Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of programmed death-ligand 1 expression with gene expression and clinicopathological parameters in Indian patients with non-small cell lung cancer

Objectives: The aim of this study is to evaluate the incidence of programmed cell death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) cases and its correlation with gene mutation and clinicopathological parameters. Methods: Samples from NSCLCs patients were studied for PD-L1 expression through immunohistochemistry (IHC) using Rabbit anti-human PDL-1/CD274 Monoclonal Antibody. Genetic mutations were studied using IHC/fluorescence in situ hybridization (FISH) methods (for anaplastic lymphoma kinase [ALK]) or polymerase chain reaction/gene sequencing analysis (for epidermal growth factor receptor [EGFR]). Pearson's correlation coefficient (r) was used for correlation analysis. PD-L1 expression was analyzed for association with clinicopathological features. Results: Of the 101 NSCLC cases, PD-L1 expression was observed in 33.66% (34/101) cases; tumor proportion score of <50%: 67.65% (23/34) and ≥50%: 32.35% (11/34) cases. PD-L1 positivity was seen in; males: 35.5%, females: 28%, smokers: 37.7%, cases with brain metastasis: 20%, cases with pleural effusion: 20.8%, and histopathological evaluation (well-differentiated: 21.42%, moderately-differentiated: 13.79%, poorly-differentiated: 36.11%, and adenosquamous disease: 40.9%). Genetic mutation studies revealed PD-L1 positivity in 18.1% cases with EGFR mutation, 50% of ALK-IHC positive cases, and 33.3% ALK-FISH positive cases. No or very weak correlation (r < 0.3) in PD-L1 expression with gene mutations or clinicopathological parameters was observed. Conclusions: The study demonstrated PD-L1 expression in ~ 1/3rd cases of NSCLC patients. No or very weak correlation was observed for PD-L1 expression with genetic mutations and other parameters studied. The presence of gene mutations in PD-L1 expressed samples suggests further investigation on PD-L1 inhibitors in such patients for decisive treatments.
Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker.

To define cellular mechanisms underlying kidney function and failure, the Kidney Precision Medicine Project (KPMP) analyzes biopsy tissue in a multi-center research network to build cell-level process maps of kidney. This study aimed to establish a single cell RNA sequencing strategy to use cell level transcriptional profiles from kidney biopsies in KPMP to define molecular subtypes in glomerular diseases.Using multiple sources of adult human kidney reference tissue samples, 22,268 single cell profiles passed KPMP quality control parameters. Unbiased clustering resulted in 31 distinct cell clusters that were linked to kidney and immune cell types using specific cell markers. Focusing on endothelial cell phenotypes, in silico and in situ hybridization methods assigned three discrete endothelial cell clusters to distinct renal vascular beds. Transcripts defining glomerular endothelial cell (GEC) were evaluated in biopsies from patients with ten different glomerular diseases in the NEPTUNE and ERCB cohort studies. Highest GEC scores were observed in patients with focal segmental glomerulosclerosis (FSGS). Molecular endothelial signatures suggested two distinct FSGS patient subgroups with alpha-2 macroglobulin (A2M) as a key downstream mediator of the endothelial cell phenotype. Finally, glomerular A2M transcript levels associated with lower proteinuria remission rates, linking endothelial function with long-term outcome in FSGS.
Clinicopathological characteristics and treatment outcome in small cell lung cancer: A single institutional experience from India

