bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance and virulence distribution in enterococci isolated from broilers reared in two farming systems
Authors: Semedo-Lemsaddek Teresa , Bettencourt Cota João , Ribeiro Tânia , Pimentel Amélia , Tavares Luís , Bernando Fernando , Oliveira Manuela 
Published: August 2021

Abstract
Background
The impact of enterococci in human health has been growing for the last decades, mainly due to their resistance to several antimicrobial agents. Human consumption of contaminated meat, especially poultry, has been identified as a possible route of transmission. The aim of the present study was to evaluate and compare the antimicrobial resistance profiles and virulence genes of enterococci isolated from Portuguese conventional and free-range broiler farms.

Results
Antibiotic susceptibility testing showed high frequencies of resistance to tetracycline in both farming systems. Resistance to erythromycin and gentamicin were detected in about half of the isolates. Resistance to penicillin was the less frequently observed and no vancomycin resistant isolates were identified. The majority of the enterococcal isolates, from either farming systems, were resistant to more than one antibiotic, and no statistical associations were found, except for penicillin resistance which associated with the genetic clusters. No differences were found between farming systems regarding the prevalence of tet(M), erm(B), aac (6′)-Ie-aph (2″)-Ia and pbp5 genes, nevertheless pbp5 prevalence was associated with the different genetic clusters. Hemolytic activity was identified in 26.47% of all isolates and gelatinase activity in 50%. The gelE gene was identified in the majority of the isolates, whereas esp and agg genes were rarely detected. The cylA determinant was not detected in any of the isolates.

Conclusions
Overall, results suggest that similar resistance patterns and virulence genes can be found in both farming systems, though enterococci in free-range conditions should be less prone to acquire further resistance genes.
Access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda: a qualitative study
Authors: Musoke David , Namata Carol , Lubega Grace Biyinzika , Kitutu Freddy Eric , Mugisha Lawrence , Amir Saba , Brandish Claire , Gonza Joviah , Ikhile Deborah , Niyongabo Filimin , Ng Bee Yean , O’Driscoll Jean , Russell-Hobbs Kate , Winter Jody , Gibson Linda 
Published: August 2021

Abstract
Background
Inappropriate use of antimicrobials in both humans and animals is a key driver of antimicrobial resistance (AMR). In addition, human behaviours such as poor disposal of antimicrobials in the environment can increase their exposure to microbes which can impact on humans and animals. However, evidence on access, use and disposal of antimicrobials for humans and animals at community level in Uganda is limited. This study therefore explored access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda.

Methods
A qualitative study was conducted that involved focus group discussions (FGDs) and key informant interviews (KIIs). Participants of the FGDs were community health workers (CHWs) and farmers involved in animal husbandry, while key informants included: officials from the Ministry of Health; Ministry of Agriculture, Animal Industry and Fisheries; human and animal health professionals; district health officials; and members of the national AMR surveillance committee. Twelve FGDs were held (8 for CHWs and 4 for farmers) while 15 KIIs were conducted. Thematic analysis in NVivo (version 12) was performed.

Results
Five main themes emerged from the study: access to antimicrobials in humans; access to antimicrobials in animals; use of antimicrobials in humans; use of antimicrobials in animals; and disposal of antimicrobials. Community members mainly accessed antimicrobials for humans from public health facilities such as government health centres, as well as private facilities, including drug shops and clinics. Antimicrobials for animals were obtained from veterinary practitioners and drug shops (both for humans and veterinary). Examples of inappropriate use of antimicrobials in both humans and animals was evident, such as sharing antibiotics among household members, and giving human-prescribed antimicrobials to food-producing animals as growth promoters. While some CHWs returned unused antimicrobials to public health facilities for proper disposal, community members mainly disposed of antimicrobials with general household waste including dumping in rubbish pits.

Conclusions
There is a need to increase awareness among the population on proper access, use and disposal of antimicrobials for both humans and animals. Development of a drug disposal system at community level would facilitate improved waste management of antimicrobials. Together, these measures would help prevent the rate of progression of AMR in communities.
Role of serum Nogo-B as a biomarker for diagnosis of chronic liver diseases and its severity
Authors: Fouad Ayman , Aref Wael , Elshenawy Ahmed , Hanafi Hadeel M. , Attallah Khaled M. , Alnaggar Alshaimaa Rezk L. R. 
Published: August 2021

Abstract
Background
Nogo-B is one of the members of the reticulon family. Nogo-B influences the proliferation of the hepatic stellate cells inducing liver fibrotic changes. We aimed at measuring the serum levels of Nogo-B in patients with chronic liver disease (CLD) with different etiologies. Ninety subjects were included, 18 of them were normal healthy individuals and 72 had liver disease (fibrosis/cirrhosis) with different etiologies: post-hepatitis C infection, post-hepatitis B infection, NASH, and autoimmune hepatitis. Serum Nogo-B was assessed using ELISA. Patients were subdivided according to the Child-Pugh score into 3 groups: group 1—Child A (24 patients); group 2—Child B (24 patients); and group 3—Child C (24 patients).

