Search

Abstract Effectively interfering with endoplasmic reticulum (ER) function in tumor cells and simultaneously activating an anti-tumor immune microenvironment to attack the tumor cells are promising strategies for cancer treatment. However, precise ER-stress induction is still a huge challenge. In this study, we synthesized a near-infrared (NIR) probe, NIR-715, which induces tumor cell death and inhibits tumor growth without causing apparent side effects. NIR-715 triggers severe ER stress and immunogenic cell death (ICD) after visible light exposure. NIR-715 induced ICD-associated HMGB1 release in vitro and anti-tumor immune responses, including increased cytotoxic T lymphocyte (GZMB+ CD8+ T cell) infiltration and decreased numbers of exhausted T lymphocytes (PD-L1+ CD8+ T cell). These findings suggest that NIR-715 may be a novel agent for “cold” tumor photodynamic therapy (PDT). Schematic illustration of NIR-715 photodynamic therapy for visible light-triggered, endoplasmic reticulum-targeting antitumor therapy.

The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children’s Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Abstract Background Epilepsy is a prevalent neurological disorder in which seizures cause recurrent episodes of unconsciousness or muscle convulsions, seriously affecting the patient’s work, quality of life, and health and safety. Timely prediction of seizures is critical for patients to take appropriate therapeutic measures. Accurate prediction of seizures remains a challenge due to the complex and variable nature of EEG signals. The study proposes an epileptic seizure model based on a multidimensional Transformer with recurrent neural network(LSTM-GRU) fusion for seizure classification of EEG signals. Methodology Firstly, a short-time Fourier transform was employed in the extraction of time-frequency features from EEG signals. Second, the extracted time-frequency features are learned using the Multidimensional Transformer model. Then, LSTM and GRU are then used for further learning of the time and frequency characteristics of the EEG signals. Next, the output features of LSTM and GRU are spliced and categorized using the gating mechanism. Subsequently, seizure prediction is conducted. Results The model was tested on two datasets: the Bonn EEG dataset and the CHB-MIT dataset. On the CHB-MIT dataset, the average sensitivity and average specificity of the model were 98.24% and 97.27%, respectively. On the Bonn dataset, the model obtained about 99% and about 98% accuracy on the binary classification task and the tertiary upper classification task, respectively. Conclusion The findings of the experimental investigation demonstrate that our model is capable of exploiting the temporal and frequency characteristics present within EEG signals.

Abstract Background Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. Case presentation We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. Conclusions Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

This study aimed to determine the associations of childhood exposure to bisphenol A (BPA) and parabens (PBs) with oxidative stress and the activity of outer hair cells (OHCs) in the cochlea of children with hearing loss (HL). A total of 641 children were enrolled in this cross-sectional study. Urinary concentrations of BPA and four PBs including methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), and butyl paraben (BP) were quantified by using liquid chromatography–tandem mass spectrometry (LC/MSMS). Four urinary biomarkers of oxidative stress, 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxynonenal mercapturic acid (HNE-MA), and 8-isoprostaglandin F2α (8-iso-PGF2α), were measured using high-performance liquid chromatography-electrospray ionization mass spectrometry. Hearing tests were conducted by an audiologist in the audiometric test room, and the results were confirmed by an otolaryngologist. The activity of OHCs in the cochlea was measured by distortion product otoacoustic emissions (DPOAEs). The associations of BPA/PB exposure and oxidative stress with the activity of OHCs at different frequencies were evaluated in the multivariable linear regression models. There were 91 children with HL, for an incidence of approximately 14.2 %. There was a significant negative association between the presence of EP (1.5 K Hz, 3 K Hz) or PP (2 K Hz) or 8-OHdG (1 K Hz, 1.5 K Hz, 2 K Hz) and the activity of OHCs in the left ear. Significant results were also observed for BPA (2 K Hz), MP (1 K Hz, 1.5 K Hz, 2 K Hz), EP (3 K Hz), and 8-OHdG (2 K Hz) in the right ear. This study revealed that exposure to BPA/PBs reduces the activity of OHCs, especially at middle frequencies, in children.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation.

