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Abstract Background Dietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow’s milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow’s milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow’s milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes. Methods MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology. Results Eligibility criteria were met by 17 trials (n = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow’s milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow’s milk resulted in moderate reductions in non-HDL-C (mean difference, − 0.26 mmol/L [95% confidence interval, − 0.43 to − 0.10]), systolic blood pressure (− 8.00 mmHg [− 14.89 to − 1.11]), and diastolic blood pressure (− 4.74 mmHg [− 9.17 to − 0.31]); small important reductions in LDL-C (− 0.19 mmol/L [− 0.29 to − 0.09]) and c-reactive protein (CRP) (− 0.82 mg/L [− 1.26 to − 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified. Conclusions Current evidence provides a good indication that replacing cow’s milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets. Trial registration ClinicalTrials.gov identifier, NCT05637866.

Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

The dietary inclusion of ingredients containing chitin has been claimed to be beneficial to fish health. However, controversial results on growth performance and nutrient digestibility have been reported in literature. The present study aimed at assessing the response of rainbow trout (Oncorhynchus mykiss) fed with increasing levels of chitin (0, 1.5, 3.0, and 4.5 %) in a semi-purified basal diet. Protein and lipid digestibility was assessed and after 10 weeks of feeding, 6 h after the last meal, fish were euthanized for the evaluation of growth performance, blood biochemistry, brush border membrane and chitinolytic enzyme activity, gene expression of enzymes and nutrient transporters as well as the major pro-inflammatory intestinal cytokines, and mid intestine microbiota. Dietary chitin inclusion of up to 3 % did not hamper growth performances, nutrient apparent digestibility, and levels of most blood enzymes and metabolites. Diet including 4.5 % chitin negatively affected growth performances and nutrient digestibility. The application of a multidisciplinary approach highlighted that the biomarkers related to gut digestion functionality and inflammation response were altered also in fish fed the diets including 1.5 and 3 % of chitin, while gut microbiota did not differ between dietary treatments, even if some taxa suggested to be important in fish physiology were not recovered. Overall, the results demonstrate a good tolerance of rainbow trout to diets including chitin up to 3 %.

Abstract A low-energy electronic recoil calibration of XENON1T, a dual-phase xenon time projection chamber, with an internal $${}^{37}$$ 37 Ar source was performed. This calibration source features a 35-day half-life and provides two mono-energetic lines at 2.82 keV and 0.27 keV. The photon yield and electron yield at 2.82 keV are measured to be ( $$32.3\,\pm \,0.3$$ 32.3 ± 0.3 ) photons/keV and ( $$40.6\,\pm \,0.5$$ 40.6 ± 0.5 ) electrons/keV, respectively, in agreement with other measurements and with NEST predictions. The electron yield at 0.27 keV is also measured and it is ( $$68.0^{+6.3}_{-3.7}$$ 68 . 0 - 3.7 + 6.3 ) electrons/keV. The $${}^{37}$$ 37 Ar calibration confirms that the detector is well-understood in the energy region close to the detection threshold, with the 2.82 keV line reconstructed at ( $$2.83\,\pm \,0.02$$ 2.83 ± 0.02 ) keV, which further validates the model used to interpret the low-energy electronic recoil excess previously reported by XENON1T. The ability to efficiently remove argon with cryogenic distillation after the calibration proves that $${}^{37}$$ 37 Ar can be considered as a regular calibration source for multi-tonne xenon detectors.

Background: Congenital prepubic sinus (CPS) is a rare congenital variant of urethral duplication, with less than 50 cases documented in the scientific literature since it was first reported by Campbell et al., in 1987. Case presentation: An 8-year-old male patient complained of an inflammatory secretion from a sinus opening on the dorsal base of his penis. Physical examination revealed an accessory orifice in the midline of the dorsal proximal penis without any penile curvature. An ultrasound (US) examination found an 8-mm collection of cutaneous and subcutaneous tissue at the dorsal base of the penis. The renal US, however, showed no abnormalities. Additionally, micturating cystourethrogram (MCUG), was negative for vesicoureteral reflux (VUR). Retrograde sinusography (RS) and urethrogram showed no communication between the urinary tract, and the sinus was found to end blindly at the level of the pubic symphysis. A surgical excision was decided, to avoid potential future complications. A 3-cm-long intact sinus was dissected and excised entirely. Histological examination confirmed the diagnosis of a urethral duplication. The postoperative course was uneventful. To date, at six-month of follow-up, the patient remains asymptomatic. Conclusions: The histological findings in this case support the theory that CPS is a variant of dorsal urethra. Urethral duplication should always be suspected in the case of accessory dorsal openings. Surgical excision is recommended at an early age, even in the absence of symptoms, to improve aesthetics, prevent recurrent infections and avoid the development of future malignant tumors.

