Calcite-Assisted Localization and Kinetics (CLocK) Microscopy.

Localization-based super-resolution imaging techniques have improved the spatial resolution of optical microscopy well below the diffraction limit, yet encoding additional information into super-resolved images, such as anisotropy and orientation, remains a challenge. Here we introduce calcite-assisted localization and kinetics (CLocK) microscopy, a multiparameter super-resolution imaging technique easily integrated into any existing optical microscope setup at low cost and with straightforward analysis. By placing a rotating calcite crystal in the infinity space of an optical microscope, CLocK microscopy provides immediate polarization and orientation information while maintaining the ability to localize an emitter/scatterer with <10 nm resolution.

Impact of the COVID-19 Pandemic on the Wellbeing of International Oncology and Hematology Fellows at the Princess Margaret Cancer Center (PMCC).

Background: The COVID-19 pandemic has led to significant disruptions across all levels of medical training. International fellows in subspecialty training programs are essential members of the frontline physician workforce, but may face additional and unique challenges as a result of being away from their home country. In this study, we aimed to understand the impact of the COVID-19 pandemic on the wellbeing of international fellows in the Hematology and/or Oncology fellowship program at the PMCC.

Knowledge, attitude, and practice of ophthalmic manifestations in COVID-19 patients at a tertiary care center.

Purpose: Since the start of the COVID-19 pandemic, various manifestations have been reported, including ophthalmic symptoms, especially with the different mutations and variants that have occurred over the last few years. In view of this, our study was conducted to gauge the knowledge, attitude, and practices of patients toward the ophthalmic manifestations of COVID-19.

Methods: This was a hospital-based, cross-sectional, observational study.

Clinical Profile and Molecular Genetic Analysis of Prader - Willi Syndrome: A Single Center Experience.

Aim: The prevalence of childhood and adolescent obesity is increasing worldwide as well as in India. Prader--Willi syndrome (PWS) is one of the most common causes of syndromic obesity with varied clinical manifestations across different lifespan. Herewith, we describe clinical and molecular characteristics of eight PWS who were diagnosed in an obesity clinic of tertiary care hospital.

The potential of Beta variant containing COVID booster vaccines for chasing Omicron in 2022.

Currently approved COVID vaccines are designed using the spike antigen derived from the ancestral strain, but health authorities are recommending changes to the vaccine strain to combat emerging variants. The goal is to ensure that next generation vaccines can tackle multiple variants of concern including the most prevalent variant for the coming season. We here discuss recent preclinical and clinical data on COVID vaccine antigens that are potential candidates for an updated vaccine.

Fabricating a Low-Cost, Microscopy-Compatible Mechanical Testing Device.

Most commercially-available mechanical testing devices are bulky, expensive, and unable to evaluate changes in sample microstructure under load. This leaves a crucial gap in understanding between material structure and bulk mechanical properties. Our objective was to fabricate a mechanical testing device small enough to fit in most upright or inverted microscopy stages and able to position samples to allow for simultaneous mechanical and microstructural characterization.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis).

A de novo matrix for macroscopic living materials from bacteria.

Engineered living materials (ELMs) embed living cells in a biopolymer matrix to create materials with tailored functions. While bottom-up assembly of macroscopic ELMs with a de novo matrix would offer the greatest control over material properties, we lack the ability to genetically encode a protein matrix that leads to collective self-organization. Here we report growth of ELMs from Caulobacter crescentus cells that display and secrete a self-interacting protein.

Circular economy priorities for photovoltaics in the energy transition.

Among the many ambitious decarbonization goals globally, the US intends grid decarbonization by 2035, requiring 1 TW of installed photovoltaics (PV), up from ~110 GW in 2021. This unprecedented global scale-up will stress existing PV supply chains with increased material and energy demands. By 2050, 1.

A small animal model of chronic hepatitis E infection using immunocompromised rats.

Background & Aims: HEV variants such as swine genotypes within species (HEV-A) and rat HEV (; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised rat model of chronic hepatitis E infection.

The Pharmacist's Role in Managing COVID-19 in Chronic Kidney Disease Patients: A Review of Existing Strategies and Future Implications.

The global burden of the COVID-19 pandemic has not only disrupted healthcare delivery but has also compromised patients' access to healthcare on account of the scarcity of medications and trained healthcare professionals. COVID-19 has been particularly challenging for patient subpopulations constituting immunocompromised individuals, geriatric patients, and those afflicted by chronic ailments. Reports indicate that diminished kidney function in chronic kidney disease (CKD) renders patients highly susceptible to complications during COVID-19 treatment.