Results
Serum Nogo-B levels were found to be significantly higher in patients (1477.92 ± 1113.50) when compared with healthy control (301.28 ± 180.87) (p < 0.001). There was a statistically significant difference in serum Nogo-B level between the three sub-groups of patients (p < 0.001). A positive correlation was found between serum Nogo-B and MELD score (r = 0.46, p-value < 0.001). However, there was no correlation found between Nogo-B and FIB-4 index or APRI score. There was a significant positive correlation between serum Nogo-B level and coagulation profile and serum bilirubin. An inverse correlation was found between serum Nogo-B with serum albumin. A ROC curve was done to examine the validity of Nogo-B in the diagnosis of liver cirrhosis, and the area under the curve was found to be 0.979, a cutoff value of 600 with a sensitivity of 97.2% and a specificity of 94.4% (p-value < 0.001).

Conclusion
Nogo-B had a high value in the identification of patients with any severity of CLD. There is a highly significant correlation between Nogo-B and the synthetic function of the liver; it could be used as a measure of hepatic functional reserve.
Scientific and clinical implications of genetic and cellular heterogeneity in uveal melanoma
Authors: de Lange Mark J. , Nell Rogier J. , van der Velden Pieter A. 
Published: August 2021

AbstractHere, we discuss the presence and roles of heterogeneity in the development of uveal melanoma. Both genetic and cellular heterogeneity are considered, as their presence became undeniable due to single cell approaches that have recently been used in uveal melanoma analysis. However, the presence of precursor clones and immune infiltrate in uveal melanoma have been described as being part of the tumour already decades ago. Since uveal melanoma grow in the corpus vitreous, they present a unique tumour model because every cell present in the tumour tissue is actually part of the tumour and possibly plays a role. For an effective treatment of uveal melanoma metastasis, it should be clear whether precursor clones and normal cells play an active role in progression and metastasis. We propagate analysis of bulk tissue that allows analysis of tumour heterogeneity in a clinical setting.
Biosimilar Use in Breast Cancer Treatment: A National Survey of Brazilian Oncologists' Opinions, Practices, and Concerns
Authors: Resende Heloísa M. , Ladislau Leandro , Cardoso Ana Carolina F. , Brandão Juliana Dinéia P. , Assis Biazi R. , Cardoso Paola , Marassi Pedro Henrique A. , Castilho Vivienne 
Published: August 2021

PURPOSE Breast cancer is the most common malignancy in Brazilian women, with 66,280 new cases in 2020 (with 20% overexpressing human epidermal growth factor receptor 2 [HER2]). The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer treatment. This study aimed to assess the current level of knowledge of biosimilars, comfort of use, extrapolation indications, and switching of practices among oncologists in Brazil. METHODS A 24-question survey was developed using an online platform that sought information regarding responders' characteristics and use of biosimilars. The survey analyzed the basic knowledge of biosimilars, trastuzumab biosimilars, level of comfort with extrapolation, switching treatment regimens, and opinions concerning the cost of HER2-positive breast cancer therapy. Data were collected between July and September 2019 and included 144 oncologists from five Brazilian regions. RESULTS In total, 95% of respondents could identify the most appropriate definition of biosimilars and 96% felt comfortable prescribing trastuzumab biosimilars. Although 63% of respondents would use the biosimilar in all settings wherein the reference biologic was approved, 35% would use the biosimilar for cases involving metastatic disease. Although 82% of oncologists were in favor of switching from a reference biologic to a biosimilar, 18% would avoid switching regimens. The lack of studies detailing switching to other regimens and the correct timing to switch was the major concern. The cost of HER2 therapy was a significant concern for most oncologists. CONCLUSION Oncologists demonstrated a high level of knowledge of biosimilars and encouraging levels of prescriber use; however, extrapolation and switching treatment regimens are barriers to the effective use of biosimilars in cancer treatment. Efforts should be concentrated on strategies involving medical education programs on biosimilars.
Is there any Nambu monopolium out there?
Authors: Azevedo D. O. R. , Bispo M. L. , Del Cima O. M. , Franco D. H. T. , Pereira A. R. 
Published: August 2021