Abstract We investigate a new proposal connecting the geometry at various radial scales in asymptotic AdS spacetime with entanglement structure at corresponding real-space length scales of the boundary theory. With this proposal, the bulk IR geometry encodes the long-scale entanglement structure of the dual quantum system. We consider two distinct types of IR geometries, namely the spherical case and the hyperbolic case, which are intimately related to the physics of differential entropy and brane-world holography separately. We explore the corresponding change in the dual long-scale entanglement structures, utilizing the tools of the Ryu-Takayanagi formula, conditional mutual information, and partial entanglement entropy. The results indicate that modifying the IR geometry leads to a redistribution of entanglement at scales longer than a critical length determined by the location of the IR region, with the two modified IR geometries corresponding to two opposite ways of redistribution. Furthermore, we establish the maximum amount of entanglement that can be modified, which is proportional to the area of the IR region.

Abstract Pole-skipping refers to the special phenomenon that the pole and the zero of a retarded two-point Green’s function coincide at certain points in momentum space. We study the pole-skipping phenomenon in holographic Green’s functions of boundary operators that are dual to massive p-form fields and the dRGT massive gravitational fields in the AdS black hole background. Pole-skipping points for these systems are computed using the near horizon method. The relation between the pole-skipping points of massive fields and their massless counterparts is revealed. In particular, as the field mass m is varied from zero to non-zero, the pole-skipping phenomenon undergoes an abrupt change with doubled pole-skipping points found in the massive case. This arises from the breaking of gauge invariance due to the mass term and the consequent appearance of more degrees of freedom. We recover the gauge invariance using the Stueckelberg formalism by introducing auxiliary dynamical fields. The extra pole-skipping points are identified to be associated with the Stueckelberg fields. We also observe that, as the mass varies, some pole-skipping points of the wave number q may move from a non-physical region with complex q to a physical region with real q.

Background: Noise pollution is a growing concern for public health and the environment. Traditional noise monitoring methods often have limitations due to short-term measurements and high costs. Objective: This study aims to develop and validate EcoDecibel, a low-cost, IoT-based sensor system for continuous noise monitoring, addressing the gaps in existing noise measurement technologies. Methods: EcoDecibel was compared with Class 1 and Class 2 sound level meters in various conditions. The system was deployed across three environmental sites in Sanzhi District, Taiwan, for one week. Time-series prediction and forecasting models (SARIMA, Prophet, LSTM) were applied to the noise data to predict and forecast noise levels. Results: EcoDecibel demonstrated strong correlation, yielding R2 values of 0.948 and 0.983 in comparison with Class 1 and Class 2 sound level meters and was able to monitor and forecast daily noise patterns effectively. The system performed well across different environments and was capable of continuous real-time monitoring. Conclusions: EcoDecibel presents a cost-effective and reliable solution for long-term environmental noise monitoring. The system is suitable for use in epidemiological studies investigating the relationship between noise exposure and public health outcomes.

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

Background: Air pollution is recognized as a modifiable risk factor for dementia, and recent evidence suggests that improving air quality could attenuate cognitive decline and reduce dementia risk. However, studies have yet to explore the effects of improved air quality on brain structures. This study aims to investigate the impact of air pollution reduction on cognitive functions and structural brain differences among cognitively normal older adults. Methods: Four hundred and thirty-one cognitively normal older adults were from the Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT), a community-based cohort of adults aged 60 and older, between year 2017– 2021. Annual concentrations of PM2.5, NO2, O3, and PM10 at participants’ residential addresses during the 10 years before enrollment were estimated using ensemble mixed spatial models. The yearly rate of change (slope) in air pollutants was estimated for each participant. Cognitive functions and structural brain images were collected during enrollment. The relationships between the rate of air pollution change and cognitive functions were examined using linear regression models. For air pollutants with significant findings in relation to cognitive function, we further explored the association with brain structure. Results: Overall, all pollutant concentrations, except O3, decreased over the 10-year period. The yearly rates of change (slopes) in PM2.5 and NO2 were correlated with better attention (PM2.5: r = -0.1, p = 0.047; NO2: r = -0.1, p = 0.03) and higher white matter integrity in several brain regions. These regions included anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, and inferior fronto-occipital fasciculus. Conclusions: Greater rate of reduction in air pollution was associated with better attention and attention-related white matter integrity. These results provide insight into the mechanism underlying the relationship between air pollution, brain health, and cognitive aging among older adults.

