Miracle-dz/UniFAR-FTUs huggingface dataset:
Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKI

Key Points The fundamental science behind the genetic associations of Shroom3 with CKD is a knowledge gap in molecular nephrology. Shroom3 regulates actomyosin dynamics in kidney tubular epithelium after AKI. This study supports that Shroom3 is a molecular player in tubular repair and provides insight into the genetic associations of Shroom3 and CKD. Visual Abstract Background Ischemia-induced AKI resulting in tubular damage can often progress to CKD and is a common cause of nephrology consultation. After renal tubular epithelial damage, molecular and cellular mechanisms are activated to repair and regenerate the damaged epithelium. If these mechanisms are impaired, AKI can progress to CKD. Even in patients whose kidney function returns to normal baseline are more likely to develop CKD. Genome-wide association studies have provided robust evidence that genetic variants in Shroom3, which encodes an actin-associated protein, are associated with CKD and poor outcomes in transplanted kidneys. Here, we sought to further understand the associations of Shroom3 in CKD. Methods Kidney ischemia was induced in wild-type (WT) and Shroom3 heterozygous null mice (Shroom3Gt/+) and the mechanisms of cellular recovery and repair were examined. Results A 28-minute bilateral ischemia in Shroom3Gt/+ mice resulted in 100% mortality within 24 hours. After 22-minute ischemic injury, Shroom3Gt/+ mice had a 16% increased mortality, worsened kidney function, and significantly worse histopathology, apoptosis, proliferation, inflammation, and fibrosis after injury. The cortical tubular damage in Shroom3Gt/+ was associated with disrupted epithelial redifferentiation, disrupted Rho-kinase/myosin signaling, and disorganized apical F-actin. Analysis of MDCK cells showed the levels of Shroom3 are directly correlated to apical organization of actin and actomyosin regulators. Conclusion These findings establish that Shroom3 is required for epithelial repair and redifferentiation through the organization of actomyosin regulators, and could explain why genetic variants in Shroom3 are associated with CKD and allograft rejection.
Implementing A Common First Year Engineering Program At Michigan Tech

In the fall of 2000, Michigan Tech made a calendar conversion from quarters to semesters and, in conjunction with this, simultaneously overhauled the engineering curricula. One of the changes that we adopted was the development of a common ﬁrst year engineering program. Prior to the calendar conversion, each academic department in the College of Engineering established its own curriculum for the entire four-year degree program. During the course of the curricular revamp-ing, we also received funding from the NSF under the Action Agenda program with a portion of the grant dedicated to the implementation of the common ﬁrst year engineering program. In designing our ﬁrst year program, we “borrowed” ideas from several engineering schools, primarily those universities involved in the various NSF coalitions. This paper describes the procedure we followed to implement this sweeping curricular change and highlights the features that we incorporated into our ﬁrst-year engineering program. Preliminary feedback and assessment from the ﬁrst-year program as well as “lessons learned” will also be presented in the paper.
Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer

Purpose This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. Methods Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon’s decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. Results Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. Conclusion PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.
Game Effectiveness of Power Ville in Promoting Science and Engineering Design

This paper presents a virtual reality (VR) game, Power Ville , which aims to infuse cyberinfrastructure (CI) learning experiences into the pre-engineering classrooms and to promote science and engineering design. The design and implementation of the game are described in detail with the focus on the CI features, metacognitive strategies, context-oriented approaches as well as their seamless integration into core game play
Trajectories of Handgun Carrying in Rural Communities From Early Adolescence to Young Adulthood

Key Points Question What are the patterns, frequency, and duration of handgun carrying among youths growing up in rural areas? Findings This cohort study of 2002 rural students found 6 distinct trajectories of handgun carrying, with many youths initiating handgun carrying at least as early as 12 years of age, and more than 20% of some groups carrying a handgun 40 or more times in the past 12 months. Meaning This study suggests that prevention programs to reduce the risk of firearm-related harm should be delivered early in the elementary school period.
Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, in silico study, and exploratory clinical appraisal

