Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model.

Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.

Research and Evaluation of the Allosteric Protein-Specific Force Field Based on a Pre-Training Deep Learning Model.

Allosteric modulators are important regulation elements that bind the allosteric site beyond the active site, leading to the changes in dynamic and/or thermodynamic properties of the protein. Allosteric modulators have been a considerable interest as potential drugs with high selectivity and safety. However, current experimental methods have limitations to identify allosteric sites. Therefore, molecular dynamics simulation based on empirical force field becomes an important complement of experimental methods. Moreover, the precision and efficiency of current force fields need improvement. Deep learning and reweighting methods were used to train allosteric protein-specific precise force field (named APSF). Multiple allosteric proteins were used to evaluate the performance of APSF. The results indicate that APSF can capture different types of allosteric pockets and sample multiple energy-minimum reference conformations of allosteric proteins. At the same time, the efficiency of conformation sampling for APSF is higher than that for ff14SB. These findings confirm that the newly developed force field APSF can be effectively used to identify the allosteric pocket that can be further used to screen potential allosteric drugs based on these pockets.

Molecular dynamics simulations reveal the inhibition mechanism of Cdc42 by RhoGDI1.

Cell division control protein 42 homolog (Cdc42), which controls a variety of cellular functions including rearrangements of the cell cytoskeleton, cell differentiation and proliferation, is a potential cancer therapeutic target. As an endogenous negative regulator of Cdc42, the Rho GDP dissociation inhibitor 1 (RhoGDI1) can prevent the GDP/GTP exchange of Cdc42 to maintain Cdc42 into an inactive state. To investigate the inhibition mechanism of Cdc42 through RhoGDI1 at the atomic level, we performed molecular dynamics (MD) simulations. Without RhoGDI1, Cdc42 has more flexible conformations, especially in switch regions which are vital for binding GDP/GTP and regulators. In the presence of RhoGDI1, it not only can change the intramolecular interactions of Cdc42 but also can maintain the switch regions into a closed conformation through extensive interactions with Cdc42. These results which are consistent with findings of biochemical and mutational studies provide deep structural insights into the inhibition mechanisms of Cdc42 by RhoGDI1. These findings are beneficial for the development of novel therapies targeting Cdc42-related cancers.

Reading and writing single-atom magnets.

The single-atom bit represents the ultimate limit of the classical approach to high-density magnetic storage media. So far, the smallest individually addressable bistable magnetic bits have consisted of 3-12 atoms. Long magnetic relaxation times have been demonstrated for single lanthanide atoms in molecular magnets, for lanthanides diluted in bulk crystals, and recently for ensembles of holmium (Ho) atoms supported on magnesium oxide (MgO). These experiments suggest a path towards data storage at the atomic limit, but the way in which individual magnetic centres are accessed remains unclear. Here we demonstrate the reading and writing of the magnetism of individual Ho atoms on MgO, and show that they independently retain their magnetic information over many hours. We read the Ho states using tunnel magnetoresistance and write the states with current pulses using a scanning tunnelling microscope. The magnetic origin of the long-lived states is confirmed by single-atom electron spin resonance on a nearby iron sensor atom, which also shows that Ho has a large out-of-plane moment of 10.1 ± 0.1 Bohr magnetons on this surface. To demonstrate independent reading and writing, we built an atomic-scale structure with two Ho bits, to which we write the four possible states and which we read out both magnetoresistively and remotely by electron spin resonance. The high magnetic stability combined with electrical reading and writing shows that single-atom magnetic memory is indeed possible.

Fenofibrate Exerts Anticancer Effects on Human Cervical Cancer HeLa Cells via Caspase-Dependent Apoptosis and Cell Cycle Arrest.

