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We show that a group that is hyperbolic relative to strongly shortcut groups is itself strongly shortcut, thus obtaining new examples of strongly shortcut groups. The proof relies on a result of independent interest: we show that every relatively hyperbolic group acts properly and cocompactly on a graph in which the parabolic subgroups act properly and cocompactly on convex subgraphs.

Deep learning approaches are currently having great success across several industries, including computer vision. Yes, it is possible to train a convolutional neural networks (CNN) model to analyse photos and recognise facial expression. In this study, we develop a system that can identify students' facial expressions of emotion. The three parts of our system are facial detection using Haar Cascades, normalisation, and emotion recognition using CNN on the FER 2013 database employing seven different expression kinds. The obtained results demonstrate that face emotion detection is practicable in education, and as a result, it can assist teachers in adapting their presentation to the emotions of the pupils.

This paper reports experimental results of fluid/structure interactions induced by shock impingement on a clamped-free/clamped-free compliant panel in a Mach 5.8 Ludwieg tube. A shock generator is used to statically impinge a shock on the panel with the aim of producing flow-induced vibrations. In turn, these vibrations create an aeroelastic coupling between the panel and the flowfield, which is dominated by the shock-wave/boundary-layer interactions. The influence of the structural compliance and shock impingement strength is assessed by testing a nominally rigid panel and compliant panels with thickness-to-length ratios of 0.0034 and 0.0068 with a shock generator at flow deflection angles of 0, 2, 3, 8, and 10 deg. One of the primary findings of the present work is that the aeroelastic response of the panel tends to shift from a structurally dominated to a fluid-dominated regime, which is sustained by either the freestream fluctuations or the fluid/structure coupling, depending on the structural compliance and shock impingement strength and location. This work is of fundamental nature, and its main goal is to analyze the interactions between high-speed flow and a thin compliant panel of canonical geometry. However, studies like this are crucial to characterize those complex couplings and provide experimental data that can help enhance the accuracy of aeroelastic modeling tools that feed into the design process of supersonic and hypersonic airframes.

Encapsulation into nanoparticles (NPs) is a potential method to deliver pharmaceutical/cosmetic actives deep into the skin. However, understanding the NP formulations and underlying mechanism of active delivery to skin has scarcely been studied. We report a

Background: Diabetes could form cholesterol gallstones more frequently because of a reduced gallbladder contraction and increased biliary cholesterol secretion. A meta -analysis study suggested that there is a strong association between diabetes mellitus and the occurrence of gallstone disease. The incidence of gallstones is higher in Type 2 Diabetes both in males and females than the non-diabetics. To study the frequency of gallbladder stones among patients with Objective: Method: type 2 Diabetes mellitus. After institutional ethical committee approval and obtaining written informed consent from the patients, an observational cross-sectional study was conducted on patients admitted in Raja Rajeswari medical college and hospital over a period of one and half year on 100 known case of type II diabetes mellites for more than or equal to 5 years. In the present study, the Results: occurrence of gallbladder stones was 21% among Type 2 diabetes mellitus participants. Even though statistical association could not be proven, a higher HbA1c level was found to be among the study participants with gall stones when compared with the study participants without gall stones. 21% of the study participants were Conclusion: diagnosed with Gall stones. 79% of the study participants were not diagnosed with gall stones

Around the world today, young adults are constantly confronted with the fear of receiving negative evaluation from others which forces them into the obscure spaces of desolation. This study examined the effects of fear of negative evaluation on the emotional/social loneliness in a sample of young adults (N=162) within the age group of 18 to 25 years.The data was collected through convenience sampling technique. Brief fear of negative evaluation scale ( Leary,1983) and emotional/social loneliness inventory (Vincenzi&Grabosky, 1987) were used. The statistical method used was Spearman Rank correlation. Findings revealed a positive correlation between fear of negative evaluation and emotional/social loneliness. The study concluded that fear of negative evaluation produces social and emotional alienation.

