bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer
Authors: Jindal Tanya , Zhu Xiaolin , Bose Rohit , Kumar Vipul , Maldonado Edward , Deshmukh Prianka , Shipp Chase , Feng Stephanie , Johnson Michelle S. , Angelidakis Austin , Kwon Daniel , Borno Hala T. , de Kouchkovsky Ivan , Desai Arpita , Aggarwal Rahul , Fong Lawrence , Small Eric J. , Wong Anthony , Porten Sima , Chou Jonathan , Friedlander Terence , Koshkin Vadim S.
Published: April 2023

Background

Enfortumab vedotin (EV) is an antibody-drug conjugate approved for patients with treatment-refractory advanced urothelial carcinoma (aUC), however data on biomarkers of response is lacking.

Methods

We retrospectively identified all aUC patients at our institution who received EV monotherapy and had next-generation sequencing (NGS) data available. Patients were considered responders if they had a complete response or partial response on restaging scans during treatment. Observed response rate (ORR) was evaluated by local investigator and compared between responders and non-responders using Chi-squared test. A univariable analysis was conducted using the Cox proportional hazard test to assess for associations between baseline characteristics and most common somatic alterations (in ≥10% of patients) with patient survival outcomes [progression-free survival (PFS) and overall survival (OS)]. Somatic alterations were then individually evaluated in separate multivariate models while accounting for patient and clinical characteristics using Cox regression models.

Results

Among 29 patients treated with EV monotherapy, 27 had available NGS data. Median age was 70, 24 (83%) were men, 19 (62%) were Caucasian, 15 (52%) had pure urothelial histology and 22 (76%) had primary tumor in the bladder. ORR was 41%, and PFS and OS for the overall cohort were 5.1 months and 10.2 months. Responders were enriched among patients with TP53, KDM6A and MDM2 alterations. Patients with these alterations, as well as those with composite TP53/MDM2 alterations (alterations in either TP53 or MDM2), also had increased ORR with EV treatment compared to patients without these alterations. In the univariable analysis, baseline albumin level ≥ 3.0g/dL and presence of composite TP53/MDM2 alterations were associated with a prolonged OS. Baseline ECOG 0/1, TP53 alterations and TP53/MDM2 alterations were associated with a prolonged PFS. In the multivariable analysis, TP53 and TP53/MDM2 alterations were genomic markers predictive of improved PFS after accounting for the relevant clinical characteristics.

Conclusion

In this single-center retrospective analysis of aUC patients treated with EV, presence of TP53 or MDM2 somatic alterations, lower ECOG PS scores (ECOG 0 or 1) and higher albumin levels (≥3 g/dL) were associated with improved outcomes with EV treatment. Prospective and external validation of these findings in larger cohorts is warranted.
Functional properties of GABAA receptors of AII amacrine cells of the rat retina
Authors: Beltrán-Matas Pablo , Hartveit Espen , Veruki Margaret L.
Published: April 2023

Amacrine cells are a highly diverse group of inhibitory retinal interneurons that sculpt the responses of bipolar cells, ganglion cells, and other amacrine cells. They integrate excitatory inputs from bipolar cells and inhibitory inputs from other amacrine cells, but for most amacrine cells, little is known about the specificity and functional properties of their inhibitory inputs. Here, we have investigated GABAA receptors of the AII amacrine, a critical neuron in the rod pathway microcircuit, using patch-clamp recording in rat retinal slices. Puffer application of GABA evoked robust responses, but, surprisingly, spontaneous GABAA receptor-mediated postsynaptic currents were not observed, neither under control conditions nor following application of high-K+ solution to facilitate release. To investigate the biophysical and pharmacological properties of GABAA receptors in AIIs, we therefore used nucleated patches and a fast application system. Both brief and long pulses of GABA (3 mM) evoked GABAA receptor-mediated currents with slow, multi-exponential decay kinetics. The average weighted time constant (τw) of deactivation was ~163 ms. Desensitization was even slower, with τw ~330 ms. Non-stationary noise analysis of patch responses and directly observed channel gating yielded a single-channel conductance of ~23 pS. Pharmacological investigation suggested the presence of α2 and/or α3 subunits, as well as the γ2 subunit. Such subunit combinations are typical of GABAA receptors with slow kinetics. If synaptic GABAA receptors of AII amacrines have similar functional properties, the slow deactivation and desensitization kinetics will facilitate temporal summation of GABAergic inputs, allowing effective summation and synaptic integration to occur even for relatively low frequencies of inhibitory inputs.
Effects of bariatric surgery on drug pharmacokinetics—Preclinical studies
Authors: Mercado Angela , Pham Anna , Wang Zhijun , Huang Wendong , Chan Patrick , Ibrahim Hajer , Gogineni Hyma , Huang Ying , Wang Jeffrey
Published: April 2023

