bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ceftiofur reduced Fusobacterium leading to uterine microbiota alteration in dairy cows with metritis
Authors: Jeon Soo Jin , Cunha Federico , Daetz Rodolfo , Bicalho Rodrigo C. , Lima Svetlana , Galvão Klibs N. 
Published: January 2021

Abstract
Background
Metritis is an inflammatory uterine disease found in ~ 20% of dairy cows after parturition and associated with uterine microbiota with high abundance of Fusobacterium, Bacteroides, and Porphyromonas. Ceftiofur is a common treatment, but the effect on uterine microbiota is poorly understood. Herein, we investigated the short-term impact of ceftiofur on uterine microbiota structure and function in cows with metritis. Eight cows received ceftiofur (CEF) and 10 remained untreated (CON). Uterine swabs were collected for PCR and metagenomic analysis at diagnosis before treatment (5 ± 1 DPP) and 2 days after diagnosis/treatment (7 ± 1 DPP) from the same individuals. Seven CEF and 9 CON passed quality control and were used for 16S rRNA gene sequencing.

Results
Ceftiofur treatment resulted in uterine microbiota alteration, which was attributed to a decrease in relative abundance of Fusobacterium and in gene contents involved in lipopolysaccharide biosynthesis, whereas uterine microbiota diversity and genes involved in pantothenate and coenzyme A biosynthesis increased. Ceftiofur treatment also reduced rectal temperature and tended to reduce total bacteria in the uterus. However, other uterine pathogens such as Bacteroides and Porphyromonas remained unchanged in CEF. The blaCTX-M gene was detected in 37.5% of metritic cows tested but was not affected by CEF. We found that β-hydroxybutyric acid, pyruvic acid, and L-glutamine were preferentially utilized by Fusobacterium necrophorum according to metabolic activity with 95 carbon sources.

Conclusions
Ceftiofur treatment leads to alterations in the uterine microbiota that were mainly characterized by reductions in Fusobacterium and genes involved in LPS biosynthesis, which may be associated with a decrease in rectal temperature. The increase in pantothenate and coenzyme A biosynthesis indicates microbial response to metabolic stress caused by ceftiofur. Preference of Fusobacterium for β-hydroxybutyric acid may help to explain why this strain becomes dominant in the uterine microbiota of cows with metritis, and it also may provide a means for development of new therapies for the control of metritis in dairy cows.
Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002)
Authors: Yom Sue S. , Torres-Saavedra Pedro , Caudell Jimmy J. , Waldron John N. , Gillison Maura L. , Xia Ping , Truong Minh T. , Kong Christina , Jordan Richard , Subramaniam Rathan M. , Yao Min , Chung Christine H. , Geiger Jessica L. , Chan Jason W. , O'Sullivan Brian , Blakaj Dukagjin M. , Mell Loren K. , Thorstad Wade L. , Jones Christopher U. , Banerjee Robyn N. , Lominska Christopher , Le Quynh-Thu 
Published: January 2021

PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline
Authors: Korde Larissa A. , Somerfield Mark R. , Carey Lisa A. , Crews Jennie R. , Denduluri Neelima , Hwang E. Shelley , Khan Seema A. , Loibl Sibylle , Morris Elizabeth A. , Perez Alejandra , Regan Meredith M. , Spears Patricia A. , Sudheendra Preeti K. , Symmans W. Fraser , Yung Rachel L. , Harvey Brittany E. , Hershman Dawn L. 
Published: January 2021

PURPOSETo develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer.METHODSASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options.RESULTSA total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations.RECOMMENDATIONSPatients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy. Additional information is available at www.asco.org/breast-cancer-guidelines .
Association Between Obstructive Sleep Apnea and Metabolic Abnormalities in Patients With Hypertrophic Cardiomyopathy
Authors: Wang Juan , Xu Haobo , Yuan Jiansong , Guo Chao , Hu Fenghuan , Yang Weixian , Song Lei , Luo Xiaoliang , Liu Rong , Cui Jingang , Liu Shengwen , Chun Yushi , Qiao Shubin 
Published: January 2021

Abstract

Objectives
Metabolic abnormalities have been associated with long-term cardiac mortality in patients with hypertrophic cardiomyopathy (HCM). Obstructive sleep apnea (OSA) is a risk factor for metabolic abnormalities in general populations, but association between OSA and metabolic abnormalities in HCM is still undefined. This study aimed to investigate the relationship between OSA and metabolic dysfunction in a large series of patients with HCM.

