bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis
Authors: Shao Wanqi , Yu Yayuan , Wang Jianzhang , Qiu Zhiruo , Mei Shuyan , Cheng Tao , Chen Yichen , Zhu Weili , Li Xiuhui , Che Xuan
Published: April 2024

This study aimed to elucidate the role of microRNA miR-92a-3p in the pathogenesis of adenomyosis. We focused on understanding how miR-92a-3p in exosomes derived from ectopic lesions influences the behavior of endometrial cells, DRG neurons, and Human Umbilical Vein Endothelial Cells (HUVECs), and its potential as a non-invasive diagnostic biomarker. Our findings revealed that MiR-92a-3p is significantly upregulated in exosomes derived from ectopic lesions of adenomyosis. This upregulation was associated with enhanced migration and invasion capabilities in eutopic endometrial cells, DRG neurons, and HUVECs. Furthermore, the study demonstrated a significant correlation between the levels of MiR-92a-3p in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidates an exosomal signaling process via miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Upregulated miR-92a-3p in biofluid exosomes shows promising non-invasive biomarker potential for diagnosis and monitoring of this disease. Our findings unveil novel targets and tools for improved clinical management.Our research uncovers the significant role of miR-92a-3p in adenomyosis pathogenesis. We demonstrate that miR-92a-3p, upregulated in exosomes from ectopic lesions, enhances migration and invasion of endometrial cells, DRG neurons, and HUVECs. Crucially, miR-92a-3p levels in urinary exosomes correlate with adenomyosis symptoms, highlighting its potential as a non-invasive biomarker. This study offers new insights into adenomyosis progression and introduces novel diagnostic and therapeutic avenues.
Direction-dependent conductivity in planar Hall set-ups with tilted Weyl/multi-Weyl semimetals
Authors: Mandal Ipsita , Ghosh Rahul
Published: April 2024

We compute the magnetoelectric conductivity tensors in planar Hall set-ups, which are built with tilted Weyl semimetals (WSMs) and multi-Weyl semimetals (mWSMs), considering all possible relative orientations of the electromagnetic fields (E and B) and the direction of the tilt. The non-Drude part of the response arises from a nonzero Berry curvature in the vicinity of the WSM/mWSM node under consideration. Only in the presence of a nonzero tilt do we find linear-in-|B| terms in set-ups where the tilt-axis is not perpendicular to the plane spanned by E and B. The advantage of the emergence of the linear-in-|B| terms is that, unlike the various |B|2-dependent terms that can contribute to experimental observations, they have purely a topological origin, and they dominate the overall response-characteristics in the realistic parameter regimes. The important signatures of these terms are that they (1) change the periodicity of the response from π to 2π, when we consider their dependence on the angle θ between E and B; and (2) lead to an overall change in sign of the conductivity depending on θ, when measured with respect to the B = 0 case.
Tunable Anti-Ambipolar Vertical Bilayer Organic Electrochemical Transistor enable Neuromorphic Retinal Pathway
Authors: Rivnay Jonathan , Laswick Zachary , Wu Xihu , Surrendran Abhijith , Zhou Zhongliang , Ji Xudong , Matrone Giovanni , Leong Wei Lin
Published: April 2024

Increasing demand for bio-interfaced human-machine interfaces propels the development of organic neuromorphic electronics with small form factors leveraging both ionic and electronic processes. Ion-based organic electrochemical transistors (OECTs) showing anti-ambipolarity (OFF-ON-OFF states) reduce the complexity and size of bio-realistic Hodgkin-Huxley(HH) spiking circuits and logic circuits. However, limited stable anti-ambipolar organic materials prevent the design of integrated, tunable, and multifunctional neuromorphic and logic-based systems. In this work, a general approach for tuning anti-ambipolar characteristics is presented through assembly of a p-n bilayer in a vertical OECT (vOECT) architecture. The vertical OECT design reduces device footprint, while the bilayer material tuning controls the anti-ambipolarity characteristics, allowing control of the device’s on and off threshold voltages, and peak position, while reducing size thereby enabling tunable threshold spiking neurons and logic gates. Combining these components, a mimic of the retinal pathway reproducing the wavelength and light intensity encoding of horizontal cells to spiking retinal ganglion cells is demonstrated. This work enables further incorporation of conformable and adaptive OECT electronics into biointegrated devices featuring sensory coding through parallel processing for diverse artificial intelligence and computing applications.
Likely technology to make the ancient Cham bricks lightweight, sculptable, and durable for constructing big engraved towers lasting thousands of years the Po Nagar Towers (Thap Ba), Nhatrang, Vietnam
Authors: Loan Nguyen Thu , Thuy Ung Thi Dieu , Duong Luong Van , Huong Tran Thi Thu , Toan Trung , Saladino Maria Luisa , Armetta Francesco , Colomban Philippe , Hreniak Dariusz , Liem Nguyen Quang
Published: April 2024

