Air pollution exposure disparities across US population and income groups.

Air pollution contributes to the global burden of disease, with ambient exposure to fine particulate matter of diameters smaller than 2.5 µm (PM2.5) being identified as the fifth-ranking risk factor for mortality globally1. Racial/ethnic minorities and lower-income groups in the USA are at a higher risk of death from exposure to PM2.5 than are other population/income groups2-5. Moreover, disparities in exposure to air pollution among population and income groups are known to exist6-17. Here we develop a data platform that links demographic data (from the US Census Bureau and American Community Survey) and PM2.5 data18 across the USA. We analyse the data at the tabulation area level of US zip codes (N is approximately 32,000) between 2000 and 2016. We show that areas with higher-than-average white and Native American populations have been consistently exposed to average PM2.5 levels that are lower than areas with higher-than-average Black, Asian and Hispanic or Latino populations. Moreover, areas with low-income populations have been consistently exposed to higher average PM2.5 levels than areas with high-income groups for the years 2004-2016. Furthermore, disparities in exposure relative to safety standards set by the US Environmental Protection Agency19 and the World Health Organization20 have been increasing over time. Our findings suggest that more-targeted PM2.5 reductions are necessary to provide all people with a similar degree of protection from environmental hazards. Our study is observational and cannot provide insight into the drivers of the identified disparities.

Self-locking and stiffening deployable tubular structures.

Deployable tubular structures, designed for functional expansion, serve a wide range of applications, from flexible pipes to stiff structural elements. These structures, which transform from compact states, are crucial for creating adaptive solutions across engineering and scientific fields. A significant barrier to advancing their performance is balancing expandability with stiffness. Using compliant materials, these structures achieve more flexible transformations than those possible with rigid mechanisms. However, they typically exhibit reduced stiffness when subjected to external pressures (e.g., tube wall loading). Here, we utilize origami-inspired techniques and internal stiffeners to meet conflicting performance requirements. A self-locking mechanism is proposed, which combines the folding behavior observed in curved-crease origami and elastic shell buckling. This mechanism employs simple shell components, including internal diaphragms that undergo pseudofolding in a confined boundary condition to enable a snap-through transition. We reveal that the deployed tube is self-locked through geometrical interference, creating a braced tubular arrangement. This arrangement gives a direction-dependent structural performance, ranging from elastic response to crushing, thereby offering the potential for programmable structures. We demonstrate that our approach can advance existing deployment mechanisms (e.g., coiled and inflatable systems) and create diverse structural designs (e.g., metamaterials, adaptive structures, cantilevers, and lightweight panels).Weanticipate our design to be a starting point to drive technological advancement in real-world deployable tubular structures.

C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases.

The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones. The C-terminal end position is essential for C-end degron function. Truncated selenoproteins generated by translation errors and the USP1 N-terminal fragment from post-translational cleavage are eliminated by DesCEND. DesCEND also targets full-length proteins with naturally occurring C-end degrons. The C-end degron in DesCEND echoes the N-end degron in the N-end rule pathway, highlighting the dominance of protein "ends" as indicators for protein elimination.

The use of bubble charts in analyzing second stage cesarean delivery rates.

