Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS.

Reproducible definition and identification of cell types is essential to enable investigations into their biological function and to understand their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands.

High-throughput analysis of dendrite and axonal arbors reveals transcriptomic correlates of neuroanatomy.

Neuronal anatomy is central to the organization and function of brain cell types. However, anatomical variability within apparently homogeneous populations of cells can obscure such insights. Here, we report large-scale automation of neuronal morphology reconstruction and analysis on a dataset of 813 inhibitory neurons characterized using the Patch-seq method, which enables measurement of multiple properties from individual neurons, including local morphology and transcriptional signature.

Immunoglobulin A Nephropathy Presenting in Young Adults as Advanced Chronic Kidney Disease and Posttransplant Early Recurrence: A Case Series.

Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease, leading to chronic kidney disease. The disease is characterized by microscopic hematuria, gross episodic hematuria, hypertension, and subnephrotic proteinuria with or without renal function impairment. It affects individuals of all age groups, commonly seen in 10-40 years of age.

Implications of chronic moderate protein-deficiency malnutrition on doxorubicin pharmacokinetics and cardiotoxicity in early post-weaning stage.

Background: Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes.

Aims: In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition.

Digitally guided root removal and simultaneous implant placement: A case study.

Background: Encountering a retained root tip post-extraction and prior to implant placement is a possible clinical complication. There are numerous approaches for removing retained roots that may be traumatic or atraumatic. Regardless of the approach, careful treatment planning is important to minimize complications, reduce morbidity, and preserve bony structures.

Micronodular thymoma with lymphoid stroma: As benign as it sounds.

Micronodular thymoma (MNT) is a rare subtype of thymoma (reported incidence is approximately 1-5%). We report a case received as a core biopsy from the "right lung mass" of a 31-year-old female. CT scan showed an 8.

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.

Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS.

Reproducible definition and identification of cell types is essential to enable investigations into their biological function, and understanding their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands.

Spinal Rosai-Dorfman disease-a report of 2 cases and review of literature.

Introduction: Rosai-Dorfman Disease (RDD) is a rare benign histiocytic disease that infrequently affects the spine. We report two cases of spinal RDD and review the relevant literature. This report addresses the various diagnostic dilemmas related to the evaluation of Spinal RDD and its treatment.

Management of vertical bony defect using novel xenogeneic/allogeneic bone graft: A case report.

Background: Guided tissue regeneration (GTR) is a common treatment modality for correcting vertical or bony defects in furcations. Multiple materials are used in GTR with allografts and xenografts being the most widely used. Each material has distinctive properties affecting the regenerative potential.

Gonococcal microparticle vaccine in dissolving microneedles induced immunity and enhanced bacterial clearance in infected mice.

There is an alarming rise in the number of gonorrhea cases worldwide. Neisseria gonorrhoeae, the bacteria that causes gonorrhea infection, has gradually developed antimicrobial resistance over the years. To date, there is no licensed vaccine for gonorrhea.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types.

Predictive and robust gene selection for spatial transcriptomics.

A prominent trend in single-cell transcriptomics is providing spatial context alongside a characterization of each cell's molecular state. This typically requires targeting an a priori selection of genes, often covering less than 1% of the genome, and a key question is how to optimally determine the small gene panel. We address this challenge by introducing a flexible deep learning framework, PERSIST, to identify informative gene targets for spatial transcriptomics studies by leveraging reference scRNA-seq data.

Preclinical evaluation of a microparticle-based transdermal vaccine patch against metastatic breast cancer.

Breast cancer is the number one cause of cancer-related deaths among females. Current chemotherapy targets both tumor and normal cells, leading to pronounced side effects. Therefore, therapeutic vaccines acting against specific cancer cells would be the choice of treatment.

Assessment of In Vitro Immunostimulatory Activity of an Adjuvanted Whole-Cell Inactivated Microparticle Vaccine Formulation.

The emergence of drug-resistant gonorrhea infections worldwide combined with the lack of a vaccine is alarming. We prepared a novel microparticulate (MP) vaccine formulation using whole-cell inactivated as the vaccine antigen, with Alum and AddaVax™ as vaccine adjuvants. The adjuvanted vaccine MP formulation was assessed for in vitro immunostimulatory activity, autophagy, and antigen presentation ability.

Cell type matching in single-cell RNA-sequencing data using FR-Match.

Reference cell atlases powered by single cell and spatial transcriptomics technologies are becoming available to study healthy and diseased tissue at single cell resolution. One important use of these data resources is to compare cell types from new dataset with cell types in the reference atlases to evaluate their phenotypic similarities and differences, for example, for identifying novel cell types under disease conditions. For this purpose, rigorously-validated computational algorithms are needed to perform these cell type matching tasks that can compare datasets from different experiment platforms and sample types.

Upper Cervical Leiomyoma in an Adolescent Male.

Introduction: Leiomyomas are benign epithelial tumors with a female preponderance usually in the uterus, gastro-intestinal tract and skin. They are well-capsulated tumors with no mitotic activity and little pleomorphism. Primary leiomyoma in the upper cervical spine region is rare and the occurrence of these lesions in young immunocompetent males is extremely rare.

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia.

Aggressive Vertebral Hemangioma Causing Recurring Myelopathy -A Rare Case Report and Review of Literature.

Introduction: Vertebral hemangiomas although benign vascular lesions few of these may be ag-gressive causing osseous, extra-osseous and/or epidural expansions with recurrence rate as low as 3%. It should be considered as one of the important differentials while dealing with lytic lesions in the dorsal spine causing compressive myelopathy.

Case Report: A 16-year-old female came with an acute history of paraparesis with bladder in-volvement.

Gynecologic surgical skill acquisition through simulation with outcomes at the time of surgery: a systematic review and meta-analysis.

Objective: To evaluate the effect of simulation training vs traditional hands-on surgical instruction on learner operative skills and patient outcomes in gynecologic surgeries.

Data Sources: PubMed, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials from inception to January 12, 2021.