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Simple Summary: Proton Beam Therapy (PBT) is an interesting therapeutic option for children and adolescents with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). In fact, if it is true that radiotherapy is a key part of the multi-modal treatment of NRSTS patients, it is also true that the risk of radiation-induced side effects represent an important limitation in its use. The unique characteristics of protons can be leveraged to minimize doses to healthy tissue, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. International cooperative efforts are required to better define the indications for PBT (based on the patient's age, estimated outcome, and tumor location), taking into account the currently limited number of available proton therapy facilities. This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking—partly due to the limited data available—PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications—based on the patient's age, estimated outcome, and tumor location—and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities. [ABSTRACT FROM AUTHOR]

Background Postoperative surgical site infections are a recognized complication following craniotomies with an associated increase in morbidity and mortality. Several studies have attempted to identify bundles of care to reduce the incidence of infections. Our study aims to clarify which perioperative measures play a role in reducing surgical infection rates further. Methods This study is a retrospective audit of all elective craniotomies in years 2018 to 2019. The primary endpoint was the surgical site infection rate at 30 days and 4 months after the procedure. Univariate analysis was used to identify factors predictive of postoperative infection. Results 344 patients were included in this study. Postoperative infections were observed in 5.2% of our cohort. No postoperative infections occurred within 4 months in patients receiving perioperative hair wash and intrawound vancomycin powder. In univariate analysis, craniotomy size (Fisher's exact test, p = 0.05), lack of perioperative hair wash, and vancomycin powder use (Fisher's exact test, p = 0.01) were predictive of postoperative infection. No complications relative to the use of intrawound vancomycin were observed. Conclusion Our study demonstrates that simple measures such as perioperative hair wash combined with intrawound vancomycin powder in addition to standard practice can help reducing infection rates with negligible risks and acceptable costs. Our results should be validated further in future prospective studies. [ABSTRACT FROM AUTHOR]

Background: Oral supplementation with some amino acids (like methionine, taurine, and cysteine) could be useful in subjects with hair loss conditions such as androgenic alopecia (AGA or FAGA) or telogen effluvium (TE). Hydrolysed collagen (HC) oral supplementation has demonstrated to have beneficial effects on nail and skin health and could improve hair growth. A food supplement in tablet formulation containing hydrolysed fish‐origin collagen (300 mg/dose), taurine, cysteine, methionine, iron, and selenium has been recently available. To date no controlled data are available regarding the clinical efficacy of this product as adjuvant to hair loss specific treatments in these clinical conditions. Study aims: To evaluate and compare the efficacy and tolerability of an oral supplementation based on HC and amino acids in subjects with hair loss due to AGA/FAGA or chronic TE in combination with drug treatments in comparison with drug treatments alone. Methods and subjects: In a prospective, 12‐week, randomized, assessor‐blinded controlled trial 83 subjects (mean age 41 ± 16 years; 26 men and 57 women) were enrolled in the study. Fifty‐nine subjects suffered from AGA/FAGA (Hamilton I‐VA, Ludwig I‐1, II‐2) and 24 from chronic TE. Subjects were randomized to oral supplementation (1 tablet day) in combination with the specify drug treatment decided by the investigator according to the type of hair loss (AGA/FAGA or TE) (Group A; N = 48) or to specific drugs treatment only (Group B; N = 35). The main outcome of the trial was the clinical efficacy evaluation using a 7‐point global assessment score (GAS) (from +3: Much Improved to ‐3 Much worsened; with score 0 representing no modification). The GAS score was evaluated using standardized photographs by an investigator unaware of the treatment groups at week 6 and at week 12. A secondary outcome was the evaluation of acceptability of the treatment regimen using a 10‐point evaluation score. Results: Seventy‐six participants (91.6%) completed the 12‐week study period. The GAS score at week 6 was 0.5 ± 0.2 in group A and 0.0 ± 0.1 in Group B (p < 0.05; Mann‐Whitney). At week 12 the GAS score in Group A was statistically significant higher in comparison with Group B (1.67 ± 0.16 and 0.66 ± 0.20, p < 0.001; Mann–Whitney test). A higher percentage of Group A subjects achieved a GAS score of ≥2 in comparison with group B (50% vs. 23%). The oral supplement was generally well tolerated. Conclusion: An oral supplement containing hydrolysed fish‐origin collagen, taurine, cysteine, methionine, iron, and selenium has demonstrated to improve the clinical efficacy of specific anti‐hair loss treatments in subjects with AGA/FAGA or chronic TE. [ABSTRACT FROM AUTHOR]

