bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune‑mediated hepatitis and hepatitis B virus reactivation induced by immunotherapy in hepatocellular carcinoma: A case report and literature review
Authors: Yang Taohua , Jia Zhidong , Chen Xu , Chen Guanyuan , Xiang Leyang , Li Zhendong
Published: March 2024

Immune checkpoint inhibitors (ICIs) are commonly used in the treatment of hepatocellular carcinoma (HCC) and performing miracles, however, the immune‑related adverse events(irAE) should not be neglected. Here, we report a patient in their 40s with advanced HCC, who treated with anti-programmed death‑1(PD‑1) monoclonal antibody and experienced immune-mediated hepatitis (IMH) and simultaneously hepatitis B virus (HBV) reactivation. The patient developed fever in the third day after receiving immunotherapy, and severe IMH, manifested as depression, abdominal distension, ascites, repeated low fever and rapid deterioration of liver function within two months, the hepatitis B virus (HBV) DNA quantity was also observed increased significantly from 3.94E+01 IU/ml to 1.1E+04 IU/ml. After receiving corticosteroid impulse therapy, anti-hepatitis B virus therapy and other symptomatic treatments, he was recovered rapidly within one week. Eight months later, the patient received anti-programmed death ligand‑1 (PD-L1) monoclonal antibody, Envafolimab, combined with tyrosine kinase inhibitor based targeted therapy, however, severe irAE and reactivation of HBV didn’t reappear, which might be attributed to the difference of mechanism between anti-PD‑1 and anti-PD‑L1 therapies. In conclusion: Anti- PD-L1 may lead to less adverse effect on immune homeostatic and better safety than anti- PD‑1, besides, anti-PD-L1 therapy, such as Envafolimab, could participated in the immune regulation of anti-HBV. This case helps to strengthen the understanding of the difference between anti- PD‑1 and anti- PD‑L1 therapy, and also provides a hope for a better cure of clearing HBV.
Tunable electronic and magnetic properties of defective g-ZnO monolayer doping with non-metallic elements
Authors: Wen Junqing , Shi Mengqian , Lin Pei , Chen Guoxiang , Zhang Jianmin
Published: March 2024

The electronic and magnetic properties of non-metallic (NM) elements doping defective graphene like ZnO (g-ZnO) monolayer including O vacancy (VO) and Zn vacancy (VZn) are studied using first principles method. VO-g-ZnO is semiconductors and VZn-g-ZnO is magnetic semiconductor. The results show that B, C, N, Si, P, 2S and 2Si doping VO-g-ZnO systems present half-metal and magnetic semiconductors, and the magnetism mainly originates from spin polarization of doping atoms. For single or double NM elements doping VZn-g-ZnO, 2P doping system presents semiconductor, while other systems present ferromagnetic metal, half-metal and magnetic semiconductor. The magnetism of single NM elements doping VZn-g-ZnO mainly comes from spin polarization of O atoms near defect point. For double NM elements doping VZn-g-ZnO, spin splitting occurs mainly in p orbitals of O atoms, dopant atoms and d orbitals of Zn atoms. NM elements doping defect g-ZnO can effectively regulate electronic and magnetic properties of the system.
Is E-health the Future for Stroke Rehabilitation? Health Professionals’ Experiences of Implementation of a Mobile Phone-supported and Family Centred Rehabilitation Intervention After Stroke in Uganda
Authors: Ytterberg Charlotte , Eriksson Gunilla , Stefansdotter Emelie , Kamwesiga Julius , von Koch Lena , Guidetti Susanne
Published: March 2024

Background
Stroke is currently increasing in low-income countries and hence it is of importance to develop modes of stroke rehabilitation adapted to the context. Information and communication technology can potentially improve stroke rehabilitation, yet mostly studied in high-income countries. The increasing usage of mobile phones in sub-Saharan region calls for studies of the implementation and use of telerehabilitation in stroke. Research concerning health professionals’ experience regarding use of telerehabilitation for stroke is lacking. The aim was to explore health professionals’ experiences of implementing a mobile phone-supported and family-centred rehabilitation after stroke, F@ce 2.0, in Uganda. An additional aim was to describe health professionals’ views of how to further develop and optimise implementation of e-health.
Method
Data were collected in semi-structured interviews with nine health professionals participating in F@ce 2.0. The data was analysed using qualitative content analysis with an inductive approach.
Results The intervention was delivered according to the predetermined design. The findings revealed several mediators and challenges in the implementation process. Three categories emerged: Bridging gaps in rehabilitation, Barriers in the implementation of the intervention and Facilitators in the implementation of the intervention. An additional independent category Improving the model and enabling sustainability emerged regarding the participants’ views regarding implementation of future e-health interventions in stroke rehabilitation.
Conclusions
The health professionals appear positive to implement tele-rehabilitation for people within the sub-Saharan context. This study contributes to knowledge on how implementation processes for similar interventions could be improved in the future and encourages further studies to be conducted in this field of research.
Maternal child maltreatment and trajectories of offspring behavioural and emotional difficulties from age 4 to 7 years – results from a prospective birth cohort study
Authors: Clemens Vera , Wernecke Deborah , Fegert Jörg M. , Jon Genuneit , Rothenbacher Dietrich , Braig Stefanie
Published: March 2024

