bluuebunny/crossref_metadata_2025 huggingface dataset:
White Blood Cell Variability and Clinical Outcomes in Hospitalized Patients With COVID-19
Authors: Yu Peng , Xia Panpan , Li Zhangwang , Zhang Jing , Ma Jianyong , Xu Minxuan , Zhou Yicheng , Shen Yunfeng , Liu Xiao
Published: February 2022

Background: Inflammation parameters, such as white blood cell (WBC) counts, are closely related to the severity and mortality of Coronavirus disease 2019 (COVID-19). Nevertheless, the association between inflammation fluctuation and clinical outcomes in patients with COVID‐19 is not clear.Methods: We performed a secondary analysis of the ORCHID trial. Inflammation fluctuation was assessed by WBC variability indices (SD [standard deviation], and CV [coefficient of variation]). Cox regression was used to compute the hazard ratio for WBC variability and associated hospitalization and death over 28 days.Results: During the 28 days post-randomization, 46 (10.8%) patients died, and 345 (81.4%) patients were discharged. In multivariable analysis, a worse clinical outcome, including decreased risk of hospital discharge (SD: HR: 2.32; P<0.001; CV: 1.72; P=0.001) and increased mortality (SD: HR: 1.51; P=0.002; CV: 1.35; P=0.006), was found with increased WBC variability. Furthermore, WBC variability had moderate performances in predicting discharge (C-index, SD: 0.705; CV: 0.703), and all-cause death over 28 days (C-index, SD: 0.632, CV: 0.688). Sensitivity analyses that involved changing 28-day mortality to in-hospital mortality, recalculating the WBC indices by using the lowest WBC value, and using the competing risk model generated confirmatory results. Most of the interactions between sex, age (>65), hydroxychloroquine treatment group, and WBC variability indices were not significant (P>0.05).Conclusion: In conclusion, our results showed that COVID-19 patients with higher WBC variability had lower discharge rates and higher mortality. Our study contributes to our understanding of the relationship between inflammation and COVID-19-related adverse outcomes.Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT04332991.
Emergency Cricothyroidotomy in Difficult Airway Simulation – A National Observational Study of Air Ambulance Crew Performance
Authors: Andresen Åke Erling L. , Kramer-Johansen Jo , Kristiansen Thomas
Published: February 2022

Background
Advanced prehospital airway management include complex procedures carried out in challenging environments, necessitating a high level of technical and non-technical skills. We aimed to describe Norwegian Air Ambulance-crews’ performance in a difficult airway scenario simulation, ending with a “cannot intubate, cannot oxygenate”-situation.
Methods
The study describes Air Ambulance crews´ management of a simulated difficult airway scenario. We used video-observation to assess time expenditure according to pre-defined time intervals and technical and non-technical performance was evaluated according to a structured evaluation-form.
Results
Thirty-six crews successfully completed the emergency cricothyroidotomy with mean procedural time 118 (SD: ±70) seconds. There was variation among the crews in terms of completed procedural steps, including preparation of equipment, patient- monitoring and management. The participants demonstrated uniform and appropriate situational awareness, and effective communication and resource utilization within the crews was evident.
Conclusions
We found that Norwegian Air Ambulance crews managed a prehospital “cannot intubate, cannot oxygenate”-situation with an emergency cricothyroidotomy under stressful conditions with effective communication and resource utilization, and within a reasonable timeframe. Some discrepancies between standard operating procedures and performance are observed. Further studies to assess the impact of check lists on procedural aspects of airway management in the prehospital environment are warranted.
The Impact of Road Safety Strategy and Policy on Admissions to A National Rehabilitation Hospital; a 5-year Retrospective Review and Reflection on Trauma Data
Authors: Carroll Áine , Sukumar Prasanth , O'Keeffe Aisling
Published: February 2022

Background:Globally, road traffic collisions (RTCs) are a common cause of death and disability. Although many countries, including Ireland, have road safety and trauma strategies, the impact on rehabilitation services is unclear. This study explores how admissions with RTC related injuries to a rehabilitation facility has changed over 5 years and how they contrast to major trauma audit (MTA) serious injury data from the same timeframe. Methods:A retrospective review of healthcare records with data abstraction in accordance with best practice was performed. Chi square test was used to determine associations and statistical process control was used to analyse variation. All patients discharged with an International Classification of Diseases (ICD) 10 coded diagnosis of Transport accidents from 2014-2018 were included. Results:338 cases were identified. Of these, 173 did not meet the inclusion criteria (readmissions) and were excluded. The total number analyzed was 165. Of these, 121 (73%) were male and 44 (27%) were female and 115 (72%) were under 40 years of age. The majority [128 (78%)] had traumatic brain injuries (TBI), 33 (20%) had traumatic spinal cord injuries and 4 (2.4%) had traumatic amputation The numbers varied over the time period of the study but showed normal variation and not special cause variation which suggests no significant impact of policy in the time frame. There was a large discrepancy between the number of severe TBIs reported in the MTA reports and the numbers admitted with RTC related TBI to the NRH. This suggests there may be many people not accessing the specialist rehabilitation services they require. Conclusion:Data linkage between administrative and health datasets does not currently exist but offers huge potential for understanding the trauma and rehabilitation ecosystem in detail. This is required to better understand the impact of strategy and policy.
PIK3CA-AKT Pathway Predominantly Acts in Developing Ipsilateral Breast Tumor Recurrence Long After Breast Conserving Surgery
Authors: Nakagomi Hiroshi , Inoue Masayuki , Hirotsu Yosuke , Amemiya Kenji , Mochiduki Hitoshi , Omata Masao
Published: February 2022

