bluuebunny/crossref_metadata_2025 huggingface dataset:
Paravascular Vitreous Adhesions in Patients with Myopia Under 30 Years by Swept Source Optical Coherence Tomography
Authors: She Xiangjun , Xie Jin , Yao Wangjing , Liang Zhi , Chen Siping , Huang Gongyu , Zhou Congying , Tao Jiwei , Wu Sulan , Mao Jianbo , Chen Yiqi , Zhang Yun , Shen Lijun
Published: December 2022

Objectives: To present the characteristics of paravascular vitreous adhesions in patients with myopia under 30 years by SS-OCT.
Methods: This was a cross-sectional study. One eye of each subject was enrolled in the study, and the paravascular, macular and optic disc regions were scanned by SS-OCT.The PVA was classified to 4 degrees, Grade 1: No visible separation. Grade2: A slit structure visible, Grade 3: Distinguished separation, but remains to the retina. Grade 4: Complete separation. The degree of macular posterior vitreous detachment (PVD), location of vitreoschisis and presence of granular hyper reflection structure were evaluated and compared within high myopic groups using SPSS.
Results: A total of 31 highly myopic eyes and 78 non-highly myopic eyes were enrolled from 5 to 29 years. The varying degrees of PVA in the superior and inferior vascular arch was 29.9% (32), 19.6% (21), 27.1%(29) and 23.4%(25) and 28.6%(30), 17.1%(18), 23.8%(25) and 30.5%(32) separately for 1 to 4 degree of PVA. The degrees of PVA were higher in patients with high myopia than in normal people (P< 0.01). A higher degree of PVA was related to macular PVD and the presence of vitreoschisis (P< 0.05). The granular hyper-reflection structure was mainly in patients without high myopia and was positively related to vitreoschisis (P=0.006, r=0.265).
Conclusions: Highly myopic subjects had a higher grade of paravascular vitreous adhesion and the presence of vitreoschisis. The degree of PVA was associated with the macular vitreous adhesion. The granular hyper-reflection structure may play a role in vitreous adhesion.
Agricultural input shocks decrease crop yields globally
Authors: Ahvo Aino , Heino Matias , Sandström Vilma , Chrisendo Daniel , Jalava Mika , Kummu Matti
Published: December 2022

Today’s food system is more global than ever. In addition to food, also the key inputs to food production such as fertilisers, machinery and pesticides are traded among countries. Shocks and disturbances in the trade flows of agricultural inputs, caused by e.g., conflict, can potentially be devastating to the food production and yields even for otherwise self-sufficient countries. However, the impact of these agricultural input shocks on crop yields has not yet been assessed globally. In this study, we modelled the effects of agricultural input shocks using global spatial data on crop yields, fertilisers, machinery and pesticides using a random forest machine learning algorithm. We show that shocks in fertilisers cause the most drastic yield losses. Areas with the highest crop yields suffer the most from all agricultural input shocks, while low-yielding areas are seldom affected. Yield losses in these high-yielding ‘breadbasket’ areas of the world would be detrimental to global food security. For example, global maize production could decrease up to 50%, and global wheat production up to 30% if agricultural input availability were to drop by 75%. Western Europe and the US are among the areas most affected by shocks in agricultural inputs. Our study provides important information in high spatial definition to be used in future discussions on food security and resilience.
Modelling nonlinear self-excited forces for bridge decks with regularised Volterra series models
Authors: Skyvulstad Henrik , Petersen Øyvind , Argentini Tommaso , Zasso Alberto , Øiseth Ole
Published: December 2022

Volterra series models are considered an attractive approach for modelling nonlinear aerodynamic forces for bridge decks since they extend the convolution integral to higher dimensions. Optimal identification of nonlinear systems is a challenging task since there are typically many unknown variables that need to be determined, and it is vital to avoid overfitting. Several methods exist for identifying Volterra kernels from experimental data, but a large class of them put restrictions on the system inputs, making them infeasible for section model tests of bridge decks. A least-squares identification method does not restrict the inputs, but the identified model often struggles with noisy (non-smooth) kernels, which is deemed to be unphysical and a sign of overfitting. In this work, regularised least-squares identification is introduced to improve the performance of model identification using least-squares. Standard Tikhonov regularisation and other penalty techniques that impose decaying kernels are also explored. The performance of the methodology is studied using experimental data from wind tunnel tests of a twin deck section. The regularised Volterra models show equal or better results in terms of modelling the self-excited forces, and the regularisation makes the models less prone to overfitting.
A Prospective Study on the Potential of Teprotumumab Ototoxicity: Evidence Based recommendations for Screening and Managing Patients at Risk of Hearing Loss
Authors: Ugradar Shoaib , Parunakian Emanuil , Tolentino Joseph , Malkhasyan Emil , Geng June , Sherman Michele , Douglas Raymond
Published: December 2022