Maternal experience of child maltreatment (CM) has been associated with maternal and child mental health. However, evidence about the course of child mental health and maternal CM is scarce. Therefore, this study aims to compare trajectories of mental health in children according to maternal CM exposure and maternal mental health. We included 327 mothers and their singleton child from the Ulm SPATZ Health Study, a prospective birth cohort study. Child mental health was determined by the Strength and Difficulties Questionnaire (SDQ) at the age of 4, 5, 6, and 7 years and maternal CM by the Childhood Trauma Questionnaire (CTQ). Results display that maternal CM is associated with more behavioural and emotional difficulties in children, a trend that tends to increase with older child age. The sum of maternal mental health problems across this time course mediates this association. Male child sex is associated with more mental health problems in the child and the mother. These results provide an important first insight into the relevance of maternal CM on the trajectories of mental health in the offspring and highlight the importance of chronicity and severity of maternal mental health. Further prospective research in cohorts with longer follow-ups up into adolescence and adulthood is needed.
Development of covariational reasoning of sine and cosine functions in high school students using GeoGebra applets: the case of Freddy
Authors: Martínez-Sierra Gustavo , Villadiego-Franco Kleiver Jesús
Published: March 2024

This research aims to investigate how to support the development of high school students’ covariational reasoning of sine and cosine functions. To achieve this goal, we conducted classroom design research where we experimented with a hypothetical learning trajectory aimed at fostering students’ continuous smooth covariational reasoning of sine and cosine functions. The Freddy’s actual learning trajectory confirms our general learning hypotheses, indicating that the visualization and manipulation of the simulation of a Ferris wheel’s movement in GeoGebra applets incorporating measuring instruments foster the development of covariational reasoning of sine and cosine functions. The results of this research are consistent with previous studies that have found that the use of interactive activities in dynamic digital environments, simulating a Ferris wheel, promotes the development of students’ covariational reasoning regarding sinusoidal functions at a smooth continuous level. Integrating covariational reasoning with hypothetical learning trajectories offers promising implications for educational practices which are discussed at the end.
A Novel Corneal Indentation Device for Comparison of Corneal Tangent Modulus before and after FS-LASIK in vivo
Authors: Zhang Yan , Lin Junyu , Lu Shu-Hao , CHONG Jones Iok-Tong , Yang Cheng , Lan Jianqing , Xie Wenjuan , Li Juan , LAM David Chuen-Chun , Cao Dan , Zeng Jin
Published: March 2024

Background
Corneal refractive laser surgery is widely used to correct myopia and astigmatism due to its safety and effectiveness. However, postoperative changes in corneal biomechanics, such as corneal ectasia, can occur, necessitating a deeper understanding of these changes. Finite Element Analysis has shown promise in predicting surgical outcomes based on corneal biomechanics. Devices like the Ocular Response Analyser (ORA) and Corvis ST provide noninvasive ways to measure corneal biomechanics, aiding in the assessment of corneal behavior post-surgery. Young's modulus and tangent modulus are crucial parameters for describing corneal elasticity, but there is limited data on the changes in tangent modulus following Femtosecond Laser-Assisted LASIK (FS-LASIK) in humans. This study aimed to investigate the effect of FS-LASIK on the corneal tangent modulus using a novel corneal indentation device (CID). The study sought to explore changes in corneal tangent modulus after FS-LASIK, taking into account central corneal thickness (CCT) and corneal radius, to enhance our understanding of the biomechanical changes induced by this surgical procedure.
Results
Sixty-six patients (66 eyes) underwent FS-LASIK, resulting in significant changes in CCT, corneal radius, and Goldmann intraocular pressure (GAT IOP) six months post-surgery (△CCT=-88 ± 31 µm, △corneal radius = 0.81 ± 0.30 mm, △GAT IOP=-3.2 ± 2.4 mmHg, p < 0.001) 6 months after surgery. However, corneal stiffness did not significantly change (△=-0.002 ± 0.011, p < 0.2). The corneal tangent modulus showed a significant increase post-surgery (△=0.263 ± 0.146, p < 0.001), exhibiting a negative correlation with CCT (r = -0.68, P < 0.001) and a positive correlation with corneal radius (r = 0.71, P < 0.001). For each 1 mm increase in corneal radius, there was a 0.23 MPa increase in corneal modulus, and for every 100 µm reduction in corneal thickness, there was a 0.14 MPa increase in corneal modulus.
Conclusions
The corneal tangent modulus, influenced by corneal radius and CCT, increased significantly following FS-LASIK. This study highlights the biomechanical changes induced by FS-LASIK, with implications for understanding corneal behavior post-surgery and its potential impact on patient outcomes.
A Retrospective Analysis: A Predictive Model Using Platelets and Neutrophil-to- Lymphocyte Ratio for the Number of Lymph Node Metastasis in Papillary Thyroid Carcinoma
Authors: Chen YuYing , Wu Fan , Ge Mengqian , Hu Tao , Qian Shuoying , Cai Yuan , Huang Xuanwei , Huang Kaiyuan , Pan Gang , Luo Dingcun
Published: March 2024

