A comparison of symptoms and quality of life between medial flap and coblation turbinator of inferior turbinate reduction in endoscopic septoturbinoplasty: an analysis of 108 cases.

Introduction: The combination of septoplasty and turbinoplasty is a common surgical and accepted intervention to correct the nasal obstruction. The coblation submucosal reduction turbinator is a new surgical device, and it started to be used recently. On the other hand, the medial flap inferior turbinoplasty is not a conservative technique, but it provides a reliable and robust reduction. Objective: This study aims to compare the symptoms as well as health-related quality of life (HQOL) in 55 patients who underwent septoplasty with concomitent medial flap inferior turbinoplasty (group 1), 53 patients who patients underwent septoplasty with concomitent coblation turbinator (group 2). Patients and methods: The authors performed a prospective, randomized study of 108 patients who consulted the otorhinolaryngology department at the university hospital for surgery of septoturbinoplasty. Results: Preoperatively, the two patient groups had quite similar symptoms and health-related quality of life, and the anterior width of the inferior turbinate showed significant differences between the contralateral and deviated sides but not the posterior part. The significant difference (P<0.05) was noted for postoperatively improved symptom scores on visual analogue scale (VAS), nasal obstruction septoplasty effectiveness (NOSE) and better HQOL [Sino-Nasal Outcome Test-22 (SNOT-22)] in all patient groups. In addition, the NOSE and SNOT-22 scores in group 2 had significantly greater improvement than group 1 (P<0.05). Conclusions: Septoturbinoplasty treatment of septum deviation and inferior turbinate hypertrophy led to less symptoms as well as better HQOL for all two patient groups. Therefore, these techniques were an effective intervention for turbinate reduction, and they are equally efficient in the long term.

Design and Implementation of a Hybrid Optical Camera Communication System for Indoor Applications.

Optical wireless communication is a promising emerging technology that addresses the limitations of radio-frequency-based wireless technologies. This study presents a new hybrid modulation method for optical camera communication (OCC), which integrates two waveforms transmitted from a single transmitter light-emitting diode (LED) and receives data through two rolling shutter camera devices on the receiver side. Then, a smart camera with a high-resolution image sensor captures the high-frequency signal, and a low-resolution image sensor from a smartphone camera captures the low-frequency signal. Based on this hybrid scheme, two data streams are transmitted from a single LED, which reduces the cost of the indoor OCC device compared with transmitting two signals from two different LEDs. In the proposed scheme, rolling-shutter orthogonal frequency-division multiplexing is used for the high-frequency signals, and M-ary frequency-shift keying is used for the low-frequency signals in the time domain. This proposed scheme is compatible with smartphone and USB cameras. By controlling the OCC parameters, the hybrid scheme can be implemented with high performance for a communication distance of 10 m.

Antimicrobial Resistance Patterns of Common Gram-Negative Microorganisms Isolated from Patients with Lower Respiratory Tract Infections in a Teaching Hospital in Vietnam.

This cross-sectional study investigated the antimicrobial resistance (AMR) patterns of gram-negative pathogens isolated from 4,789 hospitalized patients with lower respiratory tract infections (LRTIs). Of the collected specimens, 1,325 (27.7%) tested positive for gram-negative bacteria. Acinetobacter baumannii (38.6%), Pseudomonas aeruginosa (33.5%), Klebsiella pneumoniae (18.7%), Escherichia coli (5.6%), and Klebsiella aerogenes (3.5%) were the most prevalent isolates. AMR analysis revealed high resistance rates (79.9%-100%) of A. baumannii isolates to multiple classes of antibiotics except amikacin, trimethoprim/sulfamethoxazole, and colistin. P. aeruginosa displayed low resistance to colistin (< 10%) but high resistance to other antibiotics. K. pneumoniae displayed high resistance rates of 90.0%-100.0% to most penicillins, whereas resistance rates were notably lower for colistin (7.1%) and amikacin (16.7%). K. aerogenes exhibited high resistance to various antibiotics and sensitivity to amikacin (95.1%), ampicillin (100.0%), and colistin (100.0%). E. coli isolates exhibited resistance to ampicillin (96.9%) and maximum sensitivity to several antibiotics. Our study identified significant AMR trends and highlighted the prevalence of multidrug-resistant strains (93.6% for K. aerogenes and 69.1%-92.4% for other isolates). These findings emphasize the urgent need for appropriate antibiotic management practices to combat AMR in gram-negative pathogens associated with LRTIs.

