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Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and resistant to both conventional and targeted chemotherapy. Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the incidence and mortality of different types of cancers. Here, we investigated the cellular bioactivities of a series of triazolothiadiazine derivatives on HCC, which have been previously reported as potent analgesic/anti-inflammatory compounds. From the initially tested 32 triazolothiadiazine NSAID derivatives, 3 compounds were selected based on their IC50 values for further molecular assays on 9 different HCC cell lines. 7b, which was the most potent compound, induced G2/M phase cell cycle arrest and apoptosis in HCC cells. Cell death was due to oxidative stress-induced JNK protein activation, which involved the dynamic involvement of ASK1, MKK7, and c-Jun proteins. Moreover, 7b treated nude mice had a significantly decreased tumor volume and prolonged disease-free survival. 7b also inhibited the migration of HCC cells and enrichment of liver cancer stem cells (LCSCs) alone or in combination with sorafenib. With its ability to act on proliferation, stemness and the migration of HCC cells, 7b can be considered for the therapeutics of HCC, which has an increased incidence rate of ~ 3% annually.

Background: The mucogingival conditions associated with the recession defects at the mandibular anterior region, not only make plaque control difficult to be performed by the patient but also pose a problem in passively advancing the tissues at the recipient site. This surgical technique is used to treat multiple recession defects in the mandibular anterior region. Materials and Methods: Twenty-five sites in 17 subjects (11 women and 6 men) underwent modified bridge flap and de-epithelized gingival unit graft (d-GUG) as a single-step treatment modality to cover the denuded root surface, as well as increase the width of keratinized gingiva in recession type 1 gingival recession defects in the mandibular anterior region. Results: Nearly 60% of sites in our study showed complete root coverage, with a mean root coverage percentage of 88.08%. Furthermore, keratinized tissue width, keratinized tissue thickness as well as vestibular depth showed statistically significant increases as compared to baseline levels. Conclusion: Thus, the modified bridge flap technique using d-GUG within the limitations of our study design, showed promising results in terms of recession coverage as well as management of the difficult mucogingival conditions at the mandibular anterior region.

Background Accelerating door‐in‐door‐out (DIDO) times at primary stroke centers (PSCs) for patients with large vessel occlusion (LVO) acute ischemic stroke transferred for possible endovascular stroke therapy (EVT) is important to optimize outcomes. Here, we assess whether automated LVO detection coupled with secure communication at non‐EVT performing PSCs improves DIDO time and increases the proportion of patients receiving EVT after transfer. Methods From our prospectively collected multicenter registry, we identified patients with LVO acute ischemic stroke that presented to one of 7 PSCs in the Greater Houston area from January 1, 2021, to February 27, 2022. Noncontrast computed tomography and computed tomographic angiography were performed in all patients at the time of presentation, per standard of care. A machine learning (artificial intelligence [AI]) algorithm trained to detect LVO (Viz.AI) from computed tomographic angiography was implemented at all 7 hospitals. The primary outcome of the study was DIDO at the PSCs and was determined using multivariable linear regression adjusted for sex and on/off hours. Secondary outcomes included likelihood of receiving EVT post‐transfer. Results Among 115 patients who met inclusion criteria, 80 were evaluated pre‐AI and 35 post‐AI. The most common occlusion locations were middle cerebral artery (51.3%) and internal carotid artery (25.2%). There were no substantial differences in demographics or presentation characteristics between the 2 groups. Median time from onset to PSC arrival was 117 minutes (interquartile range, 54–521 minutes). In univariable analysis, patients evaluated at the PSCs after AI implementation had a shorter DIDO time (median difference, 77 minutes; P

OBJECTIVE: Oral supplementation with curcumin demonstrated a beneficial effect on some ocular diseases, including uveitis and macular edema. This study aimed to evaluate the effectiveness and safety of a curcumin formulation with the hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) as an adjuvant to standard steroid treatment in adults suffering from acute non-infectious uveitic macular edema (NIUME). PATIENTS AND METHODS: This was a monocenter prospective observational study carried out between January 2019 and May 2020 on consecutive patients with a new diagnosis of NIUME. Patients were treated with standard therapy or with a CHC add-on to standard treatment. The observation period for each patient was 12 months. The Best Corrected Visual Acuity (BCVA) and the Central Macular Thickness (CMT) were the primary outcomes; Foveal Avascular Zone (FAZ) and intraocular pressure (IOP) were also assessed, along with safety data. RESULTS: A total of 43 eyes of 26 patients were analyzed. CHC-treated eyes showed an improvement in mean BCVA from baseline (0.34 logMar) to T6 (0.20 logMar) and T12 (0.19 log- Mar; p≤0.05 and p≤0.01, respectively); CMT decreased from a mean of 320 μm (T0) to 278 μm (T6; p≤0.05) and 272 μm (T12; p≤0.01). A significant improvement of mean BCVA in the CHC group at T6 and T12 was reported compared to the control group (p≤0.01). FAZ and IOP showed no statistically significant variations in both groups. No adverse events were recorded. CONCLUSIONS: CHC as an adjuvant treatment improved the anatomical and functional outcomes, without significant side effects in eyes affected by the recent onset of NIUME, compared to the sole standard therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Vaccine hesitancy is common among incarcerated populations and, despite vaccination programs, vaccine acceptance within residents remains low, especially within jails. With the goal of assessing the Connecticut DOC’s COVID-19 vaccine program within jails we examined if residents of DOC operated jails were more likely to become vaccinated following incarceration than in the community. Specifically, we conducted a retrospective cohort analysis among people who spent at least one night in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination. Results During the study period, 3,716 people spent at least one night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 479 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% Confidence Intervals: 10.2–15.3). Conclusions We found that residents were more likely to become vaccinated in jail than in the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.