Objective The aim of this study was to investigate the high-risk clinical factors for large-number lymph node metastases (LNLNM) inthyroid papillary carcinoma (PTC).
Methods The clinicopathological data from the 731 PTC patients who underwent thyroid operation between September 2021to October 2022 in the surgical oncology of Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine were collected. Univariate and multivariate logistic analyses were conducted to identify risk factors for LNLNM in PTC. A predictive model for assessing LNLNM in PTC was established and validated by using receiver operating characteristic curves (ROC), the Hosmer-Lemeshow (HL)test, calibration curves, and decision curve analysis (DCA).
Results Age, tumor diameter, platelets and neutrophil-to-lymphocyte ratio (NLR) were identified as independent risk factors for LNLNM in PTC patients. A predictive model was developed to evaluate the risk of LNLNMwith an area under the curve (AUC) of 0.827 (P<0.001, 95%CI: 0.784-0.870) and the specificity and sensitivity were both 75.8%. The AUC of the validation group was 0.824(P<0.001, 95%CI: 0.757-0.890) with a specificity of 79.5% and a sensitivity of 76.0%. Furthermore, themodel demonstrated good calibration through the HL test and favorable diagnostic value by calibration curve and DCA.
Conclusion Age, tumor diameter, platelets and NLRare high-risk factors for LNLNM in PTC, and the predictive model established in combination with the above factors couldeffectively predict the occurrence of LNLNM in PTC. This study provides support for surgeons to accurately predict the possibility of LNLNM and develop personalized treatment plans before surgery.
Seismic stability chart for 3D Hoek-Brown rock slope: A novel approach integrated tension cutoff and dynamic seismic effect
Authors: Sun Zhibin , Lou Chenglong , Jin Can , Xu Jingshu , Dias Daniel
Published: March 2024

Stability charts are a robust tool for rapidly assessing the stability of slopes in Hoek-Brown (HB) rocks. A notable shortcoming of previous charts has been their limited focus on slip-shear failure induced by equivalent static seismic forces, largely neglecting the potential for tensile failure due to rupture of material, and the dynamic aspects of seismic motion. To enhance the precision of existing chart methodologies, this paper introduces an innovative stability chart for width-restricted HB rock slopes. Seismic safety factors (\({F_s}\)) for constructing the chart are derived through upper bound limit analysis (UBLA). To incorporate the rock's tensile strength, an equivalent linearization of the HB criterion with a tension cutoff is proposed and utilized within an advanced horn-like mechanism. This mechanism features segments that account for tensile and shear forces to facilitate the integration of slope tensile failure. The dynamic seismic influences are captured using a pseudo-dynamic approach, which assumes sinusoidal seismic wave propagation and aids in the incorporation of dynamic seismic parameters such as wave velocity, period, and amplification factor. Utilizing the UBLA-based \({F_s}\), novel charts are developed. Charts incorporating a tension cutoff are enhanced for both intact and jointed rock masses. Two correction factors are introduced to account for the impacts of phase changes and acceleration amplification. Derived from the analysis of extensive datasets, these factors enable the conversion of published chart solutions into more accurate pseudo-dynamic outcomes.
Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program
Authors: Chen Yong , Zhang Dazheng , Zhang Bingyu , Wu Qiong , Zhou Ting , Tong Jiayi , Lu Yiwen , Chen Jiajie , Wang Huiyuan , Chisolm Deena , Jhaveri Ravi , Kenney Rachel , Rothman Russel , Rao Suchitra , Williams David , Hornig Mady , Morris Jeffrey , Forrest Christopher
Published: March 2024

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.
Learning Curve Analysis of Transvaginal Natural Orifice Transluminal Endoscopic Surgery in Treating Ovarian Cysts: A Retrospective Cohort Study
Authors: Feng Dan , Liu Tianjiao , Xiao Li , Li Xin , Huang Lu , He Li , Lin Yonghong
Published: March 2024

Background：Transvaginal Natural Orifice Transluminal Endoscopy (vNOTES) is regarded as a challenging surgical technique to learn but is promising in reducing perioperative pain and significantly improves the cosmetic outcomes. Previous studies on the learning curve analysis of vNOTES mainly focuses on the hysterectomy approach, while the vNOTES ovarian cystectomy’s learning curve was merely reported thought more frequently performed than vNOTES hysterectomy. Therefore, this study seeks to analyze the learning curve of three surgeons with varying levels of experience in performing endoscopic surgery for the treatment of ovarian cysts using vNOTES.
Methods: A total of 127 patients with ovarian cysts of a variety of pathological types were treated by vNOTES ovarian cystectomy performed by three surgeons of different levels of endoscopic surgical experience. Each surgeon’s learning curve was plotted using the Cumulative Sum method and divided into three or four phases of technique learning at the turning point of the learning curve. The sociodemographic and clinical features of patients in each phase were then compared and factors potentially associated with operation time were also screened.
Results: The learning curve was presented in four phases. The operation time (OT) was significantly shorter in phases II (53.66 ± 16.55 min) and IV (54.39 ± 23.45 min) as compared with phases I (68.74 ± 15.85) and III (75.93 ± 30.55) (p <0.001). More cases of serve pelvic adhesion and chocolate cyst were assigned in the later phases. The presence of pelvic adhesion [adjusted odds ratio (OR) 7.149 (0.506, 13.792), p = 0.035] and bilateral cyst [adjusted OR 16.996 (2.155, 31.837), p = 0.025], max diameter of cyst[adjusted OR 2.799 (0.174, 5.425), p = 0.037], and surgeon’s experience [adjusted OR -6.118 (-11.814, -0.423), p =0.035] were significantly associated with OT.
Conclusion: There learning curve of ovarian vNOTES has four phases. vNOTES ovarian cystectomy could be mastered after performing seven, nine, and 16 cases by surgeons with the most, average, and least experience in gynecologic endoscopic surgeries.
Trial registration: ChiCTR2200059282 (Registered on April 28th, 2022)
Research on Robotic Polishing Process of Marble with Complex Curved Surface based on Sol-Gel Flexible Tools
Authors: Guo Yaobin , Huang Shengui , Huang Jixiang , Lu Jing
Published: March 2024