Introduction Breast cancer is the most common cancer in women in India and accounts for 14% of all cancers in women. Rise in mortality is due to lack of awareness and proper screening. Mammography and presently available serum biomarkers have low sensitivity and specificity. In our quest to identify a better biomarker, we studied mammaglobin (MAM) in patients with breast cancer and benign breast tumors. Aim To evaluate serum mammaglobin in breast cancer patients and compare it with benign breast tumor patients and healthy controls. To compare it with existing biomarkers serum carcinoembryonic antigen (CEA) and cancer antigen 15–3 (CA 15–3). Materials and methods: This is a cross-sectional, case–control study of 77 subjects, of which 27 were breast cancer patients, 20 benign breast tumor patients, and 30 healthy controls. Serum CEA and CA15–3 were estimated by electrochemiluminescence immunoassay (ECLIA) and mammaglobin (MAM) by enzyme-linked immunosorbent assay (ELISA). Results Mammaglobin and CEA levels were elevated in breast cancer patients, followed by benign breast tumors when compared with controls (P Conclusion Mammaglobin proved to be an efficacious biomarker in diagnosing breast cancer.

These datasets are related to twoairglow events observed by the Hanle imager on two successive geomagnetically quiet nights, 26 June 2021 and 27 June 2021. On 26 June 2021, a plasma depleted structure was observed simultaneously in 557.7 nm and 630.0 nm images, while on the following night, a few plasma bands were detected only in the 630.0 nm images.Using these datasets, we have explored the plausible reason behind the simultaneous observation of plasma structure on 26 June 2021.&nbsp

In this work we consider the Anderson model on Bethe lattice and prove that the integrated density of states (IDS) is as smooth as the single site distribution (SSD), in high disorder

INTRODUCTION The textile industry consists of several processes including dyeing, printing etc. and due to the exposures to various chemicals at work, these workers frequently complain of respiratory symptoms. Spirometry allows us to measure FEV1,FVC, FEV1/FVC ratio,FEF25- 75%.Diffusion Capacity of Lung for Carbon Monoxide(DLCO) test indicates the diffusion of Carbon Monoxide gas across the alveolar membrane. In 6 Minute walk Test ,Pulse rate and SpO2 is measure at the start and at the end of the test. (At 0 min and at 6 min) and then fall or rise in Pulse or SpO2 is observed. METHODOLOGY This study included all the subjects according to the inclusion criteria(40) coming to Respiratory Medicine OPD during the study period (15 months). Data was collected and analyzed .RESULTS Majority of the patients were male, (50%) and smokers. Dry cough seen in – 29 patients (72.5%) & Dyspnoea on exertion in 15(37.5%) patients. Chest X-Ray was normal in – 21patients (52.5%), followed by Prominent Broncho-Vascular markings (BVM) was seen in 10(25%) patients. On Spirometry Findings, 24 (60%) patients were normal, 8 (20%) patients showed Restrictive Pattern, 6 (15%) showed Obstructive Pattern and 2 (5%) patients showed Mixed Pattern. In DLCO ndings, 27 patients showed normal (67.5%) and 13 (32.5%) patients showed Decreased Pattern. CONCLUSION Duration of exposure to dye and smoking were signicantly associated with Clinical features, reduced 6 Minute Walk distance, Abnormal Spirometry and DLCO ndings. FEF25-75% was signicantly decreased in most of the dye-workers in present study. As the Dyeing-workers are working in hazardous environment, there should protocols be formed for routine medical check-up at frequent interval in textile industry to detect occupation related diseases at early stage and to intervene the problem timely.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

Introduction: The primary self-assessment questionnaire used for patients with chronic cough is the Leicester Cough Questionnaire (LCQ). The LCQ is a validated questionnaire that ranges in total score from 3 to 21. While it is known that a higher score on the LCQ reflects a better quality of life, normative data have not been reported for this questionnaire. Objective: The purpose of this study was to determine normative LCQ scores on a healthy population without cough. Methods: The LCQ was distributed via electronic survey to the authors’ universities, professional affiliation email lists, and personal contacts. Participants were included if they were at least 18, nonsmokers, and without abnormal cough, without pulmonary disease, and without neurological disease. Participants answered questions regarding age, gender, and race/ethnicity, and completed the 19 LCQ questions. Results: One hundred forty-three (118 women) LCQ responses were analyzed. Average participant age was 47 years (SD = 13) and 133 (93%) were Caucasian. The mean LCQ Total score was 20.23 (SD = 0.85) with scores ranging from 17.05 to 21. Conclusions: This study determined the following LCQ scores should be considered normal threshold scores: Total score – 17.68, Physical domain – 5.36, Psychological domain – 5.81, and Social domain – 6.06. The findings of this study will assist clinicians in determining severity of cough impact on quality of life using the LCQ. Further research is needed to ensure more complete participant demographic representation.

