bluuebunny/crossref_metadata_2025 huggingface dataset:
Carryover Contamination-Controlled Amplicon Sequencing Workflow for Accurate Qualitative and Quantitative Detection of Pathogens: a Case Study on SARS-CoV-2
Authors: Gao Lifen , Li Lun , Fang Bin , Fang Zhiwei , Xiang Yanghai , Zhang Min , Zhou Junfei , Song Huiyin , Chen Lihong , Li Tiantian , Xiao Huafeng , Wan Renjing , Jiang Yongzhong , Peng Hai
Published: April 2023

Accuracy, a key indicator of pathogen detection technology, is compromised by carryover contamination in the amplicon sequencing workflow. Taking the detection of SARS-CoV-2 as case, this study presents a new carryover contamination-controlled amplicon sequencing workflow.
Yeasts Have Evolved Divergent Enzyme Strategies To Deconstruct and Metabolize Xylan
Authors: Ravn Jonas L. , Ristinmaa Amanda Sörensen , Coleman Tom , Larsbrink Johan , Geijer Cecilia
Published: April 2023

Microbes that take part in the degradation of the polysaccharide xylan, the major hemicellulose component in plant biomass, are equipped with specialized enzyme machineries to hydrolyze the polymer into monosaccharides for further metabolism. However, despite being found in virtually every habitat, little is known of how yeasts break down and metabolize xylan and what biological role they may play in its turnover in nature.
Small Molecule Inhibition of an Exopolysaccharide Modification Enzyme is a Viable Strategy To Block Pseudomonas aeruginosa Pel Biofilm Formation
Authors: Razvi Erum , DiFrancesco Benjamin R. , Wasney Gregory A. , Morrison Zachary A. , Tam John , Auger Anick , Baker Perrin , Alnabelseya Noor , Rich Jacquelyn D. , Sivarajah Piyanka , Whitfield Gregory B. , Harrison Joe J. , Melnyk Roman A. , Nitz Mark , Howell P. Lynne
Published: April 2023

Present in more than 500 diverse Gram-negative and 900 Gram-positive organisms, the Pel polysaccharide is one of the most phylogenetically widespread biofilm matrix determinants found to date. Partial de-
N
-acetylation of this α-1,4 linked
N
-acetylgalactosamine polymer by the carbohydrate modification enzyme PelA is required for Pel-dependent biofilm formation in
Pseudomonas aeruginosa
and
Bacillus cereus
.
Adaptive Laboratory Evolution Reveals the Selenium Efflux Process To Improve Selenium Tolerance Mediated by the Membrane Sulfite Pump in Saccharomyces cerevisiae
Authors: Gong Ao , Liu Wenyue , Lin Yelong , Huang Laili , Xie Zhixiong
Published: April 2023

Selenium is an essential micronutrient for mammals, and its deficiency severely threatens human health. Yeast is the model organism for studying the biological role of selenium, and Se-enriched yeast is the most popular selenium supplement to solve Se deficiency.
Whole-Genome Sequencing Exhibits Better Diagnostic Performance than Variable-Number Tandem Repeats for Identifying Mixed Infections of Mycobacterium tuberculosis
Authors: Chen Yiwang , Jiang Qi , Liu Qingyun , Gan Mingyu , Takiff Howard E. , Gao Qian
Published: April 2023

Mixed infections of
M. tuberculosis
have the potential to render treatment regimens ineffective and affect the transmission dynamics of the disease. VNTR typing, currently the most widely used method for the detection of mixed infections, detects mixed infections only by interrogating a small fraction of the
M. tuberculosis
genome, which necessarily limits sensitivity.
Supplemental Material: A mechanism for transient creep in crustal shear zones
Authors: Thom Christopher A. , Kirkpatrick James D.
Published: April 2023

Supplemental Methods, Figures S1 and S2, and Tables S1 and S2.  
Prevalence of HIV in mental health service users: a retrospective cohort study
Authors: Heslin Margaret , Jewell Amelia , Croxford Sara , Chau Cuong , Smith Shubulade , Pittrof Rudiger , Covshoff Elana , Sullivan Ann , Delpech Valerie , Brown Alison , King Helena P , Kakaiya Mina , Campbell Lucy , Hughes Elizabeth , Stewart Robert
Published: April 2023

Objective

To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.

Design

Retrospective cohort study.

Setting

Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.

Participants

All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.

Primary outcome

Point prevalence of HIV.

Results

There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).

