bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive approach for microbiota and health monitoring in mouse colonies using metagenomic shotgun sequencing
Authors: Scavizzi Ferdinando , Bassi Cristian , Lupini Laura , Guerriero Paola , Raspa Marcello , Sabbioni Silvia 
Published: July 2021

Abstract
Background
Health surveillance of murine colonies employed for scientific purposes aim at detecting unwanted infection that can affect the well-being of animals and personnel, and potentially undermine scientific results. In this study, we investigated the use of a next-generation sequencing (NGS) metagenomic approach for monitoring the microbiota composition and uncovering the possible presence of pathogens in mice housed in specific pathogen-free (SPF) or conventional (non-SPF) facilities.

Results
Analysis of metagenomic NGS assay through public and free algorithms and databases allowed to precisely assess the composition of mouse gut microbiome and quantify the contribution of the different microorganisms at the species level. Sequence analysis allowed the uncovering of pathogens or the presence of imbalances in the microbiota composition. In several cases, fecal pellets taken from conventional facilities were found to carry gene sequences from bacterial pathogens (Helicobacter hepaticus, Helicobacter typhlonius, Chlamydia muridarum, Streptococcus pyogenes, Rodentibacter pneumotropicus, Citrobacter rodentium, Staphylococcus aureus), intestinal protozoa (Entamoeba muris, Tritrichomonas muris, Spironucleus muris) nematoda (Aspiculuris tetraptera, Syphacia obvelata), eukaryotic parasites (Myocoptes musculinus) and RNA virus (Norwalk virus). Thus, the use of NGS metagenomics can reduce the number of tests required for the detection of pathogens and avoid the use of sentinel mice.

Conclusions
In summary, in comparison with standard approaches, which require multiple types of test, NGS assay can detect bacteria, fungi, DNA and RNA viruses, and eukaryotic parasites from fecal pellets in a single test. Considering the need to protect animal well-being and to improve the success and reproducibility of preclinical studies, this work provides the proof-of-concept that the use of NGS metagenomics for health monitoring of laboratory mice is a feasible and dependable approach, that is able to broaden the current concept of health monitoring of laboratory mice from “pathogen surveillance” to a more inclusive “microbiota surveillance”.
E3 ubiquitin ligases: styles, structures and functions
Authors: Yang Quan , Zhao Jinyao , Chen Dan , Wang Yang 
Published: July 2021

AbstractE3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2. E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes. Thus, E3 ligases might be involved in regulating various biological processes and cellular responses to stress signal associated with cancer development. Thanks to their multi-functions, E3 ligases can be a promising target of cancer therapy. A deeper understanding of the regulatory mechanisms of E3 ligases in tumorigenesis will help to find new prognostic markers and accelerate the growth of anticancer therapeutic approaches. In general, we mainly introduce the classifications of E3 ligases and their important roles in cancer progression and therapeutic functions.
Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Update
Authors: Moy Beverly , Rumble R. Bryan , Come Steven E. , Davidson Nancy E. , Di Leo Angelo , Gralow Julie R. , Hortobagyi Gabriel N. , Yee Douglas , Smith Ian E. , Chavez-MacGregor Mariana , Nanda Rita , McArthur Heather L. , Spring Laura , Reeder-Hayes Katherine E. , Ruddy Kathryn J. , Unger Paul S. , Vinayak Shaveta , Irvin William J. , Armaghani Avan , Danso Michael A. , Dickson Natalie , Turner Sophie S. , Perkins Cheryl L. , Carey Lisa A. 
Published: July 2021

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .
“I'm Being Forced to Make Decisions I Have Never Had to Make Before”: Oncologists' Experiences of Caring for Seriously Ill Persons With Poor Prognoses and the Dilemmas Created by COVID-19
Authors: Perumalswami Chithra R. , Chen Emily , Martin Carly , Goold Susan D. , De Vries Raymond , Griggs Jennifer J. , Jagsi Reshma 
Published: July 2021

