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This study was designed to investigate the acute toxicity (mortality) and sublethal effects (fertility and potential natality) of carlina oxide, the main constituent of Carlina acaulis essential oil (EO), against adults of Metopolophium dirhodum (Walker) (Hemiptera: Aphididae). Moreover, its toxicity was evaluated against two aphid natural enemies, i.e., Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Chrysoperla carnea Stephens (Neuroptera: Chrysopidae). The highest tested concentration (3.0 mL L−1) resulted in 96.7% mortality of adults of the target pest, highlighting that this concentration of carlina oxide had a similar effectiveness as the positive control we used. Furthermore, probit analysis allowed the estimation of a LC50 of 1.06 mL L−1 and a LC90 of 2.58 mL L−1 for the target pest, which resulted in a much higher mortality rate than that found on natural enemies, i.e., A. aphidimyza (6.7 ± 4.7% ± SD when exposed to the aphid LC90) and C. carnea (7.0 ± 5.5% ± SD when exposed to the aphid LC90), showing the limited non-target impact of carlina oxide. The use of LC30 and LC50 of this compound allowed the fertility inhibition of the target pest by 35.68 ± 6.21% and 23.66 ± 10.58%, respectively, and potential natality inhibition of the target pest by 52.78 ± 4.48% and 59.69 ± 5.60%, respectively. Of note, carlina oxide showed excellent insecticidal activity against M. dirhodum, comparable to the commercial insecticide considered. Overall, the low toxicity of carlina oxide toward A. aphidimyza and C. carnea makes it a safe compound for non-target organisms as well as suitable for developing a green insecticide for the management of M. dirhodum and perhaps other insects of agricultural or medical and veterinary interest. [ABSTRACT FROM AUTHOR]

This work presents an integrated structural, kinematic, and petrochronological study of the Monte Grighini dome within the Variscan hinterland–foreland transition zone of Sardinia (Italy). The area is characterised by dextral transpressive deformation partitioned into low- and high-strain zones (Monte Grighini shear zone, MGSZ). Geothermobarometry of one sample of sillimanite-bearing mylonitic metapelite indicates that the Monte Grighini shear zone developed under high-temperature (~ 625 °C) and low-pressure (~ 0.4–0.6 GPa) conditions. In situ U–(Th)–Pb monazite geochronology reveals that the deformation in the shear zone initiated at ca. 315 Ma. Although previous studies have interpreted the Monte Grighini shear zone to have formed in a transtensional regime, our structural and kinematic results integrated with constraints on the relative timing of deformation indicate that it shows similarities with other dextral ductile transpressive shear zones in the Southern European Variscan belt (i.e., the East Variscan Shear Zone, EVSZ). However, dextral transpression in the Monte Grighini shear zone started later than in other portions of the EVSZ within the framework of the Southern European Variscan Belt due to the progressive migration and rejuvenation of deformation from the core to the external sectors of the belt. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a complex disorder characterized by abdominal obesity, elevated blood pressure, hyperlipidemia, and elevated fasting blood glucose levels. The diagnostic criteria for MetS in adults are well-established, but there is currently no consensus on the definition in children and adolescents. The etiology of MetS is believed to involve a complex interplay between genetic predisposition and environmental factors. While genetic predisposition explains only a small part of MetS pathogenesis, modifiable environmental risk factors play a significant role. Factors such as maternal weight during pregnancy, children's lifestyle, sedentariness, high-fat diet, fructose and branched-chain amino acid consumption, vitamin D deficiency, and sleep disturbances contribute to the development of MetS. Early identification and treatment of MetS in children and adolescents is crucial to prevent the development of chronic diseases later in life. In this review we discuss the latest research on factors contributing to the pathogenesis of MetS in children, focusing on non-modifiable and modifiable risk factors, including genetics, dysbiosis and chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group. Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding. [ABSTRACT FROM AUTHOR]

Aim/hypothesis: We assessed whether HOMA-IR and the Matsuda Index are associated with transitions through stages of type 1 diabetes. Methods: Autoantibody (AAb)-positive relatives of individuals with type 1 diabetes (n=6256) from the TrialNet Pathway to Prevention were studied. Associations of indicators of insulin resistance (HOMA-IR) and insulin sensitivity (Matsuda Index) with BMI percentile (BMIp) and age were assessed with adjustments for measures of insulin secretion, Index60 and insulinogenic index (IGI). Cox regression was used to determine if tertiles of HOMA-IR and Matsuda Index predicted transitions from Not Staged (<2 AAbs) to Stage 1 (≥2 AAbs and normoglycaemia), from Stage 1 to Stage 2 (≥2 AAbs with dysglycaemia), and progression to Stage 3 (diabetes as defined by WHO/ADA criteria). Results: There were strong associations of HOMA-IR (positive) and Matsuda Index (inverse) with baseline age and BMIp (p<0.0001). After adjustments for Index60, transitioning from Stage 1 to Stage 2 was associated with higher HOMA-IR and lower Matsuda Index (HOMA-IR: HR=1.71, p<0.0001; Matsuda Index, HR=0.40, p<0.0001), as with progressing from Stages 1 or 2 to Stage 3 (HOMA-IR: HR=1.98, p<0.0001; Matsuda Index: HR=0.46, p<0.0001). Without adjustments, associations of progression to Stage 3 were inverse for HOMA-IR and positive for Matsuda Index, opposite in directionality with adjustments. When IGI was used in place of Index60, the findings were similar. Conclusions/interpretation: Progression to Stages 2 and 3 of type 1 diabetes increases with HOMA-IR and decreases with the Matsuda Index after adjustments for insulin secretion. Indicators of insulin secretion appear helpful for interpreting associations of progression to type 1 diabetes with HOMA-IR or the Matsuda Index in AAb-positive relatives. [ABSTRACT FROM AUTHOR]