Conclusions

The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.
Screening for psychosocial risk in caregivers of children with medical complexity during the COVID-19 pandemic: a cross-sectional study
Authors: Pitch Natalie , Verma Rahul , Davidson Laura , Robertson Taylor , Anagnostopoulos Gregory , Sunkonkit Kanokkarn , Qazi Adam , Ambreen Munazzah , Mekhuri Samantha , Miller Michael R , Orkin Julia , Amin Reshma
Published: April 2023

Objective

The primary objective was to quantify psychosocial risk in family caregivers (FCs) of children with medical complexity (CMC) during the COVID-19 pandemic using the Psychosocial Assessment Tool (PAT). The secondary objectives were to compare this finding with the average PAT score of this population before the COVID-19 pandemic and to examine potential clinical predictors of psychosocial risk in FCs of CMC.

Design

Cross-sectional study.

Participants

FCs of CMC were recruited from the Long-Term Ventilation Clinic at The Hospital for Sick Children, Toronto, Ontario, Canada. A total of 91 completed the demographic and PAT questionnaires online from 10 June 2021 through 13 December 2021.

Main outcome measures

Mean PAT scores in FCs were categorised as ‘Universal’ low risk, ‘Targeted’ intermediate risk or ‘Clinical’ high risk. The effect of sociodemographic and clinical variables on overall PAT scores was assessed using multiple linear regression analysis. Comparisons with a previous study were made using Mann-Whitney tests and χ2analysis.

Results

Mean (SD) PAT score was 1.34 (0.69). Thirty-one (34%) caregivers were classified as Universal, 43 (47%) as Targeted and 17 (19%) as Clinical. The mean PAT score (1.34) was significantly higher compared with the mean PAT score (1.17) found prior to the COVID-19 pandemic. Multiple linear regression analysis demonstrated an overall significant model, with the number of hospital admissions since the onset of COVID-19 being the only variable associated with the overall PAT score.

Conclusion

FCs of CMC are experiencing significant psychosocial stress during the COVID-19 pandemic. Timely and effective interventions are warranted to ensure these individuals receive the appropriate support.
Theoretical study on effect of substituent on aromaticity of tetrazole ring
Authors: Yang Chunhai , Li Xue , Zhou Ning , Chen Bing , Dong Huilong , Jin Junxun , Hu Xiuli , Huang Tao , Shen Lei , Yi Jun , Wang Quan , Ouyang Dihua
Published: April 2023

Tetrazole compounds are a category of energetic materials with great potential. Their stability is inherently related to their aromatics. On the basis of research in DFT at b3lyp/6–311** level on three compounds interested, viz. 5-amino-1 H-tetrazole, 5-carboxyl-1 H-tetrazole, and 2-methyl-5-carboxyl-tetrazole, their aromatic characters are extensively analyzed by virtue of different estimation method. Analyses show that these methods, Nucleus-independent Chemical Shift, iso-chemical shielding surface, adaptive natural density partitioning, π-electrons density, and localized orbital locator of π-electron density are efficient for substituted-tetrazole ring aromaticity estimation. Conclusion denotes that both substituent and substituted position can significantly affect the aromaticity of tetrazole ring of tetrazole compound. Among these given substituents, electro-withdrawing group -COOH significantly increases the aromaticity of the tetrazole rings due to the withdrawing to π-electrons thereof but electro-donating group -NH2 weakens the one of the tetrazole rings due to the donating to π-electrons thereof. But for 2-methyl-5-carboxyl-tetrazole, the aromaticity increasing of -COOH imposed on π-electrons of tetrazole ring thereof is partially balanced by the existence of the electron-donating group -CH3 at asymmetric meta-position of tetrazole ring. Consequently, the aromaticity order is 5-Carboxyl-1 H-tetrazole > 2-methyl-5-Carboxyl-tetrazole > 5-amino-1 H-tetrazole.
From Minkowski to de Sitter vacua with various geometries
Authors: Pallis Constantinos
Published: April 2023

New no-scale supergravity models with F-term SUSY breaking are introduced, adopting Kähler potentials parameterizing flat or curved (compact or non-compact) Kähler manifolds. We systematically derive the form of the superpotentials leading to Minkowski vacua. Combining two types of these superpotentials we can also determine de Sitter or anti-de Sitter vacua. The construction can be easily extended to multi-modular settings of mixed geometry. The corresponding soft SUSY-breaking parameters are also derived.
Enumerative geometry of surfaces and topological strings
Authors: Brini Andrea
Published: April 2023