The Po Nagar Towers (Thap Ba), iconic heritages of Cham culture, have stood in Nhatrang, Vietnam, for over a thousand years. The original bricks (made during the 13-14th century) and restored (during the 2000s) ones from the Po Nagar Cham Towers have been analyzed in detail by using appropriate techniques such as X-ray fluorescence, X-ray diffraction, Raman micro-spectroscopy, thermal dilatometry, etc. The compositions, structural phases, microstructure, sintering temperatures, and open porosity of the bricks have been determined for supporting the discussion on the likely technology used to make the original Cham bricks. The results obtained support the assumption that ancient original Cham bricks were made from clay, sand, plagioclases (feldspar minerals) and grog mixed with intentionally-added carbon (charcoal powder), were then fired at temperatures of 800 oC to 1000 oC forming lightweight bricks with the mass density of 1.3–1.6 kg/dm3 and the open porosity of 18–25%. The intentional use of charcoal powder in the starting materials, in combination with firing at moderate temperatures, are considered to be the key technological factors that make the ancient Cham bricks have their sandstone-like texture and high porosity to meet requirements of the rubbing joint technique in tower construction and to contribute to the sculptability and durability of Cham towers. Using these findings, one can make proper bricks for restorations of the towers, thereby avoiding problems encountered during previous restoration attempts such as erosion damage and challenging engraving.
Clinical Epidemiology and Impact of Haemophilus influenzae Airways Infections in Adults with Cystic Fibrosis
Authors: Weyant R. Benson , Waddell Barbara J. , Acosta Nicole , Izydorczyk Conrad , Conly John M. , Church Deirdre L. , Surette Michael G. , Rabin Harvey R. , Thornton Christina S. , Parkins Michael D.
Published: April 2024

Background
Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF.
Methods
This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥3 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were genotyped using pulsed-field gel electrophoresis (PFGE) to assess relatedness.
Results
Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Four (3%) were serotype F with the rest non-typeable (97%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts.
Conclusions
Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline.
The impact of land finance and land financialisation on sustainable development ——Analysis based on provincial data of China
Authors: Dong Kai , Chen Qinmei , Liu Ying , Zhang Xin , Wang Yali , Shi Xiaolei
Published: April 2024

This paper comprehensively utilizes entropy weight method, two-way fixed effect model and TVP-SV-VAR model to investigate the impact of land finance and land financialisation on sustainable development. The results show that: as a whole, the implications of land finance and land financialization on sustainable development present inverted U-shaped characteristics conclusively. The regional heterogeneity analysis finds that inverted U-shaped impacts of land financialisation are significant in eastern and central regions, while inverted U-shaped impacts of land finance is salient in western region. Furthermore, the dynamic time-varying feature analysis implemented by different lags and time points indicating the facilitative effects of land finance and land financialization on sustainable development diminish gradually, while the inhibitory effects manifest progressively with the passage of time. We highlight that the delineation of authority and financial resources between central and local governments, optimization and reform of incentive mechanism for local government officials, and the spotlight of regional heterogeneity are paramount for effectively promotion of sustainable development.
Scoping review of fidelity strategies used in behaviour change trials delivered in primary dental care settings
Authors: Lowers Victoria , Kirby Robyn , Young Bridget , Harris Rebecca Vera
Published: April 2024

Background
Primary dental care settings are strategically important locations where randomised controlled trials (RCTs) of behaviour change interventions (BCIs) can be tested to tackle oral diseases. Findings have so far produced equivocal results. Improving treatment fidelity is posed as a mechanism to improve scientific rigor, consistency and implementation of BCIs. The National Institutes of Health Behaviour Change Consortium (NIH BCC) developed a tool to assess and evaluate treatment fidelity in health behaviour change interventions, which has yet to be applied to the primary dental care BCI literature.
Method
We conducted a scoping review of RCTs delivered in primary dental care by dental team members (in real-world settings) between 1980 and 2023. Eligible studies were coded using the NIH BCC checklist to determine the presence of reported fidelity strategies across domains: design, training, delivery, receipt and enactment.
Results
We included 34 eligible articles, reporting 24 RCTs. Fidelity reporting variations were found both between and within NIH BCC domains: strategy reporting ranged from 9.5–85.7% in design, 9.5–57.1% in training, 0 to 66.7% in delivery, 14.3–36.8% in receipt and 13.3–33.3% in enactment. The most reported domain was design (M = 0.45) and the least reported domain was delivery (M = 0.21). Only one study reported over 50% of the recommended strategies in every domain.
Conclusions
This review revealed inconsistencies in fidelity reporting with no evidence that fidelity guidelines or frameworks were being used within primary dental care trials. This has highlighted issues with interpretability, reliability and reproducibility of research findings. Recommendations are proposed to assist primary dental care trialists with embedding fidelity strategies into future research.
Developing molecular surveillance of SARS-CoV-2 in the Czech Republic (2021–2022)
Authors: Šúri Timotej , Pfeiferová Lucie , Bezdíček Matěj , Svatoň Jan , Hampl Vladimír , Berka Karel , Jiřincová Helena , Lengerová Martina , Kolísko Martin , Nagy Alexander , Tachezy Ruth , Kolář Michal , Pačes Jan
Published: April 2024

