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Background: To prevent school injuries, thorough epidemiological data is an essential foundation. We aimed to investigate the characteristics of school injuries in Asia and explore risk factors for major trauma., Methods: This retrospective study was conducted in the participating centers of the Pan-Asian Trauma Outcome Study from October 2015 to December 2020. Subjects who reported "school" as the site of injury were included. Major trauma was defined as an Injury Severity Score (ISS) value of ≥16., Results: In total, 1305 injury cases (1.0% of 127,715 events) occurred at schools. Among these, 68.2% were children. Unintentional injuries were the leading cause and intentional injuries comprised 7.5% of the cohort. Major trauma accounted for 7.1% of those with documented ISS values. Multivariable regression revealed associations between major trauma and factors, including age, intention of injury (self-harm), type of injury (traffic injuries, falls), and body part injured (head, thorax, and abdomen). Twenty-two (1.7%) died, with six deaths related to self-harm. Females represented 28.4% of injuries but accounted for 40.9% of all deaths., Conclusions: In Asia, injuries at schools affect a significant number of children. Although the incidence of injuries was higher in males, self-inflicted injuries and mortality cases were relatively higher in females., Impact: Epidemiological data and risk factors for major trauma resulting from school injuries in Asia are lacking. This study identified significant risk factors for major trauma occurring at schools, including age, intention of injury (self-harm), injury type (traffic injuries, falls), and body part injured (head, thoracic, and abdominal injuries). Although the incidence of injuries was higher in males, the incidence of self-harm injuries and mortality rates were higher in females. The results of this would make a significant contribution to the development of prevention strategies and relative policies concerning school injuries., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan-Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality., (© 2023. The Author(s).)

Children and adolescents are vulnerable to non-accidental injury. Early identification and prevention rely on detailed epidemiological studies, which are limited in Asia. This retrospective study used the registry data of Pan-Asian Trauma Outcome Study (PATOS) from October 1, 2015 to December, 31, 2020. Pediatric patients (aged < 20 years) with non-accidental injuries were enrolled, which were divided by age into preschool (0-6 years), child (7-12 years), and adolescent (13-19 years) groups. Baseline characteristics, injury epidemiology, and excess mortality ratio-adjusted injury severity score (EMR-ISS) were collected. Major trauma was defined as an EMR-ISS score > 24. The study enrolled 451 patients with non-accidental injuries, accounting for 2.81% of pediatric trauma events presented to an emergency department in the PATOS registry. The overall mortality rate was 0.9%, similar to those in Western countries. Mortality rate was high in preschool children (8.7%, p = 0.017) than in other age groups. The sex-specific incidence was higher in boys (3.10% vs. 2.13%, p = 0.001). In adolescents, more events occurred on the street (25.9%), whereas home remained the most common locale in girls of all ages. In the multivariable regression analysis, abdominal and multiple injuries were risk factors for major trauma., (© 2023. The Author(s).)

Prehospital fluid resuscitation with crystalloids in patients following trauma remain controversial. This study aimed to investigate the association between prehospital fluid resuscitation and outcomes of trauma patients in Asia. We conducted a retrospective cohort study of trauma patients between 2016 and 2018 using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital fluid resuscitation was defined as any administration of intravenous crystalloid fluid on the ambulance before arrival to hospitals. The outcomes were in-hospital mortality and poor functional outcomes, defined as Modified Rankin Scale ≥ 4. Propensity score matching (PSM) was used to equalize potential prognostic factors in both groups. This study included 31,735 patients from six countries in Asia, and 4318 (13.6%) patients had ever received prehospital fluid resuscitation. The patients receiving prehospital fluid resuscitation had a higher risk of in-hospital mortality, with an adjusted odds ratio (aOR) of 2.02, 95% confidence interval (CI) 1.32-3.10, p = 0.001 in PSM analysis. Prehospital fluid resuscitation was also associated with poor functional outcomes, with an OR 1.73, 95% CI: 1.48-2.03, p < 0.001 in PSM analysis. Prehospital fluid resuscitation in patients with major trauma (injury severity score ≥ 16) presented a higher risk of poor functional outcomes (aOR = 2.65, 95% CI: 1.89-3.73 in PSM analysis, p interaction  = 0.006) via subgroup analysis. Prehospital fluid resuscitation of trauma patients is associated with higher in-hospital mortality and poor functional outcomes in the subgroup in countries studied., (© 2022. The Author(s).)

