bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension
Authors: Rothman Abraham , Restrepo Humberto , Evans William N. , Sarukhanov Valeri , Mann David 
Published: July 2022

Abstract
Introduction and Objectives. Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. The aim of this study was to assess whether the homing peptide CAR (CARSKNKDC) improved the vasodilatory selectivity of fasudil on the pulmonary circulation vs the systemic circulation in a porcine pulmonary hypertension model. Materials and Methods. Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg) and the effects on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters. Results. Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12 % decrease in RV pressure, whereas the co-administration of CAR with fasudil resulted in a 22 % decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001). Conclusion. The homing peptide CAR selectively enhances the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.
Severity of Omicron (B.1.1.529) and Delta (B.1.1.617.2) SARS-CoV-2 infection among hospitalised adults: a prospective cohort study
Authors: Hyams Catherine , Challen Robert , Marlow Robin , Nguyen Jennifer , Begier Elizabeth , Southern Jo , King Jade , Morley Anna , Kinney Jane , Clout Madeleine , Oliver Jennifer , Ellsbury Gillian , Maskell Nick , Jodar Luis , Gessner Bradford , McLaughlin John , Danon Leon , Finn Adam 
Published: July 2022

Abstract
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults (≥18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection.

Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
WNT4 promotes macrophage polarization via granulosa cell M-CSF and reduces granulosa cell apoptosis in endometriosis
Authors: Yuan Yuan , Zhao Wen , Hu Yue , Li Yubin , Zhou Canquan , Long Tengfei , Long Lingli 
Published: July 2022

Abstract
Background
WNT4 gene polymorphism are common in endometriosis and may functionally link estrogen and estrogen receptor signaling. Previous study confirmed estrogen and estrogen receptor signaling recruit macrophage to promote the pathogenesis of endometriosis. To investigate the effect of WNT4 in endometriosis involved in macrophage polarization and whether WNT4 could reduce the apoptosis of granulosa cells.
Methods
An observational study consisting of 8 cases of women with endometriosis (diagnosed by surgery and histology) and 22 mice of endometriosis animal model was conducted. Granulosa cells were isolated from 16 patients with endometriosis and co-cultured with macrophage under WNT4 treatment using TUNEL assay, quantitative reverse transcription PCR, flow cytometry and ELISA analysis. 22 mice of endometriosis animal model confirmed the WNT4 treatment effects using histology and immunohistochemistry, Western blot and flow cytometry.
Results
We observed that the apoptotic proportion of granulosa cells was significantly decreased and M2 macrophage was significantly increased after WNT4 treatment during the granulosa cell and macrophage co-culture system. To reveal the underlying mechanism for this, we conducted a series of experiments and found that high expression of granulosa cell M-CSF led to the M2 polarization of macrophages. The animal model also suggested that the anti-apoptotic effect of WNT4 on granulosa cells were conducted by the M2 polarized macrophage.
Conclusions
WNT4 promotes macrophage polarization via granulosa cell M-CSF and reduces granulosa cell apoptosis in endometriosis.
Transformation and gene editing in the bioenergy grass Miscanthus
Authors: Trieu Anthony , Belaffif Mohammad B , Hirannaiah Pradeepa , Manjunatha Shilpa , Wood Rebekah , Bathula Yokshitha , Billingsley Rebecca L , Arpan Anjali , Sacks Erik J , Clemente Thomas E , Moose Stephen P , Reichert Nancy A , Swaminathan Kankshita 
Published: July 2022