Molecular surveillance was widely used during the COVID-19 pandemic to rapidly detect emerging variants and monitor the transmission of SARS-CoV-2 within communities. In 2021, the Czech COVID-19 Genomics Consortium (COG-CZ) was set up to coordinate a new SARS-CoV-2 molecular surveillance network. In the Czech Republic, molecular surveillance employed whole genome sequencing (WGS) and variant discrimination polymerase chain reaction (VD-PCR) on samples collected through passive, active and sentinel surveillance. All WGS data was uploaded to GISAID and the PANGO lineages used by GISAID were compared to the main variants determined by VD-PCR. To assess the effectiveness and reliability of the gathered data in adapting pandemic responses, the capabilities and turnaround times of the molecular surveillance methods are evaluated.VD-PCR enabled accurate detection of changes in major variant dominance within 48 h of sample collection during the Delta/Omicron transition. WGS detected novel mutations and infection clusters, including several genetic lineages and clades of the virus, some of which were unique to the Czech Republic, such as AY.20.1. Molecular surveillance informed the implementation of public health measures and contributed to reduced cases and mortality, however further areas for improvement have been identified for monitoring and managing future pandemics.
Construction and Validation of a Novel Model for Guiding Targeted Combined Immunotherapy in Advanced Hepatocellular Carcinoma
Authors: Tu Haibin , Feng Siyi , Chen Lihong , Huang Yujie , Zhang Juzhen , Peng Suyu , Ye Xiaojian , Lin Dingluan
Published: April 2024

In addressing the challenge of optimizing targeted combined immunotherapy for advanced hepatocellular carcinoma (HCC), this study developed and validated a novel prognostic model, the Target Immunotherapy Predict Model (TIPM), utilizing ultrasound and serological markers. Data from patients at Mengchao Hepatobiliary Hospital and Fujian Provincial Cancer Hospital were analyzed, encompassing demographics, serological markers, and ultrasound findings, including tumor and peritumoral tissue stiffness changes pre- and post-treatment. The multivariate analysis revealed the neutrophil-to-lymphocyte ratio (NLR), ΔT (tumor stiffness change), tumor diameter, and albumin levels as independent predictors of therapy response. The TIPM model, integrating these factors, demonstrated superior predictive accuracy, validated by Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis across both training and external validation cohorts. This predictive model stands to refine clinical decision-making, potentially improving treatment outcomes for advanced HCC patients by identifying those most likely to benefit from combined immunotherapy approaches
Characteristic Clustering of Thrombolytic Agent Decision-making in Acute Ischemic Stroke and Analysis of Influencing Factors
Authors: Fan Wenfeng , Ma Keke , Yang Caixia , Guo Li-na , Dong Xiaofang , Gao Renke , Liu Yanjin , Guo Yuanli
Published: April 2024

Aim
To explore the categories of different decision-making psychological characteristics of thrombolysis proxy decision-makers in acute ischemic stroke and analyze the influencing factors of different categories.
Background
Thrombolysis proxy decision-makers suffered from decision-making dilemmas, which correlated with their multiple psychosocial factors.Identifying the psychological characteristics of different decision-makers may help healthcare professionals develop decision-support programs applicable to different categories of decision-makers. This is essential for improving decision-making efficiency, reducing dilemmas, and decreasing hospital delays.
Methods To
facilitate the selection of acute ischemic stroke patients and their proxy decision makers who attended the emergency department of a comprehensive tertiary hospital in Zhengzhou City, Henan Province, from April 2023 to December 2023 as the survey subjects, and to collect the survey subjects' general information questionnaire, perceived social support scale, state anxiety scale, and decision-making dilemma scale. The final clustering was completed using K-means cluster analysis, and the influencing factors were analyzed by unordered multiclassified logistic regression.
Results
Acute ischemic stroke thrombolysis proxy decision makers can be divided into "high social support-low anxiety-high trust-decision effective", "high social support-high anxiety-moderate trust-decision conflict", "high social support-high anxiety-low trust-decision delay" three categories, which were influenced by the decision maker's gender, number of decision makers, decision maker's literacy level, whether they lived with the patient, whether they were the patient's main financial source, the patient's age, NIHSS score, and the time of the onset of the disease.
Conclusion
There are differences in the decision-making psychological characteristics of different thrombolysis agent decision-makers, and healthcare professionals should provide personalized decision-making aids for their psychological characteristics to improve the efficiency of thrombolysis decision-making, and strive for valuable time to save patients' neurological function.
Implications for nursing policy and health policy
Cluster analysis can be used to classify thrombolytic agent decision makers into three categories based on psychological characteristics and decision-making challenges. This is the first step in developing targeted decision aids for thrombolytic agent decision makers in the future.
Effects of combined application of slow-release fertilizer and nitrogen fertilizer on nitrogen uptake, utilization and yield of maize under tillage modes
Authors: Fan Mingyuan , Chen Pei , Zhang Chang , Liang Min , Xie Guangming , Zhao Li , Wang Chuangyun
Published: April 2024