With the rising worldwide obesity rates, bariatric surgeries are increasing. Although the surgery offers an effective treatment option for weight loss, the procedure causes dramatic physiological and metabolic changes. Animal models in rodents provide a valuable tool for studying the systemic effects of the surgery. Since the surgery may significantly influence the pharmacokinetic properties of medications, animal studies should provide essential insight into mechanisms underlying changes in how the body handles the drug. This review summarizes research work in rodents regarding the impact of standard bariatric procedures on pharmacokinetics. A qualitative literature search was conducted via PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE. Studies that examined bariatric surgery’s effects on drug pharmacokinetics in rodent models were included. Clinical studies and studies not involving drug interventions were excluded. A total of 15 studies were identified and assessed in this review. These studies demonstrate the possible impact of bariatric surgery on drug absorption, distribution, metabolism, excretion, and potential mechanisms. Pharmacokinetic changes exhibited in the limited pre-clinical studies highlight a need for further investigation to fully understand the impact and mechanism of bariatric surgery on drug responses.
Coronary artery properties in atherosclerosis: A deep learning predictive model
Authors: Caballero Ricardo , Martínez Miguel Ángel , Peña Estefanía
Published: April 2023

In this work an Artificial Neural Network (ANN) was developed to help in the diagnosis of plaque vulnerability by predicting the Young modulus of the core (Ecore) and the plaque (Eplaque) of atherosclerotic coronary arteries. A representative in silico database was constructed to train the ANN using Finite Element simulations covering the ranges of mechanical properties present in the bibliography. A statistical analysis to pre-process the data and determine the most influential variables was performed to select the inputs of the ANN. The ANN was based on Multilayer Perceptron architecture and trained using the developed database, resulting in a Mean Squared Error (MSE) in the loss function under 10–7, enabling accurate predictions on the test dataset for Ecore and Eplaque. Finally, the ANN was applied to estimate the mechanical properties of 10,000 realistic plaques, resulting in relative errors lower than 3%.
Hyperpolarization electrical signals induced by local action of moderate heating influence photosynthetic light reactions in wheat plants
Authors: Yudina Lyubov , Sukhova Ekaterina , Popova Alyona , Zolin Yuriy , Abasheva Karina , Grebneva Kseniya , Sukhov Vladimir
Published: April 2023

Local action of stressors induces fast changes in physiological processes in intact parts of plants including photosynthetic inactivation. This response is mediated by generation and propagation of depolarization electrical signals (action potentials and variation potentials) and participates in increasing plant tolerance to action of adverse factors. Earlier, we showed that a local action of physiological stimuli (moderate heating and blue light), which can be observed under environmental conditions, induces hyperpolarization electrical signals (system potentials) in wheat plants. It potentially means that these signals can play a key role in induction of fast physiological changes under the local action of environmental stressors. The current work was devoted to investigation of influence of hyperpolarization electrical signals induced by the local action of the moderate heating and blue light on parameters of photosynthetic light reactions. A quantum yield of photosystem II (ФPSII) and a non-photochemical quenching of chlorophyll fluorescence (NPQ) in wheat plants were investigated. It was shown that combination of the moderate heating (40°C) and blue light (540 µmol m-2s-1) decreased ФPSII and increased NPQ; these changes were observed in 3-5 cm from border of the irritated zone and dependent on intensity of actinic light. The moderate soil drought (7 days) increased magnitude of photosynthetic changes and shifted their localization which were observed on 5-7 cm from the irritated zone; in contrast, the strong soil drought (14 days) suppressed these changes. The local moderate heating decreased ФPSII and increased NPQ without action of the blue light; in contrast, the local blue light action without heating weakly influenced these parameters. It meant that just local heating was mechanism of induction of the photosynthetic changes. Finally, propagation of hyperpolarization electrical signals (system potentials) was necessary for decreasing ФPSII and increasing NPQ. Thus, our results show that hyperpolarization electrical signals induced by the local action of the moderate heating inactivates photosynthetic light reactions; this response is similar with photosynthetic changes induced by depolarization electrical signals. The soil drought and actinic light intensity can influence parameters of these photosynthetic changes.
Individual and mutual effects of elevated carbon dioxide and temperature on salt and cadmium uptake and translocation by rice seedlings
Authors: Feng Yu-Xi , Tian Peng , Li Cheng-Zhi , Zhang Qing , Trapp Stefan , Yu Xiao-Zhang
Published: April 2023

Plant kingdoms are facing increasingly harsh environmental challenges marked by the coexposure of salinity and pollution in the pedosphere and elevated CO2 and temperature in the atmosphere due to the rapid acceleration of industrialization and global climate change. In this study, we deployed a hydroponics-based experiment to explore the individual and mutual effects of different temperatures (low temperature, T1: 23°C; high temperature, T2: 27°C) and CO2 concentrations (ambient CO2: 360 ppm; medium CO2: 450 ppm; high CO2: 700 ppm) on the uptake and translocation of sodium chloride (NaCl, 0.0, 0.2, 0.6, and 1.1 g Na/L) and cadmium nitrate (Cd(NO3)2·4H2O, 0.0, 0.2, 1.8, and 5.4 mg Cd/L) by rice seedlings. The results indicated that Cd and Na exposure significantly (P< 0.05) inhibited plant growth, but T2 and medium/high CO2 alleviated the effects of Cd and Na on plant growth. Neither significant synergistic nor antagonistic effects of Cd and Na were observed, particularly not at T1 or high CO2. At increasing temperatures, relative growth rates increased despite higher concentrations of Cd and Na in both rice roots and shoots. Similarly, higher CO2 stimulated the growth rate but resulted in significantly lower concentrations of Na, while the Cd concentration was highest at medium CO2. Coexposure experiments suggested that the concentration of Cd in roots slightly declined with additional Na and more at T2. Overall, our preliminary study suggested that global climate change may alter the distribution of mineral and toxic elements in rice plants as well as the tolerance of the plants.
Time trends in cardiovascular disease mortality attributable to non-optimal temperatures in China: An age-period-cohort analysis using the Global Burden of Disease Study 2019
Authors: Wei Jiehua , Wang Peiwen , Xia Fan , Miao Junxiang , Zhou Xuan , Yang Ziqi , Gong Ziqiang , Chen Lizhang , Wang Tingting
Published: April 2023

