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The development of glycobiology relies on the sources of particular oligosaccharides in their purest forms. As the isolation of the oligosaccharide structures from natural sources is not a reliable option for providing samples with homogeneity, chemical means become pertinent. The growing demand for diverse oligosaccharide structures has prompted the advancement of chemical strategies to stitch sugar molecules with precise stereo‐ and regioselectivity through the formation of glycosidic bonds. This Review will focus on the key developments towards chemical O‐glycosylations in the current century. Synthesis of novel glycosyl donors and acceptors and their unique activation for successful glycosylation are discussed. This Review concludes with a summary of recent developments and comments on future prospects. Chasing diversity: Chemical O‐glycosylation remains a challenge for the preparation of diverse glycosidic linkages that are present in nature. The 21st century has seen a significant development in the area of chemical O‐glycosylation. This Review illustrates these developments in a comprehensive manner and concludes with the scope for further development.

Stereoselective glycosylations are one of the most challenging tasks of synthetic glycochemists. The protecting building blocks on the glycosides contribute significantly in attaining the required stereochemistry of the resulting glycosides. Strategic installation of suitable protecting groups in the C-2 position, vicinal to the anomeric carbon, renders neighbouring group participation, whereas protecting groups in the distal C-3, C-4, and C-6 positions are often claimed to exhibit remote group participation with the anomeric carbon. Neighbouring group participation and remote group participation are being widely studied to help the glycochemists design the synthetic protocols for multistep synthesis of complex oligosaccharides and in turn, standardise the process of the glycosylation towards a particular stereochemical output. While neighbouring group participation has been quite effective in achieving the required stereochemistry of the produced glycosides, remote participation exhibits comparatively less efficacy in achieving complete stereoselectivity in the glycosylation reactions. Remote participation is a still highly debated topic in the scientific community. However, implementing the participating role of the remote groups in glycosylation reactions is widely practised to achieve better stereocontrol and to facilitate the formation of synthetically challenging glycosidic linkages.

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6–8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2. A third dose of the COVID-19 vaccine mRNA-1273 is safe and boosts SARS-CoV-2 neutralizing antibody titers almost two-fold higher than the peak levels observed after completion of a two-dose series, highlighting the potential clinical benefit of a booster dose.

Combination checkpoint blockade (CCB) targeting inhibitory CTLA4 and PD1 receptors holds promise for cancer therapy. Immune-related adverse events (IRAEs) remain a major obstacle for the optimal application of CCB in cancer. Here, we analyzed B cell changes in patients with melanoma following treatment with either anti-CTLA4 or anti-PD1, or in combination. CCB therapy led to changes in circulating B cells that were detectable after the first cycle of therapy and characterized by a decline in circulating B cells and an increase in CD21lo B cells and plasmablasts. PD1 expression was higher in the CD21lo B cells, and B cell receptor sequencing of these cells demonstrated greater clonality and a higher frequency of clones compared with CD21hi cells. CCB induced proliferation in the CD21lo compartment, and single-cell RNA sequencing identified B cell activation in cells with genomic profiles of CD21lo B cells in vivo. Increased clonality of circulating B cells following CCB occurred in some patients. Treatment-induced changes in B cells preceded and correlated with both the frequency and timing of IRAEs. Patients with early B cell changes experienced higher rates of grade 3 or higher IRAEs 6 months after CCB. Thus, early changes in B cells following CCB may identify patients who are at increased risk of IRAEs, and preemptive strategies targeting B cells may reduce toxicities in these patients.

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Participatory sensing has become an effective way of sensing urban dynamics due to the widespread availability of smartphones among citizens. Traditionally, separate urban sensing applications are designed to monitor different urban dynamics like environment, transportation, mobility, etc. However, combining these applications to aggregate information can lead to various new inferences. The main objective of this work is to improve urban sensing applications by overcoming their individual limitations. A unified framework called JUSense (Judicious Urban Sensing) is proposed that can derive benefits from these applications by combining their functionalities. JUSense provides the opportunity for applications to tackle the challenges associated with data collection, aggregation of data in cloud, calibration, data cleaning, and prediction. A multi-view fusion model is proposed for spatiotemporal urban air and noise pollution map generation. Further, a random forest classifier is built to classify the driving events. Here, large scale experiments are performed to evaluate the efficacy of JUSense on real-world dataset. Both the fusion model and the random forest classifier yield better accuracies compared to the baseline methods. Additionally, case studies are conducted to show the advantages that can arise out of the mutual interactions among the applications.

In part 1 of a phase 2–3 trial, a 50-μg dose of mRNA-1273 vaccine was safe and immunogenic. In part 2, nearly 4000 6-to-11-year-olds received two doses of vaccine or placebo and were followed for a median of 82 days. The vaccine had mainly mild adverse effects and was immunogenic in 99%, similar to the results in 18-to-25-year-olds. Vaccine efficacy during a delta-variant period was 88%.

