bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Estradiol and Bone Mineral Density in Adults Aged 40-60 years
Authors: Wang Nan , Zhang Ying , Huang Chengcheng
Published: March 2022

Background: The purpose of this analysis was to explore the relationship between estradiol and total bone mineral density (BMD) in American adults aged 40 to 60 years.Methods: We used a cross-sectional study. Data for the study came from the National Health and Nutrition Examination Survey (NHANES) . The study examined data from a sample of the American population. Results: Data analysis showed a significant association between estradiol levels and total bone mineral density in US adults aged 40 to 60 years. When estradiol levels were below the threshold of 33.3pg/mL, estradiol was positively associated with total BMD in all ethnic groups. There was no significant correlation between estradiol levels above the threshold of 33.3pg/mL. When estradiol levels in men were below the threshold of 40.3pg/mL, estradiol was positively correlated with total BMD. When estradiol levels in women were below the threshold of 25pg/mL, estradiol was positively correlated with total BMD.Conclusions: In the 40-60 year old population, when estradiol level is at a lower concentration, estradiol level is positively correlated with total BMD. Increasing estradiol level can promote bone health. When estradiol levels are at higher concentrations, changes in estradiol levels may have no significant effect on bone health.
p -Coumaric acid protects against D-galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain
Authors: Juvekar Archana Ramesh , Daroi Pratibha Atul , Dhage Shrikant
Published: March 2022

D-galactose (D-gal) induced senescence in rodents is a widely used model for assessment of molecules affecting brain ageing. Chronic administration of D-gal causes neuroinflammation leading to cognitive deficit and memory impairment which represent Alzheimer’s dementia. In present study, we investigated the neuroprotective effects of the natural phenol, p-Coumaric acid (PCA) and its underlying mechanism in the chronic D-gal treated mice. Subcutaneous administration of D-gal (150 mg/kg) to Swiss albino mice for 42 consecutive days resulted in cognitive impairment as observed in Morris water maize (MWM) and Y maze test, which was ameliorated by concurrent treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.). Importantly, PCA treatment attenuated the D-gal induced oxidative stress and significantly inhibited acetylcholinesterase (AChE) activity in mice brain. Furthermore, PCA treatment significantly lowered levels of inflammatory marker nuclear factor kappa B (NFκB) and reduced levels of proapoptotic enzyme caspase 3. We also observed that PCA treatment exhibited β-secretase enzyme (BACE1) inhibitory effect. However, our results revealed that PCA treatment failed to decrease the level of advanced glycation end products (AGE) both in vitro and in vivo. Taken together, current study demonstrated the significant neuroprotective effect of PCA against D-galactose induced neuroinflammation, cognitive impairment and apoptosis.
HC-1119, a Deuterated Enzalutamide, Inhibits Migration, Invasion and Metastasis of the AR-positive Triple-negative Breast Cancer Cells
Authors: Wu Xuehong , Feng Wanru , Yang Mao , Liu Xunxi , Gao Mengdi , Li Xinghai , Gan Lin , He Tao
Published: March 2022

Triple-negative breast cancers (TNBCs) are aggressive, and they develop metastasis at earlier stages, relapse more frequently, and exhibits poorer prognosis than other subtypes of breast cancer. Due to the lack of estrogen receptor for endocrine therapy and HER2 for targeted therapy, new targeted therapies for TNBCs are urgently needed. Enzalutamide is a second-generation androgen receptor (AR) inhibitor, and HC-1119 is a new synthetic deuterated enzalutamide. Owing to the isotope effect, HC-1119 has many advantages over enzalutamide, including slow metabolism, high plasma concentration and low brain exposure. However, the efficacy of HC-1119 in inhibition of AR function in triple-negative breast cancer (TNBC) has not been studied. In this study, we found high-level AR expression in both Hs578T and SUM159PT TNBC cell lines. Activation of AR by dihydrotestosterone (DHT) in both cell lines increased AR protein, induced AR-nuclear localization, enhanced cell migration and invasion in culture, and promoted liver metastasis in mice. Importantly, cotreatment with HC-1119 of these cells efficiently abolished all of these effects of DHT on both Hs578T and SUM159PT cells. These results indicate that HC-1119 is a very effective new second-generation AR antagonist that can inhibit the migration, invasion and metastasis of the AR-positive TNBC cells.
Safety, tolerability and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth
Authors: Bayar Erna , MacIntyre David A , Sykes Lynne , Mountain Katie , Lee Yun , Parks Thomas P , Lee Peter P , Bennett Phillip R
Published: March 2022

