bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in physical activity outcomes in the Strong Hearts, Healthy Communities (SHHC-2.0) community-based randomized trial
Authors: Maddock Jay E. , Demment Margaret , Graham Meredith , Folta Sara , Strogatz David , Nelson Miriam , Ha Seong-Yeon , Eldridge Galen D. , Seguin-Fowler Rebecca A. 
Published: December 2022

Abstract
Background
Physical inactivity is a risk factor for numerous adverse health conditions and outcomes, including all-cause mortality. Aging rural women are at particular risk for physical inactivity based on environmental, sociocultural, and psychosocial factors. This study reports on changes in physical activity and associated factors from a multicomponent community-engaged intervention trial.

Methods
Strong Hearts, Healthy Communities 2.0 (SHHC-2.0) was a 24-week cluster (community) randomized controlled trial building on the results from the previous trial of SHHC-1.0. Rural women (n = 182) aged 40 and over living in 11 rural communities in upstate New York were recruited. The intervention consisted of twice-weekly experiential classes focused on exercise, nutrition, and civic engagement. Physical activity outcomes included accelerometry and self-report as well as related psychosocial measures at midpoint (12 weeks) and post-intervention (24 weeks). Data were analyzed using multilevel linear regression models with the community as the random effect.

Results
Compared to participants from the control communities, participants in the intervention communities showed a significant increase in objectively measured moderate to vigorous intensity physical activity: at 12 weeks (increase of 8.1 min per day, P < 0.001) and at 24 weeks (increase of 6.4 min per day; P = 0.011). Self-reported total MET minutes per week also increased: at 12 weeks (increase of 725.8, P = 0.003) and 24 weeks (increase of 955.9, P = 0.002). Several of the psychosocial variables also showed significant positive changes.

Conclusions
The SHHC-2.0 intervention successfully increased physical activity level and related outcome measures. Modifications made based upon in-depth process evaluation from SHHC-1.0 appear to have been effective in increasing physical activity in this at-risk population.

Trial registration
Clinicaltrials.gov: NCT03059472. Registered 23 February 2017.
Escalation of radiotherapy dose in large locally advanced drug-resistant gastrointestinal stromal tumors by multi-shell simultaneous integrated boost intensity-modulated technique: a feasibility study
Authors: Cui Haixia , Li Ying , Huang Wei , Lu Wenli , Yi Xin 
Published: December 2022

Abstract
Background
Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST.

Methods
7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P < 0.05).

Results
Compared with the Con-IMRT group, the EUD of GTV (EUDGTV) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB10-IMRT group and the SIB25-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU.

Conclusions
The proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.
Prevalence of cesarean sections in Swiss Bernese Mountain Dogs (2001–2020) and identification of risk factors
Authors: Schrank Magdalena , Sozzi Marco , Mollo Antonio 
Published: December 2022

Abstract
Background
Dystocia is an important limiting factor in animal breeding due to its cost, stress for the mother and risk of death for the neonates. Assessment of incidence and characteristics of dystocia and the inherent risk of Cesarean section are of major importance. The aim of the present study was to evaluate the reproductive performance of Bernese Mountain Dogs in Switzerland, with a particular focus on the prevalence of Cesarean sections due to dystocia, and identification of possible risk factors.

Results
The investigated population included 401 bitches, 207 sires, and 1127 litters. Litter size was significantly influenced by age and parity of the dam. Incidence of Cesarean section was 30.4%, with 2.0% of procedures being elective. History of previous Cesarean section, age of the dam, and a small litter size significantly influenced the risk for Cesarean section. The stillbirth rate was 12.0%, and the number of stillborn pups was significantly higher for litters delivered by Cesarean sections after birth of the first pup. The inbreeding coefficient had a low to non-significant impact on all reproductive parameters (e.g., litter size, number of stillborn pups).

Conclusion
The sample of Bernese Mountain Dogs of our study had an increased prevalence of Cesarean sections compared to the literature, and advanced age of the dam, litter size and prior Cesarean sections in the dam’s reproductive history was identified as significantly influencing factors. In order to improve pups’ survival rate, elective Cesarean section may be indicated in bitches that have had a previous Cesarean-section/s, are of advanced age, and/or have a small litter.
Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer
Authors: Yadav Neelima , Sunder Roma , Desai Sanket , Dharavath Bhasker , Chandrani Pratik , Godbole Mukul , Dutt Amit 
Published: December 2022

Abstract
Background
A preoperative-progesterone intervention increases disease-free survival in patients with breast cancer, with an unknown underlying mechanism. We elucidated the role of non-coding RNAs in response to progesterone in human breast cancer.

Methods
Whole transcriptome sequencing dataset of 30 breast primary tumors (10 tumors exposed to hydroxyprogesterone and 20 tumors as control) were re-analyzed to identify differentially expressed non-coding RNAs followed by real-time PCR analyses to validate the expression of candidates. Functional analyses were performed by genetic knockdown, biochemical, and cell-based assays.