This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA-1273 as primary vaccination series and booster doses were enrolled in a sequential, nonrandomized manner and received single-second boosters of mRNA-1273 ( n  = 376) or bivalent mRNA-1273.222 ( n  = 511). Primary objectives were safety and the noninferiority or superiority of neutralizing antibody (nAb) responses against Omicron BA.4/BA.5 and ancestral SARS-CoV-2 with the D614G mutation (ancestral SARS-CoV-2 (D614G)), 28 days post boost. Superiority and noninferiority were based on prespecified success criteria (lower bounds of 95% CI > 1 and < 0.677, respectively) of the mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent Omicron BA.4/BA.5-containing mRNA-1273.222 elicited superior nAb responses against BA.4/BA.5 versus mRNA-1273 and noninferior responses against ancestral SARS-CoV-2 (D614G) at day 29 post boost in participants without detectable prior SARS-CoV-2 infection. Day 29 seroresponses against Omicron BA.4/BA.5 were higher for mRNA-1273.222 than for mRNA-1273 and similar against ancestral SARS-CoV-2 (D614G), both meeting noninferiority criterion. The safety profile of mRNA-1273.222 was similar to that previously reported for mRNA-1273 with no new safety concerns identified. Continued monitoring of neutralization and real-world vaccine effectiveness are needed as additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065. An Omicron BA.4/BA.5 mRNA booster vaccine elicits high neutralizing responses to the BA.4/BA.5 variant and to ancestral SARS-CoV-2, supporting tailoring booster vaccines to the predominant Omicron variant.

Background & objectives: In India, lifestyle changes have contributed to increase in the number of people suffering from lipid profile abnormalities, which is a major risk factor for coronary artery diseases. The present study was aimed to estimate the prevalence of lipid profile abnormalities and 10 yr risk of cardiovascular disease (CVD) among the adult population in west Tripura district and to study the association of lipid profile abnormalities and increased CVD risk with sociodemography, body mass index (BMI), hypertension, random blood sugar (RBS) and haemoglobin level. Methods: This cross-sectional study was conducted amongst 445 adults of 20 to 60 yr of age from a randomly selected block in west Tripura district. The 10 yr risk of CVD was estimated using the Framingham Risk Assessment Tool. Results: The study revealed that overall 83.4 per cent adult population had lipid profile abnormalities, with 22.2, 42 and 70.3 per cent of participants having hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein level, respectively. Gender (P=0.02) and BMI (P<0.001) were the significant determinants of dyslipidaemia. Only 3.8 per cent of participants had intermediate or high risk of CVD, with all of them being males. Gender, age, occupation and RBS were significantly associated with increased CVD risk. Interpretation & conclusions: The study revealed a high burden of lipid profile abnormalities in the study population, with males having more risk of CVD. Hence, periodic screening of lipid profile abnormalities and risk of CVD should be incorporated at the primary care level to combat the CVD epidemic in India.

The objective, accurate and rapid quantification of agricultural drought is the key component of effective drought planning and management mechanism. The present study proposed a new index, i.e. multivariate phenology-based agricultural drought index (MADI), for quantification of the agricultural drought using long-term (1982–2015) crop phenological parameters. The 15-day global inventory modelling and mapping studies time-series normalized difference vegetation index (NDVI) data (~ 8 km) were interpolated at daily scale and smoothened using Savitzky and Golay filtering technique. Different crop phenological parameters, i.e. start of season, end of season, length of the growing period (lgp), integrated NDVI (iNDVI), etc., were estimated using a combination of threshold and derivative approaches for individual pixels during kharif season. Based on the time of occurrence, the agricultural droughts may lead to delay in crop sowing, reduction in cropped area and/or decreased production. Hence, the lgp and iNDVI were selected among all phenological parameters for their capability to represent alterations in crop duration and crop production, respectively. The long-term lgp and iNDVI of individual pixel were detrended and transformed into standardized lgp (Slgp) and standardized iNDVI (SiNDVI) to eliminate the existing trends developed due to technological improvements during study period and existing heterogeneity of Indian agricultural system, respectively. The MADI was calculated by fitting Slgp and SiNDVI into joint probability distribution, where the best joint distribution family along with associated parameters was selected based on the goodness-of-fit for individual pixel. The values of MADI vary between − 4 and + 4, where the negative and positive values represent drought and non-drought conditions, respectively. The efficacy of the proposed index was tested over the Indian region by comparing with the multivariate standardized drought index, which considers the impacts of both meteorological and soil moisture drought using copula approach.