SARS-CoV-2 IgG seroprevalence in the Okinawa Main Island and remote islands in Okinawa, Japan, 2020-2021.

We estimated the seroprevalence of anti-SARS-COV-2 IgG in different island groups in Okinawa. A cross-sectional sero-survey was repeated in three periods between July 2020 and February 2021. A total of 2683 serum samples were collected from six referral medical centers, each covering a separate region in Okinawa.

HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity.

HMGA1 is an abundant non-histone chromatin protein that has been implicated in embryonic development, cancer, and cellular senescence, but its specific role remains elusive. Here, we combine functional genomics approaches with graph theory to investigate how HMGA1 genomic deposition controls high-order chromatin networks in an oncogene-induced senescence model. While the direct role of HMGA1 in gene activation has been described previously, we find little evidence to support this.

Titration of RAS alters senescent state and influences tumour initiation.

Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with premalignancy. Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS dose-escalation models in vitro and in vivo, revealing a RAS dose-driven non-linear continuum of downstream phenotypes.

Scribble Deficiency Promotes Pancreatic Ductal Adenocarcinoma Development and Metastasis.

Perturbation of cell polarity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) progression. Scribble (SCRIB) is a well-characterized polarity regulator that has diverse roles in the pathogenesis of human neoplasms. To investigate the impact of SCRIB deficiency in PDAC development and progression, Scrib expression was genetically ablated in well-established mouse models of PDAC.

Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states.

Cell states are regulated by the response of signaling pathways to receptor ligand-binding and intercellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals.

Senescence of human pancreatic beta cells enhances functional maturation through chromatin reorganization and promotes interferon responsiveness.

Senescent cells can influence the function of tissues in which they reside, and their propensity for disease. A portion of adult human pancreatic beta cells express the senescence marker p16, yet it is unclear whether they are in a senescent state, and how this affects insulin secretion. We analyzed single-cell transcriptome datasets of adult human beta cells, and found that p16-positive cells express senescence gene signatures, as well as elevated levels of beta-cell maturation genes, consistent with enhanced functionality.

Determining the Compaction State of Genes Using DNA FISH.

DNA fluorescence in situ hybridization (FISH) enables the visualization of chromatin architecture and the interactions between genomic loci at a single-cell level, complementary to genome-wide methods such as Hi-C. DNA FISH uses fluorescent-labeled DNA probes targeted to the loci of interest, allowing for the analysis of their spatial positioning and proximity with microscopy. Here, we describe an optimized experimental procedure for DNA FISH, from probe design and sample preparation through imaging and image quantification.

Text mining for contexts and relationships in cancer genomics literature.

Motivation: Scientific advances build on the findings of existing research. The 2001 publication of the human genome has led to the production of huge volumes of literature exploring the context-specific functions and interactions of genes. Technology is needed to perform large-scale text mining of research papers to extract the reported actions of genes in specific experimental contexts and cell states, such as cancer, thereby facilitating the design of new therapeutic strategies.

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts.

Beyond SAHF: An integrative view of chromatin compartmentalization during senescence.

Cellular senescence, a persistent form of cell cycle arrest, has been linked to the formation of heterochromatic foci, accompanied by additional concentric epigenetic layers. However, senescence is a highly heterogeneous phenotype, and the formation of these structures is context dependent. Recent developments in the understanding of the high-order chromatin organization have opened new avenues for contextualizing the nuclear and chromatin phenotypes of senescence.

Cellular senescence: beneficial, harmful, and highly complex.

The contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology were long overlooked but have now taken centre stage. In this Editorial, we will briefly outline the review and original work articles contained in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. It is beginning to be appreciated that senescent cells can exert both beneficial and adverse effects following tissue injury.

Contamination of Blood Cultures From Arterial Catheters and Peripheral Venipuncture in Critically Ill Patients: A Prospective Multicenter Diagnostic Study.

Background: Collecting blood cultures from indwelling arterial catheters is an attractive option in critically ill adult patients when peripheral venipuncture is difficult. However, whether the contamination proportion of blood cultures from arterial catheters is acceptable compared with that from venipuncture is inconclusive.

Research Question: Is contamination of blood cultures from arterial catheters noninferior to that from venipuncture in critically ill adult patients with suspected bloodstream infection?

