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Objectives: We investigated the impact of school reopening on SARS-CoV-2 transmission in Italy, Germany, and Portugal in autumn 2022 when the Omicron variant was prevalent. Methods: A prospective international study was conducted using the case reproduction number (Rc) calculated with the time parametrization of Omicron. For Germany and Italy, staggered difference-in-differences analysis was employed to explore the causal relationship between school reopening and Rc changes, accounting for varying reopening dates. In Portugal, interrupted time series analysis was used due to simultaneous school reopenings. Multivariable models were adopted to adjust for confounders. Results: In Italy and Germany, post-reopening Rc estimates were significantly lower compared to those from regions/states that had not yet reopened at the same time points, both in the student population (overall average treatment effect for the treated subpopulation [O-ATT]: -0.80 [95% CI: -0.94;-0.66] for Italy; O-ATT-0.30 [95% CI: -0.36;-0.23] for Germany) and the adult population (O-ATT: -0.04 [95% CI: -0.07;-0.01] for Italy; O-ATT: -0.07 [95% CI: -0.11;-0.03] for Germany). In Portugal, there was a significant decreasing trend in Rc following school reopenings compared to the pre-reopening period (sustained effect: -0.03 [95% CI: -0.04; -0.03] in students; -0.02 [95% CI: -0.03; -0.02] in adults). Conclusions: We found no evidence of a causal relationship between school reopenings in autumn 2022 and Omicron SARS-CoV-2 transmission.

The foreland Claromecó Basin, located in the south-western sector of Buenos Aires province, Argentina, has a relevant economic and energetic interest due to the presence of coal layers contained in the Permian Tunas Formation, which might be considered effective source rock for gas resource generation. This study aims to reconstruct the diagenetic evolution of the Tunas Formation at the Claromecó Basin (PANG 0001 and PANG 0003 wells) and determine how the diagenesis affected the reservoir quality. To this purpose, core samples of the Tunas Formation were analysed using a combination of micro petrographic analyses (transmitted light, QEMSCAN, cathodoluminescence), fluid inclusions studies, and petrophysical methods (conventional core analysis, CCA). The analysed sedimentary successions are composed of sandstones interbedded with mudrocks, carbonaceous mudrocks, tuffs, and coals. Sandstones are medium- to fine-grained, framework-supported, and moderate-to-well-sorted. Authigenic minerals are calcite and laumontite, with minor proportions of quartz and feldspar overgrowths and clay minerals (illite, muscovite, and chlorite). Porosity is of secondary type, generated by fracturing and dissolution of feldspars and carbonate cement. Porosity determined by optical, QEMSCAN, and CCA analyses ranges from 0.1 to 4 %, with a permeability varying between 10-3 and 10-6 millidarcies. Fluid inclusion studies were performed in sandstone cements and calcite and quartz veins. Primary, pseudo-secondary, and secondary aqueous and organic fluid inclusions were recognized. Organic fluid inclusions show green and light blue fluorescence, which indicates the presence of hydrocarbons. Homogenization temperatures of fluid inclusions obtained from microthermometry studies range from 124 to 200 °C in cements and 110 to 230 °C in veins. These temperatures confirm a metagenesis stage for the Tunas Formation, within the wet to dry gas window. Given the petrophysical characteristics of the analyzed levels, sandstones could be considered unconventional tight gas sandstone reservoirs. Obtained results point out that during early diagenesis, physical compaction and precipitation of carbonate cement are the principal factors that significantly reduce the primary porosity. Furthermore, in the mesogenesis stage, chemical compaction, calcite and zeolite cements precipitation, and quartz overgrowths further contribute to porosity loss. However, secondary porosity was produced during mesogenesis due to the dissolution of unstable grains and calcite cements caused by the action of acid fluids generated during the decomposition and maturity of organic matter. Additionally, secondary porosity was also generated by fracturing due to burial and tectonic stress and by the increased pore pressure during hydrocarbon generation and migration. The reservoir properties of the Claromecó Basin have been controlled mainly by diagenetic and tectonic processes that acted during the burial history of the basin. Clasts and cements composition also influenced diagenesis together with the presence of organic-rich rocks, which could generate hydrocarbons.

