Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute exposure of mice to hydrochloric acid leads to the development of chronic lung injury and pulmonary fibrosis

Abstract Objective: Accidental exposure to hydrochloric acid (HCl) is associated with acute lung injury in humans, development of long-term chronic airway obstruction, and fibrosis. However, the mechanisms responsible for the progression to pulmonary fibrosis remain unclear. We utilized a mouse model of progressive lung injury from a single exposure to HCl to investigate the effects of HCl on the lower respiratory tract. Materials and methods: HCl (0.05–0.3 N) or saline was injected intratracheally into male C57Bl/6J mice. At 1, 4, 10 and 30 days post instillation, bronchoalveolar lavage fluid (BALF) and lung tissues were collected and examined for multiple outcomes. Results and discussion: We observed an early inflammatory response and a late mild inflammation present even at 30 d post HCl exposure. Mice treated with HCl exhibited higher total leukocyte and protein levels in the BALF compared to the vehicle group. This was characterized by increased number of neutrophils, monocytes, and lymphocytes as well as pro-inflammatory cytokines during the first 4 d of injury. The late inflammatory response exhibited a predominant presence of mononuclear cells, increased permeability to protein, and higher levels of the pro-fibrotic mediator TGFβ. Pro-fibrotic protein biomarkers, phosphorylated ERK, and HSP90, were also overexpressed at 10 and 30 d following HCl exposure. In vivo lung function measurements demonstrated lung dysfunction and chronic lung injury associated with increased lung hydroxyproline content and increased expression of extracellular matrix (ECM) proteins. The acute inflammation and severity of fibrosis increased in HCl-concentration dependent manner. Conclusions: Our findings suggest that the initial inflammatory response and pro-fibrotic biomarker upregulation may be linked to the progression of pulmonary fibrosis and airway dysfunction and may represent valuable therapeutic targets.
Joint impact of dementia and frailty on healthcare utilisation and outcomes: a retrospective cohort study of long-stay home care recipients

Objectives To examine the associations between dementia and 1-year health outcomes (urgent hospitalisation, long-term care (LTC) admission, mortality) among long-stay home care recipients and the extent to which these associations vary by clients’ frailty level. Design A retrospective cohort study using linked clinical and health administrative databases. Setting Home care in Ontario, Canada. Participants Long-stay (≥60 days) care clients (n=153 125) aged ≥50 years assessed between April 2014 and March 2015. Main outcome measures Dementia was ascertained with a validated administrative data algorithm and frailty with a 66-item frailty index (FI) based on a previously validated FI derived from the clinical assessment. We examined associations between dementia, FI and their interactions, with 1-year outcomes using multivariable Fine-Gray competing risk (urgent hospitalisation and LTC admission) and Cox proportional hazards (mortality) models. Results Clients with dementia (vs without) were older (mean±SD, 83.3±7.9 vs 78.9±11.3 years, p<0.001) and more likely to be frail (30.3% vs 24.2%, p<0.001). In models adjusted for FI (as a continuous variable) and other confounders, clients with dementia showed a lower incidence of urgent hospitalisation (adjusted subdistribution HR (sHR)=0.84, 95% CI: 0.83 to 0.86) and mortality rate (adjusted HR=0.87, 95% CI: 0.84 to 0.89) but higher incidence of LTC admission (adjusted sHR=2.60, 95% CI: 2.53 to 2.67). The impact of dementia on LTC admission and mortality was significantly modified by clients’ FI (p<0.001 interaction terms), showing a lower magnitude of association (ie, attenuated positive (for LTC admission) and negative (for mortality) association) with increasing frailty. Conclusions The strength of associations between dementia and LTC admission and death (but not urgent hospitalisation) among home care recipients was significantly modified by their frailty status. Understanding the public health impact of dementia requires consideration of frailty levels among older populations, including those with and without dementia and varying degrees of multimorbidity.
Comparative assessment of long-read error correction software applied to Nanopore RNA-sequencing data

MOTIVATION Nanopore long-read sequencing technology offers promising alternatives to high-throughput short read sequencing, especially in the context of RNA-sequencing. However this technology is currently hindered by high error rates in the output data that affect analyses such as the identification of isoforms, exon boundaries, open reading frames and creation of gene catalogues. Due to the novelty of such data, computational methods are still actively being developed and options for the error correction of Nanopore RNA-sequencing long reads remain limited. RESULTS In this article, we evaluate the extent to which existing long-read DNA error correction methods are capable of correcting cDNA Nanopore reads. We provide an automatic and extensive benchmark tool that not only reports classical error correction metrics but also the effect of correction on gene families, isoform diversity, bias toward the major isoform and splice site detection. We find that long read error correction tools that were originally developed for DNA are also suitable for the correction of Nanopore RNA-sequencing data, especially in terms of increasing base pair accuracy. Yet investigators should be warned that the correction process perturbs gene family sizes and isoform diversity. This work provides guidelines on which (or whether) error correction tools should be used, depending on the application type. BENCHMARKING SOFTWARE https://gitlab.com/leoisl/LR_EC_analyser.
Morphology of the genital organs of the female red‐rumped agouti (Dasyprocta leporina, Linnaeus, 1758) during estrous cycle phases and in advanced pregnancy

