Mitophagy in health and disease. Molecular mechanisms, regulatory pathways, and therapeutic implications.

Mitophagy, a specialised form of autophagy, selectively targeting damaged or dysfunctional mitochondria, and is crucial for maintaining cellular homeostasis and mitochondrial quality control. Dysregulation of mitophagy contributes to various pathological conditions, including cancer, neurodegenerative and cardiovascular diseases. This review presents a comprehensive analysis of the molecular mechanisms, regulatory pathways, and interplay with other cellular processes governing mitophagy, emphasizing its importance in physiological and pathological contexts.

Correction: Reproducible big data science: A case study in continuous FAIRness.

[This corrects the article DOI: 10.1371/journal.pone.

Making Common Fund data more findable: catalyzing a data ecosystem.

The Common Fund Data Ecosystem (CFDE) has created a flexible system of data federation that enables researchers to discover datasets from across the US National Institutes of Health Common Fund without requiring that data owners move, reformat, or rehost those data. This system is centered on a catalog that integrates detailed descriptions of biomedical datasets from individual Common Fund Programs' Data Coordination Centers (DCCs) into a uniform metadata model that can then be indexed and searched from a centralized portal. This Crosscut Metadata Model (C2M2) supports the wide variety of data types and metadata terms used by individual DCCs and can readily describe nearly all forms of biomedical research data.

Healthcare system engagement and algorithm-identified cancer incidence following initiation of a new medication.

Purpose: Implausibly high algorithm-identified cancer incidence within a new user study after medication initiation may result from increased healthcare utilization (HU) around initiation ("catch-up care") that increases diagnostic opportunity. Understanding the relationships between HU prior to and around initiation and subsequent cancer rates and timing is important to avoiding protopathic bias.

Methods: We identified a cohort of 417 458 Medicare beneficiaries (2007-2014) aged ≥66 initiating an antihypertensive (AHT) after ≥180 days of non-use.

Pinpoint accuracy: guided core biopsy diagnostic accuracy in musculoskeletal lesions.

Background: Core biopsy is integral in the work-up of diagnosis for musculoskeletal lesions. Prior to referral through Christchurch hospital-a tertiary referral centre for sarcomas/musculoskeletal lesions, many patients undertake guided core biopsy in peripheral hospitals. We wished to assess the accuracy of these biopsies undertaken in the peripheral centres and compare to those done in the tertiary setting.

Tibial metaphyseal cones combined with short stems perform as well as long stems in revision total knee arthroplasty.

Backgrounds: There is uncertainty around optimal tibial stem length in revision total knee arthroplasty (rTKA) utilizing a tibial trabecular metal (TM) cone. The purpose of this study was to compare: (1) functional outcomes, (2) radiographic outcomes and (3) implant survivorship in rTKA utilizing TM cones combined with either short stems (SS) or long stems (LS) at minimum 2 years follow-up.

Methods: In this retrospective, multi-centre study, patients undergoing rTKA utilizing a TM cone between 2008 and 2019 were included.

Rare germline deleterious variants increase susceptibility for lung cancer.

Although multiple common susceptibility loci for lung cancer (LC) have been identified by genome-wide association studies, they can explain only a small portion of heritability. The etiological contribution of rare deleterious variants (RDVs) to LC risk is not fully characterized and may account for part of the missing heritability. Here, we sequenced the whole exomes of 2777 participants from the Environment and Genetics in Lung cancer Etiology study, a homogenous population including 1461 LC cases and 1316 controls.

A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non-neoplastic cells.

Phytochemicals are a diverse group of compounds found in various fruits, vegetables, nuts, and legumes. Many phytochemicals have been observed to possess health benefits. Some have been found to be chemoprotective or can act as chemotherapeutics by inducing autophagy, apoptosis, or otherwise regulating the cell cycle.

Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States.

Background: Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk.

Methods: We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year.

A novel combined resveratrol/berberine phytochemotheraputic using the HePG2 cell line as a model for the treatment of hepatocarcinoma.