Background: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. Objective: To evaluate the association of long-term exposure to metal constituents in PM2.5 with the risk of liver cancer using a Taiwanese cohort study. Methods: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991–1992. Participants’ long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM2.5 was based on ambient measurement in 2002–2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991–2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM2.5 metal component and HCC. Results: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02–1.25; P = 0.023) with one unit increment on Cu normalized by PM2.5 mass concentration in the logarithmic scale. The PM2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM2.5. Conclusion: Our findings suggest PM2.5 containing Cu may attribute to the association of PM2.5 exposure with liver cancer.

Human CD93, an epidermal growth factor (EGF)-like domain containing transmembrane protein, is predominantly expressed in the vascular endothelium. Studies have shown that AA4, the homolog of CD93 in mice, may mediate cell migration and angiogenesis in endothelial cells. Soluble CD93 has been detected in the plasma of healthy individuals. However, the role of soluble CD93 in the endothelium remains unclear. Recombinant soluble CD93 proteins with EGF-like domains (rCD93D123, with domains 1, 2, and 3; and rCD93D23, with domains 2 and 3) were generated to determine their functions in angiogenesis. We found that rCD93D23 was more potent than rCD93D123 in stimulating the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Production of matrix-metalloproteinase 2 increased after the HUVECs were treated with rCD93D23. Further, in a tube formation assay, rCD93D23 induced cell differentiation of HUVECs through phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase and extracellular signal-regulated kinases-1/2 signaling. Moreover, rCD93D23 promoted blood vessel formation in a Matrigel-plug assay and an oxygen-induced retinopathy model in vivo. Our findings suggest that the soluble EGF-like domain containing CD93 protein is a novel angiogenic factor acting on the endothelium.

Abstract Quantum key distribution (QKD) holds the potential to establish secure keys over long distances. The distance of point-to-point QKD secure key distribution is primarily impeded by the transmission loss inherent to the channel. In the quest to realize a large-scale quantum network, increasing the QKD distance under current technology is of great research interest. Here we adopt the 3-intensity sending-or-not-sending twin-field QKD (TF-QKD) protocol with the actively-odd-parity-pairing method. The experiment demonstrates the feasibility of secure QKD over a 1002 km fibre channel considering the finite size effect. The secure key rate is 3.11 × 10 − 12 $3.11\times 10^{-12}$ per pulse at this distance. Furthermore, by optimizing parameters for shorter fiber distances, we conducted performance tests on key distribution for fiber lengths ranging from 202 km to 505 km. Notably, the secure key rate for the 202 km, the normal distance between major cities, reached 111.74 kbps.

Background: In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a pivotal treatment for pure native aortic regurgitation (PNAR). Given patients with severe aortic regurgitation (AR) are prone to suffer from pulmonary hypertension (PH), understanding TAVR’s efficacy in this context is crucial. This study aims to explore the short-term prognosis of TAVR in PNAR patients with concurrent PH. Methods: Patients with PNAR undergoing TAVR at Zhongshan Hospital, Affiliated with Fudan University, were enrolled between June 2018 to June 2023. They were categorized based on pulmonary artery systolic pressure (PASP) into groups with or without PH. The baseline characteristics, imaging records, and follow-up data were collected. Results: Among the 103 patients recruited, 48 were afflicted with PH. In comparison to PNAR patients without PH, the PH group exhibited higher rates of renal dysfunction (10.4% vs. 0.0%, p = 0.014), increased Society of Thoracic Surgeons scores (6.4 ± 1.9 vs. 4.7 ± 1.6, p < 0.001), and elevated Nterminal fragment of pro–brain natriuretic peptide (NT-proBNP). Transthoracic ultrasound examination revealed that patients with PH displayed lower left ventricular ejection fraction, larger left ventricle dimension, and more frequent moderate to severe tcuspid regurgitation (TR). Following TAVR, both groups experienced significant reductions in PASP, mitral regurgitation (MR) and TR. There were no significant differences in the incidence of postoperative adverse events in patients with or without PH. Conclusions: We found TAVR to be a safe and effective treatment for patients with PNAR and PH, reducing the degree of aortic regurgitation and PH without increasing the risk of postoperative adverse events.