Prehospital spinal immobilization is a widely used procedure in the emergency medical service (EMS) system worldwide, while the incidence of patients with spinal injury (SI) is relatively low, and unnecessary prehospital spinal immobilization is associated with patient complications. This study aimed to determine the association between prehospital spine immobilization and favorable functional outcomes at hospital discharge among trauma patients with SI. We conducted a retrospective cohort study using the Pan-Asia Trauma Outcomes Study (PATOS) registry data from January 1, 2016, to November 30, 2018. A total of 759 patients with SI were enrolled from 43,752 trauma patients in the PATOS registry during the study period. The subjects had a median age of 58 years (Q1-Q3, 41-72), and 438 (57.7%) patients had prehospital spine immobilization. Overall, prehospital spinal immobilization was not associated with favorable functional outcomes at discharge in multivariable logistic regression (aOR 1.06; 95% CI 0.62-1.81, p = 0.826). However, in the subgroup of cervical SI, prehospital spinal immobilization was associated with favorable functional outcomes at discharge (aOR 3.14; 95% CI 1.04-9.50; p = 0.043). Therefore, we suggest that paramedics should be more careful when determining the presence of a cervical SI and should apply full spine immobilization if possible., (© 2022. The Author(s).)

Satellite-tracking of adult bumphead sunfish, Mola alexandrini, revealed long-distance latitudinal migration patterns covering thousands of kilometers. Horizontal and vertical movements of four bumphead sunfish off Taiwan were recorded with pop-up satellite archival tags in 2019-2020. Two individuals moved northward and traveled to Okinawa Island and Kyushu, Japan and two moved southwards; crossing the equator, to Papua New Guinea and New Caledonia. During daytime, bumphead sunfish descended below the thermocline and ascended to mixed layer depths (MLD) during nighttime. The N-S migrants, however, demonstrated different habitat utilization patterns. Instead of using prevailing currents, the northward movements of sunfish cohorts exhibited extensive use of mesoscale eddies. Fish in anticyclonic eddies usually occupied deeper habitats whereas those in cyclonic eddies used near-surface habitats. On northward excursions, fish spent most of their time in regions with high dissolved oxygen concentrations. Southward movement patterns were associated with major currents and thermal stratification of the water column. In highly stratified regions, fish stayed below the thermocline and frequently ascended to MLD during daytime either to warm muscles or repay oxygen debts. These results for bumphead sunfish present important insights into different habitat use patterns and the ability to undergo long-distance migrations over varying spatial-temporal scales and features., (© 2021. The Author(s).)

Geochemical chronologies were constructed from otoliths of adult Pacific bluefin tuna (PBT) to investigate the timing of age-specific egress of juveniles from coastal nurseries in the East China Sea or Sea of Japan to offshore waters of the Pacific Ocean. Element:Ca chronologies were developed for otolith Li, Mg, Mn, Zn, Sr, and Ba, and our assessment focused on the section of the otolith corresponding to the age-0 to age-1 + interval. Next, we applied a common time-series approach to geochemical profiles to identify divergences presumably linked to inshore-offshore migrations. Conspicuous geochemical shifts were detected during the juvenile interval for Mg:Ca, Mn:Ca, and Sr:Ca that were indicative of coastal-offshore transitions or egress generally occurring for individuals approximately 4-6 mo. old, with later departures (6 mo. or older) linked to overwintering being more limited. Changepoints in otolith Ba:Ca profiles were most common in the early age-1 period (ca. 12-16 mo.) and appear associated with entry into upwelling areas such as the California Current Large Marine Ecosystem following trans-Pacific migrations. Natal origin of PBT was also predicted using the early life portion of geochemical profile in relation to a baseline sample comprised of age-0 PBT from the two primary spawning areas in the East China Sea and Sea of Japan. Mixed-stock analysis indicated that the majority (66%) of adult PBT in our sample originated from the East China Sea, but individuals of Sea of Japan origin were also detected in the Ryukyu Archipelago., (© 2021. The Author(s).)

We report spin-dependent transport properties and I-V hysteresis characteristics in an [Formula: see text]-based magnetic tunnel junction (MTJ). The bipolar resistive switching and the magnetoresistances measured at high resistance state (HRS) and low resistance state (LRS) yield four distinctive resistive states in a single device. The temperature dependence of resistance at LRS suggests that the resistive switching is not triggered by the metal filaments within the [Formula: see text] layer. The role played by oxygen vacancies in [Formula: see text] is the key to determine the resistive state. Our study reveals the possibility of controlling the multiple resistive states in a single [Formula: see text]-based MTJ by the interplay of both electric and magnetic fields, thus providing potential applications for future multi-bit memory devices.

