bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency-specific changes in prefrontal activity associated with maladaptive belief updating in volatile environments in euthymic bipolar disorder
Authors: Ruiz Maria Herrojo , Ivanova Marina , Germanova Ksenia , Petelin Dmitry , Ragymova Aynur , Kopytin Grigory , Volel Beatrice , Nikulin Vadim
Published: May 2024

Bipolar disorder (BD) involves altered reward processing and decision-making, with inconsistencies across studies. Here, we integrated hierarchical Bayesian modelling with magnetoencephalography (MEG) to characterise maladaptive belief updating in this condition. First, we determined if previously reported increased learning rates in BD stem from a heightened expectation of environmental changes. Additionally, we examined if this increased expectation speeds up belief updating in decision-making, associated with modulation of rhythmic neural activity within the prefrontal, orbitofrontal, and anterior cingulate cortex (PFC, OFC, ACC). Twenty-two euthymic BD and 27 healthy control (HC) participants completed a reward-based motor decision-making task in a volatile setting. Hierarchical Bayesian modelling revealed BD participants anticipated greater environmental volatility, resulting in a more stochastic mapping from beliefs to actions and paralleled by lower win rates and a reduced tendency to repeat rewarded actions than HC. Despite this, BD individuals adjusted their expectations of action-outcome contingencies more slowly, but both groups invigorated their actions similarly. On a neural level, while healthy individuals exhibited an alpha-beta suppression and gamma increase during belief updating, BD participants showed dampened effects, extending across the PFC, OFC, and ACC regions. This was accompanied by an abnormally increased beta-band directed information flow in BD. Overall, the results suggest euthymic BD individuals anticipate environmental change without adequately learning from it, contributing to maladaptive belief updating. Alterations in frequency-domain amplitude and functional connectivity within the PFC, OFC, and ACC during belief updating underlie the computational effects and could serve as potential indicators for predicting relapse in future research.
The impact of nutritional programming on the microbiota of different gut regions in Atlantic Salmon (Salmo salar) from first feeding in a 22-week feeding trial
Authors: Tawfik Marwa Mamdouh , Tocher Douglas R. , McMillan Stuart , Norambuena Fernando , Douglas Alex , Betancor Mónica B. , Martin Samuel A. M.
Published: May 2024

Increasing evidence suggests that gut microbiota is essential for regulating the development of the digestive system, aiding digestion, nutrient metabolism, growth, immune function, and disease resistance. Advances in high throughput sequencing technologies have allowed the development of a broader understanding of the complex gut microbiota in fish, especially in relation to the impact of dietary plant ingredients on gut health. However, to date, most studies have focused on the entire or distal gut in response to a plant-based diet. Moreover, the potential involvement of the microbiome in driving the adaptation of early-exposed Atlantic salmon to a plant-based diet during a later developmental stage, a phenomenon commonly referred to as ‘nutritional programming’, has yet to be demonstrated. The aim was to characterise and compare the microbiota composition and diversity in gut regions (pyloric caeca, middle and distal intestines) of Atlantic salmon (maintained for 22 weeks from first feeding in a recirculating aquaculture system) with and without nutritional programming using a plant-based diet. 16S rRNA amplicons sequencing was employed to monitor taxa and were identified as amplicon sequence variants. The study experiment followed a typical nutritional programming design with two experimental groups. Fish initially exposed to the plant-based diet for two weeks at first feeding and challenged later at 16 weeks post first-feeding for six weeks with a similar plant-based diet were considered the programmed group, whereas those initially fed a marine diet and challenged later with the plant-based diet were the control group. The alpha diversity was higher in the pyloric caeca than the distal intestine. Analysis of similarities showed that the microbiota of pyloric caeca differentiated in composition from each of middle and distal regions after nutritional programming in both high and low-abundant taxa. Ruminococcaceae (primarily anaerobic Clostridia) comprised the core taxa in 80% of fish in the programmed group across the three gut regions and is known to help ferment plant ingredients. Moreover, the internal environment of each gut region mainly selects their microbial assemblages. Additionally, sequencing of feed and water revealed their influence on the gut microbiota of programmed and control fish. Furthermore, Firmicutes, Proteobacteria, Actinobacteriota and Bacteroidota were the prevalent and dominant phyla regardless of the gut region. Further research is required to better understand the microbial programming and its functional consequences in carnivorous fish.
Agroeconomic and environmental implications of future labor market evolution
Authors: Zhao Xin , Sheng Di , Edmonds James , Patel Pralit , Stephanie Waldhoff , O'Neill Brian , Wise Marshall
Published: May 2024

