The synergistic effects of Korean Red Ginseng and Cervi Parvum Cornu ameliorating FeCl3-induced arterial thrombosis by downregulating ICAM-1 and VCAM-1.

In this study, we compared antithrombotic activities of Korean Red Ginseng (KRG) and Cervi Parvum Cornu (CPC) on rats with induced thrombosis. Results indicate that KRG and CPC suppressed the arterial occlusion and the combination of KRG and CPC (KRG + CPC) treatment exhibited a synergistic effect with maximum reduction in thrombosis.

Development and evaluation of two rapid lateral flow assays for on-site detection of African swine fever virus.

Introduction: African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. In the absence of a widely available and definitively proven vaccine, rapid and early detection is critical for ASF control. The quick and user-friendly lateral flow assay (LFA) can easily be performed by following simple instructions and is ideal for on-site use. This study describes the development and validation of two LFAs for the rapid detection of ASF virus (ASFV) in pig serum. Methods: The highly immunogenic antigens (p30 and p72) of ASFV Georgia 2007/1 (genotype II) were expressed in plants (Nicotiana benthamiana) and were used to immunize BALB/c mice to generate specific monoclonal antibodies (mAbs) against the p30 and p72 proteins. mAbs with the strongest binding ability to each protein were used to develop p30_LFA and p72_LFA for detecting the respective ASFV antigens. The assays were first evaluated using a spike-in test by adding the purified p30 or p72 protein to a serum sample from a healthy donor pig. Further validation of the tests was carried out using serum samples derived from experimentally infected domestic pigs, field domestic pigs, and feral pigs, and the results were compared with those of ASFV real-time PCR. Results: p30_LFA and p72_LFA showed no cross-reaction with common swine viruses and delivered visual results in 15 min. When testing with serially diluted proteins in swine serum samples, analytical sensitivity reached 10 ng/test for p30_LFA and 20 ng/test for p72_LFA. Using real-time PCR as a reference, both assays demonstrated high sensitivity (84.21% for p30_LFA and 100% for p72_LFA) with experimentally ASFV-infected pig sera. Specificity was 100% for both LFAs using a panel of PBS-inoculated domestic pig sera. Excellent specificity was also shown for field domestic pig sera (100% for p30_LFA and 93% for p72_LFA) and feral pig sera (100% for both LFAs). Conclusion: The results obtained in this study suggest that p30_LFA and p72_LFA hold promise as rapid, sensitive, user-friendly, and field-deployable tools for ASF control, particularly in settings with limited laboratory resources.

Intrinsic capacity transitions as predictors of frailty transitions in community-dwelling older adults: Findings from the Korean Frailty and Aging Cohort Study.

BACKGROUND: Frailty is associated with reduced intrinsic capacity (IC). However, studies evaluating longitudinal transitions between IC and frailty are limited. We conducted longitudinal analyses to investigate the association between intrinsic capacity (IC) and frailty transitions among community-dwelling older adults in Korea. METHODS: A total of 2,345 older adults who completed baseline and two-year follow-up surveys were selected from the Korean Frailty and Aging Cohort Study. IC was measured in five domains: locomotion, vitality, cognition, psychology, and sensory function. Frailty was defined using the Fried frailty phenotype. Transitions in IC and frailty were assessed. Logistic regression analysis was used to analyze the association between baseline IC, IC transitions, and frailty transitions. RESULTS: During the two-year follow-up, 17.8 % of participants improved, 20.4 % worsened, and 61.8 % maintained the same frailty status. Low IC (odds ratio [OR]=1.93; 95 % confidence interval [CI]=1.42-2.61) significantly predicted remaining frail or worsening frailty. Worsened IC increased the risk of remaining frail or worsening frailty, whereas improved IC decreased this risk. Among the IC domains, the onset of new locomotion (OR=3.33; 95 % CI=2.39-4.64), vitality (OR=2.12; 95 % CI=1.55-2.91), and psychological (OR=3.61; 95 % CI=2.64-4.92) impairment predicted remaining frail or worsening frailty. CONCLUSIONS: Low and worsened IC were associated with an increased risk of remaining frail or worsening frailty over two years. These findings indicate that changes in IC can predict frailty transitions, thereby emphasizing the importance of enhancing IC in preventing frailty progression.