Abstract The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij® as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment. TNs were evaluated with regard to entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Further explorations were conducted on the optimum formulation (F7). F7 showed spherical appearance with EE%, PS, PDI, and ZP of 100.00 ± 1.10%, 358.60 ± 10.76 nm, 0.51 ± 0.004, and −30.00 ± 0.80 mV, respectively. The in silico study revealed the ability of the FTN–cholesterol complex to maintain favorable interactions throughout the molecular dynamics simulation (MDS) study. Moreover, Trichophyton mentagrophytes growth was inhibited effectively by F7 than by FTN suspension applying 2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. Furthermore, a clinical appraisal on patients with tinea corporis fungal lesions confirmed the superiority of F7 compared to Miconaz® cream in the magnitude of clinical cure of tinea corporis. Thereby, TNs could be considered as promising vesicles for enhancing the antifungal potential of FTN for the topical management of tinea corporis.
“Our Unified Voice to Implement Change and Advance the View of Young Carers and Young Adult Carers.” An Appreciative Evaluation of the Impact of a National Young Carer Health Champions Programme

ABSTRACT A growing evidence base highlights the challenges and support needs of young carers and young adult carers, however research and policy frequently neglect the voice and experience of young people themselves. A team at NHS England developed the Young Carer Health Champions programme to bring together young carers and young adult carers from across England, establishing a network of peer support, sharing of experiences and improving confidence, health literacy and wellbeing. This commissioned independent evaluation aimed to explore the impact of the programme and inform future delivery. Taking a qualitative case study approach, young participants have a central voice, illuminated through the observations of the researcher during residential activities, and data generated during a focus group and telephone and on-line interviews. Findings demonstrate positive impact on the personal development and lifestyles of the Young Carer Health Champions, and their journey from beneficiary to pro-active shaper of services and policy.
Impact of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function After Non–ST-Segment–Elevation Acute Coronary Syndrome

Background: Coronary microvascular dysfunction after acute coronary syndrome is an important predictor of long-term prognosis. Data is lacking on the effects of oral P2Y12-inhibitors on coronary microvascular function in non–ST-segment–elevation acute coronary syndrome. The aim of this study was to compare the acute effects of ticagrelor versus clopidogrel pretreatment on coronary microvascular function in non–ST-segment–elevation acute coronary syndrome patients. Methods: Hospitalized non–ST-segment–elevation acute coronary syndrome patients were randomized (1:1) to ticagrelor or clopidogrel. The index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were obtained using an intracoronary pressure-temperature sensor-tipped wire. Results: In total, 128 patients were randomized between March 2018 and July 2020. Mean age 59.2±11.8 years, 84% were male, mean Global Registry of Acute Coronary Events score was 93.7±24.5. Intracoronary physiological measurements were obtained in 118 patients (60 ticagrelor, 58 clopidogrel). In the infarct-related artery, the ticagrelor group had lower baseline index of microcirculatory resistance (22.0 [13.0–34.9] versus 27.7 [19.3–29.8]; P=0.02) and higher baseline resistive reserve ratio (3.0 [2.3–4.4] versus 2.4 [1.7–3.4]; P=0.01) compared with the clopidogrel group. A total of 88 patients underwent percutaneous coronary intervention (PCI; 45 ticagrelor, 43 clopidogrel). The ticagrelor group had lower post-PCI index of microcirculatory resistance (22.0 [15.0–29.0] versus 27.0 [18.5–47.5]; P=0.02) and higher post-PCI resistive reserve ratio (3.0 [1.8–3.8] versus 1.8 [1.5–3.4]; P=0.006) compared with the clopidogrel group. The coronary flow reserve was not significantly different between the 2 groups at baseline or post-PCI. No between-group differences were seen in any of the indices in the non-infarct-related artery. Conclusions: In non–ST-segment–elevation acute coronary syndrome patients, ticagrelor significantly improved coronary microvascular function before and after PCI compared with clopidogrel. Registration: URL: https://www.anzctr. org.au; Unique identifier: ACTRN12618001610224.
Uterine septum and reproductive outcome. From diagnosis to treatment. How, why, when?

