An evolutionarily conserved mechanism controls reversible amyloids of pyruvate kinase via pH-sensing regions.

Amyloids are known as irreversible aggregates associated with neurodegenerative diseases. However, recent evidence shows that a subset of amyloids can form reversibly and fulfill essential cellular functions. Yet, the molecular mechanisms regulating functional amyloids and distinguishing them from pathological aggregates remain unclear.

Distribution shift detection for the postmarket surveillance of medical AI algorithms: a retrospective simulation study.

Distribution shifts remain a problem for the safe application of regulated medical AI systems, and may impact their real-world performance if undetected. Postmarket shifts can occur for example if algorithms developed on data from various acquisition settings and a heterogeneous population are predominantly applied in hospitals with lower quality data acquisition or other centre-specific acquisition factors, or where some ethnicities are over-represented. Therefore, distribution shift detection could be important for monitoring AI-based medical products during postmarket surveillance.

Yield reduction caused by elevated temperatures and high nitrogen fertilization is mitigated by SP6A overexpression in potato (Solanum tuberosum L.).

Potatoes (Solanum tuberosum L.) are a fundamental staple for millions of people worldwide. They provide essential amino acids, vitamins, and starch - a vital component of the human diet, providing energy and serving as a source of fiber.

INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas.

Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along with computational analyses of cancer dependency and gene expression datasets to identify the inositol-metabolizing phosphatase INPP5A as a selective dependency in GNAQ/11-mutant UM cells in vitro and in vivo. Mutant cells intrinsically produce high levels of the second messenger inositol 1,4,5 trisphosphate (IP3) that accumulate upon suppression of INPP5A, resulting in hyperactivation of IP3-receptor signaling, increased cytosolic calcium and p53-dependent apoptosis.

Prospective randomized pilot study of a novel patient-centered pathology report for colorectal polyps.

Objective: US patients have increased access to their medical records, yet the information is not always understandable. To improve patient understanding, we tested a patient-centered pathology report (PCPR) containing results for recent colon cancer screening or surveillance colonoscopy.

Methods: A pilot randomized trial assessed the impact of addition of the PCPR to a standard pathology report on knowledge accuracy, decisional self-efficacy and control, and therapeutic alliance.

A reference assembly for the legume cover crop hairy vetch ().

is an incompletely domesticated annual legume of the Fabaceae family native to Europe and Western Asia. is widely used as a cover crop and forage due to its ability to withstand harsh winters. Here, we generated a reference-quality genome assembly (Vvill1.

Single-cell Profiling Uncovers a -Expressing Metaplastic Gastric Cell Type Sustained by -driven Inflammation.

Unlabelled: Mechanisms for ()-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant infection and induction of constitutively active KRAS (+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that +KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin and the growth factor amphiregulin Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation.

Chromosome-scale assembly of the highly heterozygous genome of red clover ( L.), an allogamous forage crop species.

Relative to other crops, red clover ( L.) has various favorable traits making it an ideal forage crop. Conventional breeding has improved varieties, but modern genomic methods could accelerate progress and facilitate gene discovery.

Multi-pilot implementation experiences of patient-centered pathology reports: lessons learned for the advancement of patient-centered tools for cancer decision-making.

Purpose: New federal legislation in the United States grants patients expanded access to their medical records, making it critical that medical records information is understandable to patients. Provision of informational summaries significantly increase patient perceptions of patient-centered care and reduce feelings of uncertainty, yet their use for cancer pathology is limited.

Methods: Our team developed and piloted patient-centered versions of pathology reports (PCPRs) for four cancer organ sites: prostate, bladder, breast, and colorectal polyp.

SF3B1 facilitates HIF1-signaling and promotes malignancy in pancreatic cancer.

Mutations in the splicing factor SF3B1 are frequently occurring in various cancers and drive tumor progression through the activation of cryptic splice sites in multiple genes. Recent studies also demonstrate a positive correlation between the expression levels of wild-type SF3B1 and tumor malignancy. Here, we demonstrate that SF3B1 is a hypoxia-inducible factor (HIF)-1 target gene that positively regulates HIF1 pathway activity.

Pathology Education Powered by Virtual and Digital Transformation: Now and the Future.

Context.—: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools.

Preclinical Testing of Boron-Doped Diamond Electrodes for Root Canal Disinfection-A Series of Preliminary Studies.

While numerous approaches have meanwhile been described, sufficient disinfection of root canals is still challenging, mostly due to limited access and the porous structure of dentin. Instead of using different rinsing solutions and activated irrigation, the electrolysis of saline using boron-doped diamond (BDD) electrodes thereby producing reactive oxygen species may be an alternative approach. In a first step, experiments using extracted human teeth incubated with multispecies bacterial biofilm were conducted.