The newly developed Sol-Gel (SG) flexible tools are used to polish complex marble surfaces with a robot to achieve a high gloss, low roughness, and scratch-free surface. The SG tool is composed of semi-solid abrasive and flexible fiber pads, which can realize a dual yielding effect at both the micro and macro levels, so that the SG flexible tool can better fit to the complex curved surface. Through the simulation analysis of the contact of SG flexible tools, the relationship between different curvature surfaces and polishing force was obtained. Based on the Preston material removal theory, constant pressure polishing of surfaces of different curvature was achieved by simulating the contact force distribution between the SG flexible tool and the marble surface, as well as the constant pressure material removal profile. By optimizing the space of the polishing trajectory, the uniformity of the material removal depth was improved, and the consistency of surface quality after polishing was enhanced. By establishing a model that correlates the optimum polishing trajectory space with curvature for surfaces of different curvature, the effective prediction of material removal profiles for robotic polishing of surfaces of different curvature was achieved. These strategies aim to ensure surface consistency after polishing complex curved surface under different conditions, thereby increasing product added value. This research provides initial theoretical guidance for the application of SG flexible tools in robotic polishing of marble with complex curved surface.
The Effect of Electronic Cigarette Use on Female Sexual Functions
Authors: Culha Mehmet , Kara Tugba
Published: March 2024

Aim While the effect of tobacco use on female sexual functions is known, the effect of electronic cigarettes on female sexual functions is unknown. The aim of this study is to investigate whether electronic cigarette use influences female sexual functions.Method Female patients over the age of 18 who applied to the Chest Diseases Polyclinic between July and August 2023 were included in the study. Patients were divided into 3 groups according to smoking status. Patients who consume tobacco products, patients who consume electronic cigarettes, and patients who do not smoke. Participants filled out the Female Sexual Function Scale (FSFI), which consists of 19 questions. Participants' sexual function scores were compared between groups. Female Sexual Dysfunction (FSD) rates were evaluated between groups.Results A total of 171 women participated in the study. The mean age of the participants was 34.25 ± 7.51 (19–58). Participants who smoked were divided into two groups: tobacco smokers (n = 56) and electronic cigarette users (n = 44). 71 participants who did not smoke constituted the control group. A total of 72 patients (42.1%) were found to have FSD. When the electronic cigarette group and the control group were compared, the FSFI-orgasm, satisfaction, pain and total FSFI scores of the participants in the e-cigarette group were found to be lower than the control group (p = 0.005 for orgasm, p = 0.029 for satisfaction, p = 0.046 for pain and Total p = 0.040 for FSFI). More FSD was observed in the cigarette group and e-cigarette group than in the control group (26.8% for the control group, 48.2% for the cigarette group, 47.7% for the e-cigarette; p < 0.001).Conclusion FSD can be seen in women who use e-cigarettes as frequently as in women who smoke regular cigarettes, and FSD is seen at a higher rate than in women who do not smoke.
Nucleolar protein interacting with the FHA domain of MKI67 may be an important factor in promoting the development of colorectal cancer: a comprehensive study integrating bulk RNA-seq, scRNA-seq, protein immunohistochemistry and CRISPR
Authors: Li Hui , Tang Yu-Xing , Chen Yi , Huang Wan-Ying , He Rong-Quan , Huang Zhi-Guang , Zeng Da-Tong , Xia Zhi-Yuan , Song Rui , Zhang Han Jie , Chen Yu-Zhen , Zhao Bin-Hui , Qin Si-Ru , Luo Jia-Yuan , Chen Gang
Published: March 2024

Background
Limited evidence suggests that nucleolar protein interacting with the FHA domain of MKI67 (NIFK) plays a significant role in tumour occurrence and development. The mechanism and clinical value of NIFK in colorectal cancer (CRC) still lack a comprehensive evaluation.
Materials and Methods
Cancerous tissue and paracancerous tissue of 266 CRC patients were collected for immunohistochemistry, and the mRNA expression profiles of 2262 CRC tissue and 1297 non-CRC tissue worldwide were collected and analysed at the NIFK protein and mRNA levels. Analyse the effect of knocking out NIFK by CRISPR on the growth status of CRC cells in 43 CRC cell lines. Enrichment analysis was used to explore the potential biological behaviour of NIFK in the CRC. The impact of NIFK on the immune microenvironment and single-cell landscape of CRC tissue was also analysed. In addition, the clinical value of NIFK in CRC was also evaluated in terms of clinical pathology, targeted therapy, and immunotherapy.
Results
The expression levels of NIFK protein (p < 0.05) and mRNA (SMD = 2.13, p < 0.05) in CRC were significantly higher than those in non-CRC. CRC cells exhibit a strong requirement for NIFK for growth. Abnormal expression of NIFK may affect the progression of CRC by affecting the GALECTIN, ANGPTL, and GDF signalling pathways of malignant epithelial cells, the MIF signalling pathway of T cells, and the TGFb signalling pathway of NK cells. The high expression of NIFK protein and mRNA has a strong ability to identify CRC.
Conclusion
NIFK plays an important role in the occurrence and development of CRC. NIFK may promote the occurrence and development of CRC through the cell cycle, ribosome, and mitochondrial pathways. The T-cell MIF pathway may have certain clinical value in anti-tumour therapy.
Awareness, Knowledge, and Practice towards Medication Overuse Headache in Thailand: A University Hospital-Based Survey in a Residency Training Program
Authors: Anukoolwittaya Prakit , Pongpitakmetha Thanakit , Hiransuthikul Akarin , Thanprasertsuk Sekh , Rattanawong Wanakorn
Published: March 2024