The article stresses the need for finance and health dialogue to build resilient health systems. Topics discussed include policy levers developed by the Organization for Economic Cooperation and Development (OECD) for governments to help countries finance more resilient health systems, the Joint Network for Senior Budget and Health Officials created by the OECD to aid governments implement the policy levers, and significance of health system reforms that target the budget process.

The risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development by modulating microbiota composition. We investigated germline variants associated with the abundance of bacterial populations in the normal (non-involved) colorectal mucosa of 93 CRC patients and evaluated their possible role in disease. Using a multivariable linear regression, we assessed the association between germline variants identified by genome wide genotyping and bacteria abundances determined by 16S rRNA gene sequencing. We identified 37 germline variants associated with the abundance of the genera Bacteroides, Ruminococcus, Akkermansia, Faecalibacterium and Gemmiger and with alpha diversity. These variants are correlated with the expression of 58 genes involved in inflammatory responses, cell adhesion, apoptosis and barrier integrity. Genes and bacteria appear to be involved in the same processes. In fact, expression of the pro-inflammatory genes GAL, GSDMD and LY6H was correlated with the abundance of Bacteroides, which has pro-inflammatory properties; abundance of the anti-inflammatory genus Faecalibacterium correlated with expression of KAZN, with barrier-enhancing functions. Both the microbiota composition and local inflammation are regulated, at least partially, by the same germline variants. These variants may regulate the microenvironment in which bacteria grow and predispose to the development of cancer. Identification of these variants is the first step to identifying higher-risk individuals and proposing tailored preventive treatments that increase beneficial bacterial populations. [ABSTRACT FROM AUTHOR]

Surgical site infection (SSI) is a significant cause of postoperative morbidity and mortality. As oncologic care advances, the use of surgical adjuncts such as intraoperative ultrasound (US), 5-aminolevulinic acid (5-ALA), and neurophysiologic monitoring has increased. This study set out to identify whether the use of surgical adjuncts in supratentorial tumor surgery lead to increased operative time or increased rates of SSI. This is a retrospective study at a large tertiary clinical neurosciences center in the UK. We included all patients who underwent an elective supratentorial craniotomy for a tumor over a 12 month period. We retrospectively assessed whether patients had had a postoperative infection at 30 days or 4 months using our electronic patient record system. A total of 267 patients were included. The median age was 58 years (range: 17–87 years) with roughly equal numbers of men and women (men: 138 of 267, 52%). Most operations were carried out for gliomas (149 of 267, 56%) or metastases (61 of 267, 23%). The median length of surgery was 3 hours 6 minutes, with 24% lasting >4 hours. The overall infection rate was 4.5%. Intraoperative monitoring and 5-ALA was associated with longer operative times although not necessarily larger craniotomy sizes, whereas intraoperative US was associated with a shorter operative time and smaller craniotomy size. These adjuncts were not associated with an increased risk of infection. This study adds reassurance that although some surgical adjuncts lead to increased operative times, in our study there was no apparent increased risk of infection as a result of this. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The aim of this study is to test whether radiomic and blood-derived biomarkers are good candidates for refining the prognostic stratification in OPSCC. The results show that the integration of clinical, immunological, and computed tomography-derived features generally yields an improvement, regardless of the HPV status, in the prognostic stratification of OPSCC patients who are candidates for curative-intent radiotherapy. Specifically, we documented a significant role of the Lymphocyte-to-Monocyte Ratio (LMR) in this population, which has been scarcely investigated in OPSCC, as well as the detrimental effects of lymphopenia and anemia. Results are promising, and model performances compare favorably with available radiomic scores in the same setting. Further investigations on our findings are warranted to validate the results and include a more in-depth study of the prognostic role of the LMR in OPSCC. Future analyses of this dataset are planned to provide a more complete overview of the tumor-immune system interplay. Aims: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Methods: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. Results: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52–66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5–7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80–0.84] for OS and 0.77 [CI: 0.75–0.79] for LRPFS. Conclusions: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients. [ABSTRACT FROM AUTHOR]

