New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

Developmental and epileptic encephalopathies(DEEs)are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition,mood,sleep,social behavior,movement control,learning,and/or memory.Dravet syndrome(DS),also known as Severe Myoclonic Epilepsy of Infancy.

Pathfinding Pulsar Observations with the CVN Incorporating the FAST

The importance of Very Long Baseline Interferometry(VLBI)for pulsar research is becoming increasingly prominent and receiving more and more attention.We present the pathfinding pulsar observation results with the Chinese VLBI Network(CVN)incorporating the Five-hundred-meter Aperture Spherical radio Telescope(FAST).On MJD 60045(11th April 2023),PSRs B0919+06 and B1133+16 were observed with the phase-referencing mode in the L-band using four radio telescopes(FAST,TianMa,Haoping,and Nanshan)and correlated with the pulsar binning mode of the distributed FX-style software correlator in Shanghai.After further data processing with the NRAO Astronomical Image Processing System(AIPS),we detected these two pulsars and fitted their current positions with accuracy at the milliarcsecond level.By comparison,our results show significantly better agreement with predicted values based on historical VLBI observations than those with previous timing observations,as pulsar astrometry with the VLBI provides a more direct and model-independent method for accurately obtaining related parameters.

Association between stress hyperglycemia ratio and in-hospital outcomes:findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)Project

BACKGROUND Stress hyperglycemia ratio(SHR)could provide accurate information on the acute status of hyperglycemia.The relationship between SHR and acute coronary syndrome(ACS)prognosis remains unclear.This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS.METHODS A total of 12,010 patients were eventually enrolled in the study.The relationship between SHR and in-hospital major adverse cardiovascular events(MACEs)was then modeled by restricted cubic spline(RCS)curves,and all patients were divided into three groups according to the results.The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes,described as odds ratios(ORs)and 95%confidence intervals(CIs).Subgroup analyses were also performed on different diseases.RESULTS The median age of this cohort was 63(54,71)years old,and 8942(74.5%)were male.Group 1 was defined as SHR<0.6(n=426),Group 2 was defined as SHR between 0.6 and 1(n=5821),and Group 3 was defined as SHR>1(n=5763).Compared with Group 2,Group 1(OR=1.891,95%CI:1.028-3.479,P<0.001)and Group 3(OR=1.868,95%CI:1.434-2.434,P<0.001)had higher risks of suffering from in-hospital MACEs.SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM[OR=2.282,95%CI:1.477-3.524).CONCLUSIONS Both low and high SHR levels were independently associated with in-hospital MACEs.Young males with DM,hypertension,and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

Cardiovascular risk burden and disability:findings from the International Mobility in Aging Study(IMIAS)

BACKGROUND The association of cardiovascular risk burden with disability is unclear.We examined the association between trajectories of the Framingham general cardiovascular disease risk score(FGCRS)with the trajectories of limitations of physical function in older adults.METHODS A total of 1219 participants with no disabilities from the International Mobility in Aging Study(IMIAS)study who had up to three repeated measures of FGCRS between 2012–2016 and without a history of stroke or coronary heart disease at baseline and follow-up were included.FGCRS at baseline was assessed and categorized into tertiles.Physical function was evaluated with the Short Physical Performance Battery(SPPB).The data were analyzed using linear mixed-effects models.RESULTS At baseline,FGCRS ranged between 3–94(mean score:24±15.8),participants were 32(2.6%),502(41.2%)and 685(56.2%)in lowest,middle,and highest tertiles,respectively.In the trajectories of limitations of physical function,the lowest FGCRS had no differences,while the middle and highest had a decrease in physical performance between 2012–2014(P=0.0001).Age,being female,living in Andes Mountains,having middle and highest FGCRS,higher alcohol consumption,being obese,lack of exercise and cognitive impairment increase the probability of disability(P<0.05).Alternatively,living in more developed regions and having a higher educational level reduced the probability of disability during the follow-up time(P<0.05).CONCLUSIONS Higher cardiovascular risk burden is associated with decreased physical performance,especially in gait.Results suggest SPPB may provide a measure of cardiovascular health in older adults.

Alcohol drinking triggered decrease of oxidative balance score is associated with high all-cause and cardiovascular mortality in hypertensive individuals:findings from NHANES 1999–2014

BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.