Methods
A total of 587 patients with HCM who underwent sleep evaluations at Fuwai Hospital were included. Data from clinical characteristics, polysomnography studies, and metabolic measurements were collected.

Results
OSA was present in 344 patients (58.6%). Patients with OSA were older, more often male, and had more clinical comorbidities. Body mass index, blood pressure, fasting glucose, and triglycerides all increased (all P &lt; 0.001) and high-density lipoprotein cholesterol decreased (P = 0.046) with the severity of OSA. In multivariate analysis, moderate to severe OSA and Log (apnea-hypopnea index + 1) were independently associated with obesity (odds ratio [OR], 2.42; 95% CI, 1.48-3.95 and OR, 1.60; 95% CI, 1.31-1.95), elevated blood pressure (OR, 1.99; 95% CI, 1.42-3.26 and OR, 1.31; 95% CI, 1.08-1.60), and elevated triglycerides (OR, 1.71; 95% CI, 1.05-2.78 and OR, 1.24; 95% CI, 1.02-1.51 but not elevated fasting glucose (OR, 0.88; 95% CI, 0.50-1.52 and OR, 1.02; 95% CI, 0.82-1.28) or reduced high-density lipoprotein cholesterol (OR, 1.30; 95% CI, 0.83-2.04 and OR, 1.06; 95% CI, 0.89-1.27).

Conclusions
Severity of OSA is independently associated with some profiles of metabolic abnormalities. Clinical trials are required to determine whether OSA treatment improves metabolic abnormalities and long-term outcomes in patients with HCM.
Daytime Napping Duration Is Positively Associated With Risk of Hyperuricemia in a Chinese Population
Authors: Wang Yanjiao , Zeng Yongli , Zhang Xuehui , Meng Qiong , Mi Fei , Wang Songmei , Xu Fang , Sun Yan , Feng Yuemei , Yin Jianzhong 
Published: January 2021

Abstract

Context
Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia.

Objective
We investigated daily sleep duration (daytime napping and nocturnal sleep) with hyperuricemia risk.

Methods
We cross-sectionally analyzed data from the China Multi-Ethnic Cohort (CMEC), Yunnan region. A total of 22 038 participants aged 30 to 79 years were recruited in 2018. Hyperuricemia was defined as serum uric acid (SUA) above 7.0 mg/dL in men and above 6.0 mg/dL in women. Outcomes were associations between daily sleep duration and hyperuricemia.

Results
We found that the longest daytime napping duration was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] [95% CI], 2.22 [1.88-2.61], P &lt; .001) and in a multivariable adjustment model (OR, 1.69; 95% CI, 1.41-2.01, P &lt; .001) after adjusting for demographic, sleep habits, and metabolic risk factors. The association was moderately attenuated with additionally adjusted for serum creatinine (OR, 1.54; 95% CI, 1.28-1.86, P &lt; .001). Longer daytime napping duration was also related to higher risk of hyperuricemia combined with metabolic syndrome (MetS). Respondents in the group with daytime napping duration greater than or equal to 90 minutes presented with a higher risk of hyperuricemia combined with MetS (OR, 1.39; 95% CI, 1.06-1.79; P &lt; .001) in the fully adjusted model. We did not observe any relation between nocturnal sleep duration and risk of hyperuricemia in the study.

Conclusion
Longer daytime napping duration (but not nocturnal sleep duration) was independently associated with risk of hyperuricemia in a Chinese population.
Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible By Insulin Treatment
Authors: Wagner Isabel Viola , Klöting Nora , Savchuk Iuliia , Eifler Lisa , Kulle Alexandra , Kralisch-Jäcklein Susan , Dötsch Jörg , Hiort Olaf , Svechnikov Konstantin , Söder Olle 
Published: January 2021

Abstract
Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis and lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model. BB/OKL rats after diabetes manifestation were divided into 3 groups: those without insulin treatment and insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone, and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis. Untreated diabetic rats had significantly lower serum follicle-stimulating hormone and luteinizing hormone levels. Serum and intratesticular testosterone levels significantly decreased in untreated diabetic rats compared to healthy controls. Key markers of Leydig cell function were significantly downregulated at the RNA level: insulin-like factor 3 (Insl3) by 53% (P = .006), Star by 51% (P = .004), Cyp11A1 by 80% (P = .003), 3Beta-Hsd2 by 61% (P = .005), and Pbr by 52% (P = .002). In the insulin-treated group, only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly, the long-term insulin–treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. Tumor necrosis factor α and apoptosis were significantly increased in the long-term insulin–treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well-compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function because of the process of inflammation and apoptosis.
The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression
Authors: Wu Dan , Wang Sailan , Oliveira Daniel V. , Del Gaudio Francesca , Vanlandewijck Michael , Lebouvier Thibaud , Betsholtz Christer , Zhao Jian , Jin ShaoBo , Lendahl Urban , Karlström Helena 
Published: January 2021