Objective: The GCS-Pupils (GCS-P) score is a recently described scoring system to aid outcome prediction in patients with traumatic brain injury (TBI). The aim of this study was to provide the first external validation of the GCS-P score by identifying independent predictors of outcome in TBI patients. Methods: Review of prospective adult (≥ 16 years) TBI database at a tertiary neurosurgical center with a catchment population of 1.5 million over a 12-month period commencing October 2016. Multivariate logistic regression was used to identify predictors of discharge destination and 30-day mortality. Results: Three hundred and fifty-eight patients were included. The median age was 60 years with a male predominance of 64%. The median GCS-P was 14 (interquartile range 12–15) and the commonest GCS-P category was mild (13–15; 238/358, 66%). Discharge destination was home in 69% of patients and rehab services or equivalent in 31%. Multivariate analysis identified age (p = 0.01), CT findings of an acute subdural hematoma (p = 0.01) or diffuse axonal injury (p = 0.02), and a neurosurgical operation (p = 0.02) as independent predictors of discharge destination. The 30-day mortality rate was 11%. Within the category of severe TBI (GCS-P ≤ 8), GCS-P was able to identify patients with a very high likelihood of 30-day mortality (GCS-P ≤ 4; 16/31, 52%). Multivariate analysis revealed the Charlson comorbidity score (p = 0.01), GCS-P (p = 0.02), and traumatic subarachnoid hemorrhage (p = 0.05) as independent predictors of mortality. Conclusion: The GCS-P is a useful predictor of 30-day mortality, although its usefulness for other clinical outcomes remains to be proven. [ABSTRACT FROM AUTHOR]

A 19‐membered open‐cage fullerene derivative was prepared from C60 in 7 steps and 5.5 % yield through the peroxide‐mediate pathway. There are four carbonyl groups, an ether oxygen and a quinoxaline moiety on the rim of the orifice. A chloride anion could be inserted into its cavity by heating with hydrochloric acid at 60 °C for 4 h. Encapsulation of fluoride, bromide and iodide anions was also achieved at slightly more forcing conditions, 90 °C for 14 h. Single crystal X‐ray structures of the sodium salt of the chloride and the bromide encapsulated derivatives were obtained, which showed the halide anion in the center of the cavity and two sodium cations connecting two cages through coordination to the oxygen atoms on the rim of the orifices. The halide encapsulation ratio is quantitative in the isolated products. [ABSTRACT FROM AUTHOR]

A 19‐membered open‐cage fullerene derivative was prepared from C60 in 7 steps and 5.5 % yield through the peroxide‐mediate pathway. There are four carbonyl groups, an ether oxygen and a quinoxaline moiety on the rim of the orifice. A chloride anion could be inserted into its cavity by heating with hydrochloric acid at 60 °C for 4 h. Encapsulation of fluoride, bromide and iodide anions was also achieved at slightly more forcing conditions, 90 °C for 14 h. Single crystal X‐ray structures of the sodium salt of the chloride and the bromide encapsulated derivatives were obtained, which showed the halide anion in the center of the cavity and two sodium cations connecting two cages through coordination to the oxygen atoms on the rim of the orifices. The halide encapsulation ratio is quantitative in the isolated products. [ABSTRACT FROM AUTHOR]