This survey covers recent developments on the geometry and physics of Looijenga pairs, namely pairs [Formula: see text] with [Formula: see text] a complex algebraic surface and [Formula: see text] a singular anticanonical divisor in it. I will describe a surprising web of correspondences linking together several a priori distant classes of enumerative invariants associated to [Formula: see text], including the log Gromov–Witten invariants of the pair, the Gromov–Witten invariants of an associated higher dimensional Calabi–Yau variety, the open Gromov–Witten invariants of certain special Lagrangians in toric Calabi–Yau threefolds, the Donaldson–Thomas theory of a class of symmetric quivers, and certain open and closed BPS-type invariants. I will also discuss how these correspondences can be effectively used to provide a complete closed-form solution to the calculation of all these invariants.
Experimental Investigations Using Computer Vision for Debris Motion Generated by Solitary Waves
Authors: Kim Taeyoon , Hwang Taegeon , Baek Seungil , Hong Sunghoon , Kim Jiwon , Lee Woo-Dong
Published: April 2023

A tsunami created by the momentary release of a large amount of energy accumulated in the ocean crust destroys coastal structures and generates considerable debris, posing a serious threat to coastal communities. Hence, understanding the movement characteristics of drifting attributed to tsunamis for coastal disaster prevention is necessary. In this study, a color-based Debris mOtion Tracking (DOT) model is developed to understand the behavioral characteristics of drifting caused by solitary waves. The behavioral characteristics of drifting are analyzed quantitatively based on the weight of the debris, scale of solitary waves, and revetment type, which have not been considered previously. The DOT model tracks the drifting behavior more accurately than the existing commercial programs. In a laboratory experiment, the kinetic energy, and maximum debris velocity increase with an increase in the magnitude of solitary waves. An analysis of the drifting characteristics based on revetment type reveals that the initial acceleration of drifting in the wave absorbing revetment (WAR) is higher than that in the vertical revetment (VR). Velocities of vertical and horizontal flow develop in VR and WAR, respectively, and thus the momentum flux acted more strongly. Further, overtopping the wave characteristics based on the revetment type determines the drifting behavior.
The behavior of a host–parasitoid model with host logistic growth and proportional refuge
Authors: Kalabušić Senada , Pilav Esmir
Published: April 2023

This paper deals with the host–parasitoid model, where the logistic equation governs the host population growth, and a proportion of the host population can find refuge. The equilibrium points’ existence, number, and local character are discussed. Taking the parameter regulating the parasitoid’s growth as a bifurcation parameter, we prove that Neimark–Sacker and period-doubling bifurcations occur. Despite the complex behavior, it can be proved that the system is permanent, ensuring the long-term survival of both populations. Furthermore, it was observed that the presence of the proportional refuge does not significantly influence the system’s behavior compared to the system without a proportional refuge.
Investigating the Impact of Temperature on Magnetic-Field Behavior of Thin-Film Three-Layer Systems Co/Cu/Co and Co/Gd/Co
Authors: Makarov A. V. , Shalygina E. E.
Published: April 2023

This paper presents the results of investigating the impact of temperature on the magnetic properties of Co/Gd/Co and Co/Cu/Co thin-film three-layer systems obtained via ion-plasma magnetron sputtering. The following features of the studied samples were found. In particular, when the temperature changes from 100 to 300[Formula: see text]K, the coercive force of studied systems decreases. The magnetic moment of Co/Cu/Co sample does not dependent on temperature. Strong influence of temperature on the magnetic properties of the studied samples is observed. In particular, a compensation point was found at temperature [Formula: see text][Formula: see text]K for a Co/Gd/Co sample with thickness of gadolinium of 9.0[Formula: see text]nm.
Practice Variation in Proximal Phalangeal Fracture Management
Authors: SIVAKUMAR Brahman , ROSS Mark , GRAHAM David J.
Published: April 2023

Background: Practice variation may indicate a lack of evidence to guide management. This study investigated the preferences of operative management of proximal phalangeal fractures in Australian hand surgeons, as well as factors that may account for variations.

Methods: An electronic survey of all members of the Australian Hand Surgery Society was performed. Surgeon demographic factors and surgical preferences were investigated. Three common proximal phalangeal fracture configurations were presented as cases. Potential predictors of management were explored.

Results: A total of 51.9% of active hand surgeons responded. Orthopaedic surgeons were more comfortable with lateral plating and intramedullary screw fixation, while plastic surgeons preferred Kirschner wire (K-wire) fixation. Junior surgeons were more likely to believe that intramedullary screw fixation produced superior results. 53.0% of surgeons in a tertiary environment believed that adequate hand therapy was key (compared to 17.0% of clinicians in a secondary hospital).

Conclusions: There is significant practice variation and a lack of standards in the management of a common clinical problem, as well as a lack of consensus on the evidence underpinning common fixation methods. Further research is needed.

