Miracle-dz/UniFAR-FTUs huggingface dataset:
Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in muscle-invasive bladder cancer

ABSTRACT Immunotherapy that block PD-1–PD-L1 pathway can induce durable tumor control and result in the long-term survival of patients with advanced bladder cancers. However, these responses only occur in a subset of patients. We study gene expression profiles in 1763 muscle-invasive bladder cancers (MIBCs) and 11,835 solid tumors from TCGA. We establish an immune-based classification on the basis of the composition of the tumor microenvironment and identify six distinct phenotypes. The class F was characterized by a strong tertiary lymphoid structures (TLSs) related gene expression signature. Pan-cancer gene expression analysis of tertiary lymphoid structure markers in 11,835 solid tumors from TCGA unveiled the heterogeneity of TLSs abundance both within and between human cancer types. The class F group demonstrated improved survival and a high response rate to PD1 blockade. This work confirms the immune subtypes in patients with MIBC, and unravels the potential of TLS signatures to guide clinical decision-making and treatments.
Sidewall spacer optimization for steep switching junctionless transistors

In this work, we analyze the impact of a high permittivity (high-κ) sidewall spacer and gate dielectric on the occurrence of sub-60 mV/decade subthreshold swing (S-swing) in symmetrical junctionless (JL) double gate (DG) transistors. It is shown that steep S-swing values (≤10 mV/decade) can be achieved in JL devices with a combination of a high permittivity (high-κ) gate dielectric and a narrow low permittivity (low-κ) sidewall spacer. Implementation of a wider high-κ spacer will diminish the degree of impact ionization by the influence of the fringing component of the gate electric field, and will not be useful for steep off-to-on current transition. A wider spacer with low-κ and a narrow spacer with high-κ permittivity will be useful to limit the latching effect that can occur at lower temperatures (250 K). For high temperature operation, the decrease in the impact ionization rate can be compensated by designing a JL transistor with a thicker silicon film. The work demonstrates opportunities to enhance impact ionization at sub bandgap voltages, and proposes optimal guidelines for selecting a sidewall spacer to facilitate steep switching in JL transistors.
Complete chloroplast genome sequence of Convolvulus arvensis

Abstract The complete chloroplast genome of Convolvulus arvensis was reconstructed by reference-based assembly using Illumina paired-end data. The assembled plastome is 153,234 base pairs (bp) in length, including a pair of inverted repeat regions (IRs) of 22,662 bp each, a large single-copy region (LSC) of 89,059 bp and a small single-copy region (SSC) of 19,651 bp. A total of 115 genes were predicted from the chloroplast genome, including 74 protein coding genes, 37 tRNA genes and 4 rRNA genes. The overall GC content of C. arvensis chloroplast genome was 37.7%. Phylogenetic analysis with several reported chloroplast genomes showed that C. arvensis is closely clustered with Operculina macrocarpa. The complete chloroplast genome of C. arvensis provides new insight into the evolutionary and genomic studies of Convolvulaceae.
Accuracy of Microcomputed Tomography in Detecting Dentinal Cracks: A Correlative Study with Scanning Electron and Operative Microscopy

The aim of the study was to evaluate the accuracy of microcomputed tomography (mCT) to detect dentinal cracks when compared with scanning electron microscopy (SEM) and operating microscopy (OM). Different conditions of pixel size (10 or 17 μm), sample moisture (dry/moist), and transillumination (with/without) were evaluated. Additionally, the influence of the dentinal defect width on its detection was analyzed. The root canals of human mandibular incisors were prepared with the Reciproc R40 instrument (VDW, Munich, Germany). The roots were sectioned 5 and 10 mm from the apex, and mCT scans of middle and apical segments were performed at two pixel sizes: 10 μm and 17 μm, under dry and moist conditions (groups: 10dry, 10moist, 17dry, and 17moist). The operating microscope was used with and without transillumination (groups: OMTrans and OM). Findings showed that accuracy was moderate for the 10dry, 10moist, and OMTrans groups, poor for OM and very poor for 17dry and 17moist. The thickness of the dentin crack significantly influenced its detection by mCT using the resolution of 10 μm in both dry and wet conditions (P = .002), 17 μm in the dry condition (P = .002), and by the operating microscope using transillumination (P = .009). Some cracks visualized in SEM were not detected by mCT and an operating microscope. Not only the mCT resolution but also the sample moisture condition and the dentinal crack width can significantly influence its detection.
Fully Automated Segmentation of Brain Tumor from Multiparametric MRI Using 3D Context Deep Supervised U-Net.