The Development of a Quantitative Disability Assessment Tool in Patients with Idiopathic Parkinson's Disease.

Background/Objectives: The objective of this study was to develop a novel quantitative disability assessment tool for patients with idiopathic Parkinson's disease (IPD). Methods: A total of 47 patients with IPD were recruited from two hospitals. A specialist in Rehabilitation Medicine utilized the modified Schwab and England Activities of Daily Living Scale (mSEADL) as a reference, conducting a comprehensive medical chart review and an in-depth interview. The novel-developed disability measurement was calculated as ((mSEADL during the on-state) × (time of on-state)) + ((mSEADL during the off-state) × (time of off-state))/(waking time). Additionally, the degree of disability was assessed using the Korean version of the Modified Barthel Index during the on-state. Results: Twenty-four participants (51.1%) exhibited the off-state during waking hours. In patients exhibiting an off-state, the mSEADL score was significantly lower during the off-state than during the on-state (p < 0.05). The novel-developed disability measurement demonstrated a higher correlation coefficient with the reference mSEADL (0.960) than with the K-MBI (0.808), with statistical significance (p < 0.05). Conclusions: The results demonstrated that larger IPD patients exhibited an on-off phenomenon with greater dependency during the off-state. Therefore, the on-off phenomenon should be considered when evaluating disability in patients with IPD, with methods such as the novel-developed disability measurement tool in this study.

Short-Term and Long-Term Risk of Diabetes Mellitus among Patients with Spinal Cord Injury: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Estimating the risk of diabetes mellitus (DM) is important for the proper management of patients with spinal cord injury (SCI). We investigated the short-term and long-term risks of DM among patients with SCI, according to the presence or severity of post-SCI disability and the level of injury. METHODS: We conducted a retrospective cohort study using the Korean National Health Insurance Service (2010-2018) database. After matching by age and sex, 6129 SCI patients and 22,979 controls were included. The primary outcome was incident DM, and risk was evaluated for both the short term (within 1 year after SCI) and the long term (after 1 year of SCI diagnosis). RESULTS: The risk of DM was higher among patients with cervical- and thoracic-level SCI accompanied by disability compared to the controls during follow-up (4.6 ± 2.6 years). The short-term risk of DM was higher among patients with SCI (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.91-3.27) than among the controls and it was even higher among patients with severe disability (OR 5.38, 95% CI 2.91-9.27). According to the level of injury, patients with cervical SCI had the highest short-term risk of DM (with disability, OR 4.93, 95% CI 3.07-7.63). There was no significant increase of DM risk in the long term, after 1 year of SCI diagnosis. CONCLUSIONS: Patients with SCI accompanied by severe disability and cervical-level injury had higher risks of pronounced DM in the short term. The findings of this study emphasize the need for active surveillance of DM among patients with high-level SCI and disability, especially in the short term, in addition to continuous monitoring and proper management of DM in the long term.

Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Detection of freezing of gait in Parkinson's disease from foot-pressure sensing insoles using a temporal convolutional neural network.

Backgrounds: Freezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients. Methods: We recruited 14 PD patients and collected data from multiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model. Results: We found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to other models. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations. Conclusions: We demonstrated the potential of using wearable pressure sensors and machine learning models for FoG detection in PD patients. The TCNN model showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers.

Three-Dimensional Morphological Analysis of the Suprascapular Notch in Patients with Arthroscopic Rotator Cuff Repair.

