Two-axis MEMS positioner for waveguide alignment in silicon nitride photonic integrated circuits.

Alignment is critical for efficient integration of photonic integrated circuits (PICs), and microelectromechanical systems (MEMS) actuators have shown potential to tackle this issue. In this work, we report MEMS positioning actuators designed with the ultimate goal of aligning silicon nitride (SiN) waveguides either to different outputs within a SiN chip or to active chips, such as lasers and semiconductor optical amplifiers. For the proof-of-concept, suspended SiN waveguides implemented on a silicon-on-insulator wafer were displaced horizontally in the direction of light propagation to close an initial gap of 6.92 µm and couple the light to fixed output waveguides located on a static section of the chip. With the gap closed, the suspended waveguides showed ∼ 345 nm out-of-plane misalignment with respect to the fixed waveguides. The suspended waveguides can be displaced laterally by more than ±2 µm. When the waveguides are aligned and the gap closed, an average loss of -1.6 ± 0.06 dB was achieved, whereas when the gap is closed with a ± 2 µm lateral displacement, a maximum average loss of ∼ -19.00 ± 0.62 dB was obtained. The performance of this positioner does not only pave the way for active chip alignment, but it could also be considered for optical switching applications.

tert-Butylhydroperoxide mediated radical cyanoalkylation/cyanoalkenylation of 2-anilino-1,4-naphthoquinones with vinylarenes/arylalkynes and azobis(alkylcarbonitrile)s.

A novel sustainable methodology based on one-pot cyanoalkylation/cyanoalkenylation of 2-anilino-1,4-naphthoquinones with vinylarenes/arylalkynes and azobis(alkylcarbonitrile)s involving a three-component radical cascade pathway has been achieved. Here, tert-butylhydroperoxide (TBHP) acts as an efficient oxidant, and it smoothly drives the reaction, producing the three-component products in very good to excellent yields. This cascade reaction eliminates the use of any base, additive, metal and hazardous cyanating agent. Additionally, this protocol exclusively delivers a stereospecific product in the case of arylalkynes. The involvement of radicals is evidenced through various radical trapping experiments.

Biomarkers of liver diseases.

The liver is one of the pivotal organs in the human body and is fundamentally responsible for detoxification and metabolism. Various disorders such as non-alcoholic fatty liver disease, fibrosis, cirrhosis, hepatocellular carcinoma, and hepatitis are associated with improper functions of the liver. Hence, biomarkers are needed to determine the severity. Further, many liver enzymes, including the cascade of aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and total bilirubin (TBIL), are conventional liver biomarkers. They are not, however, unique to the liver; hence, efforts are being made to identify the precise biomarkers for liver illness that can target liver diseases. HMGB1, cytokeratin 18 (K18), glutathione-S-transferase-α (GST-α), glutamate dehydrogenase (GLDH), malate dehydrogenase (MDH), and microRNAs (miRNA) are a few examples of developing biomarkers used to detect many liver diseases. Hence, the review has highlighted various novel biomarkers of the liver so that various pathophysiological pathways and treatments can be made easier.

Integrated 1 × 3 MEMS silicon nitride photonics switch.

We present a 1 × 3 optical switch based on a translational microelectromechanical system (MEMS) platform with integrated silicon nitride (SiN) photonic waveguides. The fabricated devices demonstrate efficient optical signal transmission between fixed and suspended movable waveguides. We report a minimum average insertion loss of 4.64 dB and a maximum average insertion loss of 5.83 dB in different switching positions over a wavelength range of 1530 nm to 1580 nm. The unique gap closing mechanism reduces the average insertion loss across two air gaps by a maximum of 7.89 dB. The optical switch was fabricated using a custom microfabrication process developed by AEPONYX Inc. This microfabrication process integrates SiN waveguides with silicon-on-insulator based MEMS devices with minimal stress related deformation of the MEMS platform.

Metal-free three-component cyanoalkylation of quinoxalin-2(1H)-ones with vinylarenes and azobis(alkylcarbonitrile)s.