Abstract
Background: Miscanthus, a C4 member of Poaceae, is a promising perennial crop for bioenergy, renewable bioproducts, and carbon sequestration. Species of interest include nothospecies M. x giganteus and its parental species M. sacchariflorus and M. sinensis. Use of biotechnology-based procedures to genetically improve Miscanthus, to date, have only included plant transformation procedures for introduction of exogenous genes into the host genome at random, non-targeted sites.Results: We developed gene editing procedures for Miscanthus using CRISPR/Cas9 that enabled the mutation of a specific (targeted) endogenous gene to knock out its function. Classified as paleo-allopolyploids (duplicated ancient Sorghum-like DNA plus chromosome fusion event), design of guide RNAs (gRNAs) for Miscanthus needed to target both homeologs and their alleles to account for functional redundancy. Prior research in Zea mays demonstrated that editing the lemon white1 (lw1) gene, involved in chlorophyll and carotenoid biosynthesis, via CRISPR/Cas9 yielded pale green/yellow, striped or white leaf phenotypes making lw1 a promising target for visual confirmation of editing in other species. Using sequence information from both Miscanthus and sorghum, orthologs of maize lw1 were identified; a multi-step screening approach was used to select three gRNAs that could target homeologs of lw1. Embryogenic calli of M. sacchariflorus, M. sinensis and M. x giganteus were transformed via particle bombardment (biolistics) or Agrobacterium tumefaciens introducing the Cas9 gene and three gRNAs to edit lw1. Leaves on edited Miscanthus plants displayed the same phenotypes noted in maize. Sanger sequencing confirmed editing; deletions in lw1 ranged from 1-26 bp in length, and one deletion (433 bp) encompassed two target sites. Confocal microscopy verified lack of autofluorescence (chlorophyll) in edited leaves/sectors.Conclusions: We developed procedures for gene editing via CRISPR/Cas9 in Miscanthus and, to the best of our knowledge, are the first to do so. This included five genotypes representing three Miscanthus species. Designed gRNAs targeted all copies of lw1 (homeologous copies and their alleles); results also confirmed lw1 made a good editing target in species other than Z. mays. The ability to target specific loci to enable endogenous gene editing presents a new avenue for genetic improvement of this important biomass crop.
Effect of Goal-Directed Fluid Therapy on the Postoperative Gastrointestinal Function and Length of Stay after Major Abdominal Oncologic Surgery-A Randomized Controlled Trial
Authors: Sun Yanxia , Liang Xuan , Chai Fang , Shi Dongjing , Wang Yue , Hua Zhen 
Published: July 2022

Abstract
Background and Objective
Postoperative gastrointestinal dysfunction (POGD) is a leading cause of delayed hospital stay after abdominal surgery. Goal-directed fluid therapy (GDFT) may improve gastrointestinal (GI) function, but the evidence for beneficial effects of GDFT for recovery of GI function remains controversial. The aim of this study was to evaluate the effect of GDFT on the postoperative recovery of GI function and length of hospital stay in patients undergoing major abdominal oncologic surgery.
Methods
In this randomized, partly blinded, controlled trial, adult patients scheduled for elective major abdominal oncologic surgery with general anesthesia, were randomly divided into GDFT group where fluid management was guided by stroke volume variation (SVV) and cardiac output index (CI) and the control group where fluid infusion was given based on conventional fluid therapy. Postoperative GI function was evaluated by Intake, Feeling nauseated, Emesis, physical Exam, and Duration of symptoms (I-FEED) score system and I-FEED score ≥ 6 was defined as POGD. Time to the first flatus, time to first tolerate oral diet and the length of hospital stay were recorded.
Results
One hundred patients completed the study protocol. Two of 50 patients (4%) developed POGD in the GDFT group, whereas POGD occurred in 16 of 50 patients (32%) in the control group (P < 0.0001). GDFT significantly shorten time to first flatus by 11 hours [GDFT: 28.2 hours (9.2-48.0hours) versus Control: 39.4 hours (24.9–67.5 hours), P = 0.009] and time to first tolerate oral diet by 2 days [GDFT: 4.0 days (2.7-6.0 days) versus Control: 6.0 days (5.0-9.3days), P < 0.0001]. Moreover, the length of hospital stay was significantly shorter in GDFT group compared with the control group [GDFT: 9.0 days (5.8days) versus Control: 12.0 days (4.6days), P = 0.001].
Conclusions
GDFT guided by SVV and CI could accelerate the postoperative recovery of GI function and shorten length of hospital stay following major abdominal oncologic surgery.
Pancreatic cancer among solid organ transplant recipients in the United States
Authors: Tanaka Tomohiro , Lynch Charles , Yu Kelly , \Morawski Bozena , Hsieh Mei-Chin , Alverson Georgetta , Austin April , Zeng Yun , Engels Eric 
Published: July 2022