ABSTRACT
Infantile myofibromatosis (IMF) is a benign tumor form characterized by the development of nonmetastatic tumors in skin, bone, muscle and sometimes viscera. Autosomal-dominant forms of IMF are caused by mutations in the PDGFRB gene, but a family carrying a L1519P mutation in the NOTCH3 gene has also recently been identified. In this study, we address the molecular consequences of the NOTCH3L1519P mutation and the relationship between Notch and PDGFRB signaling in IMF. The NOTCH3L1519P receptor generates enhanced downstream signaling in a ligand-independent manner. Despite the enhanced signaling, the NOTCH3L1519P receptor is absent from the cell surface and instead accumulates in the endoplasmic reticulum. Furthermore, the localization of the NOTCH3L1519P receptor in the bipartite, heterodimeric state is altered, combined with avid secretion of the mutated extracellular domain from the cell. Chloroquine treatment strongly reduces the amount of secreted NOTCH3L1519P extracellular domain and decreases signaling. Finally, NOTCH3L1519P upregulates PDGFRB expression in fibroblasts, supporting a functional link between Notch and PDGF dysregulation in IMF. Collectively, our data define a NOTCH3–PDGFRB axis in IMF, in which an IMF-mutated NOTCH3 receptor elevates PDGFRB expression. The functional characterization of a ligand-independent gain-of-function NOTCH3 mutation is important for Notch therapy considerations for IMF, including strategies aimed at altering lysosome function.
NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells
Authors: Madsen Ralitsa R. , Longden James , Knox Rachel G. , Robin Xavier , Völlmy Franziska , Macleod Kenneth G. , Moniz Larissa S. , Carragher Neil O. , Linding Rune , Vanhaesebroeck Bart , Semple Robert K. 
Published: January 2021

ABSTRACT
Activating PIK3CA mutations are known ‘drivers’ of human cancer and developmental overgrowth syndromes. We recently demonstrated that the ‘hotspot’ PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In this study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of homozygous PIK3CAH1047R cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling strength, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant transcriptomic signature of TGFβ pathway activation in heterozygous PIK3CAH1047R was observed but was modest and was not associated with the stemness phenotype seen in homozygous mutants. Notably, the stemness gene expression in homozygous PIK3CAH1047R hPSCs was reversed by pharmacological inhibition of NODAL/TGFβ signalling, but not by pharmacological PI3Kα pathway inhibition. Altogether, this provides the first in-depth analysis of PI3K signalling in hPSCs and directly links strong PI3K activation to developmental NODAL/TGFβ signalling. This work illustrates the importance of allele dosage and expression when artificial systems are used to model human genetic disease caused by activating PIK3CA mutations.
This article has an associated First Person interview with the first author of the paper.
Multiparametric MR evaluation of uterine leiomyosarcoma and STUMP versus leiomyoma in symptomatic women planned for high frequency focussed ultrasound: accuracy of imaging parameters and interobserver agreement for identification of malignancy
Authors: Aminzadeh Parisa , Alibrahim Ekaterina , Dobrotwir Andrew , Paul Eldho , Goergen Stacy 
Published: January 2021

Objective:
To assess accuracy of and interobserver agreement on multiparametric MR findings to distinguish uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS) and soft tissue tumour of unknown malignant potential.

Methods:
Inclusion criteria: All females over 18 years with least one uterine mass measuring 5 cm or more in at least one of the three standard orthogonal dimensions on MR with histopathological confirmation of LM, LMS, or soft tissue tumour of unknown malignant potential (STUMP) in the 3 months following MR. Patients with LMS were drawn from a larger cohort being assessed for MR-guided focussed ultrasound (MRgFUS) suitability. Image evaluation: Assessed variables were: lesion margin, margin definition, T2 signal homogeneity, &gt;50% of lesion with T2 signal brighter than myometrium, haemorrhage, restricted diffusion, contrast enhancement (CE), CE pattern, local lymphadenopathy and ascites.