Structures of lactaldehyde reductase, FucO, link enzyme activity to hydrogen bond networks and conformational dynamics.

A group-III iron containing 1,2-propanediol oxidoreductase, FucO, (also known as lactaldehyde reductase) from Escherichia coli was examined regarding its structure-dynamics-function relationships in the catalysis of the NADH-dependent reduction of (2S)-lactaldehyde. Crystal structures of FucO variants in the presence or absence of cofactors have been determined, illustrating large domain movements between the apo and holo enzyme structures. Different structures of FucO variants co-crystallized with NAD or NADH together with substrate further suggest dynamic properties of the nicotinamide moiety of the coenzyme that are important for the reaction mechanism.

Targeting the FGFR Pathway in Urothelial Carcinoma: the Future Is Now.

As we come to better understand cancer genomics, we are increasingly shifting towards precision medicine. FGFR has been elucidated as one of the oncogenic driver pathways in urothelial carcinoma, leading to exciting targeted drug development. Although many agents are being investigated, erdafitinib is the only FGFR inhibitor currently approved by the FDA for treating platinum-refractory metastatic urothelial carcinoma harboring susceptible FGFR2/3 alterations, with seemingly higher response rates than second-line chemotherapy or immunotherapy.

A Framework for the Systematic Selection of Biosensor Chassis for Environmental Synthetic Biology.

Microbial biosensors sense and report exposures to stimuli, thereby facilitating our understanding of environmental processes. Successful design and deployment of biosensors hinge on the persistence of the microbial host of the genetic circuit, termed the chassis. However, model chassis organisms may persist poorly in environmental conditions.

Improving Drug Delivery While Tailoring Prodrug Activation to Modulate and by Optimization of (Carbonyl)oxyalkyl Linker-Based Prodrugs of Atazanavir.

Structure-property relationships associated with a series of (carbonyl)oxyalkyl amino acid ester prodrugs of the marketed HIV-1 protease inhibitor atazanavir (), designed to enhance the systemic drug delivery, were examined. Compared to previously reported prodrugs, optimized candidates delivered significantly enhanced plasma exposure and trough concentration ( at 24 h) of in rats while revealing differentiated PK paradigms based on the kinetics of prodrug activation and drug release. Prodrugs incorporating primary amine-containing amino acid promoieties offered the benefit of rapid bioactivation that translated into low circulating levels of the prodrug while delivering a high value of .

Application of 3D Printing in Training Health Care Providers; the Development of Diverse Facial Overlays for Simulation-Based Medical Training.

The medical simulation manikins used by healthcare learners provide the training of numerous clinical skills but often lack diversity with respect to race, ethnicity, age, and sex. Having a diverse medical education environment is imperative for exposing learners to the diverse population of patients they may encounter when in practice. In this technical report, the development of diverse and cost-effective facial overlays produced using 3D scanning, 3D printing, and silicone to be used on top of the current medical manikins at Lakeridge Health Hospital (Oshawa, Ontario, Canada) is described.

A novel methylated cell-free DNA marker panel to monitor treatment response in metastatic prostate cancer.

This study examined circulating cell-free DNA (cfDNA) biomarkers associated with androgen treatment resistance in metastatic castration resistance prostate cancer (mCRPC). We designed a panel of nine candidate cfDNA methylation markers using droplet digital PCR (Methyl-ddPCR) and assessed methylation levels in sequentially collected cfDNA samples from patients with mCRPC. Increased cfDNA methylation in eight out of nine markers during androgen-targeted treatment correlated with a faster time to clinical progression.

Kinetochore Architecture Employs Diverse Linker Strategies Across Evolution.

The assembly of a functional kinetochore on centromeric chromatin is necessary to connect chromosomes to the mitotic spindle, ensuring accurate chromosome segregation. This connecting function of the kinetochore presents multiple internal and external structural challenges. A microtubule interacting outer kinetochore and centromeric chromatin interacting inner kinetochore effectively confront forces from the external spindle and centromere, respectively.

Contribution of low population immunity to the severe Omicron BA.2 outbreak in Hong Kong.

Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong's explosive Omicron BA.2 outbreak in early 2022 could be explained by low herd immunity.