Abstract
IntroductionPancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging.MethodsWe evaluated PC among 374,106 SOT recipients during 1995–2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan-Meier curves and log-rank tests.ResultsSOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95%CI 1.29–1.52), and this increase was strongest in liver recipients (1.65, 1.41–1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95%CI 1.34–1.68) and for cases diagnosed at localized stage (1.85, 1.37–2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95%CI 1.06–1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (p = 0.08).ConclusionsPC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening.
The BDSF quorum sensing receptor RpfR regulates Bep exopolysaccharide synthesis in Burkholderia cenocepacia via interaction with the transcriptional regulator BerB
Authors: Eberl Leo , Steiner Elisabeth , Shilling Rebecca , Richter Anja , Schmid Nadine , Fazli Mustafa , Kaever Volkhard , Jenal Urs , Tolker-Nielsen Tim 
Published: July 2022

Abstract
The polysaccharide Bep is essential for in vitro biofilm formation of the opportunistic pathogen Burkholderia cenocepacia. We found that the BDSF quorum sensing receptor RpfR is a negative regulator of the bep gene cluster in B. cenocepacia. An rpfR mutant formed wrinkled colonies, whereas additional mutations in the bep genes or known bep regulators such as berA and berB restored the smooth colony morphology of the wild-type. In accordance with previous work, we found that there is a good correlation between intracellular c-di-GMP levels and bep expression when the c-di-GMP level is increased or decreased through ectopic expression of the diguanylate cyclase YedQ or the c-di-GMP phosphodiesterase PA5295. However, when the intracellular c-di-GMP level is changed by site directed mutagenesis of either the EAL or GGDEF domain of RpfR there is no correlation between intracellular c-di-GMP levels and bep expression. Apart from rpfR each of the 25 c-di-GMP phosphodiesterase and diguanylate cyclase genes encoded by B. cenocepacia can be knocked out without an effect on berA and bep gene expression. Moreover, bacterial two hybrid assays provided evidence that RpfR and BerB physically interact. Our results suggest that the specificity of RpfR-mediated regulation of the bep genes is governed by RpfR-BerB protein interaction. We suggest a model where RpfR binds BerB at low c-di-GMP levels to sequester this RpoN-dependent activator to an RpfR/RpfF complex such that BerB cannot activate expression of the transcriptional activator BerA and thus transcription of the bep genes is not activated. If the c-di-GMP levels rise, possibly by the enzymatic action of RpfR, BerB binds c-di-GMP and is released from the RpfR/RpfF complex and associates with RpoN to activate transcription of berA, and the BerA protein subsequently activates transcription of the bep genes.
Efficient Re-parameterization Operations Search for Easy-to-Deploy Network Based on Directional Evolutionary Strategy
Authors: Xinyi Yu , Xiaowei Wang , Jintao Rong , Mingyang Zhang , Linlin Ou 
Published: July 2022