Background:Medication Overuse Headache (MOH) represents a significant challenge in patient care, with physicians playing a vital role in its prevention and management. Nonetheless, awareness, knowledge, and practices concerning MOH among physicians are often found to be inadequate.
Methods:A cross-sectional university-based hospital study was conducted to investigate awareness, knowledge, and practices related to MOH among resident doctors from family medicine, internal medicine, and neurology specialties. Participants were surveyed using an internet-based questionnaire.
Results:70 out of 130 residents participated in this study. 10% of participants were unaware that analgesia could exacerbate headaches. 11.4% of participants were uncertain about the classification of MOH. 31.4% and 44.3% of participants were unsure about the frequency of simple analgesia and migraine-specific drug use leading to MOH, respectively. 22.9% of participants prescribed opioids for abortive treatment in migraine patients. Neurology residents performed better in many aspects compared with others.
Conclusion:The findings highlight the need for improved MOH education across medical specialties to enhance patient care and reduce the healthcare burden of MOH.
Blood metabolome profiling for patient stratification and assessment of disease severity among Asian Indian patients with Type 2 diabetes mellitus
Authors: Rana Sneha , Mishra Vivek , Nakrani Prajval , Kumar Ega Lakshman , Sahay Manisha , Sahay Rakesh Kumar , Wangikar Pramod P.
Published: March 2024

Introduction: Type 2 diabetes mellitus is a heterogeneous disease with broader metabolic perturbation beyond hyperglycemia, resulting in varied prognoses. Clustering analyses using clinical features have identified at least four sub-types with differing disease progression among patients with type 2 diabetes. Additionally, patients are at risk of developing complications such as diabetic kidney disease (DKD), the early stages of which are clinically silent. Metabolomics offers a comprehensive understanding of the underlying metabolic intricacies, beyond conventional clinical markers such as glucose and creatinine.
Objective: We aimed to identify significant metabolites that can help in patient stratification and early assessment of DKD in Indian patients with type 2 diabetes.
Methods: In this case-control study, we used mass spectrometry coupled to liquid (LCMS) and gas chromatography (GCMS) to profile metabolites from the whole blood samples from a cohort of Asian Indians belonging to three groups: non-diabetic, Type 2 diabetes, and DKD.
Results: We identified 290 unique metabolites using both LCMS and GCMS, of which 26 and 20 metabolites were significantly associated with Type 2 diabetes and DKD, respectively, after p-value correction for false discovery rate. K-means and hierarchical clustering revealed two distinct sub-groups within the type 2 diabetes group with nine significant metabolites indicating differences in disease severity. Furthermore, seven metabolites showed progressive changes from non-diabetic to type 2 diabetes to DKD.
Conclusion: Metabolome profiling has the potential to be used for patient stratification and early diagnosis of DKD in Indian patients with type 2 diabetes in Asian Indians, towards facilitating personalized treatment with timely intervention.
A real-world pharmacovigilance analysis of FDA adverse event reporting system database for baloxavir marboxil
Authors: Hai Le , Wu Jiaojiao , Pan Xiaohong , Tu Xiaoqin , Xie Yingying , Su Gui
Published: March 2024

Baloxavir marboxil represents a groundbreak drug as the premiere agent targeting influenza with an innovative mechanism of action. The study was to investigate the adverse events and provide reference for clinical safety. The adverse events data were collected from the U.S. FDA Adverse Event Reporting System (FAERS) database covering the first quarter of 2018 to the third quarter of 2023. Two methods, reporting odd ration (ROR) and bayesian confidence propagation neural network (BCPNN) were used to detect the adverse events risk signal. A total of 1671 adverse events reports with baloxavir marboxil as the main suspected drug were collected. More women and patients under 18 years of age were reported. It was found that the adverse events signals involved multiple systems, among which the high-risk signals included melena, altered state of consciousness, delirium, abnormal behavior, rapid severe anaphylaxis, anaphylactic shock and erythema multiforme. Safety warning signs of ischemic colitis and rhabdomyolysis, which were high risk and not mentioned in the instructions, were also detected. In addition to the adverse events recorded in the manual, ischemic colitis, neuropsychiatric symptoms, allergic reactions, severe skin adverse reactions and rhabdomyolysis in the clinical application of baloxavir marboxil also should be paid attention to ensure the safety of patients.
Headaches in SLE Patients: A Cross-Sectional Analysis of Clinical, Immunological, and Radiological Correlations
Authors: Samy Eman , Zahran Enas S. , Sabry Mona , Elshony Hosna Saad
Published: March 2024