Objective To explore the improvement of water use efficiency(WUE), dry matter accumulation(DMA), nitrogen absorption and utilization and maize yield under the two tillage methods of slow release fertilizer(S) and urea(U), aiming to screen the appropriate tillage method and appropriate fertilizer ratio for high and stable yield of maize.
Method The maize variety Qiangsheng 388 with strong drought resistance was selected as the experimental material, and a two-factor random block design was adopted from 2022 to 2023, with two tillage methods: rotary tillage (R) and rotary tillage + subsoiling (R+S). The combination of slow release fertilizer(S) and urea(U) was used as a sub-area, and 6 treatments were set: CK (no fertilization); U (100% nitrogen fertilizer); S (100% slow-release fertilizer); UNS1（U：S=2:8）； UNS2（U：S=3:7）； UNS3（U：S=4:6）. Soil moisture, dry matter accumulation, nitrogen uptake and utilization and yield of maize plants were measured at different growth stages.
Result (1) From 2022 to 2023, as the fertility period progresses, the accumulation of DMA and nitrogen under all treatments under tillage methods showed an increasing trend. In 2022, the accumulation of DMA and nitrogen in the R tillage method UNS2 was the best, which were 24898.5 and 275.25 kg·hm-2, respectively, which were 2.0% and 3.88% higher than those of the R+S tillage UNS2 treatment, respectively. In 2023, UNS2 under R+S tillage was the best, which were 24056.34 and 260.81kg·hm-2, 2.52% and 1.85% higher than UNS2 under R tillage, respectively. (2) In 2022, the yield of R tillage UNS2 treatment was the largest, which was 14712.78 kg·hm-2, which was 4.06% higher than that of R+S tillage UNS2 treatment. In 2023, the yield of R+S tillage UNS2 treatment was 13901.88 kg·hm-2, which was 2.20% higher than that of R tillage UNS2 treatment. (3) In 2022, the nitrogen utilization rate, nitrogen fertilizer utilization rate, nitrogen absorption efficiency and nitrogen harvest index of UNS2 under R tillage were the best, which were 0.13%, 4.05%, 1.36% and 4.55% higher than those under UNS2 under R+S tillage, respectively. In 2023, all indicators of R+S tillage UNS2 treatment were also the best, which were 0.34%, 2.21% , 0.25% and 2.35%, higher than those of R tillage UNS2 treatment, respectively. (4) In 2022, the WUE of R tillage UNS2 treatment was 36.28 kg·hm-2·mm-1, which was 4.66% higher than that of R+S tillage UNS2 treatment. In 2023, the WUE of R+S tillage UNS2 treatment was 34.63 kg·hm-2·mm-1, which was 2.73% higher than that of R tillage UNS2 treatment.
Conclusion This study showed that the R+S tillage effect in 2023 was better than that in 2022, and it was also better than that of R tillage treatment in 2023. UNS2 treatment could significantly improve the DMA, nitrogen uptake and utilization, WUE and yield of maize, and the optimal fertilization ratio was the most suitable fertilizer ratio.
Exploring Temperature Trends and Evapotranspiration Modelling for Effective Water Management: A Comprehensive Analysis Using Mann-Kendall Test and Seasonal ARIMA Model
Authors: Dwivedi D. K. , Pandya P. A. , Joshi V. P. , Dave Jaydeep
Published: April 2024

The variations in temperature have a profound impact on the irrigation requirement during various stages of the crops. This study aimed to analyse the temperature trends using the Mann Kendall test and also modelled various meteorological parameters by Seasonal Autoregressive Moving Average (SARIMA) model, influencing evapotranspiration (ET). The model was validated for water requirement of wheat crop in Junagadh region of Gujarat during 2023 and 2024. February, March, and April consistently exhibited a highly significant positive trend with Mann Kendall test statistic of 3.325. 2.852 and 3.131 respectively whereas July, August, and November showed no distinct trend in minimum temperatures. A conspicuously significant trend in maximum temperature was not discerned throughout any of the months. SARIMA models (2,0,0)(2,1,1)12, (1,0,0)(0,1,1)12, (1,0,1)(0,1,1)12, (1,0,0)(0,1,1)12, and (2,0,2)(0,1,1)12 were selected from a range of candidate models based on their AIC values and performance on test data for meteorological parameters including minimum temperature, maximum temperature, relative humidity, wind speed, and bright sunshine, respectively. The study estimated the climatic parameters using Penmen Monteith method, allowing us to predict reference evapotranspiration for 2023 and 2024. For the year 2024, the highest ET0 of 188.7 mm was estimated in April followed by ET0 of 186.6 mm in May 2024. The reference evapotranspiration predicted by the models were utilized to calculate the water requirement of wheat in the study area, resulting in an estimated value of 371 mm. These findings are useful for agricultural policymakers for making decisions pertaining to agricultural water management for optimal crop growth.
Abiotic nitrous oxide formation driven by sunlight in fresh and marine waters
Authors: Leon-Palmero Elizabeth , Morales-Baquero Rafael , Thamdrup Bo , Löscher Carolin , Reche Isabel
Published: April 2024