We have unveiled an efficient synthesis of cyanoalkylated quinoxalin-2(1H)-ones via a three-component radical cascade reaction of quinoxalin-2(1H)-ones with vinylarenes and azobis(alkylcarbonitrile)s. K2S2O8 takes part in the reaction as a sole oxidant under base, additive, and metal-free conditions, producing the three-component products in moderate to good yields. The protocol also works with phenylacetylene in the absence of vinyl arenes and provides the respective product. Furthermore, different control experiments with radical scavengers like 2,2,6,6-tetramethylpiperidine-1-oxyl and diphenyl ethylene prove the generation of radicals during the reaction.

One-pot synthesis of α-sulfoximinophosphonate via Kabachnik-Fields reaction.

Herein, we disclose a novel approach for the synthesis of hitherto unknown α-sulfoximinophosphonate via the Kabachnik-Fields reaction of aldehyde, dialkylphosphite and sulfoximine in the presence of InCl3 in THF at 70 °C. α-Sulfoximinophosphonate is synthesized in good yields and its synthetic utilities are proved by functionalizing bromine through the Pd-catalyzed Suzuki-Miyaura cross-coupling reaction and reduction of a nitro group through the Béchamp reduction.

Protective effects of cerebrolysin against chemotherapy (carmustine) induced cognitive impairment in Albino mice.

Chemotherapy-induced cognitive impairment (CICI) comprises different neurological problems, including difficulty in learning new things, concentrating and making decisions that affect daily life activities. Clinical reports indicate that around 70% of cancer patients receiving chemotherapy suffer from cognitive impairment. The purpose of the present study is to examine the effects of widely used anticancer medication (Carmustine) on cognitive function using mice model and investigation of the neuroprotective effects of Cerebrolysin (CBN). Cerebrolysin (CBN) is a mixture of several neurotrophic factors and active peptides with anti-inflammatory, antioxidant, and neuroprotective actions. Our study aimed to establish a mice model of Carmustine (BCNU)-induced cognitive deficits and determine the protective effects of CBN. BCNU (10 mg/kg, i.v.) was administered to mice for 28 days, and behavioral parameters were measured on a weekly basis. CBN (44 and 88 mg/kg, i.p.) was administered daily from day 1 to 28 to BCNU treatment mice. All animals were sacrificed on day 29 and brain hippocampus tissues were used for biochemical, neuroinflammatory, neurotransmitters analysis. BCNU administration animals showed impaired cognition and memory, confirmed from behavioral analysis. Further, BCNU increased oxidative stress, inflammatory cytokines release and altered neurotransmitters concentration as compared to the control group (p < 0.01). However, mice treated with CBN (44 and 88 mg/kg, i.p.) significantly and dose-dependently improved cognitive functions, reduced oxidative stress markers, inflammatory cytokines and restored neurotransmitters concentration as compared to BCNU administered mice (p < 0.05). The finding of current study suggested that CBN could be the promising compound to reverse cognitive impairment associated with use of chemotherapy.

Wide-band silicon photonic MOEMS spectrometer requiring a single photodetector.

We propose a novel integrated micro-opto-mechanical-system spectrometer design in a monochromator setup. It consists of a concave grating fabricated in a planar waveguide that is connected to a rotational electrostatic actuator, which enables angular tuning of the grating. The spectrometer covers a wide operational wavelength range (>100 nm), covering partially the E-band and fully covering the S, C, and L-bands (1416.6 nm - 1696.6 nm), and requires a single photodetector to acquire the spectrum. The spectrometer is designed to exhibit low optical losses throughout the range of motion. The spectrum can be acquired at a frequency of 1.76 kHz. The simulated acquired spectrum features an average insertion loss of -1.8 dB and a crosstalk better than -70 dB with a resolution as low as 1.62 nm. The entire device covers an area of 4 mm x 4 mm and is based on a thick silicon-on-insulator platform.

Correction: tert-Butylhydroperoxide (TBHP) mediated oxidative cross-dehydrogenative coupling of quinoxalin-2(1H)-ones with 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone and 2-hydroxy-1,4-naphthoquinone under metal-free conditions.