Community Caregivers’ Experiences and Programmatic Strategies to Improve Active Case Finding in Community Tuberculosis Care in Botswana 2016-2021

Background: The community tuberculosis care program was started to reduce the impact of TB and increase successful treatment outcomes, thus contributing to meeting WHO targets on TB. According to the Botswana Ministry of Health, community tuberculosis care was introduced with the main goal of reducing tuberculosis-related morbidity and mortality among communities through the expansion of direct observed therapy and community involvement to community settings. The community caregivers were to support tuberculosis patients throughout their treatment period until they were cured or had completed their treatment. Settings: Two major cities of Botswana, Francistown and Gaborone, with more than twenty-two health clinics offering tuberculosis care. Objective: To investigate community caregivers’ experiences and identify programmatic strategies to improve active TB case findings under the community TB care (CTBC) program in Botswana during 2016-2021. Methods: We adopted a descriptive qualitative research design, followed by convenience purposive sampling. We obtained consent and interviewed 40 participants who met the inclusion criteria, 16 out of 73 in Gaborone and 24 out of 38 from Francistown. Results: We interviewed 40 caregivers with a mean age of 43.4 years. Accepting the caregiving role was identified as the main experience by more than two thirds of the caregivers. While at least more than two-fifth felt obligated to care for the patient at home due to personal relations. More than half of the respondents found caregiving difficult or frustrating due to some challenges encountered during the caregiving role. Behavioral modifications were suggested under different subthemes as strategies to improve active case finding. [-rId13-]Conclusion: Acceptance was the major experience in CTBC. Intensification of known programmatic strategies was suggested by caregivers to improve tuberculosis active case finding in CTBC.

Hepatic organoids: ideal models for non-alcoholic fatty liver disease drug finding and molecular mechanism research

With the improvement of living standards and changes in dietary habits,the non-alcoholic fatty liver disease(NAFLD)has become one of the most common metabolic diseases clinically,with a global prevalence exceeding 25%.NAFLD often presents as a multisystem disease characterized by excessive deposition of triglycerides within hepatocytes,with over 5%of hepatocytes exhibiting steatosis.The clinical progression of NAFLD can mainly be divided into two stages:non-alcoholic fatty liver(NAFL)and non-alcoholic steatohepatitis(NASH).NAFL represents the early stage,primarily characterized by hepatocellular steatosis(which can be reversed with early intervention)and further progression leading to NASH.Besides hepatocellular steatosis,NASH also exhibits hepatocyte inflammation,injury,and fibrosis.Research indicates that 25%of NAFL patients may progress to NASH,and 35%to 50%of NASH patients further develop into liver cirrhosis or even liver cancer.Additionally,NAFLD is closely associated with various chronic diseases and tumors,such as obesity,hyperlipidemia,diabetes,breast cancer,and colorectal cancer.Despite the high and rising incidence of NAFLD,there are currently no clinically proven safe and effective drugs specifically targeting each stage of NAFLD.

Pneumoparotid with imaging findings:A case report and review of literature

BACKGROUND Pneumoparotid is a rare disease associated with retrograde airflow into the ductal system.There is no established treatment for this disease,which has no known complications.Mouth puffing and playing wind instruments are known to be the causes of this disease.CASE SUMMARY We managed a case,in which pneumoparotid suddenly recurred 4 months after surgery for purulent parotiditis.The patient did not report any obvious etiological factors,such as mouth puffing or playing a wind instrument.We reviewed 128 articles(from 1941 to 2023)that reported on a total of 166 patients with pneumoparotid,including the patient from the present case report,with imaging findings.This is the first reported case of pneumoparotid following surgery for purulent parotitis.The etiology in our case was classified as idiopathic.CONCLUSION Imaging findings could be sufficient for accurate pneumoparotid diagnoses and the exclusion of complications;computed tomography could be useful.

