Multianalytical provenance analysis of Eastern Ross Sea LGM till sediments (Antarctica): Petrography, geochronology, and thermochronology detrital data

In order to reveal provenance of detrital sediments supplied by West Antarctic Ice Sheet (WAIS), 19 glaciomarine cores of Last Glacial Maximum age were analyzed from Eastern Ross Sea and Sulzberger Bay. Analytical techniques included petrographic analysis of gravel-sized clasts, geochronology (zircon U-Pb: Zrn-UPb) and thermochronology (apatite fission track: AFT) of sand-sized fractions. Petrographic analysis revealed a similarity with the lithologies presently exposed in western Marie Byrd Land (MBL), with major roles played by low-grade metamorphic rocks and granitoids. Furthermore Zrn-UPb and AFT data allowed to identify the ages of formation and cooling of sedimentary source area, consisting of Cambrian-Precambrian basement (i.e., Swanson Formation in western MBL) which underwent at least two episodes of magma intrusion, migmatization and cooling during Devonian-Carboniferous and Cretaceous-Paleocene times. Scarcity of volcanic clasts in the region of Ross Sea along the front of West Antarctica Ice Streams in association with the occurrence of AFT Oligocene-Pliocene dates suggests a localized tectonic exhumation of portions of MBL, as already documented for the opposite side of West Antarctic Rift System in the Transantarctic Mountains. Furthermore, a Zrn-UPb and AFT population of Late Triassic-Jurassic age indicates the presence of unexposed rocks that formed or metamorphosed at that time in the sedimentary source area, which could be identified in McAyeal Ice Stream and Bindschadler Ice Stream catchment areas

Social cleavages and the political system in late 19th century Italy

Ausgehend von der Feststellung, daß es nur sehr wenige Studien im Bereich der quantitativen historischen Politikforschung über die Wandlungen des politischen Systems in Italien gibt, untersucht der Autor Wähler, Wahlverhalten, Wahlen, Politiker und das politische System in Italien zwischen 1861 und 1913. Es wird festgestellt, daß die regionalen Unterschiede in Italien einen prägenden Einfluß auf die extrem unterschiedlichen Befunde zu praktisch allen Variablen haben. So reicht die Wahlteilnahme 1861 von über 90 % auf Sizilien bis hinunter zu 20 % in den Städten des Nordens wie Bologna, Florenz, Genua und Mailand. Erklärend ist hier das Phänomen des Patronagesystems, die unterschiedlichen Einflußnahmen sozialer Kontrolle in Stadt und Land. Als weitere Besonderheit des italienischen politischen Systems muß der außergewöhnlich hohe Anteil an Berufspolitikern angesehen werden. Im Zusammenhang damit ist die im Vergleich zu anderen Ländern sehr hohe Verweildauer im Parlament der italienischen Abgeordneten zu sehen. Als wichtiges intervenierendes Phänomen wird die Korruption beschrieben, insbesondere der Stimmenkauf durch Bestechung. Dieses Verhalten war insbesondere in ländlich geprägten Regionen üblich, wo die Stimmen durch kleine Geldzahlungen, warme Mahlzeiten oder einen halben Liter Wein gekauft wurden. Im Italien des ausgehenden 19. Jahrhunderts wird die Bürokratie auf breiter Front von Korruption durchdrungen, ein Prozeß der als "Versüdlichung der Bürokratie" allseits bekannt wurde. Damit erhielten die Angehörigen der oberen Schichten aus dem Mezzogiorno Italiens die Chance, Führungspositionen in der bürgerlichen Gesellschaft des Staates einzunehmen. (ICF

Emergency Resection for Colonic Cancer Has an Independent and Unfavorable Effect on Long-Term Oncologic Outcome