BACKGROUND: The incidence of second stage cesarean delivery has been rising globally because of the failure or the anticipated difficulty of performing instrumental delivery. Yet, the best way to interpret the figure and its optimal rate remain to be determined. This is because it is strongly influenced by the practice of other 2 modes of birth, namely cesarean delivery performed before reaching the second stage and assisted vaginal birth during the second stage. In this regard, a bubble chart that can display 3-dimensional data through its x-axis, y-axis, and the size of each plot (presented as a bubble) may be a suitable method to evaluate the relationship between the rates of these 3 modes of births. OBJECTIVE: This study aimed to conduct an epidemiologic study on the incidence of second stage cesarean deliveries rates among >300,000 singleton term births in 10 years from 8 obstetrical units and to compare their second stage cesarean delivery rates in relation to their pre-second stage cesarean delivery rates and assisted vaginal birth rates using a bubble chart. STUDY DESIGN: The territory-wide birth data collected between 2009 and 2018 from all 8 public obstetrical units (labelled as A to H) were reviewed. The inclusion criteria were all singleton pregnancies with cephalic presentation that were delivered at term (≥37 weeks' gestation). Pre-second stage cesarean delivery rate was defined as all elective cesarean deliveries and those emergency cesarean deliveries that occurred before full cervical dilatation was achieved as a proportion of the total number of births. The second stage cesarean delivery rate and assisted vaginal birth rate were calculated according to the respective mode of delivery as a proportion of the number of cases that reached full cervical dilatation. The rates of these 3 modes of births were compared among the parity groups and among the 8 units. Using a bubble chart, each unit's second stage cesarean delivery rate (y-axis) was plotted against its pre-second stage cesarean delivery rate (x-axis) as a bubble. Each unit's second stage cesarean delivery to assisted vaginal birth ratio was represented by the size of the bubble. RESULTS: During the study period, a total of 353,434 singleton cephalic presenting term pregnancies were delivered in the 8 units, and 180,496 (51.1%) were from nulliparous mothers. When compared with the multiparous group, the nulliparous group had a significantly lower pre-second stage cesarean delivery rate (18.58% vs 21.26%; P<.001) but a higher second stage cesarean delivery rate (0.79% vs 0.22%; P<.001) and a higher assisted vaginal birth rate (17.61% vs 3.58%; P<.001). Using the bubble of their averages as a reference point in the bubble chart, the 8 units' bubbles were clustered into 5 regions indicating their differences in practice: unit B and unit H were close to the average in the center. Unit A and unit F were at the upper right corner with a higher pre-second stage cesarean delivery rate and second stage cesarean delivery rate. Unit D and unit E were at the opposite end. Unit C was at the upper left corner with a low pre-second stage cesarean delivery rate but a high second stage cesarean delivery rate, whereas unit G was at the opposite end. Unit C and unit G were also in the extremes in terms of pre-second stage cesarean delivery to assisted vaginal birth ratio (0.09 and 0.01, respectively). Although some units seemed to have very similar second stage cesarean delivery rates, their obstetrical practices were differentiated by the bubble chart. CONCLUSION: The second stage cesarean delivery rate must be evaluated in the context of the rates of pre-second stage cesarean delivery and assisted vaginal birth. A bubble chart is a useful method for analyzing the relationship among these 3 variables to differentiate the obstetrical practice between different units.

Influence of Inorganic Anions on the Chemical Stability of Molybdenum Disulfide Nanosheets in the Aqueous Environment.

Chemical stability is closely associated with the transformations and bioavailabilities of engineered nanomaterials and is a key factor that governs broader and long-term application. With the growing utilization of molybdenum disulfide (MoS2) nanosheets in water treatment and purification processes, it is crucial to evaluate the stability of MoS2 nanosheets in aquatic environments. Nonetheless, the effects of anionic species on MoS2 remain largely unexplored. Herein, the stability of chemically exfoliated MoS2 nanosheets (ceMoS2) was assessed in the presence of inorganic anions. The results showed that the chemical stability of ceMoS2 was regulated by the nucleophilicities and the resultant charging effects of the anions in aquatic systems. The anions promote the dissolution of ceMoS2 by triggering a shift in the chemical potential of the ceMoS2 surface as a function of the anion nucleophilicity (i.e., charging effect). Fast charging with HCO3- and HPO42-/H2PO4- was validated by a phase transition from 1T to 2H and the emergence of MoV, and it promoted oxidative dissolution of the ceMoS2. Additionally, under sunlight, ceMoS2 dissolution was accelerated by NO3-. These findings provide insight into the ion-induced fate of ceMoS2 and the durability and risks of MoS2 nanosheets in environmental applications.