Background: The morphology of the suprascapular notch (SSN) and the ossification of the superior transverse suprascapular ligament (STSL) are risk factors for injury of the suprascapular nerve (SN) during arthroscopic shoulder procedures. The purpose of the current study was to compare preoperative clinical and radiologic characteristics between patients with and without STSL ossification and to evaluate SSN morphology in patients who underwent arthroscopic rotator cuff repair using a 3-dimensional (3D) reconstructed model. Methods: Patients who underwent arthroscopic rotator cuff repair and were given a computed tomography (CT) scan from March 2018 to August 2019 were included in this study. Patients were divided into 2 groups: those without STSL ossification (group I) and those with STSL ossification (group II). Tear size of the rotator cuff and fatty infiltration of rotator cuff muscles were assessed in preoperative magnetic resonance imaging. The morphology of the SSN was classified following Rengachary's classification. The transverse and vertical diameters of the SSN and the distances from anatomical landmarks to the STSL were measured. All measurements were completed using a 3D CT reconstructed scapula model. Results: A total of 200 patients were included in this study. One hundred seventy-eight patients (89.0%) without STSL ossification were included in group I, and 22 patients (11.0%) with STSL ossification were included in group II. Group II showed a significantly advanced age (61.0 ± 7.4 vs. 71.0 ± 7.3 years, p < 0.001) and a shorter transverse diameter of SSN (10.7 ± 3.1 mm vs. 6.1 ± 3.7 mm, p < 0.001) than group I. In the logistic regression analysis, age was an independent prognostic factor for STSL ossification (odds ratio, 1.201; 95% confidence interval, 1.112-1.296; p < 0.001). Patients in type VI showed significantly shorter transverse diameters than other types (p < 0.001). The patient with type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than those with other types (p < 0.001). Conclusions: In the 3D morphological analysis, age was the independent factor associated with STSL ossification in patients who underwent arthroscopic rotator cuff repair. Type VI showed significantly shorter transverse diameters than other types. Type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than other types.

A Personalized Dose-Finding Algorithm Based on Adaptive Gaussian Process Regression.

Dose-finding studies play a crucial role in drug development by identifying the optimal dose(s) for later studies while considering tolerability. This not only saves time and effort in proceeding with Phase III trials but also improves efficacy. In an era of precision medicine, it is not ideal to assume patient homogeneity in dose-finding studies as patients may respond differently to the drug. To address this, we propose a personalized dose-finding algorithm that assigns patients to individualized optimal biological doses. Our design follows a two-stage approach. Initially, patients are enrolled under broad eligibility criteria. Based on the Stage 1 data, we fit a regression model of toxicity and efficacy outcomes on dose and biomarkers to characterize treatment-sensitive patients. In the second stage, we restrict the trial population to sensitive patients, apply a personalized dose allocation algorithm, and choose the recommended dose at the end of the trial. Simulation study shows that the proposed design reliably enriches the trial population, minimizes the number of failures, and yields superior operating characteristics compared to several existing dose-finding designs in terms of both the percentage of correct selection and the number of patients treated at target dose(s).

Changes in successful aging and its related indicators among community-dwelling older adults: The Korean Frailty and Aging Cohort Study (KFACS).

This study aims to determine the prevalence of successful aging (SA) and examine the association of changes in the indicators of SA and variations in SA status between 2016 and 2020. The study included 548 participants recruited for the Korean Frailty and Aging Cohort Study (KFACS). Compared to participants who achieved SA in 2016 (N = 393, 71.7%), the number of older adults with SA decreased by 7.8% in 2020. Among older adults preserving SA (SA→SA group, 54%), there were relatively small numbers of older adults who successfully maintained indicators, including chronic diseases (no→no, 9.5%), employment (yes→yes, 12.2%), and volunteer activities (yes→yes, 2.9%). Our findings suggest that interventions to strengthen the physical and psychological function of older adults are needed, and social support needs to be guaranteed to improve social engagement for older adults.

Potentiality of Beneficial Microbe Bacillus siamensis GP-P8 for the Suppression of Anthracnose Pathogens and Pepper Plant Growth Promotion.