Abstract The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.

Abstract The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and $$^{222}$$ 222 Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background ( $$\sim $$ ∼ 17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected $$^{222}$$ 222 Rn activity concentration in XENONnT is determined to be 4.2 ( $$^{+0.5}_{-0.7}$$ - 0.7 + 0.5 ) $$\upmu $$ μ Bq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.

Introduction SARS-Co-V2 neuroinvasive ability might be the basis for the onset of delirium and neuropsychiatric outcomes. Objectives We hypothesized that some infected patients with preexisting cognitive dysfunction may present delirium as unique manifestation of COVID-19 infection or as a prodrome of a new episode consistent with the psychiatric history. Methods We conducted a PubMed literature search to verify whether cognitive impairment might predispose to COVID-19. We included three patients with mild cognitive impairment and delirium at admission for SARS-Co-V2 suspected infection. Delirium was diagnosed according to DSM-5 criteria‚ Cognitive Assessment Method and Coma Glasgow Scale. Results Literature analysis evidenced patients presenting delirium or delirium-like symptoms as clinical manifestation of COVID-19, plus a cognitive impairment‚ from mild to severe‚ which preexisted or was evidenced during the acute phase or after the infection. Most studies described delirium in patients with a past neurological/psychiatric history. Contrasting data emerged on the potential link between COVID-19 and delirium in patients with cognitive impairment and without a past neuropsychiatric history. Our patients had no history of other medical complications. Our first patient had no psychiatric history‚ the second reported only a depressive episode‚ and the third had story of bipolar disorder. Delirium resolved completely after 2 days in the first patient. The other patients required 4 and 14 days to resolve: delirium appeared as the prodrome of a new psychiatric episode in line with their past history. Conclusions Clinicians should acknowledge the possibility that COVID-19 infection may appear as delirium and acute psychiatric sequelae as unique manifestation. Disclosure No significant relationships.

INTRODUCTION: In this paper we discuss concepts and practices that point to a new field of ubiquitous music (ubimus)research centered on domestic settings.OBJECTIVES: The objective of this paper is to document and share a preliminary study of the use of taste as a trigger forcreative decisions and a comparative study of creative music making done at home and in transitional settings.METHODS: Groundwork in this area encompasses the design, implementation and deployment of ubimus systems. Keyaspects include sonic resources and metaphors for creative action based on multimodality.RESULTS: The results indicate that unpredictable sonic environments foster originality but may compromise the subjects’creative performance — reducing their level of engagement and fun and the possibilities for collaboration, while increasingthe cognitive demands of the activity. Home seems to furnish a positive context as long as the objective is not to increasethe originality of the outcomes.CONCLUSION: The effectiveness of taste as a scaffold for creative decisions was partially confirmed, demanding furtherstudies. These results have implications for both the artistic aspects of sound making and the everyday usage of sound fordistant socializing in domestic settings, posing renewed challenges to the ongoing STEAM initiatives.