Geological evidence indicates that the deformation along the southwest Gondwana margin began during the Middle-to-Late Devonian (the Acadian-Cháñica orogenic phase in Argentina). It has been interpreted that this deformation occurred as a consequence of the collision of Chilenia from the west and Patagonia from the south-southwest with Gondwana. As both Chilenia and Patagonia collided at the same time, in this study, we proposed that these continental blocks conform to the same allochthonous drift terrain, named here as CHIPA. The geological evolution of this margin is still under debate. Field work, paleomagnetic studies, and anisotropy of magnetic susceptibility (AMS) studies were integrated from different localities along this paleomargin in Argentina. In Permian rocks, all the geological indicators show a clear regional NW-SE elongation signature and NE-SW shortening direction. The middle Devonian to Permian patterns are more complex as the result of stress interference and the overlapping of orogenic activities with different intensities and ages. The deformation that started as the product of the CHIPA collision with Gondwana during the Middle Devonian continued through the Permian (the Hercinian-San Rafael orogenic phase in Argentina) as post-collisional compressive deformation, consequence of the paleogeographic re-organization of Gondwana and Laurentia, which moved toward the Equator from the south and the north, respectively, to form the Pangea supercontinent during the Triassic.

Abstract Background Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children. As it becomes clear that the SARS-CoV-2 pandemic will last for a long time, there is a high need for studies and solutions to support safe schools opening based on scientific evidence of harms and benefits. The Lolli-Methode (LM) is a strategy for epidemiological surveillance and early intervention aiming at SARS-CoV-2 outbreaks’ reduction in schools, relying on polymerase chain reaction analysis of saliva samples. Methods In this cluster randomised trial protocol, we aim to determine whether the LM is useful to support schools opening and to reduce clusters and attack rates in schools, compared with the standard of care (SoC) surveillance by public health departments. This multicenter study will enrol 440 classes (around 8800 students, teachers and other personnel) from two countries, cluster randomised to LM or SoC. The samples from the pools will be collected and tested using PCR-based techniques. Test results will be combined with questionnaires filled in by children, parents, schoolteachers, and principals, concerning ongoing mitigation measures, their perceived psychological impact and other health and socio-economic information. An ancillary observational study will be carried out to study the prevalence of SARS-CoV-2 in schools, frequencies and size of clusters and attack rates, to compare the effectiveness of the different preventive measures adopted and to evaluate psychological issues in students and teachers in relation to the pandemic’s containment measures. Discussion By the end of this study, we will have defined and characterised the applicability of the LM for SARS-CoV-2 surveillance, as well as the impact of pandemic preventive measures on children and teachers. Trial registration International Standard Randomised Controlled Trial Number: NCT05396040, 27.05.2022.

Ilaria Cutica,1,* Silvia Riva,2,* Ester Maria Orlandi,3 Alessandra Iurlo,4 Claudia Vener,1 Chiara Elena,3 Cristina Bucelli,4 Daniele Cattaneo,1,4 Elisa Tomezzoli,5 Gabriella Pravettoni1,5 1Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; 2Department of Psychology and Pedagogic Science, St Mary’s University, London, UK; 3Hematology Unit, Foundation IRCCS Policlinico San Matteo, Pavia, Italy; 4Hematology Division, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 5Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology (IEO), IRCCS, Milan, Italy*These authors contributed equally to this workCorrespondence: Ilaria Cutica, Department of Oncology and Hemato-Oncology, University of Milan, Via Santa Sofia 9/1, Milan, 20123, Italy, Tel +39 02 50321562, Fax +39 02 50318938, Email ilaria.cutica@unimi.itPurpose: Patients with chronic myeloid leukemia (CML) who present a sustained deep molecular response (DMR) for a stable period of time might benefit from discontinuing tyrosine kinase inhibitors (TKIs). A significant number of patients seem able to reach this stage due to the availability of TKIs. However, many patients remain reluctant about TKI discontinuation and may refuse treatment interruption. The purpose of this study was to explore the clinical and psycho-cognitive factors that may influence the decision to discontinue TKI therapy, thereby gaining a better understanding of patients’ viewpoints on TKI discontinuation.Patients and Methods: One hundred and nineteen patients diagnosed with CML aged between 34 and 69 were enrolled (67 males and 52 females). Different clinical information and psycho-cognitive aspects such as attitude toward risk behaviours, risk preferences, need for cognitive closure, and tendency to resist to changes were assessed through the administration of a battery of questionnaires.Results: A higher tendency toward risk behaviours and the tendency to focus on possible gain in the short term rather than on losses might represent important predictors for the willingness to accept TKI discontinuation. Possible relapses following interruption of the therapy are the most common reason for concern. Furthermore, lower levels of resistance to change and having previously experienced the desire to interrupt the therapy might lead patients to accept a higher probability of relapse risk when facing such a decision.Conclusion: TKI discontinuation appears appealing and challenging at the same time for many CML patients, and different factors may influence this decision. Psychology plays a crucial role in assisting physician-patient communication and informed decision-making.Keywords: TKI discontinuation, chronic myeloid leukaemia, patients’ perspective, risk preferences, decision-making