BackgroundThe vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. Vaginal administration of Lactobacillus crispatus as a live biotherapeutic in non-pregnant women leads to colonisation and reduced recurrence of bacterial vaginosis and urinary tract infections. This is a first in-pregnancy observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V, Osel)) in a cohort of pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy. MethodsPregnant women at high-risk of PTB were offered a course of LACTIN-V at 14 weeks gestation for 5 consecutive days followed by weekly administration for 6 weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks’ gestation and at delivery for assessment of adverse events, compliance, and tolerance. After study completion, women completed a questionnaire to gauge experience and acceptability. Assessment of adverse events was performed in those women completing LACTIN-V therapy and those who commenced LACTIN-V but later withdrew from the study.ResultsA total of 73 women were recruited, of whom 8 withdrew, leaving a final cohort size of 61. Overall patient reported compliance to the full course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was not judged to be related to LACTIN-V and no serious adverse events occurred. One mild adverse event led to withdrawal from the study. A total of 31 women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) stated they would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) reported that the schedule of use was difficult to remember. The rate of early PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2190 women at similar background PTB risk.ConclusionsWith satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and well accepted in pregnancy, with high tolerability. Further studies are needed to assess rates of Lactobacillus crispatus CTV-05 colonisation and clinical efficacy. Trial RegistrationThe trial is registered at www.clinicaltrials.gov (NCT03992534). Date of registration was June 20, 2019
Dynamic compression locking system vs. dynamic hip screw in the treatment of femoral neck fractures: A comparative study
Authors: Chang Jian-Zhong , Xiao Ya-Ping , Li Ling , Bei Ming-Jian
Published: March 2022

Background: There is still a lack of consensus on which internal fixation method can better maintain the stability of femoral neck fractures (FNF), promote fracture healing, and avoid and reduce postoperative complications such as femoral head necrosis and nonunion. Therefore, the purpose of this study was to evaluate the clinical efficacy of the novel dynamic compression locking system (DCLS) versus dynamic hip screw (DHS) in the treatment of FNF.Methods: Fifty cases of FNF admitted from July 2018 to December 2020 were retrospectively analyzed. According to different treatment methods, they were divided into DCLS group (26 cases) and DHS group (24 cases). Baseline data, intraoperative and postoperative clinical data, complications, and Harris score were collected to evaluate the clinical efficacy. Results: All patients were followed up for 24 months, all of which were caused by falls. The baseline data of the two groups were comparable (P>0.05). There were not significant differences in the length of hospital stay and mobility between the two groups (P>0.05). The operation time, blood loss, incision length, fluoroscopy times and the degree of femoral neck shortening in the DCLS group were significantly less than those in the DHS group (all P<0.05). Harris score in the DCLS group was significantly higher than that in the DHS group (P<0.05). Complications of femoral head necrosis and nonunion in the DHS group were slightly higher than those in the DCLS group, but there was not statistical significance (P>0.05). Conclusion: DCLS is superior to DHS in the treatment of FNF, with advantages of less surgical trauma, simplified surgical procedures, lower radiation exposure dose for patients, good stability of internal fixation and better control of femoral neck shortening. However, there is not significant difference in fracture healing complications, which requires further study.
Association of mutation in the PRKAG2 with familial left ventricular non-compaction cardiomyopathy
Authors: Zhang Jing , Han Xiu , Lu Qun , Ma Aiqun , Wang Tingzhong
Published: March 2022

Left ventricular non-compaction cardiomyopathy (LVNC) is one of the most common inherited cardiovascular diseases. The genetic backgrounds of most LVNC patients are not fully understood. We collected clinical data, family histories, and blood samples and performed genetic analysis using next-generation sequencing (NGS) from a Chinese family of 15 subjects. Clinically LVNC affected subjects showed marked cardiac phenotype heterogeneity. We found that these subjects with LVNC carried a missense heterozygous genetic mutation c.905G༞A(p. R302Q) in γ2 subunit of AMP-activated protein kinase (PRKAG2) gene through NGS. Individuals without this mutation showed no symptoms or cardiac structural abnormalities related to LVNC. One subject was the victim of sudden cardiac death. To sum up, PRKAG2 mutation [c.905G༞A (p. R302Q)] caused familial LVNC. Our results described a potentially pathogenic mutation associated with LVNC, which may further extend the spectrum of LVNC phenotypes related to PRKAG2 gene mutations.
Monitoring hemoglobin levels in human blood samples using an MXene-ZnO-graphene based Surface plasmon resonance biosensor
Authors: Manavalan Balamurugan Alagar , Kuppusamy Peramandai Govindasamy , Uniyal Arun , Pal Amrindra , Karki Bhishma
Published: March 2022

The main aim of our present study is to propose a surface plasmon resonance-based biosensor design for hemoglobin concentration monitoring in human blood samples. The proposed SPR sensor is based upon the Kretschmann configuration with silver metal, MXene, ZnO, and graphene nanolayers, with a BK7 coupling prism. A He-Ne laser optical input source with a 633 nm wavelength is used following the attenuated total reflection (ATR) principle. After employing the MXene, ZnO, and graphene layers over the conventional sensor setup, an investigation is done. With the optimized structure, our main aim is to detect the presence of hemoglobin concentration in the human blood with its refractive index variation. The calculated highest sensitivity of the proposed configuration is 154 \(Degree/RIU\) with the other parameters calculated as FWHM near \(3.69 Degree\), SNR of 0.5051 \({\text{D}\text{e}\text{g}\text{r}\text{e}\text{e}}^{-1}\) and quality factor of 41.58 \({RIU}^{-1}\).
Control of dumbbell satellite orbits using moving mass actuators
Authors: Pilipchuk Valery , Shaw Steve , Chalhoub Nabil
Published: March 2022