Long-term labor market evolution shapes agricultural transformation through labor productivity growth and labor market transitions. Despite its importance in agricultural production, labor has been overlooked when exploring the agrifood-water-environment-climate nexus. Here, we incorporate evolving labor markets into multisector dynamic modeling to examine their agroeconomic and environmental implications. Our projections show that the recent decline of global agricultural employment persists, with an estimated decrease of over 40 million people per decade by 2100, strengthening the decoupling of labor from production. Exploring scenarios with varying labor productivity and supply factors, we illustrate a critical linkage between labor market dynamics and global environmental change, with a positive relationship between productivity-adjusted labor supply and agricultural emissions and more pronounced regional and sectoral responses. While highlighting the pressing need to capture labor dynamics in the integrated human-Earth systems, our study lays the foundation for further investigation into labor market responses and feedback in broader scenarios.
Multi-country evidence on societal factors to include in energy transition modeling
Authors: Fisch-Romito Vivien , Jaxa-Rozen Marc , Wen Xin , Trutnevyte Evelina
Published: May 2024

Integrated assessment and energy system models are challenged to account for societal transformation dynamics to produce feasible low-carbon pathways. Yet, empirical evidence is lacking on which factors should be incorporated, how and to what extent this would improve the quality and relevance of modeled pathways. Here, we include six societal factors related to (i) infrastructure dynamics, (ii) actors and decision making and (iii) societal and institutional context into an open-source simulation model of the national power system transition. We apply this model for 31 European countries and, using hindcasting (1990–2019), quantify which societal factors improved the modeled pathways. We find that, if well-chosen and in most cases, incorporating societal factors can improve the hindcasting performance by up to 24% in terms of modelled installed capacity of individual technologies, but there are also situations where hindcasting performance can become worse. The combinations of most relevant societal factors differ among countries and model outputs, but infrastructure lock-in, public acceptance and investment risks contribute more strongly and frequently to model performance improvement. Our study hence paves the road to evidence-based choice of societal factors to be included in energy transition modeling in a systematic and transparent way.
Clinicopathologic Features of Renal Neuroendocrine Neoplasms
Authors: Meng Lili , Jiang Zhenjian , Lin Shulan , Ni Zheng , Hu Shuying , Li Xiang , Guo Xinxin , Chen Shanghua , Ji Yuan , Hou Yingyong , Hou Jun
Published: May 2024

Primary renal neuroendocrine tumors (NENs) are a unique and rare type of tumor, with relatively limited research. In our retrospective study, we aimed to comprehensively investigate the clinicopathological features, biological behavior, and prognosis of patients that diagnosed as renal neuroendocrine tumors and treated at our center. Histological evaluations were meticulously conducted on archived diagnostic slides obtained from pathological examinations. Notably, all six cases of primary renal neuroendocrine tumors presented as solitary lesions, with a predilection for the left kidney in the majority (4/6) of cases. In accordance with the latest WHO classification, one case was diagnosed as neuroendocrine carcinoma (NEC), while the remaining five cases were identified as well-differentiated neuroendocrine tumors (NETs). Microscopically, the tumor cells exhibited distinctive organ-like structures. One case demonstrated characteristics of a large cell type, with mitotic images and visible necrosis. All tumor synaptophysin were diffusely stained, although chromogranin and CD56 staining patterns varied. Further molecular investigation using next-generation sequencing (NGS) in one case unveiled copy number amplification of the MCL-1 gene; however, no common molecular changes observed in gastroentero-pancreatic neuroendocrine tumors (GEPNEN), such as VHL, ATRX, and DAXX mutations. The limited knowledge regarding the molecular profile and survival outcomes of primary renal neuroendocrine tumors underscores the necessity for enhanced understanding of their behavior. In the process of clinical diagnosis, an improved awareness and accurate diagnosis are imperative to facilitate optimal treatment strategies for patients.
Multimodal Learning for Mapping the Genotype-Phenotype Dynamics
Authors: Khodaee Farhan , Zandie Rohola , Edelman Elazer
Published: May 2024