In vitro simulators of the human gastrointestinal (GI) tract are remarkable technological platforms for studying the impact of food on the gut microbiota, enabling continuous and real-time monitoring of key biomarkers. However, comprehensive real-time monitoring of gaseous biomarkers in these systems is required with a cost-effective approach, which has been challenging to perform experimentally to date. In this work, we demonstrate the integration and in-line use of carbon nanotube (CNT)-based chemiresitive gas sensors coated with a thin polydimethylsiloxane (PDMS) membrane for the continuous monitoring of gases within the Simulator of the Human Microbial Ecosystem (SHIME). The findings demonstrate the ability of the gas sensor to continuously monitor the different phases of gas production in this harsh, anaerobic, highly humid, and acidic environment for a long exposure time (16 h) without saturation. This establishes our sensor platform as an effective tool for real-time monitoring of gaseous biomarkers in in vitro systems like SHIME. [ABSTRACT FROM AUTHOR]

Worldwide more than 550,000 new patients suffering from malignant tumors are associated with human papillomaviruses (HPV) infection. However, only a small portion of patients infected progress to cancer, suggesting that other factors other than HPV may play a role. Some studies have investigated HPV infection in colorectal cancer (CRC) with discordant results; moreover, the role of HPV in CRC development is still unknown. We investigated HPV infection in 50 CRC from different regions, excluding the anal one, by immunohistochemistry (IHC), real-time PCR and RNA-seq. For each patient, we studied the tumor microenvironment in neoplastic and matched non-neoplastic samples, and we compared the tumor-infiltrating immune cell phenotypes among HPV-positive and negative samples. Finally, we compared the CRC-associated microbiota in HPV-positive and negative neoplastic samples by 16S rRNA sequencing. HPV infection was identified in 20% of CRC from the right side (caecum, ascending and transverse colon) and in 40% from the left side (descending colon and rectum). In all HPV-positive CRCs we found no expression of p53 and RB, thus suggesting HPV involvement in tumorigenesis. As far as the tumor microenvironment is concerned, in HPV-related cancers we observed a neoplastic environment with a reduced immune surveillance but an enhanced cytotoxic response by lymphocytes. HPV-positive and -negative CRC showed a different microbiota with lack of species normally found in CRC in the HPV-positive ones. Our results support the carcinogenic significance of HPV in CRC, suggesting a role of HPV in modulating the tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Objective: The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject. Data sources: MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included. Review methods: Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: 15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87–3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20–28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered. Conclusion: HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Developing sustainable control tools for managing noxious pests attacking stored foodstuffs is a timely research challenge. Acmella oleracea (L.) R. K. Jansen is a crop widely cultivated for its multiple usages on an industrial level. In this study, the extracts prepared with A. oleracea aerial parts were applied on wheat kernels for the management of eight important arthropod pests attacking stored products, i.e., Cryptolestes ferrugineus, Tenebrio molitor, Oryzaephilus surinamensis, Trogoderma granarium, Tribolium castaneum, Tribolium confusum, Alphitobius diaperinus (adults/larvae), and Acarus siro (adults/nymphs). Extraction of A. oleracea was optimized on the base of the yield and content of spilanthol and other N-alkylamides which were analysed by HPLC–DAD-MS. Two concentrations of n-hexane or methanol extracts (500 ppm and 1000 ppm), obtained through Soxhlet extraction, were tested to acquire mortality data on the above-mentioned pests after 4, 8, and 16 h and 1 to 7 days of exposure. Both extracts achieved complete mortality (100.0%) of C. ferrugineus adults. In the case of A. diaperinus adults, mortalities were very low at any concentrations of both extracts. In general, the n-hexane extract was more efficient than methanol extract against almost all species and stages. Considering both extracts, the susceptibility order, from most to least susceptible species/stage, was C. ferrugineus adults > A. diaperinus larvae > C. ferrugineus larvae > T. granarium adults > T. molitor larvae > O. surinamensis adults > O. surinamensis larvae > T. confusum larvae > T. castaneum larvae > A. siro adults > T. molitor adults > A. siro nymphs > T. granarium larvae > T. castaneum adults > T. confusum adults > A. diaperinus adults. Our research provides useful knowledge on the efficacy of N-alkylamides-rich A. oleracea extracts as grain protectants, pointing out the importance of targeting the most susceptible species/ developmental stages. [ABSTRACT FROM AUTHOR]

Background and Objectives: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. Methods: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. Results: The CVM study enrolled 658 first-dose vaccinees (children aged 5–11 years; n = 250 and adolescents aged 12–17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. Conclusions: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data. [ABSTRACT FROM AUTHOR]

The South-East Crater (SEC) at Mt. Etna started a period of lava fountaining in December 2020, producing over 60 paroxysms until February 2022. The activity had an intense sequence from February 16 to April 1, 2021, totaling 17 paroxysmal events separated by repose times varying from 1 to 7 days. The eruptive sequence was extensively monitored, providing a unique opportunity to relate the chemistry and texture of the erupted products to eruption dynamics. We investigate the temporal evolution of the magmatic system through this eruptive sequence by quantifying variations in the composition and texture of clinopyroxene. Clinopyroxene major element transects across crystals from five representative lava fountains allow us to determine the relative proportions of deep versus shallow-stored magmas that fed these events. We use hierarchical clustering (HC), an unsupervised machine learning technique, to objectively identify clinopyroxene compositional clusters and their variations during this intense eruptive phase. Our results show that variations of monitoring parameters and eruption intensity are expressed in the mineral record both as changes in cluster proportions and the chemical complexity of single crystals. We also apply random forest thermobarometry to relate each cluster to P-T conditions of formation. We suggest that the February–April 2021 eruptive sequence was sustained by the injection of a hotter and deeper magma into a storage area at 1–3 kbar, where it mixed with a slightly more evolved magma. The February 28 episode emitted the most mafic magma, in association with the highest mean lava fountain height and highest time–averaged discharge rate, which make it the peak of the analyzed eruptive interval. Our results show that after this episode, the deep magma supply decreased and the erupted magma become gradually more chemically evolved, with a lower time–average discharge rate and fountain height. We propose this approach as a means to rapidly, objectively, and effectively link petrological and geophysical/geochemical monitoring during ongoing eruptions. We anticipate that the systematic application of this approach will serve to shed light on the magmatic processes controlling the evolution of ongoing eruptions. [ABSTRACT FROM AUTHOR]