Study Design And Methods: In this multicenter prospective diagnostic study conducted at five hospitals, we enrolled episodes of paired blood culture collection, each set consisting of blood drawn from an arterial catheter and another by venipuncture, were obtained from critically ill adult patients with cilinical indication.

Association between hospital internal medicine physician workforce and patient admissions during the COVID-19 pandemic in Japan.

Background: Hospital physician workforce in Japan is the lowest among developed countries. Many patients with novel coronavirus disease 2019 (COVID-19) with high risk of mortality could not be hospitalized during case surges in Japan and only about 5% of total acute care beds were used as COVID-19 beds nationwide. However, the relationship between the number of hospital physicians and patient admissions remains unclear.

Bioprinting microporous functional living materials from protein-based core-shell microgels.

Living materials bring together material science and biology to allow the engineering and augmenting of living systems with novel functionalities. Bioprinting promises accurate control over the formation of such complex materials through programmable deposition of cells in soft materials, but current approaches had limited success in fine-tuning cell microenvironments while generating robust macroscopic morphologies. Here, we address this challenge through the use of core-shell microgel ink to decouple cell microenvironments from the structural shell for further processing.

Prevalence and characteristics of antibiotic prescription for acute COVID-19 patients in Japan.

COVID-19 is a viral infection and does not require antibiotics. The study aimed to elucidate a prescribing pattern of antibiotics for COVID-19. A nationwide cross-sectional study was conducted in Japan.

Inpatient antibiotic prescribing patterns using the World Health Organization (WHO) Access Watch and Reserve (AWaRe) classification in Okinawa, Japan: A point-prevalence survey.

Using point-prevalence methodology and the World Health Organization (WHO) Access, Watch, and Reserve Classification, we measured antibiotic use in 5 hospitals in Okinawa, Japan, on October 1, 2020. Overall, 29% of patients were prescribed an antibiotic on the survey date and the 3 most used antibiotics in the "Watch" category were cefazolin, ampicillin-sulbactam, and ampicillin.

The Chromatin Regulator HMGA1a Undergoes Phase Separation in the Nucleus.

The protein high mobility group A1 (HMGA1) is an important regulator of chromatin organization and function. However, the mechanisms by which it exerts its biological function are not fully understood. Here, we report that the HMGA isoform, HMGA1a, nucleates into foci that display liquid-like properties in the nucleus, and that the protein readily undergoes phase separation to form liquid condensates in vitro.

Syphilitic osteomyelitis in a patient with HIV and cognitive biases in clinical reasoning: A case report.

Rationale: Diagnosing multifactorial, multidimensional symptoms unexplained by presumptive diagnosis is often challenging for infectious disease specialists.

Patient Concerns: We report a rare case of a 30-year-old Japanese bisexual man with a history of virally suppressed human immunodeficiency virus and syphilis infections who developed chest pain and an erosive lesion under the lower midline jaw.

Diagnosis: Imaging examinations revealed erosive lesions on the sternum and left the ninth rib.

Transient Systemic Autophagy Inhibition Is Selectively and Irreversibly Deleterious to Lung Cancer.

Unlabelled: Autophagy is a conserved catabolic process that maintains cellular homeostasis. Autophagy supports lung tumorigenesis and is a potential therapeutic target in lung cancer. A better understanding of the importance of tumor cell-autonomous versus systemic autophagy in lung cancer could facilitate clinical translation of autophagy inhibition.

High Yield of Blood Cultures in the Etiologic Diagnosis of Cellulitis, Erysipelas, and Cutaneous Abscess in Elderly Patients.

Background: Cellulitis is a common disease in the elderly, and detecting etiologic organisms with blood cultures is difficult because of the low positive rate and occasional skin contamination. Therefore, routine blood cultures are not recommended for uncomplicated cellulitis. However, it is unclear whether blood culture collection for the diagnosis of cellulitis in elderly patients is useful.

Autophagy at the intersection of aging, senescence, and cancer.

Autophagy is an evolutionarily conserved cellular process in which macromolecules undergo lysosomal degradation. It fulfills essential roles in quality controlling cellular constituents and in energy homeostasis. Basal autophagy is also widely accepted to provide a protective role in aging and aging-related disorders, and its decline with age might precipitate the onset of a variety of diseases.

Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillance.

Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through the SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal cells are separated from circulating immunocytes by the endothelium, which is targeted by microenvironmental signaling.