Comparative Studies of Atomically Thin Proton Conductive Films to Reduce Crossover in Hydrogen Fuel Cells.

Hydrogen fuel cells based on proton exchange membrane fuel cell (PEMFC) technology are promising as a source of clean energy to power a decarbonized future. However, PEMFCs are limited by a number of major inefficiencies; one of the most significant is hydrogen crossover. In this work, we comprehensively study the effects of two-dimensional (2D) materials applied to the anode side of the membrane as H2 barrier coatings on Nafion to reduce crossover effects on hydrogen fuel cells, while studying adverse effects on conductivity and catalyst performance in the beginning of life testing. The barrier layers studied include graphene, hexagonal boron nitride (hBN), amorphous boron nitride (aBN), and varying thicknesses of molybdenum disulfide (MoS2), all chosen due to their expected stability in a fuel cell environment. Crossover mitigation in the materials studied ranges from 4.4% (1 nm MoS2) to 46.1% (graphene) as compared to Nafion 211. Effects on proton conductivity are also studied, suggesting high areal proton transport in materials previously thought to be effectively nonconductive, such as 2 nm MoS2 and amorphous boron nitride under the conditions studied. The results indicate that a number of 2D materials are able to improve crossover effects, with those coated with 8 nm MoS2 and 1 L graphene able to achieve greater crossover reduction while minimizing conductivity penalty.

Differentiation Between Glioblastoma and Metastatic Disease on Conventional MRI Imaging Using 3D-Convolutional Neural Networks: Model Development and Validation.

RATIONALE AND OBJECTIVES: Imaging-based differentiation between glioblastoma (GB) and brain metastases (BM) remains challenging. Our aim was to evaluate the performance of 3D-convolutional neural networks (CNN) to address this binary classification problem. MATERIALS AND METHODS: T1-CE, T2WI, and FLAIR 3D-segmented masks of 307 patients (157 GB and 150 BM) were generated post resampling, co-registration normalization and semi-automated 3D-segmentation and used for internal model development. Subsequent external validation was performed on 59 cases (27 GB and 32 BM) from another institution. Four different mask-sequence combinations were evaluated using area under the curve (AUC), precision, recall and F1-scores. Diagnostic performance of a neuroradiologist and a general radiologist, both without and with the model output available, was also assessed. RESULTS: 3D-model using the T1-CE tumor mask (TM) showed the highest performance [AUC 0.93 (95% CI 0.858-0.995)] on the external test set, followed closely by the model using T1-CE TM and FLAIR mask of peri-tumoral region (PTR) [AUC of 0.91 (95% CI 0.834-0.986)]. Models using T2WI masks showed robust performance on the internal dataset but lower performance on the external set. Both neuroradiologist and general radiologist showed improved performance with model output provided [AUC increased from 0.89 to 0.968 (p = 0.06) and from 0.78 to 0.965 (p = 0.007) respectively], the latter being statistically significant. CONCLUSION: 3D-CNNs showed robust performance for differentiating GB from BMs, with T1-CE TM, either alone or combined with FLAIR-PTR masks. Availability of model output significantly improved the accuracy of the general radiologist.

Microplastic accumulation in bivalves collected from different coastal areas of Vietnam and an assessment of potential risks.

Microplastic (MP) pollution is an emerging problem in many areas around the world and in coastal areas of Vietnam, requiring more studies dedicated to the accumulation of this pollutant in the food chain as well as its potential risk to human health. This study investigated MP levels in tissues of five common bivalve species collected from aquaculture areas along the coast of Vietnam. MPs were found in all bivalve samples, with average values of 10.84 ± 2.61 items/individual or 2.40 ± 1.34 items/g wet weight. Impacts of feeding habits of bivalves showed influences on MP abundance in the samples. Fibers were the dominant shape of MPs recorded, most of which accumulated in the gills and digestive glands of all bivalve samples, with the majority falling within the size range of 300-2000 µm. MPs found in all studied species had relatively similar chemical compositions, mainly composed of polypropylene (PP) and polyethylene (PE). In this study, a diverse diet consisting of different bivalve species and detailed data on the consumption rate of these species were used to assess the human health risk of MPs dedicated to the coastal communities of Vietnam. The results suggested a significant part of MP uptake by human could be via bivalve consumption, in which removing viscera and proper depuration should be applied prior to eating, thereby reducing the risk.

Long-Time Oxygen and Superoxide Localization in Arabidopsis thaliana Cryptochrome.