Background and Objectives: Small cell lung cancer (SCLC) constitutes 14%–20% of all lung cancers. Clinical data on SCLC are scarce in literature. To report clinical features and treatment outcome of SCLC treated at our center. Materials and Methods: This is a single institutional data review of SCLC patients treated between June 2011 and December 2018. Patients were staged as either localized or extensive disease after appropriate staging work-up. Patients with localized disease were treated with concurrent chemoradiation with platinum-based chemotherapy. Those with extensive disease were treated with platinum based palliative chemotherapy. Clinicopathological characteristics, treatment details, and outcome were recorded in this study. Patients who received at least one cycle of chemotherapy were included for survival analysis as intent-to-treat analysis. Results: A total of 181 were patients registered with a median age of 62 years (range: 35–86 years) and male: female ratio of 166:15. Eighty-seven percent (n = 157) of patients had smoking history and 15% (n = 28) of patients had symptom of superior vena cava obstruction at baseline. Twenty-seven (15%) patients had localized disease at presentation. One hundred and twenty (66%) patients took systemic chemotherapy. Chemotherapy regimen was carboplatin only in 9 (7%), etoposide-carboplatin in 54 (45%), and cisplatin-etoposide in 57 (48%). Patients received median cycle number of 6 (range: 1–6). Of the evaluable 87 (73%) patients, initial response was complete response in 4, partial response in 57, stable disease in 20, and progressive disease in 6. Twenty patients received second-line chemotherapy at time of disease progression. After a median follow-up of 8.8 months (range: 0.3–46.1), median progression-free survival (PFS) of the whole population was 9.3 months. Conclusions: Small cell carcinoma in our series had a high incidence of advanced stage (85%) and 13% of patients were nonsmoker. Only 66% of patients received palliative chemotherapy and achieved high disease control rate (>75%) in the evaluable patients with median PFS of 9.3 months.
Nlrp3 Inflammasome Inhibitor MCC950 Ameliorates Obliterative Bronchiolitis by Inhibiting Th1/Th17 Response and Promoting Treg Response After Orthotopic Tracheal Transplantation in Mice

Supplemental Digital Content is available in the text. Background. Obliterative bronchiolitis (OB) remains the major complication limiting long-term survival of patients after lung transplantation. We aimed to explore the effects of the selective NACHT, LRR, and PYD domains-containing protein 3 (Nlrp3) inflammasome inhibitor MCC950 on the pathogenesis of OB. Methods. Mouse orthotopic tracheal transplants were performed to mimic OB. MCC950 (50 mg/kg) or saline was intraperitoneally injected daily. The luminal occlusion rate and collagen deposition were evaluated by hematoxylin and eosin and Masson’s trichrome staining, respectively. Infiltration of CD4+, CD8+ T cells, and neutrophils was detected with immunohistochemical staining. The frequencies of T helper 1 cell (Th1), T helper 17 cell (Th17), and regulatory T cells (Treg) were measured by flow cytometry. Cytokine levels were measured by ELISA kits. Results. MCC950 treatment significantly inhibited Nlrp3 inflammasome activation after allogeneic tracheal transplant and markedly decreased the luminal occlusion rate and collagen deposition in the allograft. The numbers of infiltrating CD4+, CD8+ T cells, and neutrophils in the allograft were also significantly reduced by MCC950 treatment. MCC950 dramatically decreased the frequencies of Th1/Th17 cells and the levels of interferon gamma/interleukin (IL)-17A and increased the Treg cell frequencies and IL-10 level; however, these effects were abolished by the addition of IL-1β and IL-18 both in vitro and in vivo. OB was also rescued by the addition of IL-1β and/or IL-18. Conclusions. Blocking Nlrp3 inflammasome activation with MCC950 ameliorates OB lesions. The mechanistic analysis showed that MCC950 regulated the balance of Th1/Th17 and Treg cells and that this process is partially mediated by inhibition of IL-1β and IL-18. Therefore, targeting the Nlrp3 inflammasome is a promising strategy for controlling OB after lung transplantation.
Memory CD4+ T Cells in Immunity and Autoimmune Diseases

CD4+ T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4+ Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4+ T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4+ tissue-resident memory T cells and of CD4+ memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4+ T cell-mediated autoimmune diseases.
Rigid bronchoscopic interventions for central airway obstruction – An observational study

Background: Central airway obstruction (CAO) is a significant cause of morbidity and mortality in patients with thoracic malignancies. In this prospective study, we describe the role of rigid bronchoscopy (RB) in the multimodality management of CAO. Methods: Prospective description of different rigid bronchoscopic techniques used for CAO between July 2016 and July 2019. Results: A total of 152 procedures (124 therapeutic/palliative and 28 diagnostics) in 111 adults and 10 pediatric patients were performed. The mean age in 111 adults (66 males) and 10 pediatric (5 males) patients were 45.4 ± 15.8 (range 16–80) and 5.4 ± 3.6 (range 1–10) years, respectively. Palliation of the airway obstruction (48.8%) and establishment of diagnosis (23.2%) were the main indications of RB in our study. Mechanical debulking in 53 (57%) and airway dilatation in 40 (43%) patients were the most utilized interventions during the palliative or therapeutic RB. There was a significant decrease in mean (modified Medical Research Council) dyspnea scale from 3.9 ± 1.0 to 1.42 ± 0.63 and increase in mean Visual Analogue Scale from 2.06 ± 0.74 to 8.7 ± 0.54 after the procedure (P < 0.0001). Additional therapy was undertaken in 38 (31.4%) of 121 patients, and surgical excision was the primary form of definitive treatment in 17 patients Moderate bleeding was encountered in 13.3% of the procedures mainly in the diagnostic RB. The mean procedure duration was 28.4 (range, 11–49) min and 13.2 (7–22) min in the adults and pediatric patients, respectively. A total of 31 patients succumbed to the illness due to the progressive nature of their disease. Conclusions: An individualized approach to interventional procedures is safe and effective way to achieve and maintain palliation of CAO. RB with multimodality treatment achieves the goal in majority of the patients.
How Well Are Radiology Residents Prepared for Practice After Training? A Survey of French-Speaking Quebec Recent Graduates and Department Chiefs

