bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer With Uncommon Histology: A Propensity-Score-Matched Analysis
Authors: Miyashita Koichi , Karayama Masato , Inoue Yusuke , Hozumi Hironao , Suzuki Yuzo , Furuhashi Kazuki , Fujisawa Tomoyuki , Enomoto Noriyuki , Nakamura Yutaro , Kono Masato , Matsui Takashi , Niwa Mitsuru , Koda Keigo , Toyoshima Mikio , Matsushima Sayomi , Matsuura Shun , Asada Kazuhiro , Fujii Masato , Kusagaya Hideki , Matsuda Hiroyuki , Inui Naoki , Suda Takafumi
Published: June 2021

Background

Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown.
Methods

Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: 1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and 2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups.
Results

Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8–7.7 months) and overall survival (OS) (11.4 months, 95 % CI 7.4–27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1–7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6–29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC.
Conclusion

ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.
Numerical analysis and mechanic theoretical derivations for optimizing the V-thread profiles in dental implant system
Authors: Cai Yongqing
Published: June 2021

Background

The thread design of the dental implant is an important feature to be considered in the optimization of the dental implant structure. The present study aimed to investigate the effects of V-thread profile design dimensions, including depth, width, pitch, thread helix angle and triangle thread apex angle on the mechanical characteristics of the bone-implant interface. A total of 588 V-thread implant system models were constructed to investigate the effects of the dimension parameters on the stress distribution generated around the bone-implant interface under vertical occlusal force. Furthermore, the force transfer at the bone-implant interface was analyzed theoretically to analyze the force transmission mechanism at bone-implant for an optimized V-thread profile in the implants.
Results

The optimum thread pitch ranged from 1.0 mm to 1.2 mm, when the triangle thread depth and width was 0.1 mm. The theoretically derived results showed that, with the same implant diameter, when the thread depth was 0.1 mm and the thread pitch was 0.9 mm, the optimal thread width was found to be 0.1026 mm. This derived result was consistent with the simulation analysis results.
Conclusions

To design the optimal V-shape threads, the implant and thread dimensions, such as the implant diameter, thread pitch, thread width, thread helix angle and triangle thread apex angle should be comprehensively considered. The optimal designed thread in this study can dissipate the chewing load, as a result of the appropriate ratio of tensile force and shear force on bone-implant interface. The optimum designed thread profile can take full advantage of the carrying capacity of the tensile and shear of the bone, thereby bearing a high chewing load.
Intention to Obtain a COVID-19 Vaccine Among Brazilian Immigrant Women in the U.S.
Authors: Allen Jennifer D , Rocha Leticia Priebe , Rose Rebecca , Hoch Annmarie , Porteny Thalia , Fernandes Adriana , Galvão Heloisa
Published: June 2021

Background: COVID-19 has disproportionately impacted low-income communities and communities of color. Widespread uptake of COVID-19 vaccines is necessary to prevent ongoing community transmission. Little is known about the acceptability of COVID-19 vaccines among immigrant communities, many of which have been disproportionately impacted by the pandemic. Our goal was to gauge COVID-19 vaccine intentions among Brazilian immigrant women living in the U.S. Methods: We conducted an online survey in Portuguese and English among a convenience sample of Brazilian immigrant women ages 18 years and older. Women were recruited through online advertisements by community-based organizations and social media groups to complete a survey that assessed intention to get a COVID-19 vaccine, attitudes toward vaccines, and perceptions about the pandemic.Results: Of the total sample (N=364), most (70.9%) indicated they would take a COVID-19 vaccine. In bivariate analyses, vaccine intentions were significantly associated with perceptions about the severity of the pandemic, trusted sources of health information, and number of years lived in the U.S. Multinomial logistic regression models revealed that those who did not intend to be vaccinated had lived a longer time in the U.S. (OR: -0.12 95% CI: -0.19, -0.05), perceived the pandemic to be only a minor problem (OR: 1.44, 95% CI: 0.51, 2.37), and trusted information from social networks (OR: -2.04, 95% CI: -3.35, -0.73) and private news sources (OR: -1.76, 95% CI: -2.85, -0.68).Conclusions: While the majority of women reported they would get a COVID-19 vaccine, efforts to reach those who may be hesitant should target those who have lived in the U.S. for a longer time and do not perceive the pandemic to be a major crisis. Healthcare providers may be particularly suited to deliver this information given high levels of trust.
Sodium Humate And Glutamine Combined Supplementation Alleviate Diarrhea of Weaned Calves Via Alter Intestinal Microbiota And Metabolites
Authors: Wang Dong , Du Yuanyi , Jia Haotian , Huang Siqi , Lei Lei , Liu Yun
Published: June 2021