Purpose of Review: The treatment of colorectal cancer (CRC) has evolved and become more personalized during the past several years. For example, depotentiation/reduced duration of systemic therapies has proven to be beneficial in both advanced and early stages of the disease. Recent Findings: In particular, recent randomized studies of stage III and high-risk stage II CRC showed that a shorter duration (3 months), when compared to the historical 6-month comparator, provides nearly similar overall survival (OS) and disease-free survival (DFS). In the setting of advanced, inoperable CRC, a relatively short induction phase (six to eight cycles) followed by biological agents is the current standard of care in RAS wild-type (wt). versus RAS mutated cases. With regard to potentially operable stage IV disease (with the aim of converting liver metastases to operability), a relatively short number of cycles (four to six cycles) should be offered with re-staging and re-evaluation for surgery as soon as possible in most cases. For inoperable liver metastases, a relatively intensive triplet or doublet plus targeted therapy may attain conversion in some cases and may even result in cure. Rectal cancer treatment continues to be a complex disease in terms of treatment and oncological results. Recent data seem to showcase the benefits of more prolonged sequential strategies (total neoadjuvant therapy, all treatment delivered before surgery, to reduce the risk of distant metastases and local control). Summary: In recent years, different strategies regarding treatment intensity have been employed in CRC in adjuvant and metastatic setting. Introduction of triplets as first-line therapy for colon cancer and as induction phase for rectal cancer are now therapeutic options. Conversely in stage II disease or low-risk stage III resected CRC, a reduced chemotherapy length is a new standard of care. [ABSTRACT FROM AUTHOR]

There are several predictor scales to assess the patients pre-operatively and thus inferring outcomes after surgery; for example, ASA (American Society of Anesthesiologists) scoring, SORT (Surgical Outcome Risk Tool), and APACHE II (Acute Physiology and Chronic Health Disease Classification System II). However, most surgeons would see advancing age as an important predictor of surgical outcome especially after a major surgery. Chronological age may not be the only determinant outcome after surgery. In a group of colonic cancer patients, we compared standard pre-defined outcomes in subjects above 80 years to below 80 years. Specifically we compared Clinical, surgical, pathological, and survival data of 71 oldest old patients (≥80 years) and 67 younger (<80 years) patients treated by surgery between January 2018 and January 2020. No differences in terms of intra- and peri-operatory mortality, post-operative complications, length of hospital stay, and needing of Intensive Care Unit were found between the two groups. Univariate and multivariate analyses identified, above all, laparotomy, anastomotic leak, lymph node, and hematogenous metastasis as independent prognostic factors for a worse outcome. The Kaplan-Meier curves demonstrated that both the 180-day survival and the overall survival overlapped. The results of our study highlight how chronological age should not to be considered a barrier for a proper treatment, pointing at surgery as a feasible approach also in elderly patients. Our findings may open the way for planning "ad hoc" screening protocols in this subset of patient. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. Material and methods: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. Results: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III–IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29–65 and 0.3; 95% CrIs 0.03–2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19–12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). Conclusions: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS. [ABSTRACT FROM AUTHOR]

We review pre-eruptive dynamics and evidence of open-system behavior in the volcanic plumbing system beneath Campi Flegrei Caldera, together with estimates of magma residence time, magma ascent, and mixing-to-eruption timescales. In detail, we compile pre- and syn-eruptive dynamics reported in the literature for (a) the Campanian Ignimbrite ~ 40 ka, (b) the Neapolitan Yellow Tuff (~ 15 ka), and (c) the recent activity within the Phlegrean area. We first summarize geochemical and textural evidence (e.g., magma mixing, crystal disequilibria, vertical zonings, and isotopic records) of open-system behavior for the pyroclasts erupted in the last 40 ky at Campi Flegrei Caldera. We show that the fingerprint of open-system dynamics is ubiquitous in the deposits associated with the volcanic activity at the Campi Flegrei Caldera in the last 40 ky. Then, we describe the results of geophysical and petrological investigations that allow us to hypothesize the structure of the magma feeding system. We point to a trans-crustal magmatic feeding system characterized by a main storage reservoir hosted at ~ 9 km that feeds and interacts with shallow reservoirs, mainly placed at 2–4 km. Finally, we define a scenario depicting pre-eruptive dynamics of a possible future eruption and provide new constraints on timescales of magma ascent with a physical model based on magma-driven ascending dyke theory. Results show that considerably fast ascent velocities (i.e., of the order of m/s) can be easily achieved for eruptions fed by both shallow (i.e., 3–4 km) and deep (i.e., ~ 9 km) reservoirs. Comparing the results from experimental and numerical methods, it emerges that mixing-to-eruption timescales occurring at shallow reservoirs could be on the order of minutes to hours. Finally, we highlight the volcanological implications of our timescale estimates for magma ascent and mixing to eruption. In particular, explosive eruptions could begin with little physical 'warning', of the order of days to months. In this case, the onset of volatile saturation might provide pre-eruptive indicators. [ABSTRACT FROM AUTHOR]

We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient's food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m2) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2–4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6–78.9) for DEX1 vs. 72.4% (95% CI, 61.4–81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin. Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769). [ABSTRACT FROM AUTHOR]

