bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomistic Molecular Dynamics Simulation and COSMO-SAC Approach for Enhanced 1,3-Propanediol Extraction with Imidazolium-Based Ionic Liquids
Authors: Akshat Raj , Bharti Anand , Padmanabhan Padmini
Published: January 2024

1,3-Propanediol (1,3-PDO) holds significant industrial importance, but its eco-friendly extraction remains a challenge. To address this, we investigated the performance of four ionic liquids ([Bmim][NTF2], [Bmim][NPF2], [Bmim][SCN], and [Bmim][TFO]) via Molecular Dynamics simulations for 1,3-PDO extraction. Analysis of radial distribution functions (RDF) and spatial distribution functions (SDF) demonstrated enhanced 1,3-PDO coordination around [Bmim][SCN], with higher density in [Bmim][SCN] and [Bmim][TFO] compared to [Bmim][NPF2] and [Bmim][NTF2]. [Bmim][TFO] and [Bmim][SCN] exhibited pronounced RDF anion peaks, indicating robust hydrogen bonding interactions and a higher concentration of 1,3-PDO around them. [Bmim][SCN] formed the highest number of hydrogen bonds (1.639) due to its coordinating [SCN]- anion, which bonded with 1,3-propanediol's [OH]- groups. In contrast, non-coordinating anions in [Bmim][NPF2] and [Bmim][NTF2] formed fewer hydrogen bonds. Within a ternary system, [Bmim][SCN] and [Bmim][TFO] excelled at 1,3-PDO extraction, surpassing [Bmim][NPF2] and [Bmim][NTF2] with selectivity around 29. Anion variations significantly influenced distribution coefficients and selectivity values. COSMO-SAC, a predictive thermodynamic model, confirmed 1,3-PDO's strong interaction with [Bmim][SCN] and [Bmim][TFO]. This study enhances our understanding of IL-1,3-PDO systems and their potential in eco-friendly extraction processes. [Bmim][SCN] emerges as the most promising ionic liquid, offering insights into anion selection's role in shaping ionic liquid properties for 1,3-PDO extraction.
Emergence of Chaotic Resonance Controlled by Extremely Weak Feedback Signals in Neural Systems
Authors: Tran Anh Tu , Nobukawa Sou , Wagatsuma Nobuhiko , Inagaki Keiichiro , Doho Hirotaka , Yamanishi Teruya , Nishimura Haruhiko
Published: January 2024

Chaotic resonance is similar to stochastic resonance, which emerges from chaos as an internal dynamical fluctuation. In the chaotic resonance, chaos-chaos intermittency (CCI), in which the chaotic orbits shift between the separated attractor regions, synchronises with a weak input signal. Chaotic resonance exhibits higher sensitivity than stochastic resonance. However, engineering applications are needed because the internal-system-parameter adjustment requirements, especially the biological systems, to induce chaotic resonance from the outside environment is challenging. Moreover, several studies reported abnormal neural activity caused by CCI. Recently, our study proposed that the double-Gaussian-filtered reduced region of orbit (RRO) method (abbreviated as DG-RRO), using external feedback signals to generate chaotic resonance, achieved controlling CCI with a lower perturbation strength than the conventional RRO method. This study applied the DG-RRO method to two typical psychiatric neural systems with CCI behaviour which reproduces the abnormal neural activity of attention deficit hyperactivity disorder and bipolar disorder. Our finding revealed that the DG-RRO feedback method can shift abnormal irregular activity to healthy ordered activity by the chaotic resonance, maintaining extremely low perturbation of the feedback signal. This outcome has the potential application of the DG-RRO approach in treatment while minimising undesired side effects.
Novel Nomogram for Predicting Hepatocellular Carcinoma in Hepatitis C virus-associated Cirrhosis Patients after eliminating virus with Direct-acting Antivirals
Authors: tao xuemei , Zhao Youfei , Wang Zeyu , lu wei , Zhang Jing , Mi Yuqiang , Xu Liang
Published: January 2024

Background and aims:Hepatitis C virus (HCV) associated cirrhosis are in high risk of hepatocellular carcinoma (HCC), and this study aimed to explore the risk factors, and establish and validate a novel nomogram.
Methods: A total of 309 inpatients with HCV- associated cirrhosis from Tianjin Second People's Hospital were selected as the training cohort, and 363 patients from Beijing You’an Hospital were selected as the validation cohort. Both cohorts received Direct-Acting Antiviral Agents (DAAs) treatment and achieved sustained virological response (SVR). Laboratory parameters were collected at baseline and duration of follow-up. Cox regression analysis was used to explore risk factors of HCC, and a nomogram for prediction was developed and validated.
Results: HCC incidence was 5.45 100PY (95% CI, 3.91-7.40) in patients of the training cohort. Age, nonspecific liver nodules, the albumin-Bilirubin (ALBI) score and end of treatment (EOT)-AFP are independent risk factors for HCC by Cox regression analysis. A nomogram was used to predict the 1-year, 3-year and 5-year incidence of HCC, with the areas under receiver operating characteristic curves (AUROCs) of 0.866, 0.813 and 0.764, respectively. The AUROCs in validation cohort at 1, 3, and 5 years were 0.884, 0.783 and 0.692 in this nomogram, respectively.
Conclusion: This novel nomogram had a good predictive ability for HCC in patients with HCV-associated cirrhosis after eliminating virus with direct-acting antiviral agents, especially in 3 years.
Synthesis of metal-organic framework functionalized macroscopic flow-through precipitate tubes
Authors: Balog Edina , Bene Kinga , Schuszter Gábor
Published: January 2024