Abstract Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three‐round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3–6 month period and suggested a tentative cut‐off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ‐5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient‐reported outcomes. The AWGC consensus offers a comprehensive definition and user‐friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co‐morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P

Background Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). Methods We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. Results A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40–2.20] for CVD, 3.53 95% CI = [2.21–5.64] for ischemic strokes, and 17.07 95% CI = [13.82–76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). Conclusion PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

This paper aims to investigate the response and fracture of EMT carbon steel round-hole tubes (EMT carbon steel RHTs) under cyclic bending loads. The study considers four different hole orientations (0°, 30°, 60°, and 90°) and five distinct hole diameters (2, 4, 6, 8, and 10 mm). The results reveal that hole orientation and diameter exert a minimal impact on the moment-curvature relationship, leading to the formation of stable loops. The ovalization-curvature graphs demonstrate a trend of asymmetry, serration, and growth with an increasing number of bending cycles. Additionally, larger hole orientations or smaller notch diameters result in reduced ovalization. Furthermore, the double logarithmic coordinates of the controlled curvature–number of cycles required to induce fracture reveal five parallel lines for different hole diameters when the hole orientation is fixed. Finally, in adopting the formulas for smooth tubes and for 6061-T6 aluminum alloy round-hole tubes (6061 aluminum alloy RHTs), this study adjusts the related material parameters. These modifications effectively describe the controlled curvature–number of cycles required to induce fracture for EMT carbon steel RHTs with different hole orientations and diameters under cyclic bending, demonstrating reasonable agreement with the experimental results.

This paper aims to investigate the response and local buckling of locally sharp-notched C2700 brass circular tubes (LSN C2700 brass circular tubes) under cyclic bending loads. The study considers four different notch orientations (0°, 30°, 60°, and 90°) and five distinct notch depths (0.2, 0.4, 0.6, 0.8, and 1.0 mm). The results reveal that notch orientation and depth exert minimal impact on the moment–curvature relationship, leading to the formation of stable loops. The ovalization–curvature graphs demonstrate a trend of symmetry, serration, and growth with an increasing number of bending cycles. Additionally, larger notch orientations or smaller notch depths result in reduced ovalization. Furthermore, the double logarithmic coordinates of controlled curvature–number of cycles necessary to induce local buckling reveal five non-parallel lines representing different notch depths when the notch orientation is fixed. Finally, by adopting the formulas for smooth tubes and for locally sharp-notched 304 stainless steel circular tubes (LSN SS304 circular tubes), this study adjusts the related material parameters accordingly. These modifications effectively describe the controlled curvature–number of cycles necessary to induce local buckling for LSN C2700 brass circular tubes with different notch orientations and depths under cyclic bending, demonstrating reasonable agreement with the experimental results.

Objective When considering proposals to improve diets, it is important to understand how factors like price and income can affect saturated fat (SF) intake and demand. In this study, we examine and estimate the influence of price and income on intake across 160 countries, by age and sex, and derive sensitivity measures (price elasticities) that vary by age, sex and world region.Design We econometrically estimate intake responsiveness to income and prices across countries, accounting for differences by world region, age and sex. Intake data by age, sex and country were obtained from the 2018 Global Dietary Database. These data were then linked to global price data for select food groups from the World Bank International Comparison Programme and income data from the World Development Indicators Databank (World Bank).Results Intake differences due to price were highly significant, with a 1% increase in price associated with a lower SF intake (% energy/d) of about 4.3 percentage points. We also find significant differences across regions. In high-income countries, median (age 40) intake reductions were 1.4, 0.8 and 0.2 percentage points, given a 1% increase in the price of meat, dairy, and oils and fats, respectively. Price elasticities varied with age but not sex. Intake differences due to income were insignificant when regional binary variables were included in the analysis.Conclusion The results of this study show heterogeneous associations among prices and intake within and across countries. Policymakers should consider these heterogeneous effects as they address global nutrition and health challenges.