Nitrous oxide (N2O) is the main stratospheric ozone depleting agent, and the strongest greenhouse gas in the atmosphere. Classically, microbially-mediated processes, such as ammonia oxidation and denitrification are assumed to control the N2O budget in aquatic systems. Recent studies suggest that our understanding of N2O production is incomplete. Specifically, abiotic reactions like chemodenitrification may contribute significantly to N2O production, but their importance is uncertain, particularly in surface waters. Here, we experimentally demonstrate a significant and consistent production of N2O induced by sunlight under oxic abiotic conditions in two fresh and two marine waters, a novel process not considered for greenhouse gas budgets. N2O production was strongly correlated to the radiation dose. Nitrite is the main sustrate, and the nitrate can also contribute after being photoreduced to nitrite. We defined this abiotic N2O photoproduction as photochemodenitrification. Photochemodenitrification exceded biological production of N2O by ammonia oxidation in surface waters. We demonstrate that photochemodenitrification may be an essential and overlooked process occurring in fresh and marine surface waters across the globe, with particular importance in areas of high solar radiation and nitrite availability. Because it occurs in surface waters in direct contact with the atmosphere, photochemodenitrification may be responsible for a significant fraction of N2O emissions globally.
Integrated single-cell and bulk RNA-seq analysis reveals a novel T-cell signature for prognosis and treatment response in colorectal cancer
Authors: Cui Peng , Wang Haibo , Bai Zhigang
Published: April 2024

Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC. This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis (WGCNA), Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS, based on six T cell-related genes. Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immune Prognostic Score (IPS) and lower Tumor Immune Dysfunction and Exclusion (TIDE) scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor (ICI) therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-Fu-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.
Novel anthraquinone amino-derivatives as anticancer targeting human serine/threonine kinase PAK4
Authors: Hasan Hamad M. , Koua Faisal H. M. , Beit Hajer A. , Ebrahim Reem M. A. , Ismail Amar Mohamed
Published: April 2024

Anthraquinone scaffold has attracted increasing attention recently as a source for effective drug synthesis targeting various diseases. Here we demonstrate the potential of nine anthraquinone amino-derivatives (AAD) as anticancer agents. We synthesized nine Schiff bases (1–9) using anthraquinone scaffold and amino acids. We performed molecular docking against the anticancer drug target human serine/threonine p21-activated kinase 4 (PAK4) and compared it with the recently developed PAK4 inhibitor PF-3758309. Compounds 5 and 8 showed comparable docking properties to that of the PF-3758309 at two binding sites located at the c-terminal domain of PAK4. Compound 5, a tryptophan-based anthraquinone derivative, exerts a docking score of -9.3 and − 8.7 kcal/mol at two different identified cavities, cav-1 and cav-4, respectively, exceeding that of the control PF-3758309 for both cavities. Additional optimization on the indole moiety of 5 gave rise to 5b, resulting in high drug likeness (0.74) and comparable binding properties to cav-1 with − 8.6 kcal/mol and the highest achievable binding affinity to cav-4 with an average of -9.7 kcal/mol, indicating a potential allosteric inhibitory effect via cav-4. Our molecular dynamics simulation analysis on the top hits and the control compound provides important insights into the mechanism of action of these drug candidates. Additionally, all compounds exhibited promising pharmacokinetics and toxicity properties as revealed by the ADMET profiles, urging the need for comprehensive in vitro and in vivo antitumor characterization. Our results also indicate that cav-4 may serve as a target for designing specific allosteric inhibitors against PAK4-overexpressed cancer cells, suggesting a potential application in adjuvant cancer treatment.
Management of radioiodine ablation therapy in haemodialysis patients with thyroid cancer: a case series of two patients
Authors: Lin Raymond , Malaroda Alessandra , Ryder William J , Wong Veronica CK , Wong Nikki L
Published: April 2024

Background
Radioiodine (131I) therapy in treatment of thyroid cancer, has a biological clearance that is significantly reduced in end-stage kidney disease (ESKD), leading to increased radiation exposure and potential myelotoxicity. For ESKD patients on haemodialysis (HD), there is no standardized approach to 131I administration and scheduling of HD following.
Methods
Two patients with ESKD on HD were treated with 131I therapy for thyroid cancer. Local 131I treatment protocol was modified to account for ESKD and HD. Modifications were made to existing infrastructure and additional patient and staff safety precautions were undertaken, including serum 131I measurements to monitor for myelotoxicity.
Results
HD at 24-,72- and 144-hours post-131I results in a retained radiation activity profile comparable to patients with normal renal function. Radiation dose to bone marrow throughout treatment was assessed at < 0.3 Gy for both patients. The highest contribution of radiation dose to bone marrow (60% and 47% for patient 1 and patient 2 respectively) was due to the radioactivity retained in blood before the first HD session. Cumulative radiation exposure to dialysis staff during therapy was well within local safety constraints. At 18 months post-therapy, remnant thyroid ablation was successful in both patients.
Conclusions
131I therapy can be safely administered in patients with ESKD on HD with modifications to existing infrastructure and protocols. Serum 131I measurements is a simple and minimally invasive method to assess bone marrow safety during treatment. Ongoing pooling of experiences is needed to inform a standardized protocol for therapy in this population.
TMS-evoked potentials: neurophysiological biomarkers for diagnosis and response to ventriculoperitoneal shunt in normal pressure hydrocephalus
Authors: Davidy Tal , Anis Saar , Suminski Alexandra , Zauberman Yakov , Fay-Karmon Tsvia , Saar Adi , Zifman Noa , Fogel Hilla , Abulher Eden , Lesman-Segev Orit , Hassin-Baer Sharon
Published: April 2024