The guided growth and the composition control of the well-known chemical garden tubular structures has been widely studied in the literature. However, the applicability of these macroscopic hollow precipitate tubes (e.g., catalysis, sensorics, etc.) is limited, since these pipes do not have a flow-through character originally, thus the functionalization of these tubes is difficult to implement. In this work, our goal was to design a novel reactor that enables the production of these flow-through precipitate pipes with robust junctions, and thus their functionalization for further applications. We successfully built the reactor and synthesized such pipes. Their flow-through character was proven in case of various template tubes which were produced by injecting one of the reactant solutions into another in three dimensions. After the production of the template tubes, we attempted to decorate the surface with ZIF-8 crystals, which have a great interest in the literature thanks to the beneficial properties (porous structure, huge specific surface, etc.). The surface functionalization was carried out by properly exchanging the reactant solutions inside and outside the template precipitate tubes. Due to the semi-permeable nature of the tube wall, the reactants could diffuse through the membrane and react with each other. This way we successfully produced ZIF-8 crystals on the inner tube surface and thus gave a useful feature to it.
Field-testing multiple-choice questions with AI examinees
Authors: Maeda Hotaka
Published: January 2024

Field-testing is a necessary but resource-intensive step in the development of high-quality educational assessments. I present an innovative method for field-testing newly written exam items by replacing human examinees with AI examinees. The proposed approach is demonstrated using 512 four-option multiple-choice English grammar questions. One thousand pre-trained transformer language models are fine-tuned based on the 2-parameter logistic (2PL) item response model to respond like human test-takers. Each AI examinee is associated with a latent ability θ, and the item text is used to predict response selection probabilities for each of the four response options. The overall correlation between the true and predicted 2PL correct response probabilities was .68 (bias = 0.03, root-mean-squared-error = 0.19). The simulation study results were promising, showing that item response data generated from AI can be used to calculate item proportion correct, item discrimination, conduct item calibration with anchors, distractor analysis, dimensionality analysis, and latent trait scoring. However, the proposed approach still fell short of the accuracy of analyses that can be achieved with human examinee response data. If further refined, potential resource savings in transition from human to AI field-testing could be enormous. AI could shorten the field-testing timeline, prevent examinees from seeing low quality field-test items in real exams, shorten test lengths, eliminate item exposure and sample size concerns, reduce overall cost, and help expand the item bank.
Risk Factors for Infection after Percutaneous Vertebroplasty Augmentation for Osteoporotic Vertebral Compression Fracture
Authors: Chen Rongbin , Chen Jianquan , Chen Wenchuang , Pan Yizhi , Li Shunpin , Chen Maoshui , Li Yong
Published: January 2024

Background: Percutaneous vertebral augmentation (PVA) is a widely implemented treatment of osteoporotic vertebral compression fracture (OVCF). Although rare, surgical site infection (SSI) is a serious complication of PVA. Even though it is of great medical significance to minimize SSIs after PVA, there have been few reports on systematic risk factor analysis and prevention strategies.The goal of this study was to analyze the incidence and risk factors of postoperative SSI in PVA at a single center and formulate prevention strategies.
Methods: The study involved 2624 patients who underwent PVA for osteoporotic vertebral compression fracture (OVCF) at our hospital between 2015 and 2021. The case-control study method was utilized. The case group consisted of patients who developed postoperative infections, while the control group was composed of uninfected patients selected at a ratio of 1:3.We collected data on risk factors for SSIs from patients' electronic medical records, imaging findings, and laboratory test results. We then analyzed the independent risk factors for postoperative SSIs using Cox univariate and multivariate regression analyses.
Results: In our study, 17/2624 patients (0.65%) developed postoperative vertebral infections.Use of steroid drugs, NEUT%, C-type bone cement leakage after the operation were identified as risk factors in univariate analysis but not in multivariate analysis. Finally, multivariate analysis revealed the following risk factors for infectious spondylitis: age ≥ 80 years, type 2 diabetes, pulmonary infection, Alb ≤ 35 g/L, preoperative MRI indicating signs of fluid accumulation in the fractured vertebral body, and D-type bone cement leakage after the operation.
Conclusions: Multivariate analyses identified the abovementioned independent risk factors for postoperative SSIs after PVA. These data may help guide clinicians take preoperative preventive measures to reduce the incidence of postoperative SSIs after PVA.
Trial registration: This study was approved by Guangdong Province Hospital of Traditional Chinese Medicine. This article is a retrospective study. Therefore, the institution waived the requirement to obtain distinct written informed consent from the patients (approval number: ZE2023-176-01).
A randomized controlled trial comparing the efficacy of bilateral posterior tibial nerve stimulation versus biofeedback pelvic floor muscle training in the management of obstructed defecation
Authors: Ashoush Fouad , Abdelrahim Ahmed , Reddy Anil , Elshazly Walid , Sultan Mohamed , Saafan Tamer , Ali Omer , Rezkallah Emad , Harrison Sanjay , Ahmed Mooyad
Published: January 2024

