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Abstract 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.

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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]

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and endocrine disruptors that have been implicated in potential damage to human semen. However, the studies conducted so far provide contrasting results. Our study aimed to investigate the associations between PCB serum and semen levels and semen quality in high school and university students living in a highly PCB-polluted area of Italy. Subjects with a normal body mass index who did not make daily use of tobacco, alcohol, drugs, or medication were selected. All participants provided a fasting blood and a semen sample. Gas chromatography-mass spectrometry was used to determine the concentrations of 26 PCB congeners. The concentrations of PCB functional groups and total PCBs were also computed. A total of 143 subjects (median age 20, range 18–22 years) were enrolled. The median total PCB concentrations were 3.85 ng/mL (range 3.43–4.56 ng/mL) and 0.29 ng/mL (range 0.26–0.32 ng/mL) in serum and semen, respectively. The analysis of the associations between sperm PCB concentration and semen parameters showed (a) negative associations between some PCB congeners, functional groups and total PCBs and sperm total motility; (b) negative associations of total PCBs with sperm normal morphology; and (c) no association of PCBs with sperm concentration. Subjects at the highest quartile of semen total PCB concentration had 19% and 23% mean reductions in total motility and normal morphology, respectively, compared to those at the lowest quartile. The analysis of the associations of serum PCB levels with sperm parameters yielded null or mixed (some positive, other negative) results. In conclusion, the present study provides evidence of a negative effect of some PCB congeners and total PCBs in semen on sperm motility and normal morphology. However, the associations between the concentration of serum and semen PCB congeners and functional groups and sperm quality parameters were inconsistent. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between intensity of physical activity (PA) and semen quality in healthy young men., Design: A prospective cohort study with repeated measures for each subject., Setting: Not applicable., Patient(s): Healthy high school and university students who did not regularly smoke tobacco, drink alcohol, or take drugs or medicine, with normal body mass index and abdominal circumference., Intervention(s): The participants underwent urologic visit, fasting blood and semen sampling, and anthropometric measurements, and filled in the International Physical Activity Questionnaire, at enrollment and after 4 and 8 months. Duration and frequency of walking, moderate-intensity, and vigorous-intensity activities in the last week were assessed, and a score was computed for total PA., Main Outcome Measure(s): Semen specimens were taken at each visit through masturbation, after 3-5 days of abstinence, and analyzed by an expert urologist. Sperm concentration, total and progressive motility, and proportion of spermatozoa with normal morphology were measured. Linear and generalized linear mixed models with the Poisson family were fitted to assess the relationships between PA variables and sperm parameters, after adjusting for season, time, and study arm. The shape of the relationship was modeled through restricted cubic spline regression., Result(s): A total of 143 male subjects, aged 18-23 years (median, 20 years), were enrolled. They had a median PA of 1,960 (95% confidence interval, 1,055-3,182) Metabolic Equivalent of Tasks in min/wk. Statistically significant differences were found for total, progressive motility, and percent of cell with normal morphology across categories of total PA; the highest medians of total (47%) and progressive motility (34%) and of the percentage of normal morphology cells (7%) were found for medium PA. Positive associations of sperm total motility and normal morphology with medium levels of PA, and negative associations with walking and vigorous-intensity activity emerged. Spline regression analysis confirmed these findings, showing an inverse U-shape relationship, with the highest value of total motility and normal morphology for medium PA, and the lowest values for lower and higher activity., Conclusion(s): These findings support the present recommendations to practice moderate PA for health improvement, including semen quality., Competing Interests: Declaration of Interests F.D. has nothing to disclose. M.R. has nothing to disclose. E.C. has nothing to disclose. G.C.V.V. has nothing to disclose. M.M. has nothing to disclose. D.Z. has nothing to disclose. S.L. has nothing to disclose. L.M. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process., Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines., Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%)., Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Purpose: The impact of dietary counseling on body composition in early breast cancer patients (EBC) treated with aromatase inhibitors (AIs) is uncertain. The aim of this study was to assess the effects of a diet counseling program on weight, BMI, total and regional body composition in patients treated with AIs., Methods: This observational study involved 194 EBC patients, of which 97 attended a 6-month personalized counseling program, based on Mediterranean diet principles (cohort A) and 97 did not (cohort B). Dual-energy X-ray absorptiometry (DXA) scan was used to measure the total and regional fat and lean body mass, before (baseline) and after at least 18 months of AI-therapy., Results: Weight and BMI increased significantly, on the average, in cohort B, but not in cohort A. In the cohorts A and B, fat mass increased by 10 % and 7.7 % respectively, while lean mass decreased by 3.3 % and 2.6 % from before to after AI therapy, without statistically significant differences between them using the Mann-Whitney test. The changes in body composition were greater in premenopausal than in postmenopausal women at cancer diagnosis. The proportion of patients with sarcopenia, obesity and sarcopenic obesity increased from before to after AI therapy, similarly in both cohorts., Conclusions: Patients treated with AIs reported an increase in fat mass and a decrease in lean mass, and consequently an increase in sarcopenia and obesity, regardless of the participation in a dietary counseling program. A combined dietary counseling and physical exercise program may be necessary for preventing these unfavourable changes in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diastasis recti abdominis (DRA) indicates an abnormal separation of the rectus abdominal muscles from the midline, resulting in abdominal bulging. Recent literature shows a correlation between DRA and back pain, stress urinary incontinence. Primary goal of this study is to check the correlation between DRA correction in abdominoplasty and improvement of urinary symptoms., Materials and Methods: This is a prospective study on patients with post-pregnancy rectus diastasis who underwent surgical correction of diastasis through conventional abdominoplasty. All patients were asked to complete the ICIQ-FLUTS questionnaire, which assesses urinary disorders, and the SF-36 questionnaire, aimed at quantifying health-related quality of life. The questionnaires were administered to patients the day before surgery and one year after surgery., Results: The recruited patients (n = 51) were then stratified on the presence or absence of stress urinary incontinence. Of the 39 patients with preoperative incontinence, the average scores of the ICIQ-FLUTS were analyzed. In particular, for the questions relating to stress urinary incontinence a statistically significant difference was reported between the preoperative mean and the 1-year mean for all questions (p value<0.05). As regards quality of life, comparing the average scores of each question of SF-36 there is an improvement in the values of all the variables of the questionnaire., Conclusion: The strength of this study, which distinguishes it from other literature, is that the changes in abdominal pressure post-abdominoplasty which should lead to a worsening of stress incontinence, do not cause it. On the contrary, we have demonstrated the improvement of this symptom after conventional abdominoplasty surgery in most patients., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The recent co-optimization of memristive technologies and programming algorithms enabled neural networks training with in-memory computing systems. In this context, novel analog filamentary conductive-metal-oxide (CMO)/HfO x redox-based resistive switching memory (ReRAM) represents a key technology. Despite device performance enhancements reported in literature, the underlying mechanism behind resistive switching is not fully understood. This work presents the first physics-based analytical model of the current transport and of the resistive switching in these devices. As a case study, analog TaO x /HfO x ReRAM devices are considered. The current transport is explained by a trap-to-trap tunneling process, and the resistive switching by a modulation of the defect density within the sub-band of the TaO x that behaves as electric field and temperature confinement layer. The local temperature and electric field distributions are derived from the solution of the electric and heat transport equations in a 3D finite element ReRAM model. The intermediate resistive states are described as a gradual modulation of the TaO x defect density, which results in a variation of its electrical conductivity. The drift-dynamics of ions during the resistive switching is analytically described, allowing the estimation of defect migration energies in the TaO x layer. Moreover, the role of the electro-thermal properties of the CMO layer is unveiled. The proposed analytical model accurately describes the experimental switching characteristic of analog TaO x /HfO x ReRAM devices, increasing the physical understanding and providing the equations necessary for circuit simulations incorporating this technology.