Background Septate uterus is a benign congenital malformation and represents the most common uterine anomaly in women with poor reproductive outcome. Objectives To review the available scientific data concerning the biological context of the intrauterine septum and the association with poor reproductive outcome, the best methods for diagnosis and treatment. Materials and methods From July 2020 to October 2020, we searched for relevant free full text articles in PubMed, written in English, and published from the 1st of January 2000 to 31st of July 2020. Main outcome measures Association of the pathophysiology of septate uterus with poor reproductive outcome, evaluation of the different classification systems, the accuracy of diagnostic methods and the efficacy of the available treatment options. Results 259 articles were screened, and 22 articles were finally included in our study. Many theories regarding the pathophysiology of this congenital anomaly and its’ association with reproductive problems have been proposed along the recent decades. Combination of diagnostic methods should be used to avoid misclassification of this congenital anomaly. Conclusions Lack of uniformity in the different classification systems makes the diagnosis of septate uterus challenging as there is no universally accepted definition. Data regarding the reproductive outcome of women with septate uterus are still limited, thus recommendations regarding optimal treatment of these women are biased. What is new? According to new insights regarding the pathophysiology of the uterine septum, differences in the underlying embryological defects are associated with changes in the histological composition and vascularisation of septa, as well as in clinical significance.
A Novel Zinc Exporter CtpG Enhances Resistance to Zinc Toxicity and Survival in Mycobacterium bovis

Tuberculosis is caused by the bacillus Mycobacterium tuberculosis and is one of the major sources of mortality. M. tuberculosis has developed unique mechanisms to adapt to host environments, including zinc deficiency and toxicity, during infection. However, the molecular mechanism by which mycobacteria promote detoxification of zinc, and the associated signaling pathways remains largely unclear. ABSTRACT Zinc is a microelement essential for the growth of almost all organisms, but it is toxic at high concentrations and represents an antimicrobial strategy for macrophages. Mycobacterium tuberculosis and Mycobacterium bovis are two well-known intracellular pathogens with strong environmental adaptability, including zinc toxicity. However, the signaling pathway and molecular mechanisms on sensing and resistance to zinc toxicity remains unclear in mycobacteria. Here, we first report that P1B-type ATPase CtpG acts as a zinc efflux transporter and characterize a novel CmtR-CtpG-Zn2+ regulatory pathway that enhances mycobacterial resistance to zinc toxicity. We found that zinc upregulates ctpG expression via transcription factor CmtR and stimulates the ATPase activity of CtpG. The APC residues in TM6 is essential for CtpG to export zinc and enhance M. bovis BCG resistance to zinc toxicity. During infection, CtpG inhibits zinc accumulation in the mycobacteria, and aids bacterial survival in THP-1 macrophage and mice with elevated inflammatory responses. Our findings revealed the existence of a novel regulatory pathway on mycobacteria responding to and adapting to host-mediated zinc toxicity. IMPORTANCE Tuberculosis is caused by the bacillus Mycobacterium tuberculosis and is one of the major sources of mortality. M. tuberculosis has developed unique mechanisms to adapt to host environments, including zinc deficiency and toxicity, during infection. However, the molecular mechanism by which mycobacteria promote detoxification of zinc, and the associated signaling pathways remains largely unclear. In this study, we first report that P1B-type ATPase CtpG acts as a zinc efflux transporter and characterize a novel CmtR-CtpG-Zn2+ regulatory pathway that enhances mycobacterial resistance to zinc toxicity in M. bovis. Our findings reveal the existence of a novel excess zinc-triggered signaling circuit, provide new insights into mycobacterial adaptation to the host environment during infection, and might be useful targets for the treatment of tuberculosis.
Reference-Grade Genome and Large Linear Plasmid of Streptomyces rimosus: Pushing the Limits of Nanopore Sequencing

