A rare HSC-derived megakaryocyte progenitor accumulates via enhanced survival and contributes to exacerbated thrombopoiesis upon aging.

Distinct routes of cellular production from hematopoietic stem cells (HSCs) have defined our current view of hematopoiesis. Recently, we challenged classical views of platelet generation, demonstrating that megakaryocyte progenitors (MkPs), and ultimately platelets, can be specified via an alternate and additive route of HSC-direct specification specifically during aging. This "shortcut" pathway generates hyperactive platelets likely to contribute to age-related platelet-mediated morbidities.

Pregnancy Reduces Il33+ Hybrid Progenitor Accumulation in the Aged Mammary Gland.

Aging increases breast cancer risk while an early first pregnancy reduces a woman's life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary epithelial cells (MECs), but the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also inducing a differentiated cell state.

SIMS: A deep-learning label transfer tool for single-cell RNA sequencing analysis.

Cell atlases serve as vital references for automating cell labeling in new samples, yet existing classification algorithms struggle with accuracy. Here we introduce SIMS (scalable, interpretable machine learning for single cell), a low-code data-efficient pipeline for single-cell RNA classification. We benchmark SIMS against datasets from different tissues and species.

An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis.

Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production.

Recent Secular Trends of Body Mass Index in Individuals With Bipolar Disorders and in the General Population.

Objective: The aims of this study were to investigate secular trends and distribution of body mass index (BMI) among individuals with bipolar disorders and the general population between 2008 and 2019.

Methods: Data were from the Swedish National Quality Register for Bipolar Disorder, where 24,423 adults with bipolar disorders were identified, and from the national Swedish Living Conditions Surveys, where 77,485 adults from the general population were identified. Quantile regression was used to compare the 15th, 50th, and 85th percentiles of BMI across age and study years.

Unraveling Neuronal Identities Using SIMS: A Deep Learning Label Transfer Tool for Single-Cell RNA Sequencing Analysis.

Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets.

Diagnostic yield for video capsule endoscopy in gastrointestinal graft- versus -host disease: a systematic review and metaanalysis.

Background: The gastrointestinal tract is the second most involved organ for graft-versus-host disease where involvement of the small intestine is present in 50% of the cases. Therefore, the use of a non-invasive investigation i.e.

Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders.

The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included.

What Is the Role of the Environment in the Emergence of Novel Antibiotic Resistance Genes? A Modeling Approach.

It is generally accepted that intervention strategies to curb antibiotic resistance cannot solely focus on human and veterinary medicine but must also consider environmental settings. While the environment clearly has a role in transmission of resistant bacteria, its role in the emergence of novel antibiotic resistance genes (ARGs) is less clear. It has been suggested that the environment constitutes an enormous recruitment ground for ARGs to pathogens, but its extent is practically unknown.

Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response.

Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson's disease (PD) patients. However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons.

Diversity in immunogenomics: the value and the challenge.

Immunogenomics studies have been largely limited to individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations. Inclusion of a greater diversity of individuals in immunogenomics studies will substantially enhance our understanding of human immunology.

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing.

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127 ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs.

CAR T Cell Therapy Progress and Challenges for Solid Tumors.

The past two decades have marked the beginning of an unprecedented success story for cancer therapy through redirecting antitumor immunity [1]. While the mechanisms that control the initial and ongoing immune responses against tumors remain a strong research focus, the clinical development of technologies that engage the immune system to target and kill cancer cells has become a translational research priority. Early attempts documented in the late 1800s aimed at sparking immunity with cancer vaccines were difficult to interpret but demonstrated an opportunity that more than 100 years later has blossomed into the current field of cancer immunotherapy.

Central Tunnel Technique and Fat Grafting for Surgical Correction of Inverted Nipples and Introduction of a Treatment Algorithm.

Background: Inverted nipples are prevalent in 3% to 10% of women and can often cause functional, psychological, and aesthetic problems.

Objectives: The authors sought to treat inverted nipples and restore the aesthetic appearance of the nipple while minimizing ductal disruption, preserving the ability to breast-feed, and reducing recurrence rates.

Methods: A retrospective review was performed on a total of 161 inverted nipples in 86 consecutive patients who underwent correction of inverted nipples at Oslo Plastic Surgery Clinic.

Industrial wastewater treatment plant enriches antibiotic resistance genes and alters the structure of microbial communities.

Antibiotic resistance is an emerging global health crisis, driven largely by overuse and misuse of antibiotics. However, there are examples in which the production of these antimicrobial agents has polluted the environment with active antibiotic residues, selecting for antibiotic resistant bacteria and the genes they carry. In this work, we have used shotgun metagenomics to investigate the taxonomic structure and resistance gene composition of sludge communities in a treatment plant in Croatia receiving wastewater from production of the macrolide antibiotic azithromycin.

Inheritance of Susceptibility to Malignant Blood Disorders.

Malignant blood disorders depend on heritable susceptibility genes and occur in familial aggregations. We suggest a model of transgenerational segregation of the susceptibility genes based on the study of malignant blood disorders in Norwegian and Danish families with unrelated parents, and in the inbred Faroese population with related parents. This model, consisting of parental genomic imprinting and mother-son microchimerism, can explain the male predominance in most of the diseases, the predominance of affected parent-offspring when parents are not related, and the different modes of segregation in males and females.

Magnetic phase diagram of KCrO clarified by high-pressure muon spin spectroscopy.

The KCrO compound belongs to a series of quasi-1D compounds with intriguing magnetic properties that are stabilized through a high-pressure synthesis technique. In this study, a muon spin rotation, relaxation and resonance (μSR) technique is used to investigate the pressure dependent magnetic properties up to 25 kbar. μSR allows for measurements in true zero applied field and hereby access the true intrinsic material properties.

Modelling of zero-inflation improves inference of metagenomic gene count data.

Metagenomics enables the study of gene abundances in complex mixtures of microorganisms and has become a standard methodology for the analysis of the human microbiome. However, gene abundance data is inherently noisy and contains high levels of biological and technical variability as well as an excess of zeros due to non-detected genes. This makes the statistical analysis challenging.

Female Cosmetic Genital Surgery: Patient Characteristics, Motivation, and Satisfaction.

Background: Female cosmetic genital surgery is rapidly growing. However, controversy reports raised around these procedures question their indications, motives, and safety. Warning against performing this surgery might unjustly restrict surgical alleviation of symptoms.

Gluteal Augmentation With Fat: Retrospective Safety Study and Literature Review.

Background: Use of gluteal augmentation with fat increased by 3267% from 2002 to 2015, and the rate of death is highest compared with other aesthetic procedures: 1 in 3448 patients dies, compared with 1 in 55,000.

Objectives: To retrospectively investigate patients who underwent this procedure at Oslo Plastic Surgery Clinic, to review international data to determine factors causing mortality, and to provide guidelines for safety.

Methods: Patient data were searched for reason for the procedure, assessment of patients, techniques performed, and safety measures used.