Results
We identified a significant downregulation in the expression of a long non-coding RNA, Down syndrome cell adhesion molecule antisense DSCAM-AS1, in response to progesterone treatment in breast cancer. The progesterone-induced expression of DSCAM-AS1 could be effectively blocked by the knockdown of progesterone receptor (PR) or treatment of cells with mifepristone (PR-antagonist). We further show that knockdown of DSCAM-AS1 mimics the effect of progesterone in impeding cell migration and invasion in PR-positive breast cancer cells, while its overexpression shows an opposite effect. Additionally, DSCAM-AS1 sponges the activity of miR-130a that regulates the expression of ESR1 by binding to its 3’-UTR to mediate the effect of progesterone in breast cancer cells. Consistent with our findings, TCGA analysis suggests that high levels of miR-130a correlate with a tendency toward better overall survival in patients with breast cancer.

Conclusion
This study presents a mechanism involving the DSCAM-AS1/miR-130a/ESR1 genomic axis through which progesterone impedes breast cancer cell invasion and migration. The findings highlight the utility of progesterone treatment in impeding metastasis and improving survival outcomes in patients with breast cancer.
Pneumococcal vaccine schedules (PVS) study: a cluster-randomised, non-inferiority trial of an alternative versus standard schedule for pneumococcal conjugate vaccination—statistical analysis plan
Authors: Mackenzie Grant A. , Palmu Arto A. , Jokinen Jukka , Osei Isaac , Flasche Stefan , Greenwood Brian , Mulholland Kim , Nguyen Cattram 
Published: December 2022

Abstract
Rationale
The effectiveness of universal immunisation with pneumococcal conjugate vaccine (PCV) has been evident in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in several countries. Reducing the cost of PCV programmes may facilitate vaccine introduction in some countries and improve the sustainability of PCV in EPIs in low-income countries when they transition away from subsidised vaccine supply.

Methods and design
PVS is a real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard ‘3+0’ schedule). Delivery of the interventions began in late 2019 in 68 geographic clusters and will continue for 4 years. The primary endpoint is the prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2–260 weeks with clinical pneumonia in year 4. Secondary endpoints are the prevalence of vaccine-type pneumococcal carriage among all ages in year 4 and the incidence of radiological pneumonia in children enrolled to receive the interventions. Additional disease and carriage endpoints are included.

Purpose
This statistical analysis plan (SAP) describes the cohorts and populations, and follow-up criteria, to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe how analyses will account for the effect of clustering and stratified randomisation. The SAP defines the approach to non-inferiority and other analyses. Defining the SAP early in the trial will avoid bias in analyses that may arise from prior knowledge of trial findings.
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: December 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 to 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.

Graphical Abstract
Structure and function of aldopentose catabolism enzymes involved in oxidative non-phosphorylative pathways
Authors: Ren Yaxin , Eronen Veikko , Blomster Andberg Martina , Koivula Anu , Hakulinen Nina 
Published: December 2022

AbstractPlatform chemicals and polymer precursors can be produced via enzymatic pathways starting from lignocellulosic waste materials. The hemicellulose fraction of lignocellulose contains aldopentose sugars, such as d-xylose and l-arabinose, which can be enzymatically converted into various biobased products by microbial non-phosphorylated oxidative pathways. The Weimberg and Dahms pathways convert pentose sugars into α-ketoglutarate, or pyruvate and glycolaldehyde, respectively, which then serve as precursors for further conversion into a wide range of industrial products. In this review, we summarize the known three-dimensional structures of the enzymes involved in oxidative non-phosphorylative pathways of pentose catabolism. Key structural features and reaction mechanisms of a diverse set of enzymes responsible for the catalytic steps in the reactions are analysed and discussed.
The national atlas of tsetse flies and African animal trypanosomosis in Ethiopia
Authors: Gebre Tsegaye , Kapitano Berisha , Beyene Dagnachew , Alemu Dereje , Beshir Ahimedin , Worku Zelalem , Kifle Teshome , Selamu Ayana , Debas Endalew , Kalsa Aschenaki , Asfaw Netsanet , Zhao Weining , Paone Massimo , Cecchi Giuliano 
Published: December 2022

Abstract
Background
With the largest cattle population in Africa and vast swathes of fertile lands infested by tsetse flies, trypanosomosis is a major challenge for Ethiopian farmers. Managing the problem strategically and rationally requires comprehensive and detailed information on disease and vector distribution at the national level. To this end, the National Institute for Control and Eradication of Tsetse and Trypanosomosis (NICETT) developed a national atlas of tsetse and African animal trypanosomosis (AAT) for Ethiopia.

Methods
This first edition of the atlas focused on the tsetse-infested areas in western Ethiopia. Data were collected between 2010 and 2019 in the framework of national surveillance and control activities. Over 88,000 animals, mostly cattle, were tested with the buffy-coat technique (BCT). Odour-enhanced traps were deployed in approximately 14,500 locations for the entomological surveys. Animal- and trap-level data were geo-referenced, harmonized and centralized in a single database.