Introduction: The intricate process of normal defecation relies on the coordinated function of the somatic and autonomic innervation coupled with pelvic muscle activity. Obstructive defecation (OD) is a common disorder in the developed countries with a prevalence reported in literature between 3-18% of the adult population.
Aim: This study aims to compare the efficacy of Bilateral posterior Tibial Nerve Stimulation (Bi-PTNS) compared to Pelvic Floor Muscle training with Biofeedback therapy (BFT) in treatment of adult patients with OD.
Methods: Prospective randomised control study was conducted on adult patients aged ≥18 years, diagnosed with OD, who were referred to the Colorectal Surgery Department at Alexandria Main university Hospitals between 2018 and 2020. Computerized 1:1 block randomization allocated patients into two groups: Bi-PTNS group and BFT group. Wexner constipation score and Patient assessment of Constipation Quality of Life Score (PAC-QoL) were used to assess the severity of patient’s symptoms prior to and after treatment. The primary outcome was the Wexner constipation score. The secondary outcome was the PAC-QoL score.
Results: Statistically significant differences were achieved in patients who underwent Bi-PTNS as compared to BFT group with 66% Versus 50% on the Wexner score and 60% Versus 42% on the PAC-QoL score.
Conclusion: Bi-PTNS intervention was more effective than BFT in alleviating symptoms of OD compared to BFT evidenced by improvements in both Wexner and PAC-QoL scores.
Discretization of fractional fully nonlinear equations by powers of discrete Laplacians
Authors: Chowdhury Indranil , Jakobsen Espen Robstad , Lien Robin Østern
Published: January 2024

We study discretizations by powers of discrete Laplacians of fully nonlinear equations. Our problems are parabolic and of order σ є (0,2) since they involve fractional Laplace operators (-Δ)σ/2. They arise e.g. in control and game theory as dynamic programming equations, and solutions are non-smooth in general and should be interpreted as viscosity solutions. Our approximations are realized as finite-difference quadrature approximations which are 2nd order accurate for all values of σ. The accuracy of previous approximations depend on σ and are worse when σ is close to 2. We show that the schemes are monotone, consistent, L∞-stable, and convergent using a priori estimates, viscosity solutions theory, and the method of half-relaxed limits. We present several numerical examples.
2020 Mathematics Subject Classification. 49L25, 35J60, 34K37, 35R11, 35J70, 45K05, 49L25, 49M25, 93E20, 65N06, 65R20, 65N12.
Investigation of fretting wear characteristics in Zr-4 alloy tube under dual- motion conditions
Authors: Peng Jin-fang , Yang Tao , He Zhi-yi , Li Bo , Liu Jian-hua , Liu Xin-long , Zhu Min-hao
Published: January 2024

It is important to understand that the fuel cladding tube is a critical component in the primary circuit loops of a pressurized water reactor (PWR).In the PWR, the flow-induced vibration of circulating water could cause complex alternating loads between the elastic support mechanism and the cladding tube, eventually leading to complex fretting wear. However, most studies have focused on single tangential fretting wear, with limited research on dual-motion fretting wear. In this work, Zr-4 alloy tubes were subjected to tangential, radial, and dual-motion fretting wear with tube/tube point contact under different loads of three fretting wear modes are studied. The results indicate that the Ft-Dt of dual-motion fretting wear can be classified as trapezoidal (Gross Slip Region GSR), elliptical (elastoplastic coordinated Partial Slip Region PSR), and linear (elastic coordinated Partial Slip Region PSR); the peak friction coefficients of the tangential and dual-motion fretting wear are close to each other, but the latter requires more cycles to reach the peak in the PSR. Comparing the wear region characterization results from the three sets of fretting wear, it was found that the wear degree of dual-motion fretting wear was the most serious, followed by tangential fretting wear, and the wear degree of radial fretting wear was lightest. For dual-motion fretting wear, wear mechanisms change from oxidative wear and spalling to adhesive wear with the GSR to PSR.
Development and validation of a risk prediction model for incident frailty in elderly patients with cardiovascular disease
Authors: Luo Yu-Feng , Jiang Xi-Yuan , Wang Yue-ju , Ren Wen-yan , Wu Long-fei
Published: January 2024

Background
Cardiovascular disease (CVD) and frailty frequently coexist in older populations, resulting in a synergistic impact on health outcomes. This study aims to develop a prediction model for the risk of frailty among patients with cardiovascular disease.
Methods
Using data from the China Health and Retirement Longitudinal Study (CHARLS), a total of 2,457 patients with cardiovascular disease (CVD) in 2011 (n = 1,470) and 2015 (n = 987) were randomly divided into training set (n = 1,719) and validation set (n = 738) at a ratio of 7:3. LASSO regression analysis was used conducted to determine identify the predictor variables with the most significant influence on the model. Stepwise regression analysis and logistic regression model were used to analyze the risk factors of frailty in patients with cardiovascular disease. The prediction model was established by constructing a nomogram. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and calibration curve. The area under the receiver operating characteristic curve and decision curve analysis were conducted to assess predictive performance.
Results
A total of 360 patients (17.2%) had frailty symptoms. Among the 29 independent variables, it was found that gender, age, pain, grip strength, vision, activities of daily living (ADL), and depression were significantly associated with the risk of frailty in CVD patients. Using these factors to construct a nomogram model, the model has good consistency and accuracy. The AUC values of the prediction model and the internal validation set were 0.859 (95%CI 0.836–0.882) and 0.860 (95%CI 0.827–0.894), respectively. The C-index of the prediction model and the internal validation set were 0.859 (95%CI 0.836–0.882) and 0.887 (95%CI 0.855–0.919), respectively. The Hosmer-Lemeshow test showed that the model's predicted probabilities were in reasonably good agreement with the actual observations. The calibration curve showed that the Nomogram model was consistent with the observed values. The robust predictive performance of the nomogram was confirmed by Decision Curve analysis (DCA).
Conclusions
This study established and validated a nomogram model, combining gender, age, pain, grip strength, ADL, visual acuity, and depression for predicting physical frailty in patients with cardiovascular disease. Developing this predictive model would be valuable for screening cardiovascular disease patients with a high risk of frailty.
Lifehistory Trade-Offs Influence Women’s Reproductive Strategies
Authors: Grainger Sara , Dunbar Robin Ian MacDonald
Published: January 2024

We use a modeling approach parameterized with current UK lifehistory data to show that, if they are to match the reproductive performance of women in the higher socio-economic classes, women in lower socio-economic classes must opt for a significantly earlier onset of reproduction in order to offset the higher class-specific mortality and infertility rates that they face. Women from low socio-economic classes cannot afford to postpone reproduction in order to enter a career unless that career pathway facilitates upward mobility into a higher socioeconomic class.
Effect of Cell Therapy With Adipose-Derived Stem Cells in the Treatment of Acute Rupture of the Achilles Tendon in Humans
Authors: Vieira Maria Helena Costa , Schweich-Adami Laynna de Carvalho , Oliveira Rodrigo Juliano , Antoniolli-Silva Andréia Conceição Milan Brochado
Published: January 2024

The aim of this study was to evaluate the effect of adipose-derived stem cells (ADSCs) in the treatment of acute rupture of the Achilles tendon. It was a cross-sectional study involving 15 patients. Patients were randomly divided: group 1 - rupture; group 2 – suture; group 3 – rupture + ADSCs. In the AOFAS score, the score was higher in group 3 with a significant difference. In the ATRS score, the score was higher in groups 2 and 3, also with a significant difference. As for the ultrasound score, there was a significant difference between the experimental groups in relation to this score, however, in the multiple comparisons test, comparing two groups at a time, it was possible to observe a significant difference of the experimental groups. It can be concluded that cell therapy in this condition may be a treatment option due to tissue regeneration and significant recovery of function.
Indigenous-led designation and management of Culturally Significant Species
Authors: Goolmeer Teagan , Costello Oliver , Skroblin Anja , Rumpff Libby , Wintle Brendan
Published: January 2024

Globally, Indigenous peoples are actively seeking better recognition of plants and animals that are of cultural significance, also known as Cultural Keystone Species, or Culturally Significant Entities (CSE), which encompass both species and ecological communities. The acknowledgement and collaborative management of CSE in biodiversity conservation improves environmental outcomes as well as the health and wellbeing of Indigenous people. The global diversity and complexity of Indigenous knowledge, values, and obligations make achieving a universal approach to designating CSE highly unlikely. Instead, empowering local Indigenous-led governance structures with methods to identify place-based CSE will yield more culturally supported results. In this study we used a structured decision-making framework with objectives and biocultural measures developed by Indigenous experts, with the aim of prioritizing place-based CSE for collaborative management approaches on Bunjalung Country in coastal eastern Australia. Our findings support the strategic alignment of Indigenous-led objectives and biocultural measures for the place-based designation and management of CSE, by placing the decision-making authority within the local cultural governance structures. We found some congruence and some important differences between CSE priorities and management compared with the colonial focus of threatened species management underpinned by current laws and policies. We provide a reproduceable methods and demonstration of successful local CSE designation and prioritization in an Australian context that highlights opportunities for Indigenous leadership, supported by governments in designation and management of CSE.
An Unification of Type-3 Grid Connected Wecs in Open Modules Encapsulated by Boost Converter
Authors: MaryAntony A.Santhi , Karthikeyan N , Tran Tien Anh
Published: January 2024

In past three decades, consumption of energy requirements had escalated desperately. Sources were required to meet the power needs as fossil fuels were not able to balance the energy demands. The RES enacts the power needs as it was inexhaustible in nature. Henceforth, the growth rate of Renewable-Energy had been increased intensively to meet the electrical energy demand. RES were expedient and extensively available in nature. An overview of grid-connected WECS manifests type-3 variable speed WT with DFIG was expedient. The accomplishment of DC-DC converter on DFIG based grid connected system epitomize Re-Boost converter (RBC) to be superior in its performance. The Re-boost converter had effectuated in open-loop and closed-loop operation for unification of DFIG based grid connected systems. The DC link voltage of grid connected Inverter had been stabilized by shunting DC-Link Capacitors. The DC-link capacitor had been embraced between the GCS and RSC. It was shunted primarily to provide smooth input to the inverter connected to the grid. AC–DC Converters have diminished conduction & switching losses but empathizes low PF and HD to be more. DC–AC Converters have less switching-stress and harmonics but embraces higher conversion loss. AC–AC Converter achieves higher efficiency but have prevailed the drawbacks due to large size and high harmonics. DC-DC converters embraces the power boosting stage. A Boost Converter (BC) was best suited and reliable due to its better performance and lower power losses. This converter encompasses a topology with continuous input-current which invokes reduced voltage stress. The PI-Controller provides zero control error and it was insensitive to interference of the measurement control. The FOPID-Controller exhibits more adjustable time and frequency responses.
High-Dimensional Single-Cell Analysis of Natural Killer Cell Heterogeneity in Human Blood
Authors: Vivier Eric , REBUFFET Lucas , Melsen Janine , Basurto-Lozada Daniela , Bhandoola Avinash , Björkström Niklas , Bryceson Yenan , Castriconi Roberta , Cichocki Frank , Colonna Marco , Davis Daniel , Diefenbach Andreas , Escaliere Bertrand , Haniffa Muzlifah , Horowitz Amir , Lanier Lewis , Malmberg Karl-Johan , Miller Jeffrey , Moretta Lorenzo , Narni-Mancinelli Emilie , O'Neill Luke , Romagnani Chiara , Ryan Dylan , Simona Sivori , Sun Dan , Vagne Constance , Ding Yi
Published: January 2024

Natural killer (NK) cells are innate lymphoid cells (ILCs) that serve as a first line of defense against pathogens and tumors. Historically, their classification hinged on a limited array of surface protein markers. However, recent advancements in single-cell technologies, such as single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), have unveiled a more complex and nuanced understanding of NK cells. This has led to variations in nomenclature and inconsistencies across scientific literature. In our study, we utilized these technologies to dissect the heterogeneity of NK cells in healthy human blood. We identified three prominent NK cell subsets: NK1, NK2 and NK3, further differentiated into six distinct subgroups. All subsets were present in all donors, irrespective of their human cytomegalovirus (HCMV) status. Our findings delineate the unique molecular characteristics, key transcription factors, principal biological functions, significant metabolic traits, and cytokine responses of each subgroup. These data also suggest two separate
ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. We explore these pathways in depth and propose a comprehensive, standardized nomenclature for NK cells. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
RGS6 inhibits the proliferation, migration, and invasion of breast cancer through the SMAD6-HMGA1 signaling pathway
Authors: Sun Qiang , Kang Ye , Liu Yushi , Zhang Yang , Wang Yitong , Tan Xiaodong , Zhang Miss Qi
Published: January 2024

The regulator of G protein signal 6 (RGS6) is a newly discovered tumor inhibitor that protects against the development of various types of cancer such as lung and bladder cancer. However, the mechanisms underlying these tumor-inhibition effects of RGS6 are not fully understood. In this study, we described the role of RGS6 in inhibiting the proliferation, migration, and invasion of breast cancer (BC) in vivo. Using bioinformatics and experimental tools, we found that RGS6 was generally downregulated in breast cancer tissues while a low expression of RGS6 was associated with poorer survival and prognosis of patients with breast cancer compared to those with normal breast tissues. The overexpression of RGS6 inhibited the migration and invasion of tumor cells by HMGA1. The results of rescue experiments showed that SMAD6 in the TGF-β signaling pathway plays a key role in this inhibitory effect of RGS6. Additionally, the ability of RGS6 to inhibit the expression of the HMGA1 gene depends on its ability to inhibit SMAD6. Based on these results, we identified a new function of RGS6 in regulating HMGA1-induced EMT and the proliferation, migration, and invasion of BC. The results suggested that RGS6 can act as an indicator of prognosis and might be a new target for treating breast cancer. This strategy can improve the outcomes of patients and transform therapeutic approaches.
Cell restriction factors, and not receptor compatibility, block Jamaican fruit bat (Artibeus jamaicensis) susceptibility to mucosal inoculation with SARS-CoV-2 Delta variant
Authors: Port Julia R. , Riopelle Jade C. , Tol Sarah van , Wickenhagen Arthur , Bohrnsen Eric , Sturdevant Daniel E. , Rosenke Rebecca , Lovaglio Jamie , Lack Justin , Anzick Sarah L. , Cordova Kathleen , Yinda Kwe Claude , Hanley Patrick W. , Schountz Tony , Kendall Lon V. , Shaia Carl I. , Saturday Greg , Martens Craig , Schwarz Benjamin , Munster Vincent J.
Published: January 2024

The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited to have originated in bats. While SARS-CoV-2 causes asymptomatic to severe respiratory disease in humans, little is known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses in bats. SARS-CoV-2 has been shown to infect multiple mammalian species, including various rodent species, non-human primates, and Egyptian fruit bats. Here, we investigate the Jamaican fruit bat (Artibeus jamaicensis) as a possible model species to study reservoir responses. SARS-CoV-2 can utilize Jamaican fruit bat ACE2 spike for entry in vitro. However, we find that SARS-CoV-2 Delta does not efficiently replicate in Jamaican fruit bats in vivo. We observe infectious virus in the lungs of only one animal on day 1 post inoculation and find no evidence for shedding or seroconversion. This is possibly due to host factors restricting virus egress after aborted replication. Furthermore, we observe no significant immune gene expression changes in the respiratory tract but do observe changes in the intestinal metabolome after inoculation. This suggests that, despite its broad host-range, SARS-CoV-2 is unable to infect all bat species and Jamaican fruit bats are not an appropriate model to study SARS-CoV-2 reservoir infection.
Ginsenoside Rh2-induced inhibition of HDAC6 promotes autophagy and apoptosis in human leukemia cells
Authors: Liu Xiao-Xia , Shi Shi , Shi Xue-Ping , Hou Ji-Ying , Hou Yan-Hua , Li Jing , Liu Ze-Hong
Published: January 2024

Background and Objective: Previous research has demonstrated that the total saponins of Panax ginseng (TSPG) and other ginsenoside monomers can inhibit the proliferation of leukemia cells. However, the underlying mechanism remains unclear. Autophagy is a response mechanism utilized by cancer cells in response to various anticancer therapies. Therefore, we aimed to investigate the role of autophagy in the anti-leukemia effects of ginsenosides.
Methods: The proliferation and apoptosis of cultured K562 and KG1α cells were evaluated using CCK-8 and FCM assays. The cytotoxicity of bone marrow stromal cell line HS-5 was determined using the CCK-8 method to assess the individual components. Cells were transfected with a small interfering RNA (siRNA) to silence HDAC6 expression, and the effects of Rh2 on HDAC6 were investigated using CCK-8 and FCM assays. The relationships between HDAC6 and Rh2 in terms of autophagy and apoptosis were further characterized using western blot analysis and RT-PCR. In vivo experiments were conducted using K562 xenograft tumors to assess autophagy and apoptosis.
Results: TSPG and other monomers demonstrated cytotoxic effects against leukemia cells, with Rh2 exhibiting greater cytotoxicity compared to other monomers. Furthermore, Rh2 effectively killed leukemia cells while exhibiting reduced toxicity towards normal bone marrow stromal cells. Rh2 induced both apoptosis and autophagy in leukemia cells. The autophagy inhibitor 3-MA reduced the cytotoxicity of Rh2, indicating that autophagy plays a role in its mechanism of action. Silencing HDAC6 expression increased the sensitivity of leukemia cells to Rh2, suppressing HSP90 expression. Additionally, Rh2 enhanced apoptosis and autophagy in vivo, providing further evidence for its therapeutic potential in leukemia treatment.
Conclusion: Conclusion: These findings suggest that Rh2-induced autophagy serves as a cytotoxic mechanism, indicating its potential therapeutic application in leukemia treatment. Additionally, downregulation of HDAC6
The Effect of Inhaled Nitric Oxide on the Exercise Capacity of Patients with Advanced Interstitial Lung Disease: A Randomized Controlled Trial
Authors: Freidkin Lev , Kramer Mordechai R , Rosengarten Dror , Izhakian Shimon , Taieb Shani , Pertzov Barak
Published: January 2024

Purpose
To assess the impact of inhaled nitric oxide (iNO) on the six-minute walk distance in patients with advanced interstitial lung disease
Methods
In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests: one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension.
Results
Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265–409) vs 371 m (IQR 250–407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWTD with iNO and placebo, median 339 (256–402) vs 332 (238–403) for the iNO and placebo tests respectively (P = 0.50).
Conclusion
In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. (NCT03873298, MOH_2018-04-24_002331)
Defending the Integrity of Machine Learning Models in the Face of Adversarial Threats
Authors: Roy Hrittick , Anand Sourabh
Published: January 2024

The primary objective of the research is to examine the resilience of models based on machine learning when confronted with adversarial threats. The focus will be on developing effective strategies to safeguard the integrity of these models. This study employs a carefully designed framework to undertake the task of simulating adversarial attacks on machine learning models. The central objective of the research centres on the intentional manipulation of numerical variables in order to accurately simulate real-world threats. The investigation of statistical analyses, such as t-tests and comprehensive data visualisations, enables the evaluation of the impact exerted by adversarial attacks on both data distributions and model outputs. The primary objective of the current investigation is to assess the effectiveness of a mimicked defence mechanism in the domain of machine learning model restoration, with the ultimate goal of preserving model integrity. The results gathered by our study emphasise the significant significance of adversarial threats, thereby underscoring the need for a comprehensive analysis of robust defence strategies. The analysis of correlation matrices, both before and after adversarial attacks, provides valuable insights into the changes in the fundamental structure induced by these interventions. The current investigation offers valuable insights into the preservation of the integrity of machine learning models and suggests possible ways to enhance their resilience against ever-changing adversarial tactics.
A novel lab-on-chip cartridge overcoming centrifugation and slide preparation for automated urinalysis
Authors: Sahu Avinash , Kandaswamy Srinivasan , Singh Dhanu Vardhan , Thyagarajan Eshwarmurthy , Parthasarathy Arun Koushik , Naganna Sharitha , Dastidar Tathagato Rai
Published: January 2024

After haematology, urinalysis is the most common biological test performed in clinical settings. Hence, simplified workflow and automated analysis of urine elements are of absolute necessities. In the present work, a novel lab-on-chip cartridge (Gravity Sedimentation Cartridge) for the auto analysis of urine elements is developed. The GSC consists of a capillary chamber that uptakes a raw urine sample by capillary force and performs particles and cells enrichment within 5 min through a gravity sedimentation process for the microscopic examination. Centrifugation, which is necessary for enrichment in the conventional method, was circumvented in this approach. The AI100 device (Image based autoanalyzer) captures microscopic images from the cartridge at 40x magnification and uploads them into the cloud. Further, these images were auto-analyzed using an AI-based object detection model, which delivers the reports. These reports were available for expert review on a web-based platform that enables evidence-based tele reporting. A comparative analysis was carried out for various analytical parameters of the data generated through GSC (manual microscopy, tele reporting, and AI model) with the gold standard method. The presented approach makes it a viable product for automated urinalysis in point-of-care and large-scale settings.
Large language models for generating medical examinations: systematic review
Authors: Artsi Yaara , Sorin Vera , Konen Eli , Glicksberg Benjamin S. , Nadkarni Girish , Klang Eyal
Published: January 2024

Background
Writing multiple choice questions (MCQs) for the purpose of medical exams is challenging. It requires extensive medical knowledge, time and effort from medical educators. This systematic review focuses on the application of large language models (LLMs) in generating medical MCQs.
Methods
The authors searched for studies published up to November 2023. Search terms focused on LLMs generated MCQs for medical examinations. MEDLINE was used as a search database.
Results
Overall, eight studies published between April 2023 and October 2023 were included. Six studies used Chat-GPT 3.5, while two employed GPT 4. Five studies showed that LLMs can produce competent questions valid for medical exams. Three studies used LLMs to write medical questions but did not evaluate the validity of the questions. One study conducted a comparative analysis of different models. One other study compared LLM-generated questions with those written by humans.
All studies presented faulty questions that were deemed inappropriate for medical exams. Some questions required additional modifications in order to qualify.
Conclusions
LLMs can be used to write MCQs for medical examinations. However, their limitations cannot be ignored. Further study in this field is essential and more conclusive evidence is needed. Until then, LLMs may serve as a supplementary tool for writing medical examinations.
Dynamical perspective of bifurcation analysis and soliton solutions to (1+1)-dimensional nonlinear perturbed Schrödinger model
Authors: Javed Sara , Ali Asghar , Muhammad Taseer
Published: January 2024

This work simulates the (1+1)-dimensional nonlinear perturbed Schrödinger model (NLPSM). This model has various applications in mathematical physics and engineering, including hydrodynamics, elastic media, nonlinear optical fiber communication, and plasma physics. There are two primary goals for the study. First, it seeks to find unique soliton solutions such as solitary, dark, periodic, and plane wave solutions that haven’t been found in the literature before using the modified Sardar sub-equation approach (MSSEA). Second, a novel approach to analysis called bifurcation analysis is used to investigate the dynamic behavior of the model. Physical compatibility findings are supported by density, 3-D, and 2-D illustrations made with parametric variables. The analysis shows that the approach used to quickly acquire complete and typical answers was successful. This approach works well for solving challenging problems in physics, engineering, mathematics and fiber optic phenomena.
Assessment of serum essential/non-essential elements, biochemical variables and its association with semen parameters and the risk of male infertility
Authors: Kaur Mandeep , Kaur Rajinder , Kapoor Harmanpreet Singh , Chhabra Kiran , Khetarpal Preeti
Published: January 2024

Essential metals are involved in various cellular processes of the body and non-essential metals are toxic even in small amounts and have no biological role. The deficiency or over-exposure of these elements perturbs the reproductive health of males. A cross-sectional study has been conducted to investigate the association of a) essential (Cr, Co, Ni, Fe, Mn, Cu, Zn, Se) and non-essential elements (Pb, Cd, As, Ba, Bi, U, V); b) biochemical variables (glucose, triglycerides, cholesterol, HDL, LDL, albumin, and total protein) with risk of male infertility. A total of 46 males from infertile couples have been selected for the study. Serum element concentrations were estimated using ICP-MS and biochemical parameters were estimated by colorimetric methods. Statistical analysis was performed with IBM SPSS and R package. A significant difference was observed for Cr and LDL at p < 0.10 among study groups. Significant difference was found for spermatozoa volume, count and motility between study groups. Serum albumin levels are positively associated with sperm motility. Cr is negatively correlated with triglyceride levels (p = 0.03). Fe and Co are also significantly but negatively correlated with cholesterol levels (p = 0.05). Mn, Cu, Pd, Cd, and Ba are significantly positively correlated with semen volume. Cr, Co, Ni, Mn, Cu, Zn, Pd, Cd, As, Ba, U, and V are significantly positively correlated with liquefaction time (p < 0.05). The investigation of metals may help in the screening of male infertility as some metals may have therapeutic potential or toxic nature that can be used in the management of condition.
Nano-Scaffold Containing a Functional Motif of Stromal Cell-Derived Factor 1 Enhances Neural Stem Cell Behavior and Promotes Synaptogenesis in a Traumatic Brain Injury Model
Authors: Tork Mohammad Amin Bayat , Saberifar Mohsen , Yekta Hamed Joneidi , Hajinejad Mehrdad , Ravandi Hassan Hosseini , Gorji Ali , Negah Sajad Sahab
Published: January 2024

