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In artificial neural networks, the "synaptic weights" connecting the neurons are adjusted during the training. Beyond silicon, functionalizing the back‐end‐of‐line (BEOL) of CMOS circuits with novel materials is a key enabler for deploying neural network accelerators. The hardware implementation of the synaptic weights requires linear and reprogrammable resistive elements. In ferroelectric tunnel junctions, the resistance is programmed by controlling the configuration of the ferroelectric domains with electrical pulses. From ferroelectric HfZrO4 to HfO2–ZrO2 nanolaminates (NL), the crystallization temperature lowers below the upper limit of 400 °C required for CMOS BEOL. The device footprint is reduced, and the maximum‐to‐minimum conductance ratio increases from 7 to 32. Operated with pulses in the ultra‐fast (20 ns) and biological (500 µs) timescales, the synaptic plasticity exhibits several regimes. Dynamic hysteresis mode characterization after up to 1011 switching cycles indicates the coexistence of ferroelectric and non‐ferroelectric effects such as defect rearrangement. Temperature‐dependent transport measurements in the Ohmic (linear) regime support these conclusions. Multi‐level resistive switching is achieved in HfO2–ZrO2 NL co‐integrated to CMOS in the BEOL. 1T‐1R operation is demonstrated, paving the way for hardware implementation of synaptic weights for in‐memory neuromorphic computing. [ABSTRACT FROM AUTHOR]

Aim: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. Method: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. Results: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between‐treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow‐up visit. There were no other significant differences between the two groups for any of the other outcomes. Conclusion: While there was no difference in healing rates between the two treatments, PeG was more cost‐effective and associated with fewer adverse events. [ABSTRACT FROM AUTHOR]

Aim: The optimal surgical treatment for anatomical anal stenosis (AS) remains to be determined. The aim of this study was to determine the rates of complications and recurrence after anoplasty for anatomical AS and, wherever feasible, compare the outcomes for the various techniques. Method: A PROSPERO‐registered systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Medline, PubMed, Embase, Cochrane Library of Systematic Review, Scopus and Web of Science were searched for articles published up to May 2021. Studies that assessed the outcomes of anoplasty in adult patients with anatomical AS were selected. The primary outcomes were complications and recurrence. The methodological quality of studies was appraised using the Joanna Briggs Institute critical appraisal tools. Results: From the total of 2705 unique screened records, 151 were assessed for eligibility. Only 29 studies (two prospective) met the inclusion criteria, reporting data on 556 patients [mean age 53 (18–83) years, 46% female]. Previous history of surgery for haemorrhoidal disease accounted for three quarters of cases. A total of 14 types of anoplasty were found, with the Y–V flap being the most performed technique [27% of cases (n = 149)]. Complications frequently occurred, with a pooled prevalence of 10.2% (95% CI 3.9%–24.1%) after Y–V flap and 11.5% (5.3%–23.0%) after rhomboid/diamond flap. Patients undergoing house flap achieved better results in terms of clinical improvement, satisfaction and quality of life compared with Y–V flap and rhomboid/diamond flap. When considering only studies with at least 12 months of follow‐up, the pooled prevalence of recurrence was 4.7% (2.2%–9.8%), with significantly higher rates observed in the prospective versus retrospective series [pooled prevalence 18.9% (11.5%–29.5%) vs. 3.6% (1.7–7.8%), respectively; p < 0.001]. Conclusion: Both complications and recurrence were significantly lower after house flap compared with rhomboid/diamond and Y–V flap. Better designed multicentre studies with longer follow‐up are needed to confirm these findings. PROSPERO registration number: CRD42021239493. [ABSTRACT FROM AUTHOR]