Background: Weaning is one of the most stressful periods that cause gastrointestinal tract dysfunction and diarrhea in calves. HNa and Gln were reported to exert beneficial effects on promoting growth performance, decreasing diarrhea incidence, and modulating intestinal microbiota in animals. Therefore, this study investigated the effect of HNa and Gln combined supplementation on growth performance, diarrhea incidence, serum parameters, intestinal microbiome, and metabolites of weaned calves.Results: In Exp. 1, 40 calves at 51±3 days of age with similar body weight (66.82±4.31 kg) were randomly assigned to 4 treatments fed with a basal diet (NC group), and a basal diet supplemented with 100 mL of 1%, 3%, or 5% HNa+1% Gln, twice daily, respectively. In a 21-day trial, calves on the 5% HNa+1% Gln group had higher ADG and lower fecal score and diarrhea incidence than those in the control group (P < 0.05). In Exp. 2, 20 calves at 51±3 days of age with similar body weight (69.37±6.28 kg) were randomly assigned to 2 treatments fed with a basal diet (NC group) and a basal diet supplemented with 100 mL of 5% HNa+1% Gln, twice daily (H+G group, the dose was obtained from Exp. 1). In a 21-day trial, calves supplemented with HNa and Gln had higher final BW and ADG, serum IgG concentration and GSH-Px and T-AOC activities, but lower fecal score, diarrhea incidence, as well as serum DAO, D-lac, TNF-α, and MDA concentrations compared to NC group (P < 0.05). Analysis of intestinal microbiota indicated that supplemented with HNa and Gln significantly increased the abundance of phyla Firmicutes and genus of Bifidobacterium, Lactobacillus, Olsenella, Ruminiclostridium 9, Howardella, and uncultured organism, whereas the abundance of phyla Bacteroidetes, genus of Helicobacter and Lachnoclostridium were decreased as compared with NC group. Moreover, untargeted metabolomics analysis revealed that supplemented with HNa and Gln altered 18 metabolites and enriched 6 KEGG pathways (primary fatty acid biosynthesis) compared to the NC group. Conclusions: This study showed that combined supplemented with HNa and Gln could decrease diarrhea of weaned calves, which may be associated with improved intestinal microbial ecology and altered metabolism profile.
Discovery of Next-Generation Tropomyosin Receptor Kinase (TRK) Inhibitors for Combatting Resistance Associated with Protein Mutation
Authors: Zhuo Linsheng , Wang Ming-Shu , Wu Feng-Xu , Xu Hong-Chuang , Gong Yi , Yu Zhi-Cheng , Tian Yan-Guang , Pang Chao , Hao Geifei , Huang Wei , Yang Guang-Fu
Published: June 2021

Aberrant signaling from tropomyosin receptor kinases (TRKs) has been identified as the oncogenic driver in a large variety of cancers, suggesting that inhibition of TRK may be an attractive strategy of attack for anticancer therapeutics. Despite the encouraging therapeutic response to the first-generation TRK inhibitor Larotrectinib (1), the emergence of drug-resistant secondary mutations within its ATP-binding pocket cause relapse in cancer patients. A next-generation inhibitor that overcomes multiple Larotrectinib-resistant mutations is still a major “unmet clinical need”. In this study, the progressive exploration of the structure-activity relationship (SAR) through scaffold hopping, flexibilization, and fluoroalkoxy substitutions produced modifications on the reported compound 1 that led to the discovery of a superior derivative 7g. Compound 7g is a novel, orally available TRK inhibitor that showed excellent in vitro potency on a panel of Larotrectinib-resistant mutants both in biochemical and cellular assays. Compound 7g also exhibited improved in vivo antitumor efficacy in TRK wild type and mutant fusion-driven tumor xenograft models compared to the efficacy of Larotrectinib and Selitrectinib (3). These encouraging results suggest that compound 7g is a promising drug candidate to pursue for development of a TRK inhibitor to overcome clinically acquired resistance to Larotrectinib.
Exploration of "Online + Offline" Blended Teaching Mode in Molecular Biology Experiment Under the Background of COVID-19
Authors: Xu Zihan , Yu Yang , Xia Shilin , Tuhlei Breanna , Man Tengjun , Zhou Bo , Qin Yuanhua , Sun Zheng
Published: June 2021

Backgrounds: The outbreak of coronavirus has had a serious impact on the economy, life and education of virtually all countries around the world. In China, the pandemic continues to pose a great challenge to the traditional in-person education model of schools. Educators in China are facing the agonizing decision of whether to resume in-person instruction while there’s still no effective cure for the new coronavirus. Therefore, in order to ensure the quality of teaching and learning during the period of special time, we explore the "online + offline" blended teaching mode. Methods: Four hundred medical undergraduates from Dalian Medical University in China took part in a simulated teaching model to improve their learning ability of innovation and exploration. Taking molecular biology experiment - cell apoptosis as an example, we experimented with the blending of "online + offline " teaching mode and evaluated the learning outcome under this mode from the perspectives of experiment operation, report writing and group cooperation.Results: Over 95% of them totally agree with this teaching mode and expect to have it applied to other subjects, while less than 10% of the students have the opinion that the traditional teaching mode is better. The result of the innovation project competition also shows that the students trained under this teaching mode perform better than those under the traditional teaching mode in both objective questions and answers and experimental operation.Conclusions: Adoption of this "online + offline" blended teaching mode is effective and provides a new perspective to solve the problems encountered by medical students when they reach a higher level of development. In the process of carrying out this teaching mode, the cultivation of students' independent learning and innovative exploration ability were emphasized. Furthermore, it also helps students to lay a solid foundation for their future study and career development.
Circulating Tumor Cells as a Biomarker for Precise Management of Lung Cancer
Authors: Li Qian , Xu Chenyu , Yang Zhenhua
Published: June 2021