Background
Recent observational case series have reported on the potential ototoxicity of teprotumumab. This study aims to objectively evaluate the incidence of teprotumumab induced ototoxicity in patients with TED, using the gold standard of baseline and post treatment audiometry.
Methods
In this prospective observational case series, consecutive patients who had been diagnosed with TED and were to receive teprotumumab had audiometry at: baseline, prior to each infusion and at 6 months follow up post treatment. An independent audiologist assessed the audiometry. Further, the incidence and natural history of otologic symptoms was also documented.
Results
52 patients were included (43 females, 9 males, mean (SD) age: 49 (13)). On objective testing (audiometry), only 63% patients had normal baseline audiometry. At 6 months follow up, of those with normal baseline audiometry, 1 / 32 (3%) had new onset hearing loss. Of those with abnormal baseline audiometry, 20% had mild hearing dysfunction at 6 months follow up. Overall, 5/52 (10%) of patients had objective hearing loss at 6 months. Following treatment, at 24 weeks, 29% reported subjectively new otologic symptoms. At 6 months, this reduced to 7.7%. A prior history of hearing loss was the main risk factor for hearing dysfunction following treatment with teprotumumab.
Conclusions
Long term hearing loss in TED patients with normal baseline hearing is rare following treatment with teprotumumab (incidence of 3%). Patients with baseline hearing dysfunction are at greater risk of hearing change and management of the dose and interval between infusions is recommended for this group.
Kinesiophobia, exercise capacity, peripheral muscle strength and physical activity in patients with hypertension: a cross-sectional study
Authors: Katayıfçı Nihan , Hüzmeli İrem , İriş Döndü , yalcin Fatih
Published: December 2022

Functional limitations have recently shown in patients with hypertension. However, causes of kinesiophobia remain unknown. The aim was to compare functional exercise capacity (FEC), peripheral muscle strength (MS), level of kinesiophobia, physical activity (PA), fatigue, dyspnea, and quality of life (Qol) in hypertension patients and healthy controls and to investigate relationship between aforementioned outcomes in patients. Fifty-six patients and 45 age/gender-matched controls were included. FEC [6 min. walking test (6MWT)], peripheral MS (Dynamometer), kinesiophobia (Tampa Scale of Kinesiophobia), PA level [International Physical Activity Questionnaire (IPAQ)], perception of dyspnea (Modified Medical Research Council Dyspnea scale), fatigue (Fatigue Severity scale), and Qol (Short Form-36 questionnaire) were evaluated. Demographic characteristics were similar in patients (54.58 ± 11.33y,35M/21F) and healthy controls (51.11 ± 7.42y,33M/12F) (p > 0.05). Peripheral MS (p < 0.05), 6MWT, PA and Qol were significantly lower (p < 0.05); level of kinesiophobia (p < 0.001), perception of dyspnea (p < 0.001), and fatigue (p = 0.001) scores were higher in patients compared with controls. IPAQ (r=-0.556, p < 0.001), quadriceps femoris (r=-0.429, p = 0.001), hip flexor (r=-0.380, p = 0.004), shoulder abductor (r=-0.410,p = 0.002), elbow flexor (r=-0.364,p = 0.006), hand-grip strength (r=-0.355,p = 0.007), fatigue (r = 0.434, p = 0.001), SF-36 physical functioning (r = 0.404, p = 0.002), role limitations due to physical health (r=-0.370,p = 0.005), energy/fatigue (r=-0.357, p = 0.007), general health (r=-0.280, p = 0.036) was related to kinesiophobia in patients. Patients had impaired FEC, peripheral MS, higher level of kinesiophobia, perception of fatigue and dyspnea, reduced PA level, and Qol compared with healthy controls. In addition, a higher degree of kinesiophobia was related to physical inactivity, weakened upper and lower extremity MS, fatigue, impaired Qol in patients. Patients should be directed to cardiopulmonary rehabilitation.
Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice
Authors: Meulen Jan Ter , Horvath Dennis , Temperton Nigel , Neto Martin Mayora , Costa Kelly Da , Cantoni Diego , Horlacher Reinhold , Günther Armin , Brosig Alexander , Morath Jenny , Jakobs Barbara , Groettrup Marcus , Hoschützky Heinz , Rohayem Jacques
Published: December 2022

SARS-CoV-2 continues to circulate in the human population necessitating regular booster immunization for its long-term control. Ideally, vaccines should ideally not only protect against symptomatic disease, but also prevent transmission via asymptomatic shedding and cover existing and future variants of the virus. This may ultimately only be possible through induction of potent and long-lasting immune responses in the nasopharyngeal tract, the initial entry site of SARS-CoV-2. To this end, we have designed a vaccine based on recombinantly expressed receptor binding domain (RBD) of SARS-CoV-2, fused to the C-terminus ofC. perfringensenterotoxin (cCPE), which is known to target Claudin-4, a matrix molecule highly expressed on mucosal microfold (M) cells of the nasal and bronchial-associated lymphoid tissues. To further enhance immune responses, the vaccine was adjuvanted with a novel toll-like receptor 3/RIG-I agonist (Riboxxim™), consisting of synthetic short double stranded RNA. Intranasal prime-boost immunization of mice induced robust mucosal and systemic anti-SARS-CoV-2 neutralizing antibody responses against SARS-CoV-2 strains Wuhan-Hu-1, and several variants (B.1.351/beta, B.1.1.7/alpha, B.1.617.2/delta), as well as systemic T-cell responses. A combination vaccine with M-cell targeted recombinant HA1 from an H1N1 G4 influenza strain also induced mucosal and systemic antibodies against influenza. Taken together, the data show that development of an intranasal SARS-CoV-2 vaccine based on recombinant RBD adjuvanted with a TLR3 agonist is feasible, also as a combination vaccine against influenza.
Role of Troponins in haemodynamically stable penetrating injuries to the cardiac box, is it helpful?
Authors: makhadi shumani , Jacks Reuven , Moeng Stephen Maeyane
Published: December 2022