Background

Associations between non-optimal temperatures and cardiovascular disease (CVD) mortality risk have been previously reported, yet the trends of CVD mortality attributable to non-optimal temperatures remain unclear in China. We analyzed trends in CVD mortality attributable to non-optimal temperatures and associations with age, period, and birth cohort.

Methods

Data were obtained from the Global Burden of Disease Study (GBD) 2019. Joinpoint regression analysis was used to calculate annual percent change (APC) and average annual percent change (AAPC) from 1990 to 2019. We used the age-period-cohort model to analyze age, period, and cohort effects in CVD mortality attributable to non-optimal temperatures between 1990 and 2019.

Results

The age-standardized mortality rate (ASMR) of CVD attributable to non-optimal temperature generally declined in China from 1990 to 2019, whereas ischemic heart disease (IHD) increased slightly. Low temperatures have a greater death burden than high temperatures, but the death burden from high temperatures showed steady increases. Joinpoint regression analysis showed that CVD mortality decreased in all age groups except for IHD, and the decreases were greater in females than in males. The mortality of CVD attributable to non-optimal temperatures of males was higher than females. The mortality rate showed an upwards trend with age across all CVD categories. Period risks were generally found in unfavorable trends. The cohort effects showed a progressive downward trend during the entire period.

Conclusion

Although there have been reductions in CVD mortality attributable to non-optimum temperatures, the mortality of IHD has increased and the burden from non-optimal temperatures remains high in China. In the context of global climate change, our results call for more attention and strategies to address climate change that protect human health from non-optimal temperatures.
The SNABB ADHD treatment scale—An easy-to-use scale on treatment monitoring in childhood ADHD: A pilot study
Authors: Nylander Elin , Hermansson Jonas , Nygren Gudrun
Published: April 2023

Introduction

Information from parents and teachers are essential in the treatment monitoring of children with attention deficit hyperactivity disorder (ADHD). Rating scales are infrequently used in the treatment monitoring, and clinicians are signalling logistic barriers in the administration of rating scales in clinical settings. Here, we aimed to try out a new easy-to-use scale to facilitate information sharing between parents, teachers, and medical staff, in the treatment of childhood ADHD.

Methods

We examined the SNABB scale in a clinical sample of 27 child- and adolescent patients with any type of ADHD, in a routine clinical setting. We compared the outcome of the new SNABB scale with the commonly used Swanson, Nolan, and Pelham Teacher and Parent ADHD rating scale—version IV (SNAP-IV).

Results

The SNABB questions concerning ADHD cardinal symptoms hyperactivity and impulsivity were associated with the concurrent SNAP-IV subscale, with moderate to strong correlations. The SNABB inattention question failed all associations with the concurrent SNAP-IV inattention subscale. A secondary finding was that the SNABB mood regulation question correlated with the SNAP-IV ODD-subscale at all three measure points.

Conclusion

Present pilot study brings promising results for the possibility to carry out larger scale studies concerning the psychometric properties of the SNABB scale.
Continuous non-locking vs. interrupted suturing techniques for the repair of episiotomy or second-degree perineal tears: A single-blind randomized controlled trial
Authors: Faal Siahkal Shahla , Abedi Parvin , Iravani Mina , Esfandiarinezhad Parvin , Dastoorpoor Maryam , Bakhtiari Shahla , Najafian Mahin , Sharifipour Foruzan , Mohaghegh Zaynab
Published: April 2023

Objective

Perineal trauma is a serious and frequent problem after childbirth which is experienced by millions of women worldwide. The technique used for perineal repair may have an impact on pain and wound healing. The aim of the present study was to compare the continuous non-locking technique with interrupted suturing for the repair of episiotomy or second-degree perineal tears.

Methods

A single-blind randomized-controlled trial was conducted from October 2021 to August 2022 in Sina Hospital, Ahvaz, Iran. Three hundred women were selected and randomly assigned into control and intervention groups using block randomization technique. The main outcomes included pain and wound healing that were assessed using visual analog scale (VAS), as well as redness, edema, ecchymosis/bruising, discharge, and approximation scale (REEDA). The secondary outcomes were the use of analgesics, duration of perineal repair, material used for suturing, pain during urination and defecation, and resumption of sexual intercourse. The participants were followed up on the first and seventh days and in the 6th week postpartum. Mann-Whitney, Chi-square, and Generalized Estimating Equations (GEE) model were used for data analysis.

Results

Wound healing was significantly better in the continuous non-locking suture technique compared to the interrupted technique (β = −1.98; P > 0.0001). Women also experienced less pain in the continuous non-locking suture technique (β = −2.46; P > 0.0001). There was a reduction in the use of analgesics, the duration of perineal repair, and the material used for suturing in the continuous non-locking suturing technique as opposed to the interrupted method (P < 0.0001).The odds of pain during urination and defecation significantly reduced in women who underwent the continuous non-locking method (P < 0.001). Also, women in the continuous non-locking group resumed their sexual intercourse earlier (P < 0.0001).