Purpose: Ipsilateral Breast Tumor Recurrence (IBTR) after breast-conserving therapy is seen after a long interval, but the clinical classification of Residual Tumor Recurrence (RR) or Double Primary (DP) needs to be validated. We used genome profiling to identify the genetic alterations associated with IBTR. Methods: Among 1,881 breast cancer patients treated with breast-conserving therapy between 1999 and 2018, IBTR occurred in 52 patients (2.8%). Of these 22 patients who consented for genomic analysis of Primary Breast Cancer ( T1) and IBTR (T2) were studied.　 When the same gene mutations in T1 and T2 were identified, it was classified as genomic residual recurrence gRR, and when no shared mutations identified, it was classified as gDP.　The differences between clinical and genomic classification were compared. Furthermore, the pathway of the genes which were responsible for recurrence was also examined. Results: Of 13 clinically diagnosed RRs (cRRs), 11 were gRR and 2 were gDPs, while of 9 cDPs, 6 were gDP and 3 gRR, with a match rate of 17/22 (77%).　 We searched for genes involved in IBTR: PIK3CA-AKT pathway mutations were found in 12 of 14 gRRs (86%) in T1, and only 2 of 8 gDPs (25%) with significant difference (p=0.004). When both of PBC and IBTR compared, PIK3CA-AKT pathway abnormalities were 24/28 (86%) in the gRR and 5/16 (31%) in the gDP (p<0.001).Conclusions: Genome profiling revealed that abnormalities in the PIK3CA-AKT pathway in long-term residential recurrences and are a crucial molecular group in the development of IBTR.Trial registration: not applicable
Can the use of Pet Remedy’s Calming Spray elicit a calming response in domestic cats (Felis catus)?
Authors: Vaghela Vidhaata
Published: February 2022

Background research:
Phytotherapy, using olfactory enrichment, is often overlooked as a method of environmental enrichment for domestic cats. The most common example of olfactory enrichment to elicit a calming response, uses Valerian Root, which is researched to also cause an apparent euphoric response in cats. It is important that enrichment is considered to allow the cats to exhibit natural behaviours which can reduce stress and destructive behaviours. Thus, this article will explore the effectiveness of Pet Remedy’s Calming spray and the behaviours cat’s exhibit.
Methodology:
Furthering the existing research which was initially undertaken, Pet Remedy’s Calming Spray was tested on 44 domestic cats to observe their responses. All cats were blindly offered exposure to Pet Remedy and a control sample at random. The number of interactions were recorded onto behavioural ethograms. All cats had 30 minutes to acclimatise to the researcher and had at least a four-hour washout period between both exposures.
Results:
The statistical analysis of data gathered was computed using IBM SPSS Statistics 25 in form of; a Freidman’s test, Wilcoxon Signed-Rank Tests, Descriptive Statistics and Spearman’s rank-order tests. The mean number of interactions amongst Pet Remedy and the control sample were computed to find that Pet Remedy’s Calming spray had a mean number of interactions of 18.09.
Conclusions:
This study suggests that olfactory enrichment using Pet Remedy’s Calming Spray corresponds an effective means to induce a calming response.
Two-Photon Responsive Porphyrinic Metal-Organic Framework Involving Fenton-Like Reaction for Enhanced Photodynamic and Sonodynamic Therapy
Authors: Duan Wenyao , Li Bo , Zhang Wen , Li Jiaqi , Yao Xin , Tian Yupeng , Zheng Jun , Li Dandan
Published: February 2022

Designing new oxygenation nanomaterials by oxygen-generating or oxygen-carrying strategies in hypoxia-associated anti-tumor therapy is a high priority target yet challenge. In this work, we fabricated a nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy. Thereinto, the porphyrinic MOF-525 can produce singlet oxygen (1O2) via light or ultrasonic irradiation for photodynamic and sonodynamic therapy. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H2O2 into O2 to mitigate the hypoxic environment for enhanced therapy outcome. Moreover, the two-photon activity and cancer cell specific targeting capability of Pd@MOF-525@HA gave rise to deeper tissue penetration and near-infrared light-induced fluorescence imaging to achieve precise guidance for cancer therapy. This work provides a feasible way in designing new oxygenation nanomaterials to relieve tumor hypoxia for enhanced cancer treatment.
Jaw1/LRMP increases Ca2+ influx upon GPCR stimulation with heterogeneous effect on the activity of each ITPR subtype
Authors: Nishikawa Atsushi , Okumura Wataru , Kozono Takuma , Sato Hiroyuki , Takagi Tsubasa , Tonozuka Takashi
Published: February 2022