Background
Cardiac trauma is associated with a high mortality rate, but a subset of the patients presents with normal vital signs in the emergency department. Identification of cardiac injuries in these patients can be a challenge. Many investigative modalities have been used to identify penetrating cardiac injury patients. Most of these tests are expensive, specialised and not easily accessible. However, the role of Troponins in penetrating cardiac injury has not been defined. We hypothesised that cardiac troponins have a negative predictive value in penetrating cardiac injuries.
Materials and methods
We retrospectively reviewed all patients who presented to the Charlotte Maxeke Academic Hospital trauma unit over 22 months (January 2018 to October 2020). Patients were identified using the hospital database. All patients with penetrating cardiac trauma to the cardiac zone above the age of 16 years were included.
The patient’s demographics, mechanism of injury, injury severity score, vital signs, investigation findings, troponin levels, final diagnosis, type of operation, length of hospital stay, morbidities and mortalities were recorded.
Results
There was a total of 173 patients identified; 6 were females. The median age was 30 years. Most patients (160/173, 92%) had stab wounds. The median Injury Severity Score (ISS) was 12.8. Most patients sustained stab wounds on the left side of the chest (n=90), 52%. Initial ultrasound was positive for pericardial fluid in 10% of patients (n=18). The sensitivity of cardiac troponins was 19.7%, and the specificity was 98.2%. The negative and positive predictor values were 69.2% and 85.7%, respectively. The mean initial Troponins level was 50 ng/L. The mean repeat troponins were 450 ng/L in those patients with cardiac injuries. The Troponins were significantly different in those with cardiac injuries and those without cardiac injuries. In patients who had a cardiac injury, the right ventricle (3.5%) was the most commonly injured chamber, followed by the left ventricle (2.3%) and Right atrium (0.6%). Two patients sustained myocardial injuries without chamber penetration. The overall mortality rate was 0,6%(n=1). Fifty percent of the patients (n=87) were discharged home from the emergency department, 21.8% were admitted to the ward (n=38), and 15.5% (n=27) were admitted to the Trauma ICU. The average hospital stay was one day for patients with a stab to the precordium.
Conclusion
Troponins can be used to evaluate cardiac injuries in haemodynamically stable patients with penetrating chest trauma. It is highly specific for cardiac injuries (98%). More prospective data is needed to confirm our findings and then extend to clinical practice, especially in resource-limited environments.
A CRISPR/Cas9-generated mutation in the zebrafish orthologue of PPP2R3B causes idiopathic scoliosis
Authors: Seda Marian , Crespo Berta , Corcelli Michelangelo , Osborn Daniel , Jenkins Dagan
Published: December 2022

Idiopathic scoliosis (IS) is the deformation and/or abnormal curvature of the spine that develops progressively after birth. It is a very common condition, affecting approximately 4% of the general population, yet the genetic and mechanistic causes of IS are poorly understood. Here, we focus on PPP2R3B, which encodes a protein phosphatase 2A regulatory subunit that has been linked to regulation of autophagy. We found that PPP2R3B is expressed at sites of chondrogenesis within human foetuses, including the vertebrae. We also demonstrated prominent expression in myotome and muscle fibres in human foetuses, and zebrafish embryos and adolescents. As there is no rodent orthologue of PPP2R3B, we used CRIPSR/Cas9-mediated gene-editing to generate a series of frameshift mutations in zebrafish ppp2r3b. Adolescent zebrafish that were homozygous for this mutation exhibited a fully penetrant kyphoscoliosis phenotype which became progressively worse over time, mirroring IS in humans. These defects were associated with reduced mineralisation of vertebrae, resembling osteoporosis. Electron microscopy demonstrated abnormal mitochondria adjacent to muscle fibres, suggestive of abnormal mitophagy.
Evaluation of Kusuantongtiao Formula as adjunctive therapy for Insulin Resistance: An integrated in silico exploration and experimental validation
Authors: Yan Guanchi , Wang Ying , Zhu Haoyu , Fan Xuechun , Wang Guoqiang , Wang Xiuge , Mi Jia
Published: December 2022