How should anti-hypertensive medications be adjusted before screening for primary aldosteronism?

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding ß-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

Humic acid changes effect of naturally occurring oxidants on the environmental transformation of molybdenum disulfide nanosheets.

2H-phase molybdenum disulfide (2H-MoS2) has been considered to be a chemically stable two-dimensional (2D) nanomaterial. Nonetheless, the persistence of 2H-MoS2 in the presence of environmental redox-active matrices, such as naturally occurring oxidants (e.g., manganese dioxide (MnO2)) and natural organic matter (NOM), remains largely unknown. Herein, we examined the interplay between 2H-MoS2, MnO2 (a common natural oxidant), and NOM species (i.e., Aldrich humic acid (ALHA) and Suwannee River natural organic matter (SRNOM)). The results show that MnO2 accelerates the oxidative dissolution of 2H-MoS2, regardless of the presence of dissolved oxygen. The effect of NOM on the MnO2-induced fate of 2H-MoS2 was found to depend on its affinity for 2H-MoS2 and the functionality of NOM. ALHA preferentially adsorbed on hydrophobic 2H-MoS2 nanosheets due to the enrichment of reductive polycyclic aromatics and polyphenolic constituents. The preferential ALHA adsorption counteracted the MnO2-triggered oxidative transformation of 2H-MoS2, as revealed by the cathodic response of 2H-MoS2 (i.e., decreased the open circuit potential by 0.0338 V) and the emergence of reductive Mo‒C bonds at 228.8 and 231.9 eV upon the addition of ALHA. This work evaluated the persistence of 2H-MoS2, illustrating its susceptibility to decomposition by naturally occurring oxidants and the influence of NOM on it. These findings are crucial for revealing the fate and transport of MoS2 in aquatic environments and provide guidelines for related applications in natural or engineered systems for MoS2 and potentially other 2D materials.

Exploring the Effectiveness of Nurses' Usage of a Wound-Photography System.

As a result of rapid advancements in health information technology, uploading health-related information and records onto an electronic health record system has become a common practice. Photographs of patients' wounds have been uploaded electronically, but widespread acceptance by nurses has been prevented owing to issues such as file size and equipment. This research explores the attitude and satisfaction toward using an electronic health record for uploading wound photos. Through the integration of the Technology Acceptance Model, Information System Success Model, and other study results, this research aims to explore the impact of the following variables: system quality, information quality, perceived usefulness, perceived ease of use, user attitude, user satisfaction, and net benefits. We also tested nurses' understanding regarding the process of taking photographs and explored the photograph quality and the photography uploading rates. The results revealed that users were satisfied with the wound-photography system, but some believed that the system stability, processing time, and image resolution should be improved. In addition, more than 80% of the nurses correctly answered photo-taking questions, the study photos reached 70% of the quality standards, and the average uploading rate was 74%. The results could serve as guidelines for system design in the future.

Exploring Nurse Use of Digital Nursing Technology.

Technological developments and nursing shortages have become global trends. To solve the problem of shortage of healthcare professionals, technology may be used as a backup. Nurses constitute the largest working group in the healthcare system. Therefore, nurses are very important to the success of implementing digitization in hospitals. This cross-sectional study used the characteristics and adoption roles of innovation diffusion theory to understand technology use within the organization. Data were collected through structured questionnaires and open-ended questions from March 21 to May 31, 2022, in two hospitals in Taiwan. In total, 159 nurses agreed to participate in the study. The results of this study revealed that observability, simplicity, advantage, trialability, and compatibility positively improved the acceptance of digital nursing technology. In the distribution of users' innovative roles, early adopters had a significant impact on innovation characteristics and technology acceptance. Nurses in acute and critical care units perceived a greater comparative advantage and trial availability of digital nursing technology use than did those in general wards and outpatient clinics. In addition, based on user opinions and suggestions, the development of smart healthcare and the use of digital technology are expected to improve the quality of nursing care.