The study investigated the gross and microscopic anatomy of the genital organs of 20 agoutis at different stages of the estrous cycle and four in the final trimester of pregnancy. Specimens were euthanized and their reproductive organs were fixed in a 4% paraformaldehyde or 2.5% glutaraldehyde solution and submitted to routine histological techniques for light and scanning electron microscopy. In the ovary, during the proestrus phase, we observed developing follicles and corpus luteum (CL) in regression; during estrus, there were Graafian follicles; during metestrus, there was a hemorrhagic corpus, whereas in diestrus, there was a mature CL. The uterus was partially double because the cervix was cranially septate but caudally, the septum disappeared, forming a single ostium that opened into the vagina. Changes occurred along the estrous cycle in the uterine and vaginal epithelia, that is, an increase in the uterine epithelium height accompanied by an increase of thickness of the vaginal epithelium during the follicular phase and a decrease of thickness of both epithelia during the luteal phase. The endometrial lining was composed of a simple cuboidal epithelium to simple columnar epithelium with basal nuclei. The vaginal mucosa consisted of epithelium that varied from nonkeratinized stratified squamous (luteal phase) to keratinized stratified squamous (follicular phase). The clitoris was external to the vagina. It presented two protruding lateral keratinized spicules and a centralized urethra, with no common parts between the urinary and genital tracts. Anatomical and histological changes were observed mainly in the cervix, vagina and spicules of the clitoris during the EC.
Outcomes of Mini-Open Carpal Tunnel Release in Patients With Unrecordable Preoperative Nerve Conduction Potentials at a Minimum of 5 Years

Background: The aim of this study is to assess the outcomes of carpal tunnel release (CTR) in a cohort of patients with preoperatively unrecordable median nerve sensory and motor potentials in comparison with historical controls at minimum 5-year follow-up. Methods: We retrospectively identified 1297 patients who underwent CTR at a tertiary care referral center from July 2008 to June 2013. After exclusion criteria and review of available preoperative nerve conduction studies, 24 patients who underwent CTR with preoperative unrecordable sensory and motor nerve potentials were identified. Fifteen living, mentally capable patients were contacted by telephone for follow-up. Our primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). Secondary outcome measures included Disabilities of the Arm, Shoulder, and Hand (DASH) score, pain on a 0 to 10 Likert scale, and satisfaction on a 0 to 10 Likert scale. Results: Our response rate was 80% (12 out of 15) of eligible patients. Mean follow-up was 6.9 years in our study (range, 5.4-9.5 years). The mean BCTQ symptom score was 1.4, and the mean BCTQ functional score was 1.8. Mean DASH score was 15.2. On average, patient-reported pain was 0.3 and satisfaction was 8.3. No difference was found in outcomes of CTR in patients with end-stage carpal tunnel syndrome compared with historical means. Conclusions: Patients with end-stage carpal tunnel syndrome do not have worse long-term patient-reported outcomes after CTR compared with the general population. Unrecordable nerve potentials are not a contraindication for CTR.
The effect of supportive care in preventing peri-implant diseases and implant loss: A Systematic review and Meta-analysis.

OBJECTIVE To evaluate the influence of supportive treatment (SPT) during a maintenance period after implant placement on implant survival rate and incidence of peri-implant diseases. MATERIAL AND METHODS A systemic literature search for studies published up to June 2018 was conducted by two independent reviewers using Pubmed/MEDLINE, EMBASE and Cochrane Central databases. Clinical controlled trials (CCT) involved in SPT protocol with more than 1-year follow-up were included. Quantitative meta-analyses were carried out to analyze the risk ratio (RR) of survival rate (SR), the incidence of peri-implantitis and peri-implant mucositis between SPT and non-SPT groups. Any potential confounding factors were investigated using meta-regression. RESULTS Nine CCTs fulfilled the criteria. To evaluate the influence of SPT on SR, peri-implantitis and peri-implant mucositis, 6 of 9, 3 of 9 and 3 of 9 articles were included in further meta-analysis, respectively. SPT group significantly showed higher SR (RR: 1.10; p<0.001), lower prevalence of peri-implantitis (RR: 0.25; p<0.001) and peri-implant mucositis (RR: 0.57; p<0.001) than the non-SPT group. Meta-regression of the selected studies failed to find an association between SR, peri-implantitis and peri-implant mucositis and confounding factors: application of chemical agents and the frequency of SPT. CONCLUSION SPT can potentially improve peri-implant health in terms of SR, peri-implantitis and peri-implant mucositis. Additionally, the correlation in recall interval and adjunctive use of chemical agents during SPT to peri-implant diseases and implant loss could not be found. This article is protected by copyright. All rights reserved.
Sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: a magic potion to reduce heart failure?