Villarrica or Rukapillan (35.9°S; 2,847 m a.s.l.) is one of the most active volcanoes in South America and is the highest-risk volcano in Chile. It has an open conduit with a persistent lava lake. On the 3 March 2015, Strombolian activity rapidly progressed into a 1.5-km-high lava fountain, erupting at least ∼ 2.4 × 106 m3 of tephra. Soon after, the activity returned to mild Strombolian "background" explosions, which lasted until early 2017. Understanding the pre-eruptive conditions of such paroxysmal events is fundamental for volcanic hazard assessment. We present major and trace element geochemistry for glass and crystalline phases of basaltic andesite paroxysm pyroclasts (52–56 wt.% SiO2), and for the subsequent Strombolian "background" activity through February 2017 (54–56 wt.% SiO2). The lava fountain source magma was initially stored in a deeper and hotter region (9.4–16.3 km; ca. 1140 °C) and was then resident in a shallow (≤ 0.8 km) storage zone pre-eruption. During storage, crystallising phases comprised plagioclase (An66–86), olivine (Fo75–78) and augite (En46–47). Equilibrium crystallisation occurred during upper-crustal magmatic ascent. During storage in the shallower region, magma reached H2O saturation, promoting volatile exsolution and over-pressurization, which triggered the eruption. In contrast, subsequent "background" explosions involving basaltic-andesite were sourced from a depth of ≤ 5.3 km (ca. 1110 °C). Pre-eruptive conditions for the 2015 lava fountain contrast with historical twentieth-century eruptions at Villarrica, which were likely driven by magma that underwent a longer period of mixing to feed both effusive and explosive activity. The rapid transition to lava-fountaining activity in 2015 represents a challenging condition in terms of volcano monitoring and eruption forecasting. However, our petrological study of the pyroclastic materials that erupted in 2015 offers significant insights into eruptive processes involving this type of eruption. This aids in deciphering the mechanisms behind sudden eruptions at open conduit systems. [ABSTRACT FROM AUTHOR]

Introduction: The use of online education strategies has been introduced as a tool to support health care in patients with rheumatic disease. However, it is important to consider the patient's sociocultural environment. Objective: To design and assessment of bilingual audiovisual material acceptability, by means of two social networks, for patients with rheumatoid arthritis (RA) in the qom community in Argentina. Methods: A qualitative study was performed in two stages: (1) audiovisual material design, development, and validation implementing a collaborative action research method. (2) Publishing of the material on two social networks at two different times. The selected topic was the coronavirus disease 2019 impact on patients with RA. A qualitative and quantitative data analysis was performed. Results: Forty subjects participated into the initial validation stage with a 70% acceptance rate. First, 28 subjects (70%) participated on Facebook and 25 (62.5%) joined the WhatsApp group. Then, the same number of subjects participated on Facebook, while only 45% of subjects participated on WhatsApp. Most of them participated using short phrases such as "I like it." The 60% of the participants played the videos. However, less than 10% shared them. Videos in Spanish were the once most shared. Participation dramatically fell during the second time, and 40% of the WhatsApp subjects never participated. Conclusion: The strategies developed for this indigenous community were of no utility, probably because of socio-cultural, economic, and digital barriers. They should be designed and implemented identifying the target group and its environment. Key Points • Online education strategies should be designed with cultural sensitivity. • Technological barriers make digital inequality visible in vulnerable groups. • Educational interventions should have a collaborative design and they should be created together with the communities. • The COVID-19 pandemic has deepened inequalities in the health care and follow-up of patients with rheumatic diseases, especially between most socially and economically disadvantaged groups. [ABSTRACT FROM AUTHOR]

The interest in agri-food residues and their valorization has grown considerably, and many of them are today considered to be valuable, under-exploited sources of different compounds and notably proteins. Despite the beneficial properties of legumes by-products, there are also some emerging risks to consider, including their potential allergenicity. In this work the immunoreactivity of chickpea, pea, and white bean by-products was assessed, and whether the production of enzymatic hydrolysates can be an effective strategy to reduce this allergenic potential. The results presented clearly indicate that the efficiency of this strategy is strongly related to the enzyme used and the food matrix. All legume by-products showed immunoreactivity towards serum of legume-allergic patients. Hydrolysates from alcalase did not show residual immunoreactivity for chickpea and green pea, whereas hydrolysates from papain still presented some immunoreactivity. However, for white beans, the presence of antinutritional factors prevented a complete hydrolysis, yielding a residual immunoreactivity even after enzymatic hydrolysis with alcalase. [ABSTRACT FROM AUTHOR]

Stromboli (Italy) is a basaltic volcano characterized by persistent, mild strombolian activity, occasionally interrupted by lava effusion and more violent explosive events, named major explosions and paroxysms depending on their intensity and magnitude. The normal activity is fed by a shallow and degassed highly porphyritic (HP) shoshonitic basalt carrying about 50 vol.% crystals settled in a shoshonitic glassy matrix (K2O > 3.8 wt.%). The more energetic explosions erupt a deep, volatile-rich, low-porphyritic (LP) magma with < 10 vol.% crystals in a shoshonitic basaltic glassy matrix (K2O < 2.4 wt.%). Products with intermediate glass composition are also found in the more violent explosive events. In this study, we present a new data set of major and trace element contents in matrix glasses and minerals performed in products from different types of explosive activity that occurred at Stromboli between 1998 and 2020. This large data set is used to put constraints on the evolution and architecture of the intermediate plumbing system, where the transformation from LP to HP occurs. Results indicate that, compared to paroxysms, the glassy matrices of the LP pumices from major explosions are richer in incompatible trace elements (and K2O wt.%) due to < 15 wt.% fractionation of clinopyroxene and olivine. This points to a chemical zoning of the deep reservoir and suggests that major explosions are fed by magmas residing in its upper part. Among the major explosions, the homogeneous intermediate glasses in the products from the 19 July 2020 event originate from the interplay of mixing and crystal fractionation processes. The crystallization of euhedral microphenocrysts of An-rich plagioclase suggests that batches of magma can pond and crystallize for few days (< 11) at the base of the intermediate zone of the plumbing system, at pressure coinciding with the entering of plagioclase into the system (< 100 MPa). As a relevant point for understanding the pre- and syn-eruptive magma dynamics, data indicate a positive correlation between the magnitude of the explosions and the depth of the supply magma. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS). Materials and methods: We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS. Results: A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62). Conclusions: In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies. [ABSTRACT FROM AUTHOR]