The genomes of Streptomyces species are difficult to assemble due to long repeats, extrachromosomal elements (giant linear plasmids [GLPs]), rearrangements, and high GC content. To improve the quality of the S. rimosus ATCC 10970 genome, producer of oxytetracycline, we validated the assembly of GLPs by applying a new approach to combine pulsed-field gel electrophoresis separation and GLP isolation and sequenced the isolated GLP with Oxford Nanopore technology. ABSTRACT Streptomyces rimosus ATCC 10970 is the parental strain of industrial strains used for the commercial production of the important antibiotic oxytetracycline. As an actinobacterium with a large linear chromosome containing numerous long repeat regions, high GC content, and a single giant linear plasmid (GLP), these genomes are challenging to assemble. Here, we apply a hybrid sequencing approach relying on the combination of short- and long-read next-generation sequencing platforms and whole-genome restriction analysis by using pulsed-field gel electrophoresis (PFGE) to produce a high-quality reference genome for this biotechnologically important bacterium. By using PFGE to separate and isolate plasmid DNA from chromosomal DNA, we successfully sequenced the GLP using Nanopore data alone. Using this approach, we compared the sequence of GLP in the parent strain ATCC 10970 with those found in two semi-industrial progenitor strains, R6-500 and M4018. Sequencing of the GLP of these three S. rimosus strains shed light on several rearrangements accompanied by transposase genes, suggesting that transposases play an important role in plasmid and genome plasticity in S. rimosus. The polished annotation of secondary metabolite biosynthetic pathways compared to metabolite analysis in the ATCC 10970 strain also refined our knowledge of the secondary metabolite arsenal of these strains. The proposed methodology is highly applicable to a variety of sequencing projects, as evidenced by the reliable assemblies obtained. IMPORTANCE The genomes of Streptomyces species are difficult to assemble due to long repeats, extrachromosomal elements (giant linear plasmids [GLPs]), rearrangements, and high GC content. To improve the quality of the S. rimosus ATCC 10970 genome, producer of oxytetracycline, we validated the assembly of GLPs by applying a new approach to combine pulsed-field gel electrophoresis separation and GLP isolation and sequenced the isolated GLP with Oxford Nanopore technology. By examining the sequenced plasmids of ATCC 10970 and two industrial progenitor strains, R6-500 and M4018, we identified large GLP rearrangements. Analysis of the assembled plasmid sequences shed light on the role of transposases in genome plasticity of this species. The new methodological approach developed for Nanopore sequencing is highly applicable to a variety of sequencing projects. In addition, we present the annotated reference genome sequence of ATCC 10970 with a detailed analysis of the biosynthetic gene clusters.
Developing a pneumonia diagnosis ontology from multiple knowledge sources

Background: Pneumonia is difficult to differentiate from other pulmonary diseases because it shares many symptoms with these diseases. Diagnosing pneumonia in clinical practice would benefit from having access to a codified representation of clinical knowledge. An ontology represents a well-established paradigm for such codification. Objectives: The goal of this research is to create Pneumonia Diagnosis Ontology (PNADO) that brings together the medical knowledge dispersed among multiple medical knowledge sources. Material and Methods: We used several clinical practice guidelines (CPGs) describing the pneumonia diagnostic process as a starting point in developing PNADO. Preliminary version of PNADO was subsequently expanded to cover a broader range of the concepts by reusing ontologies from Open Biological and Biomedical Ontology (OBO) Foundry and BioPortal. PNADO was evaluated by examining relevant concepts from the pneumonia-specific systematic reviews, using patient data from the MIMIC-III clinical dataset, and by clinical domain experts. Results: PNADO is a comprehensive ontology and has a rich set of classes and properties that cover different types of pneumonia, pathogens, symptoms, clinical signs, laboratory tests and imaging, clinical findings, complications, and diagnoses. Conclusion: PNADO unifies pneumonia diagnostic concepts from multiple knowledge sources. It is available in the BioPortal repository.
The legacy of ZikaPLAN: a transnational research consortium addressing Zika

ABSTRACT Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission’s flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.
High-Quality Draft Genome Sequence of Kibdelosporangium philippinense, Generated by Hybrid Assembly of Short and Long Sequencing Reads

The glycopeptide antibiotic-producing soil actinobacterium Kibdelosporangium philippinense A80407 (=ATCC 49844) was sequenced using Illumina and Nanopore sequencing methodologies, and a hybrid genome assembly was generated for this type strain, with a total predicted genome length of 12,054,556 bp, 10,953 protein-coding sequences, 79 RNAs, 298 pseudogenes, and a G+C content of 65.13%. ABSTRACT The glycopeptide antibiotic-producing soil actinobacterium Kibdelosporangium philippinense A80407 (=ATCC 49844) was sequenced using Illumina and Nanopore sequencing methodologies, and a hybrid genome assembly was generated for this type strain, with a total predicted genome length of 12,054,556 bp, 10,953 protein-coding sequences, 79 RNAs, 298 pseudogenes, and a G+C content of 65.13%.