Objective: The extent of collateral artery enlargement determines the risk of limb loss due to peripheral arterial disease. Hypercholesterolemia impairs collateral artery enlargement, but the underlying mechanism remains poorly characterized. This study tests the hypothesis that hypercholesterolemia impairs collateral artery enlargement through a ten-eleven translocation 1 (Tet1)-dependent hematopoietic stem cell (HSC)-autonomous mechanism that increases their differentiation into proinflammatory Ly6Chi monocytes and restricts their conversion into proangiogenic Ly6Clow monocytes. Methods: To test our hypothesis, we induced limb ischemia and generated chimeric mouse models by transplanting HSCs from either wild-type (WT) mice or hypercholesterolemic mice into lethally irradiated WT recipient mice. Results: We found that the lethally irradiated WT recipient mice reconstituted with HSCs from hypercholesterolemic mice displayed lower blood flow recovery and collateral artery enlargement that was nearly identical to that observed in hypercholesterolemic mice, despite the absence of hypercholesterolemia and consistent with an HSC-autonomous mechanism. We showed that hypercholesterolemia impairs collateral artery enlargement by a Tet1-dependent mechanism that increases HSC differentiation toward proinflammatory Ly6Chi monocytes and restricts the conversion of Ly6Chi monocytes into proangiogenic Ly6Clow monocytes. Moreover, Tet1 epigenetically reprograms monocyte gene expression within the HSCs. Restoration of Tet1 expression in HSCs of hypercholesterolemic mice restores WT collateral artery enlargement and blood flow recovery after induction of hindlimb ischemia. Conclusions: These results show that hypercholesterolemia impairs collateral artery enlargement by a novel Tet1-dependent HSC-autonomous mechanism that epigenetically reprograms monocyte gene expression within the HSCs. : Clinical Relevance: The extent of collateral artery enlargement determines the risk of limb loss due to peripheral arterial occlusive disease, survival after acute myocardial infarction, and the occurrence of neurological deficits after ischemic stroke. Yet, the mechanisms that regulate collateral artery enlargement are incompletely characterized. We show that hypercholesterolemia impairs collateral artery enlargement by a hematopoietic stem cell (HSC)-autonomous mechanism where the monocyte number and gene expression are epigenetically reprogrammed within the HSC. Thus, therapeutic agents for peripheral arterial disease should focus on normalizing the immune response during collateral artery enlargement.

We present the first measurement of nuclear recoils from solar ^{8}B neutrinos via coherent elastic neutrino-nucleus scattering with the XENONnT dark matter experiment. The central detector of XENONnT is a low-background, two-phase time projection chamber with a 5.9 t sensitive liquid xenon target. A blind analysis with an exposure of 3.51  t×yr resulted in 37 observed events above 0.5 keV, with (26.4_{-1.3}^{+1.4}) events expected from backgrounds. The background-only hypothesis is rejected with a statistical significance of 2.73σ. The measured ^{8}B solar neutrino flux of (4.7_{-2.3}^{+3.6})×10^{6}  cm^{-2} s^{-1} is consistent with results from the Sudbury Neutrino Observatory. The measured neutrino flux-weighted CEνNS cross section on Xe of (1.1_{-0.5}^{+0.8})×10^{-39}  cm^{2} is consistent with the Standard Model prediction. This is the first direct measurement of nuclear recoils from solar neutrinos with a dark matter detector.