It is four decades since the Framingham study revealed the strong association between heart failure and type 2 diabetes mellitus (T2DM), with evidence supporting a bidirectional relationship [1,2]. Initially, research focused on the reduction of the risk of new-onset DM with pharmacological agents used in heart failure, notably candesartan, valsartan, ramipril and enalapril [2]. This changed in 2015 with the results of the EMPA-REG trial, showing for the first time that a glucose-lowering agent, empagliflozin, reduced the relative risk of hospitalization for heart failure (hHF) by 35% [3]. Thus, sodium glucose cotransporter 2 inhibitors (SGLT-2is), initially developed to target hyperglycemia, began to emerge as potential drugs to prevent heart failure in populations with and without DM [4]. Of note, cardiovascular outcome trials (CVOTs) were initiated in 2008 to prove non-inferiority as compared with placebo [5]. This started in response to the association of rosiglitazone with myocardial infarction [6]. Consequently, large CVOTs primarily focused on atherosclerosis, whereas heart failure was considered a secondary outcome.
Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma

In this review, we discuss applications of flow cytometric immunophenotyping (FCI) in the diagnostic evaluation and posttreatment monitoring of B and T lymphoblastic leukemia/lymphoma. We describe practical approaches to FCI at the time of diagnosis, with an emphasis on blast identification, lineage assignment, and distinction of B and T lymphoblastic leukemia/lymphoma from their morphologic and immunophenotypic mimics. We further review flow cytometric assays for the detection of minimal or measurable residual disease (MRD) after treatment, and illustrate both standard approaches, and newer strategies for improving sensitivity and circumventing the loss of immunophenotypic targets after immunotherapy. © 2019 International Clinical Cytometry Society
Exploring two contrasting surface‐active exopolysaccharides from a single strain of Ochrobactrum utilizing different hydrocarbon substrates

During production and characterization of exopolysaccharides (EPS) of Ochrobactrum pseudintermedium C1, it was observed that an experimental change in the basic hydrocarbon type of substrate for bacterial utilization led to elicitation of different surface‐active properties in the EPS produced. In the sugar substrate, it elicited surfactant property, while in oil substrates it elicited emulsifying property, which indicated that the EPS might be different. Consequently, attention was focused on a detailed analysis of this substrate‐specific EPS. Utilizing waste sugar, edible, and mineral oil substrates, EPS produced in each situation was characterized. Besides estimating surface activity and thermostability, each substrate‐specific EPS was analyzed by Fourier‐transform infrared spectroscopy, gas chromatography‐mass spectroscopy, 1H‐nuclear magnetic resonance, and matrix‐assisted laser desorption/ionization—time of flight mass spectroscopy to find any structural difference. The results were significantly contrasting although the similarity in molecular mass suggested a basic similarity in polysaccharide structure. Morphological differences were also evident both macroscopically and microscopically with scanning electron microscopy. As the surface‐active property of EPS was dependent on the substrate utilized, their structural differences might account for it. These diverse surface activities of EPS produced by a single bacterial strain simply by changing the nature of substrate would also augment their bioapplications. Moreover, utilization of waste and easily available substrates should make such applications convenient, ecofriendly, and cost‐worthy.
Extraoral Versus Intraoral Botulinum Toxin Type A Injection for Management of Temporomandibular Joint Disc Displacement With Reduction.

: The present study was conducted to compare between extraoral and intraoral approach for botulinum toxin type A (BTX-A) injection into the lateral pterygoid muscle (LPM) in patients suffering from anterior disc displacement with reduction (ADDWR). Fourteen patients suffering from ADDWR were included in this prospective cohort study. Patients were enrolled randomly into 2 groups according to injection approach; where extraoral used in group I, while intraoral approach used in group II. The LPM was injected with 20 IU BTX-A under electromyography (EMG) guidance. Postoperative evaluation of the patients included: mouth opening assessment, LPM tenderness, temporomandibular joint TMJ (clicking), and tenderness. The LPM insertional EMG activity was assessed. Also, magnetic resonance imaging (MRI) was performed to evaluate disc position. Descriptive and inferential analysis was conducted to compare between groups.There was significant patient's convenience during injection and significant injection time reduction in group II. A slight decrease in mouth opening immediate post-injection followed by significant improvement from 8th weeks post-injection was reported in both approaches. There was a significant improvement in TMJ clicking from 1st-week post-injection with no group difference. The EMG assessment documented LPM hyperactivity pre-injection followed by significantly decreased muscle activity at 8 and 16 weeks post-injection without statistical difference. The MRI showed no change in disc position after injection. CONCLUSION:: The BTX-A injection into LPM is a simple technique that can be used with high success and low complication rate for treatment of ADDWR. The intraoral approach was superior to the extraoral concerning patient convenience and injection duration with no statistical difference regarding other clinical outcomes.
The relation between parental chronic pain, pain‐related attention and interpretation biases in pain‐free adolescents