Ca2+ influx upon G protein-coupled receptor (GPCR) stimulation is observed as a cytosolic Ca2+ concentration oscillation crucial to initiating downstream responses including cell proliferation, differentiation, and cell-cell communication. Although Jaw1 is known to interact with inositol 1,4,5-triphosphate receptor (ITPRs), Ca2+ channels on the endoplasmic reticulum, the function of Jaw1 in the Ca2+ dynamics with physiological stimulation remains unclear. In this study, using inducible Jaw1-expressing HEK293 cells, we showed that Jaw1 increases Ca2+ influx by GPCR stimulation via changing the Ca2+ influx oscillation pattern. Furthermore, we showed that Jaw1 increases the Ca2+ release activity of all ITPR subtypes in a subtly different manner. It is well known that the Ca2+ influx oscillation pattern varies from cell type to cell type, therefore these findings provide an insight into the relationship between the heterogeneous Ca2+ dynamics and the specific ITPR and Jaw1 expression patterns.
Acidic Condition Accelerates Base Cation Release from Purple Rock in Southwestern China
Authors: Zhao Jixia , Li Chunpei , Lu Chuanhao , Deng Limei , Liu Gangcai , Fan Maopan
Published: February 2022

In spite of the fact that rock weathering performs an essential task in the evolution of the Earth’s surface, the quantitative assessment between pH and rates of chemical weathering remain unclear. This study aims to characterize the chemical weathering rate of purple rocks (Entisols in USDA Taxonomy) and then develops a model to calculate the release rates of base cations (K+, Na+, Ca2+ and Mg2+) under various pH conditions. Two types of purple rock were sampled from the Shaximiao Group (J2s) and Penglaizhen Group (J3p), and a series of laboratory experiments were performed by soaking the purple rocks in solutions with pHs from 2.5 to 7.0, over 24 treatment cycles. The results showed that the release rates of base cations apparently increased as the pH decreased. The release of Ca2+ was the dominant process of chemical weathering in J3p under various pH treatments, while K+ and Na+ were remarkably high in J2s (with the exception of the pH 2.5 treatment). Quantitative analysis revealed that the rate of cation release was significantly related to the H+ concentration (p < 0.001) and the air temperature (p < 0.001). The relationship between cation release and acidity was found to be an exponential function. Our results suggested that solution acidity serves as an important driving force for cation release rates from purple rocks and that environmental acidification would enhance rock weathering.
Novel mutations of the USH2A gene and clinical phenotypes in Chinese Usher syndrome families
Authors: Li Xiaorong , Xing Dongjun , Yu Rongguo , Wang Linni , Hu Liying , Yang Yang , Li Chang , Li Zhiqing
Published: February 2022

Background: Usher syndrome (USH) is a leading disorder of deaf–blindness. The phenotypic and genetic heterogeneity of USH makes the diagnosis of this disorder difficult. However, diagnosis can be facilitated by employing molecular approaches, especially for diseases without pronounced pathognomonic symptoms. Therefore, this study aimed to reveal the genetic defects in five USH patients using clinical targeted exome sequencing (TES).Methods: USH patients and their family members from five unrelated Chinese USH families were recruited and subjected to TES. Ophthalmic information was obtained for all patients to ensure a meaningful interpretation. The TES data were analysed using an established bioinformatics pipeline to identify causative mutations. Further verification by Sanger sequencing and cosegregation analysis were performed on available family members.Results: We identified genetic mutations in five USH patients using TES. Seven mutations, four of which were novel, were identified in the USH2A gene. One proband (F1-II-3) was found to have a homozygous mutation inherited from nonconsanguineous parents, and another proband (F5-III-1) was found to carry three USH2A gene mutations.Conclusion: In conclusion, the study revealed the importance of TES in the clinical diagnosis of USH patients with variable phenotypes. The correlation between USH2A gene mutations and clinical phenotypes will help to refine the clinical diagnosis of USH.
How does music reading experience modulate eye movement pattern in sentence reading in bilinguals?
Authors: Liao Weiyan , Li Tze Kwan , Hsiao Janet Hui-wen
Published: February 2022

Here we tested the hypothesis that in Chinese-English bilinguals, music reading experience may modulate eye movement planning in reading English but not Chinese sentences due to the similarity in perceptual demands on processing sequential symbol strings separated by spaces between music notation and English sentence reading. Chinese-English bilingual musicians and non-musicians read legal, semantically incorrect, and syntactically (and semantically) incorrect sentences in both English and Chinese. In English reading, musicians showed more dispersed eye movement patterns in reading syntactically incorrect sentences than legal sentences, whereas non-musicians did not. This effect was not observed in Chinese reading. Musicians also had shorter saccade lengths when viewing syntactically incorrect than correct musical notations and sentences in an unfamiliar alphabetic language (Tibetan), whereas non-musicians did not. Thus, musicians’ eye movement planning was disturbed by syntactic violations in both music and English reading but not in Chinese reading, and this effect was generalized to an unfamiliar alphabetic language. These results suggested that music reading experience may modulate perceptual processes in reading differentially in bilinguals’ two languages, depending on their processing similarities.
An efficient inclusion complex based fluorescent sensor for mercury (II) and its application in live-cell imaging
Authors: P Keerthana , Abbo Hanna , Cherian Anila Rose , Titinchi Salam , varghese anitha
Published: February 2022