Efficacy and tolerability of propolis special extract gh 2002 as a lip balm against herpes labialis: a randomized, double-blind three-arm dose finding study

A dose-finding study was performed with respect to the clinical applicability and tolerability of three different concentrations of propolis special extract GH 2002 in a lip balm (0.1%, 0.5% and 1%). The trial was designed as a double-blind, randomized dermatological study in 150 outpatients with Herpes labialis. The primary parameter was the duration in days until painless incrustation in 50% or 90% of the patients (observable in 121 patients). Secondary parameters were local pain (assessed on a visual analogue scale), itching, burning and tension/ swelling on a verbal rating scale, and tolerability. Visits were performed on days 2/3, 5/6 and 8/9. Best efficacy results with shortest healing time (3.4 and 5.4 days in the 50th and 90th percentile, respectively;p = 0.008 vs. 1% and 0.09 vs. 0.1%) and good tolerability were observed with the 0.5% concentration. All three concentrations achieved highly significant therapeutic results in comparison with baseline values (p < 0.0005) for all secondary parameters as early as day 2/3. Analgesia was the most prominent effect for the patients. Conclusion: The 0.5 % concentration of propolis special extract GH 2002 in a lip balm was found to have the best risk-benefit ratio for the treatment of Herpes labialis.

An Improved Bounded Conflict-Based Search for Multi-AGV Pathfinding in Automated Container Terminals

As the number of automated guided vehicles(AGVs)within automated container terminals(ACT)continues to rise,conflicts have becomemore frequent.Addressing point and edge conflicts ofAGVs,amulti-AGVconflict-free path planning model has been formulated to minimize the total path length of AGVs between shore bridges and yards.For larger terminalmaps and complex environments,the grid method is employed to model AGVs’road networks.An improved bounded conflict-based search(IBCBS)algorithmtailored to ACT is proposed,leveraging the binary tree principle to resolve conflicts and employing focal search to expand the search range.Comparative experiments involving 60 AGVs indicate a reduction in computing time by 37.397%to 64.06%while maintaining the over cost within 1.019%.Numerical experiments validate the proposed algorithm’s efficacy in enhancing efficiency and ensuring solution quality.

Direction finding of bistatic MIMO radar in strong impulse noise

For bistatic multiple-input multiple-output(MIMO)radar,this paper presents a robust and direction finding method in strong impulse noise environment.By means of a new lower order covariance,the method is effective in suppressing impulse noise and achieving superior direction finding performance using the maximum likelihood(ML)estimation method.A quantum equilibrium optimizer algorithm(QEOA)is devised to resolve the corresponding objective function for efficient and accurate direc-tion finding.The results of simulation reveal the capability of the presented method in success rate and root mean square error over existing direction-finding methods in different application situations,e.g.,locating coherent signal sources with very few snapshots in strong impulse noise.Other than that,the Cramér-Rao bound(CRB)under impulse noise environment has been drawn to test the capability of the presented method.

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial

Background:Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth,systemic features,and reduced quality of life.There are no disease-modifying treatments.A new biologic,ianalumab(VAY736),with two modes of suppressing B cells,has previously shown preliminary efficacy.This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome.

Analyzing the Form-Finding of a Large-Span Transversely Stiffened Suspended Cable System: A Method Considering Construction Processes

The precise control of the shape of transversely stiffened suspended cable systems is crucial. However, existing form-finding methods primarily rely on iterative calculations that treat loads as fixed known conditions. These methods are inefficient and fail to accurately control shape results. In this study, we propose a form-finding method that analyzes the load response of models under different sag and stress levels, taking into account the construction process. To analyze the system, a structural finite element model was established in ANSYS, and geometric nonlinear analysis was conducted using the Newton-Raphson method. The form-finding analysis results demonstrate that the proposed method achieves precise control of shape, with a maximum shape error ranging from 0.33% to 0.98%. Furthermore, the relationships between loads and tension forces are influenced by the deformed shape of the structures, exhibiting significant geometric nonlinear characteristics. Meanwhile, the load response analysis reveals that the stress level of the self-equilibrium state in the transversely stiffened suspended cable system is primarily governed by strength criteria, while shape is predominantly controlled by stiffness criteria. Importantly, by simulating the initial tensioning process as an initial condition, this method solves for a counterweight that satisfies the requirements and achieves a self-equilibrium state with the desired shape. The shape of the self-equilibrium state is precisely controlled by simulating the construction process. Overall, this work presents a new method for analyzing the form-finding process of large-span transversely stiffened suspended cable system, considering the construction process which was often overlooked in previous studies.