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, presenting a significant challenge due to the lack of effective therapies. Neural stem cells (NSCs) have shown promising potential in preclinical studies as a therapy for TBI. However, their application is limited by challenges related to poor survival and integration within the injured brain. In this study, we investigated the effect of a novel nano-scaffold containing stromal cell-derived factor 1 (SDF-1) on NSC behavior and synaptogenesis after TBI. Using an innovative design, we successfully fabricated a nano-scaffold with Young's modulus of approximately 3.21 kPa, which aligns closely with the mechanical properties exhibited by neural tissue. This achievement marks the first time such a scaffold has been created and has promising implications for its potential use in neural tissue engineering applications. Our findings demonstrate that the nano-scaffold enhances NSC proliferation, migration, and differentiation capacity in vitro. Moreover, when transplanted into the injured brain, the nano-scaffold promotes the survival and integration of NSCs, leading to increased synaptogenesis and functional recovery. These findings suggest that the use of the novel nano-scaffold containing SDF-1 could provide a promising approach to the treatment of TBI by improving NSC behavior and promoting synaptogenesis.
Characteristic Burn Temperature Markers of Bones as Revealed by Electron Paramagnetic Resonance
Authors: Knaflič Tilen , Legan Lea , Cavalli Fabio , Ropret Polonca
Published: January 2024

This research paper presents a novel methodology for determining the burn temperature of archaeological bones using Electron Paramagnetic Resonance (EPR) supported by Fourier Transform Infrared (FTIR) spectroscopy. A selection of bone samples, burned at different temperatures, were examined with EPR. The EPR spectra displayed dependency on burn temperature, showing characteristic narrow spectra of carbon radicals, Mn2+ signals and signals from different carbonate ions. This methodology was applied to selected archaeological samples of burned bones, sucessfully determining the burn temperature these bones were exposed to in the past. The extracted burn temperatures showed good agreement with those determined from a complementary reflectance FTIR study.
KDM5B/H3K4me3-mediated METTL14 regulates the function of LINC02747 through N6-methyladenosine modification in non-small cell lung cancer
Authors: Wang Jiemin , Wang Shu , Shi Kesong , Yang Haopeng , Wang Ruixuan , Liu Yueshi , Dou Le , Yu Haiquan
Published: January 2024

Background
Multiple epigenetic regulatory mechanisms exert critical roles in tumour development, understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. The main objective of this study was to elucidate the intricate crosstalk between N6-methyladenosine (m6A) modification and histone modification in the context of non-small cell lung cancer (NSCLC).
Results
Bioinformatics analyses and experiments confirmed that the m6A methyltransferase METTL14 was significantly downregulated in NSCLC tissues, with lower levels correlating with poorer overall survival. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. We confirmed using MeRIP-qPCR and dual-luciferase reporter assays that the long noncoding RNA LINC02747 was targeted and regulated by METTL14 via m6A modification, and inhibiting LINC02747 was observed to hinder the malignant progression of NSCLC by modulating the PI3K/Akt signaling pathway. Knockdown of METTL14 significantly decreased the m6A modification of LINC02747 and upregulated its expression. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the "GAACU" binding site by YTHDC2. Additionally, histone demethylase lysine-specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri-methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription, and KDM5B upregulated the expression of LINC02747 by suppressing the expression of METTL14.
Conclusions
In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3-dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a series of mechanisms that regulate the malignant phenotype of NSCLC cells, revealing the complex regulation involved in the occurrence and development of cancer.
Multiclass method for antimicrobial residue analysis in milk using liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-qTOF-MS): validation and application for real samples with ciprofloxacin
Authors: Crizel Rosane Lopes , Zandoná Giovana Paula , Barbosa Rosângela Silveira , Barreto Fabiano , Bonnet Marcelo
Published: January 2024

We developed and validated a novel method for screening and confirming 32 antimicrobial residues in raw, bovine milk using a single preparative step. Antimicrobials under the scope of the method belong to different classes, such as fluoroquinolones, tetracyclines, sulfonamides, macrolides and lincosamides. Sample preparation is simple, quick and requires just one extraction process to satisfactorily extract all analytes. Method performance requirements were found to be satisfactory according to the European (EU) Regulation 2021/808, thus confirming the applicability of LC-ESI-QTOF-MS/MS for reliable qualitative and quantitative purposes. Samples from animals undergoing ciprofloxacin treatment were also analyzed, further confirming the method´s fitness-for-purppose. This approach offers a quick and easy way to perform qualitative and quantitative assessment of 32 antimicrobial residues simultaneously, and therefore could be a valuable resource to optimize analytical routines as part of the efforts to help tackling the persistent, global public health silent pandemic of antimicrobial resistance.