Animals living on small islands are more drastically exposed to environmental changes, such as food or water starvation, and rapid temperature shifts. Facing such conditions, and probably thank to adaptive plasticity mechanisms, some animals display a Reversed Island Syndrome (RIS), a suite of traits, including skin pigmentation, voracity, sexual dimorphism, showed differently from mainland relatives. Here, we analyse a so far poorly explored aspect of RIS: the effect of this on the microbiota composition of host Italian wall lizard (Podarcis siculus), strongly influenced by the animal's lifestyle, and conditioning the same. We compare mainland and island populations, assessing the difference between their microbial communities and their response under unexpected food, experimentally provided. Our observations showed a significant difference in microbiota communities between island and mainland groups, depended mainly from changes in relative abundance of the shared genera (difference due to decrease/increase). Exposure to experimental diet regimes resulted into significative reshaping of bacterial composition of microbiota and a greater variation in body mass only in the island population. Our results could be an evidence that gut microbial community contributes to adaptive plasticity mechanisms of island lizards under RIS to efficiently respond to unexpected changes. [ABSTRACT FROM AUTHOR]

Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy. [ABSTRACT FROM AUTHOR]

A systematic analysis of the mortality of immigrant residents throughout Italy has never been carried out. The present study aimed to evaluate differences in mortality by immigrant status. A longitudinal study of the Italian resident population (native and immigrants) recorded in the 2011 National Institute of Statistics Census was conducted. This cohort was followed up from 2012 to 2018 until death, emigration, or end of the study period. The exposure variable was the immigrant status, measured through citizenship, dichotomized into Italian and immigrant. The main outcome was overall and cause-specific mortality. Age-standardized mortality ratios (SMRs) were calculated. The SMRs among immigrants were half that of Italians, both for men (SMR 0.52) and women (SMR 0.51), with the lowest SMRs observed for subjects from North Africa and Oceania. For some causes of death, mortality was higher among immigrants: tuberculosis in both men (SMR 4.58) and women (SMR 4.72), and cervical cancer (SMR 1.58), complications of pregnancy, childbirth, and puerperium (SMR 1.36), and homicide (SMR 2.13) for women. A multivariable quasi-Poisson regression analysis, adjusted for age and macro area of residence in Italy, confirmed a lower all-cause mortality for immigrants compared to Italians, both for men (RR 0.46) and women (RR 0.44). Although immigration to Italy is no longer a recent phenomenon, and the presence of immigrants is acquiring structural characteristics, our study confirms their health advantage, with a lower mortality than that of Italians for almost all causes of death and for all areas of origin. [ABSTRACT FROM AUTHOR]

Aims: Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes. Methods: Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals). Linear mixed models were adopted to estimate variation of pancreatic enzymes among the groups and to evaluate the influence of high-risk HLA genotypes and residual beta cell function on exocrine pancreas function. Results: In adults, but not children, reduced levels of P-amylase and lipase were shown in at-risk individuals, including (for P-amylase levels only) those at low-risk, and in T1Dnew. Furthermore, while high-risk HLA genotypes negatively affected P-amylase levels in autoantibody negative adult individuals, fasting C-peptide levels did not correlate with pancreatic enzyme levels. Conclusions: Exocrine pancreas dysfunction precedes the onset of type 1 diabetes in adult at-risk individuals and may be unrelated to fasting C-peptide levels. [ABSTRACT FROM AUTHOR]

We present a petrologic study of the ca. 110 ka Halarauður eruption (7 ± 6 km3 magma), associated with collapse of Krafla caldera in northeast Iceland. Whole-rock compositions of juvenile Halarauður products span a continuous range between quartz tholeiite basalt (50.0 wt% SiO2, 5.0 wt% MgO; Mg# 42) and rhyolite (74.6 wt% SiO2). Linear correlations between all major elements are consistent with two-component mixing of sub-equal volumes of these end-member magmas, whereas correlations between trace elements are influenced by diffusive fractionation during chaotic mixing. Evolved compositions (andesite to rhyolite) and compositional heterogeneity are typical of early-erupted units, reflecting tapping of the upper, more silicic regions of a compositionally heterogeneous reservoir undergoing chaotic mixing. Later-erupted deposits are more compositionally homogeneous and grade smoothly upward from andesite to basalt, reflecting tapping of denser hybrid magma and uncontaminated basalt from lower in the chamber. All erupted products host < 1–2 modal% macro-crysts, implying storage at near-liquidus temperatures. Geobarometry and MELTS modeling suggest shallow storage pressures of ~ 200 MPa (~ 8 km depth) for the quartz tholeiite. Plagioclase (An60-76) and augite (Mg# 68–75) macro-crysts crystallized from this basalt during shallow storage, while sparse glomerocrysts (plagioclase ± augite ± olivine ± orthopyroxene) in late-erupted basaltic material are derived from disaggregated cumulate mush and include more primitive compositions. Occasional narrow sodic rims on plagioclase crystals from the quartz tholeiite record short periods of re-equilibration with hybrid magmas during mixing, constrained by experimental growth rates as at most two months and possibly as short as tens of hours. A second population of calcic plagioclase (cores An83-91) with adhering primitive basaltic glass selvages (Mg# 53–59) occurs sparsely in deposits of the first eruptive phase and is scarce or absent in later-erupted units, providing evidence for eruption of a second, more primitive basalt that was of insufficient volume to skew whole-rock mixing trends. Nucleation delay models suggest that the absence of overgrowth rims or quench crystals in these glassy basaltic selvages reflect residence times of a few hours at rhyolitic temperatures before eruption. Short basalt–rhyolite mixing timescales reflect rapid destabilization of the magmatic system and triggering of the eruption by mafic recharge. The ascent of both primitive and evolved basaltic magmas from depth mirrors events in recent volcano-tectonic episodes in the north of Iceland, suggesting that mafic recharge was driven by a plate boundary rifting event. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the quality of life (QoL) of chronic myeloid leukemia (CML) patients prescribed with nilotinib as a second-line therapy and explores the influential factors. Methods: A multicenter retrospective survey was conducted via face-to-face interviews based on the EORTC QLQ-C30 questionnaire. A total of 121 adult CML patients resistant to imatinib and used nilotinib for at least 3 months were enrolled. The influential features were assessed by multiple linear regression models. Results: Patients had the mean age of 47.49 (SD = 13.67) years, dominated by middle-aged and male groups. The mean scores of functions ranged from 75 to 83, and those of symptoms were from 5 to 28, with the highest of fatigue (28.28), insomnia (22.87), and pain (21.07). The mean global health status/QoL score was 67.70 (SD = 16.80) with considerable financial difficulties (52.34 (SD = 32.15)). Male patients reported higher functional scores and fewer symptoms compared with female patients. All aspects of QoL became worse with increasing age. Besides age and gender, level of education, duration of nilotinib usage, and comorbidities were also significantly influential factors in many QoL domains. A predicted model for expected mean scores of QoL domains was built based on these factors. Conclusions: The CML patients treated with nilotinib had the above-moderate QoL scores, a light decrease of functional scores, great financial difficulties, and still experienced symptoms. Strategies and more therapeutic considerations to enhance QoL for CML patients targeted toward women, the old, low educational level, and long duration of nilotinib usage, and many comorbidities are needed in the setting. [ABSTRACT FROM AUTHOR]