Although elliptical tubes are stronger and more stable than circular tubes, few studies have fully considered the behavior of elliptical tubes under cyclic bending loads. This study experimentally investigated the response and failure of SUS304 stainless steel elliptical tubes with four different ratios of long and short axes (1.5, 2.0, 2.5, and 3.0) under cyclic bending along four different orientation angles (0°, 30°, 60°, and 90°). The wall thickness was 0.7 mm, and cyclic bending was applied until buckling failure occurred. The moment–curvature curves exhibited cyclic hardening, and stable loops were formed for all long–short axis ratios and orientation angles. Increasing the long–short axis ratio slightly decreased the peak bending moment while increasing the orientation angle increased the peak bending moment. For a given orientation angle, the curves relating the short-axis variation (i.e., change in length divided by the original length of the short axis) and curvature demonstrated symmetry, serrations, and a growth pattern as the number of cycles increased regardless of the long–short axis ratio. At long–short axis ratios of 2.0, 2.5, and 3.0, these curves even exhibited a butterfly-like trend. Increasing the long–short axis ratio increased the short-axis variation, while increasing the orientation angle decreased the short-axis variation. Regarding the curves relating the curvature and number of cycles required to initiate buckling, for each orientation angle, the four long–short axis ratios corresponded to four straight lines when plotted on double-logarithmic co-ordinates. Based on the experimental results, empirical equations are proposed to describe the above relationships. The empirical equations were applied to predicting experimental data and showed close agreement.

Background: Obesity control and prevention remains challenging. Randomized controlled trials in western countries have demonstrated efficacy of dairy supplementation on fat mass reduction and lean mass increase, when combined with energy restriction protocols. However, there is scanty information on this issue among the East Asian population. Objective: The aim of this study is to investigate the association between milk consumption and weight status in Asian. Design: First, we studied the association between milk intake and body mass index (BMI) changes in a 10-year longitudinal study of Cardiovascular Disease Risk Factor Two-township Study (CVDFACTS) with 1,644 adults. Second, taking advantage of the genetic and phenotype data of 10,000 participants collected by Taiwan Biobank (TWB), we carried out a Mendelian randomization (MR) study to investigate the causal relationship between milk intake and BMI. A lactase persistence genetic marker (rs4954490) was used as the instrumental variable. Results: We found in the longitudinal study that higher baseline milk consumption level was associated with lower odds of increasing BMI or maintaining overweight/obesity status. In the MR study, we found that G allele of the rs4954490, a surrogate of greater milk intake, was associated with lower odds of being obese (BMI > 27 kg/m2); the odds ratio (OR) for the GG versus AA is 0.85 (P = 0.037), and the OR for the GA versus AA is 0.84 (P = 0.032). Conclusions: These findings support current food guide in Asian countries to include dairy group as one of the six food groups for nutrition recommendation.

Abstract The proportion of allergic diseases attributable to atopy remains a subject of controversy. This study aimed to estimate the population risk of physician-diagnosed asthma, rhinitis and eczema attributed to atopy among a population sample of Asian school-age children. Asian children aged 5–18 years (n = 1321) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were tested for serum allergen-specific immunoglobulin E. Physician-diagnosed asthma, rhinitis and eczema were assessed by a modified International Study of Asthma and Allergies in Childhood questionnaire. Atopy was defined as the presence of serum allergen-specific immunoglobulin E. In this population-based study, 50.4% of the subjects with asthma, 46.3% with rhinitis, and 46.7% with eczema were attributable to atopy. The population attributable risk (PAR) of atopy for three allergic diseases was higher in adolescents (asthma, 54.4%; rhinitis, 59.6%; eczema, 49.5%) than younger children aged less than 10 years (asthma, 46.9%; rhinitis, 39.5%; eczema, 41.9%). Among the seven allergen categories, sensitization to mites had the highest PARs for all three allergic diseases (51.3 to 64.1%), followed by sensitization to foods (asthma, 7.1%; rhinitis, 10.4%; eczema 27.7%). In conclusion, approximately half (46.3 to 50.4%) of Asian children in Taiwan with allergic diseases are attributable to atopy.