How complex phenotypes emerge from intricate gene expression patterns is a fundamental question in biology. Quantitative characterization of this relationship, however, is challenging due to the vast combinatorial possibilities and dynamic interplay between genotype and phenotype landscapes. Integrating high-content genotyping approaches such as single-cell RNA sequencing and advanced learning methods such as language models offers an opportunity for dissecting this complex relationship. Here, we present a computational integrated genetics framework designed to analyze and interpret the high-dimensional landscape of genotypes and their associated phenotypes simultaneously. We applied this approach to develop a multimodal foundation model to explore the genotype-phenotype relationship manifold for human transcriptomics at the cellular level. Analyzing this joint manifold showed a refined resolution of cellular heterogeneity, enhanced precision in phenotype annotating, and uncovered potential cross-tissue biomarkers that are undetectable through conventional gene expression analysis alone. Moreover, our results revealed that the gene networks are characterized by scale-free patterns and show context-dependent gene-gene interactions, both of which result in significant variations in the topology of the gene network, particularly evident during aging. Finally, utilizing contextualized embeddings, we investigated gene polyfunctionality which illustrates the multifaceted roles that genes play in different biological processes, and demonstrated that for VWF gene in endothelial cells. Overall, this study advances our understanding of the dynamic interplay between gene expression and phenotypic manifestation and demonstrates the potential of integrated genetics in uncovering new dimensions of cellular function and complexity.
Bayesian spatiotemporal modelling and mapping of malaria risk among children aged below 5 years in Ghana
Authors: Takramah Wisdom Kwami , Afrane Yaw Asare , Aheto Justice Moses K.
Published: May 2024

Background
Malaria is a significant public health problem, particularly among children aged 6-59 months who bear the greatest burden of this disease. Malaria transmission is high and more pronounced in poor tropical and subtropical areas of the world. Climate change is positively correlated with the geographical distribution of malaria vectors. There is substantial evidence of spatial and temporal differences in under-five malaria risk. Thus, the study aimed to create intelligent maps of smooth relative risk of malaria in children under-5 years that highlights high and low malaria burden in space and time to support malaria prevention, control, and elimination efforts.
Method
The study extracted and merged the required data on malaria among children aged 6-59 months from 2014 Ghana Demographic and Health Surveys (GDHS), 2016 and 2019 Ghana Malaria Indicator Surveys (GMIS). The outcome variable of interest is the count of children aged 6-59 months with positive test on rapid diagnostic test (RDT) kit. Bayesian Hierarchical Spatiotemporal models were specified to estimate and map spatiotemporal variations in the relative risk of malaria. The existence of local clustering was assessed using local indicator of spatial association (LISA) and the points were mapped to display significant local clusters, hotpot, and cold spot communities.
Results
The number of positive malaria cases in children aged 6-59 months decreased marginally between the 2014 and 2019 DHS survey periods. Smooth relative risk of malaria among children aged 6-59 months has consistently increased in the Northern and Eastern regions between 2014 and 2019. Socioeconomic and climatic factors such as household size [Posterior Mean: -0.198 (95% CrI: 3.52, 80.95)], rural area [Posterior Mean: 1.739 (95% CrI: 0.581, 2.867)], rainfall [Posterior Mean: 0.003 (95% CrI: 0.001, 0.005)], and maximum temperature [Posterior Mean: -1.069 (95% CrI: -2.135, -0.009)] have all been shown as statistically significant predictors of malaria risk in children aged 6-59 months. Hot spot DHS clusters with a significantly high relative risk of malaria among children aged 6-59 months were repeatedly detected in the Ashanti region between 2014 and 2019.
Conclusion
The findings would provide policymakers with practical and insightful information for the equitable distribution of scarce health resources targeted at reducing the burden of malaria and its associated mortality among children under-five years.
Hazardous Impact of Prophetic Variables in The Development of Radicular Cyst and Associated Periapical Osteo-Invasion
Authors: Fareed Muhammad , Ahmad Shahzad , Iqbal Shazia , Ashraf Muhammad Abdul Basit , Anwar Malik Adeel , Lodhi Saood Khan
Published: May 2024

Background: The long-standing pulpitis may result in apical periodontitis, which, if left untreated, will ultimately develop into a periapical cyst. Our study aimed to evaluate the hazardous impact of prophetic variables on the development of radicular cysts and associated periapical osteo-invasion.
Methodology: One hundred patients with radicular cysts and 100 samples of individuals with normal pulp were selected. For the analytical assessment, periapical tissue samples were obtained from patients experiencing periapical surgery. Tissue homogenate was prepared by using a Potter-Elvehjem homogenizer. The levels of antioxidants and pro-oxidants were assessed by their respective protocols. The anti-inflammatory status, levels of matrix metalloproteinases (MMPs), and bone remodeling biomarkers were determined by designated ELISA kits.
Results: Increased levels of pro-oxidants and inflammatory agents while a diminished quantity of antioxidants were observed in the patients with radicular cysts. The levels of MMPs and sRANKL levels were raised, whereas OPG levels were reduced, indicating the osteo-invasion process in radicular cyst patients.
Conclusions: The underlying mechanisms of progression of the radicular cyst into adjacent peri-apical bone provide interesting relationships among the biomarkers of oxidative stress, pro-inflammatory cytokines, and bone remodeling. Thus, novel therapies based on targeting MMPs through the action of TIMPs and abrogating sRANKL-RANK interactions can play a significant role in preventing radicular cyst proliferation.
The hospital frailty risk score effectively predicts adverse outcomes in patients with atrial fibrillation in the intensive care unit
Authors: Li Xinya , Cheng Hongtao , Tang Yonglan , Tan Shanyuan , Bai Zihong , Li Tanjian , Luo Meilin , Wang yu , Jun Lyu
Published: May 2024

