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In this paper, we report the synthesis, structural characterization, and antiviral properties of palladium(II) complexes with amantadine (atd) and memantine (mtn). Elemental and mass spectrometric analyses indicated a 1:2 metal/ligand ratio. The single crystal data for Pd‐mtn revealed that the complex adopts a square geometry with the two memantine ligands bonded to Pd(II) by the nitrogen atoms of the NH2 group, in a trans configuration. Computational studies supported a similar structure for Pd‐atd. The complexes were stable in DMSO solution for 24 h. The antiviral properties of Pd‐atd and Pd‐mtn were evaluated against Zika (ZIKV) and Chikungunya (CHIKV) viruses in vitro at their highest noncytotoxic concentrations. The Pd‐atd (at 2 µM) and Pd‐mtn (at 10 µM) complexes were able to impair 76% and 96% of CHIKV replication, respectively, which points the coordination of amantadine and memantine to Pd(II) as a successful strategy to increase their anti‐CHIKV properties. Conversely, the Pd(II) complexes did not significantly inhibit the replication of ZIKV, which confirms the selectivity towards CHIKV. Interaction of the compounds with N‐acetyl‐l‐cysteine, a model disulfide‐containing peptide, and plasmid DNA pointed to Cys‐containing peptides as more likely targets than nucleotides for the complexes. [ABSTRACT FROM AUTHOR]

This study draws upon media agenda‐setting theory to investigate the relationship between negative media coverage around environmental, social, and governance (ESG) issues and the quality of integrated reporting (IR). In particular, we examine the top 100 South African listed companies in the 2013–2018 timeframe for 317 firm‐year observations. Our results reveal that IR quality is positively related to negative ESG media coverage. Thus, a company exposed to more media pressure issues higher‐quality IR consistent with its need to face scrutiny and potential reputational damage and to restore or maintain its legitimacy. Results are robust to different measures of negative ESG media coverage, controlling for ESG disclosures, and are confirmed by analyses aimed at addressing endogeneity (instrumental variable approach, firm‐fixed effects, and matched samples). Subsample analyses show that financial sector reputational concerns do not impact our results. Additional tests show no long‐term effects of negative media coverage on IR quality and that sustainability embeddedness alleviates a company's response to negative ESG news in terms of enhanced reporting. [ABSTRACT FROM AUTHOR]

Aim: Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors have revolutionized clinical medicine, but their association with urinary tract infection (UTI) risk remains debated. This study investigates the influence of dapagliflozin on UTI outcomes, focusing on kidney injury. Materials and Methods: Female non‐diabetic C57BL/6J and C3H/HeOuJ mice, along with diabetic db/db mice, were orally administered dapagliflozin (1 mg/kg or 10 mg/kg) for 7 days before transurethral uropathogenic Escherichia coli (UPEC) infection. Mice were killed either 24 h after UTI or after six additional days of dapagliflozin treatment. UPEC titers were enumerated, and kidney histopathology, injury, fibrosis and function were assessed. Results: Vehicle‐ and dapagliflozin‐treated C57BL/6J mice exhibited similar urine and bladder UPEC titers, with minimal kidney burden 24 h after UTI. In C3H/HeOuJ mice, UPEC burden was comparable in vehicle‐ and 1 mg/kg dapagliflozin‐treated groups both 24 h and 7 days after UTI. However, C3H/HeOuJ mice receiving 10 mg/kg dapagliflozin had increased UPEC titers in the urine, bladder and kidneys at both endpoints. Kidney injury and fibrosis markers, as well as kidney function, were similar in vehicle and dapagliflozin groups. In diabetic db/db mice receiving dapagliflozin, UPEC strain UTI89 titers were reduced 7 days after UTI compared to vehicle‐treated mice, but no difference in UPEC titers was observed when mice were infected with UPEC strain CFT073. Kidney injury and fibrosis markers and kidney function remained similar across treatment groups. Conclusions: Dapagliflozin does not consistently influence UTI susceptibility and shows limited impact on kidney injury or fibrosis, suggesting SGLT2 inhibitors have minimal effects on UTI‐related kidney complications. [ABSTRACT FROM AUTHOR]

We explore the use of shear wave elastography (SWE) for assessing muscle stiffness and treatment response in cerebral palsy (CP) children by way of a systematic review. SWE offers real‐time muscle stiffness measurements, showing significant differences between CP patients and controls. Studies suggest that SWE can be used to follow muscle stiffness post‐botulinum toxin treatment, correlating with clinical improvement. However, methodological variations and small sample sizes prevent comparison between different studies. Standardized protocols could enhance SWE's clinical utility. In conclusion, SWE holds promise for CP management, though standardized methodologies and larger studies are needed to validate its efficacy and integration into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Long‐term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. Methods: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance‐related genes (PD‐L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus–deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. Results: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p =.008) and tumor‐infiltrating lymphocyte infiltration was higher (p =.02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p =.001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p =.027 and p =.034, respectively). Conclusions: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC. In patients with colorectal cancer, nodal metastasis was significantly less frequent, and tumor‐infiltrating lymphocytes were higher among aspirin users. In the colorectal cancer primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment. In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users. [ABSTRACT FROM AUTHOR]

BACKGROUND: The brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is a significant threat to crop production. Alternatives to synthetic pesticides are needed for its management. Here we investigated the effect of sulphur on H. halys. Experiments were performed to evaluate both mortality and deterrence/repellence of H. halys following sulphur treatments in laboratory and semi‐field conditions. RESULTS: Brown marmorated stink bug mortality was not influenced by sulphur applications. However, in two‐choice experiments in insect cages and olfactometer, more H. halys adults moved toward the untreated control rather than the sulphur‐treated food sources, with a high effect as the concentration increased. A semi‐field experiment using potted apple plants confirmed the results observed in the laboratory, showing a deterrent and/or repellent effect of sulphur‐based products on H. halys. CONCLUSIONS: Sulphur applications were associated with a deterrent/repellent effect on the brown marmorated stink bug. The use of sulphur‐based products could represent a promising tool for Integrated Pest Management strategies against H. halys in fruit crops. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity. Synopsis: The promyelocytic leukemia protein (PML) is essential to sustain clear cell renal cell carcinoma (ccRCC) expansion via p53 inhibition and the PML-targeting drug arsenic trioxide exerts cancer inhibitory functions in ccRCC. PML is overexpressed and efficiently partitioned into PML-NBs in ccRCC. PML inhibition blocks ccRCC expansion in vitro and in vivo. Targeting ccRCC non-oncogenic addiction to PML via gene silencing or arsenic trioxide unleashes p53-dependent growth arrest and apoptosis. Arsenic trioxide is effective at inhibiting expansion of ccRCC cells with wild type and mutant p53. The promyelocytic leukemia protein (PML) is essential to sustain clear cell renal cell carcinoma (ccRCC) expansion via p53 inhibition and the PML-targeting drug arsenic trioxide exerts cancer inhibitory functions in ccRCC. [ABSTRACT FROM AUTHOR]