Objective: Radiology residents must fulfill a standardized curriculum to complete residency and pass a certification exam before they are granted a licence to practice. We sought to evaluate how well residency prepares trainees for practice as perceived by recent graduates and their department chiefs. Subjects and Methods: Radiologists who graduated from the 4 Quebec radiology residency programs between 2005 and 2016 (n = 237) and Quebec radiology department chiefs (n = 98) were anonymously surveyed. Two electronic surveys were created, for recent graduates (74 questions) and for department chiefs (11 questions), with multiple-choice questions and open questions covering all fields of radiology. Surveys were administered between April and June 2016 using the Association des radiologistes du Québec database. Results: Response rate was 75 (31.6%) of 237 from recent graduates and 96% rated their training as excellent or good. Satisfaction with training in computed tomography and magnetic resonance imaging was high, with musculoskeletal (MSK) imaging, particularly MSK ultrasound (US), as well as pediatric, cardiac, and vascular imaging needing more training. Thirty-nine (39.8%) of 98 department chiefs answered the survey and highlighted weaknesses in the interpretation of conventional radiography, obstetrical US, and invasive procedures, as well as limited leadership and administrative skills. Recent graduates and department chiefs both reported difficulties in the ability to interpret daily volume of examinations as scheduled and invasive procedure competency. Conclusion: This survey highlights areas of the radiology curriculum which may benefit from more emphasis during training. Adjustments in the residency program would ensure graduates are successful both in their certification exams and clinical practice.
Diagnosis of autism in adulthood: A scoping review

More adults are undergoing autism assessment due to recent changes in awareness, diagnostic criteria and professional practices. This scoping review aimed to summarise research on autism diagnosis in adulthood and identify any gaps for future study. The authors searched for studies involving first-time assessment and diagnosis of autism in adults, which identified 82 studies from 13 countries using various methodologies. Six themes of (1) prevalence, (2) diagnostic pathways and processes, (3) gender, (4) psychosocial characteristics, (5) co-occurring conditions and (6) experiences of diagnosis were identified across the studies. Findings suggest that receiving an autism diagnosis has a significant emotional impact on adults, but accessibility and processes are inconsistent, and formal support services are lacking. More research is needed on autism diagnosis in adults with intellectual disability, consequences of the timing of diagnosis, and support after diagnosis. Lay abstract More adults are getting assessed for possible autism. Here, we give an overview on what is already known about autism diagnosis in adulthood and find areas that need more research. We divided results from the studies we found into six topics of (1) rates of autism in different groups; (2) the process of getting an autism diagnosis in adulthood; (3) gender; (4) personality traits, abilities and behaviours of diagnosed adults; (5) mental and physical health conditions that occur together with autism; and (6) how adults think and feel about being assessed and diagnosed. We found that adults often have strong emotions after being diagnosed, the process of getting a diagnosis can be unclear and different for everyone, and not many support services are available for adults. More research on diagnosing adults with intellectual disability, differences between early and late-diagnosed adults, and support after diagnosis would be useful.
Low Doses of Methylmercury Induce the Proliferation of Thyroid Cells In Vitro Through Modulation of ERK Pathway

