bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acupuncture and related techniques for obesity and cardiovascular risk factors: a systematic review and meta-regression analysis
Authors: Chen Jianrong , Chen Dongping , Ren Qing , Zhu Weifeng , Xu Sheng , Lu Ling , Chen Xiaofan , Yan Dongmei , Nie Heyun , Zhou Xu 
Published: July 2021

Objective: To assess how acupuncture and related techniques affect weight-related indicators and cardiovascular risk factors compared with non-acupuncture interventions in overweight and obese patients. Methods: We searched PubMed, Embase and CENTRAL up to 19 April 2018 and included relevant randomised controlled trials (RCTs). Weighted mean differences (WMDs) and 95% confidence intervals (CI) were pooled using the inverse variance method with random-effects model. Prespecified hypotheses were tested in meta-regression to investigate the source of heterogeneity. Statistical software packages used were RevMan 5.3.5 and Stata 14.0. Results: Thirty-three RCTs were included (n=2503 patients). Compared with non-acupuncture interventions, acupuncture produced a greater reduction in body weight (WMD −1.76 kg, 95% CI −2.22 to −1.30, I2=77%; moderate quality), body mass index (WMD −1.13 kg/m2, 95% CI −1.38 to −0.88, I2=85%; low quality) and waist circumference (WMD −2.42 cm, 95% CI −3.22 to −1.62, I2=75%; moderate quality). Acupuncture plus lifestyle intervention resulted in a greater reduction in body weight than acupuncture alone (MD −1.94 kg, 95% CI −3.17 to −0.70). Acupuncture also led to a greater reduction in total cholesterol (WMD −12.87 mg/dL, 95% CI −22.17 to −3.57, I2=87%; very low quality) and low-density lipoprotein cholesterol (WMD −13.52 mg/dL, 95% CI −21.47 to −5.58, I2=74%; low quality). The differences were not statistically significant for blood glucose or blood pressure. Conclusion: In the short term, acupuncture and related techniques may produce a small but statistically significant degree of weight loss based on moderate- to low-quality evidence, and improve serum lipid parameters based on low- to very-low-quality evidence. Their effects on blood glucose and blood pressure remain uncertain.
Reflexive thematic analysis exploring stakeholder experiences of virtual pulmonary rehabilitation (VIPAR)
Authors: Knox Liam , Gemine Rachel , Dunning Michelle , Lewis Keir 
Published: July 2021

IntroductionTo enable greater availability of pulmonary rehabilitation (PR), video-conferencing technology was employed to link a community site to a standard outpatient PR service to deliver the programme closer to those with chronic respiratory disease. The service was called virtual pulmonary rehabilitation (VIPAR). To understand the experiences of those involved in this service, this study aimed to answer the question: How do the different stakeholders that interact with VIPAR experience the programme?MethodsFocus groups were conducted with people with chronic lung disease attending either the community or outpatient PR site, in addition to the staff involved in the running of the PR groups. A total of five focus groups were conducted. Reflexive thematic analysis was used to analyse the transcripts.ResultsParticipants who received VIPAR were positive regarding the programme and described the benefits of the service. Additionally, participants discussed the trade-off between convenience and relatedness. Staff described barriers to the service and solutions that could be employed to mitigate these, including greater training, organisation and understanding of risk.DiscussionUsing technology to increase the availability of PR is acceptable to the stakeholders involved, providing problems and organisational issues are resolved with training.
Rat model of smoke inhalation-induced acute lung injury
Authors: Leiphrakpam Premila Devi , Weber Hannah R , Ogun Tobi , Buesing Keely L 
Published: July 2021

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.
First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study
Authors: D'Angelo Sandra P , Lebbé Celeste , Mortier Laurent , Brohl Andrew S , Fazio Nicola , Grob Jean-Jacques , Prinzi Natalie , Hanna Glenn J , Hassel Jessica C , Kiecker Felix , Georges Sara , Ellers-Lenz Barbara , Shah Parantu , Güzel Gülseren , Nghiem Paul 
Published: July 2021

BackgroundAvelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.MethodsPatients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was durable response, defined as objective response (complete or partial response; assessed by independent review) lasting ≥6 months. Additional assessments included progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses.ResultsIn 116 patients treated with avelumab, median follow-up was 21.2 months (range: 14.9–36.6). Thirty-five patients had a response lasting ≥6 months, giving a durable response rate of 30.2% (95% CI: 22.0% to 39.4%). The objective response rate was 39.7% (95% CI: 30.7% to 49.2%). Median PFS was 4.1 months (95% CI: 1.4 to 6.1) and median OS was 20.3 months (95% CI: 12.4 to not estimable). Response rates were numerically higher in patients with PD-L1+ tumors, Merkel cell polyomavirus (MCPyV)-negative tumors, and tumors with increased intratumoral CD8+T-cell density. Exploratory analyses did not identify a biomarker that could reliably predict a response to first-line treatment with avelumab; however, a novel gene expression signature to identify the presence of MCPyV+ tumors was derived. Treatment-related adverse events (any grade) occurred in 94 (81.0%) patients, including grade 3/4 events in 21 (18.1%) patients; no treatment-related deaths occurred.ConclusionIn patients with mMCC, first-line treatment with avelumab led to responses in 40% and durable responses in 30%, and was associated with a low rate of grade 3/4 treatment-related adverse events.
Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: a systematic review, meta-analysis and meta-regression
Authors: Pierro Maria , Villamor-Martinez Eduardo , van Westering-Kroon Elke , Alvarez-Fuente Maria , Abman Steven H , Villamor Eduardo 
Published: July 2021

BackgroundAntenatal pathological conditions are key in the pathogenesis of bronchopulmonary dysplasia (BPD). Pathophysiological pathways or endotypes leading to prematurity and perinatal lung injury can be clustered into two groups: infection and dysfunctional placentation, which include hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). We conducted a systematic review of observational studies exploring the association between the dysfunctional placentation endotype and BPD.MethodsMEDLINE, Embase and Web of Science databases were searched up to February 2020 for studies reporting data on the diagnosis of HDP, IUGR or small for gestational age (SGA) and BPD risk. BPD was classified as BPD28 (supplemental oxygen on day 28), BPD36 (oxygen at 36 weeks postmenstrual age), severe BPD (≥ 30% oxygen or mechanical ventilation), BPD36/death and BPD-associated pulmonary hypertension.ResultsOf 6319 studies screened, 211 (347 963 infants) were included. Meta-analysis showed an association between SGA/IUGR and BPD36 (OR 1.56, 95% CI 1.37 to 1.79), severe BPD (OR 1.82, 95% CI 1.36 to 2.29) and BPD/death (OR 1.91, 95% CI 1.55 to 2.37). Exposure to HDP was not associated with BPD but was associated with decreased odds of BPD/death (OR 0.77, 95% CI 0.64 to 0.94). Both HDP (OR 1.41, 95% CI 1.10 to 1.80) and SGA/IUGR (OR 2.37, 95% CI 1.86 to 3.02) were associated with BPD-associated pulmonary hypertension.ConclusionWhen placental vascular dysfunction is accompanied by fetal growth restriction or being born SGA, it is associated with an increased risk of developing BPD and pulmonary hypertension. The placental dysfunction endotype of prematurity is strongly associated with the vascular phenotype of BPD.Prospero registration numberReview protocol was registered in PROSPERO database (ID=CRD42018086877).
Spring diet of American black bears (Ursus americanus) in a moose (Alces alces) – woodland caribou (Rangifer tarandus caribou) system in northern Ontario, Canada
Authors: McLaren A.A.D. , Jamieson S.E. , Bond M. , Rodgers A.R. , Patterson B.R. 
Published: July 2021

American black bears (Ursus americanus Pallas, 1780) are opportunistic foragers, and across most of their range in North America, their diet is predominantly vegetation with limited consumption of vertebrates and invertebrates. However, they are also predators of ungulates, especially neonates, with regional variation in the amount of predation pressure they exert. We used scat analysis to examine the diet of black bears during the calving season in a moose (Alces alces (Linnaeus, 1758)) – woodland caribou (Rangifer tarandus caribou (Gmelin, 1788)) system in the Boreal forest of northern Ontario, Canada. Bears consumed herbaceous plants (46.5%), fruits and (or) seeds (20.0%), moose (3.3% adults; 4.3% calves), American beaver (Castor canadensis Kuhl, 1820; 8.5%), and insects (mostly ants; 4.2%). Bears had the highest consumption of moose and beaver in early spring, before switching to a more vegetation-dominated diet. We did not detect evidence of caribou consumption. Based on our results, black bear consumption of moose, particularly neonates, may warrant further investigation.
A Fourier-cumulant analysis for multiharmonic flow fluctuation
Authors: Taghavi Seyed Farid 
Published: July 2021