Cryptochromes are proteins that are highly conserved across species and in many instances bind the flavin adenine dinucleotide (FAD) cofactor within their photolyase-homology region (PHR) domain. The FAD cofactor has multiple redox states that help catalyze reactions, and absorbs photons at about 450 nm, a feature linked to the light-related functions of cryptochrome proteins. Reactive oxygen species (ROS) are produced from redox reactions involving molecular oxygen and are involved in a myriad of biological processes. Superoxide O2•- is an exemplary ROS that may be formed through electron transfer from FAD to O2, generating an electron radical pair. Although the formation of a superoxide-FAD radical pair has been speculated, it is still unclear if the required process steps could be realized in cryptochrome. Here, we present results from molecular dynamics (MD) simulations of oxygen interacting with the PHR domain of Arabidopsis thaliana cryptochrome 1 (AtCRY1). Using MD simulation trajectories, oxygen binding locations are characterized through both the O2-FAD intermolecular distance and the local protein environment. Oxygen unbinding times are characterized through replica simulations of the bound oxygen. Simulations reveal that oxygen molecules can localize at certain sites within the cryptochrome protein for tens of nanoseconds, and superoxide molecules can localize for significantly longer. This relatively long-duration molecule binding suggests the possibility of an electron-transfer reaction leading to superoxide formation. Estimates of electron-transfer rates using the Marcus theory are performed for the identified potential binding sites. Molecular oxygen binding results are compared with recent results demonstrating long-time oxygen binding within the electron-transfer flavoprotein (ETF), another FAD binding protein.

Transferable Force Field for Gallium Nitride Crystal Growth from the Melt Using On-The-Fly Active Learning.

Atomic-scale simulations of reactive processes have been stymied by two factors: the lack of a suitable semiempirical force field on one hand and the impractically large computational burden of using ab initio molecular dynamics on the other hand. In this paper, we use an "on-the-fly" active learning technique to develop a nonparameterized force field that, in essence, exhibits the accuracy of density functional theory and the speed of a classical molecular dynamics simulation. We developed a force field capable of capturing the crystallization of gallium nitride (GaN) during a novel additive manufacturing process featuring the reaction of liquid Ga and gaseous nitrogen precursors to grow crystalline GaN thin films. We show that this machine learning model is capable of producing a single force field that can model solid, liquid, and gas phases involved in the process. We verified our computational predictions against a range of experimental measurements relevant to each phase and against ab initio calculations, showing that this nonparametric force field produces properties with excellent accuracy as well as exhibits computationally tractable efficiency. The force field is capable of allowing us to simulate the solid-liquid coexistence interface and the crystallization of GaN from the melt. The development of this transferable force field opens the opportunity to simulate the liquid-phase epitaxial growth more accurately than before to analyze reaction and diffusion processes and ultimately to establish a growth model of the additive manufacturing process to create the gallium nitride thin films.

AI-based classification of three common malignant tumors in neuro-oncology: A multi-institutional comparison of machine learning and deep learning methods.

PURPOSE: To determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL). METHODOLOGY: Retrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC. RESULTS: Two ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909]). CONCLUSION: Both ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR.

Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay.

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.

Advances in long-acting slow effective release antiretroviral therapies for treatment and prevention of HIV infection.

Adherence to daily oral antiretroviral therapy (ART) is a barrier to both treatment and prevention of human immunodeficiency virus (HIV) infection. To overcome limitations of life-long daily regimen adherence, long-acting (LA) injectable antiretroviral (ARV) drugs, nanoformulations, implants, vaginal rings, microarray patches, and ultra-long-acting (ULA) prodrugs are now available or in development. These medicines enable persons who are or at risk for HIV infection to be treated with simplified ART regimens. First-generation LA cabotegravir, rilpivirine, and lenacapavir injectables and a dapivirine vaginal ring are now in use. However, each remains limited by existing dosing intervals, ease of administration, or difficulties in finding drug partners. ULA ART regimens provide an answer, but to date, such next-generation formulations remain in development. Establishing the niche will require affirmation of extended dosing, improved access, reduced injection volumes, improved pharmacokinetic profiles, selections of combination treatments, and synchronization of healthcare support. Based on such needs, this review highlights recent pharmacological advances and a future treatment perspective. While first-generation LA ARTs are available for HIV care, they remain far from ideal in meeting patient needs. ULA medicines, now in advanced preclinical development, may close gaps toward broader usage and treatment options.

Magnetic Activated Carbon from ZnCl2 and FeCl3 Coactivation of Lotus Seedpod: One-Pot Preparation, Characterization, and Catalytic Activity towards Robust Degradation of Acid Orange 10.