PURPOSE:The COVID-19 pandemic has created a new set of problems for clinicians. This study examines the experiences of oncologists providing care to seriously ill persons near the end of life in the context of the COVID-19 pandemic.METHODS:Between January 2020 and August 2020, we conducted semistructured, in-depth individual interviews with 22 purposefully sampled oncologists from practices enrolled in the Michigan Oncology Quality Consortium. Deidentified transcripts of the interviews were examined using thematic analysis.RESULTS:Our respondents described several novel problems created by the COVID-19 pandemic, including: (1) ethical challenges, (2) the need to manage uncertainty—physically and emotionally—on the part of both patients and oncologists, and (3) the difficulty of integrating technology and communication for seriously ill persons. These problems were made more complex by features of the pandemic: resource scarcity (and the need to fairly allocate poor resources), delays in care, high levels of fear, and the increased importance of advance care planning. Nonabandonment served as a way to cope with increased stress, and the use of telemedicine became an increasingly important medium of communication.CONCLUSION:This study offers an in-depth exploration of the problems faced by oncologists as a result of the COVID-19 pandemic and how they navigated them. Optimal decision making for seriously ill persons with cancer during the COVID-19 pandemic must include open acknowledgment of the ethical challenges involved, the emotions experienced by both patients and their oncologists, and the urgent need to integrate technology with compassionate communication in determining patient preferences.
The Epidemiology and Genetic Analysis of Children With Idiopathic Type 1 Diabetes in the State of Qatar
Authors: Abdel-Karim Tasneem , Haris Basma , Afyouni Houda , Mohammed Shayma , Khalifa Amel , Al-Maadheed Maryam , Zyoud Mahmoud , Elawwa Ahmed , Al-Khalaf Fawziya , Petrovski Goran , Hussain Khalid 
Published: July 2021

Abstract

Context
Idiopathic type 1 diabetes is characterized by the absence of autoantibodies and the underlying mechanisms are not clear.

Objective
We aimed to study the epidemiology, describe the clinical characteristics, and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes.

Methods
This was a prospective study of type 1 diabetes patients attending Sidra Medicine from 2018 to 2020. Autoantibodies (GAD65, IAA, IA-2A, and ZnT8) were measured and genetic testing was undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes were compared with patients with autoimmune type 1 diabetes.

Results
Of 1157 patients with type 1 diabetes, 63 were antibody-negative. Upon genome sequencing, 4 had maturity onset diabetes of the young (MODY), 2 had Wolfram syndrome, 1 had H syndrome, and 3 had variants of uncertain significance in MODY genes; 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10 to 14 years. C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average body mass index was in the normal range and 33% of the patients had a history of diabetic ketoacidosis (DKA).

Conclusion
Four percent of the children had idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the 2 groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is unknown but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.
Formin 3 directs dendritic architecture via microtubule regulation and is required for somatosensory nociceptive behavior
Authors: Das Ravi , Bhattacharjee Shatabdi , Letcher Jamin M. , Harris Jenna M. , Nanda Sumit , Foldi Istvan , Lottes Erin N. , Bobo Hansley M. , Grantier Benjamin D. , Mihály József , Ascoli Giorgio A. , Cox Daniel N. 
Published: July 2021

ABSTRACT
Dendrite shape impacts functional connectivity and is mediated by organization and dynamics of cytoskeletal fibers. Identifying the molecular factors that regulate dendritic cytoskeletal architecture is therefore important in understanding the mechanistic links between cytoskeletal organization and neuronal function. We identified Formin 3 (Form3) as an essential regulator of cytoskeletal architecture in nociceptive sensory neurons in Drosophila larvae. Time course analyses reveal that Form3 is cell-autonomously required to promote dendritic arbor complexity. We show that form3 is required for the maintenance of a population of stable dendritic microtubules (MTs), and mutants exhibit defects in the localization of dendritic mitochondria, satellite Golgi, and the TRPA channel Painless. Form3 directly interacts with MTs via FH1-FH2 domains. Mutations in human inverted formin 2 (INF2; ortholog of form3) have been causally linked to Charcot–Marie–Tooth (CMT) disease. CMT sensory neuropathies lead to impaired peripheral sensitivity. Defects in form3 function in nociceptive neurons result in severe impairment of noxious heat-evoked behaviors. Expression of the INF2 FH1-FH2 domains partially recovers form3 defects in MTs and nocifensive behavior, suggesting conserved functions, thereby providing putative mechanistic insights into potential etiologies of CMT sensory neuropathies.
Suppression of Intracellular Gene Expression by Inchworm-Type PNA-PEG Conjugate Depends on Recognition of a Monobasic Mutation
Authors: Hamashita Yusuke , Kise Naoki , Sakurai Toshihiko 
Published: July 2021

Abstract
To identify a monobasic mutation in a gene and regulate gene expression in cells, we synthesized an inchworm-type PNA-PEG conjugate modified with nonaarginine (R9) as a cell-penetrating peptide (i-PPc(R9)). We found that this i-PPc recognized a monobasic mutation and suppressed luciferase expression with high sequence-specificity in cancer cells.
The Effect of the Substituent Positions on Self-Assembly Behaviors of Liquid-Crystalline 1,3,4,6,9b-Pentaazaphenalene Derivatives
Authors: Watanabe Hiroyuki , Tanaka Kazuo , Chujo Yoshiki 
Published: July 2021