Ohmic, memristive synaptic weights are fabricated with a back‐end‐of‐line compatible process, based on a 3.5 nm HfZrO4 thin film crystallized in the ferroelectric phase at only 400 °C. The current density is increased by three orders of magnitude compared to the state‐of‐the‐art. The use of a metallic oxide interlayer, WOx, allows excellent retention (only 6% decay after 106 s) and endurance (1010 full switching cycles). The On/Off of 7 and the small device‐to‐device variability (<5%) make them promising candidates for neural networks inference. The synaptic functionality for online learning is also demonstrated: using pulses of increasing (resp. constant) amplitude and constant (resp. increasing) duration, emulating spike‐timing (resp. spike‐rate) dependent plasticity. Writing with 20 ns pulses only dissipate femtojoules. The cycle‐to‐cycle variation is below 2%. The training accuracy (MNIST) of a neural network is estimated to reach 92% after 36 epochs. Temperature‐dependent experiments reveal the presence of allowed states for charge carriers within the bandgap of hafnium zirconate. Upon polarization switching, the screening of the polarization by mobile charges (that can be associated with oxygen vacancies and/or ions) within the ferroelectric layer modifies the energy profile of the conduction band and the bulk transport properties. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to show if transanal reinforcement of the suture line can prevent anastomotic leakage (AL) after rectal cancer surgery, thus avoiding the need for a covering ileostomy. Methods: This is a prospective, multicentre, parallel‐arm randomized controlled equivalence trial. After standard total mesorectal excision, patients with anastomotic line at 1–3 cm from the dentate line were randomized to have transanal suture reinforcement (TAR group) or protective ileostomy (PI group). Results: Twenty‐nine patients had PI, 25 had TAR. The two groups were comparable both for baseline characteristics and intra‐operative aspects. Clinically evident AL occurred in four (16%) and five (17.24%) patients of the TAR and PI group, respectively, resulting in a difference of −1.20% (90% CI −17.93, 15.45), while subclinical AL at proctography was absent in 15 (65.22%) and 13 (50%) patients of the TAR and PI groups, respectively, resulting in a difference of 15% (90% CI −7.74 to 38.17). Conclusion: Preliminary data suggest that transanal reinforcement of the suture line performed in rectal cancer patients with suture line at 1–3 cm from the dentate line carries a similar (even if not equivalent) AL rate to covering ileostomy, suggesting that a covering ileostomy could be avoided in this selected group of patients. This indication needs to be addressed with future larger trials (clinicaltrials.gov ID number NCT02279771). [ABSTRACT FROM AUTHOR]

Here, cation exchange (CE) reactions are exploited to radiolabel ZnSe, ZnS, and CuFeS2 metal chalcogenide nanocrystals (NCs) with 64Cu. The CE protocol requires one simple step, to mix the water‐soluble NCs with a 64Cu solution, in the presence of vitamin C used to reduce Cu(II) to Cu(I). Given the quantitative cation replacement on the NCs, a high radiochemical yield, up to 99%, is reached. Also, provided that there is no free 64Cu, no purification step is needed, making the protocol easily translatable to the clinic. A unique aspect of the approach is the achievement of an unprecedentedly high specific activity: by exploiting a volumetric CE, the strategy enables to concentrate a large dose of 64Cu (18.5 MBq) in a small NC dose (0.18 µg), reaching a specific activity of 103 TBq g−1. Finally, the characteristic dielectric resonance peak, still present for the radiolabeled 64Cu:CuFeS2 NCs after the partial‐CE reaction, enables the generation of heat under clinical laser exposure (1 W cm−2). The synergic toxicity of photo‐ablation and 64Cu ionization is here proven on glioblastoma and epidermoid carcinoma tumor cells, while no intrinsic cytotoxicity is seen from the NC dose employed for these dual experiments. [ABSTRACT FROM AUTHOR]

Abstract: Background: In spite of some evidence for positive effects of patient's education to asthma self‐management by randomized clinical trials, there are few studies on the impact of patient’ s educational programs in the real world. We aimed to assess the impact of a diagnostic therapeutic educational pathway (DTEP) on asthma control of children and adolescents by comparing frequency of outcomes indicative of asthma control before and after attending the pathway. Methods: This is a retrospective cohort study including all patients aged 6‐11 and 12‐17 years who attended the DTEP in 2007‐2014. The DTEP includes 3 specialist's evaluations at 8‐ to 12‐week intervals and two follow‐up visits. Patients and their parents receive an educational course concerning prevention measures, early recognition of symptoms, and appropriate use of drugs and devices. The rates of hospitalizations, outpatient services, emergency room visits, and drug prescriptions were considered as outcomes and computed as number of events divided by person‐time. Results: A total of 806 patients were enrolled. A statistically significant decrease in rates from before to after DTEP was observed for almost all outcomes, in both age groups, with relative risks ranging from 0.12 to 0.60. The rates of drug prescription showed a statistically significant decrease, from before to after DTEP, for each type of medicine for asthma, in both age groups, from percent difference of −66% to −24.3%. Conclusions: The positive impact of this program on the outcomes indicative of asthma control in both children and adolescents suggests that it may be valuable for asthma management. [ABSTRACT FROM AUTHOR]