Lotus seedpods (LSPs) are an abundant and underutilized agricultural residue discarded from lotus seed production. In this study, ZnCl2 and FeCl3 coactivation of LSP for one-pot preparation of magnetic activated carbon (MAC) was explored for the first time. X-ray diffraction (XRD) results showed that Fe3O4, Fe0, and ZnO crystals were formed in the LSP-derived carbon matrix. Notably, transmission electron microscopy (TEM) images showed that the shapes of these components consisted of not only nanoparticles but also nanowires. Fe and Zn contents in MAC determined by atomic absorption spectroscopy (AAS) were 6.89 and 3.94 wt%, respectively. Moreover, SBET and Vtotal of MAC prepared by coactivation with ZnCl2 and FeCl3 were 1080 m2/g and 0.51 cm3/g, which were much higher than those prepared by single activation with FeCl3 (274 m2/g and 0.14 cm3/g) or ZnCl2 (369 m2/g and 0.21 cm3/g). MAC was subsequently applied as an oxidation catalyst for Fenton-like degradation of acid orange 10 (AO10). As a result, 0.20 g/L MAC could partially remove AO10 (100 ppm) with an adsorption capacity of 78.4 mg/g at pH 3.0. When 350 ppm H2O2 was further added, AO10 was decolorized rapidly, nearly complete within 30 min, and 66% of the COD was removed in 120 min. The potent catalytic performance of MAC might come from the synergistic effect of Fe0 and Fe3O4 nanocrystals in the porous carbon support. MAC also demonstrated effective stability and reusability after five consecutive cycles, when total AO10 removal at 20 min of H2O2 addition slightly decreased from 93.9 ± 0.9% to 86.3 ± 0.8% and minimal iron leaching of 1.14 to 1.19 mg/L was detected. Interestingly, the MAC catalyst with a saturation magnetization of 3.6 emu/g was easily separated from the treated mixture for the next cycle. Overall, these findings demonstrate that magnetic activated carbon prepared from ZnCl2 and FeCl3 coactivation of lotus seedpod waste can be a low-cost catalyst for rapid degradation of acid orange 10.

Improving the photoelectrochemical water splitting performance of CuO photocathodes using a protective CuBi2O4 layer.

A heterojunction photocathode of CuO and CuBi2O4 grown on an FTO substrate (FTO/CuO/CuBi2O4) was synthesized using hydrothermal method followed by spin coating and annealing to overcome the bottlenecks encountered by CuO in photoelectrochemical (PEC) water splitting application. The synthesis methods, morphological, structural properties, and composition of each sample under each synthesis condition are discussed in detail. The photocathode with 15 coating layers annealed at 450 °C exhibited the best PEC performance. Moreover, its current density reached 1.23 mA/cm2 under an applied voltage of - 0.6 V versus Ag/AgCl in a neutral electrolyte. Additionally, it exhibited higher stability than the bare CuO thin film. The bonding of CuBi2O4 on CuO resulted in close contact between the two semiconductors, helping the semiconductors support each other to increase the PEC efficiency of the photocathode. CuO acted as the electron-generating layer, and the CuBi2O4 layer helped minimize photocorrosion as well as transport the carriers to the electrode/electrolyte interface to accomplish the hydrogen evolution reaction.

Estimation of basic reproduction number (R0) of African swine fever (ASF) in mid-size commercial pig farms in Vietnam.

African swine fever (ASF) is a devastating disease affecting the global swine industry. Recently, it has spread to many countries in Africa, Europe, Asia, and the Caribbean, leaving severe damage to local, regional, national, and global economies. Due to its highly complex molecular characteristics and pathogenesis, the development of a successful vaccine has been an unmet challenge. Therefore, ASF control relies solely on biosecurity, rapid detection, and elimination. Epidemiological information obtained from natural ASF outbreaks is critical for designing and implementing ASF control measures. Basic reproduction number (R0), an epidemiological metric used to describe the contagiousness or transmissibility of infectious agents, is an important epidemiological tool. In this study, we have calculated R0 for the in-farm spread of ASF among fattening pigs and sows in two midsize commercial pig farms, HY1 and HY2, that practice the spot removal approach in controlling ASF outbreaks in Vietnam. The R0 values for the sows and fattening pigs were 1.78 (1.35-2.35) and 4.76 (4.18-5.38) for HY1 and 1.55 (1.08-2.18) and 3.8 (3.33-4.28) for HY2. This is the first study to evaluate the transmission potential of ASF in midsize commercial pig farms in Vietnam. Based on the R0 values, we predict that the spot removal approach could be used to successfully control ASF outbreaks in midsize commercial sow barns but not in fattening pens.