The formation of an inclusion complex between hydroxypropyl-β-cyclodextrin (H-CD) and 4-acetylphenyl-4-(((6-chlorobenzo[d]thiazol-2-yl)-imino)-methyl)-benzoate (L) was investigated by FT-IR, 1H-NMR, X-ray diffraction (XRD), FT-Raman, scanning electron microscope (SEM) techniques in the solid-state, absorption and emission spectroscopy in the liquid state and the virtual state as molecular docking technique. The binding properties of the inclusion complex (H-CD: L) with cations in deionized water was observed via absorbance and photoluminescence (PL) emission spectroscopy. The fluorescence probe (H-CD: L) inclusion complex (IC) was examined for several heavy metal cations and, identified that the PL emission wavelength of the complex displayed a continuous rise in the fluorescence intensity for Hg2+. A linearity range of 1×10-8 - 11×10-8 M and limit of detection value of 2.71×10-10 M was found to be achieved for the detection of Hg2+. This outcome proves that the inclusion complex H-CD: L would be a promising material for the development a solid-state fluorescence probe for detecting Hg2+. It also shows application in real sample analysis and cell imaging.
SARS-CoV-2 Omicron variant is attenuated for replication in a polarized human lung epithelial cell model
Authors: Mache Christin , Schulze Jessica , Holland Gudrun , Bourquain Daniel , Nitsche Andreas , Dürrwald Ralf , Laue Michael , Wolff Thorsten
Published: February 2022

SARS-CoV-2 and its emerging variants of concern remain a major threat for global health. Here we introduce a novel infection model based upon polarized human Alveolar Epithelial Lentivirus immortalized (hAELVi) cells grown at the air-liquid interface to estimate replication and epidemic potential of respiratory viruses in the human lower respiratory tract. hAELVI cultures are highly permissive for different human coronaviruses and seasonal influenza A virus and upregulate various mediators following virus infection. Our analysis revealed a significantly reduced capacity of SARS-CoV-2 Omicron variant to propagate in this human model compared to earlier D614G and Delta variants, which extends early risk assessments from epidemiological and animal studies suggesting a reduced pathogenicity of Omicron.
Coaxial cell printing of a human glomerular model in vitro of the glomerular filtration barrier and its pathophysiology
Authors: Singh Narendra , Kim Jae Yun , Lee Jae Yeon , Lee Hyungseok , Gao Ge , Jang Jinah , Kim Yong Kyun , Cho Dong-Woo
Published: February 2022

Many efforts have been expended in the emulations of the kidney’s glomerular unit because of its limitless potential in the field of drug screening industry and nephrotoxicity testing in the clinics. Herein, we have fabricated a functional bilayer glomerular microvessel-on-a-chip that recapitulates the specific arrangement of glomerular endothelial cell (GE), podocyte layers, and the intervening glomerular basement membrane (GBM) in a single step. Our perfusable chip allows for the coculture of the monolayer glomerular endothelium and podocyte epithelium that display mature functional markers of glomerular cells, and their proper interactions produce GBM proteins, which are the major components of the GBM in vivo. Furthermore, we tested the selective permeability capacity, a representative hallmark function of the glomerular filtration barrier. Lastly, we evaluated the response of our glomerular model to Adriamycin- and hyperglycemia-induced injury to evaluate its applicability for drug screening and glomerular disease modeling.
Encounters And Management Of Oral Conditions At General Medical Practices In Australia.
Authors: Cheng An-Lun , Eberhard Joerg , Gordon Julie , Balasubramanian Madhan , Willink Amber , Sohn Woosung , Dai Jennifer , Harrison Christopher
Published: February 2022

Background: Poor oral health has been widely recognised as an ongoing public health issue. Patients with oral conditions may visit either a general practitioner (GP) or an oral health practitioner for management. The aims of this study are to report (i) the GP management rate of oral health conditions by patient and GP demographics, (ii) what specific oral conditions were managed, and (iii) how GPs managed oral conditions. Methods: Data from the Bettering the Evaluation and Care of Health study (2006 to 2016 inclusive) were analysed. Descriptive statistics with 95% confidence intervals around point estimates were used to summarise data. Multivariate logistic regression was performed to determine the independent effect of patient and GP characteristics. Results: A total of 972,100 GP encounters were included in the dataset, with oral condition-related encounters managed at a rate of 1.19 oral conditions per 100 GP encounters. Patients who were aged 54 years or younger, resided in a socioeconomically disadvantaged area, came from a non-English speaking background or Indigenous background were more likely to have oral conditions managed by GPs. The most commonly reported oral conditions were dental and oral mucosa-related. Over 60% of oral conditions were managed by GPs through prescribed medications. Conclusions: This study provided an overview of management of oral conditions by GPs in Australia. Patients from certain vulnerable demographic groups were more likely to attend a GP for management of oral conditions. Common oral conditions and management approaches were identified. The findings of this study contribute to public health and health policy discussions around optimising primary care provision in oral health.
MOT: a Multi-Omics Transformer for Multiclass Classification Tumour Types Predictions
Authors: Osseni Mazid Abiodoun , Tossou Prudencio , Laviolette Francois , Corbeil Jacques
Published: February 2022