Abstract
Magnetic monopoles have been a subject of study for more than a century since the first ideas by A. Vaschy and P. Curie, circa 1890. In 1974, Y. Nambu proposed a model for magnetic monopoles exploring a parallelism between the broken symmetry Higgs and the superconductivity Ginzburg-Landau theories in order to describe the pions quark-antiquark confinement states. There, Nambu described an energetic string where its end points behave like two magnetic monopoles with opposite magnetic charges —quark and antiquark. Consequently, not only the interaction among monopole and antimonopole, mediated by a massive vector boson (Yukawa potential), but also the energetic string (linear potential) contribute to the effective interaction potential. We propose here a monopole-antimonopole non-confining attractive interaction of the Nambu type, and then investigate the formation of bound states, the monopolium. Some necessary conditions for the existence of bound states to be fulfilled by the proposed Nambu-type potential, Kato weakness, Setô and Bargmann conditions, are verified. In the following, ground-state energies are estimated for a variety of monopolium reduced mass, from 102 MeV to 102 TeV, and Compton interaction lengths, from

am to

pm, where discussion about non-relativistic and relativistic limits validation is carried out.

Dedicated to the memory of Dr. César Augusto Parga Rodrigues (1939–2021).
Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency
Authors: Gurpinar Tosun Busra , Kendir Demirkol Yasemin , Seven Menevse Tuba , Kaygusuz Sare Betul , Ozbek Mehmet Nuri , Altincik Selda Ayca , Mammadova Jamala , Cayir Atilla , Doger Esra , Bayramoglu Elvan , Nalbantoglu Ozlem , Yesiltepe Mutlu Gul , Aghayev AghaRza , Turan Serap , Bereket Abdullah , Guran Tulay 
Published: August 2021

Abstract

Background
Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up.

Objective
Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment.

Design and method
Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses.

Results
Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G &gt; A, p.F130L, p.E198del, c.1122-18G &gt; A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I.

Conclusions
Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.
Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss
Authors: Imbert Alyssa , Vialaneix Nathalie , Marquis Julien , Vion Julie , Charpagne Aline , Metairon Sylviane , Laurens Claire , Moro Cedric , Boulet Nathalie , Walter Ondine , Lefebvre Grégory , Hager Jörg , Langin Dominique , Saris Wim H M , Astrup Arne , Viguerie Nathalie , Valsesia Armand 
Published: August 2021

AbstractContextAdipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes.ObjectiveTo implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI).MethodsAT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line.ResultsDuring LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes.ConclusionNetwork analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
Sobp modulates the transcriptional activation of Six1 target genes and is required during craniofacial development
Authors: Tavares Andre L. P. , Jourdeuil Karyn , Neilson Karen M. , Majumdar Himani D. , Moody Sally A. 
Published: August 2021

ABSTRACT
Branchio-oto-renal syndrome (BOR) is a disorder characterized by hearing loss, and craniofacial and/or renal defects. Variants in the transcription factor Six1 and its co-factor Eya1, both of which are required for otic development, are linked to BOR. We previously identified Sobp as a potential Six1 co-factor, and SOBP variants in mouse and humans cause otic phenotypes; therefore, we asked whether Sobp interacts with Six1 and thereby may contribute to BOR. Co-immunoprecipitation and immunofluorescence experiments demonstrate that Sobp binds to and colocalizes with Six1 in the cell nucleus. Luciferase assays show that Sobp interferes with the transcriptional activation of Six1+Eya1 target genes. Experiments in Xenopus embryos that either knock down or increase expression of Sobp show that it is required for formation of ectodermal domains at neural plate stages. In addition, altering Sobp levels disrupts otic vesicle development and causes craniofacial cartilage defects. Expression of Xenopus Sobp containing the human variant disrupts the pre-placodal ectoderm similar to full-length Sobp, but other changes are distinct. These results indicate that Sobp modifies Six1 function and is required for vertebrate craniofacial development, and identify Sobp as a potential candidate gene for BOR.
Local DNA synthesis is critical for DNA repair during oocyte maturation
Authors: Singh Ajay K. , Kumar S. Lava , Beniwal Rohit , Mohanty Aradhana , Kushwaha Bhawna , Rao H. B. D. Prasada 
Published: August 2021