We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient's food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m2) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2–4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6–78.9) for DEX1 vs. 72.4% (95% CI, 61.4–81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin. Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769). [ABSTRACT FROM AUTHOR]

Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26–0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45–1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role. [ABSTRACT FROM AUTHOR]

Introduction: The 21-gene Oncotype DX Breast Recurrence Score® test, (Genomic Health, Redwood City CA) has not been formally evaluated in an older cohort with estrogen receptor (ER)-positive breast cancer (BC) in term of physicians' treatment decisions. We determine the utility of Recurrence Score® (RS) result on adjuvant therapy prescription in elderly patients with resected early BC. Material and methods: PONDx was a multicenter, prospective, observational study, and which investigated the real-life use of the Oncotype DX® test by physicians treating early BC patients in clinical practice. Results: Data from the elderly extracted from 1724 BC patients who underwent Oncotype DX testing were available from 27 reference centers located in 6 regions of Italy (Lombardia, Lazio, Emilia Romagna, Campania, Abruzzo, and Marche). A total of 230 patients (13% of the total population) aged > 70 years were analyzed. The study primarily evaluated the impact of the Oncotype DX test on adjuvant treatment decisions. Physicians chosen chemotherapy plus endocrine therapy in 36% of elderly patients and 46% of those 50–70 years before the Oncotype DX test. After knowing the RS data, these rates fell to 23 and 33% (38 and 28% relative reduction, respectively). Conclusions: 21-gene test may be helpful even in a relatively low-risk group as elderly patients and may avoid the toxicity of adjuvant chemotherapy in a significant amount. If the Oncotype DX test is currently adopted on a large scale among the elderly and may impact the general prognosis of elderly BC patients, it is challenging and still unproven. [ABSTRACT FROM AUTHOR]

Background: Over recent years, immune checkpoint inhibitors (ICIs) have changed the clinical management and prognosis for most cancers. However, data on older patients in clinical trials are scarce. Objective: We performed a systematic review and pooled analysis of real-life studies to explore the efficacy and toxicity of ICIs in unselected older individuals in multiple tumor settings treated outside of clinical trials. Patients and Methods: We searched articles, including prospective cohort studies, observational or retrospective series, or expanded access programs, published in English from 2010 to October 2020 in PubMed, MEDLINE, the Cochrane Library, and EMBASE. We excluded hematological malignancies. Results: Forty-eight studies met the predefined criteria and were eligible for inclusion in the systematic review. We included 5524 patients. The pooled median overall survival was 8.9 (95% CI 7.3–10.5) and 14.3 (95% CI 11.3–17) months for non-small cell lung cancer (NSCLC: n = 17 studies; 95% in pretreated setting) and melanoma, respectively (n = 3). Median progression-free survival was 3.2 (95% CI 2.7–3.8) and 7.9 (95% CI 6.05–9.78) months for NSCLC and melanoma cohorts. Pooled rates of Grade 1–5 hepatitis, pneumonitis, hypothyroidism, and diarrhea were 5.3% (95% CI 3.7–7.6), 6% (95% CI 3.8–9.4), 8.3% (95% CI 5.4–12.5) and 7.6% (95% CI 5.7–10), respectively. Conclusions: Our findings suggest that ICIs could be safely administered in older individuals with comparable survival outcomes with respect to younger individuals. Future studies should include some form of geriatric assessment to improve patient stratification. [ABSTRACT FROM AUTHOR]

To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Diabetes mellitus can be categorized into two major variants, type 1 and type 2. A number of traits such as clinical phenotype, age at disease onset, genetic background, and underlying pathogenesis distinguish the two forms.Recent Findings: Recent evidence indicates that type 1 diabetes can be accompanied by insulin resistance and type 2 diabetes exhibits self-reactivity. These two previously unknown conditions can influence the progression and outcome of the disease. Unlike most conventional considerations, diabetes appears to consist of a spectrum of intermediate phenotypes that includes monogenic and polygenic loci linked to inflammatory processes including autoimmunity, beta cell impairment, and insulin resistance. Here we discuss why a shift of the classical bi-modal view of diabetes (autoimmune vs. non-autoimmune) is necessary in favor of a model of an immunological continuum of endotypes lying between the two extreme "insulin-resistant" and "autoimmune beta cell targeting," shaped by environmental and genetic factors which contribute to determine specific immune-conditioned outcomes. [ABSTRACT FROM AUTHOR]

Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42–1.57), p < 0.01] and relapse [HR = 1.36 (95% CI 1.26–1.46), p < 0.01]. The survival was reduced even in cancer at early stages [HR = 1.45 (1.36–1.55), p < 0.01]. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients' blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued. [ABSTRACT FROM AUTHOR]