Abstract Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy’s potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine’s ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture wellknown features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these largescale patterns to widespread changes linked to alterations in brain conditions. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to identify the spatial patterns of lower respiratory tract infections (LRIs) and their association with fine particulate matter (PM2.5). The disability-adjusted life year (DALY) database was used to represent the burden each country experiences as a result of LRIs. PM2.5 data obtained from the Atmosphere Composition Analysis Group was assessed as the source for main exposure. Global Moran’s I and Getis-Ord Gi* were applied to identify the spatial patterns and for hotspots analysis of LRIs. A generalized linear mixed model was coupled with a sensitivity test after controlling for covariates to estimate the association between LRIs and PM2.5. Subgroup analyses were performed to determine whether LRIs and PM2.5 are correlated for various ages and geographic regions. A significant spatial auto-correlated pattern was identified for global LRIs with Moran’s Index 0.79, and the hotspots of LRIs were clustered in 35 African and 4 Eastern Mediterranean countries. A consistent significant positive association between LRIs and PM2.5 with a coefficient of 0.21 (95% CI 0.06–0.36) was identified. Furthermore, subgroup analysis revealed a significant effect of PM2.5 on LRI for children (0–14 years) and the elderly (≥ 70 years), and this effect was confirmed to be significant in all regions except for those comprised of Eastern Mediterranean countries.

Abstract Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non‐diabetic hypertensive patients aged 20–50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24‐h ambulatory BP monitoring, and 24‐h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24‐h ambulatory BP, and 24‐h urine catecholamine excretion. In men, 24‐h urine total catecholamine levels were correlated with 24‐h SBP (r = 0.103, p = .008) and 24‐h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24‐h urine total catecholamine levels and 24‐h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01–3.29, p = .048) and 24‐h urine total catecholamine (β = 5.03, 95% CI 0.62–9.44, p = .025) were both independently associated with 24‐h SBP; being male was independently associated with 24‐h DBP (β = 3.55, 95% CI 2.26–4.85, p

Human motion has multifarious meanings that can be recognized using a facial detection machine. This article aims to explore body motion recognition to explain the relationship between students’ motions and their achievement, as well as teachers’ responses to students’ motions, and especially to negative ones. Students’ motions can be identified according to three categories; facial expression, hand gestures, and body position and movement. Facial expression covers four categories, namely, contempt, fear, happiness, and sadness. Contempt is used to express conflicted feelings, fear to express unpleasantness, happiness to express satisfaction, and sadness to express that the environment is uncomfortable. Hand gestures can likewise be grouped into four categories: conversational gestures, controlling gestures, manipulative gestures, and communicative gestures. Conversational gestures refer to communicative gestures. Controlling gestures refer to vision-based interface communications, like the ones popular in current technology. Manipulative gestures refer to ones used in human interaction with virtual objects. Communicative gestures relate to human interaction, and therefore involve the field of psychology. Body position and movement also can be classified into four categories, namely: leaning forward, leaning backward, correct posture, and physical relocation. Leaning forward happens when a user is working with a high level of concentration. Leaning backward occurs when a user has been highly concentrated on work for several hours, and needs a break or change. Correct posture is the sign of an enjoyable working position which involves sitting in a free and relaxed manner. Movement refers to a change to the student’s sitting location, reflecting some inadequacy of the learning environment. Teachers can anticipate changes of students’ emotions by good learning design, teaching metacognitive skills, self-regulated performance, exploratory talks, mastery approach/avoidance, using hybrid learning environments, and controlling space within classrooms. Teachers’ responses to students’ motions will be explored in this article

Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain’s physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field.

