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Analyses of microRNA expression profiles have shown that many microRNAs are expressed aberrantly and correlate with tumorigenesis, progression, and prognosis of various haematological and solid tumours. We aimed to assess the relation between microRNA expression and progression and prognosis of gastric cancer. 353 gastric samples from two independent subsets of patients from Japan were analysed by microRNA microarray. MicroRNA expression patterns were compared between non-tumour mucosa and cancer samples, graded by diffuse and intestinal histological types and by progression-related factors (eg, depth of invasion, metastasis, and stage). Disease outcome was calculated by multivariable regression analysis to establish whether microRNAs are independent prognostic factors. In 160 paired samples of non-tumour mucosa and cancer, 22 microRNAs were upregulated and 13 were downregulated in gastric cancer; 292 (83%) samples were distinguished correctly by this signature. The two histological subtypes of gastric cancer showed different microRNA signatures: eight microRNAs were upregulated in diffuse-type and four in intestinal-type cancer. In the progression-related signature, miR-125b, miR-199a, and miR-100 were the most important microRNAs involved. Low expression of let-7g (hazard ratio 2·6 [95% CI 1·3–4·9]) and miR-433 (2·1 [1·1–3·9]) and high expression of miR-214 (2·4 [1·2–4·5]) were associated with unfavourable outcome in overall survival independent of clinical covariates, including depth of invasion, lymph-node metastasis, and stage. MicroRNAs are expressed differentially in gastric cancers, and histological subtypes are characterised by specific microRNA signatures. Unique microRNAs are associated with progression and prognosis of gastric cancer. National Cancer Institute.

Background The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of Nrf2 protects against steatohepatitis. Method Wild-type mice (WT), Nrf2 gene-null mice ( Nrf2 -null) and Keap1 gene-knockdown mice ( Keap1 -kd), which represent the sustained activation of Nrf2, were fed a methionine- and choline-deficient diet (MCDD) for 13 weeks and analyzed. Results In Keap1 -kd fed an MCDD, steatohepatitis did not develop over the observation periods; however, in Nrf2 -null fed an MCDD, the pathological state of the steatohepatitis was aggravated in terms of fatty change, inflammation, fibrosis and iron accumulation. In WT mice fed an MCDD, Nrf2 and antioxidative stress genes regulated by Nrf2 were potently activated in the livers, and in Keap1 -kd, their basal levels were potently activated. Oxidative stress was significantly increased in the livers of the Nrf2 -null and suppressed in the livers of the Keap1 -kd compared to that of WT, based on the levels of 4-hydroxy-2-nonenal and malondialdehyde. Iron accumulation was greater in the livers of the Nrf2 -null mice compared to those of the WT mice, and it was not observed in Keap1 -kd. Further, the iron release from the isolated hepatocyte of Nrf2 -null mice was significantly decreased. Sulforaphane, an activator of Nrf2, suppressed the pathological states and oxidative stress in the livers. Conclusions Nrf2 has protective roles against nutritional steatohepatitis through inhibition of hepatic iron accumulation and counteraction against oxidative stress-induced liver injury. Nrf2 activation by pharmaceutical intervention could be a new option for the prevention and treatment of steatohepatitis.

Dual-band composite right/left-handed transmission lines with the nonreciprocal phase shift approximately proportional to the operating frequency are proposed and demonstrated by using normally magnetized ferrite microstrip lines. The nonreciprocal phase shift can be dynamically controlled by changing the externally applied dc magnetic field. Dynamic change in the nonreciprocal phase gradient along the line enables us to realize dual-band and unidirectional beam-scanning leaky-wave antennas without suffering from frequency-dependent change in the beam direction. A prototype nonreciprocal metamaterial line using polycrystalline yttrium iron garnet was fabricated and measured for verification of our basic concept.

Predictive models for determining coronavirus disease 2019 (COVID-19) severity have been established; however, the complexity of the interactions among factors limits the use of conventional statistical methods. This study aimed to establish a simple and accurate predictive model for COVID-19 severity using an explainable machine learning approach. A total of 3,301 patients ≥ 18 years diagnosed with COVID-19 between February 2020 and October 2022 were included. The discovery cohort comprised patients whose disease onset fell before October 1, 2020 ( N  = 1,023), and the validation cohort comprised the remaining patients ( N  = 2,278). Pointwise linear and logistic regression models were used to extract 41 features. Reinforcement learning was used to generate a simple model with high predictive accuracy. The primary evaluation was the area under the receiver operating characteristic curve (AUC). The predictive model achieved an AUC of ≥ 0.905 using four features: serum albumin levels, lactate dehydrogenase levels, age, and neutrophil count. The highest AUC value was 0.906 (sensitivity, 0.842; specificity, 0.811) in the discovery cohort and 0.861 (sensitivity, 0.804; specificity, 0.675) in the validation cohort. Simple and well-structured predictive models were established, which may aid in patient management and the selection of therapeutic interventions.