AbstractThe Fourier analysis of the final particle distribution followed by cumulant study of the Fourier coefficient event-by-event fluctuation is one of the main approaches for testing the collective evolution in the heavy-ion collision. Using a multidimensional generating function, we propose a method to extract any possible cumulant of multiharmonic flow fluctuations and classify them in terms of the order of cumulants and harmonics involved in them. In particular, we show that there are 33 distinct cumulants with order 2, 3, 4, 5 and harmonics 2, 3, 4, 5. We compute the normalized version of these cumulants from hydrodynamic simulation for Pb–Pb collisions based on$$_\mathtt{R}$$R++. We compare the simulation with those normalized cumulants that the LHC has measured and predict the unmeasured ones. Comparing the initial and final state fluctuation normalized cumulants, we compute the linear and nonlinear hydrodynamic response couplings. We finally introduce the genuine three-particle correlation function containing information of all third-order cumulants.
Virial theorem in scalar tensor fourth order gravity
Authors: Capolupo A. , Lambiase G. , Stabile A. , Stabile An. 
Published: July 2021

AbstractIn this paper, we study, in the Newtonian limit, the virial theorem in the context of a scalar tensor fourth order gravity. In particular, we show, that for a isolated galaxy in viral equilibrium, a specific class of scalar tensor fourth order gravity, i.e. $$f(R,\phi )+\omega (\phi )\,\phi _{;\alpha }\,\phi ^{;\alpha }$$

f

(
R
,
ϕ
)

+
ω

(
ϕ
)

ϕ

;
α

ϕ

;
α

in not suitable to explain the large fraction of dark matter necessary to have the flatness of the galaxies rotation curves experimentally observed.
The cryogenic control system of SHINE
Authors: Jiang Geyang , Ni Qing , Wang Shuhua , Sun Jiuce , Ouyang Zhengrong , Zhang Lei , Tong Zilei , Wang Yi 
Published: July 2021

AbstractThe Shanghai High repetition rate XFEL and Extreme Light Facility (SHINE), an advanced XFEL project, is now being built at Shanghai Advanced Research Institute (SARI), Chinese Academy of Sciences. It includes a hard X-ray free electron laser and a 100 pW intense laser facilities with overall length of 3.1 km. The XFEL part including an 8 GeV LINAC and 3 undulator lines is cooled with forced superfluid and supercritical helium at 2 K/4 K. The cryogenic system of SHINE consists of test facility cryogenic system (TFCS), accelerator cryogenic system (ACCS), and undulator cryogenic system (UNCS). A dedicated control system based on Experimental Physics and Industrial Control System (EPICS) will be built to automate the cryogenic system with process control, PID control loops, real-time data acquisition and storage, alarm handler and human machine interface. It is capable of automatic recovery as well. This paper describes details of control system structure, interfaces, controllers and the integration under EPICS framework.
Speeding Up Data Manipulation Tasks with Alternative Implementations
Authors: Tao Yida , Tang Shan , Liu Yepang , Xu Zhiwu , Qin Shengchao 
Published: July 2021

As data volume and complexity grow at an unprecedented rate, the performance of data manipulation programs is becoming a major concern for developers. In this article, we study how alternative API choices could improve data manipulation performance while preserving task-specific input/output equivalence. We propose a lightweight approach that leverages the comparative structures in Q&A sites to extracting alternative implementations. On a large dataset of Stack Overflow posts, our approach extracts 5,080 pairs of alternative implementations that invoke different data manipulation APIs to solve the same tasks, with an accuracy of 86%. Experiments show that for 15% of the extracted pairs, the faster implementation achieved >10x speedup over its slower alternative. We also characterize 68 recurring alternative API pairs from the extraction results to understand the type of APIs that can be used alternatively. To put these findings into practice, we implement a tool,
AlterApi7
, to automatically optimize real-world data manipulation programs. In the 1,267 optimization attempts on the Kaggle dataset, 76% achieved desirable performance improvements with up to orders-of-magnitude speedup. Finally, we discuss notable challenges of using alternative APIs for optimizing data manipulation programs. We hope that our study offers a new perspective on API recommendation and automatic performance optimization.
Armed Cats
Authors: Alglave Jade , Deacon Will , Grisenthwaite Richard , Hacquard Antoine , Maranget Luc 
Published: July 2021