PURPOSE Owing to histologic complexities of brain tumors, its diagnosis requires the use of multi-modalities to obtain valuable structural information so that brain tumor subregions can be properly delineated. In current clinical workflow, physicians typically perform slice by slice delineation of brain tumor subregions, which is a time-consuming process and also more susceptible to intra- and inter-rater variabilities possibly leading to misclassification. To deal with this issue, this study aims to develop an automatic segmentation of brain tumor in MR images using deep learning. METHOD In this study, we develop a context deep-supervised U-Net to segment brain tumor subregions. A context block which aggregates multiscale contextual information for dense segmentation was proposed. This approach enlarges the effective receptive field of convolutional neural networks, which, in turn, improves the segmentation accuracy of brain tumor subregions. We performed the 5-fold cross-validation on the Brain Tumor Segmentation Challenge (BraTS) 2020 training dataset. The BraTS 2020 testing datasets were obtained via BraTS online website as a hold-out test. For BraTS, the evaluation system divides the tumor into three regions: whole tumor (WT), tumor core (TC) and enhancing tumor (ET). The performance of our proposed method was compared against two state-of-the-arts CNN networks in terms of segmentation accuracy via Dice similarity coefficient (DSC) and Hausdorff distance (HD). The tumor volumes generated by our proposed method were compared with manually contoured volumes via Bland-Altman plots and Pearson analysis. RESULTS The proposed method achieved the segmentation results with a DSC of 0.923 ± 0.047, 0.893 ± 0.176, and 0.846 ± 0.165 and a 95% HD95 of 3.946 ± 7.041 mm, 3.981 ± 6.670 mm, and 10.128 ± 51.136 mm on WT, TC and ET, respectively. Experimental results demonstrate that our method achieved comparable to significantly (P < 0.05) better segmentation accuracies than other two state-of-the-arts CNN networks. Pearson correlation analysis showed a high positive correlation between the tumor volumes generated by proposed method and manual contour. CONCLUSION Overall qualitative and quantitative results of this work demonstrate the potential of translating proposed technique into clinical practice for segmenting brain tumor subregions, and further facilitate brain tumor radiotherapy workflow.
Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool—Toward the New Normal for Fecal Microbiota Transplantation

INTRODUCTION: Mounting evidence demonstrates potential for fecal–oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens. METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients. RESULTS: The dual-target and single-target limit of detection were 56 copies/μL and 3 copies/μL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/μL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001). DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.
Successful management of membranous duodenal stenosis by endoscopic balloon dilation and membrane resection with an insulated-tip knife

A 14-month-old girl was admitted to our department because of repeated nonbilious vomiting for > 3 months and malnutrition. Upper gastrointestinal radiography showed partial obstruction of the duodenum (▶Fig. 1). Gastroscopy confirmed a membranous duodenal stenosis with an opening of about 3mm in diameter, and no view of the duodenal papilla above themembrane (▶Fig. 2 a). We performed both balloon dilation and membrane resection (▶Video 1). First, endoscopic balloon dilation was carried out to locate the duodenal papilla (▶Fig. 2b), which was in the 10 o’clock position and 1cm below the membrane (▶Fig. 2 c). Then, following submucosal injection of diluted epinephrine (1:10000), a circumferential incision was performed contralaterally to E-Videos
Immunomodulatory Effect of Serum Exosomes From Crohn Disease on Macrophages via Let-7b-5p/TLR4 Signaling.

BACKGROUND Exosomes are extensively reported to be strongly associated with many immunologic diseases, including Crohn disease (CD). Meanwhile, the dysfunction of macrophage activation has been proposed to be critical for the pathogenesis of CD. However, it is an unsettled issue whether serum exosomes from CD could activate macrophages and participate in its pathogenesis. Our study intended to clarify the role of CD-derived exosomes on macrophages to elucidate a novel mechanism and possible diagnostic and therapeutic strategies. METHODS Serum exosomes were isolated and identified. Functional assays in vitro were performed on Raw264.7 macrophages, followed by exosomal microRNA (miRNA) profiling and bioinformatics analyses via high-throughput sequencing. In animal experiments, exosomes were intraperitoneally injected into dextran sulfate sodium-induced colitis. RESULTS In vitro CD-derived exosomes induced proinflammatory cytokine expression and increased macrophage counts. Meanwhile, the intervention of exosomes from CD with epithelial cells led to increased permeability of the intestinal epithelial barrier. In vivo, CD-derived exosomes could circulate into the intestinal mucosa and significantly aggravate colitis. Furthermore, CD changed the miRNA profile of exosomes and further analysis revealed a differential expression of let-7b-5p. Mechanistically, the let-7b-5p/TLR4 pathway was recognized as a potential contributor to macrophage activation and inflammatory response. Furthermore, serum exosome-mediated let-7b-5p mimic delivery alleviated colitis significantly. CONCLUSIONS Our study indicated that serum exosomes can circulate into the intestinal mucosa to aggravate colitis by regulating macrophage activation and epithelial barrier function. In addition, CD showed altered exosomal miRNA profiles. Furthermore, serum exosome-mediated let-7b-5p-mimic delivery may significantly alleviate colitis, providing potential novel insight into an exosome-based strategy for the diagnosis and treatment of CD.
Human health risk assessment in PM10‐bound trace elements, seasonal patterns, and source apportionment study in a critically polluted coking coalfield area of India