This study was carried out to screen the antifungal activity against Colletotrichum acutatum, Colletotrichum dematium, and Colletotrichum coccodes. Bacterial isolate GP-P8 from pepper soil was found to be effective against the tested pathogens with an average inhibition rate of 70.7% in in vitro dual culture assays. 16S rRNA gene sequencing analysis result showed that the effective bacterial isolate as Bacillus siamensis. Biochemical characterization of GP-P8 was also performed. According to the results, protease and cellulose, siderophore production, phosphate solubilization, starch hydrolysis, and indole-3-acetic acid production were shown by the GP-P8. Using specific primers, genes involved in the production of antibiotics, such as iturin, fengycin, difficidin, bacilysin, bacillibactin, surfactin, macrolactin, and bacillaene were also detected in B. siamensis GP-P8. Identification and analysis of volatile organic compounds through solid phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) revealed that acetoin and 2,3-butanediol were produced by isolate GP-P8. In vivo tests showed that GP-P8 significantly reduced the anthracnose disease caused by C. acutatum, and enhanced the growth of pepper plant. Reverse transcription polymerase chain reaction analysis of pepper fruits revealed that GP-P8 treated pepper plants showed increased expression of immune genes such as CaPR1, CaPR4, CaNPR1, CaMAPK4, CaJA2, and CaERF53. These results strongly suggest that GP-P8 could be a promising biocontrol agent against pepper anthracnose disease and possibly a pepper plant growth-promoting agent.

Ameliorative Effects of HT074-Inula and Paeonia Extract Mixture on Acute Reflux Esophagitis in Rats via Antioxidative Activity.

HT074, a multiherbal mixture containing extracts from Inula britannica flowers and Paeonia lactiflora roots, is used in Korean medicine for gastric disorders. This study investigated the protective mechanisms of HT074 against acute reflux esophagitis (RE) in rats. Nitric oxide (NO) production and mRNA expression of antioxidant-related genes (Nrf2, HO-1, SOD, CAT, and GPx2) were evaluated in LPS-induced RAW 264.7 cells. Gastroesophageal reflux (GER) was induced in rats, followed by HT074 (100, 300 mg/kg) or ranitidine (50 mg/kg) administration. Esophageal damage and histological changes were assessed. Gastric pH and protein expression levels of Nrf2, HO-1, SOD, CAT, and GPx-1/2 were measured. HT074 pretreatment reduced NO production and increased the expression of HO-1, CAT, and GPx2 in LPS-induced RAW 264.7 cells. In GER-induced rats, HT074 significantly decreased esophageal lesions and increased the expression of HO-1, SOD, GPx-1/2, and Nrf2. HT074 did not affect gastric pH. These findings suggest that HT074 protects against GER-induced esophagitis by inhibiting NO production and enhancing antioxidant activity. Therefore, HT074 could be a promising therapeutic agent for GER disease.

Analysis of adenoma detection rate of colonoscopy among trainees.

Purpose: To analyze adenoma detection rate (ADR) and related quality indicators of colonoscopy among trainees and make recommendations for appropriate colonoscopy training. Methods: ADR and related indicators of colonoscopies performed by 3 trainees and 5 colonoscopy experts between March and November 2022 were analyzed. These indicators were analyzed in both the entire patients and the screening/surveillance group. In addition, the training period of the 3 trainees was divided into 3 sections, and the changes in these indicators were examined. Results: The mean ADR of the 3 trainees was 50.6%. In the screening/surveillance group, the mean ADR of the 3 trainees was 51.8%, showing no significant difference from the experts' ADR (53.4%). When the training period was divided into 3 sections and analyzed in the screening/surveillance group, the mean ADR of the trainees gradually increased to 49.4%, 52.6%, and 53.6%, respectively; however, the difference was insignificant. Analyzing each trainee's ADR, there was a significant difference among the 3 trainees (58.5% vs. 44.7% vs. 50.2%, P=0.008). However, in the third section of the training period, the 3 trainees' ADRs were 53.0%, 49.2%, and 57.3%, respectively, showing no significant difference (P=0.606). Conclusion: In the early stages of training, the ADR was higher than recommended; however, there were variances in ADR between individuals. As the training period passed, the ADR became similar at the expert level, whereas the difference in ADR between trainees decreased. Therefore, efforts to increase ADR should be made actively from the beginning of training and continued during the training period.

