The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like ...growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment.
The purpose of the study was to examine the acute effect of static stretching exercise on the resting stiffness of gastrocnemius muscle belly. Ten healthy young adults performed standing wall ...stretching in dorsiflexion for 1 min at a time and repeated five times. Before and after stretching, the shear modulus was measured in medial and lateral heads of the resting gastrocnemius muscle with ultrasound shear‐wave elastography. After the stretching, dorsiflexion range of motion (ROM) of the ankle joint increased (P < 0.01) by 3.9° and returned in 20 min. Immediately after stretching, shear modulus decreased (P < 0.01) by 14%, compared with before stretching across muscle heads. The decrease in shear modulus returned in 20 min after stretching. In the comparison group of 10 additional subjects, the standing intervention without stretching had no influence on these measures. There was a negative correlation between dorsiflexion ROM and shear modulus in either head before and after stretching. The results demonstrate the transient decreases in the stiffness of the resting gastrocnemius muscle belly and indicate that joint flexibility is greater in individuals with lower resting stiffness of the muscle belly.
We present a new glacier inventory for high-mountain Asia named "Glacier Area Mapping for Discharge from the Asian Mountains" (GAMDAM). Glacier outlines were delineated manually using 356 Landsat ...ETM+ scenes in 226 path-row sets from the period 1999–2003, in conjunction with a digital elevation model (DEM) and high-resolution Google EarthTM imagery. Geolocations are largely consistent between the Landsat imagery and DEM due to systematic radiometric and geometric corrections made by the United States Geological Survey. We performed repeated delineation tests and peer review of glacier outlines in order to maintain the consistency and quality of the inventory. Our GAMDAM glacier inventory (GGI) includes 87 084 glaciers covering a total area of 91 263 ± 13 689 km2 throughout high-mountain Asia. In the Hindu Kush–Himalaya range, the total glacier area in our inventory is 93% that of the ICIMOD (International Centre for Integrated Mountain Development) inventory. Discrepancies between the two regional data sets are due mainly to the effects of glacier shading. In contrast, our inventory represents significantly less surface area (−24%) than the recent global Randolph Glacier Inventory, version 4.0 (RGI), which includes 119 863 ± 9201 km2 for the entirety of high Asian mountains. Likely causes of this disparity include headwall definition, effects of exclusion of shaded glacier areas, glacier recession since the 1970s, and inclusion of seasonal snow cover in the source data of the RGI, although it is difficult to evaluate such effects quantitatively. Further rigorous peer review of GGI will both improve the quality of glacier inventory in high-mountain Asia and provide new opportunities to study Asian glaciers.
The relationship between magnetic order and ferroelectric properties has been investigated for MnWO4 with a long-wavelength magnetic structure. Spontaneous electric polarization is observed in an ...elliptical spiral spin phase. The magnetic-field dependence of electric polarization indicates that the noncollinear spin configuration plays a key role for the appearance of the ferroelectric phase. An electric polarization flop from the b direction to the a direction has been observed when a magnetic field above 10 T is applied along the b axis. This result demonstrates that an electric polarization flop can be induced by a magnetic field in a simple system without rare-earth 4f moments.
COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese ...public.
This was a cross-sectional study.
This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed.
In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18–29 years; adjusted odds ratio aOR: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77).
Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.
Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer.
We performed targeted deep sequencing of ...plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status.
Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status.
ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.
A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively ...examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSA-corresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P=0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.
Results of earlier studies have demonstrated underlying diseases such as cancer, diabetes mellitus, immunodeficiency, hypertension and heart failure to be risk factors for severe outcomes and ...mortality. Furthermore, clinical trials have shown that drugs such as antiviral drugs, antibody cocktails, steroids and anti-inflammatory drugs can be expected to prevent severe COVID-19 outcomes and death.
This study, using inpatient records from the Medical Information Analysis Databank covering national hospital organizations in Japan, was conducted to evaluate the effects of underlying diseases and/or administered drugs on mortality. Subjects were all inpatients receiving oxygen administration and inpatients using respiratory ventilators, categorized by three age classes: all ages, patients 65 years old or older, and patients younger than 65 years old. We used logistic regression to analyze outcomes for underlying diseases, administered drugs, age, sex, the proportion of the mutated strains, and vaccine coverage.
Patients with hypertension, except for younger inpatients, have a lower risk of mortality (estimated coefficient 0.67 among all inpatients (
< 0.01): 0.77 among inpatients with oxygen therapy (
= 0.02) and 0.57 among inpatients with respiratory ventilation w (
= 0.01)). Except for younger inpatients, antibody cocktail (casirivimab/imdevimab or sotrovimab) administration was associated with a higher probability of survival (estimated coefficient 0.27 among all inpatients (
< 0.01)). It raised the survival probability consistently, although other drugs might have reduced the probability of survival.
These findings suggest that antiviral drugs (remdesivir, estimated coefficient 1.44 (
< 0.01)), steroids (dexamethasone, estimated coefficient 1.85 (
< 0.01)), and anti-inflammatory drugs (baricitinib, estimated coefficient 1.62 (
< 0.01), and tocilizumab, estimated coefficient 2.73 (
< 0.01)) might not contribute to survival. These results have not been reported from earlier studies. More sophisticated estimation procedures, such as treatment effect models, are necessary to obtain conclusive results.
A thermal sensor integrated with its driving circuit by using Cu on polyimide (COP) as a substrate was developed. A heater, working as the thermal flow sensor and constant temperature circuit (CTC), ...working as its driving feedback circuit, were successfully integrated on the COP substrate by photolithography, metal deposition, and sacrificial selective etching in the Cu layer. The Cu layer works to form a cavity that acts thermal isolation for the heater and electrical feedthroughs in the CTC. The electrical components, i.e., resistors, capacitors, and operational amplifiers, were mounted on the electrical pads using low-temperature solder paste of Sn–Bi at the CTC area. The areas of the thermal sensor and CTC were 11 × 23 mm and 16 × 24 mm, respectively. The area of the thermal sensor was inserted into a tube with a diameter of 5 mm acting as the flow sensor. The sensor outputs increased along with the airflow rate up to 10.0 L/min, and the calibration curve as the airflow-rate sensor was experimentally derived. The fabricated sensor outputs were not affected by variations in the airflow temperature and only depended on the airflow rate thanks to the added temperature compensation function, and a response time of 0.095 s was obtained.
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