Motivation: Breakthroughs in high-throughput technologies and machine learning methods have enabled the shift towards multi-omics modeling as the preferred mean to understand the mechanisms underlying biological processes, and to improve complex disease prognosis in clinical settings. However, most multi-omic studies only use transcriptomics and epigenomics due to their over-representation in databases and their early technical maturity compared to others omics. For complex phenotypes and mechanisms, not leveraging all the omics despite their varying degree of availability can lead to a failure to understand the underlying biological mechanisms. Results: We proposed MOT (Multi-Omic Transformer), a deep learning based model using the transformer architecture, that discriminates complex phenotypes (herein cancers types) based on five omics data type regardless of their availability: transcriptomics (mRNA and miRNA), epigenomics (DNA methylation), copy number variations (CNVs), and proteomics. At its core, MOT uses a data augmentation scheme that allows it to handle missing omics views and its attention layers give a macro level of interpretability for each phenotypes. Indeed, MOT identifies the required omic type for the best prediction for each phenotype and therefore could guide clinical decision making when acquiring data to confirm a diagnostic. It achieves an accuracy score of 96.04% after 5-fold cross-validation among 33 tumour types. The newly introduced model can integrate and analyse five different omics data while handling the missing omics views and can also identify the essential omics data for the tumour multiclass classification tasks. Availability and implementation: MOT source code is available at https://github.com/dizam92/multiomic_predictions.
Biomechanical evaluation of a new standard temporomandibular joint prosthesis and screw arrangement optimization: A finite element analysis.
Authors: Zhang Luzhu , Qin Haiyi , Abdelrehem Ahmed , He Dongmei
Published: February 2022

Background: Artificial total joint replacement is an important method of temporomandibular joint (TMJ) reconstruction, which has been advocated for TMJ osteoarthrosis, ankylosis, tumors and other diseases. We designed one type of a standard TMJ prosthesis fit for Chinese patients. This study explores the biomechanical behavior of the standard TMJ prosthesis using finite element analysis and selects an optimal screw arrangement scheme for clinical application. Methods: A female volunteer was recruited for a maxillofacial computed tomography (CT) scan, then the Hypermesh software was used to establish a finite element model of a mandibular condyle defect repaired with an artificial TMJ prosthesis. LS-DYNA software was used to calculate the stress and deformation under a simulated maximum bite force loading. Also, the forces of screws under different numbers and arrangements were analyzed. Meanwhile, we designed an experiment to verify the calculation model.Results: The average maximum stress of the fossa component of the standard prosthesis model was 19.25 MPa. The average maximum stress of the condyle component was 82.58 MPa, mainly concentrated near the top row hole. The fossa component should be fixed with at least 3 screws, and the optimal number of screws was 4. The condyle component should be fixed with at least 4 screws, and its optimal number was 6. The best scheme of screw arrangement was determined. The results of the verification experiment showed that the analysis was reliable.Conclusions: The stress distribution of the standard TMJ prosthesis is uniform, meanwhile, the number and arrangement of the screws significantly affect the contact force of the screws.
Dbias: Detecting biases and ensuring Fairness in news articles
Authors: Raza Shaina , Reji Deepak John , Ding Chen
Published: February 2022

The problem of fairness is garnering a lot of interest in the academic and broader literature due to the increasing use of data-centric systems and algorithms in machine learning. This paper introduces Dbias (https://pypi.org/project/Dbias/), an open-source Python package for ensuring fairness in news articles. Dbias can take any text to determine if it is biased. Then, it detects biased words in the text, masks them, and suggests a set of sentences with new words that are bias-free or at least less biased. We conduct extensive experiments to assess the performance of Dbias. To see how well our approach works, we compare it to the existing fairness models. We also test the individual components of Dbias to see how effective they were. The experimental results show that Dbias outperforms all the baselines in terms of accuracy and fairness. We make this package (Dbias) as publicly available for the developers and practitioners to mitigate biases in textual data (such as news articles), as well as to encourage extension of this work.
Expression quantitative trait locus rs6356 is associated with the susceptibility of heroin addiction by potentially influencing the TH gene expression in the hippocampus and nucleus accumbens
Authors: Wang Kena , Zhang Hongbo , Ji Jinshan , Zhang Rui , Dang Wei , Xie Qiaoli , Zhu Yongsheng , Zhang Jianbo
Published: February 2022

Opioid addiction is a complicated and highly heritable brain disease. Dysfunction of dopaminergic signaling is involved in the pathogenesis of addictive disorders. Encoding the synthetase of dopamine, tyrosine hydroxylase (TH) gene has long been an interesting candidate in the genetic association studies for opioid addiction. However, the underlying mechanism of the association of risk gene variants and opioid addiction remains unknown. In the present study, we first analyzed the association between TH gene variants and susceptibility and traits of heroin addiction in 801 patients with heroin addiction and 930 healthy controls. The methylation level in the promoter region of the TH gene was detected and compared between the heroin addiction and healthy control groups. To reveal the potential mechanism of the association of TH gene variants and heroin addiction, correlation between the risk TH SNPs for heroin addiction and the methylation as well expression level of TH gene were examined. Our results demonstrated that SNP rs6356 was associated with the susceptibility of heroin addiction. CpG TH_15 was hypermethylated in the heroin addiction group compared with the healthy control group. Notably, SNP rs6356 was allele-specific correlated with the expression of TH gene in the hippocampus and nucleus accumbens, but not the methylation level of CpG TH_15. Our findings suggest that the eQTL rs6356 was associated with the risk of heroin addiction by potentially affecting the expression of TH gene in the mesocorticolimbic dopamine system brain regions including hippocampus and nucleus accumbens.
Global Magnitude and Temporal Trend of Mesothelioma Burden Along with the Contribution of Occupational Asbestos Exposure in 204 Countries and Territories From 1990 to 2019: Results from the Global Burden of Disease Study 2019
Authors: Han Yali , Zhang Tongchao , Chen Hui , Yang Xiaorong
Published: February 2022