Abstract
We describe the syntheses and phase transition behaviors of liquid crystals composed of triangular π-conjugated molecules, 1,3,4,6,9b-pentaazaphenalene (5AP). Three types of 5AP derivatives having 3,4,5-tris(dodecyloxy)phenyl ((OC12)3Ph) were prepared by changing substituent positions. From thermal and structural analyses, liquid crystalline phases were observed from all derivatives. According to structural data and phase transition behaviors, it was suggested that the positions of the substituents significantly influence molecular alignments in liquid crystals as well as thermal properties. In particular, the columnar structures, which are favorable for expressing efficient carrier transportation, were observed in the 5AP derivative. These results suggest that the 5AP scaffold could be a platform for constructing a variety of aggregated structures by slightly different patterns of the molecular structures. Plausible models for these transitions are discussed.
Radiographic features in 2D imaging as predictors for justified CBCT examinations of canine-induced root resorption
Authors: Andresen Amanda K.H. , Jonsson Malin V. , Sulo Gerhard , Thelen Dorina S. , Shi Xie-Qi 
Published: July 2021

Objectives: This retrospective observational study aimed to evaluate the diagnostic accuracy of two-dimensional radiographs on canine-induced root resorption (CIRR) in lateral incisors and identify predictors of CIRR in patients with impacted maxillary canines (IMC). Methods: Ninety-nine patients aged 9–17 years, with 156 IMCs, were included in the study. All had CBCT-volumes and two-dimensional radiographs consisting of at least one panoramic radiograph. Two radiologists jointly viewed all cases twice. First, radiographic features related to the IMC and possible CIRR were recorded from two-dimensional radiographs. Then, CIRR was determined from CBCT and according to position and extension classified as mild, moderate and severe. Results: CIRRs was detected in 80% of lateral incisors (mild: 45%; moderate: 44%; severe: 11%). The sensitivity was generally low at mild and moderate cut-offs (29 and 29%), and somewhat higher for severe (50%). Corresponding specificities were 48%, 63% and 68%. Canine cusp-tip superimposing the lateral incisor’s middle third and root/crown ratio >1 was positively associated with mild CIRR, with an odds ratio (OR) of 3.8 and 6.7, respectively. In addition, the root development stage was positively associated with moderate/severe CIRR when the canine root was nearly or fully developed (OR = 3.1). Conclusions: The diagnostic accuracy of two-dimensional radiographs was inadequate for detecting CIRR amongst patients referred for CBCT examinations. Based on our results, none of the suggested two-dimensional radiographic features could predict moderate/severe CIRR except for root development stage. IMC in a later stage of root development seems to be associated with a higher risk of moderate/severe CIRR.
Association between depression, anxiety, stress and perceived quality of life in a Malaysian B40 urban community during the COVID-19 lockdown: A cross-sectional study
Authors: Sing Joo Gan , Owen Devan Daniel Mahalingam , Shao Qi Chuah , Patil Sapna Shridhar 
Published: July 2021

Background: In Malaysia, B40 communities are those with a median monthly household earning of under RM 3166. With the prolonged COVID-19 pandemic and the resulting lockdown, the livelihoods of those in these areas has been severely impacted. This has increased their vulnerability to psychological afflictions and has led to a poorer perception of their quality of life (QoL) in comparison to the rest of the population. We investigated the association between perceived levels of depression, anxiety and stress and their impact on quality of life (QoL) among B40 residents in a low-cost urban housing area in Kuala Lumpur, Malaysia. Methods: A cross-sectional study was conducted between July 2020 and February 2021 in the Seri Pantai housing settlement. The validated Malay versions of the depression, anxiety, and stress scale-21 (DASS-21) and the World Health Organization Quality of Life, brief (WHOQOL-BREF) were distributed to the participants using Google forms. The statistical significance of the association between subscales of depression, anxiety, stress and QoL domains were assessed using the Pearson’s correlation test. Results: Of the 180 participants, the majority were Malays (87.2%) and females (82.2%). The average scores were the highest for stress (5.66 ± 4.59) and the score in the environment domain of QoL (59.27 ± 17.23) was the lowest. A statistically significant negative correlation was found between the subscales of DASS-21 and the four domains of the QoL, with the social relationships and psychological domains showing a highly significant association (p < 0.001). The strongest correlation was observed between the psychological domain and depression (r= -.520) followed by psychological domain and stress (r= -.496). Conclusion: The strongest correlation was observed between psychological domain and depression. This suggests a need to address potential devastating mental health consequences of the COVID-19 pandemic and its effect on the QoL of residents in B40 communities.
The Discrepancy between Clove and Non-Clove Cigarette Smoke-Promoted Candida albicans Biofilm Formation with Precoating RNA-aptamer
Authors: Bachtiar Boy Muchlis , Gani Basri A. , Deviana Astri , Utami Nastiti Rilo , Andriyani Anissa Dien , Bachtiar Endang Winiati 
Published: July 2021