Background Severe traumatic brain injury (TBI) is one of the leading public health problems across the world. TBI is associated with high economic costs to the healthcare system specially in developing countries. Decompressive craniectomy is a procedure in which an area of the skull is removed to increase the volume of intracranial compartment. There are various techniques of decompressive craniectomy used that include subtemporal and circular decompression, and unilateral or bilateral frontotemporoparietal decompression. Objective The aim of this study was to compare the outcome of decompressive craniectomy for the management of severe TBI versus conservative management alone at the Department of Neurosurgery, Abbasi Shaheed Hospital, Karachi, Pakistan. Methods The study (randomized controlled trial) was conducted from February 1, 2014, till June 30, 2017. Results A total of 136 patients were included after following the inclusion criteria. They were randomly assigned to two groups, making it 68 patients in each study group. There were 89 males and 47 females. All the patients received standard care recommended by the Brain Trauma Foundation. The mortality rate observed at 6 months in decompressive craniectomy was 22.05%, while among conservative management group, it was 45.58%. Difference in mortality of both groups at 6 months was significant. Total 61.76% (42) of patients from decompressive craniectomy group had a favorable outcome (Glasgow outcome scale: 4–5) at 6 months. While among conservative management group, total 35.29% (24) had a favorable outcome (Glasgow outcome scale: 4–5). Difference in Glasgow outcome scale at 6 months of both groups was significant. Conclusion In conclusion, decompressive craniectomy is simple, safe, and better than conservative management alone. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the factors influencing age at diagnosis of lung adenocarcinoma are unknown, in our study, we examined the relationships of age at diagnosis with smoking habit, clinical stage of disease, and sex in Italian and German patients with lung adenocarcinoma who underwent lung adenocarcinoma resection. Our results indicated that smoking habit, advanced clinical stage (more aggressive and larger tumour), and female sex were variables associated with younger age at diagnosis. This study provides new findings on the clinical variables influencing age at diagnosis of lung adenocarcinoma and paves the way for studies on the genetic and molecular mechanisms responsible for these associations. To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers' association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet–Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has caused a worldwide epidemic of enormous proportions, which resulted in different mortality rates in different countries for unknown reasons. We analyzed factors associated with mortality using data from the Italian national database of more than 4 million SARS-CoV-2-positive cases diagnosed between January 2020 and July 2021, including > 415 thousand hospitalized for coronavirus disease-19 (COVID-19) and > 127 thousand deceased. For patients for whom age, sex and date of infection detection were available, we determined the impact of these variables on mortality 30 days after the date of diagnosis or hospitalization. Multivariable weighted Cox analysis showed that each of the analyzed variables independently affected COVID-19 mortality. Specifically, in the overall series, age was the main risk factor for mortality, with HR > 100 in the age groups older than 65 years compared with a reference group of 15–44 years. Male sex presented a two-fold higher risk of death than female sex. Patients infected after the first pandemic wave (i.e. after 30 June 2020) had an approximately threefold lower risk of death than those infected during the first wave. Thus, in a series of all confirmed SARS-CoV-2-infected cases in an entire European nation, elderly age was by far the most significant risk factor for COVID-19 mortality, confirming that protecting the elderly should be a priority in pandemic management. Male sex and being infected during the first wave were additional risk factors associated with COVID-19 mortality. [ABSTRACT FROM AUTHOR]

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. [ABSTRACT FROM AUTHOR]

• Positive sentinel node biopsy (SLNB) after neoadjuvant therapy (NAST) is an issue. • Positive SLNB is associated with high rate of residual positive lymph nodes. • Positive SLNB after NAST warrants treatment of axilla (dissection/radiotherapy-RT) • Predictors of positive axilla lymph nodes distribution might help to tailor RT fields. To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23–56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation. [ABSTRACT FROM AUTHOR]

The Lancet COVID-19 Commission Task Force for Public Health Measures to Suppress the Pandemic was launched to identify critical points for consideration by governments on public health interventions to control coronavirus disease 2019 (COVID-19). Drawing on our review of published studies of data analytics and modelling, evidence synthesis and contextualisation, and behavioural science evidence and theory on public health interventions from a range of sources, we outline evidence for a range of institutional measures and behaviour-change measures. We cite examples of measures adopted by a range of countries, but especially jurisdictions that have, thus far, achieved low numbers of COVID-19 deaths and limited community transmission of severe acute respiratory syndrome coronavirus 2. Finally, we highlight gaps in knowledge where research should be undertaken. As countries consider long-term measures, there is an opportunity to learn, improve the response and prepare for future pandemics. [ABSTRACT FROM AUTHOR]

Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54–3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53–3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41–7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor. [ABSTRACT FROM AUTHOR]

Reference 1 Fallerini C. SELP Asp603Asn and severe thrombosis in COVID-19 males. B Correction: J Hematol Oncol (2021) 14:123 b https://doi.org/10.1186/s13045-021-01136-9 The original article [[1]] mistakenly omitted a sentence in the Acknowledgements section which the authors include ahead: 'Two of several authors of this publication are members of the European Reference Network for rare haematological diseases EuroBloodNet.'. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