Comparing the electrophysiological effects of traumatic noise exposure between rodents.

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat, and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure.

Implementation and Effectiveness of a Completely Virtual Pathology Rotation for Visiting Medical Students.

Objectives: Coronavirus disease 2019 (COVID-19) upended in-person medical education, relocating many activities online. We designed a completely virtual pathology rotation to replace our traditional visiting rotation.

Methods: The virtual away rotation was listed in the Visiting Student Application Service (VSAS) and advertised on social media as well as various medical student mailing lists.

Medical Education in Pathology: General Concepts and Strategies for Implementation.

Context.—: Pathology education must evolve as medical knowledge expands and disruptive technologies emerge. The evolution in pathology teaching practices accelerated as traditional teaching modalities were suspended in March 2020 during the coronavirus disease 2019 (COVID-19) pandemic.

Interobserver agreement in pathologic evaluation of bile duct biopsies.

Intraductal biopsy is commonly used for preoperative evaluation of the etiology of biliary strictures. Interpretation of intraductal biopsies is frequently challenging. The diagnosis often suffers from interobserver disagreement, which has not been studied in the literature.

Cytosolic pH regulates proliferation and tumour growth by promoting expression of cyclin D1.

Enhanced growth and proliferation of cancer cells are accompanied by profound changes in cellular metabolism. These metabolic changes are also common under physiological conditions, and include increased glucose fermentation accompanied by elevated cytosolic pH (pHc). However, how these changes contribute to enhanced cell growth and proliferation is unclear.

Another Consequence of the Warburg Effect? Metabolic Regulation of Na/H Exchangers May Link Aerobic Glycolysis to Cell Growth.

To adjust cell growth and proliferation to changing environmental conditions or developmental requirements, cells have evolved a remarkable network of signaling cascades that integrates cues from cellular metabolism, growth factor availability and a large variety of stresses. In these networks, cellular information flow is mostly mediated by posttranslational modifications, most notably phosphorylation, or signaling molecules such as GTPases. Yet, a large body of evidence also implicates cytosolic pH (pHc) as a highly conserved cellular signal driving cell growth and proliferation, suggesting that pH-dependent protonation of specific proteins also regulates cellular signaling.

Bats as putative Zaire ebolavirus reservoir hosts and their habitat suitability in Africa.

The genus Ebolavirus comprises some of the deadliest viruses for primates and humans and associated disease outbreaks are increasing in Africa. Different evidence suggests that bats are putative reservoir hosts and play a major role in the transmission cycle of these filoviruses. Thus, detailed knowledge about their distribution might improve risk estimations of where future disease outbreaks might occur.

Remote Anatomic Pathology Medical Student Education in Washington State.

Objectives: The coronavirus disease 2019 pandemic has halted in-person medical student education in many large academic centers, including the University of Washington. We identified a unique opportunity to bring comprehensive and targeted anatomic pathology training to large numbers of medical students who would not receive it otherwise but also need credited coursework.

Methods: We developed a comprehensive 2-week remote-learning course encompassing lectures, virtual slides, discussion groups, and unique case-based activities.

Vector distribution and transmission risk of the Zika virus in South and Central America.

Background: Zika is of great medical relevance due to its rapid geographical spread in 2015 and 2016 in South America and its serious implications, for example, certain birth defects. Recent epidemics urgently require a better understanding of geographic patterns of the Zika virus transmission risk. This study aims to map the Zika virus transmission risk in South and Central America.

Utility of glutamine synthetase immunohistochemistry in identifying features of regressed cirrhosis.

The prevailing view that cirrhosis is irreversible has been challenged. It has been proposed that varying degrees of fibrosis regression can be achieved if the injurious agent is removed. In the normal liver, glutamine synthetase immunostaining is present around central veins.

Leishmaniasis in Eurasia and Africa: geographical distribution of vector species and pathogens.

Leishmaniasis is a vector-borne disease with a broad global occurrence and an increasing number of recorded cases; however, it is still one of the world's most neglected diseases. We here provide climatic suitability maps generated by means of an ecological niche modelling approach for 32 vector species with proven or suspected vector competence for five pathogens occurring in Eurasia and Africa. A GIS-based spatial overlay analysis was then used to compare the distributional patterns of vectors and pathogens to help evaluate the vector species-pathogen relationship currently found in the literature.

A case of metastatic dysgerminoma treated with two cycles neoadjuvant chemotherapy followed by fertility-sparing minimally invasive surgery.

•Neoadjuvant chemotherapy (NACT) followed by fertility-sparing surgery is a feasible treatment of metastatic dysgerminoma•As few as two cycles of NACT may result in enough of a tumor response for fertility-sparing surgery to be possible.•Tumor lysis syndrome is a possibility when administering chemotherapy to patients with metastatic dysgerminoma.