Background
Understanding the annual incidence, mortality, and disability-adjusted life-years (DALYs) for mesothelioma globally provides essential foundations for cancer control, policy decisions and resource allocation.
Materials and methods
Complying with the Global Burden of Disease Study 2019, we extracted the data of incidences, deaths and DALYs in 204 countries and territories from 1990 to 2019. Average annual percentage changes were used to quantify the temporal trends in mesothelioma burden. Besides, the population attributable fractions of the risk factor of mesothelioma were also estimated.
Results
Globally, 34511 (95% uncertainty intervals[UI]: 31199, 37771) incident cases, 29251 (95%UI: 26668, 31006) deaths and 668104 (95%UI: 608269, 716475) DALYs of mesothelioma were estimated in 2019. The age-standardized rates of incidence, mortality and DALYs all showed a slightly declining trend over the past 30 years, but the latest absolute number of mesothelioma burden almost doubled since 1990. The age-standardized burden of mesothelioma among men was around 3 times more than women in 2019, which decreased among women while remained stable among men. The burden rate decreased among the population aged under 70 years, but increased among the population aged over 80 years, especially in the High socio-demographic index (SDI) region. The age-standardized DALYs rate (ASDR) of mesothelioma attributable to occupational asbestos exposure in 2019 was positively associated with SDI at the national levels (ρ = 0.3105, P = 6.2e-06).
Conclusion
This study depicted a continuous increase in incidences, deaths and DALYs of mesothelioma globally over the past 30 years. Controlling occupational asbestos exposure will reduce the mesothelioma burden, especially for higher SDI regions.
Lung Ultrasound Targeted Recruitment (LUSTR): A Novel Protocol to Optimize Open Lung Ventilation In Critically Ill Neonates.
Authors: Chioma Roberto , Amabili Lorenzo , Ciarmoli Elena , Copetti Roberto , Villani Pier Giorgio , Stella Marcello , Natile Miria , Ancora Gina , Vento Giovanni , Storti Enrico , Pierro Maria
Published: February 2022

PurposeThe objective of this study was to investigate the effectiveness of an original Lung UltraSound Targeted Recruitment (LUSTR) protocol to improve the success of lung recruitment maneuvers (LRMs), performed as a rescue approach in critically ill neonates, as compared to the standard oxygenation-guided LRM.MethodsAll the LUSTR maneuvers, performed in infants with oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this retrospective case-control study (LUSTR-group). The LUSTR-group was matched by the initial S/F ratio (which is inversely proportional to the severity of the respiratory insufficiency) and underlying respiratory disease with a control group of lung recruitments performed following the standard oxygenation-guided procedure (Ox-group). The primary outcome was the improvement of the S/F ratio (Delta S/F) throughout the LRM. Secondary outcomes included the variation of the Oxygen Saturation Index (OSI) and the rate of air-leaks.ResultsEach group was constituted by fourteen LRMs. As compared to the standard approach, the LUSTR protocol was associated with a higher success of the procedure in terms of Delta S/F (110±47.3 vs 64.1±54.6, p = 0.02), and OSI (8.2±6.8 vs 2.8±2.2, p = 0.01). These results remained significant after adjusting for confounding variables through multiple linear regressions. All the LRM in the LUSTR group showed signs of lung recruitability and obtained the sonographic resolution of the lung derecruitment. Patient position before and during LRM was modified more frequently in the LUSTR group. A trend towards decreased rates of pneumothorax was observed in the LUSTR-group (0 vs 14.3%, p = 0.15).ConclusionThe LUSTR protocol may be a more effective and potentially safer option than the oxygenation-based procedure to guide open lung ventilation in neonates.
Aldehyde dehydrogenase 2 activator augments the beneficial effects of empagliflozin in diabetes associated HFpEF
Authors: Palaniyandi Suresh Selvaraj , Pan Guodong , Roy Bipradas , Giri Shailendra , Lanfear David E , Thandavarayan Rajarajan A. , Guha Ashrith , Ortiz Pablo
Published: February 2022

Objectives: To ameliorate diabetes mellitus associated heart failure with preserved ejection fraction (HFpEF), we plan to lower diabetes-mediated oxidative stress-induced 4-hydroxy-2-nonenal (4HNE) accumulation by pharmacological agents that either decrease 4HNE generation or increase its detoxification.Background: 4HNE, a cellular reactive carbonyl species (RCS), was significantly increased in diabetic hearts due to a diabetes-induced decrease in 4HNE detoxification by aldehyde dehydrogenase (ALDH)2, a cardiac mitochondrial enzyme that metabolizes 4HNE. Therefore, hyperglycemia-induced 4HNE is critical for diabetes-mediated cardiotoxicity and we hypothesize that lowering 4HNE ameliorates diabetes associated HFpEF. Methods: We fed high-fat diet to ALDH2*2 mice which have intrinsically low ALDH2 activity to induce type-2 diabetes. After 4 months of diabetes, the mice exhibited features of HFpEF and along with increased 4HNE adducts and we treated them with vehicle, empagliflozin (EMP) (3mg/kg/d) to reduce 4HNE and Alda-1 (10mg/kg/d), an ALDH2 activator to enhance ALDH2 activity as well as a combination of EMP + Alda-1 (E + A), via subcutaneous osmotic pumps. After 2 months of treatments, cardiac function was assessed by conscious echocardiography before and after exercise stress. Results: EMP + Alda-1 improved exercise tolerance, diastolic and systolic function, 4HNE detoxification and cardiac liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway in ALDH2*2 mice with diabetes associated HFpEF. This combination was even more effective than EMP alone. Conclusions: Our data indicate that ALDH2 activation along with the treatment of hypoglycemic agents may be a salient strategy to alleviate diabetes associated HFpEF.
Knee Joint Moments Can Accurately Predict Medial and Lateral Knee Contact Forces in Patients With Valgus Malalignment
Authors: Holder Jana , Drongelen Stefan , Uhlrich Scott David , Herrmann Eva , Meurer Andrea , Stief Felix
Published: February 2022