[Display omitted] • Using different platforms for radiomic extraction affects models' performance. • Variables' relevance is inconsistent among platforms. • MRI features are correlated to radiosurgery response in brain metastases from NSCLC. • Higher number of radiomic features does not necessarily imply better performance. Radiomics enables the mining of quantitative features from medical images. The influence of the radiomic feature extraction software on the final performance of models is still a poorly understood topic. This study aimed to investigate the ability of radiomic features extracted by two different radiomic platforms to predict clinical outcomes in patients treated with radiosurgery for brain metastases from non-small cell lung cancer. We developed models integrating pre-treatment magnetic resonance imaging (MRI)-derived radiomic features and clinical data. Pre-radiotherapy gadolinium enhanced axial T1-weighted MRI scans were used. MRI images were re-sampled, intensity-shifted, and histogram-matched before radiomic extraction by means of two different platforms (PyRadiomics and SOPHiA Radiomics). We adopted LASSO Cox regression models for multivariable analyses by creating radiomic, clinical, and combined models using three survival clinical endpoints (local control, distant progression, and overall survival). The statistical analysis was repeated 50 times with different random seeds and the median concordance index was used as performance metric of the models. We analysed 276 metastases from 148 patients. The use of the two platforms resulted in differences in both the quality and the number of extractable features. That led to mismatches in terms of end-to-end performance, statistical significance of radiomic scores, and clinical covariates found significant in combined models. This study shed new light on how extracting radiomic features from the same images using two different platforms could yield several discrepancies. That may lead to acute consequences on drawing conclusions, comparing results across the literature, and translating radiomics into clinical practice. [ABSTRACT FROM AUTHOR]

Polyphenols are known to interact with protein fractions of feed ingredients in the digestive tract thereby affecting the digestibility. These effects may differ depending on the chemical composition of the protein fractions. Thus, the objective of the study was to study the impact of a tannin-rich chestnut extract (CHE) on the in-vitro digestibility (IVD) of soy protein isolate (SPI), screw-pressed soybean (SPS) and solvent-extracted soybean (SES). In addition, CHE-derived metabolites were tested for their effects on intestinal epithelial integrity. The SPI, SPS, and SES were digested in vitro without (SPI-, SPS-, SES-) or with CHE (SPI+, SPS+, SES+) or as a control (C) solely CHE. The metabolites and the polyphenols content after digestion of the soy-based products with or without CHE were quantified. The trans-epithelial resistance (TEER) was monitored in porcine jejuna in the presence of CHE-derived metabolites at three dilutions (1:4, 1:8, and 1:16 v/v) or in their absence. The claudin-1 (CLDN1), occludin (OCLN) and zonula occludens-1 (ZO1) tight junctions-protein expressions were determined. Finally, the effects of CHE-metabolites against indomethacin (INDO)-induced decrease of TEER were tested ex vivo. The CHE decreased the IVD (P < 0.05) and decreased the detectable polyphenol content (P < 0.05) after digestion of CHE with SPI, SPS, or SES. The SPI and SPI+CHE were the samples with the highest content of metabolites generated after the digestion, while CHE presented the lowest content of metabolites. No detrimental effects on TEER were observed. The 1:8 dilution increased (P < 0.05) both ZO1 and OCLN protein expression by up to + 60% compared to the control, while the dilution 1:16 increased ZO1 expression by + 100% without affecting OCLN expression. The 1:16 dilution also protected the jejunum from the effects induced by INDO. These results suggest that the anti-nutritional effects exerted by CHE on soy-based meals IVD may depend on the meal's chemical composition. Moreover, we showed that CHE polyphenols exert protective effects on the intestinal epithelium integrity ex vivo at low concentrations. • Chestnut extracts inhibit in vitro digestibility and the total polyphenol content in soy-based products depends on their chemical composition. • Chestnut extracts are an important source of polyphenols and digestive processes affect their bioavailability. • Low concentrations of metabolites obtained by the chestnut extracts' digestion exert protective effects at intestinal level. [ABSTRACT FROM AUTHOR]