Monkeypox: a global health emergency.

Over the past 2 years, the world has faced the impactful Coronavirus Disease-2019 (COVID-19) pandemic, with a visible shift in economy, medicine, and beyond. As of recent times, the emergence of the monkeypox (mpox) virus infections and the growing number of infected cases have raised panic and fear among people, not only due to its resemblance to the now eradicated smallpox virus, but also because another potential pandemic could have catastrophic consequences, globally. However, studies of the smallpox virus performed in the past and wisdom gained from the COVID-19 pandemic are the two most helpful tools for humanity that can prevent major outbreaks of the mpox virus, thus warding off another pandemic.

Thyroid-related adverse events induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the "thyroid storm".

Deep Learning Image Analysis of Benign Breast Disease to Identify Subsequent Risk of Breast Cancer.

Background: New biomarkers of risk may improve breast cancer (BC) risk prediction. We developed a computational pathology method to segment benign breast disease (BBD) whole slide images into epithelium, fibrous stroma, and fat. We applied our method to the BBD BC nested case-control study within the Nurses' Health Studies to assess whether computer-derived tissue composition or a morphometric signature was associated with subsequent risk of BC.

PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts.

Background: Modified median and subgroup-specific gene centering are two essential preprocessing methods to assign breast cancer molecular subtypes by PAM50. We evaluated the PAM50 subtypes derived from both methods in a subset of Nurses' Health Study (NHS) and NHSII participants; correlated tumor subtypes by PAM50 with IHC surrogates; and characterized the PAM50 subtype distribution, proliferation scores, and risk of relapse with proliferation and tumor size weighted (ROR-PT) scores in the NHS/NHSII.

Methods: PAM50 subtypes, proliferation scores, and ROR-PT scores were calculated for 882 invasive breast tumors and 695 histologically normal tumor-adjacent tissues.

Gut Microbiome and the Response to Immunotherapy in Cancer.

Recent studies indicate that the composition of gut bacteria can influence the effectiveness of certain cancer immunotherapy drugs and that modulating the gut microbiome may expand the pool of patients benefiting from cancer immunotherapies. Checkpoint blockade therapy has been effective on several types of malignancies (e.g.

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples.

AMPK activation can delay aging.

AMPK controls the regulation of cellular homeostasis, metabolism, resistance to stress, cell survival and growth, cell death, autophagy, which are some of the most critical determinants of aging and lifespan. Specific AMPK activation was recently shown to delay aging and prolong lifespan in Drosophila melanogaster. Indirect AMPK activators, such as resveratrol, metformin and exercise, are currently in clinical trials for studying their impact on human aging-related characteristics, tissue homeostasis and metabolic dysfunctions.

PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor.

FOXO family members (FOXOs: FOXO1, FOXO3, FOXO4 and FOXO6) are important transcription factors and tumor suppressors controlling cell homeostasis and cell fate. They are characterized by an extraordinary functional diversity, being involved in regulation of cell cycle, proliferation, apoptosis, DNA damage response, oxidative detoxification, cell differentiation and stem cell maintenance, cell metabolism, angiogenesis, cardiac and other organ's development, aging, and other critical cellular processes. FOXOs are tightly regulated by reversible phosphorylation, ubiquitination, acetylation and methylation.

New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals.

Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role.

Discoveries: an innovative platform for publishing cutting-edge research discoveries in medicine, biology and chemistry.

Discoveries is a new peer-reviewed, open access, online multidisciplinary and integrative journal publishing high impact reviews, experimental articles, perspective articles, and editorials from all areas related to medicine, biology, and chemistry, including but not limited to: Molecular and Cellular Biology, Biochemistry, Biophysics, Genomics, Proteomics, Biotechnology, Synthetic Biology, Bioengineering, Systems Biology, Bioinformatics, Translational Medicine, Medicine/ Clinical findings, Cognitive Science, Epidemiology, Global Medicine, Family Medicine, Organic/ Inorganic/ Physical Chemistry and Ethics in Science. Discoveries brings to the research community an outstanding editorial board that aims to address several of the innovations proposed above: there is no need to format the manuscript before submission, we have a rapid and efficient submission process, there is no need for a Cover Letter and we support the need for rules for validation of critical reagents, such as antibodies. Discoveries will aim to support high quality research on human subjects materials to provide relevance for non-human studies along with mechanistic insights into human biology and chemistry.

Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells.

Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. We and others have previously established bortezomib, a selective proteasome inhibitor, as an important potential treatment in CML. Here we show that the combined regimens of bortezomib with mitotic inhibitors, such as the microtubule-stabilizing agent Paclitaxel and the PLK1 inhibitor BI2536, efficiently kill TKIs-resistant and -sensitive Bcr-Abl-positive leukemic cells.

Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP.

Successful translation of findings derived from preclinical studies into effective therapies is critical in biomedical research. Lack of robustness and reproducibility of the preclinical data, due to insufficient number of repeats, inadequate cell-based and mouse models contribute to the poor success rate. Antibodies are widely used in preclinical research, notably to determine the expression of potential therapeutic targets in tissues of interest, including tumors, but also to identify disease and/or treatment response biomarkers.