Training in translational research for graduate students at the University of Toronto

The Institute of Medical Science (IMS) was established as an institute within the School of Graduate Studies at the University of Toronto in 1968 to serve as a graduate unit for the Clinical Departments in the Faculty of Medicine. In this role,the IMS offers a doctoral stream program in medical science leading to the Master of Science and Doctor of Philosophy degrees. Translational research,as a means of moving new discovery to improvement in patient outcome,has become a central theme of graduate education in our Institute. To this end,we have developed a curriculum offering which is intended to provide all new students with a defined skill set relevant to Translational Research and at the same time,to provide students with flexible offerings which would enhance their specific research programs. The course,spread over two years,will have three separate components:(1) there will be lectures focusing on research fundamentals and the basics of translational research; (2) there will be student presentations to hone presentation skills and get valuable feedback from fellow students and faculty mentors; (3) there will be elective modules,where students can select from a number of course offerings in order to round out training. These modules include subjects such as the fundamentals of clinical trials,the basics of qualitative research,an approach to the role of proteomics and genomics in research and the business of science. As part of this modular program,we have created a program 'clinical exposure for non-clinicians' with the hope that graduate students will be able to gain some understanding of the clinical relevance of their research activities. Over time,these modular offerings will be expanded based on a needs assessment from our students. The presentation will describe the IMS and its mission and will overview the structure and content of this course offering.

Resident immune responses to spinal cord injury:role of astrocytes and microglia

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

Investigation of bioactivity and biodegradability of Mg-bioceramic implants:An in vitro study for biomedical applications

In this study,Mg-based composites,by the addition of ZnO,Ca_(2)ZnSi_(2)O_(7),Ca_(2)MgSi_(2)O_(7),and CaSiO_(3)as bioactive agents,were fabricated using friction stir processing.The microstructure and in vitro assessment of bioactivity,biodegradation rate,and corrosion behavior of the resultant composites were investigated in simulated body fluid(SBF).The results showed that during the immersion of composites in SBF for 28 d,due to the release of Ca^(2+)and PO_(4)^(3-)ions,hydroxyapatite(HA)crystals with cauliflower shaped morphology were deposited on the surface of composites,confirming good bioactivity of composites.In addition,due to the uniform distribution of bioceramic powders throughout Mg matrix,grain refinement of the Mg matrix,and uniform redistribution of secondary phase particles,the polarization resistance increased,and the biodegradation rate of composites significantly reduced compared to monolithic Mg matrix.The polarization corrosion resistance of Mg-ZnO increased from 0.216 to 2.499 kΩ/cm^(2)compared to monolithic Mg alloy.Additionally,Mg-ZnO composite with the weight loss of 0.0217 g after 28 d immersion showed lower weight loss compared to other samples with increasing immersion time.Moreover,Mg-ZnO composite with the biodegradation rate of 37.71 mm/a exhibited lower biodegradation rate compared to other samples with increasing immersion time.

Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 years.As proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple seasons.Such differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular damage.The present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged darkness.As chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our hypotheses.We predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to annuals.Chlorophyll levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using spectrophotometry.While chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as predicted.When plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,chlorophyll resynthesis rates did not consistently differ between annuals and perennials,though they tended to be higher in the latter,as predicted.Overall,our study illuminates that evolutionary transitions between life history strategies in plants have been accompanied by physiological modifications to chlorophyll dynamics that permit perennial species to better maintain chlorophyll levels—and thus photosynthetic energy acquisition-in the face of exogenous stressors,which likely underlies their capacity to survive for multiple growing seasons.Future studies should explore whether other key biomolecules(e.g.,proteins,DNA)are also better maintained in perennial plants,especially in the face of exogenous stress.

Effect of Artificial Electric Field Surface by Wave-Driven Triboelectricity on Anti-Bioadhesion for Riser Protection

Biofouling has been a persistent problem in marine riser system, resulting in energy waste and equipment damage. Inthis study, a kind of water wave-driven contact-mode flexible triboelectric nanogeneration has been prepared byusing graphene-doped PDMS as dielectric friction material. When the graphene content is 2%, the average outputvoltage can reach 46 V under the contact frequency 10 Hz. The flexible triboelectric nanogeneration encapsulationmodule is impinged by water waves to generate alternating microelectric field on the riser surface and destroy theadhesion conditions of microorganisms during the biofilm stage. In the biofouling experiments at different stages, thebiofouling area of the platymonas subcordiformis has been reduced by 53%, 62% and 61%. It provides a new ideafor effective treatment of biofouling of mussels, oysters and barnacles attached to risers.

Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

Selective Hydrodeoxygenation of Lignin-Derived Vanillin via Hetero-Structured High-Entropy Alloy/Oxide Catalysts

The chemoselective hydrodeoxygenation of natural lignocellulosic materials plays a crucial role in converting biomass into value-added chemicals.Yet their complex molecular structures often require multiple active sites synergy for effective activation and achieving high chemoselectivity.Herein,it is reported that a high-entropy alloy(HEA)on high-entropy oxide(HEO)hetero-structured catalyst for highly active,chemoselective,and robust vanillin hydrodeoxygenation.The heterogenous HEA/HEO catalysts were prepared by thermal reduction of senary HEOs(NiZnCuFeAlZrO_(x)),where exsolvable metals(e.g.,Ni,Zn,Cu)in situ emerged and formed randomly dispersed HEA nanoparticles anchoring on the HEO matrix.This catalyst exhibits excellent catalytic performance:100%conversion of vanillin and 95%selectivity toward high-value 2-methyl-4 methoxy phenol at low temperature of 120℃,which were attributed to the synergistic effect among HEO matrix(with abundant oxygen vacancies),anchored HEA nanoparticles(having excellent hydrogenolysis capability),and their intimate hetero-interfaces(showing strong electron transferring effect).Therefore,our work reported the successful construction of HEA/HEO heterogeneous catalysts and their superior multifunctionality in biomass conversion,which could shed light on catalyst design for many important reactions that are complex and require multifunctional active sites.

Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions:a systematic review and meta-analysis

Background Globally,populations afflicted by armed conflict are known to have high rates of mental health disorders.Aims This meta-analysis aims to estimate the prevalence of post-traumatic stress disorder(PTSD)and depressive symptoms among civilians residing in armed conflictaffected regions.Methods This meta-analysis was conducted in accordance with the Preferred Reporting Items forSystematic Reviews and Meta-Analyses.A literature search employing MEDLINE(R),Embase Classic+Embase,APA PsyclNFO,Ovid Healthstar,Journal@Ovid Full Text,Cochrane,PTSDpubs and CINAHL was conducted from inception until 19 March 2024 to identify relevant studies.Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies,and a Comprehensive Meta-Analysiswas usedto conduct the statistical analysis.Results The search yielded 38595 articles,of which 57 were considered eligible for inclusion.The included studies comprised data from 64596 participants.We estimated a prevalence of 23.70%(95%CI 19.50%to28.40%)forPTSD symptomsand 25.60%(95%Cl 20.70%to 31.10%)for depressive features among war-afflicted civilians.The subgroup analysis based on time since the war and the country's economic status revealed the highest prevalence for both PTSD and depressive symptoms was present during the years of war and in low/middle-incomecountries.Conclusions The results of this study provide conclusive evidence of the detrimental impacts of armed conflict on mental health outcomes.Hence,it is crucial to emphasise the significance of both physical and mental health in the aftermath of war and take appropriate humanistic measures to overcome challenges in the management of psychiatric illnesses.

Effects of fracture evolution and non-Darcy flow on the thermal performance of enhanced geothermal system in 3D complex fractured rock

In fractured geothermal reservoirs,the fracture networks and internal fluid flow behaviors can significantly impact the thermal performance.In this study,we proposed a non-Darcy rough discrete fracture network(NR-DFN)model that can simultaneously consider the fracture evolution and non-Darcy flow dynamics in studying the thermo-hydro-mechanical(THM)coupling processes for heat extraction in geothermal reservoir.We further employed the model on the Habanero enhanced geothermal systems(EGS)project located in Australia.First,our findings illustrate a clear spatial-temporal variation in the thermal stress and pressure perturbations,as well as uneven spatial distribution of shear failure in 3D fracture networks.Activated shear failure is mainly concentrated in the first fracture cluster.Secondly,channeling flow have also been observed in DFNs during heat extraction and are further intensified by the expansion of fractures driven by thermal stresses.Moreover,the combined effect of non-Darcy flow and fracture evolution triggers a rapid decline in the resulting heat rate and temperature.The NR-DFN model framework and the Habanero EGS's results illustrate the importance of both fracture evolution and non-Darcy flow on the efficiency of EGS production and have the potential to promote the development of more sustainable and efficient EGS operations for stakeholders.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces

Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.