Level of Evidence: Level IV (Therapeutic)
Proximal Interphalangeal Joint Arthrodesis of the Hand Utilising a Rigid Intramedullary Device
Authors: TAYLOR Fraser , JOHNS Nicholas , MANOHORAN Varuguna , GRAHAM David
Published: April 2023

The proximal interphalangeal joint (PIPJ) is critical for proper finger and hand function. Arthritis of this joint can lead to significant pain and functional impairment. The APEX IP® Extremity Medical fusion device (Extremity Medical, Parsippany, New Jersey, USA) is an interlocking intramedullary screw device that provides a reliable method of hand PIPJ arthrodesis with good patient outcomes. We describe an easily reproducible surgical technique guide for using this device.

Level of Evidence: Level V (Therapeutic)
Endoscopic-assisted Infraclavicular Approach for First-Rib Resection in Neurologic Thoracic Outlet Syndrome: A Report of Two Cases
Authors: SUZUKI Taku , KIMURA Hiroo , MATSUMURA Noboru , IWAMOTO Takuji
Published: April 2023

Various reported surgical approaches for the treatment of thoracic outlet syndrome (TOS) exist and no firm evidence exists for any approach. A 16-year-old and a 29-year-old male presented with numbness in the upper limb. Neurologic TOS was diagnosed, and surgery was planned for the resection of the first rib and scalene muscles. Through an infraclavicular incision, open resection of the anterior scalene muscle and the anterior aspect of the first rib was performed. With the assistance of endoscopy, the middle scalene muscles and the posterior aspect of the first rib were resected. Preoperative symptoms improved after surgery without any complications. The endoscopic-assisted infraclavicular approach enabled resection of the first rib and scalene muscles, leading to satisfactory outcomes.

Level of Evidence: Level V (Therapeutic)
Decoding Aging Hallmarks at the Single-Cell Level
Authors: Ma Shuai , Chi Xu , Cai Yusheng , Ji Zhejun , Wang Si , Ren Jie , Liu Guang-Hui
Published: April 2023

Organismal aging exhibits wide-ranging hallmarks in divergent cell types across tissues, organs, and systems. The advancement of single-cell technologies and generation of rich datasets have afforded the scientific community the opportunity to decode these hallmarks of aging at an unprecedented scope and resolution. In this review, we describe the technological advancements and bioinformatic methodologies enabling data interpretation at the cellular level. Then, we outline the application of such technologies for decoding aging hallmarks and potential intervention targets and summarize common themes and context-specific molecular features in representative organ systems across the body. Finally, we provide a brief summary of available databases relevant for aging research and present an outlook on the opportunities in this emerging field.
RNA Modification in the Immune System
Authors: Han Dali , Xu Meng Michelle
Published: April 2023

Characterization of RNA modifications has identified their distribution features and molecular functions. Dynamic changes in RNA modification on various forms of RNA are essential for the development and function of the immune system. In this review, we discuss the value of innovative RNA modification profiling technologies to uncover the function of these diverse, dynamic RNA modifications in various immune cells within healthy and diseased contexts. Further, we explore our current understanding of the mechanisms whereby aberrant RNA modifications modulate the immune milieu of the tumor microenvironment and point out outstanding research questions.
Photo Thermal Diffusion of Excited Nonlocal Semiconductor Circular Plate Medium with Variable Thermal Conductivity
Authors: El-Sapa Shreen , Lotfy Khaled , El-Bary Alaa A. , Ahmed M. H.
Published: April 2023

To examine the effects of the nonlocal thermoelastic parameters in a nanoscale semiconductor material, a novel nonlocal model with variable thermal conductivity is provided in this study. The photothermal diffusion (PTD) processes in a chemical action are utilized in the framework of the governing equations. When elastic, thermal, and plasma waves interact, the nonlocal continuum theory is used to create this model. For the main formulations to get the analytical solutions of the thermal stress, displacement, carrier density, and temperature during the nanoscale thermo-photo-electric medium, the Laplace transformation approach in one dimension (1D) of a thin circular plate is utilized. To create the physical fields, mechanical forces and thermal loads are applied to the semiconductor’s free surface. To acquire the full solutions of the research areas in the time-space domains, the inverse of the Laplace transform is applied with several numerical approximation techniques. Under the impact of nonlocal factors, the principal physical fields are visually depicted and theoretically explained.
QSPR Study and Distance-Based New Topological Descriptors of Some Drugs Used in the COVID-19 Treatment
Authors: Ravi Vignesh , Chidambaram Natarajan , Çolakoğlu Özge , Ahmed Hanan , Jaganathan Subhasri , Jaganathan Jayasri
Published: April 2023