Using a Mobile Application to Promote Patient Education for Patients With Liver Cirrhosis.

Patient education and self-management are essential for patients with liver cirrhosis. Based on Fisher and Fisher's Information-Motivation-Behavior Skills model, a Cirrhosis Care App was developed to support the education and self-management of these patients. To evaluate the effectiveness of the application, a randomized controlled trial was conducted with patients having liver cirrhosis who were being followed up in the outpatient area of ​​a medical center in Taiwan. The experimental group used the app for 1 month, whereas a control group continued to receive conventional patient education. A pretest and posttest questionnaire was used to evaluate the app's effectiveness in improving the knowledge and practice of self-care. In addition, a questionnaire was developed based on the Technology Acceptance Model to understand satisfaction with the app. Results showed that following the implementation of the Cirrhosis Care App, patients' self-care knowledge and ability to promote self-care practice improved. User satisfaction with the app was measured and reflected in its frequency of use. This study confirmed that the Cirrhosis Care App, based on the Information-Motivation-Behavior Skills model, can improve patient knowledge and self-care practice and be actively promoted to benefit patients with cirrhosis.

Exploring the Usage Effectiveness of a Nursing Charge System.

The nursing charge system for inpatient accounting has been utilized in healthcare institutions for years. However, the level of its effectiveness in meeting the needs of nursing services, including further development, has not been systematically evaluated. A cross-sectional study based in Delone and McLean's information system success model was applied to explore the level of effective nursing charge system usage across the five dimensions of system quality, information quality, service quality, user satisfaction, and net benefits. We conducted a survey of the inpatient units of a medical center in Taiwan from June 23, 2021, to July 23, 2021. A total of 214 valid questionnaires were collected. Using a 5-point Likert scale, the dimension with the highest score was information quality (3.71), followed by service quality (3.37), user satisfaction (3.36), net benefits (3.31), and system quality (3.23). Older nurses ( r = -0.176) and those with more clinical experience ( r = -0.151) viewed the nursing charge system as having less information quality. The comfort level with using the computer was positively associated with system quality ( r = 0.396), information quality ( r = 0.378), service quality ( r = 0.275), user satisfaction ( r = 0.417), and net benefits ( r = 0.355). The opinions of nurses are vital. User feedback and advice should be investigated regularly to achieve system optimization.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Screening and identification of emodin as an EBV DNase inhibitor to prevent its biological functions.

BACKGROUND: The Epstein-Barr virus (EBV) is a prevalent oncovirus associated with a variety of human illnesses. BGLF5, an EBV DNase with alkaline nuclease (AN) activity, plays important roles in the viral life cycle and progression of human malignancies and has been suggested as a possible diagnostic marker and target for cancer therapy. Methods used conventionally for the detection of AN activity, radioactivity-based nuclease activity assay and DNA digestion detection by gel electrophoresis, are not suitable for screening AN inhibitors; the former approach is unsafe, and the latter is complicated. In the present study, a fluorescence-based nuclease activity assay was used to screen several natural compounds and identify an EBV DNase inhibitor. RESULTS: Fluorescence-based nuclease activity assays, in which the DNA substrate is labelled with PicoGreen dye, are cheaper, safer, and easier to perform. Herein, the results of the fluorescence-based nuclease activity assay were consistent with the results of the two conventional methods. In addition, the PicoGreen-labelling method was applied for the biochemical characterisation of viral nucleases. Using this approach, we explored EBV DNase inhibitors. After several rounds of screening, emodin, an anthraquinone derivative, was found to possess significant anti-EBV DNase activity. We verified the efficacy of emodin using the conventional DNA-cleavage assay. Furthermore, using comet assay and micronucleus formation detection, we confirmed that emodin can inhibit DNase-induced DNA damage and genomic instability. Additionally, emodin treatment inhibited EBV production. CONCLUSIONS: Using a PicoGreen-mediated nuclease activity assay, we successfully demonstrated that emodin has the potential to inhibit EBV DNase nuclease activity. Emodin also inhibits EBV DNase-related biological functions, suggesting that it is a potential inhibitor of EBV DNase.