Background
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder presenting with diverse clinical manifestations, among which headaches are prominent. This cross-sectional study aimed to comprehensively investigate the relationship between SLE and headaches, analyzing prevalence, types, and their clinical, immunological, and radiological implications.
Method
A comparative study included 179 SLE patients categorized into Headache and Non-Headache groups. Demographics, disease activity, neurological information, immunological investigations, and brain imaging were collected. Headaches were diagnosed and classified using the International Classification System, Activity index was done using SLE disease activity index (SLEDAI).
Results
Headaches affected 55% of SLE patients, mostly as tension-type (65%) and migraine (27%) headaches. None met the lupus headache criteria. Disease activity (SLEDAI) was significantly higher in the Headache Group. Muco-cutaneous manifestations were associated with tension-type and migraine headaches. Anti-phospholipid (APL) antibody positivity showed a significant association with migraine and cluster headache. Neuropsychiatric manifestations, including ischemic stroke and venous sinus thrombosis, were more prevalent in Headache Group, although not clinically significant. Brain MRI abnormalities were observed in 8% of headache sufferers, including venous sinus thrombosis (2%), ischemic stroke (5%) and white matter hyperintensities (1%).
Conclusion
Our study reveals complex relationship between SLE and headaches, emphasizing the potential clinical relevance of headaches as markers for increased SLE disease activity. Immunological factors, particularly APL antibodies, show associations with specific headache types. Brain imaging abnormalities underscore the intricate neurobiological landscape in SLE patients with headaches. Further research is warranted to explore biomarkers, treatment impacts, and intervention strategies for managing headaches in SLE patients.
RETRACTED: Scarlet fever epidemics, deaths, effects on society and precautions taken in the Ottoman Empire and the Early Turkish Republic
Authors: Erkmen Ayşe , Tüzün Nevim , Erkmen Osman
Published: March 2024

The authors have requested that this preprint be removed from Research Square.
Qualification of the Attitude Control System of the E-band CubeSat EIVE
Authors: Eggert Marius , Bötsch-Zavřel Lena , Fugmann Martin , Holeczek Cedric , Koller Markus , Kranz Markus , Lengowski Michael , Löffler Thorben , Loidold Lukas-Maximilian , Maier Philipp , Meier Jakob , Mohr Ulrich , Müller Robin , Schweigert Robin , Starzmann Dominik , Steinert Michael , Zietz Martin , Schoch Benjamin , Haussmann Simon , Tessmann Axel , Freese Jens , Klinkner Sabine
Published: March 2024

The 6U CubeSat EIVE was developed for the verification of an E-band link from space to ground. Establishing sucha link presents challenging requirements for the development of an attitude control system of a CubeSat. To verify thefunctionality of its components, both the sensors and actuators, a number of tests were conducted prior to launch. Theseranged from simple functionality tests to performance tests and were accompanied by calibration campaigns. Qualificationof the attitude control algorithms proved to be a challenge, as a fitting simulator setup was not available. Therefore, limitedtests comparing the onboard software code to MatLab algorithms were used. This paper presents the types of testsconducted during the qualification campaign and their significance. On ground behavior is compared to in-orbit telemetry.The issues detected during ground tests as well as the issues achieving significant results from the tests are discussed andcompared to the problems detected during launch and early orbit phase. These comparisons illustrate the shortcomings ofsome of the tests executed and improvements for the validity of some tests are presented.
Estimating Quality of OCT Cubes using Phase-Level Unified Metric Evaluation (PLUME-OCT)
Authors: Milloz Alicia , Molas Grégoire , Paychère Yves , Bouillon Alexandre , Amiot Victor , Gurtler Laurent , Bardet James , Torrecillos Flavie , Bergmann Sven , Schlingemann Reinier , Vela Sofia Ortin , Meloni Ilenia , Tomasoni Mattia
Published: March 2024

Background and Aim
Optical coherence tomography (OCT) has emerged as a robust tool for in vivo retinal imaging, offering dynamic visualization of retinal microstructures in 3D (OCT Cube). This technology plays a crucial role in diagnosing, monitoring, and treating various ocular pathologies by allowing the extraction of retinal biomarkers. Quality Control (QC) measures have been developed to assess the quality of the individual 2D Scans (B-scans) that compose the OCT cube. However, during image acquisition, minor movements of the head or eye can degrade image quality by causing misalignment of individual B-scans with respect to one another, impacting the quality and reproducibility of 3D retinal biomarkers. New, reliable, automated, and efficient QC methods are needed to complement existing QC methods that evaluate the quality of 2D Scans.
Methods
We developed Phase-Level Unified Metric Evaluation for OCTs (PLUME-OCT), a novel method that quantifies the degree of misalignments of OCT cubes to produce quality metrics. PLUME-OCT was evaluated on two sets of 40 OCT cubes, manually annotated by four annotators. Additionally, we tested it on two cohort studies: the UK BioBank, comprising 88,247 individuals, and OphthalmoLaus (OL), consisting of 1,523 individuals.
Results
We demonstrated that PLUME-OCT effectively detects misalignments between B-scans. Furthermore, we established its applicability for filtering large datasets, generating metrics partially orthogonal to the Signal-to-Noise Ratio (Pearson’s r = -0.51). PLUME-OCT’s implementation is made available as a software package.
Conclusion
We introduce PLUME-OCT, a novel automated method designed for assessing the quality and volumetric coherence of OCT scans. PLUME-OCT operates without the need for reference images and utilizes minimal computational resources.
„Dagmar’s Digital Day – A Self-Assessment Game“. Ein Werkstattbericht
Authors: Heßler Daniel , Lotzow Stephanie
Published: March 2024