Background: Kusuantongtiao Formula (KSTTF) have been shown to be effective in treating insulin resistance (IR) of type 2 diabetes (T2DM), but the mechanism by which KSTTF remains unclear. Objective This study revealed the pharmacological mechanisms of KSTTF acting on IR through network pharmacology, molecular docking, dynamics andvitroexperiments. Materials and methods In this study, the ingredients and potential targets of KSTTF were obtained from the TCMSP and HERB databases, and the potential targets of IR were obtained from GeneCard and OMIM database. Cytoscape 3.9.1 constructed network and predicted potential active ingredients and targets. Protein–protein interaction network was constructed using the STRING. AutoDock Vina was used for molecular docking between active ingredients and targets. Subsequently, molecular dynamics simulation was used to analyze the conformational stability of the protein-ligand complexes by GROMACS. Furthermore, the effect and mechanism of KSTTF on insulin resistance were verified by cell viability assay, glucose uptake and western blotting. Results In the formula, we found 172 potential active compounds, such as berberine, baicalin, rhein. A total of 270 intersection targets of KSTTF and IR were obtained, including peroxisome proliferator-activated receptor-gamma (PPARG), glycogen synthase kinase 3β (GSK3B), nitric-oxide synthase (NOS2), and dipeptidyl peptidase 4 (DPP4). Gene ontology and KEGG pathway enrichment revealed that KSTTF could regulate PI3K/Akt signaling pathway. The results of molecular docking showed that GSK3B-1,2,5,6-tetrahydrotanshinone, NOS2-1,2,5,6-tetrahydrotanshinone, PPARG-1,2,5,6-tetrahydrotanshinone, and DPP4-cryptotanshinone had higher binding energy. Molecular dynamics simulation verified the stability of PPARG-1,2,5,6- tetrahydrotanshinone. Binding free energy analysis showed that van der Waals interaction was the main binding form of protein and ligand. Finally, the result fromvitroexperiments showed that KSTTF improved glucose consumption and increased the phosphorylation levels of IRS1, PI3K, and Akt in palmitic acid-induced C2C12. Conclusions This study predicted the active components and potential targets of KSTTF through network pharmacology, and analyzed its possible mechanism of action in the treatment of insulin resistance. The key targets were validated by molecular docking and molecular dynamics simulation. Thevitroexperiments confirmed that KSTTF may treat IR by promoting IRS1/PI3K/Akt conduction and glucose uptake consumption. We possess a reason to believe that their mechanisms for insulin resistance are synergy between several different signaling pathways and targets. However, further experiment is crucial to reveal the effect of KSTTF on insulin resistance.
The PaO2/FiO2 is Independently Associated with 28-Day Mortality in Patients with Sepsis: A retrospective analysis from MIMIC-IV database
Authors: Bi Hongying , Liu Xu , Chen Chi , Chen Lu , Liu Xian , Zhong Jianmin , Tang Yan
Published: December 2022

Objectives
To clarify the relationship between the PaO2/FiO2 and 28-day mortality in patients with sepsis.
Methods
This was a retrospective cohort study regarding MIMIC- IV database. A total of 35,010 patients with sepsis were included in this database. PaO2/FiO2 was exposure variable, 28-day mortality was outcome variable. PaO2/FiO2 was log-transformed as LnPaO2/FiO2. Binary logistic regression was used to explore the independent effects of LnPaO2/FiO2 on 28-day mortality using non-adjusted and multivariate-adjusted models. A generalized additive model (GAM) and smoothed curve fitting were used to investigate the non-linear relationship between LnPaO2/FiO2 and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point.
Results
A total 19,233 cases were included in the final analysis. The relationship between LnPaO2/FiO2 and risk of 28-day death in sepsis patients was U-shape. The inflection point of LnPaO2/FiO2 was 5.32(95%CI:5.22–5.39), which indicated the inflection point of PaO2/FiO2 was 204.38mmHg (95%CI: 184.93mmHg − 219.20mmHg). On the left of inflection point, LnPaO2/FiO2 was negatively correlated with 28-day mortality(OR:0.38, 95%CI༚0.33, 0.44, p < 0.0001). On the right of inflection point, LnPaO2/FiO2 was positively correlated with 28-day mortality in patients with sepsis (OR:1.67,95%CI༚1.42, 1.96, p < 0.0001).
Conclusions
In patients with sepsis, either a high or low PaO2/FiO2 was associated with an increased risk of 28-day mortality. In the range of 184.93mmHg to 219.20 mmHg, PaO2/FiO2 was associated with a lower risk of 28-day death in patients with sepsis.
Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir retreatment in hepatitis C patients with different genotypes with DAAs failure in East China
Authors: Chen Shanshan , Zhou Ke , Yang Qiao , Ma Chunlian , Jin Qian , Hu Airong , Jin Jie , Yan Dong , Lv Fangfang , Shi Yongming , Yang Jie , Hu Fangqin , Ma Li , Xun Yunhao , Huang Haijun
Published: December 2022

Background and Aim:At present, DAAs are very effective in the treatment of HCV, but there are still a small number of patients with treatment failure. Sofosbuvir/velpatavir/voxilaprevir (SOF/VEL/VOX) is a first-line retreatment recommended by HCV guidelines. The sustained virological response rate at 12 weeks (SVR12) of phase Ⅲ clinical studies reached 97%. However, SOF/VEL/VOX was only allowed into the health insurance list in January 2022 in China. So there are few data on the effectiveness and safety of SOF/VEL/VOX in East China. Meanwhile, there is a lack of international data on genotype (GT)3b retreatment therapy. This is the first real-life cohort study evaluating effectiveness and safety of SOF/VEL/VOX in prior direct-acting antiviral failure HCV from multi-center of East China. The aim of this study was to evaluate the effectiveness and safety of SOF/VEL/VOX retreatment in HCV patients with DAAs failure.Methods:A total of 13 patients with HCV who failed treatment in multiple centers in East China from January 2022 to March 2022 were collected and received 12w SOF/VEL/VOX antiviral treatment. HCV RNA, blood routine, liver and kidney function, abdominal color ultrasound or CT were measured at baseline, 4 weeks, 8 weeks, 12weeks and follow-up of 12 weeks. Virological response rate was used to evaluate the direct antiviral efficacy.Results:A total of 13 previous DAA failure HCV patients received 12w SOF/VEL/VOX without Ribavirin (RBV) retreatment, with an average age of 44.2 ± 8.5 years, with male predominance (92.3%). There were 6 patients with genotype GT3b, 5 patients of GT6（4 GT6a and 1 GT6n）, 2 patients of GT1b. All patients are non-cirrhotic patients, including 2 patients with PWID. Previous treatment included Sofosbuvir + Velpatavir, Coblopasvir + Hydrochloride + Sofosbuvir, Elbasvir + Grazoprevir. The mean value of baseline HCV-RNA was 9.45*106copies/ml, ALT was 231.6±218.1U/L, and AST was 150.7±166.4U/L. SVR12 was 100%. The common adverse reactions were gastrointestinal reactions and dizziness, which were well tolerated by the patients. No serious adverse events, death or treatment discontinuation occurred due to adverse reactions.Conclusion:SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting, and has a good virological response rate for HCV patients with different genotypes of treatment failure even for refractory GT3b.
Genetic diversity and signatures of selection in four indigenous horse breeds of Iran
Authors: Razmkabir Mohammad , Mousavi Seyedeh Fatemeh , Rostamzadeh Jalal , Seyedabadi Hamid-Reza , Naboulsi Rakan , Petersen Jessica , Lindgren Gabriella
Published: December 2022