Correction for 'tert-Butylhydroperoxide (TBHP) mediated oxidative cross-dehydrogenative coupling of quinoxalin-2(1H)-ones with 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone and 2-hydroxy-1,4-naphthoquinone under metal-free conditions' by Suraj Sharma et al., Org. Biomol. Chem., 2020, 18, 6537-6548, DOI: .

tert-Butylhydroperoxide (TBHP) mediated oxidative cross-dehydrogenative coupling of quinoxalin-2(1H)-ones with 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone and 2-hydroxy-1,4-naphthoquinone under metal-free conditions.

We report an efficient and atom-economical method of C-3 functionalization of quinoxalin-2(1H)-ones with 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone, and 2-hydroxy-1,4-naphthoquinone via the free radical cross-coupling pathway under metal-free conditions. tert-Butylhydroperoxide (TBHP) smoothly promotes the reaction furnishing the cross-dehydrogenative coupling (CDC) products in very good to excellent yields. The protocol neither uses any toxic reagents nor metal catalysts to carry out the reaction, and all the products have been obtained without column chromatography purification. Different radical trapping experiments with 2,2,6,6-tetramethylpiperidine-1-oxyl, butylated hydroxytoluene, and diphenyl ethylene confirm the involvement of radicals.

Non-technical skills curriculum incorporating simulation-based training improves performance in colonoscopy among novice endoscopists: Randomized controlled trial.

BACKGROUND AND AIMS: Non-technical skills (NTS), involving cognitive, social and interpersonal skills that complement technical skills, are important for the completion of safe and efficient procedures. We investigated the impact of a simulation-based curriculum with dedicated NTS training on novice endoscopists' performance of clinical colonoscopies. METHODS: A single-blinded randomized controlled trial was conducted at a single center. Novice endoscopists were randomized to a control curriculum or a NTS curriculum. The control curriculum involved a didactic session, virtual reality (VR) simulator colonoscopy training, and integrated scenario practice using a VR simulator, a standardized patient, and endoscopy nurse. Feedback and training were provided by experienced endoscopists. The NTS curriculum group received similar training that included a small-group session on NTS, feedback targeting NTS, and access to a self-reflective NTS checklist. The primary outcome was performance during two clinical colonoscopies, assessed using the Joint Advisory Group Direct Observation of Procedural Skills (JAG DOPS) tool. RESULTS: Thirty-nine participants completed the study. The NTS group (n = 21) had superior clinical performance during their first (P < 0.001) and second clinical colonoscopies (P < .0.001), compared to the control group (n = 18). The NTS group performed significantly better on the VR simulator (P < 0.05) and in the integrated scenario (P < 0.05). CONCLUSION: Our findings demonstrate that dedicated NTS training led to improved performance of clinical colonoscopies among novices.

Microencapsulation of retinyl palmitate by melt dispersion for cosmetic application.

Retinyl palmitate was encapsulated in wax matrix by melt dispersion for the purpose of economic and sustainable cosmeceutical formulation with minimum use of synthetic chemicals. We evaluated the effect of different process variables of microencapsulation by melt dispersion. In this study, a three level definitive screening design was applied, where the microcapsule properties were analysed through statistical analysis to understand the effect of four process variables: type of wax, theoretical loading capacity, surface concentration and stirring speed. Microparticles were characterised for size using image analysis; loading capacity and encapsulation efficiency using ultraviolet-visible spectroscopy; antioxidant activity through DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Melt dispersion method was effective to produce microcapsules with a spherical shape and mean size as small as 28 µm. The encapsulation efficiency ranged 60-80%. Theoretical loading capacity (p-value = 0.00232, significance level, α = 1%) and surfactant% (p = 0.0573, α = 10%) were found to be the most significant factors to control the actual loading capacity and size of microcapsules.

Adhesion and Stability of Nanocellulose Coatings on Flat Polymer Films and Textiles.

