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Abstract Background The optimal stimulation for brain development in the early academic years remains unclear. Current research suggests that musical training has a more profound impact on children's executive functions (EF) compared to other art forms. What is crucially lacking is a large-scale, long-term genuine randomized controlled trial (RCT) in cognitive neuroscience, comparing musical instrumental training (MIP) to another art form, and a control group (CG). This study aims to fill this gap by using machine learning to develop a multivariate model that tracks the interconnected brain and EF development during the academic years, with or without music or other art training. Methods The study plans to enroll 150 children aged 6-8 years and randomly assign them to three groups: Orchestra in Class (OC), Visual Arts (VA), and a control group (CG). Anticipating a 30% attrition rate, each group aims to retain at least 35 participants. The research consists of three analytical stages: 1) baseline analysis correlating EF, brain data, age, gender, and socioeconomic status, 2) comparison between groups and over time of EF brain and behavioral development and their interactions, including hypothesis testing, and 3) exploratory analysis combining behavioral and brain data. The intervention includes intensive art classes once a week, and incremental home training over two years, with the CG receiving six annual cultural outings. Discussion This study examines the potential benefits of intensive group arts education, especially contrasting music with visual arts, on EF development in children. It will investigate how artistic enrichment potentially influences the presumed typical transition from a more unified to a more multifaceted EF structure around age eight, comparing these findings against a minimally enriched active control group. This research could significantly influence the incorporation of intensive art interventions in standard curricula. Trial registration The project was accepted after peer-review by the Swiss National Science Foundation (SNSF no. 100014_214977) on March 29, 2023. The study protocol received approval from the Cantonal Commission for Ethics in Human Research of Geneva (CCER, BASEC-ID 2023-01016), which is part of Swiss ethics, on October 25, 2023. The study is registered at clinicaltrials.gov (NCT05912270).

Background: The optimal stimulation for brain development in the early academic years remains unclear. Current research suggests that musical training has a more profound impact on children's executive functions (EF) compared to other art forms. What is crucially lacking is a large-scale, long-term genuine randomized controlled trial (RCT) in cognitive neuroscience, comparing musical instrumental training (MIP) to another art form, and a control group (CG). This study aims to fill this gap by using machine learning to develop a multivariate model that tracks the interconnected brain and EF development during the academic years, with or without music or other art training., Methods: The study plans to enroll 150 children aged 6-8 years and randomly assign them to three groups: Orchestra in Class (OC), Visual Arts (VA), and a control group (CG). Anticipating a 30% attrition rate, each group aims to retain at least 35 participants. The research consists of three analytical stages: 1) baseline analysis correlating EF, brain data, age, gender, and socioeconomic status, 2) comparison between groups and over time of EF brain and behavioral development and their interactions, including hypothesis testing, and 3) exploratory analysis combining behavioral and brain data. The intervention includes intensive art classes once a week, and incremental home training over two years, with the CG receiving six annual cultural outings., Discussion: This study examines the potential benefits of intensive group arts education, especially contrasting music with visual arts, on EF development in children. It will investigate how artistic enrichment potentially influences the presumed typical transition from a more unified to a more multifaceted EF structure around age eight, comparing these findings against a minimally enriched active control group. This research could significantly influence the incorporation of intensive art interventions in standard curricula., Trial Registration: The project was accepted after peer-review by the Swiss National Science Foundation (SNSF no. 100014_214977) on March 29, 2023. The study protocol received approval from the Cantonal Commission for Ethics in Human Research of Geneva (CCER, BASEC-ID 2023-01016), which is part of Swiss ethics, on October 25, 2023. The study is registered at clinicaltrials.gov (NCT05912270)., (© 2024. The Author(s).)