Our study aimed to compare the effect of self-instruction with manikin feedback to that of instructor-led method on cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) skill performance. In our randomized non-inferiority trial, 64 non-healthcare providers were randomly allocated into self-instruction and instructor-led groups. Both groups watched a 27-min standardized teaching video. Participants in the self-instruction group then performed hands-on practice on the Resusci Anne QCPR with a device-driven feedback, while those in the instructor-led group practiced manikins; feedback was provided and student's questions were answered by instructors. Outcomes were measured by blinded evaluators and SkillReporter software. The primary outcome was the pass rate. Secondary outcomes were scores of the knowledge test and items of individual skill performance. The baseline characteristics of the two groups were similar. The pass rates were 93.8% in both group (absolute difference 0%, p = 0.049 for noninferiority). The knowledge test scores were not significantly different. However, the self-instruction group performed better in some chest compression and ventilation skills, but performed worse in confirming environmental safety and checking normal breathing. There was no difference in AED skills between the two groups. Our results showed the self-instruction method is not inferior to the instructor-led method.

To detect substation faults for timely repair, this paper proposes a fault detection method that is based on the time series model and the statistical process control method to analyze the regulation and characteristics of the behavior in the switching process. As the first time, this paper proposes a fault detection model using SARIMA, statistical process control (SPC) methods, and 3σ criterion to analyze the characteristics in substation's switching process. The employed approaches are both very common tools in the statistics field, however, via effectively combining them with industrial process fault diagnosis, these common statistical tolls play excellent role to achieve rich technical contributions. Finally, for different fault samples, the proposed method improves the rate of detection by at least 9% (and up to 15%) than other methods.

Bifunctional fusion protein design has been widely utilized as a strategy to increase the efficacy of protein therapeutics. Previously, we proposed a novel application of the bifunctional fusion protein design through the introduction of proinsulin-transferrin (ProINS-Tf) fusion protein as a liver-specific protein prodrug to achieve a glucose-lowering effect in type 1 diabetic mice. In this report, we studied the binding characteristics of this activated fusion protein to the insulin receptor to elucidate its mechanism in eliciting insulin receptor-mediated signaling. We found that, with the assistance of the transferrin moiety binding to the transferrin receptor, the activated ProINS-Tf exhibited significantly higher binding affinity to the insulin receptor compared with the native insulin, resulting in a prolonged and stronger Akt phosphorylation. This enhanced induction by activated ProINS-Tf overcame insulin resistance in palmitate-treated HepG2 cells. ProINS-Tf also demonstrated a better glucose-lowering effect than native insulin, even with a much lower dose and less frequent injections, in non-obese diabetic mice with insulin resistance symptoms. The activated ProINS-Tf, serving as a bivalent protein molecule, could be a new insulin analog to overcome insulin resistance, which is associated with several diseases, including type 2 diabetes and non-alcoholic fatty liver disease.

In this Letter, the graphs in Fig. 2a and c were inadvertently the same owing to a copy and paste error from the original graphs in Prism. The Source Data files containing the raw data were correct. Fig. 2c has been corrected online.

Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established 1,2 . Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1 F121A/F121A ) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1 F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho 3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are rescued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1-BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.

Inherited retinal dystrophies (IRDs) are clinically and genetically highly heterogeneous, making clinical diagnosis difficult. The advances in high-throughput sequencing (ie, panel, exome and genome sequencing) have proven highly effective on defining the molecular basis of these disorders by identifying the underlying variants in the respective gene. Here we report two siblings affected by an IRD phenotype and a novel homozygous c.1691A>G (p.(Asp564Gly)) ATF6 (activating transcription factor 6A) missense substitution identified by whole exome sequencing analysis. The pathogenicity of the variant was confirmed by functional analyses done on patients' fibroblasts and on recombinant p.(Asp564Gly) protein. The ATF6 Asp564Gly/Asp564Gly variant shows impaired production of the ATF6 cleaved transcriptional activator domain in response to endoplasmic reticulum stress. Detailed phenotypic examination revealed extinguished cone responses but also decreased rod responses together with the ability to discriminate some colours suggestive rather for cone-rod dystrophy than achromatopsia.