Optimal path finding algorithms based on SLSD road network model

A solution to compute the optimal path based on a single-line-single-directional（SLSD）road network model is proposed.Unlike the traditional road network model,in the SLSD conceptual model,being single-directional and single-line style,a road is no longer a linkage of road nodes but abstracted as a network node.Similarly,a road node is abstracted as the linkage of two ordered single-directional roads.This model can describe turn restrictions,circular roads,and other real scenarios usually described using a super-graph.Then a computing framework for optimal path finding（OPF）is presented.It is proved that classical Dijkstra and A algorithms can be directly used for OPF computing of any real-world road networks by transferring a super-graph to an SLSD network.Finally,using Singapore road network data,the proposed conceptual model and its corresponding optimal path finding algorithms are validated using a two-step optimal path finding algorithm with a pre-computing strategy based on the SLSD road network.

Predictive findings forHelicobacter pylori-uninfected, -infected and -eradicated gastric mucosa: Validation study

AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea breast test in 77 consecutive patients who underwent upper endoscopy. Based on the findings, patients were categorized as H. pylori -uninfected, -infected, or -eradicated cases. Using six photos of certain sites in the stomach per case, we determined the presence or absence of the following endoscopic findings:regular arrangement of collecting venules (RAC), linear erythema, hemorrhage, fundic gland polyp (FGP), atrophic change, rugal hyperplasia, edema, spotty erythema, exudate, xanthoma, and mottled patchy erythema (MPE). The diagnostic odds ratio (DOR) and inter-observer agreement (Kappa value) for these 11 endoscopic findings used in the determination of H. pylori infection status were calculated. RESULTS:Of the 77 patients [32 men and 45 women; mean age (SD), 39.7 (13.4) years] assessed, 28 were H. pylori uninfected, 28 were infected, and 21 were eradicated. DOR values were significantly high (< 0.05) for the following H. pylori cases:uninfected cases with RAC (11.5), linear erythema (24.5), hemorrhage (4.1), and FGP (34.5); for infected cases with atrophic change (8.67), rugal hyperplasia (15.8), edema (14.2), spotty erythema (11.5), and exudate (3.52); and for eradicated cases with atrophic change (32.4) and MPE (103.0). Kappa values were excellent for FGP (0.93), good for RAC (0.63), hemorrhage (0.79), atrophic change (0.74), and MPE (0.75), moderate for linear erythema (0.51), rugal hyperplasia (0.49), edema (0.58), spotty erythema (0.47), and exudate (0.46), and poor for xanthoma (0.19). CONCLUSION:The endoscopic findings of RAC, hemorrhage, FGP, atrophic change, and MPE will be useful for predicting H. pylori infection status.

Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis

AIM: To investigate the prevalence and implications of unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis. METHODS: The demographic and histopathological data of 1621 patients (≥ 16 years-old) who underwent appendectomy to treat an initial diagnosis of acute appendicitis between January 1999 and November 2011 were retrospectively assessed. Microscopic findings were used to classify the patients under six categories: appendix vermiformis, phlegmonous appendicitis, gan- grenous appendicitis, perforated appendicitis, supurative appendicitis, and unusual histopathologic findings. The demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and re-analysis of archived resected appendix specimens was carried out. RESULTS: A total of 912 males and 709 females, from16 to 94 years old, were included in the study and comprised 789 cases of suppurative appendicitis, 370 cases of appendix vermiformis, 243 cases of perforated gangrenous appendicitis, 53 cases of flegmaneous appendicitis, 32 cases of gangrenous appendicitis, and 134 (8.3%) cases of unusual histopathological findings. The unusual histopathological findings included fibrous obliteration (n = 62), enterobius vermicularis (n = 31), eosinophilic infiltration (n = 10), mucinous cystadenoma (n = 8), carcinoid tumor (n = 6), granulomatous inflammation (n = 5), adenocarcinoma (n = 4; one of them mucinous), and mucocele (n = 3), adenomatous polyp (n = 1), taenia sup (n = 1), ascaris lumbricoides (n = 1), appendiceal diverticula (n = 1), and B cell non-hodgkin lymphoma (n = 1). None of the 11 patients with subsequent diagnosis of tumor were suspected of cancer prior to the appendectomy. CONCLUSION: Even when the macroscopic appearance of appendectomy specimens is normal, histopathological assessment will allow early diagnosis of many unusual diseases.