OBJECTIVE: In the present study, we attempted to identify the effects of fenofibrate on human cervical cancer cells. METHODS: The cytotoxicity of fenofibrate in cervical cancer cells was determined by Cell Counting Kit-8. Immunoblotting assay was used to determine the protein expression of caspase-3, poly ADP-ribose polymerase cleavage, B-cell lymphoma 2 family protein expression, microtubule-associated protein 1A/1B-light chain 3 (LC3), as well as cyclins and cyclin-dependent kinases. Immunofluorescence imaging was used to determine the expression of cleaved caspase-3 and LC3. Flow cytometry was used to determine cell cycle and apoptosis. RESULTS: We first showed that fenofibrate treatment reduced cell viability in HeLa cervical cancer cells in a dose-dependent manner at 24 h and 48 h. Importantly, fenofibrate-induced cell death was mediated through cell cycle arrest in the G0-G1 phase and caspase-dependent apoptosis. Moreover, fenofibrate also induced autophagy activation in a dose-dependent manner and pharmacological inhibition of autophagy led to increase of sub-G1 phase and caspase-dependent cell death in HeLa cells. CONCLUSION: In conclusion, these data demonstrated that fenofibrate initially induced cell cycle arrest, followed by caspase-3-dependent cell death in cervical cancer HeLa cells. However, fenofibrate also induced autophagy activation, which is closely related to the survival of diverse cancer cells, thus reducing the anticancer effects of fenofibrate. Therefore, the combination of an autophagy inhibitor and fenofibrate might have the potential to become a new therapeutic strategy for cervical cancer.

Feasibility of Overground Gait Training Using a Joint-Torque-Assisting Wearable Exoskeletal Robot in Children with Static Brain Injury.

Pediatric gait disorders are often chronic and accompanied by various complications, which challenge rehabilitation efforts. Here, we retrospectively analyzed the feasibility of overground robot-assisted gait training (RAGT) using a joint-torque-assisting wearable exoskeletal robot. In this study, 17 children with spastic cerebral palsy, cerebellar ataxia, and chronic traumatic brain injury received RAGT sessions. The Gross Motor Function Measure (GMFM), 6-min walk test (6 MWT), and 10-m walk test (10 MWT) were performed before and after intervention. The oxygen rate difference between resting and training was performed to evaluate the intensity of training in randomly selected sessions, while the Quebec User Evaluation of Satisfaction with assistive Technology 2.0 assessment was performed to evaluate its acceptability. A total of four of five items in the GMFM, gait speed on the 10 MWT, and total distance on the 6 MWT showed statistically significant improvement (p < 0.05). The oxygen rate was significantly higher during the training versus resting state. Altogether, six out of eight domains showed satisfaction scores more than four out of five points. In conclusion, overground training using a joint-torque-assisting wearable exoskeletal robot showed improvement in gross motor and gait functions after the intervention, induced intensive gait training, and achieved high satisfaction scores in children with static brain injury.

Activation Mechanism of RhoA Caused by Constitutively Activating Mutations G14V and Q63L.

RhoA, a member of Rho GTPases, regulates myriad cellular processes. Abnormal expression of RhoA has been implicated in various diseases, including cancers, developmental disorders and bacterial infections. RhoA mutations G14V and Q63L have been reported to constitutively activate RhoA. To figure out the mechanisms, in total, 1.8 µs molecular dynamics (MD) simulations were performed here on RhoAWT and mutants G14V and Q63L in GTP-bound forms, followed by dynamic analysis. Both mutations were found to affect the conformational dynamics of RhoA switch regions, especially switch I, shifting the whole ensemble from the wild type's open inactive state to different active-like states, where T37 and Mg2+ played important roles. In RhoAG14V, both switches underwent thorough state transition, whereas in RhoAQ63L, only switch I was sustained in a much more closed conformation with additional hydrophobic interactions introduced by L63. Moreover, significantly decreased solvent exposure of the GTP-binding site was observed in both mutants with the surrounding hydrophobic regions expanded, which furnished access to water molecules required for hydrolysis more difficult and thereby impaired GTP hydrolysis. These structural and dynamic differences first suggested the potential activation mechanism of RhoAG14V and RhoAQ63L. Together, our findings complemented the understanding of RhoA activation at the atomic level and can be utilized in the development of novel therapies for RhoA-related diseases.

MicroRNA 452 regulates IL20RA-mediated JAK1/STAT3 pathway in inflammatory colitis and colorectal cancer.