The results presented herein show that at clinically relevant concentrations (0-30 µM), the well-tolerated phytochemical berberine (BER) induces cell death in cultured human hepatocarcinoma (HepG2) cells as a model for liver cancer, primarily via apoptosis. Similar, relatively low-concentration single treatments using the structurally related phytochemical resveratrol (RSV), had little or no effect on cell viability but inhibited the cell cycle, while simultaneously increasing the strength of cellular adhesion. When used in combination, an RSV/BER cotreatment appeared to retain the ability of a single RSV treatment to increase cellular adhesion, but also induced a massive loss in hepatocarcinoma cellular viability, inducing cell death in more than 90% of cells.

Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumatoid Arthritis.

Background: TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers.

Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, = 10,263).

The effect of grip position on golf driving accuracy and distance.

The grip position (GP) in golf substantially affects performance outcomes such as shot accuracy and hitting distance. However, it is unknown which specific GP (i.e.

Towards Co-Evolution of Data-Centric Ecosystems.

Database evolution is a notoriously difficult task, and it is exacerbated by the necessity to evolve database-dependent applications. As science becomes increasingly dependent on sophisticated data management, the need to evolve an array of database-driven systems will only intensify. In this paper, we present an architecture for data-centric ecosystems that allows the components to seamlessly co-evolve by centralizing the models and mappings at the data service and pushing model-adaptive interactions to the database clients.

AnthOligo: automating the design of oligonucleotides for capture/enrichment technologies.

Summary: A number of methods have been devised to address the need for targeted genomic resequencing. One of these methods, region-specific extraction (RSE) is characterized by the capture of long DNA fragments (15-20 kb) by magnetic beads, after enzymatic extension of oligonucleotides hybridized to selected genomic regions. Facilitating the selection of the most appropriate capture oligos for targeting a region of interest, satisfying the properties of temperature (Tm) and entropy (ΔG), while minimizing the formation of primer-dimers in a pooled experiment, is therefore necessary.

Risk of Rare Cancers Among Solid Organ Transplant Recipients.

Background: Immunosuppressed solid organ transplant recipients (SOTRs) have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections.

Methods: We performed a cohort study of 262 455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries.

A review of the chemopreventative and chemotherapeutic properties of the phytochemicals berberine, resveratrol and curcumin, and their influence on cell death via the pathways of apoptosis and autophagy.

Phytochemicals are a diverse group of compounds found in a variety of fruits, vegetables and herbs, and have been reported to possess a number of health benefits. Marketed as supplements by health food retailers, this group of naturally occurring compounds have been investigated for a number of years to determine if they possess any chemopreventative and/or chemotherapeutic benefits. In this comprehensive review, the phytochemicals resveratrol, berberine and curcumin will be discussed, with particular focus being given to their proposed anticancer applications.

Reproducible big data science: A case study in continuous FAIRness.

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data.

Cell death: a review of the major forms of apoptosis, necrosis and autophagy.

Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues.

Allergies and the Subsequent Risk of Cancer among Elderly Adults in the United States.

Background: Allergic conditions may prevent some cancers by promoting immune surveillance. We examined associations of allergic rhinitis, asthma, and eczema with cancer risk among elderly Americans.

Methods: We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to perform a case-control study.

The importance and implications of comparator selection in pharmacoepidemiologic research.

Purpose Of Review: Pharmacoepidemiologic studies employing large databases are critical to evaluating the effectiveness and safety of drug exposures in large and diverse populations. Because treatment is not randomized, researchers must select a relevant comparison group for the treatment of interest. The comparator group can consist of individuals initiating: (1) a similarly indicated treatment (active comparator), (2) a treatment used for a different indication (inactive comparator) or (3) no particular treatment (non-initiators).

Survival after a cancer diagnosis among solid organ transplant recipients in the United States.

Background: Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors' knowledge no study to date has comprehensively examined associations between transplantation status and mortality after a cancer diagnosis.

Methods: The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987-2014).