In chemistry and medical sciences, it is essential to study the chemical, biological, clinical, and therapeutic aspects of pharmaceuticals. To save time and money, mathematical chemistry focuses on topological indices used in quantitative structure-property relationship (QSPR) models to predict the properties of chemical structures. The COVID-19 pandemic is widely recognized as the greatest life-threatening crisis facing modern medicine. Scientists have tested various antiviral drugs available to treat COVID-19 disease, and some have found that they help get rid of this viral infection. Antiviral drugs such as Arbidol, chloroquine, hydroxychloroquine, lopinavir, remdesivir, ritonavir, thalidomide, and theaflavin are used to treat COVID-19. In this paper, reformulated leap Zagreb indices are introduced. Then, the reformulated leap Zagreb indices, leap eccentric connectivity indices, and reformulated Zagreb connectivity indices of these antiviral drugs are calculated. Curvilinear and multilinear regression models predicting the physicochemical properties of these antiviral drugs in terms of proposed indices are obtained and analyzed. The findings and models of this study will shed light on new drug discoveries for the treatment of COVID-19.
Identification of Biomarkers Associated with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy Using WGCNA and Machine Learning Algorithms
Authors: Sun Mengyi , Li Linping
Published: April 2023

Background. The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease. Methods. Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using “Metascape”. Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database. Results. We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated. Conclusion. As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF.
Study on Clinicopathological Features and Risk Factors of Patients with Multiple Primary Breast Cancers and Thyroid Disease
Authors: Li Jie , Liu Yonghong , Jin Jian , Shi Qingfeng , Ji Yanting , Zhang Bo , Hu Pengfei
Published: April 2023

Objective. To explore the clinicopathological features and risk factors of patients with multiple primary breast cancers and thyroid disease. Method. An analytic approach of the reviewing method was adopted to analyze the clinical data of 80 breast cancer patients who were admitted to our hospital from January 2020 to January 2022. They were divided into an observation group (breast cancer with thyroid lesions) and a control group (simple breast cancer) according to whether the clinical data were accompanied with thyroid lesions to compare the clinical characteristics, pathological types, staging characteristics, and molecular biological characteristics of the two groups and to research the risk factors of the two groups. Result. (1) In the comparison of clinical data, the number of people aged ≥60 in the observation group was higher than that in the control group, and there was significant difference between the groups in the menopausal status data (

P
<
0.05

). There was no statistical difference between the observation group and the control group in the comparison of clinical data of the body mass index, pregnancy frequency, labor frequency, and abortion history (

P
>
0.05

). (2) In the comparison of pathological type and staging data, there was no statistical difference in the comparison of data on the pathological type, histological grade, T staging, N staging, and TNM staging between the observation group and the control group (

P
>
0.05

). (3) In the comparison of data on molecular biology characteristics, there was a statistical difference in the nuclear proliferation antigen data between the observation group and the control group (

P
<
0.05

). There was no statistical difference in the comparison of data on the estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and molecular typing between the observation group and the control group (

P
>
0.05

). (4) Logistic regression analysis showed that age, menopausal status, and nuclear proliferation antigen index were the high-risk inflammatory factors for combined thyroid lesions (

P
<
0.05

). Conclusion. For patients with simple breast cancer, age, menopausal status, and nuclear proliferation antigen index are risk factors for combined thyroid lesions. Therefore, clinical attention should be paid to the above factors in the process of clinical treatment, and early-risk screening should be performed to achieve the purpose of improving the prognosis to the greatest extent.
Antidiabetic and Liver Histological and Ultrastructural Effects of Cynara scolymus Leaf and Flower Head Hydroethanolic Extracts in Nicotinamide/Streptozotocin‐Induced Diabetic Rats
Authors: Ahmed Osama M. , Abdel Fattah Asmaa A. , Abdul-Hamid Manal , Abdel-Aziz Ayman M. , Sakr Hader I. , Damanhory Ahmed A. , Abdel-Kawi Samraa H. , Ghaboura Nehmat , Awad Moaaz M. Y.
Published: April 2023

This study aims to investigate the effect of hydroethanolic extracts of Cynara scolymus (C. scolymus) leaf (CLHE) and C. scolymus flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose‐6‐phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C‐peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor‐α in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ‐induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill‐defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, via suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.
Can We Enhance Respectful Behaviors toward Parents with Gamification? An Observational Study of Gamification Elements and Child Attitudes toward Parents
Authors: Sarour Enas , Allinjawi Arwa , Alyahiwi Sara , Albeshri Ola
Published: April 2023