OBJECTIVE: MicroRNAs are a class of small, non-coding RNAs that play a key role in several biological and molecular processes, including tumorigenesis. We previously identified that MIR452 is upregulated in both colorectal cancer (CRC) and colitis. However, the functional mechanisms of MIR452 and its target genes in CRC and colitis are not well understood. So, we hypothesize that MIR452 can influence CRC and DSS-induced colitis model through the regulation of IL20RA and its downstream JAK-STATs signaling pathway. METHODS: We used a luciferase reporter assay to confirm the effect of MIR452 on IL20RA expression. The protein and mRNA expression of a target gene and its associated molecules were measured by western blot, quantitative RT-PCR, and immunohistochemistry. RESULTS: We found that the IL20RA was a direct target gene of MIR452. Overexpression of MIR452 in CRC cell lines significantly decreased IL20RA and its downstream Janus kinase 1 (JAK1), Signal transducer and activator of transcription 1 (STAT1) and STAT3. Knockdown of IL20RA in CRC cell lines by IL20RA gene silencing also decreased the expression of IL20RA, JAK1, and STAT3, but not of STAT1. CONCLUSION: Our results suggest that MIR452 regulates STAT3 through the IL20RA-mediated JAK1 pathway, but not STAT1. Overall, MIR452 acts as tumor suppressor in human CRC and in a mouse colitis model. These findings suggest that MIR452 is a promising therapeutic target in the treatment of cancer and colitis.

Prediction and Feature Importance Analysis for Severity of COVID-19 in South Korea Using Artificial Intelligence: Model Development and Validation.

BACKGROUND: The number of deaths from COVID-19 continues to surge worldwide. In particular, if a patient's condition is sufficiently severe to require invasive ventilation, it is more likely to lead to death than to recovery. OBJECTIVE: The goal of our study was to analyze the factors related to COVID-19 severity in patients and to develop an artificial intelligence (AI) model to predict the severity of COVID-19 at an early stage. METHODS: We developed an AI model that predicts severity based on data from 5601 COVID-19 patients from all national and regional hospitals across South Korea as of April 2020. The clinical severity of COVID-19 was divided into two categories: low and high severity. The condition of patients in the low-severity group corresponded to no limit of activity, oxygen support with nasal prong or facial mask, and noninvasive ventilation. The condition of patients in the high-severity group corresponded to invasive ventilation, multi-organ failure with extracorporeal membrane oxygenation required, and death. For the AI model input, we used 37 variables from the medical records, including basic patient information, a physical index, initial examination findings, clinical findings, comorbid diseases, and general blood test results at an early stage. Feature importance analysis was performed with AdaBoost, random forest, and eXtreme Gradient Boosting (XGBoost); the AI model for predicting COVID-19 severity among patients was developed with a 5-layer deep neural network (DNN) with the 20 most important features, which were selected based on ranked feature importance analysis of 37 features from the comprehensive data set. The selection procedure was performed using sensitivity, specificity, accuracy, balanced accuracy, and area under the curve (AUC). RESULTS: We found that age was the most important factor for predicting disease severity, followed by lymphocyte level, platelet count, and shortness of breath or dyspnea. Our proposed 5-layer DNN with the 20 most important features provided high sensitivity (90.2%), specificity (90.4%), accuracy (90.4%), balanced accuracy (90.3%), and AUC (0.96). CONCLUSIONS: Our proposed AI model with the selected features was able to predict the severity of COVID-19 accurately. We also made a web application so that anyone can access the model. We believe that sharing the AI model with the public will be helpful in validating and improving its performance.

An Artificial Intelligence Model to Predict the Mortality of COVID-19 Patients at Hospital Admission Time Using Routine Blood Samples: Development and Validation of an Ensemble Model.

BACKGROUND: COVID-19, which is accompanied by acute respiratory distress, multiple organ failure, and death, has spread worldwide much faster than previously thought. However, at present, it has limited treatments. OBJECTIVE: To overcome this issue, we developed an artificial intelligence (AI) model of COVID-19, named EDRnet (ensemble learning model based on deep neural network and random forest models), to predict in-hospital mortality using a routine blood sample at the time of hospital admission. METHODS: We selected 28 blood biomarkers and used the age and gender information of patients as model inputs. To improve the mortality prediction, we adopted an ensemble approach combining deep neural network and random forest models. We trained our model with a database of blood samples from 361 COVID-19 patients in Wuhan, China, and applied it to 106 COVID-19 patients in three Korean medical institutions. RESULTS: In the testing data sets, EDRnet provided high sensitivity (100%), specificity (91%), and accuracy (92%). To extend the number of patient data points, we developed a web application (BeatCOVID19) where anyone can access the model to predict mortality and can register his or her own blood laboratory results. CONCLUSIONS: Our new AI model, EDRnet, accurately predicts the mortality rate for COVID-19. It is publicly available and aims to help health care providers fight COVID-19 and improve patients' outcomes.