Conclusion

The findings of this study revealed that use of continuous non-locking technique for suturing was associated with reduced perineal pain and improved wound healing. Furthermore, it was associated with a shorter duration of perineal repair, less suture material used, and less need for analgesics compared with the interrupted method. There is, however, need for more studies to confirm the results of the present study.

Iranian registry for randomized controlled trials (Ref. ID: IRCT20190415043283N1).
Performance of Serum Quad Test in Screening for Fetal Down Syndrome in a Large-Scale Unselected Population in a Developing Country
Authors: Chaipongpun Nitchanut , Wanapirak Chanane , Sirichotiyakul Supatra , Tongprasert Fuanglada , Srisupundit Kasemsri , Luewan Suchaya , Traisrisilp Kuntharee , Jatavan Phudit , Sirilert Sirinart , Tongsong Theera
Published: April 2023

Objective: To assess the effectiveness of Quad test in the detection of Down syndrome (DS) in routine practice among a large-scale population and to compare the effectiveness of Quad test based on the Western reference model (WM) and that based on Thai reference model (TM).

Methods: Quad test was performed on 42,769 pregnancies at 14–21 weeks. The fetal risk of DS derived from Quad test was automatically computed based on WM and used in evaluating the effectiveness. Also, the fetal risk was calculated based on the TM.

Results: Of 39,740 women with complete follow-ups including 74 fetuses with DS, with WM, the detection and false positive rates were 81.1% and 7.2%, respectively, whereas the detection and false positive rates with TM were 87.8%, and 6.8%, respectively. According to ROC curves, the performance of Quad test based on TM was slightly but significantly better than that based on WM (AUC of 0.959 vs. 0.940, p = 0.001).

Conclusion: Quad test is highly effective in service settings and suitable for developing countries and the effectiveness is even higher when based on ethnicity-specific reference model.
An Adversarial DBN-LSTM Method for Detecting and Defending against DDoS Attacks in SDN Environments
Authors: Chen Lei , Wang Zhihao , Huo Ru , Huang Tao
Published: April 2023

As an essential piece of infrastructure supporting cyberspace security technology verification, network weapons and equipment testing, attack defense confrontation drills, and network risk assessment, Cyber Range is exceptionally vulnerable to distributed denial of service (DDoS) attacks from three malicious parties. Moreover, some attackers try to fool the classification/prediction mechanism by crafting the input data to create adversarial attacks, which is hard to defend for ML-based Network Intrusion Detection Systems (NIDSs). This paper proposes an adversarial DBN-LSTM method for detecting and defending against DDoS attacks in SDN environments, which applies generative adversarial networks (GAN) as well as deep belief networks and long short-term memory (DBN-LSTM) to make the system less sensitive to adversarial attacks and faster feature extraction. We conducted the experiments using the public dataset CICDDoS 2019. The experimental results demonstrated that our method efficiently detected up-to-date common types of DDoS attacks compared to other approaches.
Total and Differential Somatic Cell Count in Italian Local Cattle Breeds: Phenotypic Variability and Effect on Milk Yield and Composition
Authors: Magro Silvia , Costa Angela , De Marchi Massimo
Published: April 2023

Milk differential somatic cell count (DSCC) represents the percentage of polymorphonuclear neutrophils and lymphocytes out of the total somatic cell count (SCC) and has been proposed in recent years as a proxy for udder health in dairy cows. We investigated phenotypic factors affecting SCC and DSCC using 3978 records of 212 Alpine Grey and 426 Burlina cows farmed in Northern Italy. The linear mixed model accounted for the fixed effects of breed, parity, lactation stage, sampling season, and first-order interactions of breed with the other effects. Cow, herd-test-date nested within breed were random. Subsequently, four udder health status groups (UHS) were created by combining SCC and DSCC to assess the UHS impact on milk yield and quality. DSCC was greater in Alpine Grey (66.2 ± 0.8%) than Burlina cows (63.2 ± 0.6%) and, similarly to SCC, it increased with days in milk and parity regardless of breed. Milk yield and composition were affected by UHS in both breeds. These results suggest that also udder health of local breeds can be monitored on a large scale through SCC and DSCC for reduction in biodiversity loss and increased farm profitability. However, in addition to milk data, the introduction of mastitis recording and monitoring plans is advisable.
Hybrid EMD-RF Model for Predicting Annual Rainfall in Kerala, India
Authors: Jayasree Asha , Sasidharan Santhosh Kumar , Sivadas Rishidas , Ramakrishnan Jayan A.
Published: April 2023