Aims: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. Methods: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all‐cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. Results: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02–1.69); a non‐statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI:.93–1.55). Similar results were observed for all‐cause death, while no statistically significant differences were observed for IS or ICH. Conclusion: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. Clinical Trial Registration: NCT00041938. [ABSTRACT FROM AUTHOR]

Aim: The study was designed to generate real‐world evidence on IDegLira in the Italian clinical practice in two groups of patients with type 2 diabetes (T2D), switching to IDegLira either from a basal only (basal group) or basal‐bolus insulin regimen (BB group). Materials and Methods: This was a non‐interventional, multicentre, single‐cohort, prospective study assessing the long‐term glycaemic control in patients with T2D, who switched to IDegLira from a basal insulin ± glucose‐lowering medication regimen with or without a bolus insulin component for approximately 18 months, conducted in 28 Italian diabetes centres. The primary endpoint was the change in glycated haemoglobin (HbA1c) levels from baseline to 6 months after IDegLira initiation. Results: The study included 358 patients with a mean age 67.2 years and diabetes duration of 15.7 years. HbA1c significantly decreased from IDegLira start to all study time points in the overall population (basal group −1.19%; BB group −0.60% at the end of observation). Patients achieving HbA1c <7% levels increased from 12.9% (n = 43) to 40.3% (n = 110) at 18 months. Fasting blood glucose and body weight also significantly decreased in both groups, although more in the BB group. Overall, 14.3% of completed patients had an intensification of treatment (mainly in the basal group) and 48.6% had a simplification of treatment (mainly in the BB group). Conclusions: Switching to IDegLira in a real‐world clinical setting is a valid therapeutic option for patients with T2D with inadequate glycaemic control on basal or BB insulin regimen and/or need to simplify their insulin therapy, with specific reasons and therapeutic goals according to different T2D management trajectories. [ABSTRACT FROM AUTHOR]

Background: Low testosterone concentrations affect 2–13% of adult males, with a direct association between reduction in testosterone (T) concentrations and cardiovascular events. Lifestyle habits have been linked to visceral fat accumulation and endocrine disorders like secondary hypogonadism. Alcohol intake has also been a topic of debate, with studies showing a detrimental effect on sperm production and underlying mechanisms. This meta‐analysis aims to comprehensively evaluate the effect of alcohol consumption on T serum concentrations in adult men. Methods: The literature search included only controlled clinical trials comparing men who drink alcohol to men who do not, or who assumed placebo or nonalcoholic beverages. The primary outcome was the comparison of total testosterone serum concentrations between the study and control groups. The publications were examined for publication bias using Egger's test. Results: Twenty‐one studies were included in the analysis for a total of 30 trials that examined the effects of alcohol consumption on testosterone level in 10,199 subjects. The meta‐analysis showed that alcohol consumption overall is related to significant reduction in circulating concentrations of total testosterone (mean difference [MD] = −4.02; 95% CI −6.30, −1.73), free T (MD = −0.17; 95% CI −0.23, –0.12), sex hormone binding globulin (SHBG) (MD = −1.94; 95% CI −3.37, −0.48), an increase in estradiol (E2) (MD = 7.65; 95% CI 1.06, 14.23) and neutral effect on luteinizing hormone (LH) (MD = −0.15; 95% CI −0.36, 0.06), independently by age, body mass index (BMI), E2, and LH serum concentrations and alcohol intake. However, these results are evident only in healthy men exposed to chronic alcohol consumption and not in those with a recognized diagnosis of alcohol use disorder or after acute alcohol intake. Conclusion: This study suggests how chronic alcohol consumption may inhibit the gonadal axis in healthy men, although the exact pathophysiological mechanisms connecting alcohol exposure and steroidogenesis are still not completely clarified. [ABSTRACT FROM AUTHOR]

Even though quantum algorithms are designed using an idealised high‐level quantum circuit description, the execution on real devices must consider the backend physical properties. Contemporary noisy intermediate‐scale quantum (NISQ) computers are characterized by limited inter‐qubit connectivity and an exclusive set of native gates, whose execution is affected by non‐negligible errors and non‐idealities. Quantum compilation, consisting of logic and layout synthesis, aims to recast the original circuit description to the target hardware by solving the coupling‐constraint and to minimize the execution time and the error rate. While a previous article addresses the first phase, the second one is the aim of this manuscript. Currently available layout tools mainly target superconducting technology. This article tries to match the unmet need for a layout synthesis library supporting a wider range of technologies. The most promising algorithms already present in the state of the art are adapted to extend the compatibility to all the supported technologies, and new approaches, which exploit the awareness of the coupling strength in fully‐connected topologies, are proposed. The integrated procedures are benchmarked against IBM's Qiskit and Cambridge Quantum Computing's t|ket⟩$\textrm {t} \vert \textrm {ket} \rangle$ compilation toolchains, and even though these strategies can be further improved, the results are encouraging. [ABSTRACT FROM AUTHOR]

Students with intellectual disabilities (ID) have reduced access to sexuality education at school, tasking families with filling the gap. This limited access contributes to persistent health inequities, psychosocial risk, and reduced self‐determination for individuals with ID. To understand the resources that families may encounter when filling this service gap, a naturalistic scoping review and content analysis of ID‐specific sexual health curricula (SHC) was conducted. This analysis found a limited number of SHC available to family members who may seek them out online, and even fewer SHC designed for the specific needs of family‐led delivery. While curricula identified in this study generally include the minimum recommended content areas for comprehensive sexuality education, they less frequently provide actionable guidelines for caregivers tasked with adapting teaching practices and outcomes assessment to the diverse profiles of students with ID. By understanding the SHC available to families of students with ID, school psychologists can improve their partnerships with families, disseminate needed resources, implement collaborative intervention practices, and advocate for inclusive sexuality education practices. Practitioner points: Students with intellectual disability have reduced access to sexuality education, even though it has been shown to improve overall health and quality of life.There are several sexual health curricula that are easily accessible to the families of students with intellectual disability.School psychologists can partner with families to locate, evaluate, and implement sexual health curricula that meet student and family needs. [ABSTRACT FROM AUTHOR]