Possible principles of a moving mass control of the orbital parameters of an artificial satellite are discussed in the present paper. The satellite is assumed to have a dumbbell shape such that both massive parts can spin and change their relative distance upon the orbital angle according to the suggested control strategy. The latter aims at maintaining a desired satellite size and orientation with respect to the orbital radius in order to take advantage of the variations in the gravitational field along the elliptical orbit. The eccentricity of the orbit along with the energy and angular momentum of the satellite can be shown to gradually vary in an adiabatic way. In particular, the results demonstrate that the parameter of total orbital energy can follow a prescribed temporal profile by controlling the satellite orientation on the orbit to accurately track its desired target. The results from both analytical estimates and numerical integration appear to be in sufficient agreement.
A Golden Thread approach to transforming Maternal and Child Health in Singapore
Authors: Yap Fabian , Loy See Ling , Ku Chee Wai , Chua Mei Chien , Godfrey Keith M. , Chan Jerry Kok Yen
Published: March 2022

Maternal and child health (MCH) in Singapore is currently entering a new phase, with challenges different to those faced 50 years ago. The advancement of medical technologies and access to MCH resources have led to a dramatic fall in maternal and infant mortality rates. However, there has been a steep rise in the rates of obesity and related metabolic diseases. Alongside this is an emerging mental wellness challenge, with one in ten women experience depression across pre-, during and post-pregnancy. Maternal obesity and mental disorders before and during pregnancy not only increase a woman’s risk of pregnancy complications, but also program increased risks in the offspring of childhood obesity, behavioral disorders and later life metabolic disease, catalyzing vicious cycles of disease. Thus, there is a pressing need to transform the current MCH system to address a burgeoning metabolic and mental health challenge for Singapore. Initiating interventions during preconception and continuing into the postpartum has the potential to confer long-term maternal-child benefits, promoting virtuous cycles of health. However, the current MCH system emphasizes antenatal care and lacks focus on the equally, if not more important, preconception, postpartum and inter-pregnancy stages. We describe a new model-of-care framework that integrates a life-course approach to health across preconception, pregnancy and postpartum phases, with the social-ecological model comprising individual, interpersonal, institutional, community and policy as the major targets for health promotion interventions. This “golden thread” approach is being established at the Singapore KK Women’s and Children’s Hospital (KKH), to address both metabolic and mental health challenges to achieve the goal of a thriving, healthy nation. This new model-of-care is set up in KKH as a pilot program known as Healthy Early Life Moments in Singapore (HELMS). HELMS will reach out to women planning to conceive through coordinated interventions across preconception, pregnancy and postpartum periods. A mobile health platform is being developed to facilitate interventions and engage participants in the program through a digital, personalized and interactive approach. This new model-of-care is designed to secure a population with healthy life cycles, by influencing each life-course, early-in-life, to provide the best start for generations to come.
Lrg1 inhibits the activation of hepatic macrophages to alleviate NAFLD by enhancing TGF-β1 signaling
Authors: XU LONGFEI , HAN JING , YANG ZHE , YANG YANPING , CHEN JINHUI , WU XIJUN , HONG YAN , Wang Qi
Published: March 2022

Background: Non-alcoholic fatty liver disease (NAFLD) is caused by excessive hepatic lipid deposition, and is characterized by hepatocyte steatosis, the accumulation of immune cells and the increased expression of inflammatory factors. Hepatic macrophages are the main hepatic immune cells, which play a decisive role in NAFLD. The inhibition of the M1 polarization of hepatic macrophages or the depletion of hepatic macrophages can alleviate hepatic steatosis and inflammation.Methods and Results: NAFLD mouse model was established by feeding high fat diet (HFD) for 16 weeks, the expression of Lrg1 in liver tissues was detected by Real-time PCR and Western blot. Then expression of Lrg1 in steatotic hepatocytes was detected by Real-time PCR and Western blot. Finally, Western-blot analysis, Real-time PCR, HE staining and immumohistochemical staining were performed to confirm the Lrg1 inhibits the activation of hepatic macrophages to alleviate NAFLD by enhancing TGF-β1 signaling. The results of present study demonstrated that Lrg1 inhibited the polarization of M1 liver macrophages induced by steatotic hepatocyte-derived conditioned medium by enhancing TGF-β1 signaling, and Lrg1 also alleviated liver inflammation induced by a high-fat diet (HFD) via TGF-β1 signaling. In addition, the expression level of Lrg1 was significantly decreased in liver tissues from mice with HFD-induced steatosis. Conclusion: Our findings identify that HFD-induced hepatic expression of Lrg1 was significantly downregulated，Lrg1 inhibits the infiltration of hepatic macrophages to alleviates fatty liver inflammation through enhancing TGF-β1 signaling.
Quinolinic acid induces alterations in neuronal subcellular compartments, blocks autophagy flux and activates necroptosis and apoptosis in rat striatum.
Authors: Silva-Islas Carlos Alfredo , Santana-Martinez Ricardo Alberto , León-Contreras Juan Carlos , Barrera-Oviedo Diana , Pedraza-Chaverri Jose , Hernandez-Pando Rogelio , Maldonado Perla
Published: March 2022

