Conventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids.

Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.

Legal Recreational Cannabis Sales and Opioid-Related Mortality in the 5 Years Following Cannabis Legalization in Canada: A Granger Causality Analysis.

Objective: Little is known about the population-level impact of recreational cannabis legalization on trends in opioid-related mortality. Increased access to cannabis due to legalization has been hypothesized to reduce opioid-related deaths because of the potential opioid-sparing effects of cannabis. The objective of this study was to examine the relations between national retail sales of recreational (non-medical) cannabis and opioid overdose deaths in the 5 years following legalization in Canada.

Evaluating the impact of Canadian cannabis legalization on cannabis use outcomes in emerging adults: Comparisons to a US control sample via a natural experiment.

Background: Recreational cannabis legalization marked a significant policy shift in Canada, but has been difficult to evaluate because of the absence of a control group. Although it is unfeasible to evaluate legalization using a randomized controlled trial design, sophisticated statistical techniques can employ quasi-experimental designs using natural experiments. This study evaluates the impact of cannabis legalization in a longitudinal cohort of Canadian emerging adults by comparing changes in cannabis use frequency and related consequences over time to changes in a similar cohort in a United States jurisdiction where no policy change took place.

Enzymatic epimerization of monoterpene indole alkaloids in Kratom.

Monoterpene indole alkaloids (MIAs) are a large, structurally diverse class of bioactive natural products. These compounds are biosynthetically derived from a stereoselective Pictet-Spengler condensation that generates a tetrahydro-β-carboline scaffold characterized by a 3 stereocenter. However, a subset of MIAs contain a non-canonical 3 stereocenter.

High-Valent Cobalt-Difluoride in Oxidative Fluorination of Saturated Hydrocarbons.

The heme paradigm where Fe=O acts as the C-H oxidant and Fe-OH rebounds with the formed carbon-centered radical guides the design of the prototypical synthetic hydroxylation catalyst. We are exploring methods to evolve beyond the metal-oxo oxidant and hydroxide rebound, to incorporate a wider array of functional group. We have demonstrated the application of Co(OTf) (10 mol% catalyst; OTf=trimfluoromethanesulfonate) in combination with polydentate N-donor ligands (e.

Prevalence of TB-related symptoms and self-reported disability among adult TB survivors.

Background: Growing evidence suggests that post-TB-related morbidity occurs often among TB survivors, but there is limited epidemiological data on the burden of symptoms and disability after successful completion of treatment. We evaluated the prevalence of TB-related symptoms, self-reported disability, and factors associated with disability among adult TB survivors who recently completed treatment in Uganda.

Methods: Between January 2022 and October 2023, we conducted a study of adults who completed treatment for drug-susceptible TB in Kampala, Uganda.

KT-253, A Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy Than MDM2 Small Molecule Inhibitors.

Murine double minute 2 (MDM2) is an E3 ligase that inhibits the tumor suppressor protein p53. Clinical trials employing small-molecule MDM2/p53 interaction inhibitors (SMIs) have demonstrated limited activity, underscoring an unmet need for a better approach to target MDM2. KT 253 is a highly potent and selective heterobifunctional degrader that overcomes the MDM2 feedback loop seen with SMIs and induces apoptosis in a range of hematologic and solid tumor lines.

Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial.

Purpose: The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria.

Fluorescence imaging of individual ions and molecules in pressurized noble gases for barium tagging in Xe.

The imaging of individual Ba ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana nature of the neutrino. In this paper we demonstrate selective single Ba ion imaging inside a high-pressure xenon gas environment. Ba ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1 × 1 cm located inside 10 bar of xenon gas.

A decade of conservation agriculture in intensive cereal systems: Transitioning to soil resilience and stable yield trends in a climate crisis.

Climate change jeopardizes the food security gains achieved in India since the Green Revolution, especially by impacting the productivity of the rice-wheat system in the Indo-Gangetic Plain, a region that serves as the 'breadbasket' of South Asia. In this study, we characterized the potential of long-term conservation agriculture (CA) based management practices (i.e.

Efficient small fragment sequencing of human, cattle, and bison miRNA, small RNA, or csRNA-seq libraries using AVITI.