Abstract
Structural re-parameterization (Rep) methods has achieved signifificant performance improvement on traditional convolutional network. Most current Rep methods rely on prior knowledge to select the re-parameterization operations. However, the performance of architecture is limited by the type of operations and prior knowledge. To break this restriction, in this work, an improved re-parameterization search space is designed, which including more type of re-parameterization operations. Concretely, the performance of convolutional networks can be further improved by the search space. To effectively explore this search space, an automatic re-parameterization enhancement strategy is designed based on neural architecture search (NAS), which can search a excellent re-parameterization architecture. Besides, we visualize the output features of the architecture to analyze the reasons for the formation of the re-parameterization architecture. On public datasets, we achieve better results. Under the same training conditions as ResNet, we improve the accuracy of ResNet-50 by 1.82% on ImageNet-1k.
Headache Education for General Public by Leaflets Distribution During COVID-19 Vaccination and School-Based On-demand E-learning in Japanese One City -Itoigawa Geopark Headache Awareness Campaign-
Authors: Katsuki Masahito , Matsumori Yasuhiko , Kawahara Junko , Yamagishi Chinami , Koh Akihito , Kawamura Shin , Kashiwagi Kenta , Kito Tomohiro , Oguri Masato , Mizuno Shoji , Nakamura Kentaro , Hayakawa Katsushi , Ohta Osamu , Aoyama Jun , Yamazaki Isamu , Mizusawa Satoshi , Ueki Yasuhide , Nanri Maiko , Miyakoshi Yuki , Gobo Shuto , Entani Akio , Yamamoto Toshiko , Otake Miyako , Ikeda Takashi , Matsuo Mitsuhiro , Yamagishi Fuminori 
Published: July 2022

Abstract
Objective
Headache is a common public health problem, but its burden could be avoided by raising headache awareness and the appropriate use of acute medication and prophylactic medication. Few reports on raising headache awareness in the general public have been reported, and there are no reports on headache awareness campaigns in Japan. We prospectively performed Itoigawa Headache Awareness Campaign from August 2021 to June 2022 and evaluated its effectiveness to the general public.
Methods
The main target group was the general public, especially those aged 15–64 y.o. We performed 2 projects; Project 1; Leaflet and paper-based headache awareness during COVID-19 vaccination, and Project 2; On-demand e-learning and online survey through schools. In these projects, we emphasize the 6 important topics for the general public, which were described in the Clinical Practice Guideline for Headache Disorders 2021. The awareness of the 6 topics among the 2 main projects’ cohorts before and after the campaign was evaluated.
Results
We obtained 4016 valid responses in project 1 and 2577 in project 2; thus, 32.23% of the working-age population of Itoigawa city experienced these projects. The ratios of individuals who know the 6 topics significantly increased after the 2 projects from 7–40% to 64–92% (p < 0.001, all).
Conclusions
We conducted this Itoigawa Headache Awareness Campaign through 2 main projects with improved ratios of individuals who know about the headache. The 2 methods of community-based awareness projects could raise headache awareness less costly and effectively.
Utility of Radial Endobronchial Ultrasound with a Guide Sheath for Peripheral Pulmonary Lesions in Patients with Pulmonary Emphysema: A Retrospective Study
Authors: Zhou Lefei , Wang Feng , Wang Zhen , Xu Lili , Tong Zhaohui 
Published: July 2022

Abstract
Background: Radial endobronchial ultrasound with a guide sheath for transbronchial biopsy (EBUS-GS-TBB) can be considered for diagnosing peripheral pulmonary lesions (PPLs) with fewer complications in patients with emphysema. However, the utility and safety of bronchoscopy for PPLs in the proximity of emphysema-area lesions remain unclear. The aim of this study was to assess the efficacy and complications of the initial diagnostic procedure of bronchoscopy with EBUS-GS-TBB according to the proximity of PPLs to emphysema areas, along with factors affecting the successful diagnostic yield for PPLs, and to identify the feasibility of molecular and genetic testing using EBUS-GS-TBB-obtained tumor samples.Methods: The medical records of 278 consecutive patients with PPLs who underwent EBUS-GS-TBB without X-ray fluoroscopy guidance were screened. We compared PPLs with emphysema in such lesions. PPLs with emphysema were divided into two groups: PPLs located in non-emphysema areas and those inside or near emphysema areas.Results: This study included 84 patients with emphysema (non-emphysema area group=46; inside or near emphysema area group=38). The diagnostic yield was significantly higher for PPLs located in non-emphysema areas than for PPLs inside or near emphysema areas (82.6% vs. 52.6%, p=0.013). Multivariate analysis revealed that PPLs located in non-emphysema areas (odds ratio=5.614) and EBUS images within lesions were significant factors affecting diagnostic yield. Further, 91.7%–100% of EBUS-GS-TBB-obtained tissue samples were sufficient for molecular testing of PD-L1, EGFR, ALK, and ROS1.Conclusions: In patients with emphysema, the positional relation of PPLs to emphysema lesions and EBUS images within lesions were important factors affecting successful diagnosis using EBUS-GS-TBB.
Multiple invasion trajectories induce niche dynamics inconsistency and increase risk uncertainty of a plant invader
Authors: Zhang Liyun , Zhu Min , Wan Yu , Liu Xiaofei 
Published: July 2022