The Life Functioning Scale: a Measurement Tool Developed to Assess the Physical Functioning Abilities of Community-Dwelling Adults Aged 50 Years or Older.

Background: This study aimed to develop an instrument for assessing physical functioning among adults aged 50 years or older living in the community. Methods: Based on a review of various national health surveys and cohort studies, a 144-item bank was constructed for assessing physical functioning. Focus group interviews were conducted among adults aged 50 years or older to investigate their level of understanding of 60 selected items, followed by a pretest of the items on a nationally representative sample (n = 508). The final 25-item questionnaire was tested on an independent sample (n = 259) for validity and reliability based on classical test and item response theories. Predictive validity at the 6-month follow-up was tested in a separate sample (n = 263). Results: The newly developed Life Functioning (LF) scale assessed the dimensions of functional limitations, disabilities, and social activities. The scale satisfied a one-dimensionality assumption with good item fit and demonstrated criterion validity, construct validity, high internal consistency (Cronbach's alpha = 0.93), and test-retest reliability (intra-class correlation coefficient = 0.84; 95% CI, 0.76-0.89). The LF scale comprised 25 items with a total score ranging from 0 to 100. Higher scores indicated higher levels of functioning. The LF score was significantly associated with the physical functioning score at 6 months. Conclusion: The LF scale was developed to assess the physical functioning of people in their late midlife or older. Future studies should test the instrument on a national sample and evaluate its application in diverse population subgroups.

Predictive factors for size change of aorta in patients with acute blunt traumatic aortic injury.

OBJECTIVE: We aimed to investigate the changes in aorta size, the factors affecting size changes in patients with acute blunt traumatic aortic injury and to evaluate the adequacy of the current 120% thoracic endovascular aortic repair graft oversizing policy. DESIGN AND METHODS: This retrospective review study was conducted using the prospectively collected medical records of 45 patients (mean age: 53.5 years, male: 39 patients) with blunt traumatic aortic injury treated at a level 1 trauma center between 2012 and 2021. Aortic diameter was measured by computed tomography angiographic images at four different levels [ascending aorta (A), isthmus (B), descending thoracic aorta (C), and infrarenal aorta (D)] on arrival and follow-up (median time interval, 13 days). Associated factors including patient characteristics and hemodynamic parameters on arrival and follow-up were collected to determine their influence on changes in the aorta. RESULTS: The mean diameter of all four aortic levels increased on follow-up computed tomography compared to initial computed tomography (A: + 11.77%, B: + 10.19%, C: + 7.71%, D: + 12.04%). Patient age and injury severity score influenced changes in the diameter of the ascending aorta (P < 0.05). Patient age and blunt traumatic aortic injury grade were significantly associated with changes in the infrarenal aortic diameter (P < 0.05). Three cases of type 1 endoleak were observed at follow-up but all were spontaneously resolved without further intervention at next computed tomography follow-up. CONCLUSIONS: In patients with acute blunt traumatic aortic injury, aortic diameter is significantly smaller by about 10% under shock and is not considered a basis for oversizing the currently implemented 120% thoracic endovascular aortic repair graft sizing. However, in young patients under the age of 40, the change is significantly large and subsequent computed tomography follow-up is required.

Treatment for appendicitis in cancer patients on chemotherapy: a retrospective cohort study.