Tuning Single-Atom Electron Spin Resonance in a Vector Magnetic Field.

Spin resonance of single spin centers bears great potential for chemical structure analysis, quantum sensing, and quantum coherent manipulation. Essential for these experiments is the presence of a two-level spin system whose energy splitting can be chosen by applying a magnetic field. In recent years, a combination of electron spin resonance (ESR) and scanning tunneling microscopy (STM) has been demonstrated as a technique to detect magnetic properties of single atoms on surfaces and to achieve sub-microelectronvolts energy resolution. Nevertheless, up to now the role of the required magnetic fields has not been elucidated. Here, we perform single-atom ESR on individual Fe atoms adsorbed on magnesium oxide (MgO) using a two-dimensional vector magnetic field as well as the local field of the magnetic STM tip in a commercially available STM. We show how the ESR amplitude can be greatly improved by optimizing the magnetic fields, revealing in particular an enhanced signal at large in-plane magnetic fields. Moreover, we demonstrate that the stray field from the magnetic STM tip is a versatile tool. We use it here to drive the electron spin more efficiently and to perform ESR measurements at constant frequency by employing tip-field sweeps. Lastly, we show that it is possible to perform ESR using only the tip field, under zero external magnetic field, which promises to make this technique available in many existing STM systems.

Biogeography of Korea's top predator, the yellow-throated Marten: evolutionary history and population dynamics.

BACKGROUND: Peninsulas often harvest high genetic diversity through repeated southward migrations of species during glacial maxima. Studies addressing within-species evolutionary responses to climate fluctuations in northeast Asia are limited compared to other regions of the world, and more so in the Korean Peninsula. In this study, we conducted the first population-level study of the yellow-throated marten, Martes flavigula, from the Korean Peninsula, Russian, Taiwanese and Chinese localities in a biogeographic framework using mitochondrial (cyt-b, nd2, cr) and nuclear gene sequencing (ghr). RESULTS: Bayesian analyses revealed a rather young population, with a split from the most recent common ancestor at around 125 kya. Martes flavigula likely colonized the Korean Peninsula from Mainland China through the Yellow Sea twice, ca. 60 kya and 20 kya. Korean martens diversified during the Late Pleistocene with at least two dispersal events out of Korea, towards the southwest to Taiwan (ca. 80 kya) and towards the North into Russia and eastern China; most likely after the Last Glacial Maxima (ca. 20 kya). We argue that the lack of population structure and mixed populations is possibly a consequence of the high dispersal capability of the species. The Bayesian skyline plot revealed a population decline within the last 5000 years, suggesting potential negative biotic and anthropogenic effects in the area. We find that local populations are not genetically differentiated, therefore no perceptible population structure within Korea was found. CONCLUSIONS: The topography and geography of the Korean Peninsula has played a pivotal role in its colonization. Connections between the Korean Peninsula and the Mainland through sea-level drops of the Yellow Sea at times of glacial maxima and the high dispersal capability of M. flavigula adds to the lack of geographical structure in this species and the paraphyly of Korean lineages.

Loss of abcd4 in zebrafish leads to vitamin B12-deficiency anemia.