Background: Traditionally rheumatic heart disease with mitral stenosis and atrial fibrillation has been the common mechanism of cardioembolic strokes in India. However, with the increase in life span and higher detection and development of cardiac diseases, the frequency and etiologic spectrum of cardioembolic stroke in an Indian hospital may be changing. Methods: The case records of patients admitted in the year 2020 were analyzed for the presence of risk factors and identified stroke mechanisms. Results: Among 538 patients of ischemic strokes, cardioembolic source was identified in 156 (29.8%) patients. Five major cardiac sources of embolism were identified: Coronary artery disease (with acute or remote myocardial infarction) 56/156 (35.89%), non valvular atrial fibrillation, 34/156(21.79%), post cardiac intervention 28/156 (17.94%), left atrial cardiomyopathy 20/156 (12.8%), and rheumatic heart disease 13/156 (8.3%). Conclusion: Coronary artery disease, non valvular atrial fibrillation, post intervention stroke and left atrial cardiomyopathy are emerging as common causes of cardioembolic strokes. Rheumatic heart disease continues to be an important but less frequent cause of cardioembolic strokes.

Accurate femoral tunnel placement is a crucial step in Anterior Cruciate Ligament (ACL) reconstruction and non-anatomical placement of the tunnel may result in rotational instability. With advancements in arthroscopic techniques and to achieve better rotational stability, femoral tunnel placement has changed from the transtibial technique to the transportal method. Identification of ACL footprint is the foremost step during transportal drilling. In this technical note, we describe an easy way to the identification of the femoral footprint to drill the femoral tunnel during the transportal method.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery.

Synergistic cytotoxic effects of combination of eeyarestatin with sunitinib in MZCRC1 cells.

Functional categ ories of ATF4 target genes.

Supplementary Figures S1-S5

ChIP -seq profiles of ATF4 target genes (DDIT3, MKNK2, LZTFL1, SIAH1) and H3K9Ac in MZCRC1 cells treated with eeyarestatin

Ingenuity Pathway Analysis of ATF4 target genes

Medullary thyroid carcinoma (MTC) originates from the C cells of the thyroid gland, which secrete calcitonin. Lymph node and distant metastases are frequently present at diagnosis. Activating mutations of RET, a driver oncogene in MTC that encodes a tyrosine kinase receptor, prevents apoptosis through inhibition of ATF4, a key transcriptional regulator of endoplasmic reticulum (ER) stress. We hypothesized that the combination of a tyrosine kinase inhibitor (TKI) and an ATF4 inducer promotes cell death by triggering catastrophic oxidative stress and apoptotic cell death. Here, we report that the ER-associated protein degradation (ERAD) inhibitor eeyarestatin sensitized MTC cells to the TKIs, sunitinib and vandetanib, thereby leading to synergistic upregulation of ATF4 expression, accumulation of reactive oxygen species, and subsequent cell death. Genome-wide analysis of ATF4 interaction sites by chromatin immunoprecipitation (ChIP) sequencing revealed that among ATF4 target genes was KLF9 (Kruppel-like factor 9), which induces MTC apoptosis. ChIP assays revealed that ATF4 occupancy at the KLF9 promoter was increased in MTC cells treated with eeyarestatin or vandetanib alone and was further enhanced in cells treated with both drugs, leading to increased KLF9 transcription. Depletion of ATF4 by shRNA led to downregulation of KLF9 expression and prevented oxidative stress–induced cell death. Furthermore, we identified ATF4 target genes (LZTFL1, MKNK2, and SIAH1 with known tumor suppressor function) that were synergistically upregulated with the combination of TKI and ERAD inhibitor.Implications:These findings reveal a combination therapy that induces reactive oxygen species–dependent catastrophic cell death through induction of ATF4 and KLF9 transcriptional activity.