We report on the process for formal concurrency modelling at Arm. An initial formal consistency model of the Arm achitecture, written in the cat language, was published and upstreamed to the herd+diy tool suite in 2017. Since then, we have extended the original model with extra features, for example, mixed-size accesses, and produced two provably equivalent alternative formulations.
In this article, we present a comprehensive review of work done at Arm on the consistency model. Along the way, we also show that our principle for handling mixed-size accesses applies to x86: We confirm this via vast experimental campaigns. We also show that our alternative formulations are applicable to any model phrased in a style similar to the one chosen by Arm.
Modeling High-Grade Serous Ovarian Carcinoma Using a Combination ofIn VivoFallopian Tube Electroporation and CRISPR-Cas9–Mediated Genome Editing
Authors: Teng Katie , Ford Matthew J. , Harwalkar Keerthana , Li YuQi , Pacis Alain S. , Farnell David , Yamanaka Nobuko , Wang Yu-Chang , Badescu Dunarel , Ton Nu Tuyet Nhung , Ragoussis Jiannis , Huntsman David G. , Arseneau Jocelyne , Yamanaka Yojiro 
Published: July 2021

AbstractOvarian cancer is the most lethal gynecologic cancer to date. High-grade serous ovarian carcinoma (HGSOC) accounts for most ovarian cancer cases, and it is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination of in vivo electroporation and CRISPR-Cas9–mediated genome editing. Mutation of tumor suppressor genes associated with HGSOC in two different combinations (Brca1, Tp53, Pten with and without Lkb1) resulted in successfully generation of HGSOC, albeit with different latencies and pathophysiology. Implementing Cre lineage tracing in this system enabled visualization of peritoneal micrometastases in an immune-competent environment. In addition, these models displayed copy number alterations and phenotypes similar to human HGSOC. Because this strategy is flexible in selecting mutation combinations and targeting areas, it could prove highly useful for generating mouse models to advance the understanding and treatment of ovarian cancer.Significance:This study unveils a new strategy to generate genetic mouse models of ovarian cancer with high flexibility in selecting mutation combinations and targeting areas.
Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer
Authors: El-Kenawi Asmaa , Dominguez-Viqueira William , Liu Min , Awasthi Shivanshu , Abraham-Miranda Julieta , Keske Aysenur , Steiner KayLee K. , Noel Leenil , Serna Amparo N. , Dhillon Jasreman , Gillies Robert J. , Yu Xiaoqing , Koomen John M. , Yamoah Kosj , Gatenby Robert A. , Ruffell Brian 
Published: July 2021

Abstract

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted AR nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of liver X receptor (LXR)-β, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC.

Significance:
These results suggest that macrophage-targeted therapies can be combined with androgen deprivation therapy to treat patients with prostate cancer by limiting cholesterol bioavailability and the production of intratumoral androgens.
See related commentary by Al-Janabi and Lewis, p. 5399
M6A Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma
Authors: Qiu Xinyao , Yang Shuai , Wang Shan , Wu Jianmin , Zheng Bo , Wang Kaiting , Shen Siyun , Jeong Seogsong , Li Zhixuan , Zhu Yanjing , Wu Tong , Wu Xuan , Wu Rui , Liu Weiwei , Wang Hong-Yang , Chen Lei 
Published: July 2021

Abstract

N6-methyladenosine (m6A) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important m6A demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC). Regulation of PD-L1 expression by ALKBH5 was confirmed in human ICC cell lines. Sequencing of the m6A methylome identified PD-L1 mRNA as a direct target of m6A modification whose levels were regulated by ALKBH5. Furthermore, ALKBH5 and PD-L1 mRNA were shown to interact. ALKBH5 deficiency enriched m6A modification in the 3′UTR region of PD-L1 mRNA, thereby promoting its degradation in a YTHDF2-dependent manner. In vitro and in vivo, tumor-intrinsic ALKBH5 inhibited the expansion and cytotoxicity of T cells by sustaining tumor cell PD-L1 expression. The ALKBH5-PD-L1–regulating axis was further confirmed in human ICC specimens. Single-cell mass cytometry analysis unveiled a complex role of ALKBH5 in the tumor immune microenvironment by promoting the expression of PD-L1 on monocytes/macrophages and decreasing the infiltration of myeloid-derived suppressor-like cells. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with strong nuclear expression patterns of ALKBH5 are more sensitive to anti-PD1 immunotherapy. Collectively, these results describe a new regulatory mechanism of PD-L1 by mRNA epigenetic modification by ALKBH5 and the potential role of ALKBH5 in immunotherapy response, which might provide insights for cancer immunotherapies.

Significance:
This study identifies PD-L1 mRNA as a target of ALKBH5 and reveals a role for ALKBH5 in regulating the tumor immune microenvironment and immunotherapy efficacy.