Quinolinic acid (QUIN) is an agonist of N-methyl-D-aspartate receptor (NMDAr) used to study excitotoxicity in animal models. Striatal QUIN administration increases intracellular Ca2+ and oxidative stress, induces cellular damage and activates different mechanisms of cellular death. There is evidence indicating that impairment in autophagy at early times contributes to cellular damage in excitotoxicity; however, the status of autophagy in QUIN model at 7 days remain unexplored. In this study, the ultrastructural analysis of subcellular compartments and the status of autophagy in the striatum of rats administered with QUIN (120 and 240 nmol) was performed at 7 days. QUIN induced motor behavior impairment, tissue neurodegeneration and cellular damage; moreover, promoted swollen mitochondrial crests, spherical-like morphology and mitochondrial fragmentation. QUIN decreased ribosomal density in the rough endoplasmic reticulum and myelin sheaths discontinuity in axons with separation of the compact lamellae. Furthermore, QUIN induced increase and decrease in ULK1 and p-70-S6K phosphorylation, respectively, suggesting autophagy activation; however, the increased microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and sequestosome-1/p62 (SQSTM1/p62), and decreased in Beclin 1 and mature cathepsin D also indicates a blockage in autophagy flux. Additionally, QUIN administration increased tumor necrosis factor alpha (TNFα) and receptor-interacting protein kinase 3 (RIPK3) as well as decreased B-cell lymphoma 2 (Bcl-2) and increased in Bcl-2-associated X protein (Bax) levels and c-Jun N-terminal kinase (JNK) phosphorylation, suggesting an activation of necroptosis and apoptosis, respectively. These results indicate that QUIN caused subcellular compartments alteration, a blockage autophagy flux and activated necroptosis and apoptosis at 7 days.
Prediction of ALRTI caused by HRSV infection in Zhengzhou area in seasonal ARIMA model
Authors: Zhang Guang-chao , Sun Xiao-min , Chen Dan , Guo Qing , Ren Yanhong
Published: March 2022

Objective The seasonal trend of ARIMA product was used to predict the incidence of HRSV infection in Zhengzhou area and to explore the application of the model in predicting the incidence rate of ALRTI caused by HRSV infection in ARIMA.Methods Based on the time series construction model of ALRTI incidence rate from January 2018 to January 2020, the incidence rate of ALRTI caused by HRSV infection from January 2021 to January 2022 was verified by HRSV, and the results were validated.Results Model of ALRTI (1,0,1) (0,1,1) 12 is the best model, with BIC = 8.319, Ljung-Box = 20.787, P = 0.160. The average relative error of predicted and actual values of ALRTI incidence rate from March 2021 to January 2022 is 339.33%, and the actual value is within 95% confidence interval of the predicted value.Conclusion In predicting ALRTI caused by HRSV infection, ARIMA model can better predict the trend of incidence, and its effect needs to be further optimized.
Knowledge of the public about the role of lumbar puncture in the diagnosis of Alzheimer's disease in China
Authors: Guo Xiaojuan , Gao Ling , Jin Jiaoting , Liu Jie , Lu Wenhui , Wang Jin , Qu Qiumin
Published: March 2022

Background: Lumbar puncture for cerebrospinal fluid (CSF) detection has not been widely used in clinical practice in China. The aim of this study was to investigate the knowledge of the public about the role of lumbar puncture in the diagnosis of Alzheimer's disease (AD).Methods: A questionnaire survey was conducted using the "Sojump" application. The participants followed the instruction to answer the questionnaire on mobile phone. The survey included the demographic data of the participants, the knowledge about the role of lumbar puncture in the diagnosis of AD, the reasons to decide to undergo lumbar puncture examination. Univariate analysis and multivariate logistic regression analysis were used to investigate the factors associated with the decision. Results: A total of 1050 valid questionnaires were collected, including 403 (38.4%) non-medical staff and 647 (61.6%) medical staff. A total of 862 participants (82.1%) were willing to undergo lumbar puncture, of whom 508 (58.9%) considered that it was helpful to confirm the diagnosis. Multivariate analysis showed that the factors associated with willingness in non-medical staff included: age (OR=0.963, P=0.003, 95% CI: 0.939-0.987), education level (OR=2.073, P=0.037, 95% CI: 1.044-4.114), monthly income (OR=1.340, P=0.031, 95% CI: 1.028-1.748), and occupation type (OR=1.569, P=0.038, 95% CI: 1.026-2.400). The factors associated with willingness in medical staff included: residence (OR=9.182, P=0.036, 95% CI: 1.151-73.238), monthly income (OR=4.008, P=0.002, 95% CI: 1.689-9.511), and hospital Level (OR=38.311, P<0.001, 95% CI: 14.323-102.478).Conclusions: In the general population, more than 80% of people were willing to undergo lumbar puncture for AD diagnosis. However, the desire for the lumbar puncture depends on age, education level, economic status and occupation type.
The association between wheelchair sports participation and quality of life in individuals with physical disabilities
Authors: Bochkezanian Vanesa , Hill Mitchell G , Pederick Katarina , Ledger Sean J
Published: March 2022