The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic., Competing Interests: Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Léa Caplan has received an AbbVie IBD scholarship. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). None: Joseph Windsor, Stephanie Coward, Juan-Nicolás Peña-Sanchez, Sara Ghandeharian, Noelle Rohatinsky, Jake Weinstein, Tyrel Jones May, Mira Browne, Nazanin Jannati, Sahar Tabatabavakili, James Im, Saketh Meka, Quinn Goddard, Julia Gorospe, Taylor Stocks, Najla Kanaan, Daniel Stuart, Tesa Ramsay, Kelly Robinson, Diane Charron-Bishop., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men. Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD., Competing Interests: Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Natasha Bollegala has consulted for Takeda, AbbVie, Janssen and Pfizer, and has received honoraria from Takeda, AbbVie and Janssen. Vivian Huang has received consulting fees from AbbVie, Amgen, BMS, Janssen, Sandoz, Roche and Takeda. She has received speaker fees from AbbVie, Amgen, BMS, Ferring, Janssen, Merck, Organon, Pfizer, Sandoz, Takeda and Viatris. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 September, 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. James Sousa has received an AbbVie IBD scholarship. Taylor Morganstein has received an AbbVie IBD scholarship and is a member of the Patient Adboard of AbbVie Canada. Ann Weber has received an AbbVie IBD scholarship. Cynthia Seow has served on advisory boards for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi and Bristol Myers Squibb. She has received speaker honoraria from Janssen, AbbVie, Takeda, Pfizer and Fresenius Kabi. She has received funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, The Canadian Institutes of Health Research, Calgary Health Trust and New South Wales Government Health. None: Joseph Windsor, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Tal Davis, Jake Weinstein, James Im, Nazanin Jannati, Rabia Khan, Priscilla Matthews, Tyrel Jones May, Sahar Tabatabavakili, Rohit Jogendran, Elias Hazan, Mira Browne, Saketh Meka, Sonya Vukovic, Manisha Jogendran, Malini Hu, Jessica Amankwah Osei, Grace Wang, Tasbeen Akhtar Sheekha, Ghaida Dahlwi, Quinn Goddard, Julia Gorospe, Cyanne Nisbett, Shira Gertsman, & Taylor Stocks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Mist is generated by ultrasonic cavitation of water (Fisher Biograde, pH 5.5-6.5) at room temperature (20-25 °C) in open air with nearly constant temperature (22-25 °C) but varying relative humidity (RH; 24-52%) over the course of many months. Water droplets in the mist are initially about 7 μm in diameter at about 50% RH. They are collected, and the concentration of hydrogen peroxide (H 2 O 2 ) is measured using commercial peroxide test strips and by bromothymol blue oxidation. The quantification method is based on the Fenton chemistry of dye degradation to determine the oxidation capacity of water samples that have been treated by ultrasonication. It is found that the hydrogen peroxide concentration varies nearly linearly with RH over the range studied, reaching a low of 2 parts per million (ppm) at 24% RH and a high of 6 ppm at 52% RH. Some possible public health implications concerning the transmission of respiratory viral infections are suggested for this threefold change in H 2 O 2 concentration with RH., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2021.)

Hydration sites are locations of interest to water and they can be used to classify the behavior of water around chemical motifs commonly found on the surface of proteins. Inhomogeneous fluid solvation theory (IFST) is a method for calculating hydration free-energy changes from molecular dynamics (MD) trajectories. In this paper, hydration sites are identified from MD simulations of 380 diverse protein structures. The hydration free energies of the hydration sites are calculated using IFST and distributions of these free-energy changes are analyzed. The results show that for some hydration sites near features conventionally regarded as attractive to water, such as hydrogen bond donors, the water molecules are actually relatively weakly bound and are easily displaced. We also construct plots of the spatial density of hydration sites with high, medium, and low hydration free-energy changes which represent weakly and strongly bound hydration sites. It is found that these plots show consistent features around common polar amino acids for all of the proteins studied.

Tertiary amines react rapidly and reversibly with arylketenes in acetonitrile forming observable zwitterions, and these undergo amine catalyzed dealkylation forming N,N-disubstituted amides. Reactions of N-methyldialkylamines show a strong preference for methyl group loss by displacement, as predicted by computational studies. Loss of ethyl groups in reactions with triethylamine also occur by displacement, but preferential loss of isopropyl groups in the phenylketene reaction with diisopropylethylamine evidently involves elimination. Quinuclidine rapidly forms long-lived zwitterions with arylketenes, providing a model for catalysis by cinchona and related alkaloids in stereoselective additions to ketenes.