Background
Atrial fibrillation (AF) and frailty are significant global public health problems associated with advancing age. However, the relationship between frailty and older patients with AF in the intensive care unit (ICU) has not been thoroughly investigated. This study aimed to investigate whether the hospital frailty risk score (HFRS) is associated with adverse outcomes in older patients with AF in the ICU.
Methods
This was the first retrospective analysis of older patients with AF admitted to the ICU between 2008 and 2019 at a tertiary academic medical center in Boston. The HFRS was used to measure frailty severity. The outcomes of interest were in-hospital and 30-day mortality and the incidence of sepsis and ischemic stroke.
Results
There were 7,792 participants aged approximately 80 years, almost half (44.9%) of whom were female. Among this group, 2,876 individuals were identified as non-frail, while 4,916 were classified as frail. The analysis revealed a significantly greater incidence of in-hospital (18.8% compared to 7.6%) and 30-day mortality (24.5% versus 12.3%) in the frail group. After accounting for potential confounding factors, a multivariate Cox proportional hazards regression analysis revealed that frail participants had a 1.56-fold greater risk of mortality within 30 days (95% CI = 1.38–1.76, p < 0.001).
Conclusions
Frailty is an independent risk factor for adverse outcomes in older patients with AF admitted to the ICU. Therefore, prioritizing frailty assessment and implementing specific intervention strategies to improve prognostic outcomes are recommended.
Discussion on the prediction model of early judgment of critical risk in emergency patients
Authors: Li Xurui , Lv Jian , Li Hongling , Guo Hui , Zhao Qian , Li Jianguo
Published: May 2024

Objective: To establish a predictive model for early assessment of critical risk in emergency patients and evaluate its clinical clinical benefits.
Method: Clinical data of 3859 patients who visited the emergency department at Hebei General Hospital from November 2021 to December 2021 were selected. The enrolled patients were randomly divided into a training set (2703 cases) and a validation set (1156 cases) in a 7:3 ratio. In the training set, a predictive model was established based on the results of multivariate logistic stepwise regression analysis. At the same time, risk levels were divided, and the predictive efficacy and clinical benefits of the predictive model were verified.
Result: There was no statistically significant difference in clinical data between the training and validation set (P>0.05), indicating comparability between the two groups. Multivariate logistic stepwise regression analysis showed that Gender, age, HR, R, SBP, SPO2, consciousness, pupil, mental state, and pain score were independent risk factors for early assessment of critical risk (P<0.05), and a predictive model was established based on this. Using conditional inference tree, critical risks are classified into low risk (P≤0.075), medium risk (0.075＜P≤0.656), and high risk (P>0.656). Furthermore, the prediction model was internally validated in both the training and validation sets, with a training set AUC of 0.926 [95% CI (0.912-0.939), P<0.001] and a validation set AUC of 0.911 [95% CI (0.886-0.936), P<0.001], indicating good discrimination of the prediction model; The calibration curve of the training set fits the standard curve, while the calibration curve of the validation set model slightly deviates from the standard curve. In the Hosmer Limeshow test, the results of the two groups were P=0.180 and P=0.546, respectively, indicating good calibration of the predicted model; The DCA curve suggests that both groups of people can achieve good clinical benefits.
Conclusion: Establishing a predictive model for early assessment of emergency critical risk is helpful for early identification and intervention of emergency critical patients.
Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy
Authors: Lee Janghee , Park Seho , Bae Soong June , Ji Junghwan , Kim Dooreh , Kim Jee Ye , Park Hyung Seok , Ahn Sung Gwe , Kim Seung Il , Park Byeong-Woo , Jeong Joon
Published: May 2024