The use of gamification has gained important attention when it comes to developing desired behaviors in children. However, few studies have used this approach to increase respectful behaviors toward parents in Saudi Arabia. The aim of this study was to propose a gamified application by investigating the game element preferences of children and the children’s practices toward parents, and to use the interactive gamification app to enhance respectful behaviors toward parents in children aged 5 to 7 in Saudi Arabia. An interactive gamification app was conceived in order to encourage respectful behaviors in children. Parents observed their children and assessed them with a survey containing questions about respectful behaviors and application elements preferred by children. The questions had an internal consistency reliability above 0.85. There was a difference in gamification elements based on demographics, but no difference in respectful behaviors toward parents. Three gamification elements emerged as important contributors of respectful behaviors toward parents in children: points, rewards, and interaction with others. However, the time the child spent using a smart device was negatively related to respectful behaviors toward parents. A gamified application with two interfaces can be used to enhance respectful behaviors toward parents. Programs that focus on enhancing desired behavior in children aged 5 to 7 should use gamification approaches and direct particular attention to the three aforementioned elements. Moreover, parents should control the time their children spend using smart devices.
Estimating the Within-Person Change in Dental Service Access Measures during the COVID-19 Pandemic in the United States
Authors: Semprini Jason
Published: April 2023

Background. American adults delay dental care more than any other healthcare service. Unfortunately, the COVID-19 pandemic may have stalled efforts to address dental service delays. Early evidence has suggested substantial declines in dental service visits in the early phase of the pandemic; however, our study is among the first to measure within-person changes from 2019 to 2020 and conduct subgroup analyses to examine if changing dental patterns were mediated by exposure to the pandemic, risk of adverse COVID-19 outcomes, or dental insurance. Methods. We analyzed a National Health Interview Survey panel of individuals initially surveyed in 2019, with subsequent follow-up in 2020. The outcomes included dental service access measures and the interval of a most recent dental visit. By constructing a probability-weighted linear regression model with fixed-effects, we estimated the average within-person change from 2019 to 2020. Robust standard errors were clustered within each respondent. Results. From 2019 to 2020, adults reported a 4.6%-point reduction in the probability of visiting the dentist (

p
<
0.001

). Significantly higher declines were found in Northeast and West regions compared to Midwest and South regions. We find no evidence that declining dental services in 2020 were associated with more chronic diseases, older age, or lack of dental insurance coverage. Adults did not report more financial or nonfinancial access barriers to dental care in 2020 compared to 2019. Conclusions. The long-term effects of the COVID-19 pandemic on delayed dental care warrant continued monitoring as policymakers aim to mitigate the pandemic’s negative consequences on oral health equity.
Types and Distribution Characteristics of Callovian-Oxfordian Reservoir on the Right Bank of Amu Darya River in Turkmenistan
Authors: Wang Qiang
Published: April 2023

Given the characteristics of significant or enormous resources, a wide range, many reservoir types, and challenging exploration on the right bank of the Amu Darya River, we systematically studied the characteristics of its reservoirs. Based on the core description, thin sections in combination with logging and seismic facies characteristics as well as regional tectonic-sedimentary background, the Callovian-Oxfordian platform and the gentle slope sedimentary system in the Amu Darya Basin of Turkmenistan were summarized. Sedimentary subfacies such as evaporation platform, restricted platform, open platform, and platform margin reef are developed in block A and its west. In contrast, the upper slope, lower slope, and basin sedimentary subfacies are developed in the east of block A. On this basis, the main reservoir types on the right bank of the Amu Darya River are summarized, namely, porous reservoir, vuggy reservoir, fractured-porous reservoir, and fractured-vuggy reservoir. After describing the characteristics of various reservoirs in detail, the main controlling factors, development patterns, and distribution rules of the development of different reservoirs are summarized. Specifically, based on the platform reef, the porous reservoir and vuggy reservoirs are developed mainly on the concealed palaeouplift in the study area and are greatly influenced by atmospheric freshwater leaching and buried dissolution. Based on the dominant sedimentary facies, the fractured-porous reservoirs are mainly developed in the central areas on the right bank of the Amu Darya River. In the later period, hydrothermal fluid and hydrocarbon-generating acidic fluid can dissolve the reservoir through strike-slip faults and their associated fractures. Diagenetic fluid enters the reef through faults and associated fractures to form dissolved reservoir bodies of a certain scale. The fractured-vuggy reservoirs are mainly controlled by faults and dissolution and are mainly developed near the eastern thrust fault on the right bank of the Amu Darya River, effectively guiding the direction for further exploration and development in this area.
Construction of an Excellent 7 mRNAsi-Related Gene Model Based on Cancer Stem Cells for Predicting Survival Outcome of Cervical Cancer
Authors: Liu Yang , Yang Lin , Liang Hao , Zeng Jianhua , Hua Yuanyuan , Wu Huan
Published: April 2023