The COVID-19 pandemic has spread across the country negatively impacting on the economy. This paper uses the panel data of 14 prefecture-level cities from 2015 to 2020 in Hunan to determine the factors and effects of economic downturns based on the spatial econometric model. We calculate the Moran index, so-called the Moran's I, to analyse the impact of each factor on the economy. The results show that the spatial correlation of the cities around Chang-Zhu-Tan is high, and the economic growth of the entire province can be influenced by these cities. These cities should adopt strategies to improve the economy, such as reducing the tax revenues, improving the local financial revenues, and reducing the ineffective educational input. These results can also be helpful for policymakers, who will attempt to retransform the Hunan economy during the post-COVID era.

BackgroundHigher consumption of sugar-sweetened beverages (SSBs) maybe association with children's sleep pattern. However, few studies have considered this association in Asia, especially in school children. This study investigated the relationship between children's consumption frequency of such beverages and their sleep duration.MethodsParticipants aged 6–12 years were analyzed from two survey data in 2012 and 2013–2016 Nutrition and Health Surveys in Taiwan. A total of 2,628 participants were included in the analysis (2012, N = 1,267; 2013–2016, N = 1,361). Beverages weekly consumption were divided into low and high intake groups by medians cut-off points. The sleep variables were the sleep duration at night (including school days and weekends) and sleep debt. After controlling the confounders, the correlation between sugar-sweetened beverage consumption and sleep duration was examined using multinomial logistic regression analysis.ResultsThe students slept for an average of 8.8 h on school days and 9.7 h on weekends. Relative to the low SSB intake group, the high intake group exhibited shorter sleep durations on school days (P < 0.001), greater sleep debt (P = 0.049). In logistic regression, high intake group were more likely to sleep for 2 h of sleep debt than low intake group (OR = 1.41, P = 0.022).ConclusionsChildren who had consumed sugar-sweetened beverages frequently slept for shorter durations at night on school days and exhibited greater sleep debt. The causal relationship was not clear. Nonetheless, these two factors are important in promoting children health.

BackgroundPrevious studies have demonstrated that C-reactive protein (CRP) and glycated hemoglobin (HbA1c) levels are independently associated with neurodegenerative diseases, which can be improved by altering dietary patterns. This study investigates the combined effect of CRP and HbA1c, as well as the influence of dietary patterns, on the risk of dementia.MethodsA cross-sectional study was conducted with 536 participants aged ≥65 years who were recruited from the Nutrition and Health Survey in Taiwan between 2014 and 2016. The high levels of inflammation and glycation were defined as a CRP level of >0.21 mg/dl and a HbA1c level of ≥6.50%, respectively. Mild cognitive impairment (MCI) was evaluated using the Mini-Mental State Examination (MMSE) score. The dietary patterns associated with CRP and HbA1c levels were assessed using the reduced rank regression (RRR). Multivariate logistic regression analysis of both complete and imputed datasets was performed.ResultsParticipants with high levels of both CRP and HbA1c were associated with the highest odds ratio (OR) of MCI (adjusted OR [aOR] = 3.52; 95% CI = 3.48, 3.56; p < 0.001), followed by a high level of only HbA1c (aOR = 1.73; p < 0.001) and a high level of CRP (aOR = 1.49; p < 0.001). Using the reduced rank regression, an inverse relationship between higher consumption nuts and seeds and lower levels of CRP and HbA1c was found (both factors loading < −0.2). Concerning the combined effect of tertiles among the factor 1 and factor 2 analyzed by dietary patterns, group 1 with both T3 (high tertiles) was associated with the greatest OR of MCI (aOR = 4.38; 95% CI = 4.34, 4.42; p < 0.001) using multiple imputation.ConclusionsThe combined effect of high levels of inflammation and hyperglycemia was associated with an increased likelihood of MCI. Moreover, dietary patterns positively related to inflammation and hyperglycemia were associated with MCI, while eating nuts and seeds promoted better cognition.

Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24–28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.

