bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of using auditory-motor entrainment to improve walking after stroke: A multi-site randomized controlled trial of the InTandemTM neurorehabilitation system
Authors: Awad Louis , Jayaraman Arun , Nolan Karen , Lewek Michael , Bonato Paolo , Newman Mark , Putrino David , Raghavan Preeti , Pohlig Ryan , Harris Brian , Parker Danielle , Taylor Sabrina
Published: October 2023

Background: Walking slowly in the chronic phase of stroke limits community ambulation and reduces long-term health and quality of life. Our objective was to evaluate the safety and efficacy of an autonomous neurorehabilitation system designed to utilize auditory-motor entrainment to improve walking in people in the chronic phase of stroke recovery.
Methods: The multi-site, prospective, interventional, 2-arm randomized controlled trial enrolled 87 individuals >6 months post-stroke and with walking speeds between 0.5 m/s and 0.8 m/s. Participants were asked to complete 15 walking intervention sessions over a 5-week period and were assigned to either experimental (i.e., walking with the MR-001 neurorehabilitation system [InTandemTM]) or Active Control (i.e., walking without InTandem) interventions. The primary endpoint was the between-group difference in the change in walking speed, as measured by the 10-meter walk test (10mWT) before and after each intervention period. Between-group differences in the rate of responders and time course of walking speed improvement were also assessed. Responders were those with a: (1) speed increase >0.16 m/s or (2) speed increase >0.16 m/s and a post-training speed above 0.80 m/s. Safety was assessed by the frequency of adverse events (AEs).
Results: InTandem resulted in a larger increase in speed (Δ: 0.14±0.03 m/s) compared to Active Control (Δ: 0.06±0.02 m/s) (F(1,49)=6.58, p=0.013). Participants randomized to InTandem were over 3x more likely to be responders (χ2(1)≥6.47, p=0.01). InTandem was also associated with a 2.7x faster rate of speed increase over the 15-session intervention period (F(16,206)=1.790, p=0.034). Both groups experienced the same number of AEs and serious AEs.
Conclusions: InTandem uses the closed-loop control of music to autonomously individualize and progress walking rehabilitation. While further study is warranted to better understand the ideal treatment length, durability of effect, and healthcare resource utilization impact, InTandem provides a safe and effective intervention that improves walking speed in the chronic phase of stroke.
Trial registration: NCT04121754
Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC BeadChip microarrays
Authors: Zhang Wei , Young Juan I. , Gomez Lissette , Schmidt Michael A. , Lukacsovich David , Varma Achintya , Chen X. Steven , Kunkle Brian , Martin Eden R. , Wang Lily
Published: October 2023

DNA methylation (DNAm) plays a crucial role in a number of complex diseases. However, the reliability of DNAm levels measured using Illumina arrays varies across different probes. Previous research primarily assessed probe reliability by comparing duplicate samples between the 450k-450k or 450k-EPIC platforms, with limited investigations on Illumina EPIC arrays. We conducted a comprehensive assessment of the EPIC array probe reliability using 138 duplicated blood DNAm samples generated by the Alzheimer's Disease Neuroimaging Initiative study. We introduced a novel statistical measure, the modified intraclass correlation, to better account for the disagreement in duplicate measurements. We observed higher reliability in probes with average methylation beta values of 0.2 to 0.8, and lower reliability in type I probes or those within the promoter and CpG island regions. Importantly, we found that probe reliability has significant implications in the analyses of Epigenome-wide Association Studies (EWAS). Higher reliability is associated with more consistent effect sizes in different studies, the identification of differentially methylated regions (DMRs) and methylation quantitative trait locus (mQTLs), and significant correlations with downstream gene expression. Moreover, blood DNAm measurements obtained from probes with higher reliability are more likely to show concordance with brain DNA measurements. Our findings, which provide crucial reliable information for probes on the EPIC array, will serve as a valuable resource for future DNAm studies.
Approach to Multi-Attribute Decision-making Based on VIKOR under Q-Rung Orthopair Probabilistic Hesitant Fuzzy Environment
Authors: Hao Yun , Lin Zhichao , Zhou Ligang
Published: October 2023

The q-rung probabilistic hesitant fuzzy sets (q-ROPHFS) can accurately capture the initial information provided by decision makers (DMs), thereby improving the reliability and accuracy of the decision method. A new multi-attribute decision-making (MADM) method combining distance measures of q-rung probabilistic hesitant fuzzy elements (q-ROPHFEs) with the VIKOR is proposed in this paper. Firstly, a distance measurement method under the q-rung orthopair probabilistic hesitant fuzzy environment (q-ROPHFEN) is brought forward. Secondly, a maximum deviation function of q-rung probabilistic hesitant fuzzy elements is presented to determine the weights of attributes when the attribute weights are unknown. Lastly, the VIKOR is extended to solve the probabilistic hesitant fuzzy MADM problem. A numerical example is presented to demonstrate the validity of the above method.
The role of digital economy in reducing urban carbon emissions: empirical evidence from Chinese cities
Authors: PAN Sheng , HE Timan , REN Yabing , DONG Caihua , XU Xiumei
Published: October 2023

This study investigates the affiliation between the digitalized economy and carbon release in 282 Chinese urban areas from 2005 to 2019. Fixed effects models, system GMM models, and Spatial Durbin models have been utilized to exploit the consequences of digital economy on carbon release. The findings demonstrate that (1) digital economy appreciably mitigates carbon output and carbon intensity. Moreover, digital economy facilitates eco-friendly technological development and optimizes industrial structure. (2) It exerts a more profound influence on carbon reduction in the middle east region, as opposed to the western region, where economic growth has greater possibilities (3) The effect of the digital economy on reducing carbon dioxide emissions is influenced by valid duration of policies and shows a spatial effect. Drawing on findings, this paper suggests policy recommendations from three key areas: advancing industrial restructuring, fostering technological revolution, and harnessing regional radiation effects of digital economy to bolster its advancement.
High Storage and Energy Efficient Memory for Cryogenic Computing
Authors: Zhao Qing-Tai , Han Yi , Sun Jingxuan , Richstein Benjamin , Bae Jin , Allibert Frederic , Radu Ionut , Grützmacher Detlev , Knoch Joachim
Published: October 2023

Efficient computing in cryogenic environments, encompassing classical von Neumann architectures, advanced quantum and neuromorphic systems, holds the potential to revolutionize big data processing. As the demand for high storage density and energy-efficient memories grows, the absence of a clear solution for cryogenic memory remains a challenge. Here, we present a cryogenic capacitorless Random Access Memory (C2RAM) utilizing advanced Si technology. This innovation is positioned to reshape cryogenic computing, with its high scalability and the capacity to be written and erased across multiple-states, significantly boosting the storage density. Notably, the C2RAM requires only ultra-low write energies, measuring just a few zeptojoules and provides exceptionally long retention times preserving data for over a decade. This positions C2RAM as a prime contender for nonvolatile memory for cryogenic von Neumann architectures and quantum technologies. In addition, the memory unit emulates biological synapses, including potentiation and depression, enabling a seamless integration into crossbar arrays, requiring no additional selectors for neuromorphic computing. The fusion of logic and analog capabilities unlocks substantial potential for high-density cryogenic memory applications. This innovative breakthrough enables the convergence of classical von Neumann, quantum, and neuromorphic computing, harnessing the significant performance advantages anticipated at cryogenic temperatures.
Association between Sick Child Facility Readiness and Provision of Care at the Individual and Facility Level in Five Low- and Middle-Income Countries
Authors: Carter Emily D , Sheffel Ashley , Requejo Jennifer , Kosek Margaret , Campbell Harry , Eisele Thom , Munos Melinda K
Published: October 2023

Background
Raising the quality of health services is key to continued progress in improving child health, however, data on service quality are limited and difficult to interpret. The relationship between facility readiness and the provision of quality care is poorly characterized.
Methods
Using publicly available data sets from five low- and middle-income countries (LMICs), we assessed 1) how structural factors enable or restrict provision of care and 2) how closely provision of healthcare aligns with structural factors for managing sick children. We developed indices for readiness and provision of care accounting for available indicators, expert opinion, and alignment with IMCI guidelines. In each country, we assessed the association between readiness and provision of care, with and without adjusting for other factors. We considered associations overall, by domain, and by provider type, explored non-linear associations, and compared associations at the individual and facility-level.
Results
The analysis included data from 3,149 health facilities and 11,159 sick child observations. In four of the five countries included in the analysis, we observed a significant positive association between readiness and provision of care with a magnitude of approximately 0.1 after adjusting for facility type and managing authority. There was little evidence of a non-linear relationship or a threshold effect altering the relationship between readiness and provision of care. Beyond readiness, younger child age, higher cost of care, and having a respiratory, digestive, or febrile diagnosis were most often associated with a higher quality of care. Higher “human resources” readiness domain scores were most consistently associated with better provision of care, while the provision of care domain of “treatment” was the least influenced by readiness. Facility-level associations did not vary greatly from individual-level associations.
Conclusions
These analyses suggest facility readiness plays a significant but limited role in the quality of case management provided to children with common illnesses of early childhood. Data for assessing provision of health services are limited, presenting challenges for understanding health worker actions. We need better data to assess the quality of care being delivered in LMICs to understand what factors drive health worker decision-making, with the ultimate goal of improving the management of sick children.
Reversal of Disease Phenotypes in ALS and Genetic Premature Aging Cells by Redirecting Misfolded TDP-43 Proteins into Physiological TDP-43 Oligomers
Authors: Wang I-Fan , Chang Hsiang-Yu
Published: October 2023

A group of misfolded prone-to-aggregate domains in disease-causing proteins has recently been shown to adopt unique conformations that play a role in fundamental biological processes, including the formation of membrane-less sub-organelles, alternative splicing, and gene activation. The cellular responses are regulated by the conformational switching of prone-to-aggregate domains. Given this, targeting the misfolded states of disease-causing proteins to redirect them towards their physiological conformations is emerging as an effective therapeutic strategy for diseases caused by protein misfolding. In our study, we successfully identified baicalein as a potent structure-correcting agent. Our findings demonstrate that baicalein can reconfigure existing TDP-43 aggregates into an oligomeric state both in vitro and in disease cells. This transformation effectively restores the bioactivity of misfolded TDP-43 proteins in cellular models of ALS and premature aging in progeria. Impressively, in progeria cells where defective lamin A interferes with TDP-43-mediated exon skipping, the formation of pathological TDP-43 aggregates is promoted. Baicalein, however, restores the functionality of TDP-43 and mitigates nuclear shape defects in these laminopathic cells. This establishes a connection between lamin A and TDP-43 in the context of aging. Our findings suggest that targeting physiological TDP-43 oligomers could offer a promising therapeutic avenue for treating aging-associated disorders.
Decrease in UCP1 by sustained high lipid promotes NK cell necroptosis to exacerbate nonalcoholic liver fibrosis
Authors: Gong Weijuan , Gu Min , Zhang Yu , Lin Zhijie , Hu Xiangyu , Zhu Yaqin , Xiao Wei , Jia Xiaoqin , Chen Weiwei , Lu Guotao
Published: October 2023

Uncoupling protein 1 (UCP1) catalyzes the leak of protons across the mitochondrial inner membrane for thermogenesis. Compromised NK cell activity is involved in the occurrence of nonalcoholic liver fibrosis. Here, decreased UCP1 in NK cells was identified in patients with advanced nonalcoholic fatty liver disease. Although no obvious changes were observed in the NK cells of physiologic UCP1−/− mice (8–10 weeks old), impaired NK cell bioactivity was shown in methionine-choline-diet (MCD)-fed UCP1−/− mice and involved in the acerbation of nonalcoholic steatohepatitis (NASH) progress to liver fibrosis. Moreover, Bone marrow cross-transplantation experiments proved that UCP1-deficient NK cells were responsible for the aggravation of liver fibrosis. Acerbation of liver fibrosis was also seen in wild-type mice when their endogenous NK cells were replaced with UCP1−/− NK cells. Transcriptions of mitophagy-associated molecules in UCP1−/− NK cells were enhanced according to RNA-seq. Electron microscopic results showed mitochondrial injuries and autophagic vesicles in MCD-fed NKWT cells, PA-treated NKWT cells, or physiologic NKKO cells. However, the co-existence of UCP1 deficiency and high lipid can synergistically induce NK cell necroptosis via DRP1S616 accompanied with reduced mitophagy. Finally, The UCP1 in NK cells was downregulated when treated by sustained high PA (600 µM) via the PPARγ/ATF2 axis. Thus, persistent high-lipid treatment not only decreases UCP1 expression but also combines with reduced UCP1 to promote NK cell necroptosis, and it is involved in NASH progression to fibrosis.
Performance and mechanism analysis of sludge-based biochar loaded with Co and Mn as photothermal catalysts for simultaneous removal of acetone and NO at low temperature
Authors: Wang Hongqiang , Huang Sheng , Liao Lei , Mo Shengpeng , Zhou Xiaobin , fan yinming
Published: October 2023

A series of sludge-based biochar catalysts with different sludge calcination temperatures and different Co and Mn addition ratios were prepared by a simple hydrothermal synthesis method for the simultaneous removal of acetone and NO in a low-temperature photothermal co-catalytic system with acetone replacing NH3. Among them, the catalyst with sludge calcined at 400 ℃ and Co, Mn addition ratios of 4:1 (400@4:1) showed the optimal photothermal catalytic performance, with the conversion of acetone and NO reaching 42.98% and 52.41% at 240 ℃, respectively. The physicochemical properties of each catalyst were analyzed by characterization of SEM, XRD, BET, XPS, FT-IR, H2-TPR, O2-TPD, UV-vis, and transient photocurrent response (TPC). The effects of specific surface area, valence and content of Co and Mn atoms, types of surface adsorbed oxygen and lattice oxygen, optical properties, and other factors on the catalytic properties of the catalysts were investigated. A possible mechanism for the catalytic conversion of acetone and NO on the catalyst surface was proposed based on the Mars - van Krevelen (MvK) mechanism. A new strategy is provided for the resource utilization of sewage sludge and the preparation of photothermal catalysts for the simultaneous removal of acetone and NO at low cost.
Climate-dependent plant responses to earthworms in two land-use types
Authors: Liu Qun , Eisenhauer Nico , Scheu Stefan , Angst Gerrit , Bücker Miriam , Huang Yuanyuan , Meador Travis B. , Schädler Martin
Published: October 2023

Plant nutrient uptake and productivity are driven by a multitude of factors that have been modified by human activities, such as climate change and the activity of decomposers. However, interactive effects of climate change and key decomposer groups like earthworms have rarely been studied. In a field microcosm experiment we investigated the effects of a mean future climate scenario for the period between 2070 and 2100 in Germany with warming and altered precipitation and earthworms (anecic - Lumbricus terrestris, endogeic - Allolobophora chlorotica and both together) on plant biomass and stoichiometry in two contrasting land-use types (intensively-used meadow with four forage grass species and conventional farming). In contrast to previous studies we found little evidence for earthworm effects on aboveground biomass. However, future climate increased above- (+ 40.9%) and belowground biomass (+ 44.7%) of grass communities, which was mainly driven by production of the dominant Festulolium species during periods outside the projected summer drought, but slightly decreased the aboveground biomass (-36.9%) of winter wheat. Projected climate change and earthworms interactively affected the N content and C:N ratio of grasses. Earthworms enhanced the N content thereby decreasing the C:N ratio in grasses, but only under ambient climate conditions. The future climate treatment generally decreased the N content of grasses and winter wheat, resulting in an increase in plant C:N ratio. Our results suggest that climate change diminishes the positive effects of earthworms on plant nutrient uptakes due to soil water deficit, especially during summer drought.
Paclitaxel resistance of ovarian clear cell carcinoma reveals the ABC- and SLC- transporter genes to mediate glycolytic metabolism.
Authors: Lin Tsai-Yu , Li Pei-Jhen , Lin Yi-Hui , Shih Jou-Ho , Lin Tung-Yi , Gu Shin-Yuan , Chou Teh-Ying , Lee Yu-Ching , Lang Yaw-Dong , Chang Shwu-Fen
Published: October 2023

Background Ovarian clear cell carcinoma (OCCC) often becomes resistant to platinum based therapy when at an advanced stage. However, metabolic phenotypes and changes in its resistance remain unclear. Hence, we investigated the metabolic effect of paclitaxel resistance in OCCC and normal ovarian epithelium OSE2a cells.
Methods The viability and cytotoxicity of paclitaxel resistant cells were determined. Glycolytic stress was measured using a Seahorse extracellular flux analyzer. RNA sequencing (RNA-Seq) was used to elucidate differentially expressed genes upon paclitaxel resistance Comprehensive metabolomics (capillary electrophoresis time of flight mass spectrometry (CE-TOFMS and CE-QqQMS) and transcriptomics analysis (RNA-Seq) were performed to characterize metabolic pathways in paclitaxel resistant OCCC cells.
Results ES2 resistant cells had slower ATP and guanosine 5' triphosphate (GTP inflow and a greater nicotinamide adenine dinucleotide (NADH/NADH coenzyme (NAD ratio with an elevated oxygen consumption rate. Sets of ABC binding cassette (ABC- and solute carrier (SLC) transporter genes were found to be enriched in ES2 resistant cells involving glycolysis metabolism and molecular transport. We further demonstrate d that in response to high paclitaxel resistance, characteristic metabolomic changes in ES2 cells were a reduction in the energy requiring phase of glycolysis and the induction of metabolites in the energy releasing phase of glycolysis . Moreover, metabolite levels of selected cancer related nonessential amino acids, including serine glycine metabolism increased with paclitaxel resistance.
Conclusions This is the first work to elucidate metabolic profiles of paclitaxel resistance in OCCC cells, indicating possible underlying mechanisms by which cells respond to paclitaxel cells, indicating possible underlying mechanisms by which cells respond to paclitaxel therapy through therapy through ABC-- and SLC--transporter genes, thereby affecting glycolysis transporter genes, thereby affecting glycolysis metabolism metabolism inin response to paclitaxel resistance.response to paclitaxel resistance.
Mesenchymal stem cells promote ovarian reconstruction in mice
Authors: Li Jiazhao , Fan Haonan , Liu Wei , Zhang Jing , Xiao Yue , Peng Yue , Yang Weijie , Liu Wenwen , He Yuanlin , Qin Lianju , Li Jing
Published: October 2023

Background: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue could be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Since current in vitro culture techniques of primordial follicles have a low success rate in obtaining mature oocytes, an artificial ovary with primordial follicles may be good way to solve this problem.
Methods: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio and a reconstituted ovarian model was generated by using phytohemagglutin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-qPCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay.
Results: Our results revealed the addition of BM-MSCs in reconstituted ovary could mesenchymal stem cells at the single-cell level reveals that the addition of stem cells increase the survival rate of oocytes and promote the follicular growth and development. The reconstituted ovaries have normal folliculogenesis and oocyte maturation. After aggregation with ovarian cells, BM-MSCs didn’t pr oliferate and participate in the formation of follicles. On the contrary, their numbers decreased significantly along with the development of reconstituted ovary and the cells were found to be surrounded with growing follicles. When theca cells were labeled with CYP17a1, only individual theca cells showed the overlapped staining with GFP labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary.
Conclusions: BM-MSCs promoted ovarian cell survival, follicle formation and development in the artificial ovary. Since it didn’t proliferate in the reconstituted ovary, it may represent a new and safe approach on clinical fertility preservation by improving the success rate of thawed ovaries transplantation.
Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing
Authors: Sharda Deepinder , Ghosh Sandip , Kaur Pawandeep , Basu Biswarup , Choudhury Diptiman
Published: October 2023

Burn injuries are characterized by prolonged inflammatory phases, neurovascular damage, and hypermetabolism, eventually causing improper tissue regeneration. Insulin has gained considerable attention in normal and diabetic wound healing, yet its role in burn wounds remains poorly understood. In this study, insulin-chitosan nano-formulations (ICNP) were synthesized using a simple and robust mechanism and characterized to monitor specific interactions between insulin and chitosan, and the particles measuring approximately 30 nm in size exhibited mild alterations in the amide I, II, and III bonds of the insulin protein along with impressive insulin loading efficiency of 88.725 ± 0.295% under physiological conditions, and significantly improved burn wound healing in vitro (HEKa cells) and in vivo (murine third-degree burn model). The underlying mechanism behind superior wound closure and tissue remodeling was attributed to significant early phase reduction of pro-inflammatory cytokine IL-6 levels in ICNP-treated mice, while anti-inflammatory cytokine IL-10 levels became markedly elevated, resulting in enhanced re-epithelialization and collagen deposition. Furthermore, treatment of ICNP was associated with unregulated expression of Nrf-2, a key regulator of oxidative stress and inflammation, indicating their molecular crosstalk. These findings highlight the potential of ICNP as a promising therapeutic formulation for burn wound healing, promoting wound closure by modulating inflammatory phases, making it a valuable candidate for further clinical development in burn care.
Another emerging contaminant in the sinking city: The first evidence of metformin detected in Jakarta waters
Authors: Koagouw Wulan , Simanjuntak Erna , Hazell Richard J. , Subandi Riyana , Ciocan Corina
Published: October 2023

Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect non target organisms. The pharmaceutical metformin is the most commonly prescribed anti-diabetes medicine throughout the world. Metformin has been detected in numerous freshwater systems as well as in seawater at a number of sites around the world over the last few years, but has never been reported in the Indonesian capital city Jakarta. Several recent studies have highlighted various ecotoxicological effects of this medicine on aquatic organisms. Here we report the first evidence of metformin’s presence in Jakarta waters. Samples from the Angke river, one of the main rivers in Jakarta, were collected from six sites. Metformin was detected at three sites in concentrations ranging from 27 ng/L to 414 ng/L. Metformin is one of the most detected APIs (active pharmaceutical ingredients) in aquatic environments worldwide, and there is increasing concern regarding its impact on the health of wildlife and humans. However, this is the first report of metformin contamination in Jakarta waters, adding to the evidence of potentially increased pollution with pharmaceuticals, as noted in our previous studies. With no natural degradation processes, these chemical compounds can be easily reintroduced to the food chain and impact human health.
Stark effect and orbitals hybridization of moir\'e interlayer exciton in $ MoSe{2}/ WSe{2} $ heterobilayer.
Authors: Hannachi Houssem Eddine , Jaziri Sihem
Published: October 2023

We theoretically investigate the interlayer excitons response in the $WSe_{2}/MoSe_{2}$ heterobilayer under the effects of in-plane and out-of-plane static electric fields. We thoroughly analyze a wide range of properties pertaining to the interlayer exciton, including the binding energy, Stark shift, orbital hybridization, photoluminescence (PL) spectrum, and radiative lifetime. We examine various factors influencing interlayer exciton behavior, including the dielectric environment and the moir\'e traps effects.
Our results demonstrate that the in-plane electric field significantly affects the binding energies of the interlayer exciton, leading to energy splitting between states with non-zero angular momentum, such as the $2p_{\pm}$ dark states. Furthermore, we show that the applied in-plane electric field results in orbitals hybridization of the interlayer exciton, including hybrid states such as $1s$, $2p_{\pm}$, and $2s$.
In counterpart, we demonstrate that an out-of-plane electric field induced by a double-gate setup causes a quadratic Stark effect on the center of mass eigenenergies of the interlayer exciton and leads to energy splitting of degenerate states, result in an orbitals hybridization of center of mass eigenvectors. Finally, we determine the PL spectra and radiative lifetime of the moiré interlayer exciton as a function of electric field strength. Our results reveal that the $2p_{\pm}$ dark state becomes brighter through a one-photon PL process as the in-plane electric field strength increases. This phenomenon is directly attributed to the coupling between the $ns$ and $ np_{\pm} $ states generated by the in-plane electric field.
In short, our investigation can help experimenters to designing novel optoelectronic applications, such as on-chip electro-optic modulators and TeraHertz devices.
Red blood cell folate level is associated with periodontitis in American adults: results from the NHANES 2009-2014
Authors: Liu Zefei , Luo Shiyi , Jiao Ruofeng , Li Wei , Jin Fuqian , Sun Jiangling , Ma Shu , Song Jukun , Chen Zhu
Published: October 2023

Background
The relationship between folate and periodontal disease has been previously reported. Red blood cell (RBC) folate is an indicator of long-term folate nutrition. The aim of this study was to use the NHANES database to determine whether red blood cell folate is associated with moderate/severe periodontitis.
Methods
A cross-sectional analysis of 10,168 participants in the NHANES database from 2009–2014 was performed. Multivariate logistic regression was used to determine the OR and 95% CI for periodontitis in each group. Restriction cube spline model was used for analyzing dose-response relationship. Finally, subgroup analysis was performed to test whether the results were robust in different populations.
Results
After adjusting for confounding factors, there was an inverse correlation between RBC folate concentration and moderate/severe periodontitis. The lowest fraction Q1 (< 360ng/mL) of RBC folate concentration was used as the reference group, multivariable-adjusted ORs and 95% CIs of the second (360-463ng/mL), third (464-569ng/mL), fourth (570–732 ng/mL), and the highest quintile (> 733 ng/mL) categories were 0.87 (0.76–0.99), 0.81(0.70–0.93),0.75(0.65–0.88),0.62(0.53–0.73) respectively (all p < 0.05).
Conclusion
In representative samples of American adults, high red blood cell folate was at low risk for moderate/severe periodontitis. At the same time, dentists and policymakers should pay attention to the harm caused by high red blood cell folate level.
HOOK3 suppresses proliferation and metastasis in gastric cancer via the SP1/VEGFA axis
Authors: Shi Tongguo , Yang Kexi , Li Juntao , Zhu Jinghan , Chen Yuqi , He Yuxin , Wang Jiayu , Shen Kanger , Wang Kun , Chen Weichang
Published: October 2023

HOOK3, a member of the human hook microtubule-tethering protein family, has been implicated in the progression of cancer. However, the role of HOOK3 in the pathogenesis of gastric cancer (GC) remains incompletely understood. In this study, we investigated the expression of HOOK3 protein in GC tissues using immunohistochemistry (IHC). The findings of our study indicate that the expression levels of HOOK3 in GC tissues were relatively low. Furthermore, a significant negative association was seen between HOOK3 expression and the prognosis of patients with GC. The suppression of HOOK3 resulted in a notable increase in the proliferation, migration, and invasion of GC cells. Conversely, the overexpression of HOOK3 had the opposite impact, reducing these cellular processes. Moreover, in vivo tests have shown evidence that the overexpression of HOOK3 significantly inhibited the formation of tumors and the spread of GC cells to the lungs. In a mechanistic manner, the analysis of RNA-seq data demonstrated that the knockdown of HOOK3 resulted in a notable increase in the expression of VEGFA in GC cells. Furthermore, the upregulation of VEGFA counteracted the impacts of HOOK3 upregulation on the proliferation, migration, and invasion of GC cells. Furthermore, it was revealed that SP1 exhibited the ability to bind to the promoter region of VEGFA. Moreover, the overexpression of SP1 successfully counteracted the inhibitory impact of HOOK3 overexpression on the expression of VEGFA in GC cells. In summary, the results of our study indicate that HOOK3 has a role in inhibiting the growth, migration, and invasion of GC cells by modulating the SP1/VEGFA pathway. These findings contribute significant knowledge to our understanding of the underlying mechanisms involved in the development of GC.
Genome-wide identification and characterization of Aux/IAA gene family in grape and functional identification of VaIAA3 in response to cold stress
Authors: Li Min , Liang Guoping , Cheng Yongjuan , Gou Huimin , Che Lili , Lu Shixiong , Mao Juan
Published: October 2023

The Aux/IAA gene is a key gene that regulates auxin signal transduction in plants. Although IAA genes have been characterized in various plant species, the role of the IAA gene in grape cold resistance is unclear. In order to further explore the members of Aux/IAA gene family in grape and their functions, in this study, based on the genomic data of ‘Pinot Noir’ (Vitis vinefera cv. ‘Pinot Noir’) and Shanputao (Vitis amurensis), 25 VvIAA genes and 18 VaIAA genes were identified. The VaIAA genes exhibited different expression patterns under diferent temperature periods by qPCR. VaIAA3 was selected as a candidate gene for further functional analysis because of its high expression level under low temperature stress. The subcellular localization showed that VaIAA3 was localized in the nucleus. Additionally, under 4°C treatment at 24 h, the relative expression level of VaIAA3 and antioxidant enzyme activity of the three transgenic lines (OE-1, OE-2, OE-3) were significantly increased, while the contents of relative electrolytic conductivity (REC), malondialdehyde (MDA) and hydrogen peroxide (H2O2) were lower under cold stress. Taken together, these results provide some possibilities to study the identification and function of Aux/IAA gene families in different grape varieties. Importantly, heterologous over-expression of VaIAA3 can enhance resistance of Arabidopsis thaliana under cold stress, which provides a theoretical basis for further use of IAA3 gene to improve grape agronomic traits.
Quantum Magnifying Glass for Chemistry at the Nanoscale
Authors: Reiher Markus , Csizi Katja-Sophia , Steiner Miguel
Published: October 2023

Nanoscopic systems exhibit diverse molecular substructures by which they facilitate spe- cific functions. Theoretical models of them, which aim at describing, understanding, and predicting these capabilities, are difficult to build. Viable quantum-classical hybrid mod- els come with specific challenges regarding atomistic structure construction and quantum region selection. Moreover, if their dynamics are mapped onto a state-to-state mecha- nism such as a chemical reaction network, its exhaustive exploration will be impossible due to the combinatorial explosion of the reaction space. Here, we introduce a quantum magnifying glass that allows one to interactively manipulate nanoscale structures at the quantum level. The quantum magnifying glass seamlessly combines autonomous model parametrization, ultra-fast quantum mechanical calculations, and automated reaction ex- ploration. It represents a unique approach to investigate complex reaction sequences in a physically consistent manner with unprecedented effortlessness in real time. We demon- strate these features for reactions in bio-macromolecules and metal-organic frameworks, diverse systems that highlight general applicability.
PPI-hotspotID: A Method for Detecting Protein-Protein Interaction Hot Spots from the Free Protein Structure
Authors: Chen Yao Chi , Sargsyan Karen , Wright Jon D , Chen Yu-Hsien , Huang Yi-Shuian , Lim Carmay
Published: October 2023

Experimental detection of residues critical for protein-protein interactions (PPI) is a time-consuming, costly, and labor-intensive process. Hence, high-throughput PPI-hot spot prediction methods have been developed, but they have been validated using relatively small datasets, which may compromise their predictive reliability. Here, we introduce PPI-hotspotID, a novel method for identifying PPI-hot spots using the free protein structure, and validated it on the largest collection of experimentally confirmed PPI-hot spots to date. We show that PPI-hotspotID outperformed FTMap and SPOTONE, the only available webservers for predicting PPI hotspots given free protein structures and sequences, respectively. It also outperformed AlphaFold-Multimer in detecting PPI-hot spots using predicted interfaces. When combined with the AlphaFold-Multimer-predicted interface residues, PPI-HotspotID, yielded better performance than either method alone. Furthermore, we experimentally verified the PPI-hot spots of eukaryotic elongation factor 2 predicted by PPI-hotspotID. Notably, PPI-hotspotID unveils PPI-hot spots that are not obvious from complex structures, which only reveal interface residues, thus overlooking PPI-hot spots in indirect contact with binding partners. Thus, PPI-hotspotID serves as a valuable tool for understanding the mechanisms of PPIs and facilitating the design of novel drugs targeting these interactions. A freely accessible web server and the source code for PPI-hotspotID are available at https://ppihotspotid.limlab.dnsalias.org/ and https://github.com/wrigjz/ppihotspotid/, respectively.
Systematic videolaryngoscopy use: remain aware of the risks
Authors: Delatre Florian , Dubois Guillaume , Zaatar Rody , Bartoli Pauline , Radji Michael
Published: October 2023

Background:Videolaryngoscopy is a life-saving technique recommended in difficult intubation algorithms in both the operating room and critical care settings. It has demonstrated numerous advantages in terms of increasing the success rate of first-attempt intubations.
However, it is not without risks, notably in terms of injuries to the ENT area. These injuries and their incidence are very rarely described in the large trials promoting the routine use of videolaryngoscopy. This case-control study aims to highlight this risk in order to discuss the promotion of routine videolaryngoscopy use.
Case report: A 52-year-old woman undergoes an inguinal hernia repair under coelioscopy. After two failed attempts of direct laryngoscopy, intubation using videolaryngoscopy is successfully performed on the first attempt. However, in the postoperative period, a lesion resembling a perforation of the anterior pillar of the right tonsillar fossa is discovered. The injury heals well after 10 days of monitoring.
Discussion:Injuries to the ENT area following videolaryngoscopy are not uncommon and are even more frequent than after direct laryngoscopy. This can be explained by a false sense of security induced by a perfect view of the glottis on the screen, a pursuit of this perfect view even when it is not suitable for intubation with a glide scope, and the use of a too rigid stylet.
Conclusion:It is advisable to exercise caution regarding the routine use of videolaryngoscopy until more substantial studies assessing this specific risk are conducted.
Revisiting Cytomegalovirus Seroprevalence in Singapore's Antenatal Populations: A Two-Decade Update
Authors: Partana Pamela , Wan Wei Yee , Chow Venessa Xin Yu , Chan Jerry Kok Yen , Tan Lay Kok , Tan Wei Ching , Lim Gek Hsiang , Yang Liying
Published: October 2023

Purpose Cytomegalovirus (CMV) is the most common congenital infection in pregnancy with potential long-term adverse effects on the fetus. There is limited data on CMV seroprevalence in pregnant women in Singapore, with last reported study dating back over two decades. We look at the latest CMV seroprevalence in antenatal population in Singapore. Methods Between January 2021 and August 2021, 385 pregnant women receiving antenatal care at Singapore General Hospital were randomly selected for CMV IgG test to be performed on their blood samples collected during the first trimester of their pregnancies. Positivity for CMV IgG represents past exposure prior to pregnancy. Results Overall CMV seroprevalence was 71.7% (276/385). The trend of CMV IgG positivity increased with age, 68.3% in those aged 20–29, 72.5% in the 30–39 age group, and 79.0% in women over 40. Conclusions There is a declining trend in CMV seroprevalence among pregnant women in Singapore, which indicates that a substantial portion of this population faces the risk of primary maternal CMV infection during pregnancy. Emerging research suggests that prenatal treatment with valacyclovir effectively reduces the likelihood of vertical transmission. Considering this evidence, it is imperative to reevaluate the recommendations for universal maternal CMV screening during pregnancy.
Parental practices that influence children’s development: how often are they implemented and by whom. Results from the NASCITA Birth Cohort study
Authors: Pandolfini Chiara , Clavenna Antonio , Campi Rita , Cartabia Massimo , Finazzi Stefano , Bonati Maurizio
Published: October 2023

Purpose
To assess how commonly 15 parental practices, known to have positive effects on child and adult health, are carried out by families in Italy, if they are related, and which characteristics are associated with implementation.
Methods
Children participating in the NASCITA Cohort, a prospective study in which family pediatricians in Italy collect data on children and their families, were included if they had sufficient data. Data on practice implementation, socio-demographic characteristics, and interrelatedness between practices were analyzed.
Results
In all, 3337 children were included. Their mothers had an average age at birth of 33 years (range 17–52), and medium-high levels of education (85.8% of mothers) and employment (71.9%). No smoking or alcohol in pregnancy, supine infant sleeping position, and tummy time were the most commonly implemented practices (by over 85% of mothers, each), while the least common was exclusive breastfeeding at 6 months (28.3%). Parental practices are related and several socio-demographic characteristics influence their implementation, with mother’s educational level and geographic area of residence influencing most of the practices (each influencing 12 of 15 practices). Low educational level (OR 0.34), being born abroad (OR 0.43), and residing in the South (OR 0.49), most reduce the probability of implementing numerous supportive practices (all three P < 0.001).
Conclusions
Socio-demographic factors contribute significantly to carrying out supportive practices. Future interventions should address the identified inequalities, prioritizing families most in need. Direct involvement of pediatricians is warranted given their favorable position for promoting positive behaviors.
A Preliminary Study on Calcifying Nanoparticles in Dental Plaque: Isolation, Characterization, and Potential Mineralization Mechanism
Authors: Wang Siwei , Yang Lan , Bai Guohui , Gu Yu , Fan Qin , Guan Xiaoyan , Yuan Jie , Liu Jianguo
Published: October 2023

Background Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the etiology of periodontal disease.Methods Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD).Results The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate.Conclusion CNPs were found in periodontitis-related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.
Selective RNAi-silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury
Authors: Itson-Zoske Brandon , Gani Uarda , Mikesell Alexander , Qiu Chengsheng , Fan Fan , Stucky Cheryl , Hogan Quinn , Shin Seung Min , Yu Hongwei
Published: October 2023

We previously reported functional Piezo1 expression in Schwann cells of the peripheral nervous system. This study is designed to further investigate the role of Schwann cell Piezo1 in peripheral nociception. We first developed an adeno-associated viral (AAV) vector that has primary Schwann cell tropism after delivery into the sciatic nerve. This was achieved by packing AAV-GFP transcribed by a hybrid CMV enhancer/chicken β-actin (CBA) promoter using a capsid AAVolig001 to generate AAVolig001-CBA-GFP. Five weeks after intrasciatic injection of AAVolig001-CBA-GFP in naïve rats, GFP expression was detected selectively in the Schwann cells of the sciatic nerve. A short hairpin RNA against rat Piezo1 (PZ1shRNA) was designed that showed efficient physical and functional knockdown of Piezo1 in NG108 neuronal cells. A dual promoter and bidirectional AAV encoding a U6-driven PZ1shRNA and CBA-transcribed GFP was packed with capsid olig001 (AAVolig001-PZ1shRNA), and AAV was injected into unilateral sciatic nerve immediately after induction of common peroneal nerve injury (CPNI). Results showed that the development of mechanical hypersensitivity in the CPNI rats injected with AAVolig001-PZ1shRNA was mitigated, compared to rats subjected with AAVolig001-scramble. Selective in vivo Schwann cell transduction and functional block of Piezo1 channel activity of primary cultured Schwann cells was confirmed. Together, our data demonstrate that 1) AAVolig001 has unique and selective primary tropism to Schwann cells via intrasciatic delivery and 2) Schwann cell Piezo1 contributes to mechanical hypersensitivity following nerve injury.
In-Silico and In-Vitro Evaluation of the Anti-Diabetic Activity of Gmelinol
Authors: Patel Virani Anilkumar , Tirgar Pravin R.
Published: October 2023

Purpose
The present study was investigated the anti-diabetic activity of Gmelinol using the in-silico molecular docking and in-vitro study.
Methods
In-silico study was performed using TriposSybyl-X 2.0 (TriposInc, St Louis, MO, USA) software and the evaluation was conducted based on the total score and visualization. In-vitro study was performed using the α-amylase inhibitory assay and α-glucosidase inhibitory assay and measured the percentage inhibition of the enzyme. The glucose uptake assay was also performed using L6 myoblast cell and measured the glucose utilization.
Results
Molecular docking studies demonstrated that Gmelinol was able to bind the active sites of proteins and the total score of Gmelinol with α-amylase and α-glucosidase were found 6.33 and 5.04 respectively. Gmelinol showed significant α-amylase and α-glucosidase inhibitory activities (IC50 = 45.92 µg/mL on α-amylase and IC50 = 49.25 µg/mL on α-glucosidase) compare with Acarbose (IC50 = 70.63 µg/mL α-amylase and IC50 = 64.82 µg/mL on α-glucosidase). Gmelinol showed significant glucose utilization activities in the L6 myoblast cell.
Conclusion
Gmelinol has shown anti-diabetic activity in terms of reducing the hyperglycaemia through the increased glucose utilization and inhibition of enzyme involved in carbohydrate metabolism namely α-amylase and α-glucosidase.