Rainfall forecasting is critical for the economy, but it has proven difficult due to the uncertainties, complexities, and interdependencies that exist in climatic systems. An efficient rainfall forecasting model will be beneficial in implementing suitable measures against natural disasters such as floods and landslides. In this paper, a novel hybrid model of empirical mode decomposition (EMD) and random forest (RF) was developed to enhance the accuracy of annual rainfall prediction. The EMD technique was utilized to decompose the rainfall signal into six intrinsic mode functions (IMFs) to extract underlying patterns, while the RF algorithm was employed to make predictions based on the IMFs. The hybrid RF–IMF model was trained and tested using a dataset of annual rainfall in Kerala from 1871 to 2020, and its performance was compared to traditional models such as RF regression and the autoregressive moving average (ARMA) model. Mean absolute error (MAE), mean absolute percentage error (MAPE), mean squared error (MSE), root mean squared error (RMSE), and coefficient of determination or R-squared (R2) were used to compare the performances of these three models. Model evaluation metrics show that the RF–IMF model outperformed both the RF model and ARMA model.
Radial Based Approximations for Arcsine, Arccosine, Arctangent and Applications
Authors: Howard Roy M.
Published: April 2023

Based on the geometry of a radial function, a sequence of approximations for arcsine, arccosine and arctangent are detailed. The approximations for arcsine and arccosine are sharp at the points zero and one. Convergence of the approximations is proved and the convergence is significantly better than Taylor series approximations for arguments approaching one. The established approximations can be utilized as the basis for Newton-Raphson iteration and analytical approximations, of modest complexity, and with relative error bounds of the order of 10−16, and lower, can be defined. Applications of the approximations include: first, upper and lower bounded functions, of arbitrary accuracy, for arcsine, arccosine and arctangent. Second, approximations with significantly higher accuracy based on the upper or lower bounded approximations. Third, approximations for the square of arcsine with better convergence than well established series for this function. Fourth, approximations to arccosine and arcsine, to even order powers, with relative errors that are significantly lower than published approximations. Fifth, approximations for the inverse tangent integral function and several unknown integrals.
The Effects of Surfactant and Metal Ions on the Stability and Rheological Properties of Nanoemulsions Loaded with Gardenia Yellow Pigment
Authors: Gao Li , Li Bin
Published: April 2023

The present work reports the preparation of gardenia yellow pigment containing paraffin oil nanoemulsions stabilized by Span80 and Tween80. The preparation of the required nanoemulsions was optimized by testing different conditions, such as varying the hydrophilic–lipophilic balance (HLB), the emulsifier concentration (EC), the oil–water ratio (OWR), and the temperature (T), as determined by the average droplet diameter (ADD) and polydispersity index (PDI). Our results indicated that a minimum ADD of 65.9 nm and PDI of 0.116 were obtained at an optimum HLB value of 6.0, EC of 10% (w/w), OWR of 2:1, and T of 40 °C. Both the steady-state and dynamic rheological parameters were further investigated, revealing that the emulsions exhibited pseudoplastic behaviors. The long-term stabilities of the nanoemulsions after the addition of inorganic salts were monitored by observing their visual appearances. It was found that the emulsions containing pure water or 0.1 M CaCl2 and AlCl3 became slightly separated, while the emulsions containing 0.1 M KCl and NaCl showed no separation after 30 days of storage at room T. This difference among different salts could be related to the number of valence electrons of their cations. The spatial electrostatic effects of the monovalent cationic (KCl and NaCl) and the nonionic surfactants were greater than the delamination/sedimentation forces of the system, which was better than the salt based on the cations with valences greater than one (CaCl2 and AlCl3). In conclusion, the present work illustrated the formation, rheological properties, and stability of water containing gardenia yellow pigment in paraffin oil nanoemulsions, which can be of great significance for the application of gardenia-yellow-pigment-based formulations.
Sub-Seasonal Prediction of Sea-Gale Processes in the Yangtze River Estuary of China
Authors: Xie Xiao , Liang Ping , Qian Qiwen
Published: April 2023

The sea-gale process (SGP) is a significant and disastrous weather event for the marine industry. However, the sub-seasonal predictability of SGP remains unclear. In this study, we investigate the influence of low-frequency oscillation on SGP in the Yangtze River estuary from November to April, and its implications for sub-seasonal prediction. We noted that SGPs have a close relationship with the 10~30 day low-frequency component of the 10-m wind speed in the Yangtze River estuary, and typically occur during the peak phase of the low-frequency oscillation. The 10~30 day low-frequency oscillation of 10-m wind was found to be linked to the eastward propagation of extratropical Rossby waves from the North Atlantic across Europe to East Asia. This Rossby wave leads to the low-frequency oscillation of the Siberian high pressure and Japan Sea low pressure, which is indicative of the 10~30 day low-frequency oscillations of the 10-m wind speed in the Yangtze River Estuary. A sea-gale process index (SGPI) was constructed based on the low-frequency oscillation of the Siberian high and the Japan Sea low in order to predict SGPs at the sub-seasonal time scale. Hindcast and real-time forecasts showed that 2/3 of SGPs can be predicted with a leading time of 10~30 days, and that good sub-seasonal predictions of SGPs are connected with strong low-frequency oscillations at the initial forecast time. Therefore, SGPI can be adopted for the sub-seasonal prediction of SGPs in the Yangtze River Estuary.
Frost Risk Assessment in Slovenia in the Period of 1981–2020
Authors: Žnidaršič Zala , Gregorič Gregor , Sušnik Andreja , Pogačar Tjaša
Published: April 2023