Dietary administration of a postbiotic, heat-killed Pediococcus pentosaceus PP4012 enhances growth performance, immune response and modulates intestinal microbiota of white shrimp, Penaeus vannamei.

The efficacy of postbiotics on the immune-related gene expression and gut microbiota of white shrimp, Penaeus vannamei remains unexplored. A commercial heat-killed postbiotic Pediococcus pentosaceus PP4012 was used to evaluate the growth performance, intestinal morphology, immunological status, and microbial community of white shrimp after dietary administration in this study. White shrimp (0.040 ± 0.003 g) were divided into three treatments; a control, inanimate P. pentosaceus (105 CFU g feed-1) at low concentration (IPL) and inanimate P. pentosaceus (106 CFU g feed-1) at high concentrations (IPH). The diets of IPL and IPH significantly increased final weight, specific growth rate and production compared to the control group. Shrimp fed with IPL and IPH significantly utilized feed more efficiently than those fed the control diet. The IPH treatment significantly lowered the cumulative mortality rate compared to the control and IPL diet following Vibrio parahaemolyticus infection. No significant difference was observed for Vibrio-like and lactic acid bacteria in intestine of shrimp fed with the control diet and the experimental diets. Adding inanimate P. pentosaceus significantly improved immune responses such as lysozyme and phagocytic activity compared to the control group. However, the total hemocyte count, phenoloxidase activity, respiratory burst, and superoxide dismutase activity were not significantly different among treatments. The immune-related genes alf, pen3a, and pen4 expression were significantly higher in shrimp fed IPL diet compared with control and IPH. Taxonomic identification of bacterial genera in all dietary groups belonged to two predominant phyla, Proteobacteria and Bacteroidota. An abundance of Photobacterium, Motilimonas, Litorilituus, and Firmicutes bacterium ZOR0006 were identified in the intestine of shrimp fed postbiotic diets. Unique microbes such as Cohaesibacter was discovered in the shrimp fed IPL while Candidatus Campbellbacteria, uncultured Verrucomicrobium DEV114 and Paenalcaligenes were discovered in the intestines of shrimp fed IPH diet. Collectively, these data suggest that including heat-killed P. pentosaceus, particularly IPH, can enhance growth performance, promote microbial diversity, elevate immune responses, and increase shrimp's resistance to V. parahaemolyticus.

Incidence of neonatal sepsis after universal antenatal culture-based screening of group B streptococcus and intrapartum antibiotics: A multicentre retrospective cohort study.

OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.

Menstrual, fertility and psychological impacts after uterine compression sutures for postpartum hemorrhage: a prospective cohort study.

BACKGROUND: Uterine compression suture is an important conservative surgical technique in managing atonic postpartum hemorrhage. In this study, we aim to evaluate the subsequent menstrual, fertility and psychological outcomes after uterine compression sutures. METHODS: This was a prospective cohort study between 2009 and 2022 conducted in a tertiary obstetric unit (6000 deliveries per year) in Hong Kong SAR. Women with primary postpartum hemorrhage successfully treated with uterine compression sutures were followed-up in postnatal clinic for two years after delivery. Data on menstrual pattern were collected during each visit. Psychological impact after uterine compression suture was assessed using a standardized questionnaire. Subsequent pregnancies were identified by territory-wide computer registry and telephone interviews. Women with postpartum hemorrhage treated with uterotonic agents only were chosen as controls. RESULTS: In our cohort (n = 80), 87.9% of women had return of menses within six months after delivery. Regular monthly cycle was observed in 95.6% of women. Majority of women reported similar menstrual flow (75%), menstrual days (85.3%) and no change in dysmenorrhea status (88.2%) as compared before. Among eight (11.8%) women who reported hypomenorrhea after uterine compression sutures, two cases of Asherman's syndrome were diagnosed. Among 23 subsequent pregnancies (16 livebirths), no significant differences in outcome were observed except more omental or bowel adhesions (37.5% vs. 8.8%, p = 0.007), recurrence of hemorrhage (68.8% vs. 7.5%, p < 0.001) and repeated compression sutures (12.5% vs. 0%, p = 0.024) were seen in women with previous compression sutures. Over half of the couple declined future fertility after uterine compression sutures with 38.2% of women recalled unpleasant memories and 22.1% reported life-long adverse impact especially tokophobia. CONCLUSION: Majority of women with history of uterine compression sutures had similar menstruation and pregnancy outcomes as compared to those who did not have sutures. However, they had higher intrapartum risk of visceral adhesions, recurrence of hemorrhage and repeated compression sutures next pregnancy. Furthermore, couple could be more susceptible to negative emotional impact.