Background: Circulating tumor cells (CTCs) with potential utility in cancer treatment provide a less invasive way to illustrate the pathogenesis of tumor. In this study, we evaluated the efficiency of CTCs in early diagnosis and/or precisely indication of lung cancer (LC) patients responding to chemotherapy.Methods: Fifty-six patients newly diagnosed with LC were included in this study, while 42 patients with nonmalignant pulmonary disease were included as positive control group and 27 healthy individuals as control. CTCs were measured at baseline in all eligible subjects and after two cycles of chemotherapy in 25 advanced LC patients, with a strategy of negative enrichment combined with immunostaining-fluorescence in situ hybridization (imFISH). The receiver operating characteristic (ROC) curve was plotted to determine the sensitivity and specificity of the CTC for the LC diagnosis. Kaplan-Meier curve and two-sided log-rank test were used for univariate survival analysis.Results: The number of CTCs was significantly increased in LC patients, compared with positive control and healthy controls. The sensitivity and specificity were 87.5% and 95.7%, with a cutoff value of 2 cells/3.2ml (AUC=0.975, 95%CI, 0.953-0.998, p=0.001). Moreover, the sensitivity of CTCs was much higher than individual or the combination of serum tumor markers (NSE/CYFRA21-1/CEA), especially in the early diagnosis of LC. Twenty-five advanced LC patients were subsequently followed up for an average of 18.2 months (6-36 months). Decline of CTC count after two cycles of chemotherapy was highly predictive for progression free survival (PFS) (13.5 vs. 8.5 months; p=0.025) and overall survival (OS) (27.6 vs. 16.8 months; p=0.009). Among the patients classified as stable disease (SD) based on post-treatment CT scan after two cycles of chemotherapy, there was significant elevation in the PFS (14.0 vs. 8.7 months; p=0.033) and OS (25.8 vs. 15.9 months; p=0.018) in those with decreased CTC number compared with those presenting stable or elevated CTCs number.Conclusions: CTCs may act as precise biomarker for early detection and therapy monitoring of LC. It may serve as good compensation for imaging.
Increasing Access to Task-Oriented Community-Based Exercise Programs Through Healthcare-Community Partnerships to Improve Function Post-Stroke: Feasibility of a 2-Group Randomized Controlled Trial Protocol
Authors: Aravind Gayatri , Bashir Kainat , Cameron Jill I. , Howe Jo-Anne , Jaglal Susan B. , Bayley Mark T. , Teasell Robert , Moineddin Rahim , Zee Joanne , Wodchis Walter , Tee Alda , Hunter Susan , Salbach Nancy Margaret
Published: June 2021

BackgroundObjectives were to describe the feasibility of a protocol for evaluating a community-based exercise program incorporating a healthcare-community partnership (CBEP-HCP) compared to a waitlist control group on improving everyday function among people post-stroke.MethodsA pilot 2-group randomized controlled trial was conducted in three cities in Ontario, Canada. Adults (≥ 18 years) living at home for ≥ 3 months post-stroke, and able to walk ≥ 10 metres without physical assistance were stratified by site and gait speed and randomly assigned to an exercise program or waitlist control group. Trained fitness instructors delivered a 1-hour, group exercise class, involving repetitive and progressive practice of balance/mobility tasks relevant to everyday function (e.g., sit-to-stand, walking, step-ups) twice a week for 12 weeks. The waitlist group was offered the exercise program at 10 months. Blinded assessors conducted evaluations at 3, 6 and 10 months post-baseline. Sensitivity to change of two measures of everyday function (Subjective Index of Physical and Social Outcome (SIPSO) and Nottingham Extended Activities of Daily Living (NEADL)) was compared. Qualitative interviews were conducted separately with 13 participants and 9 caregivers post-intervention. Quantitative and qualitative results were triangulated.ResultsThirty-three people with stroke were randomized to the intervention (n = 16) or waitlist group (n = 17); 68% of available caregivers agreed to participate. Recruitment rates were 2.4, 1.2, and 1.1 participants/month across sites and highest in the largest urban centre. Participants preferred a familiar healthcare professional to refer them to the study. Participants described a 10- or 12-month wait as too long and two people in the waitlist group withdrew for this reason. The exercise program was implemented per protocol across sites. Attendance was lowest (63% and 71% in the intervention and waitlist group, respectively) at 10-month evaluations. Participants described inclement weather, availability of transportation, and long commutes as barriers to attending evaluations and exercise classes. The SIPSO physical scale but not the NEADL detected change in the intervention group. Quantitative and qualitative results suggested an immediate effect of the intervention on balance, balance self-efficacy, everyday function (dressing, cooking), and overall health.ConclusionChallenges with recruitment, attendance, and retention will inform protocol revisions for a future trial.Trial Registration: ClinicalTrials.gov, NCT03122626. Registered April 17, 2017 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03122626
Stochastic Analysis of an Epidemic SVIR Model With Holling Type II Incidence and Treatment Rates
Authors: Madhusudanan V , Srini M N , Amalraj L.
Published: June 2021

In the event of an epidemic, inhibitory effects play a critical role in limiting the pandemic's influence on society. The majority of infectious diseases that affect humans are still on the verge of becoming epidemics over the world. Mathematical models have long been used to investigate the complicated dynamics of infectious illnesses. This research investigates a stochastic SVIR epidemic model with Holling type II incidence and treatment rates. The Fourier transform approach is used to analyse stochastic stability around an internal steady state. Finally, numerical simulations are presented with appropriate parameter selections in order to test the efficiency of the theoretical results.
On the Effect of Nonlinear Energy Sink Damping in Seismic Vibration Attenuation
Authors: Motato Eliot , Guerrero Fabio G.
Published: June 2021

Nonlinear Energy Sinks (NESs) have been proposed for passively reducing the amplitude of vibrations in different types of structures. The main advantage of NES over traditional Tuned Mass Dampers (TMDs) lies in its capability to redistribute the vibrating energy inside a primary structure, what effectively reduces the amplitude of the structure oscillations over a wide range of frequencies. However, the performance of an NES can be substantially affected even by small variations on input energy as in the case of buildings under seismic ground excitation. In this work it is shown that the NES energy sensibility can be significantly reduced by properly selecting the NES damping coefficient. A three stories shear building model subject to seismic ground excitation is used to numerically study the effect that NES damping has on its vibration reduction performance.
Acute myocardial infarction among patients undergoing elective spinal fusion, total hip arthroplasty, and total knee arthroplasty in the United States: a retrospective cohort study
Authors: Arena Patrick J , Mo Jingping , Liu Qing , Zhou Xiaofeng , Gong Richard , Wentworth Charles , Murugesan Sundaresan , Huang Kui
Published: June 2021

Background

Acute myocardial infarction (AMI) is an uncommon but fatal complication among patients undergoing elective spinal fusion surgery (SF), total hip arthroplasty (THA), and total knee arthroplasty (TKA). Our objective was to estimate the incidence of AMI among adults undergoing elective SF, THA, and TKA in different post-operative risk windows and characterize high-risk sub-populations in the United States.
Methods

A retrospective cohort study was conducted using data from a longitudinal electronic healthcare record (EHR) database from January 1, 2007 to June 30, 2018. ICD codes were used to identify SF, THA, TKA, AMI, and selected clinical characteristics. Incidence proportions (IPs) and 95% confidence intervals were estimated in the following risk windows: index hospitalization, ≤ 30, ≤ 90, ≤ 180, and ≤ 365 days post-operation.
Results

A total of 67,533 SF patients, 87,572 THA patients, and 167,480 TKA patients were eligible for the study. The IP of AMI after SF, THA, and TKA ranged from 0.36%, 0.28%, and 0.25% during index hospitalization to 1.05%, 0.93%, and 0.85% ≤ 365 days post-operation, respectively. The IP of AMI was higher among patients who were older, male, with longer hospital stays, had a history of AMI, and had a history of diabetes.
Conclusion

The IP of post-operative AMI was generally highest among the SF cohort compared to the THA and TKA cohorts. Additionally, potential high-risk populations were identified. Future studies in this area are warranted to confirm these findings via improved confounder control and to identify effect measure modifiers.
Dietary Anti-Oxidant Capacity, Dietary Inflammation Index, and the Risk of Stroke in a Large Prospective Cohort Study.
Authors: MacDonald Conor-James , Laouali Nasser , Madika Anne-Laure , Severi Gianluca , sagnier Sharmila , Debette Stephanie , Boutron-Ruault Marie-Christine
Published: June 2021

BackgroundWhilst the Western and Mediterranean/prudent diets have long been associated with the risk of stroke, it is less clear if increased inflammation and reduction of oxidations are their respective mechanisms. This study aimed to understand the associations between the dietary inflammatory index (DII), and total anti-oxidant capacity of the diet (TAC), with regards to stroke risk.MethodsThe study population included 71,460 women free of cardiovascular disease at baseline from the E3N cohort, who completed a diet history questionnaire which was used to estimate the dietary pattern scores. Scores were considered grouped as quintiles and as splines in order to determine the dose-response shape. Hazard ratios (HRs) and 95% confidence intervals (95% CI) for hypertension were estimated with multivariate Cox models with age as the time scale, and adjusted for potential confounding factors. After Bonferroni correction, a p-value of 0.013 was considered significant.ResultsOver 14.5 years of follow-up, 414 cases of incident stroke were identified. The Western, and Prudent dietary patterns were both highly associated with the risk of stroke (Western HRQ1Q4 = 1.85 [1.27: 2.69], p-trend = 0.002, Prudent HRQ1Q4 = 0.59 [0.44: 0.78], p-trend < 0.001), as was TAC from non-coffee sources (HRQ1Q4 = 0.47 [0.33: 0.68], p-trend < 0.001). All three showed a clear dose-response, and the associations with the Western and Prudent scores were consistent in sensitivity analysis. Weaker evidence was observed for DII (HRQ1Q4 = 1.33 [1.01: 1.78], p-trend = 0.03), which did not show a clear dose-response. TAC from coffee was not associated with the risk of stroke.ConclusionThese results suggest that diets high in anti-oxidants are associated with a reduced risk of stroke, but that inflammation from the diet does not play as large a part in the risk of stroke. Factors other than inflammation may be driving associations with stroke and western diet.
Soil Nitrogen Dynamics Impact Carbon Exchange Processes in a High Arctic Wetland
Authors: Hung Jacqueline K.Y. , Scott Neal A. , Treitz Paul M.
Published: June 2021

Increased soil nutrient availability, and associated increases in vegetation productivity, could create a negative feedback between Arctic ecosystems and the climate system, thereby reducing the contribution of Arctic ecosystems to future climate change. To predict whether this feedback will develop, it is important to understand the environmental controls over nutrient cycling in High Arctic ecosystems and their impact on carbon cycling processes. This study, conducted at the Cape Bounty Arctic Watershed Observatory, Melville Island, Nunavut, examined the environmental controls over soil nitrogen availability in a High Arctic wet sedge meadow and how they influenced carbon dioxide exchange processes from 2016-2018. Moisture variability across a seemingly homogenous wet sedge meadow allowed us to investigate nutrient availability and carbon dioxide exchange across naturally occurring moisture gradients over three growing seasons. The nature of the relationships (i.e., trends) between variables was consistent over the three years, but their magnitudes varied depending on climate conditions. Soil nitrogen availability, particularly ammonium, was higher in warmer years and wetter conditions and correlated positively with gross primary production (R 2 = 0.97) and net carbon dioxide uptake (R 2 = 0.88). Drier areas within the wetland had more nitrate availability, and this correlated negatively with net carbon dioxide exchange. Projections of a warmer, wetter Arctic and increased nutrient availability due to higher soil organic matter turnover suggest that northern wetlands will remain strong carbon dioxide sinks, or become stronger sinks, contributing to a negative feedback on the climate system.
ECMO Support in HIV/AIDS with Pneumocystis Jirovecii Pneumonia: A Case Report and Short Review
Authors: lv jianlei , Li yanfen , huang kang , lv ailian
Published: June 2021

Background

We report a case of a patient with novel human immunodeficiency virus (HIV) and Pneumocystis jirovecii pneumonia (PJP) was successfully treated with veno-venous (V-V) ECMO owing to refractory hypoxemia and pneumomediastinum, and eventually discharged. In addition to the case report, several previous reports were reviewed for the discussion of some key therapies.
Case report:

A 30-year-old male patient was admitted to the our hospital presented with the shortness of breath. The patient showed a deteriorated oxygenation due to increasing pulmonary infiltrates and development of pneumomediastinum, necessitating ECMO. The diagnosis of ARDS, HIV, PJP was made. Trimethoprim/sulfamethoxazole (TMP/SMX) was provided for the treatment of PJP. After 7 days of ECMO therapy, the patient was successfully decannulated and eventually discharged.
Conclusions

ECMO may benefit adult patients with HIV/AIDS and refractory hypoxemia due to severe PCP. Post-ECMO antiretroviral therapy could improve outcomes.
Intrinsic Photoluminescence of Solid-State Gold Nanoclusters: Towards Fluorescence Lifetime Imaging of Tissue-Like Phantoms Under Two-Photon Near-Infrared Excitation
Authors: Alexandru-Milentie Hada , Craciun Ana-Maria , Astilean Simion
Published: June 2021

Gold nanoclusters (AuNCs) have attracted extensive attention as light-emissive materials with unique advantages such as high photostability, large Stoke shifts and low toxicity. However, a better understanding of their solid-state photoluminescence properties is still needed. Herein, we investigated for the first time the intrinsic photoluminescence properties of lyophilized bovine serum albumin stabilized AuNCs (BSA-AuNCs) via fluorescence lifetime imaging microscopy (FLIM) studies performed under both one and two photon excitations (OPE and TPE) on individual microflakes, combined with fluorescence spectroscopic investigations. Both in solution and solid-state, the synthesized BSA-AuNCs exhibit photoluminescence in the first biological window with an absolute quantum yield of 6% and high photostability under continuous irradiation. Moreover, under both OPE and TPE conditions, solid BSA-AuNCs samples exhibited a low degree of photobleaching, while FLIM assays prove the homogeneous distribution of the photoluminescence signal inside the microflakes. Finally, we demonstrate the ability of BSA-AuNCs to perform as reliable bright and photostable contrast agents for the visualization of cancer tissue mimicking agarose-phantoms using FLIM approach under non-invasive TPE. Therefore, our results emphasize the great potential of the as synthesized BSA-AuNCs for ex vivo and in vivo non-invasive NIR imaging applications.
RRAM-Based CAM Combined With Time-Domain Circuits for Hyperdimensional Computing
Authors: Halawani Yasmin , Kilani Dima , Hassan Eman , Tesfai Huruy , Saleh Hani , Mohammad Baker
Published: June 2021

Content addressable memory (CAM) for search and match operations demands high speed and low power for near real-time decision-making across many critical domains. Resistive RAM-based in-memory computing has high potential in realizing an efficient static CAM for artificial intelligence tasks, especially on resource-constrained platforms. This paper presents an XNOR-based RRAM-CAM with a time-domain analog adder for efficient winning class computation. The CAM compares two operands, one voltage and the second one resistance, and outputs a voltage proportional to the similarity between the input query and the pre-stored patterns. Processing the summation of the output similarity voltages in the time-domain helps avoid voltage saturation, variation, and noise dominating the analog voltage-based computing. After that, to determine the winning class among the multiple classes, a digital realization is utilized to consider the class with the longest pulse width as the winning class. As a demonstrator, hyperdimensional computing for efficient MNIST classification is considered.The proposed design uses 65nm CMOS foundry technology and realistic data for RRAM with total area of 0.0077 mm2 , consumes 13.6 pJ of energy per 1k query within 10 ns clock cycle for 10 classes. It shows a reduction of ∼ 31× in area and ∼ 3× in energy consumption compared to fully digital ASIC implementation using 65nm foundry technology. The proposed design exhibits a remarkable reduction in area and energy compared to two of the state-of-the-art RRAM designs.
WNT3 Hypopethylation Counteracts low Activity of the Wnt Signaling Pathway in the Placenta of Preeclampsia
Authors: Zhang Linlin , Sang Min , Li Ying , Li Yingying , Yang Lijun , Shi Wenli , Yuan Yangyang , Yang Bo , Yang Peifeng
Published: June 2021

Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/β-catenin signaling pathway. This study aimed to identify differentially methylated Wnt/β-catenin signaling pathway genes in the preeclamptic placenta and to study the roles of these genes in trophoblast cells in vitro. Using an Illumina Infinium HumanMethylation 850K BeadChip, we found that the Wnt signaling pathway was globally hypermethylated in the preeclamptic group compared with the term birth group but hypomethylated in the preeclamptic group compared with the preterm birth group. Among all Wnt/β-catenin signaling pathway factors, WNT3 was the most significantly differentially expressed gene and was hypomethylated in the preeclamptic group compared to the nonhypertensive groups, namely, the preterm birth group and term birth group. This result was confirmed by pyrosequencing. Through quantitative real-time PCR and western blot analysis, the WNT3 gene was found to be highly expressed in preeclamptic placental tissues, in contrast to other WNT factors, which were previously reported to be expressed at low levels in placental tissues. Additionally, in the HTR8/SVneo cell line, knockdown of WNT3 suppressed the Wnt/β-catenin signaling pathway, consistent with the findings for other WNT factors. These results prompted us to speculate that the WNT3 gene counteracts the low activation state of the Wnt signaling pathway in the preeclamptic placenta through methylation modification.
Equine Grass Sickness (A Multiple Systems Neuropathy) is Associated with Alterations in the Gastrointestinal Mycobiome
Authors: McGorum Bruce , Chen Zihao , Glendinning Laura , Gweon Hyus , Hunt Luanne , Ivens Alasdair , Keen John , Pirie Scott , Taylor Joanne , Wilkinson Toby , McLachlan Gerry
Published: June 2021

Background: Equine grass sickness (EGS) is a multiple systems neuropathy of grazing horses of unknown aetiology. An apparently identical disease occurs in cats, dogs, rabbits, hares, sheep, alpacas and llamas. Many of the risk factors for EGS are consistent with it being a pasture mycotoxicosis. To identify potential causal fungi, the gastrointestinal mycobiota of EGS horses were evaluated using targeted amplicon sequencing, and compared with those of two control groups. Samples were collected post mortem from up to 5 sites in the gastrointestinal tracts of EGS horses (EGS group; 150 samples from 54 horses) and from control horses that were not grazing EGS pastures and that had been euthanased for reasons other than neurologic and gastrointestinal diseases (CTRL group; 67 samples from 31 horses). Faecal samples were also collected from healthy control horses that were co-grazing pastures with EGS horses at disease onset (CoG group; 48 samples from 48 horses). Results: Mycobiota at all 5 gastrointestinal sites comprised large numbers of fungi exhibiting diverse taxonomy, growth morphology, trophic mode and ecological guild. FUNGuild analysis parsed most phylotypes as ingested environmental microfungi, agaricoids and yeasts, with only 1% as gastrointestinal adapted animal endosymbionts. Indices of alpha-diversity indicated that mycobiota richness and diversity varied throughout the gastrointestinal tract and were greater in EGS horses. There were significant inter-group and inter-site differences in mycobiota structure. A large number of phylotypes were differentially abundant among groups. Key phylotypes (n=56) associated with EGS were identified that had high abundance and high prevalence in EGS samples, significantly increased abundance in EGS samples, and were important determinants of the inter-group differences in mycobiota structure. Many key phylotypes were extremophiles and/or were predicted to produce cytotoxic and/or neurotoxic extrolites. Conclusions: This is the first reported molecular characterisation of the gastrointestinal mycobiota of grazing horses. Key phylotypes associated with EGS were identified. Further work is required to determine whether neurotoxic extrolites from key phylotypes contribute to EGS aetiology or whether the association of key phylotypes and EGS is a consequence of disease or is non-causal.
Pathogenic antibodies induced by spike proteins of COVID-19 and SARS-CoV viruses
Authors: Wang Huiru , Chen Qiuchi , Hu Yue , Wu Xiancong , Dai Lin , Zhang Yuekai , Li Fang , Lu Jinfeng , Chen Yuxing , Liu Xiaoling
Published: June 2021

This study, using a virus-free mouse model, explores the pathogenic roles of certain antibodies specific to the spike proteins of highly pathogenic coronaviruses such as the COVID-19 and the SARS-CoV viruses. Our data showed that these pathogenic antibodies, through a mechanism of Antibody Dependent Auto-Attack (ADAA), target and bind to host vulnerable cells or tissues such as damaged lung epithelium cells, initiate a self-attack immune response, and lead to serious conditions including ARDS, cytokine release, and death. Moreover, the pathogenic antibodies also induced inflammation and hemorrhage of the kidneys, brain, and heart. Furthermore, the pathogenic antibodies can bind to unmatured fetal tissues and cause abortions, postpartum labors, still births, and neonatal deaths of pregnant mice. Novel clinical interventions, through disrupting the host-binding of these pathogenic antibodies, can be developed to fight the COVID-19 pandemic. In addition, the new concept of ADAA explored by this study may be applicable to other infectious diseases, such as the highly pathogenic influenza infections. It should be noted that the majority of anti-spike antibodies are non-pathogenic, as only 2 of 7 monoclonal antibodies tested showed significant pathogenic effects.
Do Serial Lung Ultrasound Scores Predict Prolonged Mechanical Ventilation in Patients With Severe COVID-19? A Single-centre Retrospective Cohort Study
Authors: Taniguchi Hayato , Ohya Aimi , Yamagata Hidehiro , Iwashita Masayuki , Abe Takeru , Takeuchi Ichiro
Published: June 2021

Background: Some patients with severe coronavirus disease (COVID-19) who present with fibrosis on computed tomography (CT) require prolonged mechanical ventilation (PMV). Lung ultrasound (LUS), a rapid, bedside test, has been reported to have findings consistent with those of CT. Thus, this study aimed to assess whether serial LUS scores could predict PMV or successful extubation in severe COVID-19 patients.Methods: LUS was performed for 20 consecutive severe COVID-19 patients at three time points: admission (day 1), after 48 h (day 3), and seventh-day follow-up (day 7). We compared the LUS score with the results of chest X-rays and laboratory tests at three time points. Moreover, we assessed LUS score to determine the inter-rater reliability (IRR) of the results among examiners.Results: While there were no significant differences in mortality in each PMV and successful extubation groups, there were significant differences in LUS scores on day 3 and day 7; XP score on day 7; and P/F ratio on day 7 in the PMV group (p<0.05). There were significant differences in LUS scores on days 3 and 7, C-reactive protein (CRP) levels on day 7, and P/F ratio on day 7 in the successful extubation group (p<0.05). The areas under the curves (AUCs) of LUS score on days 3 and 7, XP score on day 7, and P/F ratio were 0.88, 0.98, 0.77, and 0.80, respectively in the PMV group; and the AUCs of LUS score on days 3 and 7, CRP levels on day 7, and P/F ratio 0.79, 0.90, 0.82, and 0.79, respectively, in the successful extubation group. Variations in serial LUS scores exhibited significant differences between the groups. The serial LUS score on day 7 was higher than that on day 1 in the PMV group but lower in the successful extubation group (p<0.05). However, there was slight IRR agreement in the LUS score changes on days 1 to 7 (κ= 0.15 [95% CI: 0-0.31]). Conclusions: The serial LUS score of severe COVID-19 patients could predicted PMV and successful extubation. To overcome IRR disagreement, the automatic ultrasound judgement, such as deep learning, would be needed.
The Income-related Distribution of Cognitive Function and Its Mobility Among the Chinese Elderly Over 14 Years
Authors: Zhou Yiting , Xu Yongjian , Zhu Liang
Published: June 2021

Background:With population aging, cognitive function among the elderly has been growing public health concern in China. This study aimed to investigate the trend of income-related inequality in cognitive function, and to track the health-related income mobility among the Chinese elderly. Methods: The data were drawn from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2005, 2008, 2011, 2014 and 2018, with a sample of 10203 Chinese aged 65 and older. The cognitive function was evaluated by the Mini-Mental State Examination (MMSE). The cross-sectional and longitudinal concentration indices were used to measure the magnitudes of inequalities at different length of time. The mobility index was used to capture the discrepancy between the short-term and long-term measures. The contribution of determinants to mobility was estimated by decomposition analysis. Results:The results showed that, the cognitive function among the Chinese elderly scored 21.13 at the baseline. Men, activities, daily living ability, education, marriage status, income, community service, vision and hearing condition were positively associated with cognitive function, whereas age, negative well-being and drinking were negatively associated with cognitive function. The cross-sectional concentration index was positive and significant only at the baseline. In the long run, however, the concentration indices were all positive and became larger over time. After five waves, the mobility reached -4.84. The largest negative contributor to the mobility index was daily living ability, followed by relaxing activity, domestic activity and hearing condition. The two largest positive contributors were negative well-being and income. Conclusion:Our study found that, as a whole, the cognitive function was not performed well among the Chinese elderly. In the long term, the weighted cross-sectional concentration indices underestimated the inequality in cognitive function and good cognitive performance was concentrated more among the rich. When formulating intervention measures, the Chinese government could give priority to vulnerable groups, especially the elderly who are poor or downwardly income mobile.
Efficacy of High-flow Nasal Cannula Oxygen Therapy in Patients with Mild Hypercapnia
Authors: Su Lingling , Zhao Qinyu , Liu Taotao , Xu Yujun , Li Weichun , Zhang Aiping
Published: June 2021