ABSTRACT
Mammalian oocytes can be very long-lived cells and thereby are very likely to encounter DNA damage during their lifetime. Defective DNA repair may result in oocytes that are developmentally incompetent or give rise to progeny with congenital disorders. During oocyte maturation, damaged DNA is repaired primarily by non-homologous end joining (NHEJ) or homologous recombination (HR). Although these repair pathways have been studied extensively, the associated DNA synthesis is poorly characterized. Here, using porcine oocytes, we demonstrate that the DNA synthesis machinery is present during oocyte maturation and dynamically recruited to sites of DNA damage. DNA polymerase δ is identified as being crucial for oocyte DNA synthesis. Furthermore, inhibiting synthesis causes DNA damage to accumulate and delays the progression of oocyte maturation. Importantly, inhibition of the spindle assembly checkpoint (SAC) bypassed the delay of oocyte maturation caused by DNA synthesis inhibition. Finally, we found that ∼20% of unperturbed oocytes experienced spontaneously arising damage during maturation. Cumulatively, our findings indicate that oocyte maturation requires damage-associated DNA synthesis that is monitored by the SAC.
This article has an associated First Person interview with the first author of the paper.
Practical Recommendations for High-Intensity Interval Training for Adults with Cardiovascular Disease
Authors: Way Kimberley L. , Terada Tasuku , O’Neill Carley D. , Vidal-Almela Sol , Keech Andrew , Reed Jennifer L. 
Published: August 2021

Apply It!
• High-intensity interval training (HIIT) can be implemented safely in adults with cardiovascular disease (CVD) after a graded exercise test assessing exercise responses at a high intensity (e.g., to 85% heart rate peak [HRpeak] or a rating of perceived exertion [RPE] of 15).
• Always involve the patient in the decision-making process for selecting the mode of exercise to perform HIIT to increase adherence, compliance, and enjoyment to the exercise program.
• Given the low exercise tolerance that is typically experienced by patients with CVD, short duration high-intensity bouts (e.g., 30 seconds to 1 minute) may be necessary to increase exercise tolerance and self-efficacy. Active or passive recovery interspersed between high-intensity intervals should be equal to or greater than the duration of the high-intensity intervals. Passive recoveries should be avoided if a person experiences vasovagal symptoms/events.
Application of conventional ultrasonography combined with contrast-enhanced ultrasonography in the axillary lymph nodes and evaluation of the efficacy of neoadjuvant chemotherapy in breast cancer patients
Authors: Han Xue , Jin Shiyang , Yang Huajing , Zhang Jinxing , Huang Zhenfeng , Han Jiguang , He Chuan , Guo Hongyan , Yang Yue , Shan Ming , Zhang Guoqiang 
Published: August 2021

Objective:
Axillary lymph node status assessment has always been an important issue in clinical treatment of breast cancer. However, there has been no effective method to accurately predict the pathological complete response (pCR) of axillary lymph node after neoadjuvant chemotherapy (NAC). The objective of our study was to investigate whether conventional ultrasonography combined with contrast-enhanced ultrasonography (CEUS) can be used to evaluate axillary lymph node status of breast cancer patients after NAC.

Methods:
A total of 74 patients who underwent NAC were recruited for the present study. Prior to and after NAC, examinations of conventional ultrasonography and CEUS were performed. After evaluating the images of conventional ultrasonography, four characteristics were recorded: lymph node medulla boundary, cortex of lymph node, lymph node hilus, and lymph node aspect ratio. Two additional imaging characteristics of CEUS were analyzed: CEUS way and CEUS pattern. Receiver operating characteristiccurve analysis was applied to evaluate their diagnostic performance.

Results:
After 6~8 cycles of NAC, 46 (71.9%) patients had negative axillary lymph node, and 18 (28.1%) patients turned out non-pCR. According to statistical analysis, lymph node medulla, lymph node aspect ratio and CEUS way were independently associated with pCR of axillary lymph node after NAC. The area under the curve of the prediction model with three imaging characteristics was 0.882 (95% confidence interval: 0.608–0.958), and the accuracy to predict the patients’ lymph node status was 78.1% (p &lt; 0.01).

Conclusions:
Conventional ultrasonography combined with CEUS technology can accurately predict axillary lymph nodes status of breast cancer patients after NAC.

Advances in knowledge:
The usefulness of CEUS technology in predicting pCR after neoadjuvant chemotherapy is highlighted.