This study explores the influence of precoating aptamer (Ca-apt1) on C. albicans viability while the fungus was growing in the presence of exposing condensed cigarette smoke (CSC), prepared from clove (CCSC) and non-clove (NCSC) cigarettes, for 48 h. Using qPCR, we found that mRNA expression of adhesion-associated genes (ALS3 and HWP1) was impaired by precoating C. albicans yeast cells with the aptamer. Conversely, the gene transcription was upregulated when aptamer-uncoated yeast was pre-treated with either CSC. In addition, by analysing the result of MTT ([3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay, we found that the presence of added CCSC or NCSC in growth medium for 48 h was significantly enhanced C. albicans biofilm development. However, the presence of precoated aptamer was significantly impaired biofilm development accelerated by the NCSC. The inhibitory effect of the Ca-apt1 was not dependent on the precoated aptamer (1 and 10%). Interestingly, we noted that the enhancer effect of treated CCSC was no longer effective when the yeast had been precoated with 10% aptamer tested. Additionally, light microscopy analysis revealed that precoating aptamer alleviates morphological changes of C. albicans (from yeast to hypha formation) that are enhanced by adding CCSC or NCSC in the growth medium. In conclusion, these results suggest that administration on Ca-ap1 exhibits a significant protective effect on CSC-induced biofilm formation by C. albicans.
PhD students in life sciences can benefit from team cohesion
Authors: Vida Zsófia Viktória , Járay István Péter , Lengyel Balázs 
Published: July 2021

Background: Scientific progress during doctoral studies is a combination of individual effort and teamwork. A recently growing body of interdisciplinary literature has investigated the determinants of early career success in academia, in which learning from supervisors and co-authors play a great role. Yet, it is less understood how collaboration patterns of the research team, in which the doctoral student participates, influences the future career of students. Here we take a social network analysis approach to investigate this and define the research team as the co-authorship network of the student. Methods: We use the Hungarian Scientific Bibliography Database, which includes all publications of PhD students who defended theses from the year 1993. The data also include thesis information, and the publications of co-authors of students. Using this data, we quantify cohesion in the ego-network of PhD students, the impact measured by citations received, and productivity measured by number of publications. We run multivariate linear regressions to measure the relation of network cohesion, and publication outputs during doctoral years with future impact. Results: We find that those students in life sciences, but not in other fields, who have a cohesive co-author network during studies and two years after defence receive significantly more citations in eight years. We find that the number of papers published during PhD years and closely after the defence correlates negatively while the impact of these papers correlates positively with future success of students in all fields. Conclusions: These results highlight that research teams are effective learning environments for PhD students where collaborations create a tightly knit knowledge network.
Funders’ responsibility to ensure value in research: a self-audit by the Health Research Board Ireland
Authors: Cody Anne , Hiney Maura , Clarke Patricia , O'Driscoll Mairead 
Published: July 2021

As a public funder of health research, the Health Research Board (HRB) Ireland has an obligation to manage its funds well and to maximise the value of the research that it funds. Ways in which research funding can be wasted have been examined by researchers over the years, and a seminal series on research waste was published in the Lancet in 2014. The series systematically analysed every step of the funding lifecycle in five major stages and made recommendations to various actors including research funders. Prompted by its participation in the Ensuring Value in Research Funders’ Forum, between June and October 2019 the HRB undertook a self-audit against the 17 recommendations identified in the Lancet series. Key HRB staff collated relevant policies and practices regarding each recommendation and sub-recommendation and assessed the HRB’s performance under each heading. The self-assessment reflects the state of HRB policies and practices in October 2019. Of the 17 recommendations, five were found to be areas of strength and six were found to be areas of partial strength. Areas of strength reflect work over many years such as support for evidence synthesis, strong processes around award selection, driving research integrity and open data including an HRB-funded open publishing platform. Four recommendations were found to be areas for growth. These mostly revolve around real time reporting of study protocols and of ongoing funded research outside of clinical trials. Work is progressing to address some of these areas. Two were found not to apply to the HRB.