Objective: The human papillomavirus (HPV) is implicated in the pathogenesis of several cancers among humans. The role of HPV as one of the etiological agents in esophageal carcinogenesis is partially unknown. We assessed whether the available evidence supports the association of HPV with risk and prognosis in patients with esophageal squamous cell carcinomas (ESCCs). Design: For this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and SCOPUS were searched up to February 2021. The included studies were prospective or retrospective studies that evaluated the incidence, risk, and prognosis of HPV-16/18–related ESCCs in adult subjects. The primary outcome was the incidence rate of ESCC in HPV-16/18 carriers. Secondary outcomes included the risk of ESCCs compared with healthy HPV-16/18 carriers (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]) and the survival of HPV + versus HPV- ESCCs. Results: The search identified 1649 unique citations, of which 145 met the inclusion criteria and were included in the pooled analysis (16,484 patients). The pooled HPV prevalence in ESCCs was 18.2% (95% CI 15.2–21.6%; P < 0.001). A significantly increased ESCC risk was associated with HPV infection (OR = 3.81; 95% CI 2.84–5.11; P < 0.001). Main limitation were methods of HPV detection (DNA only), race of populations included (mainly Asiatic countries) and lack of adjustment for other prognostic factors. Conclusions: The findings suggest that HPV-16/18 is detectable in about 1 on 5 cases of ESCC with different prevalences across the world. It is moderately but significantly associated with a diagnosis of ESCC. Further epidemiological studies are needed to confirm and increase the current knowledge of the subject. [ABSTRACT FROM AUTHOR]

Background: The relative risk (RR) of infection for patients treated with immune checkpoint inhibitors (ICIs) is unknown. Objectives: This study evaluated the risk of infection for patients with solid tumors undergoing ICI therapy based on a systematic review and meta-analysis. Patients and Methods: The Cochrane Library, EMBASE, and Pubmed databases were searched up to 1 December 2020. Randomized trials comparing any ICI alone, with chemotherapy (CT), or with other agents versus placebo, CT, or other agents were included. Three independent reviewers extracted the data. The primary outcome was the RR of all-grade (G) and G3–5 infections for patients receiving ICI-based treatments. Random or fixed-effect models were used according to statistical heterogeneity. Results: A total of 21,451 patients from N = 36 studies were eligible. ICIs were associated with a similar risk of all-grade infections (RR = 1.02; 95% CI 0.84–1.24; P = 0.85) versus non-ICI treatments (G1–5 events: 9.6 versus 8.3%). When the ICIs alone were compared to CT, their use was associated with 42% less risk of all-grade infections (RR = 0.58, 95% CI 0.4–0.85; P = 0.01). Compared to CT, the combination of ICIs and CT increased the risk of all-grade (RR = 1.37, 95% CI 1.23–1.53; P < 0.01) and severe infections (RR = 1.52, 95% CI 1.17–1.96; P < 0.01). In anti-PD-1, anti-PD-L1, anti-CTLA-4, monotherapy, and combination trials, the RR of all-grade infections was 0.72 (95% CI 0.49–1.05; P = 0.09), 1.18 (95% CI 0.95–1.46; P = 0.13), 1.74 (95% CI 1.13–2.67; P = 0.01), 0.97 (95% CI 0.79–1.19; P = 0.75) and 2.26 (95% CI 1.34–3.8; P < 0.01), respectively. Conclusions: Compared to CT alone, ICIs were safer and are recommended for frail patients. Conversely, CT + ICIs or ICIs combinations increased infection risk. Further studies are required to identify high-risk patients and evaluate the need for CT dose reduction or prophylactic myeloid growth factors. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them achieves long-term benefit from trastuzumab-based upfront strategy. To advance precision oncology, we investigated the therapeutic efficacy of different HER2-targeted strategies, in HER2 "hyper"-amplified (≥ 8 copies) tumors. Methods: We undertook a prospective evaluation of HER2 targeting with monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates, in a selected subgroup of HER2 "hyper"-amplified gastric patient-derived xenografts (PDXs), through the design of ad hoc preclinical trials. Results: Despite the high level of HER2 amplification, trastuzumab elicited a partial response only in 2 out of 8 PDX models. The dual-HER2 blockade with trastuzumab plus either pertuzumab or lapatinib led to complete and durable responses in 5 (62.5%) out of 8 models, including one tumor bearing a concomitant HER2 mutation. In a resistant PDX harboring KRAS amplification, the novel antibody–drug conjugate trastuzumab deruxtecan (but not trastuzumab emtansine) overcame KRAS-mediated resistance. We also identified a HGF-mediated non-cell-autonomous mechanism of secondary resistance to anti-HER2 drugs, responsive to MET co-targeting. Conclusion: These preclinical randomized trials clearly indicate that in HER2-driven gastric tumors, a boosted HER2 therapeutic blockade is required for optimal efficacy, leading to complete and durable responses in most of the cases. Our results suggest that a selected subpopulation of HER2-"hyper"-amplified GC patients could strongly benefit from this strategy. Despite the negative results of clinical trials, the dual blockade should be reconsidered for patients with clearly HER2-addicted cancers. [ABSTRACT FROM AUTHOR]

Introduction: The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available. Methods: We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity. We assessed the rate of treatment-related and panitumumab-related adverse events (AEs), treatment intensity, progression-free survival (PFS), and overall survival (OS). Results: A total of 226 patients, out of the 229 enrolled in the Valentino study, were eligible for the analysis. Overall, 143 (63%) and 83 (37%) patients received or not the antibiotic prophylaxis for skin toxicity. Any grade and G3/4 panitumumab-related AEs were reported in 89% versus 92% (p = 0.650) and 27% versus 27% (p = 1.000) patients who received or not the pre-emptive prophylaxis, respectively. Any grade and G3/4 skin rash occurred in 81% versus 90% (p = 0.085) and 27% versus 25% (p = 0.876) patients receiving or not the prophylaxis, respectively. No significant differences in terms of treatment duration, treatment delays or dose reductions, PFS, and OS were observed in the two sub-populations. Conclusion: The adequate management of anti-EGFR-related skin toxicity is fundamental to optimize the outcome of mCRC patients, balancing the survival benefit with patients' quality of life, especially in the first-line setting. [ABSTRACT FROM AUTHOR]