As spring frost proves to be an increasing risk throughout Slovenia and Europe, a better assessment of frost risk is needed. The statistical approach presented in this article consists of the conditional probability that the last spring frost occurs before budburst or flowering. The analysis was conducted using two separate phenological models and phenological data of various grapevine (Vitis vinifera L.), apple (Malus domestica), and sweet cherry (Prunus avium L.) varieties in locations across Slovenia. The increase in risk of spring frost for grapevine ranged from 1 to 1980, from 0.06 to 12 for apple, and from 1 to 180 for sweet cherry. Overall, the varieties most prone to frost proved to be Refošk (Teran) and Merlot grapevine varieties as well as the Germersdorf sweet cherry variety. We have identified the location in the hilly region with moderate climate where the Bobovec apple variety is grown as the least exposed to frost. Although counterintuitive, the GDD generally proved somewhat more efficient than the two-phase phenological model BRIN, although not in all cases. For the purpose of the study, the phenological models were calibrated, and the model parameters can serve as invaluable information for further research of this topic.
The Relevance of Serum Macrophage Migration Inhibitory Factor Level and Executive Function in Patients with White Matter Hyperintensity in Cerebral Small Vessel Disease
Authors: Zhao Jianhua , Wang Xiaoting , Yu Miao , Zhang Shiyun , Li Qiong , Liu Hao , Zhang Jian , Cai Ruiyan , Lu Chengbiao , Li Shaomin
Published: April 2023

(1) Objective: To investigate the relationship between serum macrophage migration inhibitory factor (MIF) level and white matter hyperintensity (WMH) and executive function (EF) in cerebral small vascular disease (CSVD), and assess the impact and predictive value of MIF level and Fazekas scores in CSVD-related cognitive impairment (CI) (CSVD-CI); (2) Methods: A total of 117 patients with WMH admitted to the First Affiliated Hospital of Xinxiang Medical College from January 2022 to August 2022 were enrolled. According to the Montreal cognitive assessment (MoCA) scale, subjects were divided into a normal cognitive group and an impaired group. All subjects required serum MIF level, 3.0 T MRI, and neuropsychological evaluation to investigate the risk factors for CDVD-CI, analyze the correlation between MIF level, WMH, and EF, and to analyze the diagnostic value of MIF and WMH degree in predicting CSVD-CI; (3) Results: 1. Fazekas score and MIF level were the risk factors of CSVD-CI. 2. The Fazekas score was negatively correlated with MoCA score, positively correlated with Stroop C-Time, Stroop C-Mistake, Stroop interference effects (SIE)-Time, SIE-Mistake, and color trails test (CTT) interference effects (CIE) (B-A). 3. The MIF level was positively correlated with Fazekas score, Stroop C-Time, SIE-Time, CTT B-Time, and CIE (B-A), and negatively correlated with MoCA score. 4. Fazekas score and MIF level were significant factors for diagnosing CSVD-CI; (4) Conclusion: The Fazekas score and MIF level may be the risk factors of CSVD-CI, and they are closely correlated to CI, especially the EF, and they have diagnostic value for CSVD-CI.
Pattern of Distribution of Lymph Node Metastases in Individual Stations in Middle and Lower Gastric Carcinoma
Authors: Brisinda Giuseppe , Chiarello Maria Michela , Fico Valeria , Puccioni Caterina , Crocco Anna , Bianchi Valentina , Vanella Serafino
Published: April 2023

(1) Background: Lymph node (LN) dissection is the cornerstone of curative treatment of GC. The pattern of distribution of LN metastases is closely related to several factors. The aim of this study is to evaluate the factors determining the distribution of nodal metastases in a population of N+ distal GC patients undergoing gastrectomy and D2 lymphadenectomy. (2) Methods: The medical charts of 162 N+ GC patients who underwent surgical resection over a 15-year period were retrospectively analyzed. Clinical, pathological and anatomical characteristics were evaluated to identify the factors affecting the patterns and prevalence of metastases in individual LN stations. (3) Results: LN metastasis is correlated with the depth of the tumor and to diffuse-type tumors. A higher number of metastatic nodes was documented in patients with middle-third tumors (8.2 ± 7.3 vs. 4.5 ± 5.0 in lower-third tumors, p = 0.0001) and in patients with tumors located on the lesser curve. Station 4 showed the highest rate of metastases (53.1%). Concerning stations 7 to 12, station 8 showed the highest metastasis rate (28.4%). Metastases at stations 1, 2, 4 and 7 to 11 were dominant in middle-third cancer, whereas stations 5 and 6 were dominant in lower-third cancers. Station 4, 5, 6, 10 and 11 metastases were dominant when the cancer was located on the greater curve, whereas stations 1, 2, 7, 8 and 12 were dominant in lesser-curve cancers. (4) Conclusions: The study documented that in patients with distal GC, the distribution of nodal metastases at individual stations is closely related to primary tumor location.
Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder
Authors: Murakami Yuki , Imamura Yukio , Kasahara Yoshiyuki , Yoshida Chihiro , Momono Yuta , Fang Ke , Sakai Daisuke , Konishi Yukuo , Nishiyama Toshimasa
Published: April 2023

Several studies show that genetic and environmental factors contribute to the onset and progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one of the major environmental factors driving this process. The kynurenine pathway (KP) is a major route of the essential amino acid L-tryptophan (Trp) catabolism in mammalian cells. Activation of the KP following neuro-inflammation can generate various endogenous neuroactive metabolites that may impact brain functions and behaviors. Additionally, neurotoxic metabolites and excitotoxicity cause long-term changes in the trophic support, glutamatergic system, and synaptic function following KP activation. Therefore, investigating the role of KP metabolites during neurodevelopment will likely promote further understanding of additional pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). In this review, we describe the changes in KP metabolism in the brain during pregnancy and represent how maternal inflammation and genetic factors influence the KP during development. We overview the patients with ASD clinical data and animal models designed to verify the role of perinatal KP elevation in long-lasting biochemical, neuropathological, and behavioral deficits later in life. Our review will help shed light on new therapeutic strategies and interventions targeting the KP for neurodevelopmental disorders.
Metformin Pre-Treatment as a Means of Mitigating Disuse-Induced Rat Soleus Muscle Wasting
Authors: Mirzoev Timur M. , Paramonova Inna I. , Rozhkov Sergey V. , Kalashnikova Ekaterina P. , Belova Svetlana P. , Tyganov Sergey A. , Vilchinskaya Natalia A. , Shenkman Boris S.
Published: April 2023

Currently, no ideal treatment exists to combat skeletal muscle disuse-induced atrophy and loss of strength. Because the activity of AMP-activated protein kinase (AMPK) in rat soleus muscle is suppressed at the early stages of disuse, we hypothesized that pre-treatment of rats with metformin (an AMPK activator) would exert beneficial effects on skeletal muscle during disuse. Muscle disuse was performed via hindlimb suspension (HS). Wistar rats were divided into four groups: (1) control (C), (2) control + metformin for 10 days (C+Met), (3) HS for 7 days (HS), (4) metformin treatment for 7 days before HS and during the first 3 days of 1-week HS (HS+Met). Anabolic and catabolic markers were assessed using WB and RT-PCR. Treatment with metformin partly prevented an HS-induced decrease in rat soleus weight and size of slow-twitch fibers. Metformin prevented HS-related slow-to-fast fiber transformation. Absolute soleus muscle force in the HS+Met group was increased vs. the HS group. GSK-3β (Ser9) phosphorylation was significantly increased in the HS+Met group vs. the HS group. Metformin pre-treatment partly prevented HS-induced decrease in 18S+28S rRNA content and attenuated upregulation of calpain-1 and ubiquitin. Thus, pre-treatment of rats with metformin can ameliorate disuse-induced reductions in soleus muscle weight, the diameter of slow-type fibers, and absolute muscle strength.
Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-β-Smad2/3 Pathway
Authors: Geng Fei , Zhao Lan , Cai Yuhao , Zhao Ying , Jin Fuyu , Li Yaqian , Li Tian , Yang Xinyu , Li Shifeng , Gao Xuemin , Cai Wenchen , Mao Na , Sun Ying , Xu Hong , Wei Zhongqiu , Yang Fang
Published: April 2023

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis. The present study aimed to determine the therapeutic effect of quercetin on silicotic mice and macrophage polarity. We found that quercetin suppressed silicosis in mice. It was observed that SiO2 activated macrophage polarity and the macrophage-to-myofibroblast transition (MMT) by transforming the growth factor-β (TGF-β)-Smad2/3 signaling pathway in silicotic mice and MH-S cells. Quercetin also attenuated the MMT and the TGF-β-Smad2/3 signaling pathway in vivo and in vitro. The present study demonstrated that quercetin is a potential therapeutic agent for silicosis, which acts by regulating macrophage polarity and the MMT through the TGF-β-Smad2/3 signaling pathway.
Host-Based Treatments for Severe COVID-19
Authors: Mondini Lucrezia , Salton Francesco , Trotta Liliana , Bozzi Chiara , Pozzan Riccardo , Barbieri Mariangela , Tavano Stefano , Lerda Selene , Hughes Michael , Confalonieri Marco , Confalonieri Paola , Ruaro Barbara
Published: April 2023

COVID-19 has been a global health problem since 2020. There are different spectrums of manifestation of this disease, ranging from asymptomatic to extremely severe forms requiring admission to intensive care units and life-support therapies, mainly due to severe pneumonia. The progressive understanding of this disease has allowed researchers and clinicians to implement different therapeutic alternatives, depending on both the severity of clinical involvement and the causative molecular mechanism that has been progressively explored. In this review, we analysed the main therapeutic options available to date based on modulating the host inflammatory response to SARS-CoV-2 infection in patients with severe and critical illness. Although current guidelines are moving toward a personalised treatment approach titrated on the timing of presentation, disease severity, and laboratory parameters, future research is needed to identify additional biomarkers that can anticipate the disease course and guide targeted interventions on an individual basis.
Perspective for Studying the Relationship of miRNAs with Transposable Elements
Authors: Mustafin Rustam Nailevich , Khusnutdinova Elza
Published: April 2023

Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological conditions may indicate a programmed pattern of transposable elements’ activation. This reflects the species-specific composition and distribution of transposable elements in genomes, which underlie gene regulation in every cell division, including during aging. TEs’ expression is also regulated by epigenetic factors (DNA methylation, histone modifications), SIRT6, cytidine deaminases APOBEC3, APOBEC1, and other catalytic proteins, such as ERCC, TREX1, RB1, HELLS, and MEGP2. In evolution, protein-coding genes and their regulatory elements are derived from transposons. As part of non-coding regions and introns of genes, they are sensors for transcriptional and post-transcriptional control of expression, using miRNAs and long non-coding RNAs, that arose from transposable elements in evolution. Methods (Orbld, ncRNAclassifier) and databases have been created for determining the occurrence of miRNAs from transposable elements in plants (PlanTE-MIR DB, PlaNC-TE), which can be used to design epigenetic gene networks in ontogenesis. Based on the data accumulated in the scientific literature, the presence of 467 transposon-derived miRNA genes in the human genome has been reliably established. It was proposed to create an updated and controlled online bioinformatics database of miRNAs derived from transposable elements in healthy individuals, as well as expression changes of these miRNAs during aging and various diseases, such as cancer and difficult-to-treat diseases. The use of the information obtained can open new horizons in the management of tissue and organ differentiation to aging slow down. In addition, the created database could become the basis for clarifying the mechanisms of pathogenesis of various diseases (imbalance in the activity of transposable elements, reflected in changes in the expression of miRNAs) and designing their targeted therapy using specific miRNAs as targets. This article provides examples of the detection of transposable elements-derived miRNAs involved in the development of specific malignant neoplasms, aging, and idiopathic pulmonary fibrosis.
The Link between Magnesium Supplements and Statin Medication in Dyslipidemic Patients
Authors: Nartea Roxana , Mitoiu Brindusa Ilinca , Ghiorghiu Ioana
Published: April 2023

Many investigations have discovered a connection between statins and magnesium supplements. On one hand, increasing research suggests that chronic hypomagnesemia may be an important factor in the etiology of some metabolic illnesses, including obesity and overweight, insulin resistance and type 2 diabetes mellitus, hypertension, alterations in lipid metabolism, and low-grade inflammation. Chronic metabolic problems seem to be prevented by a high Mg intake combined with diet and/or supplements. On the other hand, it is known that statins lower the frequency of cardiac events, stroke, and mortality, not by lowering LDL-C, but by the capacity to reduce mevalonate formation. That will enhance endothelial function, inhibit vascular smooth muscle cell proliferation and migration and encourage macrophages to promote plaque stability and regression while reducing inflammation. Taking these factors into consideration, we did an extensive analysis of the relevant literature, comparing the effects of Mg2 and statin medications on lipoproteins and, implicitly, on the key enzymes involved in cholesterol metabolism.
Multifunctionalization and Increased Lifespan of a Worsted Wool Fabric
Authors: Belhaj Rhouma Amira , Campagne Christine , Massika Behary Nemeshwaree , François Sebastien , Lanceron Charles , Vieillard Julien
Published: April 2023

A lack of dimensional stability of worsted fabrics when laundering leads to a rapid increase in wool textile waste. Dry cleaning is thus highly recommended; however, it requires solvent(s), which are not eco-friendly. The aim of this study was to produce a machine-washable, 100% worsted wool woven as an outer fabric for men’s suit jacket that is also water-repellent in order to reduce the number of washes required during use. Chemical treatments were applied through successive paddings, using a blend of aqueous dispersion of polyurethane and polysiloxane (PUPX) for shrink-proofing/dimensional stability, followed by a second blend of an aqueous emulsion of fluorotelomer methacrylate and paraffin/hydrocarbon waxes (C6PW) polymers for water-repellency. The dimensional change of the finished fabric did not exceed 2%, meeting Woolmark requirements AW-1. Zeta potential measurements confirm that the fabric coated with PUPX has an overall anionic nature, which allows the good adhesion of the successive cationic C6PW polymer blend used in the second padding. Additionally, Scanning Electron Microscopy (SEM) analysis confirmed the good adhesion of the first blend (PUPX) to the wool fiber surface and inter-fiber bonding. After the application of (C6PW) resin, the fabric exhibited durable water repellency with a 5/5 spray test rating after 10 washes and dimensional stability, as well as high resistance to wear and abrasion, while retaining a soft feel and good flexibility.
Experimental Study on Bond Behavior between Steel Rebar and PVA Fiber-Reinforced Concrete
Authors: Zhang Xuhui , Lu Qi , Wang Yang
Published: April 2023

An experimental test was performed to study the bond behavior between steel rebar and concrete reinforced by polyvinyl alcohol (PVA) fibers. Twenty specimens were prepared and subjected to the pull-out test. Four different fiber volume contents (0%, 0.2%, 0.4%, and 0.6%) were considered and the concrete with the strength grade of C35 was designed in the present study. The effects of PVA fibers, rebar diameter, and cover depth on bond behavior were clarified. The effects of PVA fibers on the mechanical property of concrete were also studied. The results show that PVA fibers decreased the compressive strength of concrete, but increased splitting tensile, flexural, and direct tensile strength. PVA fibers negatively affected bonding in the ascending branch both for the pull-out and the splitting failure cases, but improved the bonding in the descending branch after peak stress for the splitting failure case. In the present test, the maximum decrement of bond strength was about 16.2% for specimens with less than 0.6% PVA fibers. PVA fibers restricted both the macro-cracking and micro-cracking for the splitting cases, the former were much more significant than the latter. The effects of rebar diameter and cover depth on bonding became slight and significant with the increasing content of PVA fibers, respectively.