Compressive knee joint contact force during walking is thought to be related to initiation and progression of knee osteoarthritis. However, joint loading is often evaluated with surrogate measures, like the external knee adduction moment, due to the complexity of computing joint contact forces. Statistical models have shown promise for predicting joint contact force from easily measured joint moments in individuals with osteoarthritis or joint replacements. This approach may also be effective in young patients with valgus deformities. The purpose of this study was to evaluate how accurately medial and lateral knee joint contact forces could be estimated by linear mixed-effects models during walking for children with and without valgus malalignment. Knee joint moments were strongly correlated (R2 > 0.85, p < 0.001) with both medial and lateral knee joint contact forces. The knee flexion and adduction moments were significant covariates in most of the models, strengthening the understanding of the contribution of both moments to medial and lateral knee joint contact force. In the future, these models could be used to predict knee joint contact forces using joint moments from motion capture software, obviating the need for time-consuming musculoskeletal simulations.
Seismic evidence for uniform crustal accretion along slow-spreading ridges in the equatorial Atlantic Ocean
Authors: Wang Zhikai , Singh Satish
Published: February 2022

The crustal accretion along mid-ocean ridges is known to be spreading-rate dependent. Along fast-spreading ridges, two-dimensional sheet-like mantle upwelling creates relatively uniform crust. In contrast, the crust formed along slow-spreading ridges shows large along-axis thickness variations with thicker crust at segment centres, which is hypothesised to be due a three-dimensional plume-like mantle upwelling with melt focusing to segment centres. Using wide-angle seismic data acquired from the equatorial Atlantic Ocean, we show that the crustal thickness is nearly uniform (~5.5 km) across five segments for crust formed at the slow-spreading Mid-Atlantic Ridge with age varying from 8 to 70 Ma. The crustal velocities indicate that this crust is predominantly of magmatic origin. We suggest that this uniform magmatic crustal accretion is due to a two-dimensional sheet-like mantle upwelling, contradicting previous hypothesis. Our results also indicate that the lateral extend of magmatic accretion could be used to define the sheet-like mantle upwelling regions beneath the global ridge system.
Early life microbial exposures shape the Crassostrea gigas immune system for lifelong and intergenerational disease protection
Authors: Fallet Manon , Montagnani Caroline , Petton Bruno , Lorgeril Julien , Comarmond Sébastien , Chaparro Cristian , Toulza Eve , Boitard Simon , Escoubas Jean-Michel , Vergnes Agnès , Grand Jacqueline Le , Bulla Ingo , Gueguen Yannick , Vidal-Dupiol Jérémie , Grunau Christoph , Mitta Guillaume , Cosseau Céline
Published: February 2022

Background
The interaction of organisms with their surrounding microbial communities influences many biological processes, a notable example of which is the shaping of the immune system in early life. In the Pacific oyster, Crassostrea gigas, the role of the environmental microbial community on immune system maturation – and, importantly, protection from infectious disease – is still an open question.
Results
Here, we demonstrate that early life microbial exposure durably improves oyster survival when challenged with the pathogen causing Pacific Oyster Mortality Syndrome (POMS), both in the exposed generation and in the subsequent one. Combining microbiota, transcriptomic, genetic, and epigenetic analyses, we show that the microbial exposure induced changes in epigenetic marks and a reprogramming of immune gene expression leading to long-term and intergenerational immune protection against POMS.
Conclusions
We anticipate that this protection likely extends to additional pathogens and may prove to be an important new strategy for safeguarding oyster aquaculture efforts from infectious disease.
Low-Loss Coupling from Coated Plano Convex Lens to Single Mode Solid Core Fibers Laser by Lensing Scheme
Authors: Khan Noor Zamin , Sohail Muhammad , Khan Noor Zamin , Mehmood Ikhtisham , Chen Tenghui , Khan Sayed Ali
Published: February 2022

For the first time, to the best of our knowledge, we experimentally demonstrated the new scheme for a coated Plano-convex lens (CPCL) fiber with a maximum coupling efficiency \((\eta\)max). In the single-mode solid core fiber (SMSCF), the fiber coupling efficiency is ~ 68% injected pump power 632.8 nm (1.5-dB loss was measure with a laser diode) which is difficult to achieve by using conventional technology, and also we reported, without fiber tapering technology has been used to realize low loss coupling from CPCL to SMSCF at low power level, and compare with published data. This is very useful for implementing all optical fiber systems. In addition, it also investigates the effect of bending the output power and beam profile of SMSCF. The Gaussian-like output beam profile is maintained up to \(\cong 7cm\) bending radius. The output mode field with good beam quality shows the mode filtering characteristics of SMSCF. Finally, the result of the fiber coupling efficiency (FCE) illustrates that the scheme of the lens coupling system is the most sensitive scheme to the misalignment and the lensing scheme is the least sensitive to misalignment.
A Control Method with Considering Error Coupling in Milling Multi Feature Thin-Walled Parts
Authors: Zuo Xiaoyan , Zhou Yin , Xiong Tao , Zhang Chengjun , Zhang Chi , Zhou Xiangyang
Published: February 2022

The error coupling analysis is important for machining accuracy of thin-walled parts. However, most of the error coupling analysis methods only based on multiple error sources with a single feature, without considering the coupling relationship of these errors between features. This paper no longer focuses on analyzing the machining error of a single feature, but discusses the error coupling phenomenon between each other and interrelated features. First, interactive factors during machining multiple features are analyzed. Subsequently, according to the main interactive factors, the models about geometric interaction and machining interaction of multi feature processing are established. Afterwards, based on the comprehensive error model obtained through the transformation of the coordinate systems, an efficient error control method of multi feature thin-walled parts is proposed. Finally, the approach has been validated through an illustrative case study using a sample part with complex machining features.
Short (seven days) versus standard (fourteen days) oestrogen administration in a programmed frozen embryo transfer cycle: a retrospective cohort study
Authors: Jiang Wen-Jing , Song Jing-Yan , Sun Zhen-Gao
Published: February 2022

Research question: What influence does seven days of oestrogen administration versus fourteen days have on the reproductive outcomes of frozen-thawed embryo transfer (FET) in programmed endometrial preparation cycles?
Design: In a retrospective study, conducted at a university-affiliated tertiary hospital, a total of 2628 infertile patients (4142 FET cycles) were divided into one of two groups between January 2014 and December 2020: group A (n=1406, seven days of oestrogen before progesterone (P4) supplementation) and group B (n=2716, fourteen days of oestrogen before P4 supplementation). The primary outcome was cumulative live birth rate (CLBR). Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications.
Results: No significant difference in CLBR was observed when comparing seven versus fourteen days of oestrogen administration before starting P4 supplementation (47.6% vs. 48.8%, P=0.537). Furthermore, multivariable logistic regression analysis revealed that oestrogen administration in programmed FET cycles (7 days vs. 14 days) was not significantly associated with CLBR (OR 1.04, 95% CI 0.89-1.23). The risks of maternal and neonatal complications were comparable between the two groups.
Conclusions: Variation in the duration of oestradiol supplementation before P4 initiation does not impact FET reproductive outcomes. For infertile women who desire to conceive as soon as feasible, short (seven days) oestrogen administration in a programmed FET cycle may be a suitable alternative.
Trophoblast Cell-Surface Antigen 2 (TROP2) Expression in Triple-Negative Breast Cancer
Authors: Jeon Yeonjin , Jo Uiree , Hong Jongmoo , Gong Gyungyub , Lee Hee Jin
Published: February 2022

Background Trophoblast cell-surface antigen 2 (TROP2) is related to tumor proliferation enhancement and poor prognosis. An antibody targeting TROP2 was developed to treat metastatic triple-negative breast cancer (TNBC) which has a limited treatment modality. To characterize the TROP2 expressing tumors in TNBC, we analyzed TROP2 expression in three cohorts; (1) primary tumor without neoadjuvant chemotherapy, (2) primary tumor with neoadjuvant chemotherapy, and (3) metastatic tumor. Methods A total of 807 TNBC cases were evaluated for TROP2 immunohistochemical expression. We evaluated the TROP2 H-score distribution in the three cohorts. Tumors were divided into two groups based on TROP2 expression (high vs. low). We analyzed the relationship between clinicopathologic features and markers, including EGFR, CK5/6, p53, and Ki-67, and prognostic significance at high vs. low TROP2 expression. Results There was no difference in TROP2 H-score distribution between the three cohorts. Moderate-to-strong membranous expression of TROP2 in at least 10% of tumor cells was present in 662 cases (82.0%) in Cohort 1, 59 cases (89.4%) in Cohort 2, and 23 cases (88.5%) in Cohort 3. There was no significant difference in clinicopathologic features between high vs. low TROP2 in all cohorts. TROP2 H-score was an independent poor prognostic factor for overall survival in Cohort 3. Conclusion TNBC showed similar TROP2 expression regardless of neoadjuvant treatment or primary tumor/metastasis. Although the prognostic significance of TROP2 expression in metastatic TNBC has been revealed, further evaluation of the predictive value of TROP2 expression for targeted therapy is needed.
Changing in Dental Setting and Postural Analysis – A Case Report
Authors: Palandri Sergio
Published: February 2022

BackgroundDental structure and posture is now well known to be closely linked to each other. This work is not intended to be the definitive proof of this link, but rather the exposure of a case that presents the particularity of an absolute procedural asepsis as the operator was not aware of the change in the dental setting of the subject examined.Material sand MethodsThe study began in 2020 and ended in 2021. The subject involved was a young woman of about 37 years old, weighing 52Kg and 1.58m tall, at the first postural analysis performed on 2020 January the third. Subsequently, two other postural analysis were performed, 13 months and 22 months after the first respectively. For the postural analysis, an identical protocol was followed in the three analyzes performed.ResultsObserving the results obtained in the three analysis, it can be deduced that approximately 63% of the controlled parameters (12 out of 19) underwent modifications, even if not all of them could be related to the variation of the dental setting.ConclusionThe study, even within the limits of its design, highlights how the different systems that make up the human body are interdependent and an action performed on one of them can be found as a modification of the initial state of others.