Introduction:
The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST.
Methods
This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model.
Results
Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypNmi). Multivariate analysis revealed no significant association between ypNmi and RFS in patients post-NST (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.42–2.49; P = 0.958). Notably, over half of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001). Furthermore, SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (HR, 2.23; 95% CI, 1.12–4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%).
Conclusions
While ypNmi does not influence the prognosis compared to ypN0, SLNmi emerges as a significant negative prognostic factor and a robust predictor of additional metastases. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.
Combination of albumin-lymphocyte score and skeletal muscle index predicts prognosis of ovarian patients after primary debulking surgery: A multicenter retrospective study
Authors: Gong Han , Kang Quanmin , Nie Dan , Zhang Peng , Zhou Xiaoxia , Li Zhaoci , He Xinlin , Hu Yulan , Li Zhengyu
Published: May 2024

Background Accumulating evidence underscores the significant aspects of inflammation and nutrition in the tumors. We aimed to assess related prognostic preoperative variables and their combined impact for ovarian cancer patients. Methods A retrospective research was proceeded among 347 primarily diagnosed ovarian cancer patients across multiple medical centers. They were divided into a discovery cohort (237 patients) and a validation cohort (110 patients). Serological tests and plain CT images were utilized to quantify ALS and SMI. We intended to inspect the impact of ALS, SMI, and their combined indicator-CAS grade on clinical features and prognosis of the patients. Results Patients illustrating decreased ALS and increased SMI demonstrated improved overall survival (OS) and recurrence-free survival (RFS). Upon stratification by CAS grade, distinct results were observed: grade 1 patients displayed higher body mass index (BMI) and the most favorable survival prognosis, while grade 3 patients were in connection with poorest OS and RFS. Independent variables for OS and RFS included residual disease and elevated CAS grades. These findings were also validated in another independent cohort. Conclusion The CAS grade - combination of ALS and SMI is a ponderable and independent predictor for prognosis in ovarian cancer patients.
Induction and Characterization of Spreading Depolarizations in Swine Following Superior Sagittal Sinus Occlusion: A Novel Gyrencephalic Model Study
Authors: Porras Renan Sánchez , Cuapio Francisco Leonardo Ramírez , Hernandez Mildred Alejandra Guitérrez , Lagunes Angel Alberto Puig , Palmarola Pablo Albiña , Navarro Juan Manuel López , Guitérrez Marcos Suárez , Peregrino Roberto Díaz , López Diego Alberto Sandoval , Fischer Gregor , Vazifehdan Farzam , Woitzik Johannes , Santos Edgar
Published: May 2024

Cerebral sinus thrombosis, which constitutes a small percentage of all strokes, usually affects young individuals and can lead to venous stroke. Stroke is associated with Spreading Depolarization (SD) waves in brain tissue propagating through the affected areas, causing transient ionic homeostasis and neuronal function disruption. This interaction highlights the complexity of the neurological consequences associated with SD. In this study, we investigated the occurrence of SDs following the occlusion of the superior sagittal sinus (SSS) in a gyrencephalic model, specifically swine. To instigate an occlusion, we surgically clipped the middle third of the SSS. The animals were grouped and monitored using one of three methods: electrocorticography (ECoG) alone, ECoG with intrinsic optical signal (IOS) imaging, or ECoG in conjunction with laser speckle contrast and oxygen imaging (LSCI). Post-mortem, the brains were analyzed using 2,3,5-triphenyl tetrazolium chloride (TTC) staining to check for venous infarction. Our results confirmed the induction of SDs in the gyrencephalic swine brain after SSS occlusion, which was detectable via all monitoring methodologies. SD activity was most frequent in the first-hour post-occlusion, subsequently diminishing. IOS imaging identified four unique hemodynamic responses, while TTC staining indicated no infarction. This research is the first to document SDs in the gyrencephalic swine brain following SSS occlusion, laying the groundwork for future investigations in both animal models and human clinical studies.
Primary Adenocarcinoma of the Spermatic Cord: A Case Report with Review of the Literature
Authors: Sun Qi , Yang Yuan-Zhong , Chen Ya , An Xin , Zhang Yijun
Published: May 2024

Background
Primary malignant neoplasms of the spermatic cord are extremely rare, with most reported cases being sarcomas or metastatic carcinomas. However, primary adenocarcinoma of the spermatic cord has not been previously reported.
Case presentation:
A 34-year-old male with a solid mass in the right spermatic cord, was eventually diagnosed with primary adenocarcinoma. Histological examination revealed a moderately-to-poorly differentiated adenocarcinoma exhibiting glandular, cribriform, or nested growth patterns, characterized by medium to large-sized cells and focal extracellular mucus. Immunohistochemical analysis demonstrated positive staining for CK (AE1/AE3), CK8/18, CK19, MOC31 (EP-CAM), and Ber-EP4, while negative staining was observed for CK7, D2-40, WT-1, MC, PAX-8, NKX3.1, PSA, CEA, TTF-1, and NapsinA. Furthermore, a complete loss of INI-1 expression and consistent BRG1 expression were noted in all tumor cells. Next-generation sequencing revealed SMARCB1 deletion, low tumor mutation burden (TMB-L), and microsatellite stability (MSS).
Conclusion
We reported the first case of primary adenocarcinoma of the spermatic cord with SMARCB1 (INI-1) deficiency. This case contributes to the expanding understanding of rare neoplasms and underscores the importance of further research into therapeutic strategies targeting SMARCB1-deficient tumors.
A fast open data reduction workflow for the electron microprobe flank method to determine Fe3+/ΣFe contents in minerals
Authors: Hezel Dominik C. , Höfer Heidi E. , Fichtner Andreas
Published: May 2024