Neben dem reinen Unterhaltungsfaktor besteht das Potenzial von Serious Games darin, spielerisch zu lehren, zu lernen und zu forschen. Dieses Potenzial soll am Beispiel von „Dagmar’s Digital Day – A Self-Assessment Game“ (LevelUp, 2023) aufgezeigt werden. Das Spiel ist auf Datenerhebung, Datenexport und Datenmodifikation ausgelegt und leistet damit einen innovativen Beitrag zur Forschung sowie ein Angebot zur Weiterbildung im Bereich digitaler Kompetenz. In diesem Werkstattbericht geben die Entwickler:innen des Spiels einen Einblick in den Produktionsprozess und zeigen neben den zentralen Funktionen auch die Herausforderungen auf, die im Spannungsfeld von Forschung und Gamification entstehen.
Application of kinetic models to study the sorption rate in the ‘ammonium ions–calcined sorbent’ system
Authors: Korotkova G. T. , Zakolyukina A. M. , Bushumov S. A.
Published: March 2024

This study examines sorption kinetics for the extraction of ammonium ions from an aqueous solution under static conditions using 5 g of sorbent. The sorbent was obtained by calcining ash and slag waste accumulated in the ash dump following hydraulic ash removal. The initial concentrations of ammonium ions in the model solutions were 5, 20, 50 and 100 mg/dm3. The volume of the model solution was 50 cm3. For each initial concentration, the kinetic curves of the ammonium ion sorption at the sorption duration of 10, 30, 60, 90, 120, 150 and 180 min were obtained. The kinetic curves were processed using the Lagergren (pseudo-first order), Ho and McKay (pseudo-

second order), Morris-Weber (diffusion) and Elovich kinetic equations. It was demonstrated that all kinetic equations adequately describe the experimental data. The linear correlation of the equations was given. The Boyd equation was used to determine the limiting stage in the Morris–Weber model. It was established that the external diffusion mechanism is limiting for the sorption of ammonium ions by a calcined sorbent. The Lagergren model, with a coefficient of determination R2 of 0.9801–0.9949, best described the experimental data on sorption kinetics. Sorption rate curves as a function of the adsorption value and sorption time were given. The latter are described by exponential and polynomial dependence according to the Lagergren model, polynomial dependence according to the Ho and McKay model and exponential dependence according to the Morris–Weber and Elovich models. The sorption rate was the highest at the initial stage of sorption for all dependencies, which is consistent with previous studies on the sorption of pollutants from aqueous solutions using various sorbents.
Influence of structure-forming agent on rheological properties of polymer mixture based on low and high density polyethylene
Authors: Mustafayeva F. A. , Kakhramanov N. T. , Arzumanova N. B. , Nuraliyeva G. H.
Published: March 2024

The paper considers the effect of a structure-forming agent (titanium dioxide) on the rheological characteristics of a polymer mixture based on low and high density polyethylene, taken in a 50/50 ratio. The titanium dioxide concentration was 1 wt%. The rheological behavior of melts of polymer composites was studied using a CEAST MF50 capillary rheometer (Instron, Italy) at temperatures of 190, 210, 230, 250 °С and loads of 3.8, 5.0, 10.0, 12.5, and 21.6 kg. The effect of temperature and shear stress on the regularity of changes in effective viscosity and shear rate has been established. According to the Arrhenius – Frenkel – Eyring model, the activation energy of the viscous flow of composites is determined. The “apparent” activation energy of the viscous flow varies within 16.04–33.10 kJ/mol for the initial polyethylene mixture and in the range of 6.96–33.10 kJ/mol for composites modified with a structurant based on a mixture of low and high density polyethylene. A universal temperature-invariant characteristic of the viscosity properties of polymeric materials has been constructed, which makes it possible, by extrapolating this dependence to the region of high shear rates, to predict the technological mode of their processing by injection molding and extrusion.
Protatrans – growth biostimulants for centomopathogenic bacteria Bacillus thuringiensis
Authors: Adamovich S. N. , Vyatchina O. F. , Rubanenko N. A. , Oborina E. N. , Katerinich M. D. , Gritsenko I. M. , Dzhioev Yu. P. , Ushakov I. A. , Grigorieva A. S. , Bugdaeva B. A. , Zalutskaya K. M. , Stepanenko L. A. , Arefieva N. A. , Salovarova V. P. , Zlobin V. I.
Published: March 2024

The study investigates the use of protatran compounds as growth stimulators for Bacillus thuringiensis bacteria, which are widely used as producers of biopesticides. Cultivation of the Bacillus thuringiensis strain subsp. kurstaki was carried out in a Luria-Bertani (LB) liquid medium. Protatrans (2-Me-C6H4OCH2COO- were added to the NN+(CH2CH2OH)3 (1), 4-Cl-C6H4 -SCH2COO-NN(CHCHOH) (2) and 4-Cl-CSOCHCOO NN+(CH2CH2OH)3 (3) media in concentrations of 1×10-4–1×10-8wt %. The LB medium without the addition of compounds 1–3 was used as a control. Cultures were incubated at a temperature of 30°C for 24 hours. The number of Bacillus thuringiensis cells was determined by serial dilution. The maximum growth was observed in a medium containing 1×10-4wt % of protatran 3. The number of cells was almost 10 times (966.7%) higher than in the control. In media with 1×10-5, 1×10-6, 1×10-7 and 1×10-8 wt % of compound 3, the number of cells was 4–7 times higher than in the control (by 371.7–666.7%). Protatrans 1 and 2 had a positive effect on Bacillus thuringiensis, increasing the number of cells by 83–292% compared to control. Therefore, it was demonstrated for the first time that commercially available non-toxic protatran compounds in microconcentrations are powerful growth stimulators for the entomopathogenic bacteria Bacillus thuringiensis. This indicates the potential for significant improvement and cost reduction of biotechnology for the production of bacterial insecticides based on Bacillus thuringiensis, used in agriculture, forestry and homesteads to control harmful insects.
Biologically active compounds in selected Sempervivoideae (Sedoideae) cultivated in Western Siberia
Authors: Fomina T. I. , Kukushkina T. A.
Published: March 2024