Abstract
Our knowledge of how niche dynamic patterns respond to invasion trajectories and influence invasion risk prediction is elusive for the majority of notorious invaders, hindering scientific understanding, biosecurity planning and practice, and management implementation. We used Mikania micrantha, one of the most notorious invasive alien species in the world, to test the hypothesis that multiple invasion trajectories could induce niche dynamics inconsistency and increase risk uncertainty of invasive alien species. We compiled a robust database of M. micrantha occurrence across its native range in Central and South America and invaded ranges in China. This database was used to clarify different invaded ranges and invasion trajectories of M. micrantha in China. Principle Component Analysis of climatic variables associated with the database was used to detect its niche dynamic patterns associated with multiple invasion trajectories. Maximum Entropy algorithm was used to predict the high-risk area of M. micrantha invasion using occurrence datasets for invaded ranges where niches remained conservative, and to identify area changes with the inclusion of occurrences datasets for invaded ranges where niche shifts occurred. M. micrantha invasion occurred in three geographically distinct regions, with conservative climate niches in southern and southeastern China and climatic niche shifts in southwestern China. A high-risk area for M. micrantha invasion spanned multiple provinces and cities, and expanded considerably with the inclusion of the occurrence dataset for southwestern China. Our findings contribute to the theoretical understanding of invasion mechanisms and the practical optimization of biosecurity planning and implementation.
Comparative De Novo Transcriptome Analysis and Random UV mutagenesis: Application in High Biomass and Astaxanthin Production Enhancement for Haematococcus pluvialis
Authors: Telli Murat , Selçuk Ünlü Ercan 
Published: July 2022

Abstract
Astaxanthin is a natural carotenoid with strong antioxidant capacity. The high demand on astaxanthin by cosmetic, food, pharmaceutical and nutraceutical industries promote its value in the biotechnological research. Several organisms have been characterized as direct or indirect source for astaxanthin. Haematococcus pluvialis has been characterized as one of the most promising species for astaxanthin biosynthesis. Even though H. pluvialis as an advantage in producing astaxanthin, its slow grow-yield limits usage of the species for large-scale production. In this study we generated mutated H. pluvialis strain by using one-step random UV mutagenesis approach for higher biomass production in the green flagellated period and in turn higher astaxanthin accumulation in red stage. Isolated mutant strains were tested for the astaxanthin accumulation and yield of biomass. Among tested strains only mutant strain designated as only MT-3-7-2 showed a consistent and higher growth pattern, the rest had shown a fluctuated and then decreased growth rate than wild type. To demonstrate the phenotypical changes in MT-3-7-2 is associated with transcriptome, we carried out comparative analysis of transcriptome profiles between MT-3-7-2 and the wild type strains. De novo assembly was carried out to obtain the transcripts. Differential expression levels for the transcripts were evaluated by functional annotation analysis. Data showed that increased biomass for the MT-3-7-2 strain was different from wild type with expression of transcripts upregulated in carbohydrate metabolism and downregulated in lipid metabolisms. Our data suggests a switching mechanism is enrolled between carbohydrate and lipid metabolism to regulate cell proliferation and stress responses.