One of the defining features of acute myeloid leukemia (AML) is an arrest of myeloid differentiation whose molecular determinants are still poorly defined. Pharmacological removal of the differentiation block contributes to the cure of acute promyelocytic leukemia (APL) in the absence of cytotoxic chemotherapy, but this approach has not yet been translated to non‐APL AMLs. Here, by investigating the function of hypoxia‐inducible transcription factors HIF1α and HIF2α, we found that both genes exert oncogenic functions in AML and that HIF2α is a novel regulator of the AML differentiation block. Mechanistically, we found that HIF2α promotes the expression of transcriptional repressors that have been implicated in suppressing AML myeloid differentiation programs. Importantly, we positioned HIF2α under direct transcriptional control by the prodifferentiation agent all‐trans retinoic acid (ATRA) and demonstrated that HIF2α blockade cooperates with ATRA to trigger AML cell differentiation. In conclusion, we propose that HIF2α inhibition may open new therapeutic avenues for AML treatment by licensing blasts maturation and leukemia debulking. Synopsis: Hypoxia‐inducible transcription factor HIF2α contributes to acute myeloid leukemia (AML) pathogenesis by taking part to the molecular network that suppresses differentiation of leukemic blasts along the myeloid lineage. Hypoxia‐inducible factors HIF1α and HIF2α promote leukemia progression in cell and patient‐derived models of established AML.In AML cells, HIF2α regulates a novel gene signature that contains Runx2 and BCL11A and transcriptional repressors implicated in suppressing AML myeloid differentiation programs.HIF2α targeting via gene silencing or pharmacological inhibition triggers a myeloid differentiation program and promotes leukemia debulking.All‐trans retinoid acid induces HIF2α expression via direct activity of RAR proteins.Targeting HIF2α cooperates with ATRA to promote myeloid differentiation. [ABSTRACT FROM AUTHOR]

Best practices for technology use in academic settings, specifically those preparing students for postsecondary transition (ages 18–21) are not well documented and research studies commenting on the use of technology for acquisition of social and adaptive skills is limited. Literature indicates that students with mild–moderate intellectual and developmental disabilities (IDD) benefit from adaptive‐skills programs and curricula. School psychologists, special educators, and school‐based interventionists are in a unique position to provide adaptive skill services and tier‐3 interventions that are evidence‐based, innovative, and serve the most vulnerable students. This manuscript utilizes a sign‐case design to test the use of virtual reality (VR) as an individualized intervention and teaching modality to a student in a center‐based high school program with IDD. Results yield promising findings, indicating those with IDD may master VR as a tool, learn new skills with VR programming, and generalize those skills to real‐world settings. Further, VR offers unique benefits that can shape the way school interventionists view technology and how innovative practices can be used for students with IDD. Practitioner points: There is a clear need for further research in appropriate intervention instruments for students with intellectual and developmental disabilities (IDD), specifically those in high school who may be preparing for postsecondary transition and learning independent living skills.This manuscript utilizes a sign‐case design to test the use of virtual reality (VR) as an individualized intervention and teaching modality to a student in a center‐based high school program with IDD.Results yield promising findings, indicating those with IDD may master VR as a tool, learn new skills with VR programming, and generalize those skills to real‐world settings. [ABSTRACT FROM AUTHOR]

Herein we report the first example of a supramolecular cage that works as a catalytic molecular reactor to perform transformations over fullerenes in aqueous medium. Taking advantage of the ability of metallo–organic Pd(II)‐subphthalocyanine (SubPc) capsules to form stable host:guest complexes with C60, we have prepared a water‐soluble cage that provides a hydrophobic environment for conducting cycloadditions over encapsulated C60, namely, Diels–Alder reactions with anthracene. Indeed, the presence of catalytic amounts of SubPc cage dissolved in water promotes co‐encapsulation of insoluble C60 and anthracene substrates, allowing the reaction to occur inside the cavity under mild conditions. The lower stability of the host:guest complex with the resulting C60 cycloadduct facilitates its displacement by pristine C60, which grants catalytic turnover. Moreover, bis‐addition compounds are regioselectively formed inside the cage when using excess anthracene. [ABSTRACT FROM AUTHOR]

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF‐α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF‐α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma. [ABSTRACT FROM AUTHOR]

Multinomial logistic regression (MLR) is often used to model the association between a nominal outcome variable and one or more covariates. The results of MLR are interpreted as relative risk ratios (RRR) and warrant a more coherent interpretation than ordinary logistic regression. Some authors compare the results of MLR to ordinal logistic regression (OLR), irrespective of the fact that these estimate different quantities. We aim to investigate the time trends in the use and misuse of MLR in studies including stroke patients, specifically the extent to which (1) the results are denoted as anything other than RRR, (2) comparisons are made of results with results of OLR and (3) results have been interpreted coherently. Secondarily, we examine the use of model validation techniques in studies with predictive aims. We searched EMBASE and PubMed for articles using MLR on populations of stroke patients. Identified studies were screened, and information pertaining to our aims was extracted. A total of 285 articles were identified through a systematic literature search, and 68 of these were included in the review. Of these, 60 articles (88%) did not denote exponentiated coefficients of MLR as relative risk ratios but rather some other measure. Additionally, 63 articles (93%) interpreted the results of MLR in a non‐coherent manner. Two articles attempted to compare MLR results with those of OLR. Nine studies attempted to use MLR for predictive means, and three used relevant validation techniques. From these findings, it is clear that the interpretation of MLR is often suboptimal. [ABSTRACT FROM AUTHOR]

Aim: To evaluate associations between oral hygiene and gingival abrasion (GA) in a rural population from southern Brazil. Materials and Methods: A population‐based sample representative of individuals from a rural community in southern Brazil was included. Individuals aged 15 years or older and who had five teeth or more present were selected for this analysis. GA extent was defined as the total number of abrasions per individual. An adjusted multilevel negative binomial regression analysis was used to investigate the associations between site‐, tooth‐ and individual‐level variables and GA. Mean ratios (MR) and 95% confidence intervals (95% CI) were calculated. Results: Five hundred ninety‐five dentate individuals aged 15–82 years were analysed. In the adjusted models, brushing more than twice a day (MR = 1.13; 95% CI 1.02–1.26) and brushing with a hard/medium‐bristle toothbrush (MR = 1.11; 95% CI 1.01–1.23) were significantly associated with more generalized GA. Conclusions: The extent of GA was independently associated with greater brushing frequency and the use of a toothbrush with harder bristles in residents of a rural area. [ABSTRACT FROM AUTHOR]

Introduction: Recent advances in long-acting antiretroviral therapy (LA-ART) could provide new options for HIV treatment and reduce adherence barriers, if regimens are acceptable to patients. We elicited preferences for key attributes of potential LA-ART regimens among people with HIV (PWH) in the United States, focusing on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), product characteristics and location of administration. Methods: A discrete choice experiment was conducted among PWH aged ≥18 years recruited from HIV clinics in Washington State and Atlanta, Georgia from March 2021 to June 2022. Participants responded to 17 choice scenarios, each with three options: two systematically generated hypothetical LA-ART regimens and a constant opt-out (their current daily oral treatment). LA-ART regimen descriptions included treatment mode, pain, dosing frequency, location, pre-treatment time with undetectable viral load, pre-treatment negative reaction testing and "late-dose leeway" (i.e. flexibility or forgiveness in timing the next dose). We used conditional logistic regression, with an interaction between treatment mode and pain, to estimate preference weights for all attribute levels. Results: Seven hundred participants (350 at each site) enrolled, with median age 51 years (range 18-73); 70% identified as cisgender male, 24% as cisgender female and 6% as non-binary or transgender. LA oral tablets were the only mode preferred over current daily oral treatment, with annual implants and injections the next most preferred LA-ART option. Longer time between doses was preferred, and administration at home was preferred to clinics, which were preferred to pharmacies. Attributes with less impact on preferences included oral lead-in treatment to achieve viral suppression or test for negative reactions and late-dose leeway around the prescribed dosing interval. Participants in Atlanta were more likely to prefer their current daily oral ART than participants from Seattle. Conclusions: PWH in the United States may soon have several options for LA-ART. Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some. Future research should investigate sources of preference heterogeneity and actual uptake of and adherence to LA-ART products, when available. [ABSTRACT FROM AUTHOR]

Bench top and pilot lead corrosion studies are gaining more interest, considering revisions and upcoming improvements to the Lead and Copper Rule. This literature review identified studies ranging from simpler month(s)‐long bench top dump‐and‐fill stagnant water tests (coupon tests/standing pipe tests) to more complicated year(s)‐long intermittent flow pilot studies (recirculating pipe loops/once through pipe rigs). With increasing complexity in design and operation, studies more closely approximated real plumbing conditions (e.g., by incorporating harvested lead pipes and intermittent flow regimes) at increased cost, footprint, and duration. Comparison of bench top and pilot designs (in terms of lead test piece age/dimensions/configuration/replicates, study duration, sample collection, and other factors) can assist drinking water utilities, consultants, academics, and others to select a design that matches their needs and constraints. No matter the choice, surrogate systems cannot replace actual system water testing and are best complemented by other corrosion assessment tools. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effectiveness of follicle‐stimulating hormone (FSH) administration in male idiopathic infertility in a clinical setting. Methods: A retrospective real‐world study was carried out, including all consecutive FSH‐treated infertile men attending the Andrology Unit of Modena (Italy) from June 2015 to May 2022. Medical history, physical and andrological examinations, hormonal and seminal parameters, therapeutic management and pregnancy data were collected. The primary endpoint was the number of pregnancies obtained after FSH administration, whereas semen parameters change was the secondary outcome. Results: A total of 194 of 362 (53.6%) infertile men, eligible according to the Italian Health System regulations, were treated with FSH (mean age 37.9 ± 6.1 years). Following FSH administration (mean therapy duration 9.1 ± 7.1 months), 43 pregnancies were recorded (27.6%), of which 22 occurred naturally and 21 after assisted reproduction. A significant increase in sperm concentration (9.9 ± 12.2 vs. 18.9 ± 38.9 million/mL, p = 0.045) was detected after treatment, together with a significant increase in normozoospermia (from 1.0% to 5.1%, p =.044) and a reduction in azoospermia rate (from 9.8% to 7%, p = 0.044). Dividing the cohort in FSH‐responders and non‐responders, in terms of pregnancy achieved, higher sperm concentrations (15.7 ± 26.6 vs. 22.2 ± 25.7 million/mL, p = 0.033) and progressive sperm motility (18.0 ± 18.2 vs. 27.3 ± 11.3, p = 0.044) were found in pregnancy group. Conclusion: Our experience suggests that FSH, empirically administered to men with idiopathic infertility, leads to pregnancy in one out of four patients and increases sperm concentration. Although the expected limits because of a real‐world data study, the number of FSH‐treated patients required to achieve one pregnancy seems to be lower in clinical setting if compared to previously published data. [ABSTRACT FROM AUTHOR]

SUMMARY: Transposable elements (TEs) are an important source of genome variability, playing many roles in the evolution of eukaryotic species. Besides well‐known phenomena, TEs may undergo the exaptation process and generate the so‐called exapted transposable element genes (ETEs). Here we present a genome‐wide survey of ETEs in the large genome of sunflower (Helianthus annuus L.), in which the massive amount of TEs, provides a significant source for exaptation. A library of sunflower TEs was used to build TE‐specific Hidden Markov Model profiles, to search for all available sunflower gene products. In doing so, 20 016 putative ETEs were identified and further investigated for the characteristics that distinguish TEs from genes, leading to the validation of 3530 ETEs. The analysis of ETEs transcription patterns under different stress conditions showed a differential regulation triggered by treatments mimicking biotic and abiotic stress; furthermore, the distribution of functional domains of differentially regulated ETEs revealed a relevant presence of domains involved in many aspects of cellular functions. A comparative genomic investigation was performed including species representative of Asterids and appropriate outgroups: the bulk of ETEs that resulted were specific to the sunflower, while few ETEs presented orthologues in the genome of all analyzed species, making the hypothesis of a conserved function. This study highlights the crucial role played by exaptation, actively contributing to species evolution. Significance Statement: The molecular domestication of transposable elements leads to the formation of novel genes through exaptation. By setting up a protocol for systematically discovering exapted transposable elements (ETEs) in large genome species, we identified and validated 3,530 ETEs in sunflower genome. The identification of ETEs in Helianthus annuus can be considered further proof of the fundamental contribution that TEs had in the rising of genetic novelties, probably influencing different biological processes during the evolution of the sunflower. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a major non‐communicable disease that affects the health‐related quality of life (HRQoL) of patients. However, data on HRQoL and symptom control in AR patients with comorbid asthma (AR + asthma) are lacking. Methods: In this multicentre, cross‐sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire (30, 'not at all bothered' ‐ 150 'very much bothered') and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT) (0, 'no control' ‐ 30, 'very high control'). Results: Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate‐severe intermittent AR, followed by moderate‐severe persistent AR (34%). Compared to the patients with AR alone, patients with AR + asthma had significantly higher RHINASTHMA (e.g., median RHINASTHMA‐total score 48.5 vs. 84, respectively) and a significantly lower CARAT score (median CARAT‐total score 23 vs. 16.5, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than those with mild persistent asthma. The association was significantly higher among non‐obese participants compared to obese ones, with RHINASTHMA‐upper symptoms score but not with CARAT. Conclusions: Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition. [ABSTRACT FROM AUTHOR]

The development of genetically modified mosquitoes (GMM) and their subsequent field release offers innovative approaches for vector control of malaria. A non‐gene drive self‐limiting male‐bias Ag(PMB)1 strain has been developed in a 47‐year‐old laboratory G3 strain of Anopheles gambiae s.l. When Ag(PMB)1 males are crossed to wild‐type females, expression of the endonuclease I‐PpoI during spermatogenesis causes the meiotic cleavage of the X chromosome in sperm cells, leading to fertile offspring with a 95% male bias. However, World Health Organization states that the functionality of the transgene could differ when inserted in different genetic backgrounds of Anopheles coluzzii which is currently a predominant species in several West‐African countries and thus a likely recipient for a potential release of self‐limiting GMMs. In this study, we introgressed the transgene from the donor Ag(PMB)1 by six serial backcrosses into two recipient colonies of An. coluzzii that had been isolated in Mali and Burkina Faso. Scans of informative Single Nucleotide Polymorphism (SNP) markers and whole‐genome sequencing analysis revealed a nearly complete introgression of chromosomes 3 and X, but a remarkable genomic divergence in a large region of chromosome 2 between the later backcrossed (BC6) transgenic offspring and the recipient paternal strains. These findings suggested to extend the backcrossing breeding strategy beyond BC6 generation and increasing the introgression efficiency of critical regions that have ecological and epidemiological implications through the targeted selection of specific markers. Disregarding differential introgression efficiency, we concluded that the phenotype of the sex ratio distorter is stable in the BC6 introgressed An. coluzzii strains. [ABSTRACT FROM AUTHOR]

The enormous amount of agroindustrial residues generated in Brazil can be used as biomass to produce fermentable sugars. This study compared the pretreatments with different proportions of dilute acid. The method involved pretreatment with 0.5%, 1%, and 1.5% (v/v) sulfuric acid, followed by hydrolysis using the halotolerant and thermostable endoglucanase from Botrytis ricini URM 5627. The physicochemical characterization of plant biomass was performed using XRD, FTIR, and SEM. The pretreatment significantly increased the production of fermentable sugars following enzymatic saccharification from wheat bran, sugarcane bagasse, and rice husk: 153.67%, 91.98%, and 253.21% increment in sugar production; 36.39 mg⋅g−1 ± 1.23, 39.55 mg⋅g−1 ± 1.70, and 42.53 mg⋅g−1 ± 7.61 mg⋅L−1 of glucose; and 3.26 ± 0.35 mg⋅g−1, 3.61mg⋅g−1 ± 0.74 and 3.59 mg⋅g−1 ± 0.80 of fructose were produced, respectively. In conclusion, biomass should preferably be pretreated before the enzymatic saccharification using B. ricini URM 5627 endoglucanase. [ABSTRACT FROM AUTHOR]

Synoeca‐MP is a 14‐residue amidated peptide, belongs to the mastoparan family and it is found in the venom of the wasp Synoeca surinama and has antibacterial and antifungal activity. The low cytotoxicity of the peptide also makes it an excellent candidate for drug development. To better understand its selectivity and interaction with the membrane, the peptide behavior in membrane‐like environments was studied here and the peptide structure in SDS micelles was determined by NMR spectroscopy. The behavior of the peptide in hydrophobic media and in different pH ranges was studied by CD spectroscopy. The incorporation of residues into the anionic micelles was studied by hydrogen‐deuterium exchange. The peptide stability and insertion in the micelles was studied by molecular dynamics simulations. Synoeca‐MP, bound to SDS micelles, exhibits a partial α‐helix conformation, with the first five residues and the last two unfolded. H/D exchange showed that the peptide has a slow exchange rate. After 164 h, four residues had not yet completed H/D substitution, suggesting parallel alignment of the peptide with the micelle, mainly due to the hydrophobic interface. This may indicate a carpet interaction model of the peptide with micelles. The molecular simulation study of peptide showed that the peptide consists of a well‐folded alpha‐helix core and unfolded extremities, which are responsible for the nature of the peptide interaction. The biophysical analyses can improve the atomic understanding of the mode of action of the peptide and help in future improvements of the peptide for clinical usage. [ABSTRACT FROM AUTHOR]

Estimates of the earthquake ground motion intensity over a geographical area have multiple uses, that is, emergency management, civil protection and seismic fragility assessment. In particular, with reference to fragility assessment, it is of interest to have estimates of the values of different ground‐motion intensity measures in order to correlate them with the observed damage. To this purpose, the present paper uses a procedure recently proposed in the literature to estimate the ground‐motion intensity for the 2012 Emilia mainshocks, considering different ground motion intensity measures and directionality effects. Ground motion prediction equations based on different site effect models, and spatial correlation models are calibrated for the Emilia earthquakes. The paper discusses the accuracy of the shakemaps obtained using the different soil effect models considered and presents the obtained shakemaps as supplementary material. The procedure presented in the paper is aimed at providing ground motion intensity values for seismic fragility assessment and is not intended as a tool to estimate shakemaps for rapid emergency assessment. [ABSTRACT FROM AUTHOR]

Background: The predictive role of sperm motility and morphology was recently detected in a large sample of more than 20000 assisted reproductive technology (ART) fresh cycles. However, the complete ART procedure consisted of both fresh and frozen‐embryos transfers and only a comprehensive evaluation of the entire process could really confirm if these parameters really predict the ART success. The aim of the study was to evaluate which sperm parameter could predict the success of ART. Methods: A retrospective, real‐world data analysis was performed, enrolling all couples attending ART from 2008 to 2021, including both fresh and frozen cycles and both in vitro fertilization (IVF) and intra‐cytoplasmic sperm injection (ICSI) procedures. Results: Fresh cycles success (considering live birth rate) was predicted by female age (1.04 [1.02–1.06]), injected oocytes (0.96 [0.93–0.99]), embryo number (0.79 [0.75–0.83]) and progressive sperm motility (0.98 [0.97‐0.99]). On the contrary, frozen cycle outcomes were predicted only by sperm motility (0.97 [0.95–0.99]). This prediction was confirmed in IVF but not in ICSI cycles. Conclusion: Both female and male parameters predicted the ART success considering the entire path. However, frozen cycle success was predicted only by progressive sperm motility in IVF cycles, suggesting that the potential amelioration of this male parameter is relevant to improve ART success. Those couples expected to obtain the highest embryos after fertilization (low female age and better semen parameters) will have more attempts with frozen cycles and thus would benefit from a potential treatment focused to improve sperm parameters. [ABSTRACT FROM AUTHOR]

Although clinical trials[5] and real-world studies[[6], [8], [10]] have investigated its role in these patients, there are no comparative studies specifically evaluating the efficacy of Risankizumab according to body mass index (BMI). All these data lead us to postulate that Risankizumab represents an optimal molecule for the management of patients with moderate-to-severe psoriasis, regardless of BMI. Real-life effectiveness of Risankizumab according to body mass index: Results of an Italian multicentre retrospective study. [Extracted from the article]

EDITORIAL EVOLUTION AND EFFORTS TO IMPROVE QUALITY OF SUBMITIONS In 2017 the new Chief Editor, Manuela Simoni was appointed by EAA and joined Doug Carrell behind the wheel of I Andrology i . The current Chief Editor, Marie-Claude Hofmann and the new Deputy Editor, Aleksander Giwercman will strive to keep improving the journal for the benefit of the two organizations, EAA and ASA, entire andrology community, but also the society at large. An important part of the Academy's history is its scientific publishing activity, which started with the I International Journal of Andrology (Int J Androl) i , and continued with I Andrology i , the journal created and overseen jointly by the EAA and the American Society of Andrology (ASA). Marking the first decade of Andrology - Conception and early development of the journal. [Extracted from the article]

In mountain rivers, long‐term observations of water and sediment fluxes are crucial for understanding the dynamics of bedload fluctuations. We analyze 7 years of continuous data gathered from eight geophone plates at a monitoring station in the glacier‐fed Sulden/Solda River (South Tyrol, Italy) to estimate the bedload flux at 1‐min scale. Sixty‐five bedload samples were used to derive the calibration equations adopted to quantify the transported bedload mass. The signal power is proposed as a more effective metric than threshold‐based impulses for calculating bedload masses. Results show (a) a remarkable variability of bedload rates for the same value of flow discharge, (b) the joint effect of storm‐driven flood events and seasonal changes in sediment supply on bedload rates, and (c) the strong impact of climatic factors (i.e., temperature and snow cover) on bedload fluxes. Moderate bedload rates occurring in late spring/early summer are likely related to the mobilization of riverbed sediments, while sustained bedload transport during melt flows in July–August—corresponding to the effective bedload discharge range—is associated with the activation of glacial and proglacial sediment sources. The data set shows a complex climatic control on bedload transport at the basin scale, where precipitation, air temperature, and snow cover determine flow and glacier melting dynamics. These findings suggest how the effects of climate change in the Alps likely will lead to an increase in peak bedload rates in a context of declining annual bedload yields as melt flows will progressively reduce in the next decades. Plain Language Summary: Water flowing in mountain rivers can transport a large amount of bedload, which is the coarse sediments that jump and roll on the river bed. The knowledge of the bedload flux matters for both improved understanding of the ecosystem and of the effects of human activities. Measuring how much bedload is transported is difficult as particles move below the water level. In this study, we employ seismic sensors installed on the river bed to quantify bedload transported by an Alpine river originating from a glacierized area. Moving particles produce ground vibrations that are more intense when the river transports more material. We found that the intensity of bedload measured by this "seismic noise" is extremely variable during the year and controlled by weather conditions. In particular, the river can rapidly increase the transport of sediments during high runoff peaks induced by glacier melt and summer thunderstorms. These findings are particularly relevant in the context of ongoing global warming that is dramatically impacting mountain areas where newly exposed stream reaches are emerging from the rapidly melting glaciers. Key Points: The power of the geophone‐plate seismic signal better reflects the variability of bedload rate than the number of threshold‐based impulsesHighest bedload rates (>103 kg m−1 min−1) produced by summer rainstorm events occur during snow‐ and glacier‐melt periodsTemperature‐controlled glacier melt flows are most effective in transporting bedload, followed by rainfall‐driven 1.5–2 years floods [ABSTRACT FROM AUTHOR]

Introduction: Although a trustworthy connection between doctor and patient is crucial in clinical practice, it could be hindered by different cultural and linguistic backgrounds. Moreover, an effective doctor–patient interaction could be even more challenging in andrological fields, in which psychological and social components are predominant. Aim: To analyse the doctor–patient relationship in the andrological field, applying both qualitative and quantitative analyses. Methods: monocentric, cross‐sectional, observational study was performed between May and December 2018. During the study, all patients aged >18 years attending the Modena Andrology Unit for couple infertility or erectile dysfunction were enrolled and the doctor–patients interaction recorded. Patients were divided into two groups depending on their medical seeking and were further divided between native and non‐native speakers of Italian. All patients underwent a routine andrological examination. Every first medical consultation was audio‐recorded and transcribed using "ELAN" software for socio‐linguistic analysis. Transcriptions underwent qualitative analysis through conversation analysis. Then, quantitative analyses were performed, and interaction parameters underwent correlation analyses. Results: Twenty‐five patients were enrolled. The analysis of the andrological interview allowed to recognise five consecutive phases, following a semi‐standardized pattern. Patients without linguistic barriers and with infertility problems showed more autonomous contribution during the consultation. No difference arose in the sexual dysfunctions group. Doctor's explanations were frequent, but when linguistic barrier was present or Italian patients seemed less talkative, explanations were shorter, and doctors tried to use other conversational mechanisms to promote understanding. Patient's variables were significantly lower compared to the doctor, considering the number of turns (p = 0.025) and their minimum (p = 0.032), maximum (p < 0.001), and average durations (p < 0.001). Only patient's latency was significantly higher than the doctor's (p = 0.001). Conclusion: This is the first attempt to analyse the doctor–patient relationship in andrology using authentic audio‐recorded consultations. The results confirmed that a patient‐centred communication must be applied also in andrological consultations. However, the topics discussed may require more "medical formulation" to be acceptable to the participants in this context. [ABSTRACT FROM AUTHOR]

We briefly describe the case of a 4‐year‐old girl, referred for imaging of a small, firm, round, skin‐colored, subcutaneous nodule that suddenly appeared at her right sternoclavicular junction. A plain radiograph was non‐contributory, but ultrasonography revealed a small cystic structure, leading to the diagnosis of a sternoclavicular ganglion cyst. Sternoclavicular ganglion cysts are a rare diagnosis, with only seven reported pediatric cases. A watchful waiting approach can be adopted so long as they remain asymptomatic. [ABSTRACT FROM AUTHOR]

Seismic geophones have been frequently used in combination with metal plates to indirectly estimate bedload flux in gravel bed mountain rivers. This indirect method has been calibrated with direct measurements in several conditions and proved effective to provide relevant information on spatial and temporal scales otherwise impossible to explore. Notwithstanding, a detailed description of the vibration modes of the plate is still lacking, limiting the possibility to interpret the signal. Here, we report on two sets of experiments where we explored the geoplate response in terms of frequency and amplitude of different vibrational modes. A first set of dry experiments was designed to investigate the variability of the signal as a function of the impact location on the plate. A second set reproduced standard flow conditions, with single pebbles transported by the flow. Results highlighted the occurrence of two main vibration modes, with a first rapid phase (about 5 ms) characterized by higher frequencies, and a second longer and more stable phase of vibration with a frequency in the range of 300–400 Hz. The signal of single impacts showed a good correlation with pebble mass, with only the number of impacts on the plate depending on the flow conditions. The evaluation of the grain size is a challenge given the variability of the signal generated by similar impacts. We propose a filtering strategy to improve grain size estimation. Our analysis shows that a more detailed understanding of the vibrational modes helps identifying best practices for an improved signal acquisition and elaboration. Plain Language Summary: Vibration produced by sediments transported on the riverbed can be used to indirectly estimate sediment flux in rivers. A commonly used method involves the installation of metal plates on the riverbed. Their vibration is measured by geophones and converted into metrics related to sediment flux. In this work, we performed laboratory experiments to better understand the vibration modes of the plate, measuring the frequency and amplitude of the different harmonics through a Fourier analysis. In a first set of experiments, we investigated the variability of the signal as a function of the hitting spot on the plate, in dry conditions. A second set reproduced standard flow conditions, with single particles transported by the flow. Results showed that the plate vibrates mainly with its natural frequency (about 350 Hz), with higher frequencies related to higher vibration modes damping very rapidly. Particles hit the plate one or more times, generating impacts with amplitudes related mainly to their mass, whereas the number of impacts also depends on the flow conditions. Filtering the impacts as a function of their vibration spectra may result in more accurate relationships between the recorded signal and sediment flux and may help designing improved signal acquisition and elaboration tools. Key Points: Fourier and wavelet analysis of the geophone signal highlights the plate vibrates with a fundamental frequency in the range of 300–400 HzAmplitude of the fundamental mode depends on particles mass and is not affected by flow conditions, whereas the number of impacts isAmplitude of the main vibration mode is related to grain size, but also pebble shape has a significant role [ABSTRACT FROM AUTHOR]

A new family of 3T1R parallel manipulators (PMs) with self‐aligning property, named TetraFLEX, is presented. 3T1R manipulators have many applications in different fields. Moreover, self‐aligning property refers to the presence of passive joints in the PM limbs that are conceived to compensate for possible misalignments between the sliding directions of the actuated prismatic(P)‐pairs. This property allows the fixation of the limbs in different frame geometries. Thus, this advantage broadens the PM applications to field robotics in several scenarios. Here, the position and singularity analyses of the new family of self‐aligning PMs is addressed with a unified approach. The results are that both the direct and the inverse position analyses have simple closed‐form solutions and that wide free‐from‐singularity regions of TetraFLEX PMs' workspace exist. The effectiveness of the technical proposal is also illustrated by discussing their design criteria and kinetostatics performances in a case study. [ABSTRACT FROM AUTHOR]

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio‐physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive‐vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS‐2 bone‐derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano‐scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm−2 wall shear stress), large enough for inducing a physiologically‐relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS‐2 cell differentiation, leading to 20‐fold higher collagen deposition compared to static cultures, and to 1.6‐ and 1.2‐fold higher deposition than the perfused‐ or vibrated‐only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high‐volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five‐tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0‐3 vs pTRG 4; mrTRG 2‐5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73‐0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that "T3 greater than 5 mm extent" was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15‐0.68, P =.0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI. [ABSTRACT FROM AUTHOR]

Background: The recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking. Objective: To identify which parameters could predict psychological erectile dysfunction. Moreover, we suggest a new intracavernosal injection procedure to optimize the erectile dysfunction diagnostic workup. Materials and methods: A retrospective, real‐world analysis was carried out including all men who underwent intracavernosal injection procedure at the Modena Andrology Unit from 2018 to 2021. A first intracavernosal injection procedure with 5 µg of prostaglandin E‐1 (PGE‐1) was performed. In the absence of a full drug‐induced erection (immediate or delayed), an echo‐color Doppler penile evaluation after administration of PGE‐1 10 µg was conducted, measuring intracavernosal blood flows, to document a possible vascular etiology. Hormonal evaluations were performed. Results: Out of 179 enrolled patients, 70.4% showed psychological erectile dysfunction, 21.7% vascular erectile dysfunction, and 7.8% hormonal genesis. Multinomial logistic regression analysis identified absence of cardiovascular disease (p = 0.017), presence of spontaneous morning erections (p = 0.018), and normal penile erections with masturbation (p = 0.035) as predictors of psychological erectile dysfunction. Clinically, normal intracavernosal injection test response was detected in 86 patients and abnormal response in 93 subjects. Among the latter, 54 patients experienced a delayed response. The combination of intracavernosal injection test with late penile erections evaluation was able to diagnose psychological erectile dysfunction (sensitivity 97%, specificity 100%), avoiding unnecessary retesting. Discussion: We propose a two‐step intracavernosal injection procedure that allows to recognize psychological erectile dysfunction with a high sensitivity/specificity, saving costs and time, and limiting adverse events. Moreover, the presence of spontaneous morning erections and valid penile erections after masturbation could guide the diagnostic workup, indirectly identifying those patients deserving of a deeper evaluation of vascular health. [ABSTRACT FROM AUTHOR]

Alpha‐1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy [ABSTRACT FROM AUTHOR]

Background: Aims: To describe typical phonological development of Brazilian Portuguese (BP)‐speaking children, considering the following parameters: age of customary production, acquisition and mastery. Methods & Procedures: Data were collected from 857 children aged between 3 years and 8 years 11 months with typical language and speech development. The sample was grouped into 6‐month age bands. The data were analysed using one‐way analysis of variance (ANOVA) followed by Games–Howell post‐hoc tests. Outcomes & Results: Stops (/p, b, t, d, k, g/), nasals (/m, n, ɲ/) and some fricatives (/f, v, s, z/) were mastered before the age of 3 years (age of mastery). The age of acquisition for phonemes /ʃ, ʒ/ was 3;6, though both were only mastered at 4;0 years. The liquid /l/ was acquired at 3;0 and mastered at age 3;6, while /x/ was acquired and mastered at age 3;6. The phoneme /ʎ/ was acquired at 7;0 and mastered at age 8;6. The tap /ɾ/ was acquired between the ages of 4;0 and 4;6, and mastered at 4;6. In coda position, /n, l/ were acquired at 3;0, while /s/ was mastered at 4;6 and /ɾ/ between 4;6 and 5;0 years. Clusters involving /ɾ/ were acquired at 6;0, while those with /l/ were acquired between the ages of 6;6 and 7;0. Conclusions & Implications: This study presented acquisition for consonants in BP and can be used as a reference for the assessment of developmental speech disorders. In this study, stops and nasals were acquired first, followed by fricatives and, lastly, liquids. This finding is corroborated by previous studies in BP and other languages. What this paper adds: What is already known on the subject: What this paper adds to existing knowledge: What are the potential or actual clinical implications of this work?: [ABSTRACT FROM AUTHOR]

This paper investigates the consequences of business model (BM) disclosures. Content analysis is used to assess the mandatory disclosure of BM in in 75 publicly listed companies' annual reports across a three‐year period (2014–2016). The research applies a novel content analysis methodology that considers the way in which the relevance of BM disclosures is dependent on which particular BM a given company adopts. The empirical results show notably low levels of BM disclosure and no significant association between BM disclosures and market value. However, we find that BM disclosure provides insights into earnings quality by means of enhanced earnings persistence. These findings reveal that information about the BM itself does not make a difference to investors when it is not linked to financial outcomes. Instead, BM acts as a framework for organizing other disclosures, and provides complementary information about value generation, helping users understand how earnings are generated. These results are important for informing the policy‐making process around extra‐financial disclosures (e.g., EU Directive 2014/95/EU) and answer calls for research to inform future improvements to corporate and integrated reporting. [ABSTRACT FROM AUTHOR]

With lead service lines (LSLs) remaining for decades to come, scale analyses are critical to helping limit lead exposure from drinking water. This laboratory has used an integrated suite of analytical techniques to characterize the elemental composition, mineral identification, and physical features of scales, helping the water industry to evaluate, predict, and reduce lead corrosion. The methods used in this laboratory to prepare and analyze the LSL scale, and guidance to achieving reliable and meaningful results, are described. Primary methods include the following: optical microscopy, powder X‐ray diffraction, inductively coupled plasma spectroscopy, X‐ray fluorescence, scanning electron microscopy with energy dispersive spectroscopy, combustion and coulometric analyses of C and S, and X‐ray absorption spectroscopy. Examples of associated pitfalls and ways to avoid them are provided, including pipe excavation/transport, sample preparation, analysis, and data interpretation. Illustrative examples are presented of practical scale analysis questions that could be answered by combinations of pipe scale analyses. [ABSTRACT FROM AUTHOR]

Background: The connection between testicular ultrasound (US) parameters and testicular function, including both spermato‐ and steroidogenesis has been largely suggested, but their predictive properties are not routinely applied. Radiomics, a new engineering approach to radiological imaging, could overcome the visual limit of the sonographer. Objectives: This study is aimed at extracting objective testicular US features, correlating with testicular function, including both spermato‐ and steroidogenesis, using an engineering approach, in order to overcome the operator‐dependent subjectivity. Materials and methods: Prospective observational pilot study from December 2019 to December 2020 on normozoospermic subjects and patients with semen variables alterations, excluding azoospermia. All patients underwent conventional semen analysis, pituitary‐gonadal hormones assessment, and testicular US, performed by the same operator. US images were analyzed by Biolab (Turin) throughout image segmentation, image pre‐processing, and texture features extraction. Results: One hundred seventy US testicular images were collected from 85 patients (age 38.6 ± 9.1 years). A total of 44 first‐order and advanced features were extracted. US inhomogeneity defined by radiomics significantly correlates with the andrologist definition, showing for the first time a mathematical quantification of a subjective US evaluation. Thirteen US texture features correlated with semen parameters, predicting sperm concentration, total sperm number, progressive motility, total motility and morphology, and with gonadotropins serum levels, but not with total testosterone serum levels. Classification analyses confirmed that US textural features predicted patients' classification according to semen parameters alterations. Conclusions: Radiomics texture features qualitatively describe the testicular parenchyma with objective and reliable quantitative parameters, reflecting both the testicular spermatogenic capability and the action of pituitary gonadotropins. This is an innovative model in which US texture features represent a mirror of the pituitary‐gonadal homeostasis in terms of reproductive function. [ABSTRACT FROM AUTHOR]

Background: An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%–30%. Considering the assisted reproductive technology‐related economic and psycho‐social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. Study design: Retrospective, observational study. Objectives: To evaluate whether conventional semen parameters could predict assisted reproductive technology success. Materials and methods: All couples attending a single third‐level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end‐point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. Results: Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut‐off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). Discussion: Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples. [ABSTRACT FROM AUTHOR]

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