It is recognized that different fasciae have different type of innervation, but actually nothing is known about the specific innervation of the two types of deep fascia, aponeurotic and epymisial fascia. In this work the aponeurotic thoracolumbar fascia and the epymisial gluteal fascia of seven adult C57-BL mice were analysed by Transmission Electron Microscopy and floating immunohistochemistry with the aim to study the organization of nerve fibers, the presence of nerve corpuscles and the amount of autonomic innervation. The antibodies used were Anti-S100, Anti-Tyrosine Hydroxylase and Anti-PGP, specific for the Schwann cells forming myelin, the sympathetic nerve fibers, and the peripheral nerve fibers, respectively. The results showed that the fascial tissue is pervaded by a rhomboid and dense network of nerves. The innervation was statistically significantly lower in the gluteal fascia (2.78 ± 0.6% of positive area, 140.3 ± 31.6/mm2 branching points, nerves with 3.2 ± 0.6 mm length and 4.9 ± 0.2 µm thickness) with respect to the thoracolumbar fascia (9.01 ± 0.98% of innervated area, 500.9 ± 43.1 branching points/mm2, length of 87.1 ± 1.0 mm, thickness of 5.8 ± 0.2 µm). Both fasciae revealed the same density of autonomic nerve fibers (0.08%). Lastly, corpuscles were not found in thoracolumbar fascia. Based on these results, it is suggested that the two fasciae have different roles in proprioception and pain perception: the free nerve endings inside thoracolumbar fascia may function as proprioceptors, regulating the tensions coming from associated muscles and having a role in nonspecific low back pain, whereas the epymisial fasciae works to coordinate the actions of the various motor units of the underlying muscle. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) represent a cornerstone for the treatment of many advanced tumors. When 65 is considered as a cut-off age, ICIs are equally effective in younger and older patients. However, the efficacy of ICIs among patients aged ≥ 75 remains uncertain, since those patients were generally under-represented in clinical trials. We performed a pooled analysis of major randomized trials including data of outcome in very older population. Material and methods: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from the inception of each database to November 22th, 2019. We only included (1) randomized studies comparing ICIs alone or in combinations with no ICIs, (2) studies reporting data of patients older than 75 years, (3) studies for solid tumors, and (4) studies with HR and 95% confidence interval (CI) available for OS based on 75 years as cut-off age. All data were expressed as the combination of HR and 95% CI, and P < 0.05 was considered to be statistically significant. Results: A total of n = 8 publications for a total of n = 12 randomized studies were aggregated in the quantitative analysis. Overall, the pooled analysis showed a borderline significant OS benefit for ICIs compared to no ICIs arms (HR = 0.84, 95% CI 0.7–1; P = 0.05) in particular in first-line trials with HR = 0.77 (95%CI 0.61–0.96; P = 0.02). Conclusion: We conclude that ICIs may be offered in patients older than 75 years, providing a complete geriatric and clinical evaluation is performed in all subjects before starting therapy. [ABSTRACT FROM AUTHOR]

Introduction/objectives: The objective of this study is to describe the local healthcare system from the perspective of the health professionals, community health workers, and local representatives of the qom community living in the province of Chaco, Argentina. Methods: A qualitative study, with an ethnographic approach, was carried out using two techniques: non-participant observations and semi-structured interviews. A guide for the interviews was designed and developed by a multidisciplinary group of GLADERPO researchers. The main aspects included were the following: reference into the local healthcare system and accessibility to the system. Andersen's base conceptual model of health service utilization was applied for the analysis and for structuring the results. Results: A total of 21 people were interviewed, twelve women and nine men with an age ranging between 25 and 60 years old. The main findings were different barriers (communication and cultural) between the community and the healthcare system; "navigation" within the health system carried out by the qom community; and migration and bureaucratization of the health system. Conclusions: These findings should be incorporated into educational strategies to improve access to healthcare system and adherence to medical treatment, establishing an interaction between the different levels of the local care system and providing community health workers with an appropriate training with the support of the community representatives. Key Points • The different barriers between the community and the healthcare system were described. • The "navigation" within the health system carried out by the qom community and the migration were relevant points. • The bureaucratization of the health system and the need to design and implement educational strategies in the future were highlighted. [ABSTRACT FROM AUTHOR]

Carlina acaulis root essential oil (EO) is one of the most potent mosquito larvicides (LC50 < 2 ppm). This EO is mainly composed of carlina oxide (> 90%). Poor water solubility and rapid degradation from UV light and oxygen in the environment limit the real-world use of this EO. Herein, we developed nanocarrier-based formulations, namely micro- and nanoemulsions (ME and NE, respectively) containing C. acaulis EO or carlina oxide (both at 0.5%) as active ingredients (a.i.). The larvicidal activity of ME and NE was evaluated against Culex quinquefasciatus. The highest larvicidal activity was achieved by the ME containing 0.5% of the EO (M1); its LC50(90) was 579.1 (791.3) µL L−1. Sublethal effects of this ME and its a.i. were assessed testing both at the LC16, LC30, LC50 and LC90 on mosquito larvae exposed to each product for 1–7 h, and then monitoring mortality for 18 days. At variance with the EO, ME application, even at LC16, led to 100% mortality at 18 days. The EO and its encapsulated form were scarcely toxic to human keratinocytes (HaCaT) and human fibroblast (NHF A12) cell lines. The acute toxicity of C. acaulis EO and its ME (M1) was also evaluated in Wistar rats through oral administration; EO LD50 was 1098 mg kg−1 bw, whereas its ME, even at 5000 mg kg−1 bw (considered the upper testing limit to establish safety to mammals), was not toxic. This study highlights the outstanding efficacy of C. acaulis EO ME for developing long-lasting and safe larvicides against Cx. quinquefasciatus. [ABSTRACT FROM AUTHOR]

Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations. T regulatory (Treg) cells can differentiate into effector Treg (eTreg) cells that might be functional in inflammatory diseases. Using RNA sequencing and epigenetic profiling, the authors show that eTreg signatures in juvenile idiopathic arthritis joints are similar to tumour microenvironment (TME) Treg cells and are affected by tissue-specific epigenetic regulation. [ABSTRACT FROM AUTHOR]