Discovery of Potent Glycosidases Enables Quantification of Smoke-Derived Phenolic Glycosides through Enzymatic Hydrolysis.

When grapes are exposed to wildfire smoke, certain smoke-related volatile phenols (VPs) can be absorbed into the fruit, where they can be then converted into volatile-phenol (VP) glycosides through glycosylation. These volatile-phenol glycosides can be particularly problematic from a winemaking standpoint as they can be hydrolyzed, releasing volatile phenols, which can contribute to smoke-related off-flavors. Current methods for quantitating these volatile-phenol glycosides present several challenges, including the requirement of expensive capital equipment, limited accuracy due to the molecular complexity of the glycosides, and the utilization of harsh reagents. To address these challenges, we proposed an enzymatic hydrolysis method enabled by a tailored enzyme cocktail of novel glycosidases discovered through genome mining, and the generated VPs from VP glycosides can be quantitated by gas chromatography-mass spectrometry (GC-MS). The enzyme cocktails displayed high activities and a broad substrate scope when using commercially available VP glycosides as the substrates for testing. When evaluated in an industrially relevant matrix of Cabernet Sauvignon wine and grapes, this enzymatic cocktail consistently achieved a comparable efficacy of acid hydrolysis. The proposed method offers a simple, safe, and affordable option for smoke taint analysis.

Beneficial Use of the Combination of Gemcitabine and Dacarbazine in Advanced Soft Tissue Sarcomas: Real-World Data.

BACKGROUND: The combination of gemcitabine and dacarbazine has exhibited efficacy in terms of progression-free survival (PFS) and overall survival (OS) for aSTSs, albeit without robust confirmation from larger clinical trials. METHODS: We conducted a retrospective study in a single institution involving aSTS patients treated with gemcitabine and dacarbazine. RESULTS: 95 patients were assessed, pointing to a benefit in PFS of 3.5 months and an OS of 14.2 months. Patients with translocated histotypes had better PFS, while those with platelet-lymphocyte ratios (PLRs) surpassing a specific threshold or lower albumin levels had poorer overall survival. CONCLUSIONS: This study validates previous findings from three phase I-II trials, affirming the utility of this treatment approach in routine clinical practice.

Electrical-biological hybrid system for carbon efficient isobutanol production.

We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO2 to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO2 sequestration is notoriously slow compared to electrochemical CO2 reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form in biological systems. A hybrid system provides a promising method for combining the benefits of both biology and electrochemistry. Previously, Escherichia coli was engineered to assimilate formate and CO2 in central metabolism using the reductive glycine pathway. In this work, we have shown that chemical production in E. coli can benefit from single carbon substrates when equipped with the RGP. By installing the RGP and the isobutanol biosynthetic pathway into E. coli and by further genetic modifications, we have generated a strain of E. coli that can consume formate and produce isobutanol at a yield of >100% of theoretical maximum from glucose. Our results demonstrate that carbon produced from electrocatalytically reduced CO2 can bolster chemical production in E. coli. This study shows that E. coli can be engineered towards carbon efficient methods of chemical production.

Silica Nanoparticle/Fluorescent Dye Assembly Capable of Ultrasensitively Detecting Airborne Triacetone Triperoxide: Proof-of-Concept Detection of Improvised Explosive Devices in the Workroom.

We describe the proof of concept of a portable testing setup for the detection of triacetone triperoxide (TATP), a common component in improvised explosive devices. The system allows for field testing and generation of real-time results to test for TATP vapor traces in air by simply using circulation of the air samples through the sensing mechanism under the air conditioning system of an ordinary room. In this way, the controlled trapping of the analyte in the chemical sensor gives reliable results at extremely low concentrations of TATP in air under real-life conditions, suitable for daily use in luggage storage for airlines or a locker room for a major sporting event. The reported fluorescent methodology is very sensitive and selective, allowing for the trapping of triacetone triperoxide in the chemical sensor to give reliable results at very low concentrations in air under ambient conditions, by comparing the fluorescence of the material before and after exposition to TATP traces in air.

Incidence, prevalence, and treatment patterns in metastatic hormone-sensitive prostate cancer in Spain: ECHOS study.

INTRODUCTION AND OBJECTIVE: The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has changed in recent years due to the approval of new drugs. The aim of this study was to evaluate the prevalence, incidence, and treatment patterns in mHSPC in Spain. PATIENTS AND METHODS: Multicenter, observational, longitudinal, retrospective study in routine clinical practice of patients diagnosed with mHSPC treated in Spanish hospitals between 2015 and 2019 (ECHOS study). Electronic medical records were extracted from BIG-PAC database, which contains geographically representative Spanish centers. RESULTS: Data from 379 men with mHSPC were included. The prevalence of mHSPC ranged between 12.2-14.6% per year, representing from 671 to 824 annual cases with an increasing trend. The mean incidence along the 4-year period was 2.5%, with annual incidence ranging 2.2-3.0%. New annual cases of de novo and recurrent disease ranged between 7-11 and 77-104, respectively, with no trend being observed. These patients were mostly recurrent (91%) with high-volume disease (68.6%). The most common first-line therapy was ADT combined with docetaxel (53%), followed by ADT alone (23.8%), combination of ADT and abiraterone (11.2%), and radiotherapy (8.6%). In the last 12 months before diagnosis of metastasis, most men had been submitted to radical prostatectomy (84.9%). The remaining patients had received radiotherapy (12%) or no treatment at all (3.8%). CONCLUSIONS: The ECHOS study provides epidemiologic data and current patterns of treatment in clinical practice of patients with mHSPC in Spain. These results emphasize the medical need of targeted treatments in these clinical settings.