Aim of the current study was to evaluate the inter‐observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the “PreventCD” study, a multinational‐ prospective‐ randomized study in children with at least one‐first‐degree relative with CD and positive for HLA‐DQ2/HLA‐DQ8. Ninety‐eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza‐Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh‐Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well‐controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist. [ABSTRACT FROM AUTHOR]

Background & aims In the natural history of hepatitis B virus ( HBV) chronic infection, the hepatocellular carcinoma ( HCC) risk is unclear. We assessed incidence and predictors of HCC by a systematic review and meta-analysis. Methods We included longitudinal studies and randomized controlled trials assessing HCC incidence in untreated patients with HBV chronic infection. Incidence rates and their 95% confidence intervals were extracted by each study and pooled together in random effects models. Results Sixty-six studies were included with a total of 347 859 patients. According to liver disease status, the summary incidence rates were in Europe, North America and East Asia, respectively: (a) asymptomatic carriers: 0.07 (95% confidence interval: 0.05-0.09), 0.19 (0.07-0.31) and 0.42 (0.21-0.63) per 100 person-years, respectively; (b) inactive carriers: 0.03 (0.0-0.10), 0.17 (0.02-0.62) and 0.06 (0.02-0.10), respectively; (c) chronic hepatitis: 0.12 (0.0-0.27), 0.48 (0.22-0.91) and 0.49 (0.32-0.66), respectively; (d) compensated cirrhosis (Child-Pugh A): 2.03 (1.30-2.77), 2.89 (1.23-4.55) and 3.37 (2.48-4.26) respectively. Multivariate meta-regression showed a significant increase in incidence rates for age, and for status of a symptomatic carrier, chronic hepatitis and compensated cirrhosis compared to inactive carrier, but not for geographical area after adjusting for age. An increase in the incidence rates was also observed for alcohol intake ≥60 g/dl, HBV genotype C with respect to B and HBV- DNA serum levels >2000 IU/ml, in Asian studies. Conclusions Hepatocellular carcinoma risk in untreated subjects with HBV chronic infection is strongly related with age and liver disease status. [ABSTRACT FROM AUTHOR]

Background The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes. Methods Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation ( FC) or constipation-predominant irritable bowel syndrome ( IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms ( PAC- SYM), and the treatment satisfaction questionnaire for medication ( TSQM-2). Wave 2 only included a global rating of change ( GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC- SYM item 3. Key Results The average age was 50.1 years ( SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% ( n = 1970). Bloating was associated with SF-12 Physical Composite Score ( p < 0.01), SF-12 Mental Composite Score ( p < 0.01), GRC ( p < 0.01), Satisfaction with treatment effectiveness ( p < 0.01), convenience of administration ( p < 0.01), and side effects ( p < 0.01) after adjustment for possible confounders. Conclusions & Inferences Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient-reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain. [ABSTRACT FROM AUTHOR]