Eeyarestatin in combination with sunitinib synergistically induce cell death in MZCRC1 spheres

CI analysis of sunitinib (SU) or vandetanib (Van) combined with eeyarestatin in TT cells.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome, which results in the development of hundreds of adenomatous polyps carpeting the gastrointestinal tract. NSAIDs have reduced polyp burden in patients with FAP and synthetic rexinoids have demonstrated the ability to modulate cytokine-mediated inflammation and WNT signaling. This study examined the use of the combination of an NSAID (sulindac) and a rexinoid (bexarotene) as a durable approach for reducing FAP colonic polyposis to prevent colorectal cancer development. Whole transcriptomic analysis of colorectal polyps and matched normal mucosa in a cohort of patients with FAP to identify potential targets for prevention in FAP was performed. Drug-dose synergism of sulindac and bexarotene in cell lines and patient-derived organoids was assessed, and the drug combination was tested in two different mouse models. This work explored mRNA as a potential predictive serum biomarker for this combination in FAP. Overall, transcriptomic analysis revealed significant activation of inflammatory and cell proliferation pathways. A synergistic effect of sulindac (300 μmol/L) and bexarotene (40 μmol/L) was observed in FAP colonic organoids with primary targeting of polyp tissue compared with normal mucosa. This combination translated into a significant reduction in polyp development in ApcMin/+ and ApcLoxP/+-Cdx2 mice. Finally, the reported data suggest miRNA-21 could serve as a predictive serum biomarker for polyposis burden in patients with FAP. These findings support the clinical development of the combination of sulindac and bexarotene as a treatment modality for patients with FAP.Prevention Relevance:This study identified a novel chemopreventive regimen combining sulindac and bexarotene to reduce polyposis in patients with FAP using in silico tools, ex vivo, and in vivo models. This investigation provides the essential groundwork for moving this drug combination forward into a clinical trial.

Supplementary Tables S1-S4

Primers used for ChIP sequencing validation.

Supplementary Figures S1-S6

Supplementary Material and Methods

Supplementary Tables S1-S9

Lynch syndrome is the most common cause of hereditary colorectal cancer and is secondary to germline alterations in one of four DNA mismatch repair (MMR) genes. Here we aimed to provide novel insights into the initiation of MMR-deficient (MMRd) colorectal carcinogenesis by characterizing the expression profile of MMRd intestinal stem cells (ISC). A tissue-specific MMRd mouse model (Villin-Cre;Msh2LoxP/LoxP) was crossed with a reporter mouse (Lgr5-EGFP-IRES-creERT2) to trace and isolate ISCs (Lgr5+) using flow cytometry. Three different ISC genotypes (Msh2-KO, Msh2-HET, and Msh2-WT) were isolated and processed for mRNA-seq and mass spectrometry, followed by bioinformatic analyses to identify expression signatures of complete MMRd and haplo-insufficiency. These findings were validated using qRT-PCR, IHC, and whole transcriptomic sequencing in mouse tissues, organoids, and a cohort of human samples, including normal colorectal mucosa, premalignant lesions, and early-stage colorectal cancers from patients with Lynch syndrome and patients with familial adenomatous polyposis (FAP) as controls. Msh2-KO ISCs clustered together with differentiated intestinal epithelial cells from all genotypes. Gene-set enrichment analysis indicated inhibition of replication, cell-cycle progression, and the Wnt pathway and activation of epithelial signaling and immune reaction. An expression signature derived from MMRd ISCs successfully distinguished MMRd neoplastic lesions of patients with Lynch syndrome from FAP controls. SPP1 was specifically upregulated in MMRd ISCs and colocalized with LGR5 in Lynch syndrome colorectal premalignant lesions and tumors. These results show that expression signatures of MMRd ISC recapitulate the initial steps of Lynch syndrome carcinogenesis and have the potential to unveil novel biomarkers of early cancer initiation.Significance:The transcriptomic and proteomic profile of MMR-deficient intestinal stem cells displays a unique set of genes with potential roles as biomarkers of cancer initiation and early progression.