Objectives: To investigate the indications of high-flow nasal cannula (HFNC) oxygen therapy among patients with mild hypercapnia and to explore the predictors of intubation when HFNC fails.Methods: This retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients with mild hypercapnia (45<PaCO2≤60 mmHg) received either HFNC or noninvasive ventilation (NIV) oxygen therapy. Propensity score matching (PSM) was implemented to increase between-group comparability. The Kaplan-Meier method was used to estimate overall survival and cumulative intubation rates, while 28-day mortality, 48-hour and 28-day intubation rates were compared using the Chi-square test. The predictive performances of HR/SpO2 and the ROX index (the ratio of SpO2/FiO2 to respiratory rate) at 4 hours were assessed regarding HFNC failure, which was determined if intubation was given within 48 hours after the initiation of oxygen therapy. The area under the receiver operating characteristic curve (AUC) for HR/SpO2 and the ROX index were calculated and compared.Results: A total of 524,520 inpatient hospitalization records were screened, 106 patients in HFNC group and 106 patients in NIV group were successfully matched. No significant difference in 48-hour intubation rate between the HFNC group and the NIV group (14.2% vs. 8.5%, P=0.278); patients receiving HFNC had higher 28-day intubation rate (26.4% vs. 14.2%, P=0.029), higher 28-day mortality (17.9% vs. 8.5%, P=0.043), longer ICU length of stay (4.4 vs. 3.3 days, P=0.019), compared to those of NIV group. The AUC of HR/SpO2 at 4 hours after the initiation of HFNC yielded around 0.660 for predicting 48-hour intubation, greater than that of the ROX index with an AUC of 0.589 (P<0.01).Conclusions: HFNC therapy cannot completely replace NIV for patients with mild hypercapnia. As opposed to the ROX index, a modest, yet improved predictive performance is demonstrated using HR/SpO2 in predicting the failure of HFNC among these patients.
International Publication Trends in Low Back Pain Research: A Bibliometric and Visualization Analysis
Authors: Huang Fan , Zheng Beisi , Wu Cunshu , Zhao Siyi , Xu Yuanyue , Li Ziyuan , Huang Chuyu , Fan Zhiyong , Wu Shan
Published: June 2021

Background

Despite the increasing research on low back pain, the bibliometric literature in the field of low back pain is limited. The aim of this study was to perform a bibliometric and visualization analysis of low back pain.
Methods

The authors searched the Web of Science database to extract publications regarding low back pain in the last 22 years. A total of 12,201 publications were eligible. We classified and analyzed publications such as total citations, average citations per item, H-index, research types, countries/regions, institutions and journals by using standard bibliometric indicators. Bibliometric methods and tools were used to explore the trends of low back pain research.
Results

Over the past 22 years, the number of publications on low back pain in the world had continually remained a increasing trend. Regional differences existed in the research of low back pain and developed countries played a leading role in the research. Research institutions and researchers have successively invested in the research of low back pain. However, there were limitations to the present study that should be noted that the study was relatively scattered and a systematic summary of the trends and characteristics was lacking. Visualization analysis provides valuable information for researchers to identify new perspectives on potential collaborators and cooperative institutions, which promote indirect cooperation. Besides, the most burst keywords were “primary-care”, “lumbar spine” and “disability”.
Conclusion

This study provided a number of important insights into the global research trends and current status related to low back pain which is helpful for clinicians, researchers and policy makers to understand the research field and predict its dynamic directions. Our article could be used for quantify and academic publications about low back pain in order to obtain an overview of the given field of study and provide references and suggestions for the future work of low back pain.
Field-Dependent Rheological Properties of Graphite Based Magnetorheological Grease
Authors: Nasir Nur Alyaa Mohd , Nazmi Nurhazimah , Mohamad Norzilawati , Ubaidillah Ubaid , Nordin Nur Azmah , Mazlan Saiful Amri , Aziz Siti Aishah Abdul , Shabdin Muhammad Kashfi
Published: June 2021

The utilization of high viscous grease as a medium in Magnetorheological grease (MRG) has benefits in avoiding the sedimentation from occurred, however, it limits the expansion of yield stress in on-state condition thus reduced the application performance upon operation. Therefore, in present study, improvement of the rheological properties of MRG has been investigated by introduction of graphite as an additive. MRG with 10 wt% of graphite (GMRG) was fabricated and the analysis of the properties was compared to the reference sample, MRG. The microstructure of GMRG was characterized through Environmental Scanning Electron Microscope, (ESEM). While, the rheological properties including apparent viscosity, yield stress and viscoelastic properties for both samples were examined using shear rheometer under rotational and oscillatory mode. The results demonstrated slightly increment of apparent viscosity in GMRG and shows a significant improvement in term of yield stress by 38.8% at 3A with growth about 32.7% higher compared to MRG from 0A to 3A. Also, an expansion of linear viscoelastic region (LVE) from 0.01 to 0.1% was observed in the GMRG credited to the domination of elastic properties on the sample. These results obtained was confirmed based on ESEM that displayed the contribution of graphite towards constructing more stable chain structure in GMRG. In conclusion, this study highlights the influence of graphite towards improving the rheological properties of MRG. Hence, addition of graphite in MRG is a great potential to be applied in many applications in near future.