Purpose: The purpose of this paper is to report the increasing incidence of contact-lens related Acanthamoeba keratitis (AK) in a tertiary ophthalmology department in Umbria, central Italy., Methods: Observational and retrospective case series were carried out. A total of nine eyes with a diagnosis of AK were examined. All patients underwent a full slit lamp examination, in vivo confocal microscopy (IVCM) and corneal scraping. The IVCM was repeated at one and two-week and at one, three and six-month intervals. Samples of domestic tap water were also examined for PCR analysis. Patients were treated with levofloxacin0,5%, Polyhexamethylene biguanide 0.02%, and Propamidine Isetionate0,1%., Results: All patients were contact lens wearers. The average patient age was 27.75 (range 18-45), with three men and five women. The main clinical features were ciliary congestion, diffuse epitheliopathy with punctuated keratitis, multiple, small sub-epithelial, greyish, corneal infiltrates with epithelial defect, pseudodendritic corneal lesions, perineural infiltrates, corneal stromal cellularity, and stromal infiltrates. IVCM was indicative of Acanthamoeba in seven out of the nine eyes. All the positive IVCM images were section images showing double walled, bright-spot cysts with a clear chain-like arrangement of five or more cysts identified in three of the patients. PCR analysis of the water was negative in all cases., Conclusion: Although PCR is the most common method used, the increased incidence of AK could mainly be related to a proper IVCM interpretation. A broad-spectrum antibiotic, such as levofloxacin might play a role in the early treatment of AK reducing the virulence of the amoeba., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Despite recommendations to increase plant food consumption for public and planetary health and the role that soy foods can play in plant-predominant diets, controversies around the effects of soy foods and especially soy isoflavones, are a barrier to their intake. Given their cardioprotective effects and ability to alleviate menopausal symptoms, addressing these concerns is particularly relevant to women., Objective: This systematic review and meta-analysis of randomized controlled trials aimed to determine the effect of soy isoflavones on measures of estrogenicity in postmenopausal women., Methods: MEDLINE, Embase, and Cochrane Library were searched through August 2024 for randomized trials 3-months investigating soy isoflavones versus non-isoflavone controls in postmenopausal women. Outcomes included endometrial thickness (ET), vaginal maturation index (VMI), follicle-stimulating hormone (FSH), and estradiol. Independent authors extracted data and assessed risk of bias. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess certainty of evidence., Results: We included 40 trials (52 trial comparisons, n=3285) assessing the effect of a median reported dose of 75mg/day of soy isoflavones in substitution for non-isoflavone controls over a median of 24 weeks. Soy isoflavones had no statistically significant effect on any measure of estrogenicity; ET (mean difference, -0.22mm [95% confidence interval, -0.45, 0.01mm], P MD =0.059), VMI (2.31 [-2.14, 6.75], P MD =0.310), FSH (-0.02IU/L [-2.39, 2.35IU/L], P MD =0.987), and estradiol (1.61pmol/L [-1.17, 4.38pmol/L], P MD =0.256). The certainty of evidence was high-to-moderate for all outcomes., Conclusions: Current evidence suggests that soy isoflavones do not exhibit estrogenic effects compared to non-isoflavone controls on 4 measures of estrogenicity in postmenopausal women. This synthesis supports that soy isoflavones likely act as selective estrogen receptor modulators, differing clinically from the hormone estrogen. Addressing public health concerns may promote soy foods as high-quality plant protein sources with low environmental impact and cost, particularly benefiting postmenopausal women, and aligning with sustainable dietary patterns and guidelines., Registration: PROSPERO (CRD42023439239)., 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. ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Laura Chiavaroli reports financial support was provided by the United Soybean Board (the US Department of Agriculture soy check-off program). John L Sievenpiper reports financial support was provided by Canadian Institutes of Health Research (funding reference number, 129920) through the Canada-wide Human Nutrition Trialists’ Network. John L Sievenpiper reports financial support was provided by Ontario Ministry of Research and Innovation. Mark Messina reports financial support was provided by Soy Nutrition Institute. Gabrielle Viscardi reports financial support was provided by Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Andreea Zurbau is a part-time research associate at INQUIS Clinical Research Ltd, a contract research organization, and has received consulting fees from Glycemic Index Foundation. Tauseef A Khan has received research support from the Canadian Institutes of Health Research (CIHR), the International Life Science Institute (ILSI), and National Honey Board. He has been an invited speaker at the Calorie Control Council Annual meeting for which he has received an honorarium. He has received funding from the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. Mark Messina was employed by the Soy Nutrition Institute Global, an organization that receives funding from the United Soybean Board (USB) and from members involved in the soy industry. Cyril WC Kendall has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada (AAFC), Almond Board of California, Barilla, Canadian Institutes of Health Research (CIHR), Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands Ltd, the Peanut Institute, Pulse Canada and Unilever. He has received in-kind research support from the Almond Board of California, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from the Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Lantmannen, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, McCormick Science Institute and Oldways Preservation Trust. He is a founding member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. David JA Jenkins has received research grants from Saskatchewan & Alberta Pulse Growers Associations, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever Canada and Netherlands, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg's Company, Canada, Quaker Oats, Canada, Procter & Gamble Technical Centre Ltd., Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, International Nut & Dried Fruit Council (INC), Soy Foods Association of North America, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Soy Nutrition Institute (SNI), the Canola and Flax Councils of Canada, the Calorie Control Council, the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI)and the Ontario Research Fund (ORF). He has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, WhiteWave Foods. He has been on the speaker's panel, served on the scientific advisory board and/or received travel support and/or honoraria from Nutritional Fundamentals for Health (NFH)-Nutramedica, Saint Barnabas Medical Center, The University of Chicago, 2020 China Glycemic Index (GI) International Conference, Atlantic Pain Conference, Academy of Life Long Learning, the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system), the Coca-Cola Company, Epicure, Danone, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute (SNI), Herbalife Nutrition Institute (HNI), Saskatchewan & Alberta Pulse Growers Associations, Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, Abbott Laboratories, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael's Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the United States Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian Diabetes Association (CDA). He is a member of the International Carbohydrate Quality Consortium (ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8)and his sister, Caroline Brydson, received funding through a grant from the St. Michael's Hospital Foundation to develop a cookbook for one of his studies. He is also a vegan. John L Sievenpiper has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, American Society for Nutrition (ASN), International Nut and Dried Fruit Council (INC) Foundation, National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (USDA soy “Checkoff” program), Protein Industries Canada (a Government of Canada Global Innovation Clusters), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), The Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and The Nutrition Trialists Network Research Fund at the University of Toronto (a fund which has received donations from the Calorie Control Council, Physicians Committee for Responsible Medicine, and vegan grants through the Karuna Foundation). He has received food donations to support randomized controlled trials from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, Danone, Nutrartis, Soylent, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from ASN, Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, International Sweeteners Association, International Glutamate Technical Committee, Arab Beverages Association, and Phynova. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Inquis Clinical Research, Ingredion, and Brightseed. He is a former member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves as an unpaid member of the Board of Trustees of IAFNS and formerly served as an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a Director at Large of the Canadian Nutrition Society (CNS), founding member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. Laura Chiavaroli has received research support from Protein Industries Canada (a Government of Canada Global Innovation Clusters). If there are other authors, they 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Even if vesicoureteral reflux is a common condition in children, there are no guidelines about the best therapeutic approach. This study aims to compare the results of endoscopic injection and ureteral reimplantation in children with grade III, IV and V VUR. A multicenter retrospective study included children with grade III, IV and V VUR treated from 2003 to 2018 at three Departments of Pediatric Surgery. Patients were divided into Group A (endoscopic injections) and Group B (anti-reflux surgery), B1 (open, OUR), B2 (laparoscopic, LUR) and B3 (robot-assisted laparoscopic RALUR). Follow-up was at least 5 years. 400 patients were included, 232 (58%) in group A and 168 (42%) in group B. Mean age at surgery was 38.6 months [3.1-218.7]. Mean follow-up was 177.8 months [60-240]. Group A had shorter operative time than group B (P < 0.01); lower analgesic requirement (p < 0.05), shorter hospital stay (P < 0.05) and lower overall costs (p < 0.05), but higher postoperative PNPs (p < 0.01), lower success rate (p < 0.01) and higher redo-surgery percentage (p < 0.01). No differences in terms of postoperative complications, success rate and mean radiation exposure between the two groups. Endoscopy is associated with shorter operative time, shorter hospitalization and lower cost, also in case of multiple injections. Recurrence rate after surgery is lower meaning lower rate of re-hospitalization and radiation exposure for children., (© 2024. The Author(s).)