Renewable nanocellulose materials received increased attention owing to their small dimensions, high specific surface area, high mechanical characteristics, biocompatibility, and compostability. Nanocellulose coatings are among many interesting applications of these materials to functionalize different by composition and structure surfaces, including plastics, polymer coatings, and textiles with broader applications from food packaging to smart textiles. Variations in porosity and thickness of nanocellulose coatings are used to adjust a load of functional molecules and particles into the coatings, their permeability, and filtration properties. Mechanical stability of nanocellulose coatings in a wet and dry state are critical characteristics for many applications. In this work, nanofibrillated and nanocrystalline cellulose coatings deposited on the surface of polymer films and textiles made of cellulose, polyester, and nylon are studied using atomic force microscopy, ellipsometry, and T-peel adhesion tests. Methods to improve coatings' adhesion and stability using physical and chemical cross-linking with added polymers and polycarboxylic acids are analyzed in this study. The paper reports on the effect of the substrate structure and ability of nanocellulose particles to intercalate into the substrate on the coating adhesion.

Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis.

BACKGROUND & AIMS: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. METHODS: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation. RESULTS: Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120points), medium-risk (120-240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts. CONCLUSION: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. LAY SUMMARY: HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.

The applicability of hepatocellular carcinoma risk prediction scores in a North American patient population with chronic hepatitis B infection.

BACKGROUND: Patients with chronic hepatitis B (CHB) infection are at an increased risk of developing hepatocellular carcinoma (HCC). Risk scores have been developed in Asian populations to predict HCC risk over time. AIM: To assess the performance of HCC risk prediction models in a heterogeneous population of patients with CHB. METHODS: Scores were calculated at baseline using CU-HCC, REACH-B, NGM1-HCC, NGM2-HCC and GAG-HCC models and the incidence of HCC was determined. The predictive ability of each score was evaluated using the area under the receiver operating characteristic curve (AUROC), Cox regression and plots of observed versus predicted HCC. The predictive value of the scores was compared between Asian and non-Asian patients and between cirrhotic versus non-cirrhotic with and without treatment. RESULTS: Of 2105 patients, 70 developed HCC. Increasing risk score was associated with HCC in all models. The CU-HCC model had the highest AUROC in Asian (0.85) and non-Asian (0.91) patients. Patients identified as low risk by any model had a very low incidence of HCC (0-0.15 per year), with the highest proportion of patients identified as low risk using CU-HCC (67%) or GAG-HCC (78%). The risk of HCC was similar to predicted for low-risk and medium-risk patients but was lower than predicted for high-risk patients. Treated patients had a lower than predicted risk of HCC, particularly in non-cirrhotic high-risk patients with longer follow-up. CONCLUSIONS: Although all models predicted the risk of HCC, models that incorporated parameters of liver function or cirrhosis (CU-HCC/GAG-HCC) were most accurate. Low-risk patients likely require reduced HCC surveillance.

Immigration and viral hepatitis.

WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

Management of HCV in cirrhosis-a rapidly evolving landscape.

Despite the rapid progress in treatment, chronic hepatitis C virus (HCV) infection remains a growing cause of liver-related mortality globally. Patients who have been infected for decades are now presenting with advanced liver disease with the complications of cirrhosis and liver cancer. Early attempts at treatment with peginterferon and ribavirin were limited by toxicity, long treatment duration, and limited efficacy. This was especially relevant for patients with cirrhosis, where exposure to peginterferon-based therapy was relatively ineffective and led to high rates of toxicity. However, the recent development of multiple novel direct-acting antivirals (DAAs) has revolutionized the treatment of HCV. The majority of patients can now be cured with short courses of extremely well-tolerated all-oral regimens. However, the real test of these regimens comes in patients with more advanced liver disease, both in terms of safety and efficacy. Patients with cirrhosis have the greatest need for therapy and have traditionally been the most difficult to cure. The new therapies are rapidly changing this paradigm. Accumulating data suggest that high cure rates are achievable in patients with compensated cirrhosis and may even be possible in patients with signs of liver failure. This review will focus on the treatment of HCV in patients with cirrhosis, with an emphasis on the challenges that remain and strategies to deal with this important population.