Exposure to environmental endocrine disruptors has been associated with an increased frequency of thyroid pathology. In this study, we evaluated the effects of various concentrations of methylmercury (MeHg) on immortalized, non-tumorigenic thyroid cells (Nthy-ori-3-1). Exposure to MeHg at 2.5 and 5 µM for 24 h caused a reduction in cell viability with a decrease of the cell population in sub-G0 phase, as detected by MTT and flow cytometry. Conversely, MeHg at the lower concentration of 0.1 µM increased the cell viability with a rise of G2/M phase. An immunoblot analysis showed higher expression levels of phospho-ERK and not of phospho-Akt. Further enhancement of the cell growth rate was observed after a prolonged exposure of the cells up to 18 days to MeHg 0.1 µM. The present findings demonstrate the toxicity of high concentrations of MeHg on thyroid cells, while showing that treatment with lower doses of Hg, as may occur after prolonged exposure to this environmental contaminant, exerts a promoting effect on thyroid cell proliferation, by acting on the ERK-mediated pro-oncogenic signal transduction pathway.
Aggregation of Lipid A variants: A hybrid particle-field model.

Lipid A is one the three components of bacterial lipopolysaccharides constituting the outer membrane of Gram-negative bacteria, and is recognized to have an important biological role in the inflammatory response of the immune system. Its biological activity is modulated by the number of acyl-chains that are present in the lipid and by the dielectric medium, i.e., the type of counter-ions, through electrostatic interactions. In this paper, we report a coarse-grained model of poly-acyl Lipid A based on the hybrid particle field molecular dynamics approach (hPF-MD). In particular, we investigate the stability of Lipid A bilayers for two different hexa- and tetra-acylation states. Comparing particle density profiles along bilayer cross-sections, we find good agreement between our hPF-MD and reference all-atom simulation results for both bilayers. hPF-MD models of constituted bilayers composed by hexa-acylated Lipid A in water are stable within the simulation time. We further validate our model by verifying that the phase behavior of Lipid A/counterion/water mixtures is correctly reproduced. In particular, hPF-MD simulations predict the correct self-assembly of different lamellar and micellar phases from an initially random distribution of Lipid A molecules with counterions in water. Finally, it is possible to observe the spontaneous formation and stability of Lipid A vesicles by fusion of micellar aggregates.
Serum Fetuin-A and Insulin Levels in Classic Congenital Adrenal Hyperplasia

Abstract Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R2=42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients.
Physical Demands of Elite Women's Ultimate Frisbee Between Halves and Across Matches in an International Tournament

Abstract Palmer, JA, Landers, G, Buttfield, A, and Polglaze, T. Physical demands of elite women's Ultimate Frisbee between halves and across matches in an international tournament. J Strength Cond Res 36(3): 838–844, 2022—To quantify the physical match demands of elite women's Ultimate Frisbee across a tournament, elite female Ultimate players (N = 9) from the Australian Under 24 Women's team wore global positioning system units in all 12 matches of the 2018 Under 24 World Championship competition. Temporal, displacement, and energetic parameters were obtained. Distribution of activity above and below a generic speed threshold (12.42 km·h−1) and its equivalent metabolic power value (16.02 W·kg−1) were determined. Players spent 12:44 ± 6:41 min:s on the field, covered 1,559 ± 741 m and expended 8.95 ± 4.21 kJ·kg−1 during a match. The mean stint duration was 2:00 ± 0:48 min:s, mean bench duration was 13:25 ± 7:05 min:s, and work-to-recovery ratio was 0.22 ± 0.11. Players performed 57 ± 27 high-speed runs per match and 45 ± 20 high-accelerations. Mean match speed was 127 ± 18 m·min−1, mean metabolic power was 12.2 ± 1.7 W·kg−1, and mean intermittency index was 1.24 ± 0.04. No differences were found between halves for any parameters. Compared with the first 4 matches, the last 4 matches were shorter and more intense (p < 0.05). At the international level, Ultimate is an intense and highly intermittent sport, characterized by brief playing stints interspersed with long periods of recovery, which allow playing intensity to be maintained throughout a match and elevated in the latter stages of a tournament. The information gained from this research can be used to guide the creation of Ultimate-specific conditioning programs for elite female players.
Radiprodil, a NR2B negative allosteric modulator, from bench to bedside in infantile spasm syndrome

Infantile spasm syndrome (ISS) is an epileptic encephalopathy without established treatment after the failure to standard of care based on steroids and vigabatrin. Converging lines of evidence indicating a role of NR2B subunits of the N‐methyl‐D‐aspartate (NMDA) receptor on the onset of spams in ISS patients, prompted us to test radiprodil, a negative allosteric NR2B modulator in preclinical seizure models and in infants with ISS.