IntroductionThe closure of sports centres was implemented as a preventive measure to mitigate the transmission of SARS-CoV-2. Given the observed global decline in physical activity and concurrent rise in sedentary behaviour, even among younger age groups, a retrospective cross-sectional study was undertaken to evaluate the effects of this measure on mental health in children, adolescents, and young adults during the initial phases of the COVID-19 pandemic.MethodsA total of 1,717 non-professional athletes (age range: 6–25; 53.9% males, 44.6% females) completed an online questionnaire including widely used and validated measures for mental health assessment (SDQ and PGWB-S) and questions regarding sociodemographic characteristics (such as gender), physical activity, and screen time. The association between mental health and sociodemographic characteristics, physical activity, and screen time was evaluated by using univariate and multivariable logistic regression models.ResultsIn children and adolescents, the incidence of psychological difficulties was associated with not being physically active (OR = 1.49; 95% CI: 1.09, 2.07; p = 0.015). Engaging in physical activity during the period of closures, particularly if more than twice a week, was significantly associated with less psychological difficulties for children/adolescents (OR = 0.54; 95% CI: 0.35, 0.82; p = 0.004) and psychological symptoms (i.e., psychological well-being lower than the median) for youth/young adults (OR = 0.25; 95% CI: 0.14, 0.45; p < 0.001). More psychological difficulties were also found in males for children and adolescents (OR = 1.37; 95% CI: 1.06, 1.79; p = 0.018). However, young adult males showed less psychological symptoms than females (OR = 0.35; 95% CI: 0.22, 0.55; p = 0.001). Additionally, a greater amount of screen time was associated with a higher incidence of psychological symptoms in the whole sample.ConclusionsOur results confirm the positive impact of physical activity on mental health during the COVID-19 pandemic among younger age groups. They also provide valuable insights into the risk-benefit relationship of interrupting sports activities as a preventive measure for infectious diseases.

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.

Abstract At the east of the Ventana Ranges, Buenos Aires, Argentina, outcrops the Carboniferous-Permian Pillahuincó Group (Sauce Grande, Piedra Azul, Bonete and Tunas Formation). We carried out an Anisotropy of Magnetic Susceptibility (AMS) study on Sauce Grande, Piedra Azul and Bonete Formation that displays ellipsoids with constant Kmax axes trending NW–SE, parallel to the fold axes. The Kmin axes are orientated in the NE–SW quadrants, oscillating from horizontal (base of the sequence-western) to vertical (top of the sequence-eastern) positions, showing a change from tectonic to almost sedimentary fabric. This is in concordance with the type and direction of foliation measured in petrographic thin sections which is continuous and penetrative to the base and spaced and less developed to the top. We integrated this study with previous Tunas Formation results (Permian). Similar changes in the AMS pattern (tectonic to sedimentary fabric), as well as other characteristics such as the paleo-environmental and sharp curvature in the apparent polar wander path of Gondwana, marks a new threshold in the evolution of the basin. Those changes along the Pillahuincó deposition indicate two different spasm in the tectonic deformation that according to the ages of the rocks are 300–290 Ma (Sauce Grande to Bonete Formation deposition) and 290–276 Ma (Tunas Formation deposition). This Carboniferous-Permian deformation is locally assigned to the San Rafael (Hercinian) orogenic phase, interpreted as the result of rearrangements of the microplates that collided previously with Gondwana, and latitudinal movements of Gondwana toward north and Laurentia toward south to reach the Triassic Pangea.