Background Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) remain controversial. This study aims to assess short- and long-term outcomes of emergency versus elective CRC surgery. Methods In this single-center retrospective cohort study, patients undergoing emergency or elective colonic resections for CRC from January 2013 to December 2017 were included. Primary outcome was long-term survival. As secondary outcomes, we sought to analyze potential differences on postoperative morbidity and concerning the oncological standard of surgical resection. The Kaplan-Meier curves and Cox proportional hazard model were used to compare survival between the groups. Results Overall, 225 CRC patients were included. Of these 192 (85.3%) had an elective and 33 (14.7%) an emergency operation. Emergency indications were due to obstruction, perforation, or bleeding. Patients in the emergency group had higher ASA score (p = 0.023), higher Charlsson comorbidity index (CCI, p = 0.012), and were older than those in the elective group, with median age 70 (IQR 63-79) years and 78 (IQR 68-83) years, for elective and emergency, respectively (p = 0.020). No other preoperative differences were observed. Patients in the emergency group experienced significantly more major complications (12.1% vs. 3.6%, p = 0.037), more anastomotic leakage (12.1% vs. 1.6%, p = 0.001), need for reoperation (12.1% vs. 3.1%, p = 0.021), and postoperative mortality (2 patients vs. 0, p < 0.001). No differences in terms of final pathological stage, nor in accuracy of lymphadenectomy were observed. Overall survival was significantly worse in case of emergency operation, with estimated median 41 months vs. not reached in elective cases (p < 0.001). At the multivariate analysis, emergency operation was confirmed as independent unfavorable determinant of survival (with hazard rate HR = 1.97, p = 0.028), together with age (HR = 1.05, p < 0.001), postoperative major morbidity (HR = 3.18, p = 0.012), advanced stage (HR = 5.85, p < 0.001), and need for transfusion (HR = 2.10, p = 0.049). Conclusion Postoperative morbidity and mortality were increased in emergency versus elective CRC resections. Despite no significant differences in terms of accuracy of resection and pathological stages, overall survival was significantly worse in patients who underwent emergency procedure, and independent of other determinants of survival

Minimally invasive lymphadenectomy for gastric cancer: Could the robotic approach provide any benefits than laparoscopy?

Gastrectomy is the cornerstone of treatment for gastric cancer. Since the introduction of minimally invasive techniques, the main challenge for surgeons has been to achieve the same surgical radicality, adequate lymphadenectomy, and negative resection margins as with the open approach. Previous Eastern trials showed non-inferiority of laparoscopic gastrectomy, whereas Western trials reported a higher number of complications. This may depend on the different eligibility criteria to select patients and surgeons. Currently, the increased availability of robotic systems has led to renewed enthusiasm. We present a critical review of published randomized control trials (up to October 2024) to investigate the real benefits of robotic compared to open and laparoscopic approaches. Robotic gastrectomy has shown similar oncological outcomes in survival and lymph node retrieval, particularly in suprapancreatic stations, with the advantage of a more acceptable rate of pancreatic fistula and feasible anastomotic reconstruction. Some clinical situations, such as postchemotherapy interstitial fibrosis and distortion of anatomical planes, may increase the technical difficulty. Only four published trials assessed the implications of a pre-operative therapy, with no robotic surgery cases. Robotic systems may reduce intraoperative blood loss, the risk of conversion and allow more extensive lymphadenectomies in cancers with a high risk of extraperigastric metastases, or with clinically proven para-aortic node metastases, although clinical trials evaluating robotic gastrectomy after neoadjuvant therapy have not yet been published. © The Author(s) 2025

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

The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study

Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04–3.04]), primary schooling or less (RR 2.16 [1.21–3.87]), being overweight (RR 4.34 [1.04–19.01]) or obese (RR 6.55 [1.57–27.37]), having public prenatal care (RR 2.16 [1.01–4.68]), planned pregnancies (RR 2.09 [1.15–3.78]), onset of infection in postpartum period (RR 6.00 [1.37–26.26]), chronic hypertension (RR 2.15 [1.37–4.10]), pre-existing diabetes (RR 3.20 [1.37–7.46]), asthma (RR 2.22 [1.14–4.34]), and anaemia (RR 3.15 [1.14–8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.Outra Agênci

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways