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This paper employs quantitative and qualitative methods to examine the link between banking competition, branching and financial distress during the interwar period in Europe, focusing on Italy as a case study. Regression analysis and a systematic review of printed sources show that banks experiencing distress had opened scores of branches and operated in areas with harsher competition. Poor managerial choices led banks to have higher operational costs, pushing them to more remunerative but riskier activities. The 1920s saw a profound transformation of the Italian banking system, with extensive branch expansion and cut‐throat competition for deposits. This paper argues that these changes in the structure of the banking system rendered it more fragile when the international crisis hit. Available evidence on other European countries suggests that Italy was not an isolated case. The study contributes to the literature on banking crises during the Great Depression and the effects of banking competition on financial stability. [ABSTRACT FROM AUTHOR]

Background: Blinding is thought to minimise expectancy effects and biases in double‐blind randomised‐controlled trials (RCTs). However, whether blinding integrity should be assessed and reported remains debated. Furthermore, it is unknown whether blinding failure influences the outcome of RCTs in anxiety disorders. We carried out a systematic review to understand whether blinding integrity is assessed and reported in anxiolytic RCTs. A secondary aim was to explore whether blinding integrity is associated with treatment efficacy. Method: Our protocol was pre‐registered (PROSPERO CRD42022328750). We searched electronic databases for placebo‐controlled, randomised trials of medication in adults with generalised and social anxiety disorders, and in panic disorder, from 1980. We extracted data regarding blinding integrity and treatment efficacy. Risk of bias was assessed with the Cochrane risk of bias tool. Where possible, we subsequently calculated Bang's Blinding Index, and assessed the association between blinding integrity and treatment effect size. Results: Of the 247 RCTs that met inclusion criteria, we were able to obtain assessments of blinding integrity from nine (3.64%). Overall, blinding failed in five of these trials (55.56%), but blinding was intact in 80% of placebo arms. We found a significant association between reduced blinding integrity among assessors and increased treatment effect size (betas < −1.30, p's < 0.001), but this analysis involved only four studies of which two were outlying studies. In patients, we saw a non‐significant trend where reduced blinding integrity in the placebo groups was associated with increased treatment efficacy, which was not present in active medication arms. [Correction added on 19 August 2024, after first online publication: Results of the RCTs and its assessment of blinding integrity have been updated.] Conclusion: Consistent with work in other psychiatric disorders, blinding integrity is rarely reported in anxiolytic RCTs. Where it is reported, blinding appears to often fail. We found signals that suggest unblinding of clinician assessors (driven by two studies with complete unblinding), and of patients in placebo arms, might be associated with larger treatment effect sizes. We recommend that data regarding blinding integrity, along with the reasons patients and assessors offer for their beliefs regarding group allocation, are systematically collected in RCTs of anxiolytic treatment. [ABSTRACT FROM AUTHOR]

Let d$d$ be any positive and non‐square integer. We prove an upper bound for the first two moments of the length T(d)$T(d)$ of the period of the continued fraction expansion for d$\sqrt {d}$. This allows to improve the existing results for the large deviations of T(d)$T(d)$. [ABSTRACT FROM AUTHOR]

Understanding the predictability drivers for the North Atlantic Oscillation (NAO) during boreal winter at seasonal time scales remains challenging. This study uses large ensembles with the ECMWF seasonal forecasting system to investigate the relative impact of tropical Indian and Pacific heating on NAO predictability by examining the tropical forcing, teleconnection pathways, and sources of uncertainty. We select three case studies ‐ 1997/98, 2015/16 and 2019/20 ‐ with strong Indian Ocean heating anomalies, but with different El Niño conditions. We show that in 2019/20, with neutral ENSO conditions, Indian Ocean SSTs favor a positive NAO response via stratospheric and tropospheric pathways. In the cases with strong El Niño, we find contrasting results: in 1997/98, the Pacific forcing dominates, producing a negative NAO. In 2015/16, despite the strong El Niño, the Indian Ocean forcing dominates, leading to a positive NAO via intensification of the stratospheric polar vortex (SPV). While the stratospheric pathway exhibits varying responses to Indian Ocean forcing ‐ being weaker in 1997/98 and strongest in 2015/16, the Indian Ocean‐related tropospheric pathway remains robust along the Pacific subtropical jet across years. However, there is destructive interference between teleconnections from Indian and Pacific SST anomalies in both the tropospheric and stratospheric pathways. The competing effects of tropical heating in both basins, uncertainties in the Rossby wave response to tropical heating and SPV variability contribute to uncertainty in seasonal NAO predictions. The flow‐dependent nature of the stratospheric pathway underscores the complexity of seasonal forecast predictability, and the existence of windows of opportunity. Plain Language Summary: The NAO is a phenomenon that manifests as a pressure see‐saw in the North Atlantic, affecting the seasonal climate in many parts of the northern hemisphere. In this study, we demonstrate that the predictability of the phases of the NAO can be affected by the remote and opposing influence of surface temperatures in the tropical Indian and Pacific oceans, which propagate via the troposphere and stratosphere. This interplay, in turn, contributes to the uncertainty of seasonal forecasts of the NAO. Key Points: Large ensemble seasonal forecasts reveal a predictable link between tropical heating and the NAO via a flow‐dependent stratospheric pathwayThe impact of Indian Ocean heating on the NAO can be stronger than that of El Niño in the presence of an anomalously strong stratospheric pathwayCompetition between basins, flow‐dependent response, and intrinsic variability contribute to the uncertainty in seasonal forecasts of NAO [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to analyze epidemiology, clinical presentation, histopathological features, treatment and oncological outcomes in laryngeal mucoepidermoid cancer (MEC) in order to improve the knowledge on the management of such a rare malignant neoplasm. Specifically, authors highlight patients' and tumors' features about local, regional, and distant recurrence of disease. PRISMA 2020 guidelines were applied in this systematic literature review. A computerized search was performed using the Embase/Pubmed, Scopus, and Cochrane databases, for articles published from 1971 to December 2023. A descriptive and univariate analysis including selected papers with low or intermediate risk of bias was performed. Twenty‐seven papers (11 case series and 16 case reports) were included in this review. Fifty‐six patients were included in the analyses, with a mean age of 56.7 years; 84% of them were males. Most patients (86%) underwent a primary surgical approach. Clinical stage was reported as follows: early stage (26 patients) and locally advance and advanced stage (19 patients). Overall survival (OS) and disease‐free survival (DFS) at 2 years was 80% and 78%, respectively. The mean time to local recurrence was 18.7 months (range 8–36 months). The survival after recurrence is about 85% and 70% at 5 years, respectively. The mean time of lymph node recurrence was 14.7 months (range 7–19 months). Finally, the mean time of distant recurrence was 15 months (range 7–36 months) with a poor prognosis: all patients died due to the disease in a range of 0–7 months after metastasis evidence. Laryngeal MEC is a rare neoplasm of minor salivary glands in the larynx. No guidelines or indications about the management of this neoplasm are reported in the literature. The lower incidence of regional recurrence of the disease and the better OS and DFS underline how the prognosis of MEC is more favorable respect to other malignant histotypes. [ABSTRACT FROM AUTHOR]

Diffuse idiopathic skeletal hyperostosis (DISH) is a disease that can cause symptoms such as difficulty swallowing or breathing. Surgical treatment for DISH can be effective in restoring normal functions. This article presents a case study of an 86-year-old man with DISH who underwent surgery to remove osteophytes in the cervical spine. The surgery was successful, and the patient experienced improvement in dysphagia and respiratory symptoms. The article also discusses the causes and mechanisms of dysphagia in DISH and the importance of a multidisciplinary approach to treatment. [Extracted from the article]

This article discusses a case study of a patient who developed tracheal stenosis as a result of a percutaneous tracheostomy following a Sars-Cov2 infection. The patient underwent a tracheal resection and anastomosis surgery using the Tritube® ventilation device. The article highlights the challenges of managing airways in post-Covid-19 patients and emphasizes the importance of accurate monitoring and evaluation to diagnose and treat laryngotracheal stenosis. The use of the Tritube® device allowed for optimal visualization of the surgical field and smooth ventilation during the procedure. The article concludes by sharing the successful outcome of the surgery and raising awareness about post-Covid-19 laryngotracheal stenosis. [Extracted from the article]

Telemedicine approaches have proved to be valuable solutions for the delivery of treatment for many health‐related issues, and crucial during the pandemics. Nonetheless, the efficacy of such Web‐based practices in developmental dyslexia needs to be thoroughly evaluated. To this aim, the effects of a multi‐componential program for neuropsychological intervention in dyslexia delivered as an outpatient program were compared with those obtained with a remotely delivered, Web‐based treatment, based on the same methodological principles and delivered with the same duration and intensity. The treatment‐related changes obtained with a combination of visual hemisphere‐specific stimulation and training of visual–spatial attention through action video games, were compared to those obtained through remote treatment via the Tachidino Web‐based platform. Both treatments had a duration of 4 weeks. The same battery of reading and phonemic awareness tests was delivered in presence, before and after treatment, as well as at 6‐months follow‐up. User satisfaction was assessed through parents and user questionnaires. Both treatments were significantly and similarly effective in improving reading speed, reading accuracy, and writing accuracy. No reduction in the effects was observed after treatment discontinuation. The Web‐based treatment may thus offer a valid alternative to in‐person intervention, optimizing the flexibility, capillary diffusion and cost‐effectiveness of intervention. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is associated with a hyper‐focused visual attentional style, impacting higher‐order social and affective domains. The understanding of such peculiarity can benefit from the use of multivariate pattern analysis (MVPA) of high‐resolution electroencephalography (EEG) data, which has proved to be a powerful technique to investigate the hidden neural dynamics orchestrating sensory and cognitive processes. Here, we recorded EEG in typically developing (TD) children and in children with ASD during a visuo‐spatial attentional task where attention was exogenously captured by a small (zoom‐in) or large (zoom‐out) cue in the visual field before the appearance of a target at different eccentricities. MVPA was performed both in the cue‐locked period, to reveal potential differences in the modulation of the attentional focus, and in the target‐locked period, to reveal potential cascade effects on stimulus processing. Cue‐locked MVPA revealed that while in the TD group the pattern of neural activity contained information about the cue mainly before the target appearance, the ASD group showed a temporally sustained and topographically diffuse significant decoding of the cue neural response even after the target onset, suggesting a delayed extinction of cue‐related neural activity. Crucially, this delayed extinction positively correlated with behavioral measures of attentional hyperfocusing. Results of target‐locked MVPA were coherent with a hyper‐focused attentional profile, highlighting an earlier and stronger decoding of target neural responses in small cue trials in the ASD group. The present findings document a spatially and temporally overrepresented encoding of visual information in ASD, which can constitute one of the main reasons behind their peculiar cognitive style. Lay Summary: This study unveils how incoming visual input is encoded at the neural level in children with autism spectrum disorder (ASD), and how this encoding impacts on their attentional selection. Using multivariate pattern analysis (MVPA) of high‐resolution EEG data, we show that children with ASD exhibit a temporally prolonged and topographically broader overrepresentation of visual information, as compared to their typically developing peers. Such excessive stimulus encoding could in turn lead to difficulties in reorienting attentional resources to subsequent relevant incoming stimuli, leading to their peculiar hyperfocused attentional profile. This study not only provides new evidence about important neural mechanisms of visual information processing in ASD, but it also shows that MVPA approaches can detect neural dynamics that may remain otherwise largely blind to other univariate analyses approaches. [ABSTRACT FROM AUTHOR]

A very attractive approach toward 1,3‐polyheterocyclic systems was provided exploiting the copper‐catalyzed reaction of aminoalcohols and diaminoalkanes, in oxidative conditions and in the presence of methanol. The synthetic pathway showed the involvement of methanol both as solvent and as a reagent, making the procedure particularly efficient and sustainable for the synthesis of five‐, six‐, and seven‐membered polyheterocyclic rings. [ABSTRACT FROM AUTHOR]

Self‐assembled monolayers (SAMs) of N‐heterocyclic olefins (NHOs) have been prepared on Au(111) and their thermal stability, adsorption geometry, and molecular order were characterized by X‐ray photoelectron spectroscopy, polarized X‐ray absorption spectroscopy, scanning tunneling microscopy (STM), and density functional theory (DFT) calculations. The strong σ‐bond character of NHO anchoring to Au induced high geometrical flexibility that enabled a flat‐lying adsorption geometry via coordination to a gold adatom. The flat‐lying adsorption geometry was utilized to further increase the surface interaction of the NHO monolayer by backbone functionalization with methyl groups that induced high thermal stability and a large impact on work‐function values, which outperformed that of N‐heterocyclic carbenes. STM measurements, supported by DFT modeling, identified that the NHOs were self‐assembled in dimers, trimers, and tetramers constructed of two, three, and four complexes of NHO−Au‐adatom. This self‐assembly pattern was correlated to strong NHO−Au interactions and steric hindrance between adsorbates, demonstrating the crucial influence of the carbon‐metal σ‐bond on monolayer properties. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: To determine the location of the rectus femoris (RF) motor branch nerve, as well as its coordinates with reference to anatomical and ultrasound landmarks. Methods: Thirty chronic stroke patients with stiff knee gait (SKG) and RF hyperactivity were included. The motor nerve branch to the RF muscle was identified medially to the vertical line from anterior superior iliac spine and the midpoint of the superior margin of the patella (line AP) and vertically to the horizontal line from the femoral pulse and its intersection point with the line AP (line F). The point of the motor branch (M) was located with ultrasound, and nerve depth and subcutaneous tissue thickness (ST) were calculated. Results: The coordinates of the motor branch to the RF were 2.82 (0.47) cm medially to the line AP and 4.61 (0.83) cm vertically to the line F. Nerve depth and subcutaneous tissue thickness were 2.71 (0.62) cm and 1.12 (0.75) cm, respectively. Conclusion: The use of specific coordinates may increase clinicians' confidence when performing RF motor nerve block. This could lead to better decision‐making when assessing SKG in chronic stroke patients. [ABSTRACT FROM AUTHOR]

Secularization theory allows for transitory religious revivals under certain conditions, such as extreme societal crises or state weakness. The country of Georgia has witnessed the largest religious revival of Orthodox countries and one of the most striking religious resurgences worldwide. This paper gives both a statistical and historical description of this revival and asks whether it is a counterexample to secularization theory. We show that the main thrust of the religious revival in Georgia lasted 25 years and seized the entire society in what was mainly a period effect. The most significant cause for the revival was a major societal and economic crisis starting in 1985 combined with a very weak state, creating massive individual insecurity. In these circumstances, the Georgian Orthodox Church was able to provide identity for individuals and legitimacy for governments. Other possible causes of the revival—state funding, too rapid modernization, or emigration—can be excluded as primary drivers of the process. The Georgian case shows a situation in which secularization theory expects transitory revivals and is thus not a counterexample. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. Materials and methods: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology‐Head and Neck Surgery divisions. Disease‐specific survival (DSS) and disease‐free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut‐off values. Results: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5‐year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. Conclusion: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

It is still unclear whether and to what extent the motor difficulties are specific to autism. This study aimed to determine whether a multimodal assessment of motor skills could accurately discriminate autistic children from attention‐deficit/hyperactivity disorder (ADHD) and typically developing (TD) peers. Seventy‐five children, aged 7–13, equally divided into three groups, were assessed with the developmental coordination disorder questionnaire (DCDQ), the movement assessment battery for children 2 (MABC2), the sensorimotor subtests of NEPSY‐II, and the kinematic analysis of a reach‐to‐drop task. Principal component analysis (PCA) on DCDQ subscales revealed one factor—Caregiver Report—, whereas MABC2/NEPSY‐II scores identified three factors—namely, Object Interception and Balance, Motor Imitation, and Fine‐Motor Skills—. Lastly, PCA on kinematic variables identified four factors: PC1, loaded by the parameters of velocity and acceleration throughout the task, PC2 and PC3 involved the temporal parameters of the two submovements, and PC4 accounted for the wrist inclination at ball drop. When comparing autistic and TD children, Caregiver Report and Motor Imitation factors predicted membership with 87.2% of accuracy. In the model comparing ADHD and TD groups, Caregiver Report and Fine‐Motor Skills predicted membership with an accuracy of 73.5%. In the last model, the Object Interception and Balance factor differentiated autistic children from ADHD with an accuracy of 73.5%. In line with our previous findings, kinematics did not differentiate school‐aged autistic children from ADHD and TD peers. The present findings show that specific motor profiles in autism and ADHD can be isolated with a multimodal investigation of motor skills. Lay Summary: It is still unclear whether and to what extent the motor difficulties are specific to autism. Using a multimodal assessment, we found that difficulties in object control and balance were distinctly associated with autism, while challenges in fine‐motor skills characterized attention‐deficit/hyperactivity disorder. Our work can suggest developing specific support programs for children with neurodevelopmental conditions. [ABSTRACT FROM AUTHOR]

This Review summarizes the advances in the catalytic enantioselective mono‐ and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved. [ABSTRACT FROM AUTHOR]

The response of the Euro‐Atlantic wintertime circulation to climate change is deeply uncertain. The Atlantic jet is caught in a "tug‐of‐war" between rapid warming trends in both the tropics and the Arctic leading to debate over the changing "waviness" of the jet, which is subject to strong non‐linearity and internal variability. From the complementary perspective of weather regimes, there is considerable uncertainty in how atmospheric blocking will alter under climate change. By applying the hybrid approach of geopotential‐jet regimes to 6th phase of the coupled model inter‐comparison project projections, we show that the centers of action of anticyclonic regimes hardly alter even under severe warming. Instead, regimes are expected to become less persistent, with zonal flow conditions becoming more prevalent, although models disagree on the details of regime changes. Finally, we show the regime response can be captured qualitatively in a simple Lorenz‐like model, emphasizing the conceptual link between observed regimes and those in basic mathematical systems. Plain Language Summary: The impact of climate change on European weather can be broken into two components: a thermodynamic part relating to increasing air temperature and humidity, and a dynamic part relating to changes in the atmospheric circulation such as the direction and strength of prevailing winds. While the thermodynamic part is relatively well understood, the dynamic part is very uncertain and this is a major problem in constraining European climate projections. Looking at the winter season, we study the dynamic response of CMIP6 models under climate change using so‐called "regimes," and show that the types of prevailing circulation are not predicted to change strongly. However the regimes are projected to be less long lived. We also show that these features can be well captured in a simple 5 equation model of regime dynamics, providing a potentially useful tool for understanding regime systems in more detail. Key Points: The spatial structure of anticyclonic circulations over Europe are projected to stay the same under climate changeThe persistence of anticyclonic circulations are in general expected to decrease, although there is considerable inter‐model variabilityWe show that these qualitative features of the atmospheric response can be reproduced in a simple forced regime model [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that antenatal exposure to maternal stress signals affects the development of the infant stress response systems. Animal studies indicate that maternal sensitive caregiving can reverse some of these effects. However, the generalizability of these findings to humans is unknown. This study investigated the role of maternal caregiving in the association between multiple markers of maternal antenatal stress and infant stress regulation. Methods: The sample consisted of 94 mother‐infant (N = 47 males, mean postnatal weeks = 12; SD = 1.84) dyads. Maternal levels of Interleukin‐6, C‐Reactive Protein (CRP), diurnal cortisol and alpha amylase, depressive and anxiety symptoms were assessed in late pregnancy (mean gestational age = 34.76; SD = 1.12), whereas postnatal symptomatology, caregiving, and infant cortisol response to the inoculation were evaluated at 3 months. Results: Hierarchical linear models (HLMs) showed a significant interaction between maternal antenatal cortisol, caregiving, and time on infant cortisol reactivity, while controlling for gender, maternal age, and postnatal depression. Specifically, higher levels of maternal antenatal cortisol were associated with greater cortisol response only among infants of less emotionally available mothers. All other markers of antenatal stress were not significantly associated with infant cortisol reactivity either independently or in interaction with maternal caregiving. Conclusions: Albeit preliminary, results provide the first evidence in humans that maternal sensitive caregiving may eliminate the association between antenatal maternal cortisol and infant cortisol regulation. [ABSTRACT FROM AUTHOR]

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty‐five patients underwent salvage surgery (20.1%) and their 5‐year mortality rate, overall survival and disease‐free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow‐up. [ABSTRACT FROM AUTHOR]

Easily accessible isoxazol‐5(4H)‐ones are useful precursors of heterocycles. In this context, we report the ruthenium‐catalyzed transformation of 4‐alkenyl‐substituted isoxazol‐5‐ones to afford 1H‐pyrrole derivatives. The operative conditions were proven to be effective also on cyclohexane‐fused isoxazolones giving 4,5,6,7‐tetrahydroindoles. The reactions, which allow for access to tri‐and tetra‐substituted pyrroles in moderate to high yields, occur through decarboxylative ring‐opening/ring‐closure involving C−H functionalization of the alkenyl moiety. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) have complex genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ even among closely related viruses. Accessory proteins often play a role in the suppression of immune responses and may represent virulence factors. Despite their relevance for CoV phenotypic variability, information on accessory proteins is fragmentary. We applied a systematic approach based on homology detection to create a comprehensive catalogue of accessory proteins encoded by CoVs. Our analyses grouped accessory proteins into 379 orthogroups and 12 super‐groups. No orthogroup was shared by the four CoV genera and very few were present in all or most viruses in the same genus, reflecting the dynamic evolution of CoV genomes. We observed differences in the distribution of accessory proteins in CoV genera. Alphacoronaviruses harboured the largest diversity of accessory open reading frames (ORFs), deltacoronaviruses the smallest. However, the average number of accessory proteins per genome was highest in betacoronaviruses. Analysis of the evolutionary history of some orthogroups indicated that the different CoV genera adopted similar evolutionary strategies. Thus, alphacoronaviruses and betacoronaviruses acquired phosphodiesterases and spike‐like accessory proteins independently, whereas horizontal gene transfer from reoviruses endowed betacoronaviruses and deltacoronaviruses with fusion‐associated small transmembrane (FAST) proteins. Finally, analysis of accessory ORFs in annotated CoV genomes indicated ambiguity in their naming. This complicates cross‐communication among researchers and hinders automated searches of large data sets (e.g., PubMed, GenBank). We suggest that orthogroup membership is used together with a naming system to provide information on protein function. [ABSTRACT FROM AUTHOR]

Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death‐ligand 1 (PD‐L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD‐L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta‐analysis we demonstrate a lack of prognostic significance of PD‐L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD‐L1 evaluation and discuss future opportunities such as leveraging digital pathology. [ABSTRACT FROM AUTHOR]

The overarching goal of this work is to present new theoretical and practical tools to implement robust−t−probing security. In this work, a low‐latency multiplication gadget that is secure against probing attacks that exploit logic glitches in the circuit is presented. The gadget is the first of its kind to present a 1‐cycle input‐to‐output latency while belonging to the class of probing security by optimized composition gadgets [6]. In particular, the authors show that it is possible to construct robust‐t‐strong‐non‐interferent gadgets without compromising on latency with a moderate increase in area. The authors provide a theoretical proof for the robustness of the gadget and show that, for t≤4, the amount of randomness required can even be reduced without compromising on robustness. [ABSTRACT FROM AUTHOR]

Atypical sensory responses are included in the diagnostic criteria of autism spectrum disorder (ASD). Autistic individuals perform poorly during conditions that require integration across multiple sensory modalities such as audiovisual (AV) integration. Previous research investigated neural processing of AV integration in infancy. Yet, this has never been studied in infants at higher likelihood of later ASD (HR) using neurophysiological (EEG/ERP) techniques. In this study, we investigated whether ERP measures of AV integration differentiate HR infants from low‐risk (LR) infants and whether early AV integration abilities are associated with clinical measures of sensory responsiveness. At age 12 months, AV integration in HR (n = 21) and LR infants (n = 19) was characterized in a novel ERP paradigm measuring the McGurk effect, and clinical measures of sensory responsiveness were evaluated. Different brain responses over the left temporal area emerge between HR and LR infants, specifically when AV stimuli cannot be integrated into a fusible percept. Furthermore, ERP responses related to integration of AV incongruent stimuli were found to be associated with sensory responsiveness, with reduced effects of AV incongruency being associated with reduced sensory reactivity. These data suggest that early identification of AV deficits may pave the way to innovative therapeutic strategies for the autistic symptomatology. Further replications in independent cohorts are needed for generalizability of findings. [ABSTRACT FROM AUTHOR]

Automated contact detection by means of proximity loggers permits the measurement of encounters between individuals (animal‐animal contacts) and the time spent by individuals in the proximity of a focal resource of interest (animal‐fixed logger contacts). The ecological inference derived from contact detection is intrinsically associated with the distance at which the contact occurred. But no proximity loggers currently exist that record this distance and therefore all distance estimations are associated with error. Here we applied a probabilistic approach to model the relationship between contact detection and inter‐logger distance, and quantify the associated error, on free‐ranging animals in semi‐controlled settings. The probability of recording a contact declined with the distance between loggers, and this decline was steeper for weaker radio transmission powers. Even when proximity loggers were adjacent, contact detection was not guaranteed, irrespective of the radio transmission power. Accordingly, the precision and sensitivity of the system varied as a function of inter‐logger distance, radio transmission power, and experimental setting (e.g., depending on animal body mass and fine‐scale movements). By accounting for these relationships, we were able to estimate the probability that a detected contact occurred at a certain distance, and the probability that contacts were missed (i.e., false negatives). These calibration exercises have the potential to improve the predictability of the study and enhance the applicability of proximity loggers to key wildlife management issues such as disease transmission rates or wildlife use of landscape features and resources. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross‐sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods: This was a multi‐centre, nationwide study. Data were collected in three studies from the CISAI group – SIMOne, HIV‐HY and STOPSHIV – and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results: Overall, the mean age was 46.9 ± 10.2 years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52–0.78) in 2011 and 0.56 (95% CI: 0.46–0.69) in 2015 compared with 2005, while BMI (kg/m2) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p < 0.0001). Conclusions: In recent years, PHIV have had a significantly improved metabolic profile compared with previously, despite increasing weight and BMI. [ABSTRACT FROM AUTHOR]

Herein, we describe the clinical features of a series of TL patients who contracted SARS-CoV-2 and developed severe tracheitis, focusing on its management, clinical course and histological features. Keywords: airway obstruction; case series; SARS-CoV-2; total laryngectomy; tracheitis; tracheobronchitis EN airway obstruction case series SARS-CoV-2 total laryngectomy tracheitis tracheobronchitis 203 206 4 12/27/21 20220101 NES 220101 Key Points SARS-CoV-2 is a possible cause of acute severe tracheitis in laryngectomees. Case series, airway obstruction, tracheobronchitis, SARS-CoV-2, total laryngectomy, tracheitis METHODS This is a retrospective study on patients subjected to TL who presented with acute tracheitis and concomitant positive testing for SARS-CoV-2. [Extracted from the article]

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph‐chromosome and the BCR‐ABL tyrosine‐kinase (TK). Target‐therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second‐generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in‐vivo activity and timecourse of first‐line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty‐seven CP‐CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per‐Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK‐STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed. [ABSTRACT FROM AUTHOR]

An oxidative Pd‐catalyzed intra‐intermolecular dioxygenation of (aza‐)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent‐iodine compounds have been compared. In particular, by using a C‐6 modified pyridinyl‐oxazoline (Pyox) ligand and hypervalent iodine bearing an aromatic ring, an excellent enantio‐ and diastereoselectivity has been achieved. [ABSTRACT FROM AUTHOR]

Objective: Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion: In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence: III [ABSTRACT FROM AUTHOR]

Delays in language are a hallmark feature of Autism Spectrum Disorder (ASD). However, little is known about the predictive role of language developmental trajectories on ASD. The present study aimed at identifying early different language developmental profiles of infants at high familial risk for ASD (HR‐ASD) and testing their predictive role on ASD symptoms at 2 years. The role of gestures on socio‐communicative skills has also been explored. Trajectories of expressive vocabulary were investigated in 137 HR‐ASD infants at 12, 18, and, 24 months of age. Parents were requested to complete the Italian version of the MacArthur‐Bates Communicative Development Inventory and ASD symptoms were measured by ADOS‐2. Latent class growth analysis defined four trajectories: above average language development group (above‐average LD, 18.2%), normal language development group (NLD, 38.7%), late‐onset language development group (late‐onset LD, 11.7%), and a group of children with stable language delay (SLD, 31.4%). Results showed that the SLD group obtained higher communicative difficulties and restricted/repetitive behavior compared to the other groups. Examining early increase of produced gestures in the different language classes, we found fewer produced gestures between 12 and 18 months in the SLD group compared to the late‐onset LD group. The results identified clusters of HR infants who follow similar estimated trajectories based on individual differences in language development. These patterns of early language acquisition, together with produced gestures, may be predictive of later ASD symptoms and useful for planning prompt intervention. Lay Summary Language/gesture deficits are hallmark features of Autism Spectrum Disorder (ASD), but the predictive role of communicative trajectories on ASD remains unclear. In a longitudinal Italian sample of infants at high familial risk for ASD (HR‐ASD), we tested if language trajectories and their link with gestures can predict ASD symptoms. We found four trajectories and HR infants with a stable language delay (SLD) trajectory showed more ASD symptoms later on. SLD infants produced fewer gestures compared to late‐onset language development group that show more typical communicative skills. [ABSTRACT FROM AUTHOR]

The great variety of spirooxindole three‐dimensional scaffolds encompasses relevant bioactive natural alkaloids as well as useful therapeutic agents. In view of the challenging features of the spirooxindole skeletons and their desirable properties, several synthetic routes have been devoted to their preparation. Because of the variety of both 1,3‐dipolar species and 2‐oxindoles bearing a C=X double bond (X=C<, N−, O) in the 3‐position, a prominent role relies upon a 1,3‐dipolar cycloaddition as the key step of the whole synthetic sequence. The present paper aims to discuss the developments in the field of spirooxindole synthesis via a 1,3‐dipolar cycloaddition occurred in the 2011–2020 decade. The literature data on this subject are reviewed in a systematic way according to the type of the 1,3‐dipole and the oxindole dipolarophile. [ABSTRACT FROM AUTHOR]

A useful aminohalogenation reaction for the cyclization of O‐alkynyl carbamates under copper catalysis has been developed. N‐Halosuccinimides have been used as a halogen source. The intramolecular C−N bond formation occurs selectively affording haloalkylidene substituted heterocycles. Just in the case of α,α‐cyclohexyl‐substituted propargyl carbamate, the alkoxyhalogenation pathway was operative. The mechanism for the two alternative reaction pathways was investigated by modeling the corresponding transition states at the DFT level. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the clinical features of mild‐to‐moderate coronavirus disease 2019 (COVID‐19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory‐confirmed COVID‐19 infection were recruited. Patients completed a survey‐based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild‐to‐moderate COVID‐19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above‐mentioned disorders was found (rs: 0.412; P <.001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory‐confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P <.05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild‐to‐moderate Italian COVID‐19 patients is significant both in suspected and laboratory‐confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea. Highlights: This study evaluates the clinical features of mild‐to‐moderate COVID‐19 in a sample of adult Italian patients. The structural equation model (SEM) built to examine the clinical characteristics of the infection, confirms significant standardised paths between all the evaluated variables and underlines the absence of a significant correlation between smell and taste disorders and all the other variables. Furthermore, the study reveals a strong correlation between smell and taste alterations with a significant prevalence of these symptoms both in suspected (clinical diagnosis) and laboratory‐confirmed (pcr) cases. [ABSTRACT FROM AUTHOR]

The simulation and prediction of winter Northern Hemisphere atmospheric blocking in the seasonal prediction systems from the European Centre for Medium-Range Weather Forecasts (ECMWF) is analysed. Blocking statistics from the operational November-initialised seasonal hindcasts are evaluated in three generations of models: System3, System4, and System5 (SEAS5). Improvements in the climatological representation of blocking are observed in the most recent model configurations, with reduced bias over North Pacific and Greenland. Minor progress is seen over the European sector, where SEAS5 still underestimates the observed blocking frequency. SEAS5 blocking interannual variability is underestimated too and is proportional to the climatological frequency, highlighting that a negative bias in the blocking frequency implies an underestimation of the interannual variance. SEAS5 predictive skill and signal-to-noise ratio remain low, but interesting positive results are found over Western and Central Europe. Improved forecasts with reduced ensemble spread are obtained during El Niño years, especially at low latitudes. Complementary experiments show that the statistics of blocking are improved following atmospheric and oceanic resolution increase. Conversely, they remain largely insensitive to coupled model sea-surface temperature (SST) errors. On the other hand, the implementation of stochastic parameterisations tends to displace blocking activity equatorward. Finally, by comparing seasonal hindcasts with climate runs using the same model, we highlight that the largest contributors to the chronic underestimation of blocking are persistent errors in the atmospheric model. It is also shown that SST errors have a larger impact on blocking bias in climate runs than in seasonal runs, and that increased ocean model resolution contributes to improved blocking more effectively in climate runs. Seasonal forecasts can thus be considered a suitable test-bed for model development targeting blocking improvement in climate models. [ABSTRACT FROM AUTHOR]

High‐throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up‐to‐date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high‐burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome‐wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13‐R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region‐level complexity‐of‐infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared. [ABSTRACT FROM AUTHOR]

Antenatal exposure to maternal stress is a factor that may impact on offspring cognitive development. While some evidence exists of an association between maternal antenatal depressive or anxiety symptoms and infants' cognitive outcomes, less is known about the role of biological indices of maternal antenatal stress in relation to infant cognitive development. The current study investigated the association between maternal depressive and anxiety symptoms, stress and inflammatory markers during pregnancy and infant's cognitive development in a sample of 104 healthy pregnant women (mean gestational age = 34.76; SD = 1.12) and their 12‐week‐old infants (mean postnatal weeks = 11.96; SD = 1.85). Maternal depressive and anxiety symptoms were evaluated during pregnancy, alongside measurements of serum Interleukin‐6 (IL‐6), C‐Reactive Protein (CRP), salivary cortisol, and alpha amylase (sAA) concentrations. Infant cognitive development, maternal caregiving and concurrent anxiety or depressive symptoms were assessed 12 weeks after delivery. Hierarchical linear regressions indicated that higher maternal diurnal cortisol and CRP levels were independently associated with lower infant cognitive development scores, while adjusting for infant gender and gestational age, maternal IQ, caregiving, depressive, or anxiety symptoms. Though correlational, findings seem suggestive of a role for variation in maternal biological stress signals during pregnancy in influencing infants' early cognitive development. [ABSTRACT FROM AUTHOR]

Comments on "Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C" Keywords: Anti-hepatitis C virus DAA (directly acting antivirals); Antiviral agents; Hepatitis C virus; Hepatitis virus; Virus classification EN Anti-hepatitis C virus DAA (directly acting antivirals) Antiviral agents Hepatitis C virus Hepatitis virus Virus classification 436 438 3 12/13/21 20220201 NES 220201 Elhence et al.1 assessed the retreatment outcomes of direct-acting antivirals (DAAs) therapy failure in a cohort of 40 patients with chronic hepatitis C (HCV) and previous virological failure (VF) to DAAs. Addressing hesitancy in HCV retreatment prescription and nonadherence to second-line DAAs with a tailored approach is crucial to scale up HCV treatment and eradicate HCV infection in people with previous VF to DAAs. [Extracted from the article]

The 1,3‐dipolar cycloadditions of azomethine‐ylides and ‐imines, nitrones, nitrilimines, and azides catalysed by inorganic nanoparticles are described. Emphasis is given to the nanometric catalysts involved, their structure, characterisation, and recyclability and, when remarkable, their preparation. Whenever possible, the improvements with respect to cycloadditions performed with the usual (non‐nano) catalysts are discussed. [ABSTRACT FROM AUTHOR]

Background: Studies concerning programmed death‐ligand 1 (PD‐L1) expression in precancerous lesions of head and neck (HN) region have shown variable results. Methods: We systematically reviewed the published evidence on PD‐L1 expression in HN precancerous lesions. Results: Of 1058 original articles, 14 were included in systematic review and 9 in meta‐analysis. The pooled estimate of PD‐L1 expression was 48.25% (confidence interval [CI] 21.07‐75.98, I2 98%, tau2 0.18). PD‐L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65‐4.03, I2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43‐1.08, I2 91%, tau2 0.22). Conclusions: PD‐L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD‐L1 expression in HN precancerous lesions. [ABSTRACT FROM AUTHOR]

Background: Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti‐spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. Methods: This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. Results: Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. Conclusions: There is a clear need for new larger multicentre well‐designed clinical trials with a duration that allows the persistence of the effects and the long‐term safety of the interventions to be evaluated. [ABSTRACT FROM AUTHOR]

Background: In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales. Methods: Diffusion tensor (DT) and 3D T1‐weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult = 11.6 years; 72.7% in chronic condition) and 31 age‐matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRI indices were obtained from several supra‐ and infra‐tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6 months from the event) vs. chronic (≥6 months) condition were performed. Results: Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto‐occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measure scores. Conclusions: The study isolated a distributed fronto‐temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI. [ABSTRACT FROM AUTHOR]