Knowing the Fe3+/ΣFe ratio in minerals is important to understand the formation and evolution of minerals and their host rocks. Variable Fe3+/ΣFe in, e.g., garnet is accompanied by a change of their characteristic FeLα and FeLβ X-ray emission lines, which can be quantified with electron microprobe measurements using the flank method. Previously, the required data reduction process to determine the Fe3+/ΣFe was complex. Here, we present a new data reduction tool taking garnet data as an example. This new Flank Reduction app is a freely available, graphical user interface (GUI)-driven, web-based application to reduce flank method data quickly and easily. The entire data reduction process is achieved in minutes compared to hours or days, as it was before. Flank Reduction provides comprehensive insights into, e.g., the flank method standards employed, data obtained, and errors through a wide array of controls and visualization tools. Documentation with comprehensive information on the flank method, data reduction, as well as training material such as video tutorials or sample data sets, are available on a dedicated webpage. Flank Reduction emphasizes the high value of Findable, Accessible, Interoperable, Reproducible (FAIR) and open research software and demonstrates how current developments in coding and app implementation can facilitate the development of powerful and expandable research software.
The difference between estimated and perceived item difficulty: An empirical study
Authors: Sayın Ayfer , Bulut Okan
Published: May 2024

Test development is a complicated process that demands examining various factors, one of them being writing items of varying difficulty. It is important to use items of a different range of difficulty to ensure that the test results accurately indicate the test-taker's abilities. Therefore, the factors affecting item difficulty should be defined, and item difficulties should be estimated before testing. This study aims to investigate the factors that affect estimated and perceived item difficulty in the High School Entrance Examination in Türkiye and to improve estimation accuracy by giving feedback to the experts. The study started with estimating item difficulty for 40 items belonging to reading comprehension, grammar, and reasoning based on data. Then, the experts' predictions were compared with the estimated item difficulty and feedback was provided to improve the accuracy of their predictions. The study found that some item features (e.g., length and readability) did not affect the estimated difficulty but affected the experts' item difficulty perceptions. Based on these results, the study concludes that providing feedback to experts can improve the factors affecting their item difficulty estimates. So, it can help improve the quality of future tests and provide feedback to experts to improve their ability to estimate item difficulty accurately.
Evaluation of phosphate insecticides and common herbicides: monitoring and risk assessment in water treatment plant, distribution networks, and underground water wells
Authors: Tahmasebi Ali Akbar , Tabatabaei Zeynab , Azhdarpoor Abooalfazl , Salimi Beni Alireza
Published: May 2024

Despite the negative effects that the use of pesticides (such as herbicides and insecticides) have on human health and water resources, a significant portion of the world's agricultural production depends on them. The purpose of this study was to determine selected residual concentrations of pesticides (diazinon, ethion, malathion, alachlor, methyl-parathion, trifluralin, atrazine, chlorpyrifos, and azinphos-methyl) in samples from Shiraz potable water sources. For this purpose, water treatment plant, groundwater wells, treated surface water, and a mixture of groundwater and treated surface water were taken. In addition, statistical and risk analyses (carcinogenic and non-carcinogenic) were used. According to the results, chlorpyrifos with 84.4% had the highest removal efficiency and methyl-parathion with 10% had the lowest removal rate in the Shiraz water treatment plant process. The highest mean concentration was related to azinphos-methyl (1.5 μg/L) and chlorpyrifos (0.59 μg/L) in the groundwater samples. All measured compounds in water source samples were below standard levels, except for chlorpyrifos and azinphos-methyl, which were reported in groundwater above the limit recommended by the Environmental Protection Agency (EPA). The results showed that while the selected pesticides measured had a low non-carcinogenic risk for both adults and children, malathion and trifluralin posed a high carcinogenic risk for adults.
Endotoxin, a novel biomarker for the rapid risk assessment of faecal contamination of coastal and transitional waters
Authors: Good Christian R. , White Alistair , Brandao Joao , Jackson Simon
Published: May 2024