Background Sinonasal mucosal melanoma is a rare malignancy with poor prognosis. Methods Patients with sinonasal malignant melanoma who underwent surgery by different approaches were included in this study. Overall survival (OS) and event-free survival were calculated, and statistically significant variables by univariate analysis were entered in a multivariate Cox regression model. Results Pathological staging was pT3, pT4a, and pT4b in 30 cases (51.7%), 17 cases (29.3%), and 11 cases (19.0%). At 3 and 5 years, OS was 43.5% and 29% and event-free survival was 23.6% and 12.4%, respectively. At univariate analysis, OS was significantly influenced by male sex, advanced pT classification, positive margins, and surgical approach; event-free survival was affected by positive margins. At multivariate analysis, the risk of death was independently associated with male sex (hazard ratio [HR] = 2.27; p = .04) and positive margins (HR = 2.32; p = .03). Conclusion Male sex and positive margins were negative prognostic factors. Endoscopic resection did not show an increased risk of death compared with more extensive surgical approaches. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1737-E1745, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to assess survival, prognostic factors, and complications in a cohort of patients with intestinal-type adenocarcinoma (ITAC) treated with transnasal endoscopic surgery ± radiotherapy (RT). Methods Patients with ITAC who underwent endoscopic surgery ± RT at 2 tertiary centers were retrospectively reviewed. Overall survival (OS) and event-free survival were calculated, and statistically significant variables were entered in a multivariate Cox regression model. Complications were also analyzed. Results One hundred-sixty-nine patients were included. Major complications occurred in 9.5% of patients. Adjuvant RT was delivered in 58.6% of patients. Five-year OS and event-free survival were 68.9% and 63.6%, respectively. Advanced pT classification, high-grade, and positive surgical margins were independently predictive of poor survival. Conclusion Endoscopic surgery ± RT is a valid treatment option in most cases of ITAC. When compared with series based on external surgery, our results support a definitive paradigm shift in the management of ITAC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E996-E1003, 2016 [ABSTRACT FROM AUTHOR]

Background & Aims: The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. Methods: We studied 59 patients with chronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. Results: We found early acute normochromic normocytic haemolytic anaemia (4-8 weeks) followed by a late macrocytic hypo-regenerative anaemia with inappropriate low reticulocyte count (12-24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane-cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. Conclusions: The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic-like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis. [ABSTRACT FROM AUTHOR]

Background Immigrants represent a good epidemiological model to evaluate the relative influence of environmental and inherited factors on the development of allergy. Several studies on allergy in adults have been published, but few data in children are available. We aimed to investigate the differences, between Italian and immigrant children, in clinical characteristics of respiratory allergy. Methods This was a multicentre cross-sectional study involving children born in Italy from Italian parents and children born either in Italy or abroad from immigrants. Children referred firstly for allergic respiratory disease (rhinitis/asthma), with an ascertained clinical diagnosis and IgE sensitization to inhalants, were included. Demographic features, comorbidities, severity of disease, and sensitization profile were compared between Italians and immigrants, separating also those born in Italy from immigrant parents and those born abroad. Results One hundred and sixty-five immigrant allergic children were enrolled (100 male, mean age 8.3 yr), 128 of whose had both parents immigrated. Italian children were 237 (156 male, mean age 8.4 yr). The Italian and immigrant children were similar, apart from pet's ownership and family size. There was no difference in the severity of rhinitis/asthma between the groups, whereas significant differences were found in the pattern of sensitization: immigrant children were more frequently sensitized to house dust mites (73.3% vs. 51%, respectively; p = 0.002) and less to grass (41.8% vs. 57.8%; p = 0.002); this was retained also in monosensitized children. Immigrant children born in Italy (n = 105) had a lower prevalence of rhinitis vs. Italians (68.3% vs. 87.6%, respectively, p = 0.003) and of sensitization to grass (28.3% vs. 49.5%, respectively, p = 0.008). No difference was found among macro-regions of origin and demographic or clinical features. Conclusions Immigrant children born either in Italy or abroad did not show significant differences in the clinical pattern of the respiratory allergic disease when compared to children born from Italian parents. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Distal sensory neuropathy is the most common form of diabetic neuropathy. We developed a novel antidromic technique for assessment of distal nerve function for early diagnosis of diabetic neuropathy. Methods: Diabetic and control groups underwent standard and more distal sensory nerve conduction studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital branches of the medial plantar nerve were recorded with our method after stimulation at the sole and recording from digits I and II. Results: Comparison between controls and diabetics showed a statistically significant difference in mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs was obtained with our technique than with either conventional or more distal NCS in all patients. Conclusions: As compared with clinical evaluation and other NCS, our antidromic stimulation was the most sensitive method to detect abnormal sensory nerve conduction in symptomatic and asymptomatic diabetic patients. Muscle Nerve 50:193-199, 2014 [ABSTRACT FROM AUTHOR]