Background. Cervical cancer (CC) is one of the most frequent female malignancy. Cancer stem cells (CSCs) positively affect survival outcomes in cancer patients, but in cervical cancer, the mechanism of tumor stem cells is still uncertain. Methods. RNA-seq data and related clinical follow-up of patients suffering from CC were from TCGA. Consensus clustering screened prognostic mRNAsi-related genes and identified molecular subtypes for CC. Based on the overlapping differentially expressed genes (DEGs) in subtypes, we employed LASSO and multivariate Cox regression to screen prognostic-related genes and established the RiskScore system. The patients were grouped by RiskScore, the prognosis was analyzed by the Kaplan-Meier (K-M) curve among the various groups, and the precision of the RiskScore was assessed by the ROC curve. Finally, the potential worth of RiskScore in immunotherapy/chemotherapy response was assessed by evaluating TIDE scores and chemotherapy drug

IC

50

values. Results. We noticed that patients with low mRNAsi had a shorter survival and then identified three molecular subtypes (C1-3), with the C1 having the worst prognosis and the lowest mRNAsi. Finally, we identified 7 prognostic-related genes (SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8) via LASSO and Cox regression analysis. We established a 7-gene model defined RiskScore to predict the prognosis of CC patients. K-M curve indicated that low RiskScore patients had improved prognosis, and ROC curves indicated that RiskScore could precisely direct the prognostic evaluation for those suffering from the cancer. This was also confirmed in the GSE44001 and GSE52903 external cohorts. Patients were more sensitive to immunotherapy if with low RiskScore, and RiskScore exhibited precise assessment ability in predicting response to immunological therapy in CC patients. Conclusion. CC stemness is associated with patient prognosis, and the RiskScore constructed based on stemness characteristics is an independent prognostic index, which is expected to be a guide for immunotherapy, providing a new idea for CC clinical practice.
Survival of Middle Eastern and North African Individuals Diagnosed with Colorectal Cancer: A Population-Based Study in California
Authors: Zaki Timothy A. , Ziogas Argyrios , Chang Jenny , Murphy Caitlin C. , Anton-Culver Hoda
Published: April 2023

Background:

Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer–specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California.

Methods:

We identified adults (ages 18–79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer–specific survival and used Cox proportional hazards regression models to examine the association of race/ethnicity and survival, adjusting for clinical and socio demographic factors.

Results:

Of 110,192 persons diagnosed with colorectal cancer, five-year colorectal cancer–specific survival was lowest in Black (61.0%) and highest in MENA (73.2%) individuals. Asian (72.2%) individuals had higher survival than White (70.0%) and Hispanic (68.2%) individuals. In adjusted analysis, MENA [adjusted HR (aHR), 0.82; 95% confidence interval (CI), 0.76–0.89], Asian (aHR, 0.86; 95% CI, 0.83–0.90), and Hispanic (aHR, 0.94; 95% CI, 0.91–0.97) race/ethnicity were associated with higher, and Black (aHR, 1.13; 95% CI, 1.09–1.18) race/ethnicity was associated with lower survival compared with non-Hispanic White race/ethnicity.

Conclusions:

To our knowledge, this is the first study to report colorectal cancer survival in MENA individuals in the United States. We observed higher survival of MENA individuals compared with other racial/ethnic groups, adjusting for sociodemographic and clinical factors.

Impact:

Future studies are needed to identify factors contributing to cancer outcomes in this unique population.
Tobacco Smoke Is a Major Source of Aromatic Amine Exposure in U.S. Adults: 2013–2014 National Health and Nutrition Examination Survey (NHANES)
Authors: Seyler Tiffany , Mazumder Shrila , Ahamed Rayaj , Zhu Wanzhe , Blount Benjamin C. , Apelberg Benjamin J. , Wang Lanqing
Published: April 2023

Background:

Cigarette smoking increases the risk of cancer, cardiovascular diseases, and premature death. Aromatic amines (AA) are found in cigarette smoke and are well-established human bladder carcinogens.

Methods:

We measured and compared total urinary levels of 1-aminonaphthalene (1AMN), 2-aminonaphthalene (2AMN), and 4-aminobiphenyl (4ABP) in adults who smoked cigarettes exclusively and in adult nonusers of tobacco products from a nationally representative sample of non-institutionalized U.S. population in the 2013–2014 National Health and Nutrition Examination Survey.

Results:

Sample-weighted geometric mean concentrations of AAs in adults who smoked cigarettes exclusively compared with adult nonusers were 30 times higher for 1AMN and 4 to 6 times higher for 2AMN and 4ABP. We evaluated the association of tobacco-smoke exposure with urinary AAs using sample-weighted multiple linear regression models to control for age, sex, race/ethnicity, diet, and urinary creatinine. Secondhand smoke exposure status was categorized using serum cotinine (SCOT) among adult nonusers (SCOT ≤ 10 ng/mL). The exposure for adults who smoked cigarettes exclusively (SCOT > 10 ng/mL) was categorized on the basis of the average number of self-reported cigarettes smoked per day (CPD) in the five days prior to urine collection. The regression models show AAs concentration increased with increasing CPD (P < 0.001). Dietary-intake variables derived from the 24-hours recall questionnaire were not consistently significant predictors of urinary AAs.