Current methods for testing water for faecal contamination rely on the culture of faecal indicator bacteria (FIB; Escherichia coli and Enterococci) that take 24–48 h, which leads to delays in taking proactive measures and poses a risk to public health. More rapid methods are therefore required. Here, we have tested a rapid, portable assay (Bacterisk) that detects the bacterial biomarker endotoxin in 30 min to quantify the bacterial biomass present, to evaluate 159 coastal water samples and to compare the results with the traditional culture of FIB. There was a significant correlation between the Bacterisk data given in endotoxin risk (ER) units and FIB culture that could accurately distinguish between poor and sufficient or good quality bathing water using the EU bathing directive values. Receiver operating characteristic analysis was used to determine the optimal ER threshold for coastal water samples, and the area under the curve was 0.9176 with a p-value of <0.0001. The optimal threshold was 7,300 ER units with a sensitivity of 95.45% and a specificity of 83.48%. In conclusion, we have shown that the Bacterisk assay provides a rapid and easy-to-use in situ method to assess bathing water quality.
Estimating rainfall-runoff parameters for ungauged catchments: a case study in Turkiye
Authors: Tuna M. Cihat , Aytaç Ayça
Published: May 2024

Determining water yield and flood discharges in catchments is a vital aspect of hydrology. This entails considering precipitation and runoff as key hydrological parameters. Constructing infrastructure like hydroelectric plants and regulators over streams necessitates continuous, accurate flow, and meteorological observations spanning at least 25 years. However, in developing nations, economic factors often impede such observations. This study proposes a method to estimate peak rainfall and flow values for ungauged basins with varying return periods by utilizing from gauged basins and spatial variables. Flood calculations were carried out for the ungauged Rabat River basin. In this study, regional flood frequency analysis was carried out using the flow values of the flow gauging stations neighboring the basin. In addition, maximum flow values were calculated using Moscus and the DSI synthetic method. Two- and three-parameter distributions were used to estimate 50-, 100-, 200- and 500-year flood return values at stations with observation periods ranging from 15 to 64 years. Kolmogorov–Smirnov and Probability Line Correlation coefficient (Chi-square) tests were applied to check the suitability of these distributions and the most appropriate distributions were found. This yielded an estimation for the flow values of the Rabat River, indicating the method's reliability for forecasting runoff-rainfall in the ungauged basin.
Amyloid fibril–bacterial cellulose nanohybrid membrane cartridge for efficient removal of heavy metal from industrial wastewater
Authors: Vaidh Sachin , Surana Aastha , Nagariya Viraj , Rahewar Ravindrasinh , Prajapati Harsh , Patel Dhaval , Pandya Alok , Vishwakarma Gajendra Singh
Published: May 2024

Worldwide, the harmful ion contamination of water has become a serious problem because of unregulated industry, energy production, and mining, which greatly increase the concentration of pollutants in water. The novel membranes through adsorbent self-assembly, such as protein amyloids, were explored for wastewater treatment. Herein, we report amyloid fibril (AF)-embedded bacterial cellulose nanohybrid membrane for efficient removal of heavy metal from industrial effluent. AFs are synthesized by heat treatment using bovine serum albumin and embedded with bacterial cellulose nanomembrane (BCN). The AF-embedded BCN (AF/BCN) was characterized using microscopy and spectroscopic methods. In addition, the well-ordered multi-layered AF/BCN filtration assembly was fabricated in the commercial cartridge and validated for the removal of heavy metals (Pb2+ and Hg2+) from wastewater and treatment of industrial wastewater sample containing heavy metals. Our multi-layered filtration assembly removed Hg2+ and Pb2+ with efficiency of 95 and 78.34%, respectively. A computational study using molecular docking has also been performed for the identification of metal entrapment sites. Moreover, our AF/BCN filtration assembly showed high regeneration capacity up to four cycles. The isotherm model also revealed a strong fit and good adsorption behaviour. This makes potential filtration assembly for low-cost, high-efficiency for the removal of heavy metal from wastewater.
Identifying and Validating an Angiogenesis-related Signature for the
Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Hou Yueting , Pang Haifeng , Xu Xuemei , Zhao Dong
Published: May 2024

Aims::

The present study aimed todevelop a prognostic model for HNSCC
treatment on the basis of angiogenesis-related signatures.

Background::

Head and Neck Squamous Cell Carcinoma (HNSCC) is the most frequent
malignancy with poor prognostic outcomes in the head and neck. Angiogenesis plays a
critical role in tumorigenesis and is expected to be an effective therapeutic target.