Jharia Coalfield (JCF) has been affected by coalmine fire and subsidence problems for several years. The emission of particulate pollutants is due to the history of unscientific and unregulated coal mining in the JCF area. In the present study (conducted in the year 2019), seasonal variations, possible causes, and human health hazards of particulate matter (PM10)‐bound trace metals like Cd, Cu, Fe, Cr, Ni, Mn, Co, Pb, Zn, and As were estimated. The mean concentration of PM10 (418 ± 67 µg/m3) exceeded the limit of NAAQS (National Ambient Air Quality Standards India, 2009) by a factor of 4.18. PM10‐bound trace metal concentrations were found in the order of Fe > Mn > Cu > Zn > Cr > Pb > Co > Ni > Cd > As. The maximum trace metal concentrations of all the metals studied were observed at the mining areas of JCF affected by coalmine fire. Human health carcinogenic and noncarcinogenic risks in children and adults were estimated through exposure pathways, ingestion, dermal contact, and inhalation. The cancer risk was evaluated as excess cancer risk (ECR). Noncancer risk estimates were evaluated as the hazard index (HI) and the hazard quotient (HQ). The HI and HQ values for Cr, Cu, Cd, As, and Pb at coalmine‐fire‐affected areas were observed to be higher than the value of safe dose (≤1), showing a possible noncarcinogenic risk to the inhabitants as a result of multielemental toxicity. The ECR values (>10−6) in JCF areas suggested a carcinogenic risk to the populace of the area, owing to inhalation of PM10‐linked Cd. Active mine fire (related to mining activities), higher transportation load, and resuspended particulate matter from road transportation were identified as the possible causes of the estimated risks based on principal component analysis and Pearson correlation analyses. Integr Environ Assess Manag 2022;18:469–478. © 2021 SETAC
Interaction of Cobalt Nanoparticles with Oxygen- and Nitrogen-Functionalized Carbon Nanotubes and Impact on Nitrobenzene Hydrogenation Catalysis

The type and the amount of functional groups on the surface of carbon nanotubes (CNTs) were tuned to improve the activity of supported Co nanoparticles in hydrogenation catalysis. Surface nitrogen species on CNTs significantly promoted the decomposition of the cobalt precursor and the reduction of cobalt oxide, and improved the resistance of metallic Co against oxidation in ambient atmosphere. In the selective hydrogenation of nitrobenzene in the gas phase, Co supported on CNTs with the highest surface nitrogen content showed the highest activity, which is ascribed to the higher reducibility and the lower oxidation state of the Co nanoparticles under reaction conditions. For Co nanoparticles supported on CNTs with a smaller amount of surface nitrogen groups, a repeated reduction at 350 °C was essential to achieve a comparable high catalytic activity reaching 90% conversion at 250 °C, pointing to the importance of nitrogen species for the supported Co nanoparticles in nitrobenzene hydrogenation.
Exchange Mechanisms in Macroscopic Ordered Organic Magnetic Semiconductors