Ferromagnetic resonance driven spin pumping (FMR-SP) is a novel method to transfer spin current from the ferromagnetic (FM) layer into the adjacent normal metal (NM) layer in an FM/NM bilayer system. Consequently, the spin current could be probed in NM layer via inverse spin Hall effect (ISHE). In spite of numerous ISHE studies on FM/Pt bilayers, La 0.7 Sr 0.3 MnO 3 (LSMO)/Pt system has been less explored and its relevant information about interface property (characterized by spin mixing conductance) and spin-charge conversion efficiency (characterized by spin Hall angle) is a matter of importance for the possible applications of spintronic devices. In this work, the technique of FMR-SP has been applied on two series of LSMO/Pt bilayers with the thickness of each layer being varied. The thickness dependences of ISHE voltage allow to extract the values of spin mixing conductance and spin Hall angle of LSMO/Pt bilayers, which are (1.8 ± 0.4) × 10 19  m -2 and (1.2 ± 0.1) % respectively. In comparison with other FM/Pt systems, LSMO/Pt has comparable spin current density and spin mixing conductance, regardless its distinct electronic structure from other ferromagnetic metals.

The effect of erythropoiesis-stimulating agent (ESA) on dialysis initiation in advanced chronic kidney disease (CKD) patients is not clear. We retrospectively analyzed the outcome of dialysis initiation in a stage 5 CKD cohort with ESA reimbursement limited to the maximal standardized monthly ESA dose equivalent to epoetin beta 20,000 U by the National Health Insurance program. Totally 423 patients were followed up for a median of 1.37 year. A time-dependent Cox regression model, adjusted for monthly levels of estimated glomerular filtration rate (eGFR) and hemoglobin, was constructed to investigate the association between ESA and outcome. The standardized monthly ESA dose in ESA users was 16,000 ± 3,900 U of epoetin beta. Annual changes of hemoglobin were -0.29 ± 2.19 and -0.99 ± 2.46 g/dL in ESA users and ESA non-users, respectively (P = 0.038). However, annual eGFR decline rates were not different between ESA users and non-users. After adjustment, ESA use was associated with deferred dialysis initiation (hazard ratio 0.63, 95% confidence interval 0.42-0.93, P = 0.021). The protective effect remained when the monthly ESA doses were incorporated. Our data showed that restricted use of ESA was safe and associated with deferred dialysis initiation in stage 5 CKD patients.

Building integrated photovoltaics (BIPV) have attracted considerable interests because of its aesthetically attractive appearance and overall low cost. In BIPV, system integration on a glass substrate like windows is essential to cover a large area of a building with low cost. However, the conventional high voltage devices in inverters have to be built on the specially selected single crystal substrates, limiting its application for large area electronic systems, such as the BIPV. We demonstrate a Magnesium Zinc Oxide (MZO) based high voltage thin film transistor (HVTFT) built on a transparent glass substrate. The devices are designed with unique ring-type structures and use modulated Mg doping in the channel - gate dielectric interface, resulting in a blocking voltage of over 600 V. In addition to BIPV, the MZO HVTFT based inverter technology also creates new opportunities for emerging self-powered smart glass.

Intratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments. VAMPIRE analysis of ~39,000 cells from 13 previously sequenced patient-derived pancreatic cancer samples indicate that metastasized cells present significantly lower heterogeneity than primary tumor cells. We found the same morphological signature for metastasis for a cohort of 10 breast cancer cell lines. We further decipher the relative contributions to heterogeneity from cell cycle, cell-cell contact, cell stochasticity and heritable morphological variations.

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

The magnetic state of a ferromagnet can affect the electrical transport properties of the material; for example, the relative orientation of the magnetic moments in magnetic multilayers underlies the phenomenon of giant magnetoresistance. The inverse effect--in which a large electrical current density can perturb the magnetic state of a multilayer--has been predicted and observed experimentally with point contacts and lithographically patterned samples. Some of these observations were taken as indirect evidence for current-induced excitation of spin waves, or 'magnons'. Here we probe directly the high-frequency behaviour and partial phase coherence of such current-induced excitations, by externally irradiating a point contact with microwaves. We determine the magnon spectrum and investigate how the magnon frequency and amplitude vary with the exciting current. Our observations support the feasibility of a spin-wave maser' or 'SWASER' (spin-wave amplification by stimulated emission of radiation).