Purpose: Whether to perform surgery or conservatively manage appendicitis in immunosuppressed patients is a concern for clinicians. This study aimed to compare the outcomes of these 2 treatment options for appendicitis in patients with cancer undergoing chemotherapy. Methods: This retrospective study included 206 patients with cancer who were diagnosed with acute appendicitis between August 2001 and December 2021. Among them, patients who received chemotherapy within 1 month were divided into surgical and conservative groups. We evaluated the outcomes, including treatment success within 1 year, 1-year recurrence, and the number of days from the diagnosis of appendicitis to chemotherapy restart, between the 2 groups. Results: Among the 206 patients with cancer who were diagnosed with acute appendicitis, 78 received chemotherapy within 1 month. The patients were divided into surgery (n = 63) and conservative (n = 15) groups. In the surgery group, the duration of antibiotic therapy (7.0 days vs. 16.0 days, P < 0.001) and length of hospital stay (8.0 days vs. 27.5 days, P = 0.002) were significantly shorter than conservative groups. The duration from the diagnosis of appendicitis to the restart of chemotherapy was shorter in the surgery group (20.8 ± 15.1 days vs. 35.2 ± 28.2 days, P = 0.028). The treatment success rate within 1 year was higher in the surgery group (100% vs. 33.3%, P < 0.001). Conclusion: Surgical treatment showed a significantly higher success rate than conservative treatment for appendicitis in patients less than 1 month after chemotherapy. Further prospective studies will be needed to clinically determine treatment options.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

Efficacy of commercial recombinant HVT vaccines against a North American clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus in chickens.

The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI.

No Additional Effects of Sequential Facilitatory Cerebral and Cerebellar rTMS in Subacute Stroke Patients.

The aim of this study was to investigate the additional effects of cerebellar rTMS on the motor recovery of facilitatory rTMS over affected primary motor cortex (M1) in subacute stroke patients. Twenty-eight subacute stroke patients were recruited in this single-blind, randomized, controlled trial. The Cr-Cbll group received Cr-Cbll rTMS stimulation consisting of high-frequency rTMS over affected M1 (10 min), motor training (10 min), and high-frequency rTMS over contralesional Cbll (10 min). The Cr-sham group received sham rTMS instead of high-frequency rTMS over the cerebellum. Ten daily sessions were performed for 2 weeks. A Fugl-Meyer Assessment (FMA) was measured before (T0), immediately after (T1), and 2 months after the intervention (T2). A total of 20 participants (10 in the Cr-Cbll group and 10 in the Cr-sham group) completed the intervention. There was no significant difference in clinical characteristics between the two groups at T0. FMA was significantly improved after the intervention in both Cr-Cbll and Cr-sham groups (p < 0.05). However, there was no significant interaction in FMA between time and group. In conclusion, these results could not demonstrate that rTMS over the contralesional cerebellum has additional effects to facilitatory rTMS over the affected M1 for improving motor function in subacute stroke patients.

Attojoule Hexagonal Boron Nitride-Based Memristor for High-Performance Neuromorphic Computing.

In next-generation neuromorphic computing applications, the primary challenge lies in achieving energy-efficient and reliable memristors while minimizing their energy consumption to a level comparable to that of biological synapses. In this work, hexagonal boron nitride (h-BN)-based metal-insulator-semiconductor (MIS) memristors operating is presented at the attojoule-level tailored for high-performance artificial neural networks. The memristors benefit from a wafer-scale uniform h-BN resistive switching medium grown directly on a highly doped Si wafer using metal-organic chemical vapor deposition (MOCVD), resulting in outstanding reliability and low variability. Notably, the h-BN-based memristors exhibit exceptionally low energy consumption of attojoule levels, coupled with fast switching speed. The switching mechanisms are systematically substantiated by electrical and nano-structural analysis, confirming that the h-BN layer facilitates the resistive switching with extremely low high resistance states (HRS) and the native SiOx on Si contributes to suppressing excessive current, enabling attojoule-level energy consumption. Furthermore, the formation of atomic-scale conductive filaments leads to remarkably fast response times within the nanosecond range, and allows for the attainment of multi-resistance states, making these memristors well-suited for next-generation neuromorphic applications. The h-BN-based MIS memristors hold the potential to revolutionize energy consumption limitations in neuromorphic devices, bridging the gap between artificial and biological synapses.