Current practice for normal pressure hydrocephalus (NPH) relies upon clinical presentation, imaging and invasive clinical procedures for indication of treatment with ventriculoperitoneal shunt (VPS). Here we assessed the utility of a TMS-evoked potentials (TEPs)-based evaluation, for prediction of response to VPS in NPH, as an alternative for the cerebrospinal fluid tap test (CTT). 37 "possible iNPH" patients and 16 age-matched healthy controls (HC) were included. All subjects performed Delphi (TMS-EEG and automated analysis of TEP), in response to primary motor cortex (M1) and dorsolateral prefrontal (DLPFC) stimulations. Sixteen patients underwent VPS and response was evaluated with change in modified Rankin Scale (MRS), clinical global impression of change (CGIC) regarding gait and the change on a repeated 3-meter timed up and Go (TUG) after 3 months. TEP Delphi-NPH index was most successful in discrimination of iNPH responders to VPS (ROC-AUC of 0.91, p = 0.006) compared to CSF Tap-Test (CTT) (AUCCTT=0.65, p = 0.35) and other imaging measures. The TEP M1 P60 and P180 latencies were earlier in responders compared to controls (pM1 P60=0.016, pM1 P180=0.009, respectively). TEPs, may be an alternative for CTT, in prediction of response to VPS in patients suspected as iNPH, exhibiting higher efficacy with reduced patient discomfort and risks.
Assessment the knowledge of community pharmacists in diabetic patients counseling in Ha’il, Saudi Arabia
Authors: Osman Mhdia , Saleh Hanadi , Ayed Alanoud , Alhejaili Saba , Salih Rabab , Hassoun Shimaa
Published: April 2024

Background
Diabetes is one of the most common chronic diseases that may contribute to severe morbidity, mortality, and disability. Community Pharmacists are essential to optimizing drug use and enhancing patient outcomes—
this study aims to assess community pharmacist knowledge and services currently provided to diabetic patients.
Method
a cross-sectional study was done in the Hail region by a structured questionnaire including a demographic profile of the participant with the variables (gender, age, nationality, education, and experience) as well as supporting characteristics, evaluation of diabetes care services, MCQ of pharmacists’ diabetes-related knowledge and perceived barriers for providing diabetic care services. The data analysis is completed by SPSS and with the endnote program for reference citation.
Results
the majority of pharmacists working in community pharmacies in the Hail region were males (82.9%), young (24-34year) 68.5%, non-Saudi (70.5%), about (64–65%) of pharmacists delivered pharmaceutical care services to diabetic patients; always provide counseling for smoking cessation, drug administration, glucose monitoring, and diabetes complications. The majority of community pharmacists (61%) have moderate diabetes-related knowledge and have various counseling barriers like limited knowledge about diabetes counseling and lack of time.
Conclusion: Hail region community pharmacists have a moderate understanding of diabetes counseling, so they need further training and workshops about diabetes counseling.
Assessment Methods and Practices in Anatomy Departments among Sudanese Medical Schools in 2020
Authors: Emam Mohamed O. , Ali Wisam A. , Babiker Ahmed B. A. , Amin Mohammed Hammad Jaber
Published: April 2024

Background
Assessment could be the most challenging part in the teaching process of anatomy for establishing students’ competency. This study aimed to review how anatomy is assessed in medical schools in Sudan to provide a baseline data for future plans.
Methods
This is a cross-sectional descriptive study involving medical schools in Sudan. A pre-designed electronic questionnaire (Google Form) was sent to the heads of anatomy departments at the different medical schools in Sudan. The questionnaire included questions about duration of anatomy teaching in the curriculum, the types of assessment for anatomy leaning applied, pattern of examination included in the written examination and type of curriculum. Additionally, a variety of questions assessing how oral and spotter exams take place and information related to students` feedback following examinations.
Results
Total of 50 universities responded to the electronic questionnaire out of 66 universities (with a response rate of 75.7%). The results showed that 80% of the universities used summative and formative approaches to the assess students, about 84% of the universities had continuous assessment, all the participating universities used MCQs as a part of their student assessment and only 5% used True or False questions. A 96% of the participating universities use spotter exams, about 16% of the universities perform oral examination to all students and 22% of the participating universities give students feedback after every exam.
Conclusion
Sudanese medical schools use different assessment methods and practices for Anatomy. The most commonly practiced assessment tools were MCQs and spotter examination while oral examination and long assay type of questions are less used. Medical schools need to work on teachers training on the principles of medical education and review of examination by examination committees.
Ultrasound evaluation of uterine healing after vaginal repair of cesarean section scar defect: An observational study
Authors: Qiao Huayuan , Wang Yizhi , Chen Huihui , Wang Xipeng
Published: April 2024