Long-Time Oxygen Localization in Electron Transfer Flavoprotein.

Reactive oxygen species (ROS) exert a wide range of biological effects from beneficial regulatory function to deleterious oxidative stress. The electron transfer flavoprotein (ETF) is ubiquitous to life and is associated with aerobic metabolism and ROS production due to its location in the mitochondria. Quantifying oxygen localization within the ETF complex is critical for understanding the potential for electron transfer and radical pair formation between flavin adenine dinucleotide (FAD) cofactor and superoxide during ROS formation. Our study employed all-atom molecular dynamics simulations and identified several novel, long-lived oxygen binding sites within the ETF complex that appear near the FAD cofactor. Site locations, the local electrostatic environment, and characteristic oxygen binding times for each site were evaluated to establish factors that may lead to possible charge transfer reactions and superoxide formation within the ETF complex. The study revealed that some oxygen binding sites are naturally linked to protein domain features, suggesting opportunities to engineer and control ROS production and subsequent dynamics.

Haploinsufficiency of a Circadian Clock Gene Bmal1 (Arntl or Mop3) Causes Brain-Wide mTOR Hyperactivation and Autism-like Behavioral Phenotypes in Mice.

Approximately 50-80% of children with autism spectrum disorders (ASDs) exhibit sleep problems, but the contribution of circadian clock dysfunction to the development of ASDs remains largely unknown. The essential clock gene Bmal1 (Arntl or Mop3) has been associated with human sociability, and its missense mutation is found in ASD. Our recent study found that Bmal1-null mice exhibit a variety of autism-like phenotypes. Here, we further investigated whether an incomplete loss of Bmal1 function could cause significant autism-like behavioral changes in mice. Our results demonstrated that heterozygous Bmal1 deletion (Bmal1+/-) reduced the Bmal1 protein levels by ~50-75%. Reduced Bmal1 expression led to decreased levels of clock proteins, including Per1, Per2, Cry 1, and Clock but increased mTOR activities in the brain. Accordingly, Bmal1+/- mice exhibited aberrant ultrasonic vocalizations during maternal separation, deficits in sociability and social novelty, excessive repetitive behaviors, impairments in motor coordination, as well as increased anxiety-like behavior. The novel object recognition memory remained intact. Together, these results demonstrate that haploinsufficiency of Bmal1 can cause autism-like behavioral changes in mice, akin to those identified in Bmal1-null mice. This study provides further experimental evidence supporting a potential role for disrupted clock gene expression in the development of ASD.

Circadian activities of the brain MNK-eIF4E signalling axis contribute to diurnal rhythms of some cognitive functions.

Although it is well recognized that the circadian timing system profoundly influences cognitive performance, the underlying molecular mechanisms remain poorly defined. Our previous work has found that the mitogen-activated protein kinase-interacting kinase (MNK)-eukaryotic translation initiation factor 4E (eIF4E) axis, a conserved cellular signalling pathway regulating mRNA translation, modulates the function of the suprachiasmatic nucleus (SCN), the master circadian clock. Here, with the use of a combination of genetic, biochemical and behavioural approaches, we investigated the distribution and temporal regulation of eIF4E phosphorylation in the brain and its role in regulating the diurnal oscillations of some aspects of cognition in mice. We found that activities of the MNK-eIF4E axis, as indicated by the level of eIF4E phosphorylation at Ser209, exhibited significant circadian oscillations in a variety of brain regions, including but not limited to the prefrontal cortex, the hippocampus, the amygdala and the cerebellum. Phosphorylated eIF4E was enriched in neurons but not in astrocytes or microglia. Mice lacking eIF4E phosphorylation (eIF4ES209A/S209A ) or the MNKs (Mnk1-/-,2-/- ), the kinases that phosphorylate eIF4E, exhibited impaired diurnal variations of novel object recognition, object location memory, Barnes maze learning and ambulatory activities. Together, these results suggest that circadian activities of the MNK-eIF4E axis contribute to the diurnal rhythms of some cognitive functions, highlighting a role for rhythmic translational control in circadian regulation of cognitive performance.

Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition.