Background Taiwan has the highest prevalence of chronic kidney disease (CKD). Impaired cognition and quality of life are significant phenomena in the late stages of CKD. We sought to obtain an overview and the attributable effect of impaired glomerular filtration on multiple domains in cognition and dimensions of quality of life for community-based healthy older adults in Taiwan. Methods The study was derived from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013–2016, a nationwide cross-sectional study conducted to sample healthy, community-based older adults aged ≥65 years in Taiwan. Participants were categorized into four CKD groups: CKD stage 1, stage 2, stages 3a and 3b, and stages 4–5. The Mini-Mental State Examination (MMSE) and the QoL questionnaire derived from the 12-item Short Form Health Survey (SF-12) were measured. Generalized linear mixed models (GLMMs) and principal component regressions were employed for the analysis and validation, respectively. Results Participants with moderate CKD (stages 3a and 3b) showed deficits in global MMSE, domain orientation to time, calculation, complex commands, and role-physical and vitality in QoL questionnaires. In GLMMs, impaired eGFR per 30 mL/min/1.73 m² was associated with lower global MMSE scores (β = -0.807, standard error [SE] = 0.235, P = 0.0007), domain orientation to time (β = -0.155, SE = 0.047, P = 0.0011), calculation (β = -0.338, SE = 0.109, P = 0.0020), complex commands (β = -0.156, SE = 0.079, P = 0.0494), and role-physical (β = -2.219, SE = 0.779, P = 0.0046) dimensions of QoL. Conclusions Elderly Han Chinese adults with moderately impaired renal filtration could manifest cognitive deficits in orientation to time, calculation, and impaired quality of life in physical role functioning.

Abstracts: Functional connectivity, which reflects the spatial and temporal organization of intrinsic activity throughout the brain, is one of the most studied measures in human neuroimaging research. The noninvasive acquisition of resting state functional magnetic resonance imaging (rs-fMRI) allows the characterization of features designated as functional networks, functional connectivity gradients, and time-varying activity patterns that provide insight into the intrinsic functional organization of the brain and potential alterations related to brain dysfunction. Functional connectivity, hence, captures dimensions of the brain's activity that have enormous potential for both clinical and preclinical research. However, the mechanisms underlying functional connectivity have yet to be fully characterized, hindering interpretation of rs-fMRI studies. As in other branches of neuroscience, the identification of the neurophysiological processes that contribute to functional connectivity largely depends on research conducted on laboratory animals, which provide a platform where specific, multi-dimensional investigations that involve invasive measurements can be carried out. These highly controlled experiments facilitate the interpretation of the temporal correlations observed across the brain. Indeed, information obtained from animal experimentation to date is the basis for our current understanding of the underlying basis for functional brain connectivity. This review presents a compendium of some of the most critical advances in the field based on the efforts made by the animal neuroimaging community.

Objective: This study aimed to develop machine learning-based prediction models to predict masked hypertension and masked uncontrolled hypertension using the clinical characteristics of patients at a single outpatient visit.Methods: Data were derived from two cohorts in Taiwan. The first cohort included 970 hypertensive patients recruited from six medical centers between 2004 and 2005, which were split into a training set (n = 679), a validation set (n = 146), and a test set (n = 145) for model development and internal validation. The second cohort included 416 hypertensive patients recruited from a single medical center between 2012 and 2020, which was used for external validation. We used 33 clinical characteristics as candidate variables to develop models based on logistic regression (LR), random forest (RF), eXtreme Gradient Boosting (XGboost), and artificial neural network (ANN).Results: The four models featured high sensitivity and high negative predictive value (NPV) in internal validation (sensitivity = 0.914–1.000; NPV = 0.853–1.000) and external validation (sensitivity = 0.950–1.000; NPV = 0.875–1.000). The RF, XGboost, and ANN models showed much higher area under the receiver operating characteristic curve (AUC) (0.799–0.851 in internal validation, 0.672–0.837 in external validation) than the LR model. Among the models, the RF model, composed of 6 predictor variables, had the best overall performance in both internal and external validation (AUC = 0.851 and 0.837; sensitivity = 1.000 and 1.000; specificity = 0.609 and 0.580; NPV = 1.000 and 1.000; accuracy = 0.766 and 0.721, respectively).Conclusion: An effective machine learning-based predictive model that requires data from a single clinic visit may help to identify masked hypertension and masked uncontrolled hypertension.