Background
Many cesarean section scar defects (CSD) patients worry about thin thickness of the residual myometrium (TRM) and want to avoid uterine rupture in subsequent pregnancies. In addition, some blood flow indices could be possible predictive markers for impaired wound healing. To date, there is no method to dynamically assess the healing process in the uterine repair of CSD. To evaluate the association between uterine healing and uterine artery blood flow changes after vaginal repair of CSDs with two-dimensional power Doppler ultrasound and Doppler velocimetry.
Methods
A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 98 women with CSDs underwent VR, between June 2021 and March 2022. During follow up 9 patients withdrew from the study. After vaginal repair, all patients were followed by traditional two-dimensional power Doppler ultrasound scanning and Doppler velocimetry preoperatively and at 2 days, 1 month and 3 months postoperatively. The size and location of the CSDs, TRM and Doppler velocimetry of the uterine arteries were evaluated.
Results
The thickness of the residual myometrium was significantly improved after vaginal repair (P < 0.05). However, it gradually became thinner over time. There was a significant (P < 0.05) progressive reduction in the uterine scar area from 82% on the second day in the first month to 67% in the third month. The pulsation index (PI), resistance index (RI), and systolic peak flow rate/diastolic flow rate (S/D) of the uterine artery showed little change after vaginal repair. The peak systolic velocity (PSV) value of the uterine artery significantly increased from 50.35 preoperatively to 53.92 on the second day after repair (p = 0.006). In total, 89 women had the symptom of postmenstrual spotting before repair, and 71.9% (64/89) of these patients returned to normal menstruation after repair. According to the preoperative duration of menstruation, the patients were divided into two groups (menstruation duration ≤ 7 days group and menstruation duration > 7 days group). The PSV values of the uterine artery in the first postoperative month were 53.32 ± 8.49 and 48.24 ± 7.35, respectively, and there was a significant difference between the two groups (p = 0.028).
Conclusion
The TRMs of CSD patients can be improved by vaginal repair. Traditional two-dimensional ultrasound and Doppler velocimetry can dynamically assess the healing process of the uterus after vaginal repair. Moreover, the PSV value in the first month after surgery may be a marker for predicting wound healing.
A cohort study of transjugular intrahepatic portal systemic shunt in portal hypertension in cirrhosis
Authors: fan Wu Yi , Ding H , Zhang Ke , Wang Lei , Yue Zhendong , Fan Zhenhua , Dong Chengbin , Zhang Yu , Li Qi mei , Liu Fuquan
Published: April 2024

Background
TIPS can effectively reduce the portal pressure, alleviate clinical symptoms, PPG for the portal pressure gradient, studies show that for patients with esophageal and gastric varices rupture bleeding, postoperative PPG maintenance at 6-12mmHg is best, but these studies are for Europe and the United States population, for Asian portal hypertension with refractory ascites, what level of postoperative PPG is reasonable, there is no clear study., Therefore, we conducted this study.
Methods
This is a retrospective study of patients who received TIPS at multiple tertiary centers. Patients were recruited from January 2014 to December 2018 at Beijing Shijitan Hospital of Capital Medical University, PLA General Hospital and You'an Hospital affiliated to Capital Medical University. In this study, a total of 147 patients with cirrhosis with refractory ascites received TIPS. According to the postoperative PPG value of the enrolled patients, they were divided into three parts according to the order of small to large, and then the enrolled patients were divided into three groups: first group: 5mmHg < PPG < 12mmHg; second group: 13mmHg < PPG < 20mmHg; and third group: 21mmHg < PPG < 28mmHg. Statistical differences between the three groups in 5-year survival rate, the incidence of postoperative hepatic encephalopathy and postoperative ascites recurrence rate were calculated for the three groups. The 5-year survival rate of the three groups was 58.1%, 30%, and 22.2% (P = 0.002), among the three groups. The incidence of ascites recurrence in the three groups was 20.3%, 43.3% and 44.4% (P = 0.012), respectively, among the three groups. The incidence of hepatic encephalopathy in the three groups was 31.1%, 16.7% and 0% (P = 0.034), respectively, among the three groups.
Result
For patients with refractory ascites, postoperative maintenance of PPG in between 5 and 12mmHg can reduce the probability of postoperative hepatic encephalopathy and ascites recurrence, which has a good clinical guidance significance.
Complexity indexes from instrumented timed-up-and-go test reveal depression-related movement differences
Authors: Fransvea Giulia , Patron Elisabetta , Vendrame Eleonora , Truppa Luigi , Mura Francesca , Cipriani Christian , Gentili Claudio , Mannini Andrea
Published: April 2024

Major Depressive Disorder (MDD) is one of the most common psychological disorders. The multiplicity of its clinical patterns, the varieties of symptoms and the different types of clinical evolution generate many diagnostic difficulties. Currently, MDD assessment is performed through the use of assessment scales and interviews with the patient. This highlights the need to adopt methods that can make an objective, rapid and effective diagnosis. Mental disorders and embodiment can alter the brain processes that are related to cognition and therefore to the motor system. As a result, movement analysis by means of wearable sensors is attracting the attention of clinicians as it represents a solution that can be quickly translated into ecological environments. In this study we explored the potential of an instrumented movement assessment, targeting the long-term goal of self-administered assessment in ecological settings. Using 4 inertial measurement units (IMUs), we tested parameters that could be predictive of pathology during a timed up and go test. By means of age/sex adjusted logistic regression we identified instrumental parameters significantly discriminating MDD patients and controls. Building on earlier findings in literature for pathology recognition in movement, a particular attention was devoted to parameters concerning movement complexity evaluated by multiscale entropy analysis of signals. Our tests confirmed that complexity parameters can significantly discriminate between patients and controls (Nagelkerke’s R2 = 0.523).
Seed Priming With Anabaena Minutissima Extract Ameliorates the Stress Response of Tomato Plantlets to Soilborne Pathogens
Authors: Righini Hillary , Galletti Stefania , Cianchetta Stefano , Quintana Antera Martel , Francioso Ornella , Roberti Roberta
Published: April 2024

This study assessed the effectiveness of the treatment of tomato seeds with an aqueous extract of the dried biomass of the microalgae Anabaena minutissima in protecting the plants from diseases caused by soilborne pathogens like Rhizoctonia solani and Pythium ultimum. The extract, obtained by an autoclave-assisted method at 100°C, was rich in proteins and carbohydrates (56.6 and 26.9% of total solids). Preliminary tests were performed revealing: i) a moderate direct activity toward pathogen in vitro growth, with ± 9% stimulation/inhibition, depending on the pathogen; ii) a stimulatory/inhibitory activity toward seedling growth, depending on the dose; iii) no effect on the mycelial growth by root exudates of treated plantlets. Then, a greenhouse experiment was set up to test the response of tomato plants in substrates artificially inoculated with the single pathogens, after seed treatment with the extract at different doses (0, 2.5, 5, and 10 mg mL− 1). The treatment generally increased the percentage of standing plants and restored plant development up to the level of healthy controls. Moreover, the disease incidence and severity progressively reduced at increasing doses. Finally, the seed treatment significantly increased some markers of induced systemic resistance like endochitinase and glucanase activity, in hypocotyls of 14-day-old seedlings, compared to non-treated controls. Besides, the treatment increased epicotyls’ carotenoid and chlorophyll a and b content. Overall, these results demonstrate that seed priming with A. minutissima aqueous extract is a promising eco-friendly tool to ameliorate tomato plant responses towards soilborne pathogens, stimulating plant growth and activating induced resistance mechanisms.
Combating fall armyworm (Spodoptera frugiperda) with moringa-synthesized silica nanoparticles and its combination with some insecticides
Authors: Elnabi Amany Abd , Badawy Mohamed E. I.
Published: April 2024

The fall armyworm (Spodoptera frugiperda) is a major agricultural pest known for developing resistance to insecticides. This study investigated a novel approach to manage the fall armyworm by silica nanoparticles (SiNPs) synthesized from eco-friendly Moringa oleifera leaf extract. This green synthesis method offers a sustainable and potentially safer alternative to traditional chemical processes. SiNPs formation was confirmed by various techniques: UV–visible spectrophotometer, X-ray spectroscopy with energy dispersive (EDX), scanning electron microscopy (SEM), and dynamic light scattering (DLS). The effectiveness of SiNPs alone and its combination with three common insecticides (emamectin benzoate, indoxacarb, and chlorpyrifos) were evaluated against third instar larvae of fall armyworm. While, SiNPs after 24 h by leaf dipping method recorded limited insecticidal activity (LC50 = 9947.59 mg/L), it significantly enhanced the potency of all three insecticides. Combining SiNPs with emamectin benzoate resulted in the most dramatic increase in effectiveness compared to the insecticide alone with LC50 = 0.295 mg/L and 0.42 mg/L, respectively. This research suggests that moringa extract can be a valuable resource for the green synthesis of nanoparticles potentially useful in pest control. This approach could potentially reduce the amount of insecticide needed for effective pest control, leading to a more sustainable and environmentally friendly agricultural practice.
Role of projectile ion mass in vacancy formation on muscovite mica
Authors: Mukherjee Joy , Bhowmick Sudip
Published: April 2024

This article investigates the impact of energetic projectile ion mass on defect/vacancy formation on muscovite mica. Utilizing low-energy bombardment (10 keV), the effects of two different projectile ions (Ar+, O+) irradiation on multi-elemental muscovite mica under normal and grazing incidence conditions, are examined theoretically. The findings reveal varying amounts of vacancy formation in the constituent elements of mica, with heavier Ar-ions inducing the maximum vacancy production compared to oxygen ions, owing to the greater energy available (Tdam) for vacancy formation. Despite of a similar energy transfer by each ion, the resulting damage and vacancy production differ across ions, is investigated here. Additionally, a shift in the ion distribution profile towards deeper penetration depths compared to the energy distribution profile (Bragg's peak), for different ions is observed for two different incidence angles. The qualitative explanation for vacancy formation and its dependence on projectile mass, is elucidated using the NRT displacement model and Monte Carlo simulations (SRIM) simulations. This study provides insights into the intricate interplay between projectile mass, energy transfer by projectile ions, and vacancy formation on muscovite mica.