Small molecule organic semiconductors such as phthalocyanines and their derivatives represent a very interesting alternative to inorganic semiconductor materials for the development of flexible electronic devices such as organic thin field effect transistors, organic Light Emitting Diodes and photo-voltaic cells. Phthalocyanine molecules can easily accommodate a variety of metal atoms as well in the central core of the molecule, resulting in wide range of magnetic properties. Exploration of optical properties of organic crystalline semiconductors thin films is challenging due to sub-micron grain sizes and the presence of numerous structural defects, disorder and grain boundaries. However, this can be overcome by fabricating macroscopically ordered semiconductor films by solution processing. Presence of fewer grain boundaries and defects while modifying the π orbital overlap by controlling the molecular stacking by forming macroscopic long range ordered grains, was essential in understanding the delocalization and diffusion length and its role in magnetic exchange mechanisms in this system. The origins of magnetic exchange mechanism between delocalized ligand electrons and spins in organic semiconductors has been of key interest as it underlies many complex optical and transport properties and is investigated in this thesis. The interaction between magnetic ions in organic magnetic semiconductors is quite challenging to interpret due to competing exchange mechanisms present in crystalline thin films. Better understanding of these exchange mechanisms is essential for tuning of magnetic exchange interaction to suit the need of practical magnetic storage and spintronic devices. Optical techniques such as linear dichroism, magnetic circular dichroism and magneto-photoluminescence are used and provided key understanding about the relation between excitons, spin exchange mechanisms and collective magnetic behavior of delocalized electrons in organic semiconductors. An enhancement in the collective magnetization of the crystalline thin films with strong exchange coupling between the delocalized ligand electrons and d-electrons is observed. The electronic states responsible for magnetic exchange are identified utilizing magnetic field and temperature dependent studies. Furthermore, soluble organics allowed engineering of organic analogues to diluted magnetic semiconductors (DMS) by creation of metal/metal-free Pc alloys. Optical studies provided crucial information about delocalization and diffusion lengths in these systems allowing fine tuning of this delocalization length scale and metal-metal distance. The exploration of magnetic behavior in metal/metal-free Pc alloys opens an avenue for tuning magnetic properties through an exchange similar to Ruderman-Kittel-Kasuya Yosida (RKKY) type interaction in organic magnetic semiconductors. Dedicated to my family, for all the love and sacrifice during these years. Their patience and encouragement kept me going every day.
Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 (BRCA1/BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/BRCA2 mutations, and the secondary objective was to correlate BRCA1/BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.
Automated Prediction of Ischemic Brain Tissue Fate from Multiphase Computed Tomographic Angiography in Patients with Acute Ischemic Stroke Using Machine Learning

Background and Purpose Multiphase computed tomographic angiography (mCTA) provides time variant images of pial vasculature supplying brain in patients with acute ischemic stroke (AIS). To develop a machine learning (ML) technique to predict tissue perfusion and infarction from mCTA source images. Methods 284 patients with AIS were included from the Precise and Rapid assessment of collaterals using multi-phase CTA in the triage of patients with acute ischemic stroke for Intra-artery Therapy (Prove-IT) study. All patients had non-contrast computed tomography, mCTA, and computed tomographic perfusion (CTP) at baseline and follow-up magnetic resonance imaging/non-contrast-enhanced computed tomography. Of the 284 patient images, 140 patient images were randomly selected to train and validate three ML models to predict a pre-defined Tmax thresholded perfusion abnormality, core and penumbra on CTP. The remaining 144 patient images were used to test the ML models. The predicted perfusion, core and penumbra lesions from ML models were compared to CTP perfusion lesion and to follow-up infarct using Bland-Altman plots, concordance correlation coefficient (CCC), intra-class correlation coefficient (ICC), and Dice similarity coefficient. Results Mean difference between the mCTA predicted perfusion volume and CTP perfusion volume was 4.6 mL (limit of agreement [LoA], –53 to 62.1 mL; P=0.56; CCC 0.63 [95% confidence interval [CI], 0.53 to 0.71; P<0.01], ICC 0.68 [95% CI, 0.58 to 0.78; P<0.001]). Mean difference between the mCTA predicted infarct and follow-up infarct in the 100 patients with acute reperfusion (modified thrombolysis in cerebral infarction [mTICI] 2b/2c/3) was 21.7 mL, while it was 3.4 mL in the 44 patients not achieving reperfusion (mTICI 0/1). Amongst reperfused subjects, CCC was 0.4 (95% CI, 0.15 to 0.55; P<0.01) and ICC was 0.42 (95% CI, 0.18 to 0.50; P<0.01); in non-reperfused subjects CCC was 0.52 (95% CI, 0.20 to 0.60; P<0.001) and ICC was 0.60 (95% CI, 0.37 to 0.76; P<0.001). No difference was observed between the mCTA and CTP predicted infarct volume in the test cohort (P=0.67). Conclusions A ML based mCTA model is able to predict brain tissue perfusion abnormality and follow-up infarction, comparable to CTP.