These datasets are related to an event observed by the Hanle imager in whichmultipledark bands of MSTID were involved in two dynamic interactions. Using these datasets, we have explored the plausible mechanisms behind the observed interactions.&nbsp

To date, plasma cell (PC)–targeted therapies have been limited by suboptimal PC depletion and antibody rebound. We hypothesized this is partly because of PC residence in protective bone marrow (BM) microenvironments. The purpose of this proof-of-concept study was to examine the effects of the CXCR4 antagonist, plerixafor, on PC BM residence; its safety profile (alone and in combination with a proteasome inhibitor, bortezomib); and the transcriptional effect on BMPCs in HLA-sensitized kidney transplant candidates. Participants were enrolled into 3 groups: group A (n = 4), plerixafor monotherapy; and groups B (n = 4) and C (n = 4), plerixafor and bortezomib combinations. CD34(+) stem cell and PC levels increased in the blood after plerixafor treatment. PC recovery from BM aspirates varied depending on the dose of plerixafor and bortezomib. Single-cell RNA sequencing on BMPCs from 3 group C participants pretreatment and posttreatment revealed multiple populations of PCs, with a post-treatment enrichment of oxidative phosphorylation, proteasome assembly, cytoplasmic translation, and autophagy-related genes. Murine studies demonstrated dually inhibiting the proteasome and autophagy resulted in greater BMPC death than did monotherapies. In conclusion, this pilot study revealed anticipated effects of combined plerixafor and bortezomib on BMPCs, an acceptable safety profile, and suggests the potential for autophagy inhibitors in desensitization regimens.

The increase in new cars and customers' economic inability, global sales of old cars are expanding. As a result, there exists a pressing need for a second-hand automobile method for predicting prices that accurately calculates the value of a car based on number of factors. In the current circumstance, the existing system involves a mechanism in which a seller sets a price at random and the buyer has no knowledge of the car or its value. In fact, the seller doesn't even know the current value of the car or the price at which the car should be sold. To solve this problem, we have developed a very effective model. Regression algorithms are used to provide continuous values as output rather than classified values. This allows for the prediction of the car's real price rather than its price range.

This paper deals with providing privacy-preserving access control in Internet of Things (IoT) systems. Here, a user/IoT device requests access to services provided by other IoT devices and multiple requests are combined to a request-specific service chain. An anonymous delegated credential based system architecture is proposed, where the requester’s identity is not exposed to the services. The paper presents the proposed architecture’s various components including the security aspects. Various options for implementing the architecture on resource-full and resource-constrained services are presented. A prototype of the proposed architecture is then implemented using Linux-based containers to emulate the services. Two representative systems, namely, a small-scale home automation system using a short service chain and a large-scale industrial automation system using a long service chain are considered. Timing measurements from the implementation are presented to demonstrate that the architecture is feasible and can be adapted for practical use in large-scale IoT systems.

STUDY OBJECTIVES: To assess the effectiveness of continuous positive airway pressure (CPAP) management guided by CPAP machine downloads in newly diagnosed patients with obstructive sleep apnea (OSA) using electronic health record–derived health care utilization, biometric variables, and laboratory data. METHODS: Electronic health record data of patients seen at the University of Utah Sleep Program from 2012–2015 were reviewed to identify patients with new diagnosis of OSA in whom CPAP adherence and residual apnea-hypopnea index as measured by a positive airway pressure adherence tracking device data for ≥ 1 year were available. Biometric data, laboratory data, and system-wide charges were compared in the 1 year before and after CPAP therapy. Subgroups were divided by whether patients met tracking criteria, mean nightly usage, and OSA severity. RESULTS: 976 consecutive, newly diagnosed participants with OSA (median age 55 years, 56.6% male) met inclusion criteria. There was a mean decrease of systolic blood pressure (BP) of 1.2 mm Hg and diastolic BP of 1.0 mm Hg within a year of initiation of CPAP therapy. BP improvements in the subgroup meeting CPAP tracking targets were 1.36 mmHg (systolic) and 1.37 mmHg (diastolic). No significant change was noted in body mass index, glycated hemoglobin, or serum creatinine values within a year of starting CPAP therapy, and health care utilization increased (mean acute care visits 0.22 per year to 0.53 per year; mean charges of $3,997 per year to $8,986 per year). CONCLUSIONS: An improvement in BP was noted within a year of CPAP therapy in newly diagnosed patients with OSA, with no difference in the magnitude of improvement between those meeting tracking system adherence targets. CITATION: Locke BW, Neill SE, Howe HE, Crotty MC, Kim J, Sundar KM. Electronic health record–derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems. J Clin Sleep Med. 2022;18(3):885–894.