Indigenous Iranian horse breeds were evolutionarily affected by natural and artificial selection in distinct phylogeographic clades which shaped their genomes in several unique ways. The principal aims of this study were to evaluate genetic diversity and genome-wide selection signatures in four indigenous Iranian horse breeds. We evaluated 169 horses from Caspian (n = 21), Turkmen (n = 29), Kurdish (n = 67) and Persian Arabian (n = 52) populations, using genome-wide genotyping data. The contemporary effective population sizes were 59, 98, 102 and 113 for Turkmen, Caspian, Persian Arabian, and Kurdish, respectively. Analysis of population genetic structure classified the north breeds (Caspian and Turkmen) and west/southwest breeds (Persian Arabian and Kurdish) into two phylogeographic clades reflecting their geographic origin. Using de-correlated composite of multiple selection signals (DCMS) statistics based on six pairwise comparisons, we detected different number of significant SNPs under putative selection from 13 to 28 for the six pairwise comparisons (FDR < 0.05), respectively. The identified SNPs under putative selection coincided with genes previously associated with known QTLs for morphological, adaptation and fitness traits. Our results showed HMGA2 and LLPH as strong candidate genes for height variation between Caspian with a small size and the other studied breeds with a medium size. Using results of studies for human height retrieved from the GWAS catalog, we suggested 38 new putative candidate genes under selection. These results suggest that the identified sweeps might have been enriched as an adaptation to environmental conditions or a response to human-mediated artificial selection.
Does controlled ovarian hyperstimulation in women with a history of borderline tumor influence recurrence rate?
Authors: Gao Han , Wei Wei , Li Yibing , wang ning
Published: December 2022

Purpose
To determine the recurrence rate in the women with controlled ovarian hyperstimulation after a history of borderline ovarian tumors (BOT).
Methods
This was a retrospective analysis of 275 patients with BOT undergoing surgery for fertility preservation in our hospital between 2001 and 2017. Cases were divided into an assisted reproductive technology (ART) treatment group (n = 15) and a non-ART treatment group (n = 260). We compared the recurrence rate, survival rate and pregnancy outcomes between these two groups.
Results
The ART group had a higher recurrence rate (33.33% vs. 10.80%, P = 0.023). Survival analysis indicated that the recurrence time in patients undergoing ART was significantly shorter (P = 0.026). A low pregnancy rate before diagnosis, and high intraoperative blood loss, were associated with postoperative ART treatment (P < 0.05). Multivariate analysis showed that ART treatment and bilateral lesions both significantly increased the risk of recurrence (P < 0.05). The pathological type of recurrent tumors was often the same as the initial tumor.
Conclusion
The postoperative use of ART in patients with BOT significantly increased the recurrence rate, but does not significantly affect the overall survival rate of patients. Therefore, ART in such patients should be individualized, and close follow-up is necessary after ART.
The moderating effects of parenting style on the relationship between parental stress and behavioral problems in girls with precocious puberty in Korea: A Cross-sectional Study
Authors: Kwon Ahreum , Cho Young Il , Kim Hyo Jin , Suh Junghwan , Kim Dong Hee
Published: December 2022

Background: This study aimed to examine the mediating effects of parenting style on the relationship between parental stress and behavioral problems of girls with precocious puberty.
Methods: This cross-sectional study analyzed a convenience sample of 200 mothers of girls with precocious puberty at a university hospital located in a metropolitan area. The Parental Stress measurement, Parents as Social Context Questionnaire, and Korean version Child Behavior Checklist (K-CBCL) 6-18 were measured via self-report questionnaires. Descriptive, t-test, Pearson correlation, and bootstrapping analyses were used to analyze the data.
Results: Negative parenting styles had a full mediating effect on the relationship between parental stress and internalizing and externalizing behavioral problems.
Conclusions: Care plans for parents of girls with precocious puberty should be designed and applied in health care settings to reduce internalizing and externalizing behavioral problems by decreasing negative parenting styles.
The recognition method for the fractal and the dynamic on the tool flank of a high-energy-efficiency milling cutter
Authors: Jiang Bin , Ji Simin , Zhao Peiyi , Fan Lili
Published: December 2022