Results
AAT occurrence was confirmed in 86% of the districts surveyed (107/124). An overall prevalence of 4.8% was detected by BCT in cattle. The mean packed cell volume (PCV) of positive animals was 22.4, compared to 26.1 of the negative. Trypanosoma congolense was responsible for 61.9% of infections, T. vivax for 35.9% and T. brucei for 1.7%. Four tsetse species were found to have a wide geographic distribution. The highest apparent density (AD) was reported for Glossina pallidipes in the Southern Nations, Nationalities and People's Region (SNNPR) (3.57 flies/trap/day). Glossina tachinoides was the most abundant in Amhara (AD 2.39), Benishangul-Gumuz (2.38), Gambela (1.16) and Oromia (0.94) regions. Glossina fuscipes fuscipes and G. morsitans submorsitans were detected at lower densities (0.19 and 0.42 respectively). Only one specimen of G. longipennis was captured.

Conclusions
The atlas establishes a reference for the distribution of tsetse and AAT in Ethiopia. It also provides crucial evidence to plan surveillance and monitor control activities at the national level. Future work on the atlas will focus on the inclusion of data collected by other stakeholders, the broadening of the coverage to tsetse-free areas and continuous updates. The extension of the atlas to data on control activities is also envisaged.

Graphical Abstract
Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer
Authors: Oliero Manon , Hajjar Roy , Cuisiniere Thibault , Fragoso Gabriela , Calvé Annie , Dagbert François , Loungnarath Rasmy , Sebajang Herawaty , Schwenter Frank , Wassef Ramses , Ratelle Richard , De Broux Éric , Richard Carole S. , Santos Manuela M. 
Published: December 2022

Abstract
Background
Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes.

Methods
Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR.

Results
We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%).

Conclusions
Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.
Using whole-genome sequencing (WGS) to plot colorectal cancer-related gut microbiota in a population with varied geography
Authors: Shuwen Han , Yinhang Wu , Xingming Zhao , Jing Zhuang , Jinxin Liu , Wei Wu , Kefeng Ding 
Published: December 2022

Abstract
Background
Colorectal cancer (CRC) is a multifactorial disease with genetic and environmental factors. Regional differences in risk factors are an important reason for the different incidences of CRC in different regions.

Objective
The goal was to clarify the intestinal microbial composition and structure of CRC patients in different regions and construct CRC risk prediction models based on regional differences.

Methods
A metagenomic dataset of 601 samples from 6 countries in the GMrepo and NCBI databases was collected. All whole-genome sequencing (WGS) data were annotated for species by MetaPhlAn2. We obtained the relative abundance of species composition at the species level and genus level. The MicrobiotaProcess package was used to visualize species composition and PCA. LEfSe analysis was used to analyze the differences in the datasets in each region. Spearman correlation analysis was performed for CRC differential species. Finally, the CRC risk prediction model was constructed and verified in each regional dataset.

Results
The composition of the intestinal bacterial community varied in different regions. Differential intestinal bacteria of CRC in different regions are inconsistent. There was a common diversity of bacteria in all six countries, such as Peptostreptococcus stomatis and Fusobacterium nucleatum at the species level. Peptostreptococcus stomatis (species level) and Peptostreptococcus (genus level) are important CRC-related bacteria that are related to other bacteria in different regions. Region has little influence on the accuracy of the CRC risk prediction model. Peptostreptococcus stomatis is an important variable in CRC risk prediction models in all regions.

Conclusion
Peptostreptococcus stomatis is a common high-risk pathogen of CRC worldwide, and it is an important variable in CRC risk prediction models in all regions. However, regional differences in intestinal bacteria had no significant impact on the accuracy of the CRC risk prediction model.
Visualizing chemical space networks with RDKit and NetworkX
Authors: Scalfani Vincent F. , Patel Vishank D. , Fernandez Avery M. 
Published: December 2022

AbstractThis article demonstrates how to create Chemical Space Networks (CSNs) using a Python RDKit and NetworkX workflow. CSNs are a type of network visualization that depict compounds as nodes connected by edges, defined as a pairwise relationship such as a 2D fingerprint similarity value. A step by step approach is presented for creating two different CSNs in this manuscript, one based on RDKit 2D fingerprint Tanimoto similarity values, and another based on maximum common substructure similarity values. Several different CSN visualization features are included in the tutorial including methods to represent nodes with color based on bioactivity attribute value, edges with different line styles based on similarity value, as well as replacing the circle nodes with 2D structure depictions. Finally, some common network property and analysis calculations are presented including the clustering coefficient, degree assortativity, and modularity. All code is provided in the form of Jupyter Notebooks and is available on GitHub with a permissive BSD-3 open-source license:https://github.com/vfscalfani/CSN_tutorialGraphical Abstract