ABCD4, a member of the ATP-binding cassette transporter superfamily, is associated with the transport of vitamin B12 which is crucial for the development of red blood cells (RBCs) and may also be involved in its metabolism. However, the molecular function of ABCD4 during RBC development in zebrafish is mostly unknown. Using a morpholino-based knockdown approach, we found that abcd4-knockdown resulted in abnormal RBCs of irregular shapes and various sizes. o-Dianisidine staining, as an indicator of hemoglobin in RBCs, further confirmed that abcd4 morphants possessed fewer hemoglobinized cells and impaired blood circulation. Multiple protein sequence alignment revealed that the amino acid sequence for residues 13-292, which is the domain of vitamin B12 transport, of the zebrafish Abcd4 was highly conserved compared to that of other species. Accordingly, the abcd4 morphants can be rescued with human ABCD4, demonstrating a conserved role of ABCD4 in vertebrates. Notably, the vitamin B12-deficient phenotype in abcd4 morphants, which causes anemia, was recapitulated in the newly-established abcd4 mutant, indicating the possibility that the abcd4 mutant could be used as a disease model of vitamin B12-deficiency anemia. Our study provides an insight that the analysis of the newly-established abcd4 mutant may contribute to understanding its roles in ABCD4-related vitamin B12-deficiency anemia and the associated pathogeneses in humans.

Tuning the Exchange Bias on a Single Atom from 1 mT to 10 T.

Shrinking spintronic devices to the nanoscale ultimately requires localized control of individual atomic magnetic moments. At these length scales, the exchange interaction plays important roles, such as in the stabilization of spin-quantization axes, the production of spin frustration, and creation of magnetic ordering. Here, we demonstrate the precise control of the exchange bias experienced by a single atom on a surface, covering an energy range of 4 orders of magnitude. The exchange interaction is continuously tunable from milli-eV to micro-eV by adjusting the separation between a spin-1/2 atom on a surface and the magnetic tip of a scanning tunneling microscope. We seamlessly combine inelastic electron tunneling spectroscopy and electron spin resonance to map out the different energy scales. This control of exchange bias over a wide span of energies provides versatile control of spin states, with applications ranging from precise tuning of quantum state properties, to strong exchange bias for local spin doping. In addition, we show that a time-varying exchange interaction generates a localized ac magnetic field that resonantly drives the surface spin. The static and dynamic control of the exchange interaction at the atomic scale provides a new tool to tune the quantum states of coupled-spin systems.

Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024.

This cohort study evaluates the risk of death in patients hospitalized for COVID-19 or seasonal influenza following the emergence of the JN.1 variant in winter 2023.

Bone morphogenetic protein signaling governs biliary-driven liver regeneration in zebrafish through tbx2b and id2a.

Upon mild liver injury, new hepatocytes originate from preexisting hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast-like cells (HB-LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration. Using a zebrafish model of near-complete hepatocyte ablation, we show that bone morphogenetic protein (Bmp) signaling is required for BEC conversion to hepatocytes, particularly for LPC differentiation into hepatocytes. We found that severe liver injury led to the up-regulation of genes involved in Bmp signaling, including smad5, tbx2b, and id2a, in the liver. Bmp suppression did not block BEC dedifferentiation into HB-LCs; however, the differentiation of HB-LCs into hepatocytes was impaired due to the maintenance of HB-LCs in an undifferentiated state. Later Bmp suppression did not affect HB-LC differentiation but increased BEC number through proliferation. Notably, smad5, tbx2b, and id2a mutants exhibited similar liver regeneration defects as those observed in Bmp-suppressed livers. Moreover, BMP2 addition promoted the differentiation of a murine LPC line into hepatocytes in vitro. CONCLUSIONS: Bmp signaling regulates BEC-driven liver regeneration through smad5, tbx2b, and id2a: it regulates HB-LC differentiation into hepatocytes through tbx2b and BEC proliferation through id2a; our findings provide insights into promoting innate liver regeneration as a novel therapy. (Hepatology 2017;66:1616-1630).

Euzebyella algicola sp. nov., a marine bacterium of the family Flavobacteriaceae, isolated from green algae.

A Gram-negative, yellow-pigmented, non-flagellated, gliding, rod-shaped and aerobic bacterium, designated MEBiC 12267T, was isolated from green algae of Jeju Island. 16S rRNA gene sequence analysis revealed that the strain MEBiC 12267T was affiliated to the genus Euzebyella of the family Flavobacteriaceae and showed the highest similarity to Euzebyella marina KCTC 42440T (98.5 %). The DNA-DNA relatedness value of strain MEBiC 12267T with E. marina KCTC 42440T was 25 %. Growth was observed at 10-37 °C (optimum, 30-33 °C), at pH 6.0-9.5 (optimum, 8.0-8.5) and with 0.5-9.0 % (w/v) NaCl (optimum, 2.5-3.5 %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The major respiratory quinone was MK-6. Polar lipids included phosphatidylethanolamine, seven unidentified lipids and two unidentified aminolipids. The DNA G+C content was 40.7 mol%. On the basis of the data from the polyphasic taxonomic study, it was concluded that the strain MEBiC 12267T represents a novel species within the genus Euzebyella, for which the name Euzebyella algicola sp. nov. is proposed. The type strain of E. algicola is MEBiC 12267T (=KCCM 43264T=JCM 32170T).