Background: Next-Generation Sequencing (NGS) catalyzed breakthroughs across various scientific domains. Illumina's sequencing by synthesis method has long been central to NGS, but new sequencing methods like Element Biosciences' AVITI technology are emerging. AVITI is reported to offer improved signal-to-noise ratios and cost reductions.

Bedside Utilization of Intestinal Pathology in Preterm Infants with Surgical Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with multiorgan dysfunction, multiple systemic morbidities, and mortality. The resected bowel commonly shows evidence of coagulative necrosis, inflammation, interstitial hemorrhages, and reparative changes on the pathology examination. The severity of these pathological abnormalities may correlate with the disease's severity and pace of progression and may assist in the prediction of clinical outcomes.

A recurrent neural network and parallel hidden Markov model algorithm to segment and detect heart murmurs in phonocardiograms.

The detection of heart disease using a stethoscope requires significant skill and time, making it expensive and impractical for widespread screening in low-resource environments. Machine learning analysis of heart sound recordings can improve upon the accessibility and accuracy of diagnoses, but existing approaches require further validation on larger and more representative clinical datasets. For many previous algorithms, segmenting the signal into its individual sound components is a key first step.

Transitions to crop residue burning have multiple antecedents in Eastern India.

Unlabelled: Far removed from the agricultural fire "hotspots" of Northwestern India, rice residue burning is on the rise in Eastern India with implications for regional air quality and agricultural sustainability. The underlying drivers contributing to the increase in burning have been linked to the adoption of mechanized (combine) harvesting but, in general, are inadequately understood. We hypothesize that the adoption of burning as a management practice results from a set of socio-technical interactions rather than emerging from a single factor.

Simultaneous use of alcohol, cannabis, and energy drinks predicts increased daily alcohol consumption and alcohol consequences.

Simultaneous alcohol and cannabis (SAM) use and alcohol mixed with energy drinks (AmED) days are associated with heavier drinking and negative consequences compared to alcohol-only days. However, it remains unclear if SAM and AmED days differ from one another in terms of consumption and negative consequences. It also remains unclear how often days characterized by both SAM + AmED occur and if these days are associated with incremental risk for heavier drinking and negative consequences.

Effect of conservation agriculture on soil fungal diversity in rice-wheat-greengram cropping system in eastern Indo-Gangetic plains of South Asia.

Introduction: Conservation agriculture (CA) is emerging as an eco-friendly and sustainable approach to food production in South Asia. CA, characterized by reduced tillage, soil surface cover through retaining crop residue or raising cover crops, and crop diversification, enhances crop production and soil fertility. Fungal communities in the soil play a crucial role in nutrient recycling, crop growth, and agro-ecosystem stability, particularly in agricultural crop fields.

A Structural and Functional Mimic of P680.

One or multiple chlorophyll a molecules are employed in the reaction center of photosystem II's main electron donor (defined as P680). We have a poor understanding of how the reaction center facilitates water oxidation in photosystem II and the roles that mono- and/or multimeric chlorophyll groups play when P680 oxidizes a neighboring tyrosine in order to drive water oxidation at the oxygen evolving complex. We have prepared a dimeric Mg-porphyrin complex [Mg(BTPP)] (1, H-BTPP=1,2-bis-(10,15,20-triphenylporphyrin-5-yl)-benzene) as a structural and functional mimic of the dimeric core of P680.

Climate change impacts on Aotearoa New Zealand: a horizon scan approach.

Many of the implications of climate change for Aotearoa (New Zealand) remain unclear. To identify so-far unseen or understudied threats and opportunities related to climate change we applied a horizon-scanning process. First, we collated 171 threats and opportunities across our diverse fields of research.

Late subsequent leukemia after childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

Background: Subsequent short-latency leukemias are well-described among survivors of childhood cancer. However, late (5-14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied.

Internalizing symptoms, negative urgency, and coping motives: Potential pathways to alcohol consequences.

Objective: Building upon prior research, the present study tested coping motives as a mediator of relations between both negative urgency and internalizing symptoms (depression, anxiety, and stress), and alcohol-related consequences using longitudinal data. We also tested negative urgency as a moderator of prospective relations between specific internalizing symptoms and alcohol-related consequences.

Method: The study utilized data from a longitudinal study of young adults ( = 448; = 22.