessing antidepressant continuation and reinitiation during pregnancy. This study aimed to examine antidepressant prescribing practice among Chinese pregnant women in Hong Kong. Methods: This population-based study identified women aged 15–50 years who delivered their first and singleton child, and had redeemed at least one antidepressant prescription within 3 months pre-pregnancy and/or during pregnancy between 2003 and 2018, using data from the health-record database of Hong Kong public healthcare services. Antidepressant utilization patterns before and during pregnancy, and factors associated with antidepressant continuation and reinitiation following medication discontinuation were evaluated. Results: Of 466,358 pregnancies, 3019 (0.67%) received antidepressants within 3 months of pre-pregnancy and/or during pregnancy, and 2700 (0.58%) had prenatal antidepressant use. There was a significant rising trend of prenatal antidepressant use over time (0.6% in 2003 to 1.3% in 2018; odds ratio: 1.09, 95% confidence interval = [1.08, 1.10], p < 0.001). A consistent pattern of decreasing overall antidepressant use from 3 months pre-pregnancy to the second trimester was observed, followed by a slight increase in the third trimester. Almost half ( n = 949, 49.5%) of 1918 women on antidepressants in 3 months pre-pregnancy continued treatment beyond the first trimester. A total of 8.2% that discontinued antidepressants in 3 months pre-pregnancy or in the first trimester reinitiated treatment in the later stage of pregnancy. Older age at conception (⩾35 years), recent calendar year of delivery (2015–2018), pre-existing depression/anxiety disorders, longer-term pre-pregnancy antidepressant treatment and pre-pregnancy prescription of other psychotropics were significantly associated with antidepressant continuation. Antidepressant reinitiation was predicted by pre-existing depression/anxiety disorders. Conclusions: Our results that prenatal antidepressant use is increasingly prevalent and half of pregnant women discontinued antidepressants 3 months before or after conception underscore the need for future research to clarify the risk and benefit of antidepressant continuation versus discontinuation to facilitate development of evidence-based guidelines, so as to optimize maternal and fetal outcomes.
The Role of Self-Study in Addressing Competency Decline Among Airline Pilots During the COVID-19 Pandemic
Authors: Mizzi Andrew , Lohmann Gui , Carim Junior Guido 
Published: July 2022

Objective This study aimed to investigate the self-study methods used by pilots while grounded and their perception of competence decline and confidence upon their return to flying. Background Previously, long absences from flying were managed on a case-by-case basis. Thousands of pilots returning to flying as the pandemic eases have burdened airline training systems. Limited research has been conducted on the decline in skills of airline pilots while operationally absent from the cockpit. Few studies have considered this topic in the context of a pandemic. Method A questionnaire study was conducted with 234 airline pilots who were grounded during the COVID-19 pandemic. Results Uncertainty regarding sudden and indefinite periods of grounding made it challenging to maintain motivation to self-study. This matter was aggravated by the additional financial and personal stress caused by the state of the airline industry and the outcomes of the pandemic. The participants anticipated a decline in manual flying skills as the worst outcome after being absent from the flight deck. However, these pilots proved quick to recover these skills when they resumed flying. It took significantly more time for pilots to regain proficiency in applying knowledge, procedures and compliance with regulations, situation awareness and workload management. Conclusion The study proposes recommendations for pilots and airlines to harness essential self-study practices in competency areas identified to have significantly declined. Application The outcome of this paper guides airlines, pilots and regulators in better understanding how grounded pilots observe skill decline in a broader range of competencies.
Experimental study of composite materials based on ecological wastes
Authors: Er-rradi Hafida , Idchabani Rachida , Oubrek Mohamed , Bojji Chakib , Boukhattem Lahcen , Doublali Asmaa , Jilbab Abdelilah 
Published: July 2022

Thermal insulation is a good strategy for saving energy and reducing the emission of CO2 especially when produced locally with ecological materials. The hereby document aims at evaluating the thermal and mechanical properties of eco-composite materials based on plaster and wood waste or granular cork. The proportion of used additives were respectively 20 and 30%. Two wood waste types were used as sawdust and wood chips; several granular sizes were used for granular cork. The thermal characterization consists of determining the thermal conductivity, and thermal effusivity of all samples. Flexural and compressive strength were also tested. Results show that the composite materials with 20% wood shaving, 20% granular cork size 3.35–6.7 mm, and 30% sawdust have improved thermal performance with acceptable mechanical resistances. The thermal simulation proves that using these composite materials as plasterboards in buildings can generate thermal energy gain about 38%, compared to reference building. These results indicate that the use of ecological composites based on plaster has a promising future in thermal building insulation.