Disorders of potassium homeostasis after kidney transplantation

Disturbances of potassium balance are often encountered when managing kidney transplant recipients(KTR).Both hyperkalemia and hypokalemia may present either as medical emergencies or chronic outpatient abnormalities.Despite the high incidence of hyperkalemia and its potential life-threatening implications,consensus on its management in KTR is lacking.Hypokalemia in KTR is also well-described,although it is given less attention by clinicians compared to hyper-kalemia.This article discusses the etiology,pathophysiology and management of both types of potassium disorders in KTR.Once any emergent situation has been corrected,treatment approaches include correcting insulin deficiency if present,adjusting non-immunosuppressive and immunosuppressive medications,elimi-nating or supplementing potassium as needed,and dietary counselling.Although commonly of multifactorial etiology,ascertaining the specific cause in a particular patient will help guide successful management.Monitoring KTR through regular laboratory testing is essential to detect serious disturbances in potassium balance since patients are often asymptomatic.

The FRB-searching Pipeline of the Tianlai Cylinder Pathfinder Array

This paper presents the design,calibration,and survey strategy of the Fast Radio Burst(FRB)digital backend and its real-time data processing pipeline employed in the Tianlai Cylinder Pathfinder Array.The array,consisting of three parallel cylindrical reflectors and equipped with 96 dual-polarization feeds,is a radio interferometer array designed for conducting drift scans of the northern celestial semi-sphere.The FRB digital backend enables the formation of 96 digital beams,effectively covering an area of approximately 40 square degrees with the 3 dB beam.Our pipeline demonstrates the capability to conduct an automatic search of FRBs,detecting at quasi-realtime and classifying FRB candidates automatically.The current FRB searching pipeline has an overall recall rate of88%.During the commissioning phase,we successfully detected signals emitted by four well-known pulsars:PSR B0329+54,B2021+51,B0823+26,and B2020+28.We report the first discovery of an FRB by our array,designated as FRB 20220414A.We also investigate the optimal arrangement for the digitally formed beams to achieve maximum detection rate by numerical simulation.

Beware the Demon of Love Jihad! The Gendered and Sexual Abjectification of Muslim Masculinities by Hindu Nationalists on Twitter

In this paper,I examine the Twitter accounts of right-wing extremist groups(RWEGs)in India,arguing that the abjectification of Muslim masculinities is central to the narratives of Hindu supremacist groups.The abjectification process on Twitter serves as a rhetorical device to:a)criticize and problematize Muslim masculinities;b)idealize and glorify Hindu and white masculinities;c)promote Hindu and white masculine nationalist projects;and d)unify Hindu supremacists against Muslim others.By analyzing the gender ideologies expressed implicitly or explicitly on the Twitter accounts of RWEGs,and using the“Love Jihad”conspiracy case as a focal point,I demonstrate how the abjectification of Muslim masculinities is constructed in opposition to the idealized Hindu masculinities.This study highlights the intersection of gender and nationalism in the digital discourse of Hindu supremacist groups,offering insights into the mechanisms through which social media platforms are used to reinforce and propagate Islamophobic ideologies.

Layoff Factors Analysis:Evidence from 2021 China General Social Survey

This paper analyzes factors that explain company layoffs,given the individual layoff data in 2021,China.Using the Probit regression model,we find that gender inequality exists in layoffs,an employee’s work experience becomes less critical in the company’s layoff decisions,and how an employee’s health reasons affect work affects its probability of being laid off.Since we consider a significant endogeneity issue with education,using parents’education as an instrumental variable suggests that political status cannot be a significant advantage for employees to lower the chance of being laid off.Moreover,evidence implies that policymakers encouraging the pursuit of higher educational degrees can foster stability in the labor market.

Practical approach to linear endoscopic ultrasound examination of the gallbladder

The gallbladder(GB)is a susceptible organ,prone to various pathologies that can be identified using different imaging techniques.Transabdominal ultrasound(TUS)is typically the initial diagnostic method due to its numerous well-established advantages.However,in cases of uncertainty or when a definitive diagnosis cannot be established,computed tomography(CT)or magnetic resonance imaging may be employed to provide more detailed information.Nevertheless,CT scans may sometimes offer inadequate spatial resolution,which can limit the differentiation of GB lesions,particularly when smaller yet clinically relevant abnormalities are involved.Conversely,endoscopic ultrasound(EUS)provides higher frequency compared to TUS,superior spatial resolution,and the option for contrast-enhanced harmonic imaging,enabling a more comprehensive examination.Thus,EUS can serve as a supplementary tool when conventional imaging methods are insufficient.This review will describe the standard EUS examination of the GB,focusing on its endosonographic characteristics in various GB path-ologies.

Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029

Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.