This paper proposes novel methods for extracting a single Speech signal of Interest (SOI) from a multichannel observed signal in underdetermined situations, i.e., when the observed signal contains more speech signals than microphones. It focuses on extracting the SOI using prior knowledge of the SOI’s Direction of Arrival (DOA). Conventional beamformers (BFs) and Blind Source Separation (BSS) with spatial regularization struggle to suppress interference speech signals in such situations. Although Switching Minimum Power Distortionless Response BF (Sw-MPDR) can handle underdetermined situations using a switching mechanism, its estimation accuracy significantly decreases when it relies on a steering vector determined by the SOI’s DOA. Spatially-Regularized Independent Vector Extraction (SRIVE) can robustly enhance the SOI based solely on its DOA using spatial regularization, but its performance degrades in underdetermined situations. This paper extends these conventional methods to overcome their limitations. First, we introduce a time-varying Gaussian (TVG) source model to Sw-MPDR to effectively enhance the SOI based solely on the DOA. Second, we introduce the switching mechanism to SRIVE to improve its speech enhancement performance in underdetermined situations. These two proposed methods are called Switching weighted MPDR (Sw-wMPDR) and Switching SRIVE (Sw-SRIVE). We experimentally demonstrate that both surpass conventional methods in enhancing the SOI using the DOA in underdetermined situations.

During the COVID-19 pandemic, older adults living in the community experienced reduced physical activity (PA) and heightened loneliness, particularly those with less frequent outings-a key factor of social frailty. Promoting PA may foster social participation, increase outings, and reduce loneliness. This study investigates the effects of a multi-component intervention on PA and loneliness in socially frail older adults. This single-blind, randomized controlled trial included 64 participants aged ≥ 60 years with social frailty and pre-frailty defined according to Makizako's Social Frailty Index. Participants were randomly assigned to either the intervention (n = 34) or the control (n = 30) group. Over eight weeks, the intervention group attended a weekly 60-min multi-component program that included health education, exercise, and self-monitoring. A simple exercise booklet was distributed to the control group at baseline. For both groups, outcome measures were assessed at baseline and after eight weeks. PA was assessed using a triaxial accelerometer. Loneliness was measured using the three-item version of the UCLA Loneliness Scale. We used repeated-measures analysis of variance with group-by-time interactions to estimate the intervention effects following the intention-to-treat approach. PA was not affected by the intervention. A significant group-by-time interaction was observed for loneliness, with a medium effect size (p < 0.05), indicating that loneliness was significantly reduced in the intervention group compared to the control group. The multi-component program aimed at promoting PA may contribute to the building of social relationships and reducing loneliness in older adults with social frailty and pre-frailty.

Background Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. Methods This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. Results Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. Conclusions Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

We provided fall prevention programs using home floor plans for older adult patients discharged from an acute-care hospital and verified the fall prevention measures’ effectiveness six months after discharge. The research design was a preliminary randomized controlled trial. Orthopedic patients with a falls’ history were randomized to the control (n = 30) or the intervention groups (n = 30). Before discharge, the control group was treated with general physiotherapy for their disease characteristics. The intervention group received the same programs before discharge; additionally, a simple house evaluation was conducted using the subject’s home floor plan. A six-month follow-up survey was conducted on falls and near-falls after discharge, completed by 51 of the 60 subjects (85%). Within two months, falls occurred in 7.7% of the control group but not in the intervention group, after which, falls occurred in the intervention group, and no significant difference was noted between the two groups (three-month (p = 0.322) and six-month (p = 0.931) follow-ups). The intervention group had significantly fewer near-falls than the control group within three months (p = 0.034), but no significant difference was observed after three months. The results suggested that our program effectively expanded the role of an acute care hospital for discharged patients who need to transition from hospital care to home health care.

The dynamic interaction of chromatin-binding proteins with their nucleosome binding sites is an important element in regulating the structure and function of chromatin in living cells. Here we review the major factors regulating the intranuclear mobility and chromatin binding of the linker histone H1, the most abundant family of nucleosome-binding proteins. The information available reveals that multiple and diverse factors modulate the interaction of H1 with chromatin at both a local and global level. This multifaceted mode of modulating the interaction of H1 with nucleosomes is part of the mechanism that regulates the dynamics of the chromatin fiber in living cells.

The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.