The friction contact boundary between the tool flank of the milling cutter and the machining transition surface is important indicator to reveal the third deformation zone tool contact relationship and assessing the frictional wear performance of milling cutter. The existing models for friction boundary identification pay attention to the maximum width of accumulated friction and wear on the tool flank, ignoring the variability of the overall and local morphology of the friction boundary on the flank. Aimed at the influence of milling vibration on the instantaneous position of the cutter teeth and the machining transition surface, the solution and discrimination for the instantaneous position vector on the flank was proposed. Based on the mutagenicity of the instantaneous temperature and stress distribution, the influence of the instantaneous contact, extrusion and deformation between the tool flank and the machined transition surface on the friction area was recognized. The calculation model of friction boundary of the flank was established. The irregularities of the distributions of the friction boundaries of the tool flank were revealed. The fractal recognition methods for instantaneous and cumulative friction boundary of the flank were proposed. And response was studied and verified with experiments. The results showed that it could effectively identify the irregular distribution of the friction boundary on the flank with the use of the above models. The formation and evolution of the friction boundary on the tool flank of the high-energy-efficiency milling cutters were revealed.
Circular RNAs in Parkinson’s Disease: Reliable Biological markers and targets for Rehabilitation
Authors: Duan Yinan , Wang Yixuan , Liu Yonghong , Jin Zhaohui , Liu Cui , Yu Xin , Chen Keke , Meng Detao , Xi Jianing , Fang Boyan
Published: December 2022

In clinical practice, the underlying pathogenesis of Parkinson’s disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgical has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-Synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437), the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.
FDC-SP as a diagnostic and prognostic biomarker and modulates immune infiltrates in renal cell carcinoma
Authors: Chang Fan , Zhang Jiang-Hui , Wu Wen-Song , Tang Shuai , Lv Zheng , Chen Fangmin
Published: December 2022

Background
One of the top 10 causes of cancer death, renal cell carcinoma (RCC) accounts for more than 90% of all occurrences of primary renal cancer globally. Follicular dendritic cell-secreted protein (FDC-SP) particularly attaches to activated B cells and controls the production of antibodies. It is also believed to encourage the invasion and migration of cancer cells, which may aid in tumor metastases. The purpose of this study was to evaluate the utility of FDC-SP in the diagnosis and prognosis of RCC and to examine how immune infiltration in RCC relates to it.
Results
FDC-SP mRNA and protein levels were significantly higher in RCC tissues compared to normal tissues. The T stage, histological grade, pathological stage, M stage, OS event, DSS event, and PFI event were all associated with the high expression level of FDC-SP. Immune response regulation, complement, and coagulation were the key pathways that were enriched, according to functional enrichment analysis. The levels of FDC-SP expression were found to be significantly correlated with immune cell infiltration, immunological checkpoints, and therapeutic targets. The prognosis of RCC patients with greater FDC-SP expression levels was worse, and FDC-SP expression levels demonstrated the ability to precisely discriminate tumor tissues from healthy tissues (area under the curve (AUC) = 0.635). The AUC values for one, three, and five-year survival rates were all greater than 0.58. An independent predictive biomarker of OS in RCC patients is FDC-SP expression.
Conclusion
FDC-SP may be a prospective therapeutic target in RCC as well as a possible diagnostic and prognostic biomarker associated with immune infiltration.
Normality and the treatment-enhancement distinction
Authors: Martin Daniel , Rueda Jon , Earp Brian D. , Hannikainen Ivar R.
Published: December 2022

People overwhelmingly recognize patients’ needs for medical care intended to restore cognitive or physical health that has deteriorated below what is considered typical, due to disease or disorder (e.g., psychostimulant medication to sustain attention in the case of attention deficit disorder). When asked whether a healthy individual may undergo the sameintervention for the purpose of exceeding typical functioning, people often express greater hesitation. The present work examines this phenomenon, known as the treatment-enhancement distinction, and builds on prior research in moral philosophy and cognitive science to ask why it might arise. In two experiments, we provide evidence that the accessibility of health-related interventions determines their perceived descriptive normality (Experiment 1), and that gains in descriptive normality of such interventions weaken the moral distinction between treatment and enhancement (Experiment 2). In short, these findings suggest that the treatment-enhancement distinction may be driven, at least in part, by assumptions about descriptive abnormality; and raise the possibility that normalizing novel biomedical interventions by promoting access could alleviate people’s selective opposition toward enhancement, rendering it morally equivalent to treatment.
Akt2 deficiency alleviates oxidative stress in the heart and liver during high fat diet-induced obesity
Authors: Kong Weixian , Peng Yue , Ji Caoyu , Li Zhe , Liu Zekun , Gao Shuya , Zhang Yuexin , Chen Jiawen , Li Xie , Bao Mengmeng , Zhang Yubin , Jiang Qizhou , Wang Ruopu , Yan Fangrong , Bian Xiaohong , Ye Junmei
Published: December 2022