Little is known about how bow mechanical characteristics objectively and quantitatively influence violinists' preferences and performance. Hypothesizing that the bow shape (i.e., camber) and mass distribution modifications would alter both violinists' appreciations of a bow and objective assessments of their performance, we recruited 10 professional violinists to play their own violin using 18 versions of a single bow, modified by combining three cambers and six mass distributions, in random order. A musical phrase, composed for this study, was played legato and spiccato at three octaves and two tempi. Each violinist scored all 18 bows. Then, experts assessed the recorded performances according to criteria inspired by basic musical analysis. Finally, 12 audio-descriptors were calculated on the same note from each trial, to objectivise potential acoustic differences. Statistical analysis (ANOVA) reveals that bow camber impacted the violinists' appreciations (p < 0.05), and that heavier bow tips gave lower scores for spiccato playing (p < 0.05). The expert evaluations reveal that playing with a lighter bow (tip or frog), or with a bow whose camber's maximum curvature is close to the frog, had a positive impact on some violinists' performance (NS to p < 0.001). The “camber-participant” interaction had significant effects on the violinists' appreciations (p < 0.01 to p < 0.001), on the expert's evaluation and on almost all the audio-descriptors (NS to p < 0.001). While trends were identified, multiple camber-participant interactions suggest that bow makers should provide a variety of cambers to satisfy different violinists.

Background: Prognosis of patients affected by metastatic esophageal–gastric junction (EGJ) or gastric cancer (GC) remains dismal. Trastuzumab, an anti-HER2 monoclonal antibody, is the only targeted agent approved for the first-line treatment of patients with HER2-overexpressing advanced EGJ or GC in combination with chemotherapy. However, patients invariably become resistant during this treatment. We recently identified the overexpression of fibroblast growth factor (FGF) receptor 3 (FGFR3) as a molecular mechanism responsible for trastuzumab resistance in GC models, providing the rationale for the inhibition of this receptor as a potential second-line strategy in this disease. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. Methods: The FiGhTeR trial is a phase II, single-arm, open-label study to assess safety and activity of the FGFR inhibitor pemigatinib as second-line treatment strategy in metastatic EGJ/GC patients progressing under trastuzumab-containing therapies. The primary endpoint is the 12-week progression-free survival rate. Plasma and tumor tissue samples will be collected for translational research analyses at baseline, during treatment, and at progression on pemigatinib. Discussion: Co-alterations in genes coding for different tyrosine-kinase receptors are emerging as relevant mechanisms of acquired resistance to anti-HER2 therapeutic strategies in GC. In particular, our group has recently identified that in GC models the overexpression of FGFR3 sustains the acquired resistance to trastuzumab. This trial aims to assess the safety, tolerability and activity of the FGFR inhibitor pemigatinib as a second-line treatment in metastatic EGJ/GC patients refractory to first-line trastuzumab-containing therapies. Furthermore, this study offers the opportunity to prospectively study mechanisms and pathways involved in trastuzumab resistance. Protocol number: CRC2017_02 EudraCT Number: 2017-004522-14

Simple Summary: The clinical behaviour of signet ring cell histology in gastric cancer has long been a subject of controversy. Recent years have underscored the pressing issue of a lack of a standardised definition for signet ring cell histology, leading to its often-ambiguous placement within broader categories associated with poor prognosis. Conversely, comparisons of signet ring cell gastric cancer have been made against a wide spectrum of non-signet ring cell cases, introducing significant heterogeneity. The primary objective of this literature search and subsequent meta-analysis was to gain a deeper understanding of signet ring cell gastric cancer. Our findings revealed that the prognosis of signet ring cell gastric cancer is intricately tied to the disease stage, yet it is also contingent on the specific comparison group employed. The variability in signet ring cell cancer's clinical behaviour may stem from the absence of a standardised definition. Therefore, it is imperative to work towards a uniform classification system for gastric cancer to enhance clarity and coherence in future research and clinical practice. Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. Methods: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. Results: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. Conclusions: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications. [ABSTRACT FROM AUTHOR]