Children of chronic pain patients run greater risk for developing chronic pain themselves. Exposure to chronic pain of the parent might install cognitive (e.g., pain catastrophizing, interpretation and attentional bias) and affective (e.g., pain anxiety) vulnerability which increase the risk for the development of chronic pain complaints in offspring. This study examines whether pain‐free offspring of parents with chronic pain complaints make more health‐threatening interpretations and display a stronger pain‐related attentional bias compared to the offspring of pain‐free parents. We furthermore examined differences between both groups on pain catastrophizing, pain anxiety and somatic symptoms and explored the relations between parental pain catastrophizing and aforementioned pain vulnerability measures in offspring.
Effects of the strain rate on mechanical properties of tendon structures in knee extensors and plantar flexors in vivo

ABSTRACT The purpose of present study was to investigate site differences in the effects of strain rate on tendon properties between knee extensors and plantar flexors. Elongation of tendon structures (L) in vastus lateralis and medial gastrocnemius muscles was measured by ultrasonography while participants performed ramp and ballistic contractions to their voluntary maximum, followed by ramp and sudden relaxation. The relationship between muscle force (Fm) and L was fit to linear regression, the slope of which was defined as stiffness of tendon structures. Hysteresis of tendon structures was calculated as ratio of area within Fm–L loop to area beneath loading portion of curve. In knee extensors and plantar flexors, L values at all force levels were significantly lower during ballistic than ramp contractions. However, no significant differences were observed in stiffness of tendon structures between two contractions at both measured sites. Hysteresis of tendon structures was significantly higher during ballistic than ramp contractions for knee extensors and plantar flexors. In conclusion, elongation of tendon structures was lower and hysteresis was greater during ballistic than ramp contractions. Furthermore, site differences in the effects of strain rate on tendon properties were not found between knee extensors and plantar flexors.
Targeting the differentiation of gastric cancer cells (KATO-III) downregulates epithelial-mesenchymal and cancer stem cell markers

The aim of the present study was to analyze the acquisition of the differentiated phenotype in the human gastric signet ring cell adenoma cancer KATO-III cell line in vitro. The morphology of KATO-III cells was explored by microcinematography. Different cytokines secreted by both adherent and non-adherent KATO-III cells into medium were observed. The cancer stem cell phenotypes were identified by reverse transcription-quantitative polymerase chain reaction using primers (E-Cad, Slug, Snail, vimentin, NANOG, NESTIN, OCT3/4 and C-X-C motif chemokine receptor 4) or antibodies [cluster of differentiation (CD)90 and CD117] by flow cytometry (FACS). The influence of the induction media for the differentiation of mesenchymal cells was studied through viability and proliferation assays, by evaluating gene expression and the expression of markers via FACS. Cell viability and cell cycle distribution were evaluated following the treatment of KATO-III with acetyl salicylic acid and using the induction media as an inhibitor of epithelial-mesenchymal transition (EMT) and heparanase. A total of 3 phenotypes of KATO-III were observed (adherent, non-adherent and cell cluster), which have internal potential for cell transition into one of the other phenotypes. KATO-III was differentiated into adipocyte-, chondrocyte-, osteocyte- and neurocyte-like cells by the induction media. Identification of the induced cells was conducted using cell dyes. Reduced mRNA expression of EMT-associated molecules, stem cell markers and heparanase was observed with acetyl salicylic acid and induction media. An inhibitory effect of acetyl salicylic acid and the induction media was also noted in regard to cell proliferation. In addition, acetyl salicylic acid induced G0/G1 phase cell cycle arrest in KATO-III cells. In conclusion, the induction of the differentiation of cancer stem cells into non-proliferating cells offers the possibility for novel drug design to overcome the issues associated with metastasis, drug resistance and systemic toxicity with improved therapeutic efficacy.
MAID chemotherapy regimen as a treatment strategy for metastatic malignant ameloblastoma

Abstract Rationale: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. Patients concerns: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). Diagnoses: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. Interventions: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. Outcomes: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. Lessons: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.