The AKT family plays key roles in global metabolism. However, the function of different AKT isoforms during obesity-associated hepatic and cardiac injury remained unclear. This study aims to elucidate the role of AKT2 in the pathogenesis of hepatic and cardiac lipotoxicity due to nutrition overload-induced obesity and explore the signaling pathway that it involves. Akt2 KO mice were fed with high fat diet (HFD) to induce obesity model in vivo. The oxidative stress of the normal human hepatic cell line (L02 cells) and neonatal rat cardiomyocytes (NRCMs) were measured by using Oil Red O and Rho123 staining as well as Flow cytometry. Protein levels were determined by using western blot technique. We observed that during HFD-induced obesity, Akt2 loss-of-function mitigated lipid accumulation and oxidative stress in the liver and heart tissue. Mechanistically, during HFD-induced obesity, Akt2 deficiency promotes SIRT6 expression in the hepatocytes and cardiomyocytes. Upregulation of SIRT6 deacetylates SOD2, which promotes SOD2 activity and thus alleviating oxidative stress-induced injury of hepatocytes and cardiomyocytes. Furthermore, We also proved that AKT2 inhibitor protects hepatocytes and cardiomyocytes from HFD-induced oxidative stress. This study demonstrates that Akt2 deficiency plays a beneficial role in protecting hepatocytes and cardiomyocytes from oxidative stress via SIRT6-dependent SOD2 deacetylation during lipid overload-induced obesity, indicating an important function of AKT2 in the regulation of obesity-induced lipid metabolic disorder in the liver and heart. Our study also indicates AKT2 inhibitor as a potential therapy for obesity-induced hepatic and cardiac injury.
Association Between Serum 25(OH)D and Risk of All-Cause Mortality in Adults with Prior Cardiovascular Disease: A Cohort Study From NHANES 2007-2018
Authors: Hu Ben , Chen Jian , Shi Yihang , Hou Linlin
Published: December 2022

Background
Serum vitamin D deficiency is common in the patients with cardiovascular disease (CVD), but the association between serum vitamin D levels and risk of all-cause mortality in patients with CVD is controversial.
Objective
This study aimed to understand better the association between serum 25(OH)D status and risk of all-cause mortality in patients with prior CVD.
Method
We conducted a cohort study using data from the National Health and Nutrition Examination Survey from 2007–2018 to investigate the association between serum 25(OH)D and the risk of all-cause mortality using multivariate Cox regression models, with further subgroup analyses and interactions smooth curve fitting to address possible nonlinearities.
Result
A total of 3220 participants with prior CVD were included in this study, with a total of 930 deaths over a median follow-up of 5.52 years, with multivariable-adjusted serum vitamin D levels (< 25 nmol/L) as a reference in COX regression, and corrected HRs and 95% CIs of 1.00 (reference), 0.74 (0.55, 1.00), 0.69 (0.51, 0.93), and 0.58 (0.43, 0.79) for all-cause mortality, respectively. Results remained robust in the stratified analysis of interactions, but a U-shaped relationship was detected. We identified an inflection point of 89.8 nmol/L after multivariate adjustment through a two-stage linear regression model and recursive algorithm.
Conclusion
Our findings demonstrate that increasing serum 25(OH)D levels may have a U-shaped relationship with risk of all-cause mortality and that increases in serum 25(OH)D levels do not continue to reduce the risk of all-cause mortality beyond specific criteria have a diminished protective effect.
Efficacy and safety of berberine hydrochloride for glycemic control in prediabetic individuals: a double-blind, placebo-controlled, and randomized trial
Authors: Panigrahi Antarmayee , Mohanty Susant
Published: December 2022

Background: Prediabetes and diabetes involve alterations in glucose homeostasis, including elevated fasting blood glucose and impaired glucose tolerance. Berberine has been identified as a potential regulator of glucose homeostasis with implications on the management of type 2 diabetes mellitus (DM). Given a paucity of data on berberine in prediabetes, evaluation of its effect in prediabetic individuals may prove clinically valuable. The present study aimed to investigate the effect of daily oral berberine on markers of glycemic control and insulin resistance among prediabetic individuals.
Methods: A randomized, double-blinded, placebo-controlled trial was conducted for 12 weeks among 34 prediabetic individuals as defined by the American Diabetes Association (fasting plasma glucose (FPG) between 5.6 and 6.9 mmol/L, glycosylated hemoglobin (HbA1c) between 5.7% and 6.4%, or 2-hour 75-gram oral glucose tolerance test (2h-OGTT) between 7.8 and 11.1 mmol/L). HIMABERB® 500 mg was given three times daily to the treatment group, and placebo was administered three times daily to the control group. Glycemic control markers and physical parameters were evaluated for both groups on days 0, 28, 56, and 84. The glycemic control markers assessed included FPG, fasting insulin (FI), 2h-OGTT, HbA1c, and homeostatic model assessment-insulin resistance (HOMA-IR). The observed outcomes were analyzed using independent t-test statistics to determine the significance of differences over time after treatment initiation and between treatment and control groups.
Results: Significant decreases in all markers of glycemic control were observed in the treatment group at intermediate time points and the endpoint of the study compared to baseline levels and to the control group. For the treatment group, FPG decreased from 6.75 ± 0.23 mmol/L to 5.33 ± 0.28 mmol/L, FI from 9.81 ± 0.36 to 7.88 ± 0.52 mmol/L, 2h-OGTT from 10.44 ± 0.52 to 8.12 ± 0.40 mmol/L, HbA1c from 6.40% ± 0.20% to 5.43% ± 0.21%, and HOMA-IR from 3.61 ± 0.31 to 2.41 ± 0.14. The decreases in glycemic control markers compared to the control group were clinically and statistically significant (p<0.00001). No severe adverse effects, kidney or liver toxicity were detected.
Conclusion: After 12 weeks, berberine (HIMABERB®) intervention in prediabetic individuals significantly reduced glycemic control markers, with mean FPG and 2h-OTGG being reduced to below prediabetic thresholds, supporting the investigation of the use of HIMABERB® for delaying progression to diabetes mellitus.
Trial registration: http://ctri.nic.in (CTRI/2021/12/038751) 20/12/2021
Identification and promoter analysis of a GA-stimulated transcript 1 gene from Jatropha curcas
Authors: Lei Shikang , Zhao Liangqing , Chen Yuqian , Xu Gang
Published: December 2022