Results:
32 LM, 10 LMS and 1 STUMP were evaluated. Ill-defined (p-value = 0.0003–0.0004) or irregular (p = 0.003–0.004) lesion margin, T2 hyperintensity &gt;50% (p = 0.001–0.004), and peripheral CE (p = 0.02–0.05) were significantly more common in LMS/STUMP than LM for both radiologists. 10/11 (Reader 2) and 11/11 (Reader 1) LMS/STUMP displayed restricted diffusion but so did 63–80% of LM. Agreement was greatest for margin characteristics (κ = 0.73–0.81).

Conclusion:
Irregular/ill-defined lesion margin best distinguished LMS/STUMP from LM with good interrater reliability.

Advances in knowledge:
Assessment of agreement regarding MR parameters distinguishing LM from LMS and STUMP has not previously been undertaken in a cohort including a large number of patients with LMS. This will help inform evaluation of females considering minimally invasive LM treatment.
Evaluating the use of video communication technology in a hospital specialist palliative care team during the COVID-19 pandemic
Authors: Crosby Benjamin , Hanchanale Sarika , Stanley Sarah , Nwosu Amara Callistus 
Published: January 2021

Background: Healthcare professionals’ use of video communication technology has increased during the novel coronavirus disease (COVID-19) pandemic, due to infection control restrictions. Currently there is little published data about the experiences of specialist palliative care teams who are using technology to communicate during the COVID-19 pandemic. The aim of this evaluation was to describe the experience of a UK based hospital specialist palliative care team, who were using video communication technology to support care during the COVID-19 pandemic. Methods: An online survey was distributed to the specialist palliative care team at a University teaching hospital in the North West of the UK. We asked participants to provide their views on the scope of use, barriers and future opportunities to use technology for communication in hospital palliative care. Results: The survey was completed by 14 healthcare professionals. Participants indicated that the most common reasons for using the technology was to receive team updates (n= 14, 100%), participate in multidisciplinary team meetings (n=14, 100%), for education (n=12, 86%) and to facilitate cross-site working (n=9, 64%). We identified barriers to using the technology, which were summarised as: (1) user-based difficulties; (2) inadequate technological infrastructure; (3) data security, privacy and ethical concerns; and (4) concerns regarding staff wellbeing. Participants stated that technology can potentially improve care by improving communication with hospital and community teams and increasing access to education. We have used these findings to develop recommendations to help palliative care teams to implement this technology better in clinical practice. Conclusion: Video communication technology has the potential to improve specialist palliative care delivery; however, it is essential that healthcare organisations address the existing barriers to using this technology, to ensure that these systems work meaningfully to improve palliative care for those who are most vulnerable beyond the COVID-19 pandemic.
Operationalisation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 trials in a low and lower-middle income critical care learning health system.
Authors: Aryal Diptesh , Beane Abi , Dondorp Arjen M. , Green Cameron , Haniffa Rashan , Hashmi Madiha , Jayakumar Devachandran , Marshall John C. , McArthur Colin J. , Murthy Srinivas , Webb Steven A. , Acharya Subhash P. , Ishani Pramodya G. P. , Jawad Issrah , Khanal Sushil , Koirala Kanchan , Luitel Subekshya , Pabasara Upulee , Paneru Hem Raj , Kumar Ashok , Patel Shoaib Siddiq , Ramakrishnan Nagarajan , Salahuddin Nawal , Shaikh Mohiuddin , Tolppa Timo , Udayanga Ishara , Umrani Zulfiqar 
Published: January 2021

The Randomized Embedded Multifactorial Adaptive Platform (REMAP-CAP) adapted for COVID-19) trial is a global adaptive platform trial of hospitalised patients with COVID-19. We describe implementation in three countries under the umbrella of the Wellcome supported Low and Middle Income Country (LMIC) critical care network: Collaboration for Research, Implementation and Training in Asia (CCA). The collaboration sought to overcome known barriers to multi centre-clinical trials in resource-limited settings. Methods described focused on six aspects of implementation: i, Strengthening an existing community of practice; ii, Remote study site recruitment, training and support; iii, Harmonising the REMAP CAP- COVID trial with existing care processes; iv, Embedding REMAP CAP- COVID case report form into the existing CCA registry platform, v, Context specific adaptation and data management; vi, Alignment with existing pandemic and critical care research in the CCA. Methods described here may enable other LMIC sites to participate as equal partners in international critical care trials of urgent public health importance, both during this pandemic and beyond.