Although representative species of the Ochitaceae subfamily (Sedoideae) have long been used as medicinal plants, the biochemical composition of most species remains understudied. This hinders their use in pharmacology and medicine. This study quantifies the content of the main groups of biologically active substances in the aboveground part of the Sempervivoideae at the beginning and end of the vegetation period. Freshly harvested vegetative shoots of the following species (raw materials) were examined: Aizopsis aizoon (L.) Grulich, Aizopsis hybrida (L.) Grulich, Aizopsis kurilensis (Vorosch.) S. Gontch., Hylotelephium ewersii (Ledeb.) H. Ohba, Sedum acre L., Sedum album L., Sedum hispanicum L., Sedum reflexum L., Sedum rupestre L. and Sedum spurium M. Bieb. Conventional methods of phytochemical analysis were used. The solid content was determined by drying 1 g of raw materials to a constant weight. The amount of phenolic compounds, pectin substances and total sugars was determined by the spectrophotometric method in ethanolic extracts by calculating the indicators relative to the solid mass of the raw materials. Titrimetric analysis was used to determine the concentration of ascorbic acid in the wet weight of the raw material. The content of solid (7.22–18.98%), catechins (0.14–6.01 mg%), flavonols (0.59–3.11%), tannins (4.44–26.73%), pectins (0.14–3.51%), protopectins (3.10–11.82%), total sugars (10.25–57.96%) and ascorbic acid (43.4–94.4 mg%) was determined. The tendency to accumulate phenolic compounds, sugars and solids, along with a decrease in the content of pectin polysaccharides, by the end of the vegetation was revealed. The results indicate the potential for the cultivation of Sempervivoideae as a source of various bioactive compounds.
Resin acid derivatives: fungicidal properties and prediction of the spectrum of biological activity
Authors: Tsyrulnikova A. S. , Popova L. M. , Ivanchenko O. B. , Suy H. , Pochkaeva E. I. , Vershilov S. V.
Published: March 2024

Biologically active substances that confer antiviral, anti-tumour and antimicrobial effects, which are found among the components of plant raw materials, as well as the products of their chemical modification, are the subject of considerable research interest. These objects include tricyclic diterpenoids – extractives of wood of abietic and pimaric types (resin acids). The presence of two reaction centres (double bonds and a carboxyl group) in the structure of resin acids opens up a wide range of possibilities for synthesising useful compounds on their basis. One of the most promising areas for the study of resin acids and their derivatives consists assessing their fungicidal properties to inform their introduction into compositions as additives, as well as in the application of protective films to increase the resistance of composite building materials against the aggressive effects of microorganisms. In the present work, the fungicidal activity of the N-phenylimide of maleopimaric acid and its polyfluoroalkyl ethers synthesised by us was evaluated on the cells of the filamentous fungi Aspergillus niger, Alternaria alternata and Penicillium sp. by the rate of colony formation and growth. A comparative analysis of the biological activity of resin acids and their in silico derivatives was performed. According to the AntiBag Pred forecast, the test compounds having the maximum values of the probabilities of the presence and absence of each type of activity are characterised by the manifestation of antibacterial activity in relation to strains of gram-positive bacteria. The results of the predictive model are consistent with previous experimental data. However, AntiFun Pred data related to the calculation of fungicidal activity were not confirmed in vitro.
Internal determinants of bank deposit flows under different market conditions in Ghana
Authors: Fekadu Zerihun Mulatu
Published: March 2024

This study analyzes the effect of internal factors of bank performance on deposit flows, considering the changes in the stock market conditions in Ghana. A panel dataset covering 2007 to 2021 of 18 banks in Ghana is applied in a dynamic panel model for the analysis. The results show that the lagged deposit growth exerts an impressive influence of 0.68 percent on the future deposit flows of banks, thus positing a favorable implication for their trading momentum. Also, liquidity was found to have a negative relationship of –0.64 percent with deposit growth. This implies that the holding of excess liquidity diminishes investors’ confidence in a bank’s ability to generate more revenue to enhance the value of their funds, as high liquidity ratios reduce the bank’s capacity to grant more loans for profit. Furthermore, the analysis revealed a positive effect of 1.93 percent by expenditure on deposit growth, which suggests that depositors recognize a rise in operational costs as an indication of a bank’s potential for growth and rapid expansion. Moreover, the analysis found the existence of a negative effect of –0.88 percent by the stock market conditions on deposit growth, which implies that bullish market conditions reduce bank deposits. This verifies that the determinants of deposit flows adapt to the changes in market conditions. Policy strategies should include non-performance metrics such as an increase in the interest paid on customers’ deposits, product promotions, and targeted advertisements to sustain the inflow of depositors’ funds under changing market conditions.