Acupuncture for symptomatic gastroparesis.

BACKGROUND: Gastroparesis, a state of delayed gastric emptying in the absence of mechanical obstruction of the stomach, has a substantial impact on people's daily function and quality of life when symptomatic. Current treatment options are based on limited evidence of benefits. Acupuncture is widely used to manage gastrointestinal disorders, although its role in people with symptomatic gastroparesis is unclear. We therefore undertook a systematic review of the evidence. OBJECTIVES: To assess the benefits and harms of acupuncture, in comparison with no treatment, sham acupuncture, conventional medicine, standard care, or other non-pharmacological active interventions for symptom management in people with gastroparesis. SEARCH METHODS: On 26 March 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus, PsycINFO, AMED, Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, and the National Assembly Library), and Chinese databases (including the China Academic Journal). We also searched two clinical trials registries for ongoing trials. We imposed no language limitations. SELECTION CRITERIA: We selected all randomised controlled trials comparing the penetrating type of acupuncture with no treatment, sham acupuncture, conventional medicine, standard care, and other non-pharmacological active interventions for people with symptomatic gastroparesis of any aetiology (i.e. surgical, diabetic, or idiopathic). Trials reporting outcomes at least four weeks from baseline (short-term outcomes) were eligible. We defined long-term outcomes as those measured after 12 weeks from baseline. The primary outcome was improvement of gastroparesis symptoms in the short term. Secondary outcomes were: improvement of symptoms measured after three months, change in the rate of gastric emptying, quality of life, use of medication, and adverse events in the short and long term. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials based on predefined selection criteria. Two review authors independently extracted data and evaluated the risk of bias. The review authors contacted investigators to obtain missing information wherever possible. MAIN RESULTS: We included 32 studies that involved a total of 2601 participants. Acupuncture was either manually stimulated (24 studies) or electrically stimulated (8 studies). The aetiology of gastroparesis was diabetes (31 studies) or surgery (1 study). All studies provided data on the proportion of people with symptoms 'improved', although the definition or categorisation of improvement varied among the studies. Most measured only short-term outcomes (28 studies), and only one study employed validated instruments to assess subjective changes in symptoms or reported data on quality of life or the use of medication. Reporting of harm was incomplete; minor adverse events were reported in only seven trials. Most studies had unclear risk of bias in terms of allocation concealment (29/32), outcome assessor blinding (31/32) and selective reporting (31/32), as well as high risk of bias in terms of participant/personnel blinding (31/32). Acupuncture was compared with sham acupuncture (needling on non-acupuncture points), three different types of gastrokinetic drugs (domperidone, mosapride, cisapride), and a histamine H2 receptor antagonist (cimetidine).There was low-certainty evidence that symptom scores of participants receiving acupuncture did not differ from those of participants receiving sham acupuncture at three months when measured by a validated scale.There was very low-certainty evidence that a greater proportion of participants receiving acupuncture had 'improved' symptoms in the short term compared to participants who received gastrokinetic medication (4 to 12 weeks) (12 studies; 963 participants; risk ratio (RR) 1.25; 95% confidence interval (CI) 1.17 to 1.33, I² = 8%). Short-term improvement in overall symptom scores favouring acupuncture was also reported in five studies with considerable heterogeneity.Acupuncture in combination with other treatments, including gastrokinetics, non-gastrokinetics and routine care, was compared with the same treatment alone. There was very low-certainty evidence in favour of acupuncture for the proportion of participants with 'improved' symptoms in the short term (4 to 12 weeks) (17 studies; 1404 participants; RR 1.22; 95% CI 1.16 to 1.28; I² = 0%). Short-term improvement in overall symptom scores, favouring acupuncture, were also reported (two studies, 132 participants; MD -1.96, 95% CI -2.42 to -1.50; I² = 0%).Seven studies described adverse events, including minor bleeding and hematoma, dizziness, xerostomia, loose stool, diarrhoea, abdominal pain, skin rash and fatigue. The rest of the trials did not report whether adverse events occurred.Subgroup analyses revealed that short-term benefits in terms of the proportion of people with 'improved' symptoms did not differ according to the type of acupuncture stimulation (i.e. manual or electrical). The sensitivity analysis revealed that use of a valid method of random sequence generation, and the use of objective measurements of gastric emptying, did not alter the overall effect estimate in terms of the proportion of people with 'improved' symptoms. The asymmetric funnel plot suggests small study effects and publication bias towards positive reporting. AUTHORS' CONCLUSIONS: There is very low-certainty evidence for a short-term benefit with acupuncture alone or acupuncture combined with gastrokinetic drugs compared with the drug alone, in terms of the proportion of people who experienced improvement in diabetic gastroparesis. There is evidence of publication bias and a positive bias of small study effects. The reported benefits should be interpreted with great caution because of the unclear overall risk of bias, unvalidated measurements of change in subjective symptoms, publication bias and small study reporting bias, and lack of data on long-term outcomes; the effects reported in this review may therefore differ significantly from the true effect. One sham-controlled trial provided low-certainty evidence of no difference between real and sham acupuncture in terms of short-term symptom improvement in diabetic gastroparesis, when measured by a validated scale. No studies reported changes in quality of life or the use of medication.Due to the absence of data, no conclusion can be made regarding effects of acupuncture on gastroparesis of other aetiologies. Reports of harm have remained largely incomplete, precluding assessments of the safety of acupuncture in this population. Future research should focus on reducing the sources of bias in the trial design as well as transparent reporting. Harms of interventions should be explicitly reported.