Like other pandemics, COVID-19 also created a huge socioeconomic imbalance and distress in people. Often, every pandemic is characterized as chaotic and complex. Hence, the nature of the virus spread and deaths should be analyzed to prepare for the next similar pandemic. In this analysis, the popular and well-known time series in chaos theory is implemented, and the results are deduced for the states of India. The phase space reconstruction algorithm is implemented, and false nearest neighbor (FNN) method is applied to determine the dimensionality, and also Lyapunov exponent of the time series is estimated. The chaotic nature of COVID-19 cases showed a less severe and low complexity, with the FNN dimension range of 3–5, whereas the COVID-19 deaths showed moderate complexity with FNN dimensions 2–7. Policymakers should take action on medical availability in rural states and control people's movement in highly populated areas.

Due to rapid urban growth and population increase, accurately tracking land use and cover changes (LULC) is vital for predicting outdoor thermal comfort. We used high-res Landsat 8 imagery and on-site weather data, employing a Support Vector Machine (SVM) with PCA to estimate thermal comfort. The PCA addressed variable multicollinearity, and LULC was classified using decision trees. Notable LULC trends emerged. In Hyderabad, built-up areas rose from 37% to 48% (2009–2019) and barren lands fell from 42% to 18%. In Bangalore, built-up areas surged from 25% to 80%, causing vegetation loss (25% to 2%) and reduced barren land (50% to 18%). Jaipur saw a 12% built-up area increase with a slight vegetation uptick. The thermal comfort analysis highlighted Bangalore’s intense urbanization and Jaipur’s limited expansion. Discomfort ranked highest in barren lands, followed by urban, vegetation, and water areas.

Penelitian ini bertujuan untuk mengetahui tingkat kecemasan dan motivasi atlet basket Bangka Belitung saat menjelang pertandingan. Penelitian ini adalah penelitian kuantitatif deskriptif. Alat ukur yang digunakan dalam penelitian ini adalah kuesioner. Responden dalam penelitian yaitu 30 orang atlet basket di wilayah Bangka Belitung. Responden mengisi kuesioner melalui google formulir yang terdiri dari 10 butir pernyataan yang disebarkan lewat whatsapp kepada atlet basket Bangka Belitung. Penelitian ini menggunakan metode survei dan dianalisis secara deskriptif kuantitatif. Berdasarkan hasil penelitian tingkat kecemasan atlet yaitu 30% dan masuk dalam kategori rendah, sedangkan tingkat motivasi atlet yaitu 70% dan masuk dalam kategori tinggi.

BackgroundThe benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection.Methods and findingsWe conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results.ConclusionsIn this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Background: At present, India is in the decreasing phase of the second wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But India as a country is in the second position in a high number of confirmed cases (33,678,786) in the world (after the United States of America) and third position in the number of COVID-19 deaths (after the United States and Brazil) at 465,082 deaths. Almost above numbers are dominantly seen in the second wave only. Thus, future long-term projections are required to mitigate the impact. Methods: The conventional SIR model was modified so that a new compartment Q(quarantine) is added to the conventional SIR model to analyze the COVID-19 impact. The parameter optimal control technique was used to fit the curve by estimating the infection, susceptible, etc. Results: The model predicts the cumulative number of cases of 2.6928E7 with a confidence interval of 95%, CI[2.6921E7,2.6935E7], and an accuracy of 99.3% on May 25, 2020(480th day from 30 to 01–2020). The estimated R0 is 1.1475. The model's mean absolute error(EMAE) is 1.79E4, and the root-mean-square error is (ERMSE) is 3.19E4. The future projection are,3.48E7(Lockdown), 3.80E7(periodic-lockdown), 4.52E7(without lockdown). The whole model accuracy is 99%, and projection accuracy is about 94% up to 01-Nov-2021, The goodness of fit value 0.8954. Conclusion: The model is over-estimating corona cases initially and then showed a decreased trend. As the number of days increases, the model accuracy decreases; thus, more control points of the cost function are required to fit the model best.