Upper limb manual training for children with cerebral palsy: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: There are different upper limb manual training protocols, namely constraint-induced movement therapy, modified constraint-induced movement therapy, hand-arm bimanual intensive training, hand-arm bimanual intensive training including lower extremity, action observation training, and mirror therapy, available for improving functional outcomes in children with cerebral palsy. However, the effect and priority of these strategies remain unclear. DATA SOURCES: We searched the PubMed, Cochrane Library, and Embase databases for relevant articles from inception to October 12, 2022. REVIEW METHODS: To assess the effect and priority of different strategies of upper limb manual training protocols through a systematic review and network meta-analysis of randomized controlled trials. RESULTS: We included 22 randomized controlled trials in this network meta-analysis. The ranking probability and standard mean differences with 95% credible intervals of the comparison between placebo and other forms of upper limb manual training were as follows: mirror therapy = 2.83 (1.78, 3.88), hand-arm bimanual intensive training including the lower extremity = 0.53 (0.09, 0.96), constraint-induced movement therapy = 0.44 (0.18, 0.71), hand-arm bimanual intensive training = 0.41 (0.15, 0.67), modified constraint-induced movement therapy = 0.39 (0.03, 0.74), and action observation training = 0.18 ( - 0.29, 0.65). No significant inconsistency was noted between the results of direct and indirect comparisons. CONCLUSION: We suggest that mirror therapy could be the upper limb manual training protocol of choice for improving functional outcomes in patients with cerebral palsy.

Progressively Unsupervised Generative Attentional Networks with Adaptive Layer-Instance Normalization for Image-to-Image Translation.

Unsupervised image-to-image translation has received considerable attention due to the recent remarkable advancements in generative adversarial networks (GANs). In image-to-image translation, state-of-the-art methods use unpaired image data to learn mappings between the source and target domains. However, despite their promising results, existing approaches often fail in challenging conditions, particularly when images have various target instances and a translation task involves significant transitions in shape and visual artifacts when translating low-level information rather than high-level semantics. To tackle the problem, we propose a novel framework called Progressive Unsupervised Generative Attentional Networks with Adaptive Layer-Instance Normalization (PRO-U-GAT-IT) for the unsupervised image-to-image translation task. In contrast to existing attention-based models that fail to handle geometric transitions between the source and target domains, our model can translate images requiring extensive and holistic changes in shape. Experimental results show the superiority of the proposed approach compared to the existing state-of-the-art models on different datasets.

Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy.

A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.

Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.

Lung cancer is the leading cause of cancer-associated death, with a global 5-year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug-resistance, and is a potential target for drug development. In this study, we found that in non-small cell lung cancer (NSCLC), BMI1 and MCL1 play crucial roles of cancer stemness including invasion, chemo-resistance and tumour initiation. JNK signalling serves as a link between oncogenic pathway or genotoxicity to cancer stemness. The activation of JNK, either by mutant EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3-ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small-molecule, BI-44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI-44 provides the basis for a new therapeutic approach in NSCLC treatment.