Members of Gibberellic acid-stimulated Arabidopsis (GASA) gene family play roles in plant growth and development, particularly in flower induction and seed development. However, there is still relatively limited knowledge of GASA genes inJatropha curcas. Herein, we identified a GASA family gene fromJatropha curcas, namelyJcGAST1, which encodes a protein containing a conserved GASA domain. Sequence alignment showed that JcGASAT1 protein shares 76% sequence identity and 80% sequence similarity with SlGAST1.JcGAST1had higher expression and protein levels in the male flowers than in the female flowers. Overexpression ofJcGAST1in tobacco promotes plant growth but inhibits pistil development.JcGAST1expression was upregulated by GA and downregulated by MeJA. Promoter analysis indicated that the pyrimidine box and CGTCA motif were the GA-and MeJA-responsive elements of theJcGAST1promoter. Using a Y1H screen, six transcription factors were found to interact with the pyrimidine box, and three transcription factors were found to interact with theCGTCA motif. Overall, the results of this study improve our understanding of theJcGAST1gene and provide useful information for further studies.
Multi-objective optimization of urban water allocation considering recycled water
Authors: Chen Siwei , Yue-Ping Xu , Guo Yuxue , Yu Xinting
Published: December 2022

The use of recycled water is an essential means of resolving urban water scarcity. To realize the coordinated allocation of conventional and recycled water, a multi-objective water resources optimal allocation model with recycled water is established. The model takes into account the impact of the carbon footprint on the regional ecology during the total water allocation process, which has not been given enough attention before. Simultaneously, this study combined direct policy search, nonlinear approximation networks and multi-objective evolutionary algorithms to design Pareto approximation operating policies for joint conventional and recycled water allocation. The AHP-Entropy method based on combinatorial assignment of weights is then used to perform multi-attribute decision making on the optimized operating policies for scientific selection of solutions. The proposed model is demonstrated in Yiwu City, China, which suffers from the water shortage due to the rapid development of industry. Results show that radial basis functions can effectively design Pareto approximation operating policies for the water supply system of Yiwu City. The inclusion of recycled water can result in a 31.67% reduction in water shortage and an 8.45% increase in economic benefit, while carbon emissions only increase by 1.78%. This result illustrates the use of recycled water can alleviate urban water scarcity, increase economic benefits, and mitigate carbon emissions to some extent. Multi-attribute decision making based on the AHP-Entropy method provides a scientific basis for optimalurban multi-water allocation.
Lack of casual association between non-alcoholic fatty liver disease and bone mineral density: A mendelian randomization analysis
Authors: Hudabaierdi Munire , Wang Fei , Liu Yan-shi , Wang Zong-ding , Aimaiti Abudousaimi , Cui Lei
Published: December 2022

Background
Many observational studies focus on the relationship between Nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). However, the conclusions are controversial and the causal relationship between NAFLD and BMD remains unclear.
Method
A bi-directional two-sample Mendelian randomization (MR) analysis was performed to investigate the potential causal links between NAFLD and BMDs. We applied genetic variants as instrumental variables obtained from the Genetic Factors for Osteoporosis (GEFOS) dataset and several published genome-wide association studies (GWASs). We obtained summary statistics for heel (H) BMD (n = 426,824), femoral neck (FN) BMD (n = 32,735), lumbar spine (LS) BMD (n = 28,498), ultra-distal forearm (UF) BMD (n = 21,907), and total body (TB) BMD (n = 56,284) from some GWAS meta-analyses. Additionally, the NAFLD GWAS included 377,988 individuals of European ancestry which consist of 4,761 NAFLD cases and 373,227 control cases. We used inverse variance weighted (IVW), four supplemental methods, and several sensitivity analyses to estimated and cross-validate the potential causal relationship in the present MR analysis.
Results
The sensitivity analyses do not find any violation of the MR assumptions. We found that NAFLD has no causal association with H-BMD (beta − 0.017; 95%CI -0.0458,0.0117; p = 0.2461), FN-BMD (beta − 0.0166; 95%CI -0.1592,0.1259; p = 0.8191), LS-BMD (beta − 0.021; 95%CI -0.1475,0.1055; p = 0.7446), UF-BMD (beta − 0.0524; 95%CI -0.1726,0.0679; p = 0.3935), TB-BMD (beta − 0.0596, 95%CI -0.1236,0.0044; p = 0.0678). Similarly, reverse MR analysis provided little support for a causal effect of BMDs on NAFLD.
Conclusion
This MR study found no evidence to support a bi-directional causality between NAFLD and BMD.