Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling

A nickel-catalyzed reductive cross-electrophile coupling between the redox-active N-trifluoroeth-oxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance (30 examples). A combined computational and experimental investigation revealed a pivotal solvent assisted 1,2-Hydrogen Atom Transfer (HAT) process to generate a nucleophilic α-hydroxy-α-trifluoromethyl C-centered radical for theC sp2Csp3 bond forming process

Graphene-Oxide Mediated Chemodivergent Ring-Opening of Cyclobutanols

The chemodivergent ring-opening of cyclobutanols is described under the carbocatalytic assistance of graphene oxide (GO). The protocol enables the synthesis of diversely functionalized dienes or indenes (26 examples) based on the amount of GO employed. Spectroscopic (XPS and ssNMR) as well as experimental investigations revealed a direct involvement of the π-domains of GO in tuning the stability of carbocationic intermediates during the reaction

The Apicomplexa-specific glucosamine-6-phosphate N-acetyltransferase gene family encodes a key enzyme for glycoconjugate synthesis with potential as therapeutic target

Apicomplexa form a phylum of obligate parasitic protozoa of great clinical and veterinary importance. These parasites synthesize glycoconjugates for their survival and infectivity, but the enzymatic steps required to generate the glycosylation precursors are not completely characterized. In particular, glucosamine-phosphate N-acetyltransferase (GNA1) activity, needed to produce the essential UDP-N-acetylglucosamine (UDP-GlcNAc) donor, has not been identified in any Apicomplexa. We scanned the genomes of Plasmodium falciparum and representatives from six additional main lineages of the phylum for proteins containing the Gcn5-related N-acetyltransferase (GNAT) domain. One family of GNAT-domain containing proteins, composed by a P. falciparum sequence and its six apicomplexan orthologs, rescued the growth of a yeast temperature-sensitive GNA1 mutant. Heterologous expression and in vitro assays confirmed the GNA1 enzymatic activity in all lineages. Sequence, phylogenetic and synteny analyses suggest an independent origin of the Apicomplexa-specific GNA1 family, parallel to the evolution of a different GNA1 family in other eukaryotes. The inability to disrupt an otherwise modifiable gene target suggests that the enzyme is essential for P. falciparum growth. The relevance of UDP-GlcNAc for parasite viability, together with the independent evolution and unique sequence features of Apicomplexa GNA1, highlights the potential of this enzyme as a selective therapeutic target against apicomplexans

Bacterial and Fungal Communities Are Specifically Modulated by the Cocoa Bean Fermentation Method

Cocoa bean fermentation is carried out in different production areas following various methods. This study aimed to assess how the bacterial and fungal communities were affected by box, ground or jute fermentation methods, using high-throughput sequencing (HTS) of phylogenetic amplicons. Moreover, an evaluation of the preferable fermentation method was carried out based on the microbial dynamics observed. Box fermentation resulted in higher bacterial species diversity, while beans processed on the ground had a wider fungal community. Lactobacillus fermentum and Pichia kudriavzevii were observed in all three fermentation methods studied. Moreover, Acetobacter tropicalis dominated box fermentation and Pseudomonas fluorescens abounded in ground-fermented samples. Hanseniaspora opuntiae was the most important yeast in jute and box, while Saccharomyces cerevisiae prevailed in the box and ground fermentation. PICRUST analysis was performed to identify potential interesting pathways. In conclusion, there were noticeable differences between the three different fermentation methods. Due to its limited microbial diversity and the presence of microorganisms that guarantee good fermentation, the box method was found to be preferable. Moreover, the present study allowed us to thoroughly explore the microbiota of differently treated cocoa beans and to better understand the technological processes useful to obtain a standardized end-product

Focolaio di COVID-19 in un campo estivo nella Regione Piemonte (2021): descrizione, lezioni apprese e raccomandazioni per futuri campi estivi

COVID-19 outbreak at a summer camp in Piedimont region in 2021: description, lessons learned and recommendations for future summer camps Introduction In August 2021, an outbreak of coronavirus disease 2019 (COVID-19) occurred in a summer camp in Piedmont region, Italy, affecting primarily campers aged ≤16 years. We conducted a retrospective cohort study among campers and personnel (attendees) to determine the attack rate (AR), evaluate possible factors associated with transmission and propose recommended measures for the organization of future summer camps. Materials and methods A de-identified database including demographic, role of attendees, cohorting, means of transportation to the camp, inter-camper interactions, SARS-CoV-2 testing results and symptomatology was used. All analysis data came from a collection of data carried out by the organizing private company and the information related to the mitigation protocol put in place was provided by the health care personnel. All campers were asked to have an antigen/molecular test within 72 hours before departure. Nine dedicated buses departed from different Italian regions towards the camp. All travellers wore a surgical mask during the trip. Upon arrival, regardless of the bus used, the campers were divided into 11 subgroups with no further contact between them unless they were blood relatives. No SARS-CoV-2 screening tests were scheduled for campers after arrival and during the camp period. On the other hand, personnel had a screening test at each shift change. During the camp period, antigen tests were performed at cases with symptoms suggestive of infection. Only attendees enrolled in the private company and those who received at least one test since arrival at the camp were considered in the study. We calculated overall AR and relative risk (RR) along with specific, transmission-focused risk factors. Results Among the 187 study participants, the median age was 14 years (range: 6-45). Seven days after arrival at the camp, 8 campers developed symptoms and tested positive. The overall AR was 33.7% (63 out of 187), and 34.2% (50/146) for campers and 31.7% (13/41) for staff, respectively. Among those with available symptoms information, 72% (36/50) were asymptomatic at the time of testing. Only 17.1% of campers had direct contact with blood relatives from other subgroups. The AR of participants using a bus was 36.2% (59/163) with an RR of 1.18 (95% CI = 0.51-2.73,) and the AR of those belonging to a subgroup was 35% (62/177) with an RR of 3.5 (95% CI = 0.54-22.7). For personnel, participation to a subgroup gave an AR of 38.7% (12/31) and an RR of 3.87 (95% CI = 0.57-26.18). All but four subgroups had a high AR (>33,3). Conclusions Getting tested prior to traveling and campers separation into low-contact subgroups was not sufficient enough to avoid a high number of infections in this summer camp. Analysis did not allow the identification of an index case or helped to understand whether the outbreak originated from the attendees who travelled on the same bus. The high AR observed in all subgroups suggest that there was frequent contact between attendees belonging to different subgroups. Sharing of common areas such as the canteen and contact between attendees are possible factors that have contributed to the spread of the outbreak. The experience gained by the analysis of this data was used for the review of measures for the organization of summer camps in 2022

Course and Lethality of SARS-CoV2 Epidemic in Nursing Homes after Vaccination in Florence, Italy

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents

reference architecture and framework

M. Adorni, F. Arcelli, S. Bandini, L. Baresi, C. Batini, A. Bianchi, D. Bianchini, M. Brioschi, A. Caforio, A. Cali, P. Cappellari, C. Cappiello, T. Catarci, A. Corallo, V. De Antonellis, C. Franza, G. Giunta, A. Limonta, G. Lorenzo, P. Losi, A. Maurino, M. Melideo, D. Micucci, S. Modafferi, E. Mussi, L. Negri, C. Pandolfo, B. Pernici, P. Plebani, D. Ragazzi, C. Raibulet, M. Riva, N. Simeoni, C. Simone, G. Solazzo, F. Tisato, R. Torlone, G. Vizzari, and A. Zill

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients