bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Two Years of Virginia’s Substantial Risk Order
Authors: Geller Lisa , McConnell Natalie , Zelle Heather , Roskam Kelly , Haas Lori , Bonnie Richard
Published: July 2023

Background.
Gun violence is a public health crisis in the United States. Extreme risk protection orders, called substantial risk orders in Virginia, are a prevention tool that temporarily remove firearms from individuals at risk of harm to self or others. To date, no peer-reviewed papers have explored the use of substantial risk orders in Virginia.
Methods.
We reviewed risk order data from Virginia from July 1, 2020, to June 30, 2022. The risk order data included in this study was obtained from the Virginia State Police Criminal Justice Information Services Division. We calculated descriptive statistics for the number and type of risk order (in total and by locality), demographic variables (sex, race, and age), and incidence rates.
Results.
There were 281 emergency risk orders and 173 final risk orders between July 2020 and June 2022. Most risk order respondents were white males in their mid-to-late 30s. Fifty-eight of the 133 localities in our study reported at least one risk order. However, the ten localities that issued the greatest numbers of risk orders issued 73% of all emergency risk orders and 67.6% of all final risk orders. Across the 58 localities in our dataset, the average incidence of emergency risk orders was 3 per 100,000 people per year and the average incidence of final risk orders was 2 per 100,000 people per year.
Conclusions.
The risk order is a relatively new law in Virginia. Though many of the descriptive statistics we calculated in Virginia are similar to what we see in other states with this law, more time is needed to examine its impact on gun violence.
Emerging Combination Strategy: FANCI Inhibition Induces PARP1 Redistribution to Enhance Efficacy of PARP Inhibitors in Breast Cancer
Authors: Huang Yu-zhou , Sang Ming-Yi , Xi Pei-wen , Xu Ruo-xi , Cai Meng-Yuan , Wang Zi-Wen , Zhao Jian-Yi , Li Yi-Han , Yin Peng , Wei Ji-Fu , Ding Qiang
Published: July 2023

Background
While PARP inhibitors have made advancements in the treatment of breast cancer, challenges such as chemotherapy resistance and limited application persist. FANCI, a DNA repair protein associated with breast cancer development, represents a potential target for novel combination therapeutic strategies. However, the role of FANCI in breast cancer and its impact on the efficacy of PARP inhibitors require further investigation.
Methods
In this study, we analyzed FANCI expression in breast cancer tissues and cell lines, and its correlation with clinical parameters and patient prognosis. Lentiviral vectors were utilized and functional assays were performed to evaluate the effects of FANCI modulation on breast cancer cell growth and metastasis. Co-immunoprecipitation assays and protein interaction analysis were conducted to identify the interaction between FANCI and PARP1 and determine the specific binding region. The functionality and nuclear distribution of PARP1 were assessed upon FANCI modulation. Finally, the sensitivity of breast cancer cells to the PARP inhibitor talazoparib upon FANCI knockdown was evaluated in vitro and in vivo.
Results
Our findings demonstrated that FANCI was overexpressed in breast cancer and associated with poor prognosis. FANCI significantly promoted breast cancer cell proliferation both in vitro and in vivo. We identified the interaction between FANCI and PARP1, specifically at the FANCI HD2 binding site. FANCI inhibition led to reduced nuclear localization of PARP1 and decreased PARP1 activity. Importantly, combination treatment with FANCI knockdown and talazoparib significantly inhibited cancer growth in vitro and in vivo. Additionally, we found that the CDK4/6 inhibitor palbociclib, which effectively suppresses FANCI protein expression, exhibited a robust synergistic effect with talazoparib both in vitro and in vivo.
Conclusion
FANCI is a novel therapeutic target for breast cancer. Inhibition of FANCI regulates PARP1 redistribution and activity, making cells more responsive to PARP inhibitors. This combination therapeutic strategy shows potential in enhancing the effectiveness of PARP inhibitors for breast cancer treatment, regardless of BRCA mutations.
Full-band Electromagnetic Stealth
Authors: Su Jian Xun , Qu Meijun , Yu Hang , Li Wen Yu , Yin Hong Cheng , Cui Tie Jun
Published: July 2023

The existing technologies to reduce radar cross sections (RCSs) face numerous challenges in bandwidth expansion, and hence they have a long way to achieve full-band stealth. Additionally, the control mechanism of RCS reduction level is deficient. Here, we explore the root of problem to cause the bandwidth blind zones and propose a mathematical model to establish a mapping relation between the array factor (AF) in spatial domain and the RCS reduction in frequency domain. The mathematical model of full-band stealth for general oblique incidence is also constructed, which guides to design a diffuse artificial meta-structure (AMS) to validate the proposed model. Then we build a mathematical model based on the Chebyshev polynomial for RCS reductions with RdB equal-amplitude in controlling the scattering fields. As proof of principle, a diffuse AMS is designed, fabricated, and measured to reach the RCS reductions with preseted 21 dB equal-amplitude. The simulated and measured results are in good agreement, proving that the proposed theoretical models provide a cornerstone of the future advanced stealth technologies.
Construct for Use and Recurring Use of Over-the-counter Herbal Health Products: Qualitative Insights From in-depth Interviews in Malaysia
Authors: Din Wardah Mustafa , Mahadi Zurina , Amin Latifah
Published: July 2023

Background
Inclination towards Herbal Health Products (HHP) among patients and consumers are increasing, especially after the Covid-19 pandemic. The aim of this study is to explore the various reasons behind the usage and recurring use of HHP among patients and consumers in Malaysia and understand the construct that motivates consumers to make a recurring purchase of HHPs.
Methods
To explore the purpose underlying usage of herbal health products (HHP) and its constructs of preferred choice and motivations for recurring use among Malaysians, this study employs a qualitative approach of in-depth interviews with 30 participants whom are consumers of any herbal health products in Malaysia. Participants were interviewed regarding their experiences and opinions using a semi-structured protocol, and data were transcribed and thematically analyzed.
Results
There are three main purpose of HHP usage among Malaysians, which are to treat illness, to control symptoms or pain related to illness and to prevent illness or promote general health. Among these identified purpose of usage, it is observed that usage of HHP for treatment are for non-chronic illnesses, whereas usage to control symptoms are for chronic illnesses. To explore the reasons further, it is observed that there are few constructs that make HHP the preferred choice among consumers which are perceived safety of the herbal products; its effectiveness to treat or control illness; perceived to have less side effects compared to conventional medicine; religious beliefs; and price worthiness of the product. Motivational constructs for repurchase of HHPs are perceived efficacy to health and well-being, reduction in prescribed medicine dosage and reasonable price.
Conclusion
In summary, there are myriad of reasons underlying the preferences towards the consumption of HHP among Malaysians and motivation for repurchase according to individual objectives. Awareness for safe use of HHP among consumers pertaining to the herbal ingredients needs to be promoted to align the purpose of use and its real efficacy towards illness management. Initiatives for safe use of HHP must be done in order to safeguard consumers from unnecessary health risks and adverse effects in HHP consumption.
The relationship between psychosocial behavior and the quality of life of male gout patients in southwest china: a cross-sectional study based on an information-motivation-behavioral skills model
Authors: Wang Ying , Guo Xin , Chen Bo , Chen Yanling , Chen Hong , Ma Ling , Liu Huan
Published: July 2023

Background
The health-related quality of life (HRQoL) of gout patients is poor, and studies have shown that providing psychosocial behaviors interventions can improve the HRQoL of gout patients, but there is no cross-sectional study on whether psychosocial behaviors affect the HRQoL of gout patients.
Methods
For this cross-sectional study, 225 male patients with gout were enrolled. HRQoL was assessed using the gout impact scale, and the gout knowledge questionnaire was used to assess patients´ degree of knowledge about the disease. The positive psycap questionnaire was used to assess positive psychological capacity and finally, the gout patient self-management assessment scale was used to assess self-management behaviors. Multiple linear regression was used to analyze the factors affecting HRQoL in gout patients.
Results
The overall mean gout impact scale score was 52.7 (maximum possible = 100). Factors associated with the total gout impact scale score were tophi (β = 4.746), pain intensity (β = 1.294), and resiliency (β=-0.559). In addition, demographic characteristics (education level, smoking and marital status), clinical characteristics (tophi, pain intensity, number of attacks over 6 months, and number of affected joints) and psychosocial behavior variables (resiliency, hope, disease treatment management, diet management) were associated with several dimensions of the gout impact scale.
Conclusions
The HRQoL of male gout patients in Southwest China was assessed as at a medium level. We found that clinical characteristics and psychosocial behaviors are important factors affecting the HRQoL in men with gout, and should be the focus for interventions.
Quality of Chronic Disease (Diabetes & Hypertension) Care in Health Care Facilities in High Diseas Burden Areas in Sidama Region: Cross-Sectional Study
Authors: Derese Bedilu Deribe , Tadesse Fikru , Dadi Gezaheng Bekele , Ayalew Mohammed , Borie Yacob Abraham , Alemayehu Tinbete Samuel , Aynalem Amdehiwot , Gechere Ephrem Geja , Gebrekidan Martha Girma , Debiso Alemu Tamiso , Alemayehu Akalewold , Jisso Meskerem , Mihrete Kindalem Worku , Fikre Rekik , Ejeso Amanuel , Abera Wendwesen
Published: July 2023

Background: Diabetes and hypertension are major synergistic risks factors for microvasculopathy, macroangeophathy and neuropathy problems among patients with chronic disorder. Control of hypertension and diabetes have significant value in delaying these complications. The key for delaying complications in diabetes and hypertension is the quality of care.
Objectives: This study explored the quality of diabetes-hypertension care in health care facilities with high disease burden in Sidaama region.
Methodology: An institution-based cross-sectional study was carried out. Patients with Diabetes and hypertension were included in the study. A total of 844 patients were included in the study. The Data was collected using the application software Kobocollect. For data analysis, SPSS version 25 was used. Logistic regression was used to identify factors associated with quality of care. To measure quality, we employed patient outcome indicators focusing on long-term complications of the eye, heart, fasting blood pressure, and neuropathic complications. Ethical approval clearance was obtained from Hawassa University, college of medicine and health sciences ethical review board.
Result: The mean age of patients was 47.99 + 15.26 years with a range of 18–90 years while. Men make up 62% of the overall number of respondents. In terms of marital status, 700 (82.9%) were married. Concerning place of residence; 433 (51.3%) were from rural area. The primary diagnosis is diabetes for 419(49.6%) patients and nearly 23% of patients have both Diabetes and hypertension. Regarding blood pressure the mean diastolic blood pressure was 82.6 mmhg with mean systolic blood pressure of 129.6 mmhg. Among study participants 391 (46.33%) patients received poor quality of chronic disease care. Patients living alone, patients who have professional work, fasting blood glucose in normal range, patients with higher education and patients with serum creatinine receives relatively good chronic illness care.
Optimizing the Process Conditions of Corn Oil Methyl Ester for Bioresin Production
Authors: Huda Md Sanaul , Odegaard Michael , Sarker Niloy , Webster Dean , Monono Ewumbua
Published: July 2023

The conversion of corn oil into quality methyl ester through the transesterification process is an age-old concept. Because of its higher degree of unsaturation, similar to soybean oil, transesterified corn oil has promising properties to produce bio-based resin. Replicating published methods did not result in desired quantity and quality of corn methyl ester needed for bio-resin production, which requires further investigation. This research investigated the effect of different reaction conditions on the yield and quality of methyl ester produced from corn oil. The reaction was conducted at 60°C with a methanol-oil ratio of 6:1 and NaOH as a catalyst. Hypothesized recovered yield (> 70%) of corn methyl ester was achieved after stopping the reaction with HCl. The process was conducted at different reaction times (0.5, 1, and 1.5 h) and acid amounts (0, 1.3, 2.6, 3.9, and 5.2 mL). The methyl ester yield ranged from 45–79%. A statistical model was obtained with linear and quadratic terms, and the recovered yield varied significantly with the acid amount, reaction time, and their interactions. The addition of 2.6 mL acid after the transesterification process resulted in a 15–25% increased yield compared to no acid treatment. On the other hand, the yield was reduced 18–24% with increasing time when no acid was added. All the measured characteristics of the produced corn methyl ester sample were found within the limits of ASTM D6751 pure methyl ester. Overall, the optimization of the transesterification process showed promise in increasing the yield of quality methyl ester from corn oil.
Inflammasomes in Rheumatoid Arthritis: A Pilot Study
Authors: Jiang Qi , Wang Xin , Xu Xiuping , Hu Liangfeng , Zhou Guozhong , Liu Rui , Yang Guocan , Cui Dawei
Published: July 2023

Background
The inflammasome plays an important role in rheumatoid arthritis (RA), which was little systematically reported. The aim of this study was to understand whether the levels of inflammasome were related to the severity of RA disease, which might provide a stronger theoretical basis for RA treatment.
Methods
The mRNA expression levels of some inflammasomes and associated molecules including IL-1beta and IL-18 in peripheral blood peripheral blood mononuclear cells (PBMCs) from 30 RA patients (n = 30) and 16 healthy controls (HC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of plasma IL-1beta and IL-18 were also measured by Enzyme-Linked Immunosorbent Assay (ELISA). Moreover, clinical characteristics and laboratory results of the patients were collected and analyzed in this study.
Results
Compared to HC group, the relative mRNA expression levels of NLRP3, NLRC4, AIM2, caspase-1, and IL-1beta were significantly higher, but notably lower in NLRP1, NLRP2 and NLRC5 in RA group. Moreover, the plasma IL-1beta and IL-18 levels were markedly increased in RA group. Additionally, the mRNA level of AIM2 was negatively correlated with DAS28 by stepwise linear regression analysis. and ESR was positively correlated with DAS28 by multiple linear regression analysis in RA group.
Conclusions
These findings implied the critical role of NLRP3, NLRC4, AIM2, caspase-1 mRNA, plasma IL-1beta and IL-18 in the pathogenesis of RA patients, which provided potential targets for the diagnosis and treatment of RA.
Finnish Internet Parsebank
Authors: Luotolahti Juhani , Kanerva Jenna , Luoma Jouni , Skantsi Valtteri , Pyysalo Sampo , Laippala Veronika , Ginter Filip
Published: July 2023

We present a Finnish web corpus with multiple text sources and rich additional annotations. The corpus is based in large parts on a dedicated Internet crawl, supplementing data from the Common Crawl initiative and the Finnish Wikipedia. The size of the corpus is 6.2 billion tokens from 9.5 million source documents. The text is enriched with morphological analyses, word lemmas, dependency trees, named entities and text register (genre) identification. Paragraph-level scores of an n-gram language model, as well as paragraph duplication rate in each document are provided, allowing for further filtering of the dataset by the end user. Thanks to changes in the 2023 Finnish copyright legislation, the corpus is openly available for research purposes, and can also be accessed through the NoSketchEngine concordance tool and the dep search dependency tree query tool, all at https://turkunlp.org/finnish nlp.html.
Codon usage bias analysis of the gene encoding NAD+-dependent DNA ligase protein of invertebrate iridescent virus 6
Authors: DIZMAN YESIM AKTÜRK
Published: July 2023

The genome of Invertebrate iridescent virus 6 (IIV6) contains a sequence that shows similarity to eubacterial NAD+-dependent DNA ligases. The 615-amino acid open reading frame (ORF 205R) consists of several domains, including an N-terminal domain Ia, followed by an adenylation domain, an OB-fold domain, a helix-hairpin-helix (HhH) domain, and a BRCT domain. Notably, the zinc-finger domain, typically present in NAD+-dependent DNA ligases, is absent in ORF 205R. Since the protein encoded by ORF 205R (IIV6 DNA ligase gene) is involved in critical functions such as DNA replication, modification, and repair, it is crucial to comprehend the codon usage associated with this gene. In this paper, the codon usage bias (CUB) in DNA ligase gene of IIV6 and 11 reference iridoviruses was analyzed by comparing the nucleotide contents, relative synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation index (CAI), relative abundance of dinucleotides and other indices. Both the base content and the RCSU analysis indicated that the A- and T-ending codons were mostly favoured in the DNA ligase gene of IIV6. The ENC value of 35.64 implied a high CUB in the IIV6 DNA ligase gene. The ENC plot, neutrality plot, parity rule 2 plot, correspondence analysis revealed that mutation pressure and natural selection had an impact on the CUB of the IIVs DNA ligase genes. This findings will improve our comprehension of the CUB of IIV6 DNA ligase and reference genes, which may provide the required information for a fundamental evolutionary analysis of these genes.
Investigation of Tensile behaviour, Seizure Conditions and Frictional Characteristics of Al-Zn-Cu-Mg Alloy based composites
Authors: Kumar Ashish , Rana R. S. , Purohit Rajesh , Baghel Madhusudan , Namdev Anurag , Kumar Rajan
Published: July 2023

In a current scenario, light weighted composites are the prime need of manufacturers in aerospace, automotive, marine and other applications due to their excellent properties compared to traditional materials. The current study includes the fabrication of Al Alloy 7068-based composites reinforced with Si3N4 nanoparticles by 0.5 to 2.0 wt. % by maintaining a difference of 0.5 wt. % through stir casting approach advanced with ultrasonic treatment. Wear resistance and tensile strength were significantly improved with Si3N4 addition. A small decrement in tensile strength was noticed at 2 wt. % due to the agglomeration of particles. Wear loss increased with applied stress, sliding velocity and sliding distance. COF also increased with sliding distance but decreased with applied stress. There is a significant increment in seizure pressure noticed with reinforcement addition. Abrasive wear dominates at a higher applied stress and sliding distance due to the clustering of particles.
Calculating kill intervals for a specific prey from GPS location cluster data of a predator
Authors: Vogt Kristina , Roth Tobias , Signer Sven , Willisch Christian , Amrhein Valentin
Published: July 2023

An increasing number of GPS telemetry studies have helped to gain important insights into predator-prey relationships in the last years. However, considerable time and effort have to be invested to evaluate whether GPS location clusters (GLCs) reflect predation events. To reduce field effort, predictive models are being developed to calculate predator kill intervals, but few studies have attempted to do this for one specific prey species. Between 2013 and 2018, we studied predation of 13 GPS-collared Eurasian lynx (Lynx lynx) on Alpine chamois (Rupicapra rupicapra) in the Northwestern Swiss Alps. Our objectives were to predict the total number of killed chamois, including potential kills in unchecked GLCs, and to evaluate if model predictions were accurate enough for practical use. We built a set of generalized linear models (GLM) predicting the occurrence of GLCs containing killed chamois versus GLCs containing other prey types or no prey and compared their predictive performance by means of k-fold cross-validation. We found that model performance was very similar for all candidate models, with the full model yielding the best cross-validation result (accuracy = 0.83, sensitivity = 0.43, specificity = 0.94). Female lynx killed on average one chamois every 11.9 days (10.6–13.0 days, 95% CI); male lynx killed one chamois every 7.2 days (6.7–7.6 days, 95% CI). We conclude that our modelling results were sufficient for practical application. However, this approach does not replace extensive fieldwork but depends both on fieldwork and thorough knowledge of the predator’s ecology and prey community. It may provide useful results only for binary classifications in rather simple predator-prey systems, and results cannot easily be extrapolated from one study area to another.
Annual and Lunar-Related Breeding Rhythmicity in the Acorn Barnacle Tetraclita kuroshioensis (Chan, Tsang & Chu, 2007) in Okinawa, Japan
Authors: Katayama Aoi , Tan Ee Suan , Takekata Hiroki , Takemura Akihiro
Published: July 2023

Barnacles, a class of marine crustaceans, have adapted to various environments. This study investigated the breeding activity of Tetraclita kuroshioensis, a species prevalent on the coast of Okinawa Island, Japan, with a focus on gonadal development, the retention of eggs and larvae at different levels of attachment sites, and the role of environmental factors in their breeding rhythmicity. Monthly collections of T. kuroshioensis were conducted around the full moon from September 2019 to October 2020. Histological observations showed varying oocyte developmental stages in ovaries collected from September to October 2019 and March to September 2020. Developed testes were obtained from April to October. The breeding season of this species lasts for at least 7 months and is influenced by water temperature. Samples collected in April, August, and October displayed little variation in ovarian development across attachment sites; however, there was a noticeable vertical difference in egg and larval retention, with a preference for the new moon phase in the upper and middle parts of attachment sites in August and October. The findings indicate that T. kuroshioensis larval release exhibits seasonal variation, influenced by the lunar and tidal cycles of their habitat.
Construction Risk Assessment of Super- Large-Diameter Shield Tunnel in Karst Area Based on FAHP-TOPSIS Method
Authors: Wenzhou Wang , Xifeng Yang , Yong Cheng , Jiguo Liu , ming Song , cong Zhang
Published: July 2023

In recent years, construction accidents happen frequently in shield tunnel crossing karst caves due to the complex karst geological structure. These are more obvious in super-large-diameter shield tunnel during construction. In the past, the results of risk assessment tended to be subjective since these reviews were mainly based on experience. A super-largediameter tunnel model is constructed by using calculation principle of FAHP-TOPSIS method based on quantitative analysis and objective weighting method to conduct risk assessment in karst area based on risks evaluated in a shield tunnel project under construction in a city. The risk classification is formulated, and the risk assessment system for a super-large-diameter shield tunnel under construction in karst area is developed to perform computation for assessment. The results show that the closeness of the construction risk for shield tunnel with super-large-diameter crossing the karst area is 0.034, and the risk level is V, that is, high risk, which brings great potential safety hazard to tunnel construction. The computation results are consistent with those of site conditions to verify the feasibility and effectiveness of the method. The results have provided reference for the risk assessment of similar engineering practice under construction.
Glutamate Secretion by Embryonic Stem Cells as an Autocrine Signal to Promote Proliferation
Authors: Lin Teng , Qin Qin , Zhou Ziyi , Zhou Fei , Cao Chunyu , Yang Jian , Ding Jia wang
Published: July 2023

Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate NMDA receptor, and cell membrane excitatory amino-acid transporter. We directly quantified the released glutamate signal using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.
Mechanistic study on the micro-optical morphology and electrical properties of microchannel plates by acid-base alternating corrosion processes
Authors: Li Tao , Wang Jian , Cong Xiaoqing , Pan Kai , Li Wankai , Jin Ge , Qiu Xiangbiao , Lin Yanjian
Published: July 2023

As a two-dimensional vacuum electron multiplier device, the microchannel plate is made by solid method with lead silicate glass as the base material, and acid-base etching to remove the core material is a key step in the formation of the microchannel plate, which mainly affects the microstructure, morphology and composition of the inner wall surface, and then affects the electrical properties of the microchannel plate. The microscopic morphology of silicate glass under different etching processes was studied by scanning electron microscopy, and it was found that with the increase of acid-base alternation during the etching process, the particle density of the inner wall of the channel gradually decreased, and the energy spectrum analysis of the particles revealed that the main contents were Pb and Bi; further by AFM analysis, the particle peak height was reduced from 31.1 nm to 1.9 nm with roughness. The results of the electrical and noise properties of the microchannel plates show that an appropriate increase in acid-base alternation can effectively reduce the bulk resistance and dark current without reducing the gain of the microchannel plates. This shows that increasing the "erosion intensity" of the acid-base alternation multiple times during corrosion can effectively improve the core-skin diffusion layer, further affecting the physical and chemical transformation of the nanoscale morphology, pointing to a new direction for improving the electrical properties of microchannel plates made of silicate glass.
Semiautomated approach focused on new genomic information results in time and effort- efficient reannotation of negative exome data
Authors: Ferrer Alejandro , Duffy Patrick , Olson Rory J. , Meiners Michael A. , Schultz-Rogers Laura , Macke Erica L. , Safgren Stephanie , Morales-Rosado Joel A. , Cousin Margot , Oliver Gavin R. , Rider David , Williams Megan , Pichurin Pavel N. , Deyle David R. , Morava Eva , Gavrilova Ralitza H , Dhamija Radhika , Wierenga Klass J. , Lanpher Brendan C. , Babovic-Vuksanovic Dusica , Kaiwar Charu , Vitek Carolyn R. , McAllister Tammy M. , Wick Myra J. , Schimmenti Lisa A. , Lazaridis Konstantinos N. , Vairo Filippo Pinto e , Klee Eric W.
Published: July 2023

Introduction:
Most rare disease patients (75 − 50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding disease-causing variants and genes, increasing this diagnostic yield. However, time and resource constraints have limited reanalysis of genetic data in clinical laboratories setting. We developed RENEW, (REannotation of NEgative WES/WGS) an automated reannotation procedure that uses relevant new information in on-line genetic databases to enable rapid review of genetic findings.
Methods
We tested RENEW in an unselected cohort of 1,066 undiagnosed cases from the Mayo Clinic Center for Individualized Medicine using new information in ClinVar, HGMD and OMIM between the date of previous analysis/testing and April of 2022.
Results
5,741 variants prioritized by RENEW were rapidly reviewed by variant interpretation specialists. Mean analysis time was approximately 20 seconds per variant (32 hours total time). Reviewed cases were classified as: 879 (93.0%) undiagnosed, 63 (6.6%) putatively diagnosed, and 4 (0.4%) definitively diagnosed.
Discussion
New strategies are needed to enable efficient review of genomic findings in unsolved cases. We report on a fast and practical approach to address this need and improve overall diagnostic success in patient testing through a recurrent reannotation process.
Crosstalk between glial Cx43 and neuronal Panx1 and P2X7 receptors modulate presynaptic homeostatic plasticity
Authors: Rafael Alberto , Tizzoni Marina , Justet Cristian , Cairus Andrea , Abudara Verónica , Vitureira Nathalia
Published: July 2023

The emerging role of glial cells in the modulation of neuronal excitability and synaptic strength is a growing field in neuroscience. An increased number of studies indicate that gliotransmission is mediated by both the classical Ca2+-dependent release and the non-vesicular route mediated by connexin and pannexin hemichannels. Recent reports highlighted the role of gliotransmission in the homeostatic adjustment of synaptic strength. In particular, glial-derived ATP arises as a key mediator in this process. However, very little is known about the glial non-vesicular ATP-release pathway and how this ATP could participate in the modulation of synaptic strength. Here we investigated the functional changes occurring in the presynaptic terminal and the role of the purinergic signaling, connexin43 and pannexin1 hemichannels in this process. By using hippocampal dissociated cultures, we show that glial connexin43-dependent ATP release triggers the homeostatic adjustment of presynaptic remodeling and function upon chronic activity silencing. Notably, activated neuronal P2X7Rs play an essential role in this process by mediating the entrance of Ca2+ to the presynaptic cell; our data also suggest that the functional crosstalk between neuronal P2X7Rs and pannexin1 hemichannels is required for the compensatory adjustment of presynaptic function. Interestingly, we show that neuronal permeability is regulated during chronic inactivity and, in particular, we found that neuronal pannexin1 hemichannels are gradually opened, increasing their activity upon 12h of neuronal inactivity. Hence, our results show for the first time the glial-dependent changes occurring in the presynaptic terminal upon chronic activity silencing and highlight the role of the interaction between presynaptic P2X7Rs and pannexin1 in the homeostatic adjustment of presynaptic strength.
Primate-specific isoform of Nedd4-1 regulates substrate binding via Ser/Thr phosphorylation and 14-3-3 binding
Authors: Kefalas George , Rotin Daniela
Published: July 2023

Nedd4 (Nedd4-1) is an E3 ubiquitin ligase involved in crucial biological processes such as growth factor receptor signaling. While canonical Nedd4-1 comprises a C2-WW(4)-HECT domain architecture, alternative splicing produces non-canonical isoforms that are poorly characterized. Here we characterized Nedd4-1(NE), a primate-specific isoform of Nedd4-1 that contains a large N-terminal Extension (NE) that replaces most of the C2 domain. We show that Nedd4-1(NE) mRNA is ubiquitously expressed in human tissues and cell lines. Moreover, we found that Nedd4-1(NE) is more active than the canonical Nedd4-1 isoform, likely due to the absence of a C2 domain-mediated autoinhibitory mechanism. Additionally, we identified two Thr/Ser phosphoresidues in the NE region that act as binding sites for 14-3-3 proteins, and show that phosphorylation on these sites reduces substrate binding. Finally, we show that the NE region can act as a binding site for the RPB2 subunit of RNA polymerase II, a unique substrate of Nedd4-1(NE) but not the canonical Nedd4-1. Taken together, our results demonstrate that alternative splicing of the ubiquitin ligase Nedd4-1 can produce isoforms that differ in their catalytic activity, binding partners and substrates, and mechanisms of regulation.
An innovative mobile application (CAITOM ® ) for assessment of oral and maxillofacial trauma
Authors: de Souza Glaciele Maria , de Oliveira Gabriel Narcisio Vieira , Lacerda Allysson Steve Mota , Falci Saulo Gabriel Moreira
Published: July 2023

The use of technological resources, such as mobile applications, in the health area has become a growing reality that aims to improve service delivery from diagnosis to prognosis with greater practicality.
Background/ Aim: present an epidemiological survey of victims of maxillofacial trauma and the technological development of a checklist for auxiliary diagnostic evaluation of these patients.
Methods: A questionnaire was used to study the epidemiological profile of victims of maxillofacial trauma. For the development of the mobile application, a previously developed and validated checklist was used. This application developed was called CAITOM® (Checklist for Initial Assessment of Oral and Maxillofacial Trauma).
Result: The epidemiological profile found in this study is similar to those found in literature wherein victims of facial trauma are male, with age in the second or third decade of life, without marital bond, lower income and low education, rural workers, and victims of traffic accidents. Concurrently with this investigation, the Caitom® was designed for the Android system. Its layout is simple and intuitive so that any professional with knowledge of specific technical terms can use it. Through Caitom® the professional has a screenplay to help him in the initial assessment of victims of maxillofacial trauma.
Conclusion: It is estimated that the use of CAITOM® can practically systematize the diagnostic evaluation of patients with oral and maxillofacial trauma.
Identification of Clinically Relevant Patient Endotypes in Traumatic Brain Injury Using Latent Class Analysis
Authors: Qiu Hongbo , Zador Zsolt , Lannon Melissa , Farrokhyar Forough , Duda Taylor , Sharma Sunjay
Published: July 2023

Traumatic brain injury (TBI) is a complex condition where heterogeneity impedes the advancement of care. Understanding the diverse presentations of TBI is crucial for personalized medicine. Our study aimed to identify clinically relevant patient endotypes in TBI using latent class analysis based on comorbidity data. We used the Medical Information Mart for Intensive Care III database, which includes 2,629 adult TBI patients. We identified five stable endotypes characterized by specific comorbidity profiles: Heart Failure and Arrhythmia, Healthy, Renal Failure with Hypertension, Alcohol Abuse, and Hypertension. Each endotype had distinct clinical characteristics and outcomes: The Heart Failure and Arrhythmia endotype had lower survival rates than the Renal Failure with Hypertension despite featuring less comorbidities overall. Patients in the Hypertension endotype had higher rates of neurosurgical intervention but shorter stays in contrast to the Alcohol Abuse endotype which had lower rates of neurosurgical intervention but significantly longer hospital stays. Both endotypes had high overall survival rates comparable to the Healthy endotype. Logistic regression models showed that endotypes improved the predictability of survival compared to individual comorbidities alone. This study validates clinical endotypes as an approach to addressing heterogeneity in TBI, and demonstrates the potential of this methodology in other complex conditions.
Characterization of changes in annual urban air temperature with special reference to the city of Modena: Comparison between regression models and proposal for a new index to evaluate relationship between environmental variables.
Authors: Morlini Isabella , Albertson Sean , Orlandini Stefano
Published: July 2023

It is commonly recognized that the observed increase in global mean annual air temperature is strongly related to the increase in global CO2 concentration C, and that both these variables are related to global development. It remains, however, unclear the degree to which local mean annual urban air temperature T is affected by local variables such as annual precipitation depth P and urban area extent A. This study assumes that A is a proxy of local development and C is a proxy of global development and investigates the commingled effects of A, P, and C on T by using long-term annual data observed over the years 1881–2019 from the Modena Observatory in Italy. Linear relationships between T, C and A are found to be spurious since all these series have a monotonic increasing trend with time. Parametric analytic models like logistic functions are found to lack flexibility. Smoothing splines can only give insights into the strength of the relationships but not on their shape defining the functional relationship between variables. Advanced nonlinear models like generalized additive models, instead, are found to combine flexibility in a parametric form, and appear therefore to be suitable models for explaining the complex relationships between A, P, and C on T. The different models are evaluated using traditional goodness of fit statistics like R2, BIC, AIC and a new index of relation IR which is introduced to jointly evaluate the goodness-of-fit of relationships between variables that may either be dependent or independent.
Diversity of Heading date 1 (Hd1) gene that conditioning flowering time in traditional tropical japonica and traditional indica rice from Thailand
Authors: Prathepha Preecha
Published: July 2023

The traditional rice cultivars are genetic resources in breeding programs that possess variable of DNA sequence of genes, but variants of gene of these resources have been limited in Thailand. Therefore, DNA sequence variation of the heading date 1 (Hd1) gene was explored in these rice cultivars collected from north (tropical japonica rice) and northeastern (indica rice) regions of the country. Results from re-sequencing of the Hd1 gene identified 3 non-synonymous SNPs in coding sequence (exon2) and there are four SNPs in noncoding sequence of the gene. First nonsynonymous SNP, AGT/GGT leading to amino acid sequence changes in Hd1 protein at position 339 of 407 residues. The allele S (AGT:Serine) of Hd1 gene were dominant in tropical japonica rice in northern region. Whereas the allele G (GGT:Glycine) was mostly found in indica rice from northeastern region. In addition, two traditional cultivars from the northern, a premature stop codon at exon2 was identified. Furthermore, 2 others nonsynonymous SNPs was distributed in both populations, including allele S (AGC:Serine) was dominant in tropical japonica rice, while the allele A (AGA:Arginine) were mostly found in indica rice. The muations may affect Hd1 gene structures and may contribute to intraspecific flowering time adaptations.
Plasma Modification of Graphene Nanoplatelets Surfaces
Authors: Johnson Tyler , Wang Keliang , Fan Qi Hua , Lee Andre
Published: July 2023

Atmospheric plasma processing, which combines the efficacy of chemical processes and the safety of physical processes, has been used to modify the surface characteristic of graphite-based materials. In this work, two distinct plasma source gases, C4F8 and O2, with the addition of a rotary reactor were used. The effectiveness to modify the basal plane of intercalated graphite nanoplatelets (GnP) was investigated with various analytical techniques and the visual observation of the dispersion of these plasma-treated GnP in solvents was also reported. It is shown that this low-temperature plasma processing technique can be used to successfully modify the GnP surface without significantly changing the intrinsic structure of the GnP, which is desirable in many applications. With the C4F8 plasma treatment, the immersion characteristics in solvents can be tuned and the functional groups present on the surface can be tailored to produce desired bonding environments. This surface chemistry tunability is expected to provide the needed functionalities in creating graphene-containing composite materials.
Turing cationic antimicrobial peptide KR-12 into Self-assembled nanobiotics with potent bacterial killing and LPS neutralizing activities
Authors: Lei Ruyi , Sun Yaqi , Zhu Tao , Yang Chujun , Zhu Zhiqiang , Li Dejian , Yang Yunqing , Hao Liman , Li Yang , Wu Shuijing , Cui Hongwei , Jiang Yuming , Xie Jiafeng , Pei Hui , Li Jiye , Mao Yujing , Lan Chao , Zhu Changju , Fang Xiangming
Published: July 2023