Blastocystis in ulcerative colitis patients:Genetic diversity and analysis of laboratory findings

Objective:To determine Blastocystis frequency and subtypes(ST) in ulcerative colitis(UC) patients and analyse some laboratory findings between Blastocystis positive and negative cases.Methods:Faecal samples from 150 UC patients in Adnan Menderes University,Training and Research Hospital were examined by direct microscopy and cultivated in Jones medium.Blastocystis positive cultures were subjected to DNA isolation and subtypes were identified by sequencing of barcode region.A retrospective analysis was conducted on C reactive protein(CRP),leukocyte counts(WBC),neutrophil counts,and sedimentation rates.Results:The overall positive rate of Blastocystis was 8%(12 patients) and the most abundant subtype was ST3(eight isolates,66.7%),followed by ST1,ST2 and ST7.Laboratory findings between Blastocystis infected and non-infected UC patients were not significantly different.Blastocystisfrequency was 3.8% among the patients in active stage,while it was 11.8% among the patients in remission stage.Conclusions:The present study confirms previous findings that have indicated the predominance of Blastocystis ST3 in humans and contributes additional evidence that suggests the low colonization of Blastocystis infection in ulcerative colitis patients during active stage.

A Research of the Finding and Distribution Law of Taisui in Modern China

The academic world is still uncertain about the classification of Taisui. It is debating whether Taisui is living or not, myxomycete complex or fungi. The passage studies the 228 finding reports of Taisui in modern China. It confirms that the first finding time of Taisui in modern China is 1963, and the first reported time is 1992. Taisui has been found in 25 administrative divisions. Taisui occurs the most times in Shandong Province. Besides, provinces where Taisui has been found most times are in northern China. Finding locations of Taisui vary from place to place. Taisui is most often found in normal earth layer, with different burying depth. Taisui is mainly found through seeing, tramping, and digging. Taisui findings lack subjective motivations and are connected with the life and production of the finders. Conclusion: Taisui is an object growing in earth layer.

Non-alcoholic steatohepatitis and influence of age and gender on histopathologic findings

AIM:To characterize the histopathologic specifications of non-alcoholic steatohepatitis(NASH)according to age and gender.METHODS:An analytical cross-sectional study was conducted in two private gastroenterology clinics on biopsy proven patients suffering from NASH.Biopsy histopathologic findings as well as demographic and laboratory data of the patients at the time of biopsy were gathered retrospectively from clinical records.The grading and staging of histopathologic findings were performed according to the Brunt method after reevaluation of the slides by a pathologist.Patients were divided into two groups according to age(belowand above 55 years).Mean quantitative grade of all pathologic findings were also calculated according to Brunt scoring values.RESULTS:A total number of 77 NASH patients,consisting of 58 males(75.3%)and 19(24.7%)females with a mean age of 41.99±11.80 years(range,18-70 years),were enrolled.The mean age(48.72±13.99 years vs 39.74±10.16 years,P=0.004)and aspartate aminotransferase level(75.11±29.68 U/L vs 52.78± 25.00 U/L,P=0.002)was significantly higher in female patients.Mean quantitative grade of hepatosteatosis was significantly higher in females(2.00±0.82 vs 1.59 ±0.68,P=0.031)compared to males.Fifty four percent(34/65)of young patients had mild hepatosteatosis (GradeⅠ)while only one patient(11.2%)in the older group had gradeⅠhepatosteatosis.Patients aged≥55 had significantly more severe hepatosteatosis(GradeⅢ) (44.4%vs 9.5%,P=0.007)and the mean quantitative grade of hepatosteatosis was significantly higher among them(2.33±0.71 vs 1.56±0.67,P=0.002).Multivariate analysis after omitting the confounding role of age revealed a higher grade of hepatosteatosis in female patients(P=0.010).CONCLUSION:These findings point toward the possible influence of age in the severity of steatohepatitis,portal and lobar inflammation in patients suffering from NASH while gender independently might contribute to the level of steatohepatitis.

To Improve the Accuracy of Laser Pulse Range Finding by Time Scale-Up

A method of improving the accuracy of laser pulse range finding from ±10 m to ±1 m inexpensively by means of time scale up is described. Time scale up can stretch the entire flight time by a factor of 1 000 and then the stretched result is counted to calculate the distance. The use of this technique decreases the resolution of counting from nanosecond to microsecond, therefore a separate counting oscillator followed by an interpolation operation is unnecessary. This technique can improve the accuracy of laser pulse range finding inexpensively and effectively.