Mapping capability of linear correlation statistics for characterization of complex materials using laser-induced breakdown spectroscopy.

In this work, the capability of linear correlation statistics for chemical mapping by laser-induced breakdown spectroscopy (LIBS) has been studied for the first time for the characterization of samples with compositional changes on surface and in depth. For that purpose, a corrosion layer of varied spread has been caused in brass samples by chemical treatment and afterwards analyzed by LIBS. Correlation depth profiles, two-dimensional (2D) correlation maps and three-dimensional (3D) correlation maps have been generated from LIBS data to contrast the results obtained from treated and non-treated samples and zones. Conventional LIBS maps based on signal intensity have also been generated for comparison. The conclusions of this study demonstrate the capability and benefits of using the linear correlation method for 3D mapping by LIBS of samples with non-uniform composition. In this sense, the proposed methodology has allowed to determine the location of the corroded regions in the analyzed volume, even in the non-treated zones also affected by the byproducts originated from the chemical attack, in contrast to conventional LIBS mapping based on signal representation.

Influence of Alcohol Consumption, Personality and Attention Deficit Hyperactivity Disorder on Traffic Offenders.

BACKGROUND: Despite the authorities' efforts to promote responsible driving, traffic accidents are a notable cause of death in many countries. Scientific research shows that variables such as alcohol abuse and personality dimensions can contribute to explaining this social phenomenon and the rising number of traffic offences. The present study aims to explore how alcohol abuse, personality disorders and Attention Deficit Hyperactivity Disorder (ADHD) are associated with risky driving behaviour. METHOD: The sample included 300 subjects: the study group (199 convicted of traffic offences) and the control group (101 subjects from the general driving population). The tools used were the International Personality Disorder Scale, the Alcohol Use Disorders Identification Test and the Adult ADHD Self-Report Scale (ASRS). RESULTS: A higher incidence of signs of paranoid, antisocial, impulsive, borderline and anxious personality traits was detected for the study group, as well as a higher prevalence of alcohol abuse. CONCLUSIONS: This research offers indications for the design of effective preventive and reinsertion interventions. It also highlights the importance of considering psychological dimensions to ensure road safety.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

[Alveolar rhabdomyosarcoma: Two fusion-negative cases lacking PAX3-FOXO1 and PAX7-FOXO1]. / Rabdomiosarcoma alveolar. Dos casos negativos para la fusión PAX3-FOXO1 y PAX7-FOXO1.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and adolescence. Morphologically, two major forms are described: alveolar and embryonal rhabdomyosarcoma. The former is generally associated with a poorer prognosis and it usually harbors a characteristic fusion gene, PAX3/7-FOXO1, that is used to confirm the diagnosis. We present two cases, both of which exhibited the classic alveolar histology with immunohistochemical myogenic differentiation (Desmin, MYOD-1 and Myogenin expression) and lacked the characteristic fusion gene PAX3/7-FOXO1. The aim of this report is to highlight the importance of the molecular status in the study and diagnosis of these cases, as it seems to be not only a useful diagnostic tool, but also an important prognostic factor.

Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Adaptive laboratory evolution for improved tolerance of isobutyl acetate in Escherichia coli.

Previously, Escherichia coli was engineered to produce isobutyl acetate (IBA). Titers greater than the toxicity threshold (3 g/L) were achieved by using layer-assisted production. To avoid this costly and complex method, adaptive laboratory evolution (ALE) was applied to E. coli for improved IBA tolerance. Over 37 rounds of selective pressure, 22 IBA-tolerant mutants were isolated. Remarkably, these mutants not only tolerate high IBA concentrations, they also produce higher IBA titers. Using whole-genome sequencing followed by CRISPR/Cas9 mediated genome editing, the mutations (SNPs in metH, rho and deletion of arcA) that confer improved tolerance and higher titers were elucidated. The improved IBA titers in the evolved mutants were a result of an increased supply of acetyl-CoA and altered transcriptional machinery. Without the use of phase separation, a strain capable of 3.2-fold greater IBA production than the parent strain was constructed by combing select beneficial mutations. These results highlight the impact improved tolerance has on the production capability of a biosynthetic system.

Uncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS -GROUP). Part II.

Among all Soft Tissue sarcomas there are some subtypes with low incidence and/or peculiar clinical behaviour, that need to be consider separately. Most of them are orphan diseases, whose biological characteristics imply a clearly different diagnostic and therapeutic approach from other more common sarcoma tumors. We present a brief and updated multidiciplinary review, focused on practical issues, aimed at helping clinicians in decision making. In this second part we review these subtypes: Alveolar Soft Part Sarcoma, Epithelioid Sarcoma, Clear Cell Sarcoma, Desmoplastic Small Round Cell Tumor, Rhabdoid Tumor, Phyllodes Tumor, Tenosynovial Giant Cell Tumors, Myoepithelial Tumor, Perivascular Epithelioid Cell Neoplasms (PEComas), Extraskeletal Myxoid Chondrosarcoma, NTRK-fusions Sarcomas. Most of them present their own radiological and histopathological feautures, that are essential to know in order to achieve early diagnosis. In some of them, molecular diagnosis is mandatory, not only in the diagnosis, but also to plan the treatment. On the other hand, and despite the low incidence, a great scientific research effort has been made to achieve new treatment opportunities for these patients even with approved indications. These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.