MAJOR RISK FACTORS, CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA; A RETROSPECTIVE STUDY AT TIKUR ANBASSA HOSPITAL, ADDIS ABABA UNIVERSITY, ADDIS ABABA, ETHIOPIA.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide accounting for over half a million deaths per year. Hepatocellular carcinoma can occur secondary to viral hepatitis, HBV or HCV. It can also occur secondary to other causes of Cirrhosis (alcoholism being the other most common cause). OBJECTIVES: To describe clinical and laboratory characteristics of Hepatocellular carcinoma in a tertiary care hospital in Addis Ababa, Ethiopia. METHODS: A retrospective study was conducted in patients admitted to Tikur Anbassa specialized Hospital with a diagnosis of Hepatocellular carcinoma during the period of January 1, 2013 to Dec. 31, 2015. Data were collected using structured questionnaire on basic demographic factors, behavioral risks, laboratory profiles and imaging reports. Descriptive analysis was performed on the data collected. RESULTS: Fifty one patients fulfilled the criteria for Hepatocellular carcinoma in the study period. Thirty nine were males and 12 were females. Hepatitis B and C viruses were found to be the causes for HCC in 48% of the cases. History of alcohol abuse was documented in 45% % of the individuals. About 26% of the patients had Ascites, 35% were found to have portal vein thrombosis, The child-Pugh score for patients who had complete profile were Child A 46%, Child B an equal percentage of 46% andfor Child C 0.7%. CONCLUSION: The contribution of Hepatitis virus is high with equivalent proportion of HBV and HCV. Alcohol intake and unidentified risk factors have also played for another half of the causes. Almost a third of patients have Portal vein thrombosis and 96% were either Child Pugh A or B. Enhancing immunization coverage frequent use of infection prevention and availability of treatment for viral hepatitis will help to reduce Hepatocellular carcinoma.

Acute hepatitis C: management in the rapidly evolving world of HCV.

The acute phase of hepatitis C (HCV) infection is typically defined as the initial 6 months following exposure to the virus; however, in some individuals, the acute phase of the infection can last much longer (Orland et al. Hepatology 33:321-27, 2001). Although some patients have symptoms of acute hepatitis, most infected individuals are entirely asymptomatic. As a result, many patients are unaware of the infection until it progresses to chronic infection, and may not develop symptoms until decades later with the onset of decompensated cirrhosis or hepatocellular carcinoma (HCC). A substantial proportion (20-40%) of infected patients clear the virus during the acute phase. Interferon-based treatment is also much more likely to be successful in the acute phase of infection but is relatively poorly tolerated. Therefore, recognition of acute HCV infection is critical to prioritize those patients who do not spontaneously clear the infection for immediate therapy. However, the promise of highly effective well-tolerated all-oral therapies in development may alter the management approach. This review will focus on the epidemiology, natural history, diagnosis, and treatment of acute HCV infection.

Accounting for NAD Concentrations in Genome-Scale Metabolic Models Captures Important Metabolic Alterations in NAD-Depleted Systems.

Nicotinamide adenine dinucleotide (NAD) is a ubiquitous molecule found within all cells, acting as a crucial coenzyme in numerous metabolic reactions. It plays a vital role in energy metabolism, cellular signaling, and DNA repair. Notably, NAD levels decline naturally with age, and this decline is associated with the development of various age-related diseases. Despite this established link, current genome-scale metabolic models, which offer powerful tools for understanding cellular metabolism, do not account for the dynamic changes in NAD concentration. This impedes our understanding of a fluctuating NAD level's impact on cellular metabolism and its contribution to age-related pathologies. To bridge this gap in our knowledge, we have devised a novel method that integrates altered NAD concentration into genome-scale models of human metabolism. This approach allows us to accurately reflect the changes in fatty acid metabolism, glycolysis, and oxidative phosphorylation observed experimentally in an engineered human cell line with a compromised level of subcellular NAD.