Purpose: To investigate the association between wheelchair sports and quality of life among individuals with physical disabilities living in Australia. Methods: 54 participants aged 18-65 years with physical disabilities completed an online survey. The survey contained the WHOQOL-BREF as the primary outcome measure to assess the quality of life in participants.Results: Participants consisted of 16 females (30%), 37 males (69%) and one who identified as other (1%). Of the 54 participants, 31 (57%) lived in a metropolitan area and 23 (43%) lived in a non- metropolitan area. The total number of participants who actively participated in wheelchair sports (Group 1) was 31 (57%), whilst 23 (43%) did not actively participate in any wheelchair sport (Group 2). Of the 54 participants, 42 (78%) had reported barriers to participation. There was a higher, but non-significant difference (6.9, 95%CI -3.8, 17.6, p=0.20) in quality of life scores between those participating in wheelchair sport (61.1±16.9) and those who did not (54.2±20.8). Discussion: This study showed that there was a positive relationship between participation in wheelchair sports and improved quality of life. The findings of this study were consistent with previous research that concluded that regular physical activity had a positive influence on an individual’s quality of life. Scores were higher in those who actively participates in wheelchair sports. Overall, the results from this study found a positive association between participation in wheelchair sports and increased quality of life.
Factors Influencing Organic Food Purchase of Young Indian Consumers
Authors: Mahongnao Mirinchonme , Varah Franky , Varah Sophayo Khamrang
Published: March 2022

As organic food consumption rises throughout the world, there is a greater need for study on the factors that influence organic food consumption. Previous research yielded mixed results and failed to present a complete picture of organic food consumers in India. The goal of this study is to figure out what factors influence young Indian consumers' desire to buy organic foods. A comprehensive questionnaire study of Indian young consumers aged 15 to 30 years old was created in order to examine the relationship between the established key factors. Data was acquired from 289 young Indian customers in New Delhi, India, using a self-administered structured questionnaire. The findings show that young consumers’ organic food purchase intention is largely determined by their environmental concern, product quality, and social pressure. However, the impact of health consciousness, fear, trust, and price, on organic food purchase intention has been found insignificant. The findings have ramifications for organic food producers, marketers, and policymakers in India who are working to increase organic food consumption.
Visual oscillation effects on dynamic balance control in people with multiple sclerosis
Authors: Riem Lara , Beardsley Scott A. , Obeidat Ahmed Z. , Schmit Brian D.
Published: March 2022

Background: People with multiple sclerosis (PwMS) have balance deficits while ambulating through environments that contain moving objects or visual manipulations to perceived self-motion. However, their ability to parse object from self-movement has not been explored. The purpose of this research was to examine the effect of medial-lateral oscillations of the visual field and of objects within the scene on gait in PwMS and healthy age-matched controls using virtual reality (VR).Methods: Fourteen PwMS (mean age 49 ± 11 years) and eleven healthy controls (mean age: 53 ± 12 years) participated in this study. Dynamic balance control was assessed while participants walked on a treadmill at a self-selected speed while wearing a VR headset that projected an immersive forest scene. Visual conditions consisted of (1) no visual manipulations (speed-matched anterior/posterior optical flow), (2) 0.175 meter mediolateral translational oscillations of the scene that consisted of low pairing (0.1 and 0.31 Hz) or (3) high pairing (0.15 and 0.465 Hz) frequencies, (4) 5 degree medial-lateral rotational oscillations of virtual trees at a low frequency pairing (0.1 and 0.31 Hz), and (5) a combination of the tree and scene movements in (3) and (4).Results: We found that both PwMS and controls exhibited greater instability and visuomotor entrainment to simulated mediolateral translation of the visual field (scene) during treadmill walking. This was demonstrated by significant (p<0.05) increases in mean step width and variability and center of mass sway. Visuomotor entrainment was demonstrated by high coherence between center of mass sway and visual motion (magnitude square coherence = ~ 0.5 to 0.8). Only PwMS exhibited significantly greater instability (higher step width variability and center of mass sway) when objects moved within the scene (i.e., swaying trees).Conclusion: Results suggest the presence of visual motion processing errors in PwMS that reduced dynamic stability. Specifically, object motion (via tree sway) was not effectively parsed from the observer’s self-motion. Identifying this distinction between visual object motion and self-motion detection in MS provides insight regarding stability control in environments with excessive external movement, such as those encountered in daily life.
Biomineralized Ferroptosis-Inducing Nanovaccine Based on Combination of Photothermal Therapy and Checkpoint Blockade for Melanoma
Authors: Ma Siyu , Yang Jie , Fang Tianxu , Zhang Jun , Pan Xiuhua , Wei Yawen , Yang Ning , Liu Zengyi , Shen Qi
Published: March 2022