Gram-negative sepsis has become one of major increasing medical burdens globally, which is subjected to growing antibiotic resistance problem and the relatively delayed development of new antibiotics. LL-37, the only type of Cathelicidin identified in humans, has diverse biological activities including direct bactericidal action, regulation of inflammation and LPS-neutralization. The KR-12 peptide is the smallest portion of LL-37 with antibacterial action, which has been shown that could be modified into more effective antimicrobials. Here, we synthesize two myristoylated derivatives of KR-12, Myr-KR-12N and Myr-KR-12C, which can spontaneously form nanoparticles when mixed with deionized water. We show that myristoylated KR-12 derivatives possess a broad-spectrum and more powerful bactericidal activity through interrupting the membranes of bacteria. Myr-KR-12N rescues mice from lethal sepsis induced by E. coli, even more potent rescuing activity than meropenem. We also demonstrate that myristoylated KR-12 nanobiotic can significantly bind with LPS and inhibit the inflammation in vitro and Myr-KR-12N rescue mice from LPS-induced sepsis in vivo, even more potent rescuing activity than polymyxin B. Toxic experiments indicate that neither Myr-KR-12N nor Myr-KR-12C nanobiotics exhibits meaningful hemolytic activity, liver and kidney injury. We thus developed a novel nanobiotic with dual bactericidal and LPS-neutralization properties, which may provide good insights for clinical translation of antimicrobial peptides and the creation of new antibiotics.
Carbothermal Reduction of SiO2 using different coal
Authors: Li Fei , Yang Kaixin , Fu Wangwang , Wang Dahui
Published: July 2023

In this study, the carbon thermal reduction of agglomerate composed of pure silica and carbon was studied at 1898 K, 1923 K, and 1948 K. The main product of this reaction is silicon carbide. Compare the reduction effects of four types of coal from different industrial silicon enterprises on the analysis of pure silica, and explore the application of different coal in silicon production. C4 coal has high SiO reactivity, while C1 coal has low SiO reactivity. An increase in temperature will reduce the reaction matching degree of coal and increase the amount of SiO gas escaping. C4 coal has a high and stable reaction matching degree, and the reaction rate is less affected by temperature, making it the best coal among the four types to produce SiC.
Dietary Patterns and Common Diseases in Chinese Elderly: Exploring Associations and Providing Guidance for Personalized Interventions
Authors: Tian Zheng , He Jingchun , Li Yimiao , Zhang Zhijun , Zhang Nan , Wang Lan
Published: July 2023

Background: Specific dietary patterns significantly ameliorate or worsen the risk of certain diseases. However, the relationship between multiple geriatric diseases and dietary patterns remains unclear and the dietary patterns in the current literature may not apply to the Chinese elderly population. This study sought to analyze the major dietary patterns of the Chinese elderly in a large sample population and explore the association between these dietary patterns and 16 prevalent diseases to guide dietary interventions for geriatric populations.
Methods: CLHLS 2018 were analyzed in the present study. 13 types of food and 16 common diseases were extracted from the CLHLS database. Principal component analysis was employed to identify the main dietary patterns of the Chinese elderly, and binary logistic regression models were used to analyze the associations between these dietary patterns and the 16 common diseases.
Results: Four main dietary patterns were identified in the Chinese elderly population: Egg-Milk Pattern, Salt-preserved vegetable-Nut Pattern, Vegetable-Fruit Pattern, and Fish-Meat Pattern. Higher scores for the Egg-Milk Pattern were associated with a greater risk of heart disease, stroke or cardiovascular disease, respiratory disease, glaucoma, prostate tumor, and Parkinson's disease in older adults (p<0.05). Higher scores for Salt-preserved vegetable-Nut Pattern correlated with a greater risk of hypertension, heart disease, and uterine tumors and a lower risk of rheumatism or rheumatoid disease in older adults (P<0.05). The higher scores of the Vegetable-Fruit Pattern were associated with a lower risk of heart disease in older adults (p<0.05). Finally, higher scores of the Fish-Meat Pattern correlated with a lower risk of heart disease, stroke, and cardiovascular disease and a greater risk of rheumatic or rheumatoid disease in older adults (p<0.05).
Conclusions: Much heterogeneity surrounds the recommended dietary patterns for common diseases in elderly patients. A Salt-preserved vegetable-nut pattern is recommended for rheumatic diseases, while vegetable-fruit and fish-meat patterns are recommended for heart disease. Patients with stroke or cardiovascular disease are recommended to adopt the fish-meat pattern. However, the same dietary pattern may have contrasting effects on different diseases. Therefore, dietary guidance for elderly individuals should be personalized based on their specific health conditions. Accurate and tailored recommendations are crucial for promoting optimal health outcomes.