Background: Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity., Methods: We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures., Results: SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults., Conclusions: Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MC declared a past co-authorship with the author PR to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Damanti, Citterio, Zagato, Brioni, Magnaghi, Simonini, De Lorenzo, Ruggiero, Santoro, Senini, Messina, Vitali, Manunta, Manfredi, Lanzani and Rovere Querini.)

Background: Acute sarcopenia refers to the swift decline in muscle function and mass following acute events such as illness, surgery, trauma, or burns that presents significant challenges in hospitalized older adults., Methods: narrative review to describe the mechanisms and management of acute sarcopenia., Results: The prevalence of acute sarcopenia ranges from 28% to 69%, likely underdiagnosed due to the absence of muscle mass and function assessments in most clinical settings. Systemic inflammation, immune-endocrine dysregulation, and anabolic resistance are identified as key pathophysiological factors. Interventions include early mobilization, resistance exercise, neuromuscular electrical stimulation, and nutritional strategies such as protein supplementation, leucine, β-hydroxy-β-methyl-butyrate, omega-3 fatty acids, and creatine monohydrate. Pharmaceuticals show variable efficacy., Conclusions: Future research should prioritize serial monitoring of muscle parameters, identification of predictive biomarkers, and the involvement of multidisciplinary teams from hospital admission to address sarcopenia. Early and targeted interventions are crucial to improve outcomes and prevent long-term disability associated with acute sarcopenia.

