Quantitative Screening of Cervical Cancers for Low-Resource Settings: Pilot Study of Smartphone-Based Endoscopic Visual Inspection After Acetic Acid Using Machine Learning Techniques

Background: Approximately 90% of global cervical cancer (CC) is mostly found in low- and middle-income countries. In most cases, CC can be detected early through routine screening programs, including a cytology-based test. However, it is logistically difficult to offer this program in low-resource settings due to limited resources and infrastructure, and few trained experts. A visual inspection following the application of acetic acid (VIA) has been widely promoted and is routinely recommended as a viable form of CC screening in resource-constrained countries. Digital images of the cervix have been acquired during VIA procedure with better quality assurance and visualization, leading to higher diagnostic accuracy and reduction of the variability of detection rate. However, a colposcope is bulky, expensive, electricity-dependent, and needs routine maintenance, and to confirm the grade of abnormality through its images, a specialist must be present. Recently, smartphone-based imaging systems have made a significant impact on the practice of medicine by offering a cost-effective, rapid, and noninvasive method of evaluation. Furthermore, computer-aided analyses, including image processing-based methods and machine learning techniques, have also shown great potential for a high impact on medicinal evaluations

First-Principles Calculation of the Superconducting Transition in MgB2 within the Anisotropic Eliashberg Formalism

We present a study of the superconducting transition in MgB2 using the ab-initio pseudopotential density functional method and the fully anisotropic Eliashberg equation. Our study shows that the anisotropic Eliashberg equation, constructed with ab-initio calculated momentum-dependent electron-phonon interaction and anharmonic phonon frequencies, yields an average electron-phonon coupling constant lambda = 0.61, a transition temperature Tc = 39 K, and a boron isotope-effect exponent alphaB = 0.31 with a reasonable assumption of mu* = 0.12. The calculated values for Tc, lambda, and alphaB are in excellent agreement with transport, specific heat, and isotope effect measurements respectively. The individual values of the electron-phonon coupling lambda(k,k') on the various pieces of the Fermi surface however vary from 0.1 to 2.5. The observed Tc is a result of both the raising effect of anisotropy in the electron-phonon couplings and the lowering effect of anharmonicity in the relevant phonon modes.Comment: 4 pages, 3 figures, 1 tabl

Who will benefit more from low-dose alteplase in acute ischemic stroke?

Objectives: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Methods: Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Results: Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Conclusion: Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.</p

Unusual epileptic deterioration and extensive white matter lesion during treatment in Wilsons disease

Background : Wilsons disease (WD) is a genetic disorder which can be controlled fairly well with decupuration therapy. However, symptoms, on rare occasions, can worsen even when WD is being treated. Herein, we report a case involving unusual neurological deterioration during decupuration therapy for WD. Case presentation : A 28-year-old man was diagnosed with WD 13 years prior to his clinical visit; however, his drug compliance has been poor over the years. He was treated with trientine because tremors and dysarthria have presented in recent years. However, dysarthria and dystonia developed in his limbs, which were worse on the right side and had been aggravated for several weeks despite good drug compliance. His symptoms were fluctuating. It was initially misdiagnosed as dystonia; although, it turned out to be a seizure due to cortical degeneration. These symptoms were completely resolved with antiepileptic drugs. Moreover, the cortical enhancement of bifrontal degeneration has disappeared on the MRI. Conclusion : This case showed unusual epileptic neurologic deterioration due to cortical degeneration during decupuration therapy. Seizures in WD can easily be mistaken as part of dystonia. However, the fluctuating symptoms suggest a seizure.This work was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea, grant number A101038.Peer Reviewe

Modulation Doping via a 2d Atomic Crystalline Acceptor

Two-dimensional (2d) nano-electronics, plasmonics, and emergent phases require clean and local charge control, calling for layered, crystalline acceptors or donors. Our Raman, photovoltage, and electrical conductance measurements combined with \textit{ab initio} calculations establish the large work function and narrow bands of $\alpha$-RuCl$_3$ enable modulation doping of exfoliated, chemical vapor deposition (CVD), and molecular beam epitaxy (MBE) materials. Short-ranged lateral doping (${\leq}65\ \text{nm}$) and high homogeneity are achieved in proximate materials with a single layer of \arucl. This leads to the highest monolayer graphene (mlg) mobilities ($4,900\ \text{cm}^2/ \text{Vs}$) at these high hole densities ($3\times10^{13}\ \text{cm}^{-2}$); and yields larger charge transfer to bilayer graphene (blg) ($6\times10^{13}\ \text{cm}^{-2}$). We further demonstrate proof of principle optical sensing, control via twist angle, and charge transfer through hexagonal boron nitride (hBN)

Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection

Background &amp; Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF). Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.5 mg QW, or placebo. Combination therapy continued until week (W)24, followed by TAF monotherapy until W48; patients then discontinued TAF and were followed until W96 (treatment-free follow-up [TFFU] period). The primary efficacy endpoint was the proportion with ≥1 log10 IU/ml HBsAg decline at W24. Results: Sixty-seven patients received study drug; 27 were followed during TFFU. Nausea, headache, vomiting, fatigue, and dizziness were the most common adverse events. Most adverse events were grade 1. Alanine aminotransferase flares were not observed up to W48. Four patients experienced alanine aminotransferase and hepatitis flares during TFFU; all had HBV DNA increases. Selgantolimod increased serum cytokines and chemokines and redistributed several circulating immune cell subsets. No patients achieved the primary efficacy endpoint. Mean HBsAg changes were −0.12, −0.16, and −0.12 log10 IU/ml in the selgantolimod 3 mg, selgantolimod 1.5 mg, and placebo groups, respectively, at W48; HBV DNA declined in all groups by ≥2 log10 IU/ml as early as W2, with all groups rebounding to baseline during TFFU. No HBsAg or HBeAg loss or seroconversion was observed throughout TFFU. Conclusions: Selgantolimod up to 3 mg was safe and well tolerated. Pharmacodynamics and antiviral activity in viremic patients support continued study of selgantolimod in combination CHB therapies. Impact and implications: Novel therapeutics for chronic HBV infection are needed to achieve a functional cure. In this study, we confirmed the safety and tolerability of selgantolimod (formerly GS-9688, a TLR8) when administered with tenofovir alafenamide over 24 weeks in viremic patients with chronic HBV infection. Overall, declines in HBsAg levels with selgantolimod treatment were modest; subgroup analysis indicated that patients with alanine aminotransferase levels greater than the upper limit of normal had significantly greater declines compared to those with normal alanine aminotransferase levels (–0.20 vs. –0.03 log10 IU/ml; p &lt;0.001). These findings suggest a potential differential response to selgantolimod based on patients’ baseline HBV-specific immune response, which should be considered in future investigations characterizing the underlying mechanisms of selgantolimod treatment and in HBV cure studies using similar immunomodulatory pathways. Clinical trial number: NCT03615066 be found at https://www.gileadclinicaltrials.com/transparency-policy/.</p

Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection

Background &amp; Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF). Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.5 mg QW, or placebo. Combination therapy continued until week (W)24, followed by TAF monotherapy until W48; patients then discontinued TAF and were followed until W96 (treatment-free follow-up [TFFU] period). The primary efficacy endpoint was the proportion with ≥1 log10 IU/ml HBsAg decline at W24. Results: Sixty-seven patients received study drug; 27 were followed during TFFU. Nausea, headache, vomiting, fatigue, and dizziness were the most common adverse events. Most adverse events were grade 1. Alanine aminotransferase flares were not observed up to W48. Four patients experienced alanine aminotransferase and hepatitis flares during TFFU; all had HBV DNA increases. Selgantolimod increased serum cytokines and chemokines and redistributed several circulating immune cell subsets. No patients achieved the primary efficacy endpoint. Mean HBsAg changes were −0.12, −0.16, and −0.12 log10 IU/ml in the selgantolimod 3 mg, selgantolimod 1.5 mg, and placebo groups, respectively, at W48; HBV DNA declined in all groups by ≥2 log10 IU/ml as early as W2, with all groups rebounding to baseline during TFFU. No HBsAg or HBeAg loss or seroconversion was observed throughout TFFU. Conclusions: Selgantolimod up to 3 mg was safe and well tolerated. Pharmacodynamics and antiviral activity in viremic patients support continued study of selgantolimod in combination CHB therapies. Impact and implications: Novel therapeutics for chronic HBV infection are needed to achieve a functional cure. In this study, we confirmed the safety and tolerability of selgantolimod (formerly GS-9688, a TLR8) when administered with tenofovir alafenamide over 24 weeks in viremic patients with chronic HBV infection. Overall, declines in HBsAg levels with selgantolimod treatment were modest; subgroup analysis indicated that patients with alanine aminotransferase levels greater than the upper limit of normal had significantly greater declines compared to those with normal alanine aminotransferase levels (–0.20 vs. –0.03 log10 IU/ml; p &lt;0.001). These findings suggest a potential differential response to selgantolimod based on patients’ baseline HBV-specific immune response, which should be considered in future investigations characterizing the underlying mechanisms of selgantolimod treatment and in HBV cure studies using similar immunomodulatory pathways. Clinical trial number: NCT03615066 be found at https://www.gileadclinicaltrials.com/transparency-policy/.</p