Although circadian and sleep disorders are frequently associated with autism spectrum disorders (ASD), it remains elusive whether clock gene disruption can lead to autistic-like phenotypes in animals. The essential clock gene Bmal1 has been associated with human sociability and its missense mutations are identified in ASD. Here we report that global Bmal1 deletion led to significant social impairments, excessive stereotyped and repetitive behaviors, as well as motor learning disabilities in mice, all of which resemble core behavioral deficits in ASD. Furthermore, aberrant cell density and immature morphology of dendritic spines were identified in the cerebellar Purkinje cells (PCs) of Bmal1 knockout (KO) mice. Electrophysiological recordings uncovered enhanced excitatory and inhibitory synaptic transmission and reduced firing rates in the PCs of Bmal1 KO mice. Differential expression of ASD- and ataxia-associated genes (Ntng2, Mfrp, Nr4a2, Thbs1, Atxn1, and Atxn3) and dysregulated pathways of translational control, including hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling, were identified in the cerebellum of Bmal1 KO mice. Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice. Importantly, conditional Bmal1 deletion only in cerebellar PCs was sufficient to recapitulate autistic-like behavioral and cellular changes akin to those identified in Bmal1 KO mice. Together, these results unveil a previously unidentified role for Bmal1 disruption in cerebellar dysfunction and autistic-like behaviors. Our findings provide experimental evidence supporting a putative role for dysregulation of circadian clock gene expression in the pathogenesis of ASD.

Demand for Mobile Health in Developing Countries During COVID-19: Vietnamese's Perspectives from Different Age Groups and Health Conditions.

BACKGROUND: Vietnam's economy and intellectual standards have witnessed significant development, improving conditions for residents to acquire novel mHealth applications. Additionally, the outbreak of the COVID-19 pandemic has influenced Vietnamese awareness of healthcare; however, previous studies have only been clinician-centered rather than customer-centered. METHODS: This study addresses this literature gap by interviewing 50 Vietnamese participants grouped by age, namely Generation X, Generation Y, and Generation Z, and health conditions, namely whether participants or family members have chronic illness. The study utilized semi-structured and in-depth interviews to collect the data and used thematic analysis to analyze the data under the unified theory of acceptance and use of technology framework. RESULTS: Most participants were willing to adopt this technology and demanded a convenient and user-friendly one-stop-shop solution, endorsements from credible and authoritative sources, and professional customer services. However, each group also had distinctive demands and behaviors. CONCLUSION: This study contributes theoretically by providing context-rich demand for Vietnamese customers across three generations and healthcare conditions during the COVID-19 pandemic and comparing their behavior with pre-COVID literature. While this research provides helpful information for potential app developers, this study also suggests that mHealth developers and policymakers should pay more attention to the differences in the demand of age groups and health conditions.

Impact of Novel Guidelines on Multifactorial Control and Its Association with Mortality in Adult Patients with Hypertension and Newly Diagnosed Type 2 Diabetes: A 4-Year Prospective Multicenter Study.

METHODS: This prospective, observational study involved adult hypertensive patients with newly diagnosed type 2 diabetes mellitus at two university hospitals in Vietnam. The median time of follow-up was 4 years (August 2016-August 2020). The primary outcome was time to all-cause mortality. RESULTS: 246 patients were included with a mean age of 64.5 ± 10.4. 58.5% were females. 64.2% were categorized as high risk. At baseline, ischemic heart disease, dyslipidemia, and chronic kidney disease (CKD) were present in 54.9%, 67.1%, and 41.1% of patients. Renin-angiotensin-aldosterone inhibitor, metformin, and statin were prescribed in 89.8%, 66.3%, and 67.1%. Among three risk factors, LDL-c control was the hardest to achieve, increasing from 5.7% to 8.5%. In contrast, blood pressure control decreased from 56.1% in 2016 to 30.2% in 2020, when the second wave of COVID-19 hit our nation. While contemporary targets resulted in persistently low simultaneous control at 1.2%, significant improvement was observed with conventional criteria (blood pressure < 140/90 mmHg, HbA1c < 7%, LDL-c < 70 mg/dl), increasing from 14.6% to 33.7%. During follow-up, the mortality rate was 24.4 events per 1000 patient-years, exclusively in patients with early newly diagnosed diabetes. Improving control overtime, not at baseline, was associated with less mortality. Conversely, age >75 years (HR = 2.6) and CKD (HR = 4.9) were associated with increased mortality. CONCLUSION: These findings demonstrated real-world difficulties in managing hypertension and newly diagnosed diabetes, especially with stringent criteria from novel guidelines. High-risk profile, high mortality, and poor simultaneous control warrant more aggressive cardiorenal protection, focusing more on aging CKD patients with early newly diagnosed diabetes.