MerQuaCo: a computational tool for quality control in image-based spatial transcriptomics.

Image-based spatial transcriptomics platforms are powerful tools often used to identify cell populations and describe gene expression in intact tissue. Spatial experiments return large, high-dimension datasets and several open-source software packages are available to facilitate analysis and visualization. Spatial results are typically imperfect.

Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits.

We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies.

Influence of Ethanol Grade on Captures of Ambrosia Beetles in Tree Fruit Orchards, Ornamental Nurseries, and Lumber Yards.

Ambrosia beetles, particularly invasive species within the tribe Xyleborini, such as (Blandford, 1894), pose significant threats to various ecosystems and managed habitats worldwide. Monitoring these invaders is vital for effective pest management, typically accomplished through ethanol-baited traps. We compared trap efficacy using denatured ethanol versus absolute ethanol in orchards, tree nurseries, and lumber yards in northeastern Ohio, USA, finding that absolute ethanol traps captured significantly more .

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.

Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial.

Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis.

Long-Term Efficacy and Safety of Damoctocog Alfa Pegol Prophylaxis in Patients with Haemophilia A Aged 12-<18 Years at Enrolment into PROTECT VIII.

Introduction: The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12-<18 years at enrolment.

Method: PROTECT VIII was a multicentre, open-label study of previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%).

Type and duration of water stress influence host selection and colonization by exotic ambrosia beetles (Coleoptera: Curculionidae).

Fungus-farming ambrosia beetles in the tribe Xyleborini tunnel into plants and trees to establish chambers for cultivating their nutritional fungal mutualists and rearing offspring. Some xyleborine ambrosia beetles preferentially infest and perform better in living but weakened trees. Flood stress predisposes horticultural tree crops to infestation, but the impact of drought stress has not been well studied.

Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge.

Cell-type specific molecular signatures of aging revealed in a brain-wide transcriptomic cell-type atlas.

Biological aging can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function. Aging is a complex and dynamic process which influences distinct cell types in a myriad of ways. The cellular architecture of the mammalian brain is heterogeneous and diverse, making it challenging to identify precise areas and cell types of the brain that are more susceptible to aging than others.

Interim analyses of the multinational real-world prospective cohort HEM-POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A.

Objectives: To assess effectiveness and safety of damoctocog alfa pegol in interim analyses of the ongoing real-world hemophilia A HEM-POWR study.

Methods: HEM-POWR (NCT03932201) is a multinational Phase 4 prospective observational study. The primary objective was annualized bleeding rate (ABR) in previously treated patients (PTPs) with hemophilia A.

Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species.

Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes.

Differential encoding of temporal context and expectation under representational drift across hierarchically connected areas.

The classic view that neural populations in sensory cortices preferentially encode responses to incoming stimuli has been strongly challenged by recent experimental studies. Despite the fact that a large fraction of variance of visual responses in rodents can be attributed to behavioral state and movements, trial-history, and salience, the effects of contextual modulations and expectations on sensory-evoked responses in visual and association areas remain elusive. Here, we present a comprehensive experimental and theoretical study showing that hierarchically connected visual and association areas differentially encode the temporal context and expectation of naturalistic visual stimuli, consistent with the theory of hierarchical predictive coding.

Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: analysis from the PROTECT VIII study.

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities to transform the care of people with hemophilia.

Background: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A.

Background: Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously.

Methods: We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×10 vector genomes of valoctocogene roxaparvovec per kilogram of body weight.

A laparoscopic approach to address massive splenomegaly, symptomatic cholelithiasis, and a planned postoperative pregnancy: A case report.

We report long-term follow-up of a patient who underwent a tailored laparoscopic procedure for symptomatic cholelithiasis, massive splenomegaly, and a planned pregnancy. There were no complications, and the patient remained symptom-free at the 5-year follow-up. We supplemented our case report with national surgical data demonstrating the safety of laparoscopic splenectomy.

Attraction of Myzus persicae (Hemiptera: Aphididae) to Volatiles Emitted From the Entomopathogenic Fungus Beauveria bassiana.

Beauveria bassiana (Balsamo) Vuillemin infects a wide variety of insects, including the green peach aphid, Myzus persicae (Sulzer). Volatiles emitted from B. bassiana can act as semiochemical attractants or repellents, with most responses reported to date resulting in insects avoiding B.