Background: Until now, treatment of refractory tumors and uncontrolled metastasis has not yet achieved satisfactory therapeutic results due to the immunosuppressive tumor microenvironment. The crucial point is inadequate in vivo immune response after tumor initial cure ablation. Here, we proposed the construction of a photothermal nanovaccine based on biomineralized ovalbumin induced ferroptosis after near-infrared triggering. Fe3+ were chelated inside exogenous antigen ovalbumin by biomineralization, and photosensitizer IR820 was loaded on the outer layer by electrostatic incorporation. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade was combined to offer incomparable opportunities for high-effcient synergistic therapy which consists of ferroptosis, photothermal therapy and cancer immunotherapy.Results: After injection treatment, Fe3+ in the vaccine consumed glutathione (GSH) in cells, affected the expression of GPX4 and initiated Fenton reaction, resulting in ferroptosis, which promoted the immunogenic cell death (ICD). After ICD initiation, released tumor endogenous antigens aroused immune cells activation together with ovalbumin. T cells were successfully recruited and infiltrated into tumor, promising the primary tumor received direct therapy and was effectively suppressed. The photothermal effect was triggered by near-infrared irradiation. Photothermal effect of nanovaccine effectively amplified mild immune response by ferroptosis. With combining with CTLA-4 checkpoint blockade, the related cytokines and other immune indicators all showed increasing levels, which had a significant inhibition effect on distal simulated metastases growth. Conclusion:Fe@OVA-IR820 nanovaccine successfully treated primary and metastatic melanoma with combination therapy. Therefore, we could propose Fe@OVA-IR820 nanovaccine combined checkpoint blockade as a potential therapeutic strategy for melanoma treatment in the future.
Evaluation of Fiber and Debris Release from Protective COVID-19 Mask Textiles and in Vitro Acute Cytotoxicity Effects.
Authors: Meier Philipp , Zabara Mahsa , Hirsch Cordula , Gogos Alexander , Tscherrig Dominic , Richner Gilles , Nowack Bernd , Wick Peter
Published: March 2022

Since the start of the current COVID-19 pandemic, for the first time a significant fraction of the world's population cover their respiratory system for an extended period with mostly medical facemasks and textile masks. This new situation raises questions about the extent of mask related debris (fibers and particles) being released and inhaled and possible adverse effects on human health. This study aimed to quantify the debris release from a textile-based facemask in comparison to a surgical mask and a reference cotton textile using both liquid and air extraction. Under liquid extractions, cotton-based textiles released up to 29'452 ± 1'996 fibers g− 1 textile while synthetic textiles released up to 1'030 ± 115 fibers g− 1 textile. However, when the masks were subjected to air-based extraction scenarios, only a fraction (0.1–1.1%) of this fiber amount was released. Several metals including copper (up to 40.8 ± 0.9 µg g− 1) and iron (up to 7.0 ± 0.3 µg g− 1) were detected in acid dissolved textiles. Additionally the acute in vitro toxicity of size-fractionated liquid extracts (below and above 0.4 µm) were assessed on human alveolar basal epithelial cells. The current study shows no acute cytotoxicity response for all the analyzed facemasks.
Precision synthesis and atomistic analysis of deep blue cubic quantum dots made via self-organization
Authors: Chevalier Olivier , Nakamuro Takayuki , Sato Wataru , Miyashita Satoru , Chiba Takayuki , Kido Junji , Shang Rui , Nakamura Eiichi
Published: March 2022

As a crystal approaches a few nm in size, atoms become nonequivalent, bonds vibrate, and quantum effects emerge. To study quantum dots (QDs) with structural control common in molecular science, we need atomic precision synthesis and analysis. We describe here the synthesis of QDs of lead bromide perovskite via self-organization of a lead malate chelate complex and PbBr3– under ambient conditions. Millisecond and angstrom resolution electron microscopic analysis revealed the structure and the dynamic behavior of individual QDs—structurally uniform cubes made of 64 lead atoms, where eight malate molecules are located on the eight corners of the cubes, and oleylamonium cations lipophilize and stabilize the edges and faces. Lacking translational symmetry, the cube is to be viewed as a molecule rather than a nanocrystal. The QD exhibits quantitative photoluminescence and stable electroluminescence at approx. 460 nm with a narrow half-maximum linewidth of 15 nm, reflecting minimum structural defects. This controlled synthesis and precise analysis demonstrate the potential of cinematic chemistry for the characterization of nanomaterials beyond the conventional limit.
Suppression of humping bead in high-speed triple-wire gas indirect arc welding
Authors: Wang Zeli , Zhang Tianyi , Dong Xiaonan , Liu Liming
Published: March 2022

Triple-wire gas indirect arc welding (TW-GIA) is a new technology with the advantages of low heat input and high deposition rate. However, the humping bead restricts the improvement of welding efficiency. In this article, the high-speed cameras and infrared thermal imaging system were used to characterize the formation mechanism of the TW-GIA humping bead. The physical model was established to discuss the force mechanism of the weld poor. And The influence of process parameters on humping bead was studied. The results showed that the increase of the welding angle reduced the arc pressure and droplet impact force in the opposite direction of welding, which was beneficial to eliminate the hump. When the welding height was lower than 3 mm, the excessive arc pressure led to the humping bead with arc crater. When the welding height was greater than 20 mm, the distance between the droplets of side wires was far, forming the humping bead with "double bead" defect. In addition, the flow distance of the liquid metal shortened as the welding current decreased, which could suppress the humping bead. When the ratio of the total wire feeding speed to the welding speed was 10, the critical current was 360 A, and the critical current increased as the ratio increased. The maximum TW-GIA welding speed of bead on plate was 4.2 m/min, which was 137% higher than that of high-speed GMAW.
Drug-related hospital admissions and emergency department visits: a feasibility study and an updated version of the AT-HARM10 assessment tool
Authors: Kempen Thomas , Hedman Anton , Gillespie Ulrika
Published: March 2022

Background: AT-HARM10 has been used as a research tool to identify drug-related hospital admissions. Its potential use to assess emergency department (ED) visits and an updated version of the tool have been requested.Aim: The aim of this study was to investigate the feasibility to identify drug-related ED visits with AT-HARM10 and provide an updated version of the tool.Method: A random sample of 400 patients aged 65 years or older from a clinical trial in four Swedish hospitals was selected. All patients’ ED visits within 12 months after discharge were assessed with AT-HARM10. The main outcome measures were the percentage of successfully assessed ED visits and the inter-rater reliability (IRR; Cohen’s kappa). AT-HARM10 was revised based on experience from its use in recent studies.Results: The patients had in total 184 ED visits, of which 179 (97%) were successfully assessed. Fifty-three ED visits (29%) were possibly drug-related. The Cohen’s kappa value was 0.70 (substantial). The instructions and one of the ten questions of AT-HARM10 were changed.Conclusion: It is feasible to identify possible drug-related ED visits in addition to hospital admissions in older patients with AT-HARM10 and the tool has been updated to support its use in clinical research.
Differential Neuropathology, Genetics, and Transcriptomics in Two Kindred Cases with Alzheimer’s Disease and Lewy Body Dementia
Authors: Palmieri Ilaria , Poloni Tino Emanuele , Medici Valentina , Zucca Susanna , Davin Annalisa , Pansarasa Orietta , Ceroni Mauro , Tronconi Livio , Guaita Antonio , Gagliardi Stella , Cereda Cristina
Published: March 2022

Background
Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia, but their pathology may involve the same cortical areas with overlapping cognitive manifestation. Dementia cases within the same family share a common genetic background. Nonetheless, the clinical phenotype may be different due to the different underlying molecular processes that come up apart from genetics, causing diverse neurodegeneration. The aim of this study was to define commonalities and differences in the pathological processes of dementia in two kindred cases, a mother and a son, who developed a classical AD and an aggressive form of AD/LBD respectively, through neuropathological, genetic and transcriptomic comparison of four different brain areas (substantia nigra, hippocampus, parietal lobe and basal ganglia).
Results
Genetic analysis did not reveal any pathogenic variants in the principal AD/LBD-causative genes. RNA sequencing highlighted high transcriptional dysregulation within the substantia nigra in LBD pathology, while AD underwent lower degree of transcriptional dysregulation, with the parietal lobe being the most involved brain area. Conversely, hippocampus (the most degenerated area) and basal ganglia (lacking specific lesions) expressed the lowest level of dysregulation.
Conclusions
Our data suggest that there is a link between the transcriptional dysregulation and the amount of tissue damage accumulated across time, assessed through neuropathology. Moreover, we highlight that the molecular bases of AD and LBD follow very different pathways, which underlie their neuropathological signatures. Indeed, the transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological analysis for a deeper understanding of AD and LBD pathogenesis.
Feasibility Study of Ultrasound-Guided Percutaneous Laser Discectomy for Cervical Radicular Pain
Authors: Hu Rong , Zhu Xiaolei , Zhou Yi , Zhang Jianping , Huang Dong , Zhou Haocheng
Published: March 2022

BACKGROUND CONTEXT: Percutaneous laser discectomy is one common and effective treatment for cervical radicular pain. Currently, the surgery is performed with blind cannulation technique, mainly relies on the experience of surgeon. However, it still remains unsafe and difficult to reach the target. As an alternative, ultrasound-guided cannulation provides visualization of important structures, thus increasing the precision and safety. PURPOSE: The primary goal of this study is to report the detail of the ultrasound-guided technique in the percutaneous laser cervical discectomy. The secondary purpose is to evaluate the feasibility of the novel therapy.STUDY DESIGN/SETTING: This is a single center, feasibility study conducted in one teaching hospital. PATIENT SAMPLE: Thirteen intervertebral discs in 9 patients presented with cervical radicular pain.OUTCOME MEASURES: Accuracy of the cannulation with ultrasonic guidance was confirmed by the anterior-posterior and lateral view of fluoroscopy. We compared the pain severity pre- and post-treatment with Visual Analogue Score (VAS), and functional improvement was assessed with the modified Macnab Criteria and Neck Disability Index (NDI) respectively.METHODS: Ultrasonic short-axis was used to scan the cervical nerve root, and its transition was used to identify the distinct intervertebral space. Following the recognition of targeted cervical level, the ultrasound probe was moved medially for the visualization of the surface of the cervical vertebrae. In plane cannulation was then applied to avoid the injury of the vessels. The location of cannula was confirmed by the fluoroscopic imaging. Low-power laser was set for the cervical disc ablation in this cohort. RESULTS: The majority of the surgical sites maintained in the C5/6 level (38%), and 31% for the C6/7 level respectively. Despite the distinct cervical level, the tip of needle was properly placed near by the targeted intervertebral disc in all participants, which was confirmed by the imaging of fluoroscopy. We did not observe any obvious complications during the procedure. The mean VAS decreased from 7.6 ± 1.1 to 2.3 ± 2.7 one month after discharge, and 2.1 ± 2.6 at the last follow-up. All patients reported significant improvement of NDI up to last follow-up (p=0.0105). Meanwhile, the good to excellent rate was reported in 8 of 9 patients (89%) according to the modified Macnab Criteria.CONCLUSIONS: The finding of this feasibility assessment indicates the ultrasound-based cannulation technique is capable of guiding the cannulation for the percutaneous laser discectomy. It may facilitate identifying the corresponding site of cervical intervertebral disc and prevent the damage of vessel.
Application of blood brain barrier models in pre-clinical assessment of glioblastoma- targeting CAR-T based immunotherapies
Authors: Jezierski Anna , Huang Jez , Li Betty (Ying) , Charlebois Claudie , Nguyen Tina , Liu Ziying , Bloemberg Darin , Zafer Ahmed , Baumann Ewa , Sodja Caroline , Leclerc Sonia , Fewell Gwen , Liu Qing , Prabhakarpandian Balabhaskar , McComb Scott , Stanimirovic Danica B.
Published: March 2022