On-orbit radiometric calibration of Suomi NPP VIIRS reflective solar bands using the Moon and solar diffuser.

Radiometric calibration of the Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (VIIRS) reflective solar bands relies mainly on the onboard solar diffuser (SD) observations. The SD reflectance degrades over time due to the exposure to solar ultraviolet radiation. The uncertainties embedded in characterizing the SD bidirectional reflectance distribution function (BRDF) directly affect the accuracy of sensor radiometric calibration coefficients, such as F-factors, which are proxies of detector gain. The Moon-based radiometric calibration provides an independent way of validating and correcting the SD-based calibration. This study focuses on the comparison of the long-term SD F-factors with lunar F-factors by using two independent lunar irradiance models, i.e., Miller and Turner (MT) model and the Global Space-based Inter-Calibration System Implementation of ROLO (GIRO) model. To monitor the long-term detector response changes, the lunar F-factor differences are matched to the SD F-factors by applying the best fit scaling factors. Overall, the two lunar F-factors agree well, within 2% of one sigma standard deviation in the reflective solar bands compared to the SD F-factors. The lifetime standard deviations of difference between the GIRO-based lunar and SD F-factors show better long-term match than that of MT-based lunar F-factors. The GIRO-based lunar F-factors show increasing differences over time in comparison with the SD F-factors especially for bands M1 to M4, which indicates the underestimation of the VIIRS detector degradation by SD F-factors for these bands. Using standard SD calibration method and the GIRO-based lunar model, long-term difference between the lunar and SD F-factors shows there are 1.6%, 1.3%, 1.0%, and 0.9% increases in lunar F-factor trend for bands M1 to M4 at the end of year 2015. To mitigate these time-dependent biases, NOAA Ocean Color (OC) group and NASA VIIRS characterization support team (VCST) developed lunar correction methods and applied them to their specific products. However, the amounts of band-dependent lunar corrections are not consistent between these two teams, especially in the short-wavelength bands from M1 to M4, depending on the versions of lunar models and SD F-factor calculation algorithms. Using the standard SD F-factor algorithm and the multi-agency endorsed GIRO model, we derived lunar correction factors based on the quadratic fits between the SD and lunar F-factors. The differences with the NOAA OC group and NASA VCST team are compared and described in this study.

Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023.

This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.