Background: In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients., Methods: Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring., Results: Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with 2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with

Background: Dietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow's milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow's milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow's milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology., Results: Eligibility criteria were met by 17 trials (n = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow's milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow's milk resulted in moderate reductions in non-HDL-C (mean difference, - 0.26 mmol/L [95% confidence interval, - 0.43 to - 0.10]), systolic blood pressure (- 8.00 mmHg [- 14.89 to - 1.11]), and diastolic blood pressure (- 4.74 mmHg [- 9.17 to - 0.31]); small important reductions in LDL-C (- 0.19 mmol/L [- 0.29 to - 0.09]) and c-reactive protein (CRP) (- 0.82 mg/L [- 1.26 to - 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified., Conclusions: Current evidence provides a good indication that replacing cow's milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets., Trial Registration: ClinicalTrials.gov identifier, NCT05637866., (© 2024. The Author(s).)

Aim: To define the prognostic significance of first-line TKI in mRCC patients receiving nivolumab. Materials and methods: A total of 571 mRCC patients who received ≥second line nivolumab were included in this subanalysis. The correlation between prior TKI (sunitinib vs. pazopanib) and overall response rate (ORR), disease control rate, progression-free survival and overall survival were investigated. Additionally, the impact of TKI choice according to the International Metastatic RCC Database Consortium prognostic score was examined. Results: There was no significant difference between sunitinib and pazopanib groups in terms of mPFS, mOS, overall response rate and disease control rate. Moreover, no difference between sunitinib and pazopanib was found according to the International Metastatic RCC Database Consortium prognostic score. Conclusion: There is no conclusive evidence favoring pazopanib or sunitinib treatment before initiating nivolumab therapy in metastatic renal cell carcinoma patients.

In this paper, an assessment of the natural radioactivity level, radon exhalation, metal contamination, and mineralogy of a granodiorite rock sample from Stilo, in the Calabria region, Southern Italy is presented as a case study. This rock was employed as a building material in the area under study. The specific activity of 226 Ra, 232 Th and 40 K natural radioisotopes was assessed through high-purity germanium (HPGe) gamma-ray spectrometry. Then, several indices such as the absorbed gamma dose rate (D), the annual effective dose equivalent (AEDE), the activity concentration index (ACI) and the alpha index (I α ), were quantified to determine any potential radiological health risk related to radiation exposure from the analyzed rock. Furthermore, E-PERM electret ion chambers and inductively coupled plasma mass spectrometry (ICP-MS) measurements were carried out to properly quantify the radon exhalation rate and any possible metal pollution, respectively. In particular, to further address metal pollution factors, the geo-accumulation index (I geo ) was calculated to properly address the toxicity levels of the ecosystem originating from the detected metals. Finally, with the aim of successfully discriminating the provenance of such naturally occurring radionuclides, a combined approach involving X-ray diffraction (XRD) and µ-Raman spectroscopy was employed for the identification of the main radioisotope-bearing minerals characterizing the investigated granodiorite. The results achieved in this case study can be taken as the basis for further inquiries into background levels of radioactivity and chemical contamination in natural stone employed as building materials.

Objectives: To describe a new penoscrotal reconfiguration technique, named "V-I penoscrotal reconfiguration" for the surgical reconstruction of a congenital webbed penis (CWP)., Methods: Twenty-one patients who underwent the "V-I penoscrotal reconfiguration technique" were included in this retrospective study. The CWP severity was assessed according to El-Koutby's classification. Demographic and clinical data, surgical data, and postoperative outcomes were scheduled and analyzed. Specifically, the postoperative follow-up included both physical and psychological assessments at 2 weeks, 1, 6, and 12 months after surgery. Parents' satisfaction degree was quantified by the Likert scale., Results: CWP was grade 3 in 11 (52%) patients, 2 in five (24%), and 1 (24%) in five. Five (24%) CWP were isolated malformations, 11 (52%) were associated with phimosis, three (14%) with hypospadias, and two (10%) with hypospadias and phimosis. There were no postoperative complications and no cases of redo surgery. The cosmetic outcomes were excellent in all cases: the parents' satisfaction score was 4 in 17 (81%) cases and 3 (9%) in the other four cases., Conclusions: CWP may cause psychological distress and functional problems, especially during sexual intercourse. Its correction in childhood is advocated to prevent psychological and sexual issues. The "V-I reconfiguration technique" is simple, and easy with excellent cosmetic and functional outcomes., (© 2024 The Japanese Urological Association.)