Human blood brain barrier (BBB) models derived from induced pluripotent stem cell (iPSC) have become an important tool for discovery and preclinical evaluation of central nervous system (CNS) targeting cell and gene-based therapies. Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary form of gene-modified cell-based immunotherapy with potential for targeting solid tumors, such as glioblastomas. Crossing the BBB is an important step in the systemic application of CART therapy for the treatment of glioblastomas and other CNS malignancies. In addition, even CART therapies targeting non-CNS antigens such as the well-known CD19-CART therapies, are known to trigger CNS side-effects including brain swelling due to BBB disruption. In this study, we used iPSC-derived brain endothelial-like cell (iBEC) transwell co-culture model to assess BBB extravasation of CART based immunotherapies targeting U87MG human glioblastoma (GBM) cells overexpressing the tumor-specific mutated protein EGFRvIII (U87vIII). Two types of anti-EGFRvIII targeting CART cells with varying tonic signaling profiles (CAR-F263 and CAR-F269) and control Mock T cells were applied on the luminal side of BBB model in vitro. CAR-F263 and CAR-F269 T cells triggered a decrease in transendothelial electrical resistance (TEER) and an increase in permeability. CART cell extravasation and U87vIII cytotoxicity were assessed from the abluminal compartment using flow cytometry and IncuCyte real-time viability imaging, respectively. A significant decrease in U87vIII cell viability was observed over 48 hrs, with the most robust cytotoxicity response observed for the constitutively activated CAR-F263. CAR-F269 T cells showed a similar cytotoxic profile but were both approximately 4-fold less efficient at killing the U87vIII cells compared to CAR-F263, despite similar transmigration rates. Visualization of CART cell extravasation across the BBB was further confirmed using iBEC-on-CHIP models. The described BBB assay was able to discriminate cytotoxic efficacies of the different EGFR-CARs and to provide a measure of potential alterations to BBB integrity. Collectively, we illustrate how BBB models in vitro can be a valuable tool in deciphering the mechanisms of CAR-T–induced BBB disruption, accompanying toxicity and effector function on post-barrier target cells.
Review of the Strengthening Methods and Mechanical Properties of Recycled Aggregate Concrete (RAC)
Authors: Liu Chuanqi , Kong Fanlei , Zhang Xuanhao , Zhou Shenghao , Ma Chong , Sun Jilin
Published: March 2022

Replacing natural aggregate (NA) by recycled aggregate (RA) has contributed to the trend of sustainable development in civil construction. In this background, improvements in the mechanical properties of RAC and the scientific design of the mixture ratio are calling more concerns in recent years. This paper is a review of the recent research, including the following aspects: the mixture design of RAC; the improved mechanical properties of recycled concrete with steel fibers; the performance of the main components. In addition, the primary composition materials, properties, and calculation methods of the mixture ratio of RAC are summarized. The mechanical properties, durability and microscopic analysis of RAC are also discussed. The accurate calculation of mixture proportion can significantly facilitate the work of preparing a test mix of RAC. Through the mixture-ratio optimization and physical and chemical strengthening of RA, the mechanical properties of RAC can be improved to promote the wider application of this eco-friendly material.
Musical training refines audiovisual integration but does not influence temporal recalibration
Authors: O’Donohue Matthew , Lacherez Philippe , Yamamoto Naohide
Published: March 2022

When the brain is exposed to a temporal asynchrony between the senses, it will shift its perception of simultaneity towards the previously experienced asynchrony (temporal recalibration). It is unknown whether recalibration depends on how accurately an individual integrates multisensory cues or on experiences they have had over their lifespan. Hence, we assessed whether musical training modulated audiovisual temporal recalibration. Musicians (n = 20) and non-musicians (n = 18) made simultaneity judgements to flash-tone stimuli before and after adaptation to asynchronous (± 200 ms) flash-tone stimuli. We analysed these judgements via an observer model that described the left and right boundaries of the temporal integration window (decisional criteria) and the amount of sensory noise that affected these judgements. Musicians’ boundaries were narrower (closer to true simultaneity) than non-musicians’, indicating stricter criteria for temporal integration, and they also exhibited enhanced sensory precision. However, while both musicians and non-musicians experienced cumulative and rapid recalibration, these recalibration effects did not differ between the groups. Unexpectedly, cumulative recalibration was caused by auditory-leading but not visual-leading adaptation. Overall, these findings suggest that the precision with which observers integrate audiovisual temporal cues does not predict their susceptibility to recalibration.