Cyclobutenediones 5 disubstituted with HO (a), MeO (b), EtO (c), i-PrO (d), t-BuO (e), PhO (f), 4-MeOC6H4O (g), 4-O2NC6H4O (h), and 3,4-bridging OCH2CH2O (i) substituents upon laser flash photolysis gave the corresponding bisketenes 6a-i, as detected by their distinctive doublet IR absorptions between 2075 and 2106 and 2116 and 2140 cm-1. The reactivities in ring closure back to the cyclobutenediones were greatest for the group 6b-e, with the highest rate constant of 2.95 x 10(7) s-1 at 25 degrees C for 6e (RO = t-BuO) in isooctane, were less for 6a (RO = OH, k = 2.57 x 10(6) s-1 in CH3CN), while 6f-i were the least reactive, with the lowest rate constant of 3.8 x 10(4) s-1 in CH3CN for 6h (RO = 4-O2NC6H4O). The significantly reduced rate constants for 6f-i are attributed to diminution of the electron-donating ability of oxygen to the cyclobutenediones 5f-h by the ArO substituents compared to alkoxy groups and to angle strain in the bridged product cyclobutenedione 5i. The reactivities of the ArO-substituted bisketenes 6f-h in CH3CN varied by a factor of 50 and gave an excellent correlation of the observed rate constants log k with the sigma p constants of the aryl substituents. Computational studies at the B3LYP/6-31G(d) level of ring-closure barriers are consistent with the measured reactivities. Photolysis of squaric acid (5a) in solution provides a convenient preparation of deltic acid (7).

Hitherto unknown diamino-substituted bisketenes with both free (14) and tethered (16) amino substituents have been generated by using laser flash photolysis for ring opening of the corresponding cyclobutenediones. The time-resolved kinetics of ring closure of the amino bisketenes back to the cyclobutenediones were measured by IR or UV spectroscopy, and give first-order rate constants which vary by a factor of 7.5x10(4), and the bis(Me2N) bisketene 14 is the most reactive in ring closure that has been reported. Rate constants for ring closure of these and previously observed bisketenes vary by a factor of 10(13). The dialkylamino bisketenes 16 (R=Me, n-Bu) with tethered substituents and restricted geometries are less reactive than the bis(Me2N) bisketene 14 by factors of 1700 and 540, respectively. Computational results obtained with DFT methods suggest angle strain in the tethered cyclobutenediones 15 inhibits facile cyclization of bisketenes 16.

Morphology of the lymph nodes was examined in six bottlenose dolphins (Tursiops truncatus) and three striped dolphins (Stenella coeruleoalba) from the Adriatic Sea. All animals had been found dead in nature. One group of the nodes was taken from the tracheal branching area and was marked as bifurcational lymph node, and the other group was taken from the mesenteric root and was marked as mesenteric lymph node. Microscopic analysis showed that the lymph nodes in both dolphin species were surrounded by a connective tissue capsule comprising smooth muscle cells. The parenchyma of the mesenteric and bifurcational lymph nodes in bottlenose dolphin was divided into the peripherally situated cortex with the lymphatic nodules and diffuse lymphatic tissue, and the centrally situated medulla structured of the medullary cords separated by the medullary sinuses. These lymph nodes structurally correspond to the lymph nodes in the majority of terrestrial mammals. The mesenteric lymph node of striped dolphin also had a peripherally situated cortex and a centrally positioned medulla as the majority of terrestrial mammals. In the bifurcational lymph nodes of striped dolphin, there was a central dense lymphatic tissue with the lymphatic nodules and a peripheral less dense lymphatic tissue structured of the cell cords and sinuses. The bifurcational lymph node in striped dolphin resembled porcine lymph nodes and belonged to the inverse lymph nodes.