Conclusions:

This is the first characterized total urinary AA concentrations of the U.S. adult non-institutionalized population. Our analyses show that smoking status is a major contributor to AA exposures.

Impact:

These data provide a crucial baseline for exposure to three AAs in U.S. non-institutionalized adults.
Data from BLEACH&STAIN 15-marker multiplexed imaging in 3098 human carcinomas reveals 6 major PD-L1-driven immune phenotypes with distinct spatial orchestration
Authors: Bady Elena , Moeller Katharina , Mandelkow Tim , Raedler Jonas B. , Yang Cheng , Ebner Julia , Lurati Magalie C.J. , Simon Ronald , Vettorazzi Eik , Buescheck Franziska , Luebke Andreas M. , Dum David , Menz Anne , Sauter Guido , Hoeflmayer Doris , Weidemann Soeren , Fraune Christoph , Uhlig Ria , Bernreuther Christian , Jacobsen Frank , Clauditz Till S. , Wilczak Waldemar , Burandt Eike , Steurer Stefan , Minner Sarah , Lennartz Maximilian , Blessin Niclas C.
Published: April 2023

Abstract
Multiplex fluorescence immunohistochemistry (mfIHC) approaches were yet either limited to 6 markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, CD31) in 3098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence-based framework –incorporating 17 different deep-learning systems– was established. Unsupervised clustering showed that the three PD-L1 phenotypes (PD-L1+tumor and immune cells, PD-L1+immune cells, PD-L1 negative) were either inflamed or non-inflamed. In the inflamed PD-L1+patients, spatial analysis revealed that an elevated intratumoral M2-macrophages as well as CD11c+dendritic cell infiltration (p<0.001 each) was associated with a high CD3+CD4±CD8±FOXP3±T-cell exclusion and a high PD-1 expression on T-cells (p<0.001 each). In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival (AUC: 0.72, p<0.001) compared to the commonly used percentage of PD-L1+ tumor cells (AUC: 0.54). In conclusion, our deep learning-based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance.
Implications: The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment and enables to study the prognostic relevance of more than 130 immune cell subpopulations.
Data from Tumor-derived CCL5 recruits cancer-associated fibroblasts and promotes tumor cell proliferation in esophageal squamous cell carcinoma
Authors: Dunbar Karen J. , Karakasheva Tatiana A. , Tang Qiaosi , Efe Gizem , Lin Eric W. , Harris Michael , Sahu Varun , Sachdeva Uma M. , Hu Jianhua , Klein-Szanto Andres J. , Henick Brian , Diehl J. Alan , Nakagawa Hiroshi , Rustgi Anil K.
Published: April 2023

Abstract
Cancer-associated fibroblasts (CAFs) can promote tumor growth, metastasis and therapeutic resistance in esophageal squamous cell carcinoma (ESCC), but the mechanisms of action remain elusive. Our objective was to identify secreted factor(s) that mediate the communication between CAFs and ESCC tumor cells with the aim of identifying potential druggable targets. Through unbiased cytokine arrays, we have identified CC motif chemokine ligand 5 (CCL5) as a secreted factor that is increased upon co-culture of ESCC cells and CAFs, which we replicated in esophageal adenocarcinoma (EAC) with CAFs. Loss of tumor-cell derived CCL5 reduces ESCC cell proliferation in vitro and in vivo and we propose this is mediated, in part, by a reduction in ERK1/2 signaling. Loss of tumor-derived CCL5 reduces the percentage of CAFs recruited to xenograft tumors in vivo. CCL5 is a ligand for the CC motif receptor 5 (CCR5), for which a clinically approved inhibitor exists, namely Maraviroc. Maraviroc treatment reduced tumor volume, CAF recruitment and ERK1/2 signaling in vivo, thus, mimicking the effects observed with genetic loss of CCL5. High CCL5 or CCR5 expression is associated with worse prognosis in low grade esophageal carcinomas.

Implications: These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5-CCR5 axis in ESCC.
Methods and Software to Analyze Gene-Environment Interactions under a Case-Mother-Control-Mother Design with Partially Missing Child Genotype
Authors: Bureau Alexandre , Tian Yuang , Levallois Patrick , Giguère Yves , Chen Jinbo , Zhang Hong
Published: April 2023

Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype. Methods: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype. Results: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of small-for-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates. Conclusion: We recommend the robust version of the modified retrospective likelihood.