Background: Neutrophil-to-eosinophil ratio (NER) has been described to be associated with outcomes to immune checkpoint inhibitors (ICI) in several tumor types, but less is known about its role of in the response to avelumab in advanced urothelial cancer (aUC). Thus, we reported outcomes by NER of aUC patients treated with avelumab as maintenance after initial response to platinum-based chemotherapy and enrolled in the Maintenance with AVeLumAb ([MALVA] in advanced urothelial neoplasms in response to first-line chemotherapy: an observational retrospective study) study (Meet-URO 25)., Patients and Methods: Median NER at baseline and after 3 cycles of avelumab were calculated. Progression-free survival (PFS) and overall survival (OS) by NER were reported., Results: At the cutoff date (April 15, 2023), a total of 109 patients were included. The median NER was 28.05 at baseline and 24.46 after 3 cycles of avelumab, respectively. Median PFS was not reached for patients with baseline NER less than the median (

Background: The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population., Methods: Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors., Results: One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07-0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05-0.1, p < 0.001) and pre-sarcopenia (without obesity B 0.03, 95% C.I, 0.007-0.044, p < 0.001, with obesity B 0.11, 95% C.I. 0.05-0.16, p < 0.001) were associated with frailty. Fat mass percentage predicted frailty in people aged 65-70 years whereas, muscle strength predicted general frailty in people aged 70-81 years., Conclusion: Pre-sarcopenia and SO represent potentially treatable predictors of frailty., (© 2024. The Author(s).)

The global food system faces a challenge of sustainably producing enough food, and especially protein, to meet the needs of a growing global population. In developed countries, approximately 2/3 of protein comes from animal sources and 1/3 from plants. For an assortment of reasons, dietary recommendations call for populations in these countries to replace some of their animal protein with plant protein. Because it is difficult to substantially change dietary habits, increasing plant protein may require the creation of novel foods that meet the nutritional, orosensory, and functional attributes consumers desire. In contrast to plant-based milks, plant-based cheeses have not been widely embraced by consumers. The existing plant-based cheeses do not satisfactorily mimic dairy cheese as plant proteins are unable to replicate the functional properties of casein, which plays such a key role in cheese. One possible solution to overcome current constraints that is currently being explored, is to produce hybrid products containing soy protein and soybean-derived casein. Producing soybean-derived casein is possible by utilizing traditional genetic engineering tools, like Agrobacterium -mediated plant transformation, to express genes in soybeans that produce casein. If a cheese containing soy protein and soybean-derived casein satisfactorily mimics dairy, it presents an opportunity for increasing plant protein intake since US dairy cheese consumption has been steadily increasing. Soybeans are an excellent choice of crop for producing casein because soybeans are widely available and play a large role in the US and world food supply. Additionally, because a casein-producing soybean offers soybean farmers the opportunity to grow a value-added crop, expectations are that it will be welcomed by the agricultural community. Thus, there are benefits to both the consumer and farmer., Competing Interests: Author MM was employed by Soy Nutrition Institute Global, which received a contribution from Alpine Bio for the writing of this manuscript. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Messina and Messina.)

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant connective tissue disease resulting from pathogenic variants in the collagen type III alpha 1 chain ( COL3A1 ) gene, encoding type III procollagen. Patients with vEDS present with severe tissue fragility that can result in arterial aneurysm, dissection, or rupture, especially of medium-caliber vessels. Although early reports have indicated a very high mortality rate in affected patients, with an estimated median survival of around 50 years, recent times have seen a remarkable improvement in outcomes in this population. This shift could be related to greater awareness of the disease among patients and physicians, with improved management both in terms of follow-up and treatment of complications. Increasing use of drugs acting on the cardiovascular system may also have contributed to this improvement. In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS. However, the evidence on the true benefits and possible mechanisms responsible for the protective effect of celiprolol in this specific setting remains limited. Drugs targeting the extracellular matrix organization and autophagy-lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention.

Background: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment., Materials and Methods: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses., Results: A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders., Conclusion: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy., (© 2024. The Author(s).)