Objective::

The RNA-seq dataset TCGA-HNSCC and the hallmark gene set were used
for angiogenesis-related RiskScore model construction.

Methods::

The RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA),
and the hallmark gene set was used to measure the angiogenesis score using the
GSVA R package. Then, the optimal cutoff point for prognostic classification was calculated
by the survminer package, and Weighted Gene Co-expression Network Analysis
(WGCNA) was used to identify angiogenesis gene modules . Multi/univariable and Lasso
Cox analyses were performed to develop the RiskScore model, and the classifier efficiency
was evaluated by the Receiver Operating Characteristic curve (ROC). Furthermore,
a nomogram was designed for survival probability prediction, and the immune infiltration
and immunotherapy differences among different risk patients were assessed.

Results::

After calculating the angiogenesis score, we found that this indicator and patients’
prognosis were closely correlated, especially when patients with a high angiogenesis
score had a poor prognosis. Then, WGCNA identified a blue gene module positively
correlated with angiogenesis. Multivariate and Lasso Cox analysis further identified 9
risk model genes for developing a RiskScore, which was used to divide low- and high-
-risk groups of patients. Those with a high risk tended to show poor prognosis, immune
infiltration, and higher immune escape. Finally, a nomogram was developed to optimize
the risk model, and it exhibited excellent short- and long-term survival prediction performance.

Conclusion::

We constructed a reliable RiskScore model for the prognostic prediction of
HNSCC patients, contributing to precise therapeutic intervention of the cancer.
Profiles of Circulating Exosomal Mirna in Patients with SAPHO Patients by High-Throughput Sequencing
Authors: Zhang Yunan , Zhen Jianhua , Sun Yuxiu , Li Yini , Zhou Yali , Li Chen , Tian Lichun
Published: May 2024

Background:

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome
is a rare disease that is characterized by autoinflammatory lesions on both bones and skin.
The diverse manifestations and limited understanding of its etiology have hindered the diagnosis
and treatment of this condition. SAPHO syndrome is also classified as a primary inflammatory
osteitis. The onset of osteoarticular involvement in this disease is typically gradual, and the identification
of associated biomarkers may be crucial for accurate diagnosis, effective treatment, and
a better understanding of its underlying mechanisms.

Methods:

We enrolled a total of 6 SAPHO patients and 3 healthy volunteers for this study. The
miRNA expression profile in circulating exosomes was analyzed using next-generation sequencing.
A total of 45 miRNAs were found to be differentially expressed in SAPHO patients. Linear
discriminant analysis effect size analysis and Wilcoxon rank-sum test were employed to identify
biomarkers based on these differentially expressed miRNAs. Among them, we selected 4 miRNAs
as biomarkers for SAPHO syndrome, resulting in an area under the receiver operating characteristic
curve of 1.

Results:

The differentially expressed miRNAs indicated enrichment in immune system and endocrine
system-related KEGG pathways, as well as infectious diseases and cancers. Furthermore,
the most significantly enriched molecular functions in GO analysis were protein binding and catalytic
activity.

Conclusion:

The exosomal miRNA profile in SAPHO syndrome exhibited significant changes,
suggesting its potential as a candidate biomarker for diagnostic assistance, although further investigation
is warranted to elucidate their role in the pathology.
The Antimicrobial Activity of Combination of Vitamin D3 and Omega-3 against Pathogenic Microorganisms
Authors: Al-Najjar Mohammad A. A. , Abdulrazzaq Shaymaa B. , Al-Shaer Shatha , Barakat Muna , Omar Amin , Zrieq Rafat , Hasen Eliza , Abu Samak Mahmoud
Published: May 2024

Background:

Food supplements such as vitamin D3 and omega-3 have a significant
role in activating the immune system and impacting the diversity of gut microbiota; thus, controlling
the growth of invading pathogens indirectly.

Objective:

This study aims to evaluate the direct antimicrobial activity of vitamin D3 and omega-
3 individually, combined together, and combined with low concentrations of gentamicin or
amphotericin B against selected pathogenic microorganisms. In addition, this study hypothesizes
the potential antimicrobial mechanism and recommends suitable studies to be conducted.

Method:

Minimum inhibitory concentration of different serial dilutions of vitamin D3
[0.7μg/mL-83.3μg/mL] or omega-3 [0.7mg/mL-100mg/mL] or combined [vitamin
D3:1.3μg/mL-83.3μg/mL and omega-3:1.56mg/mL-100mg/mL] with/without antibiotic have
been investigated on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and
Candida albicans using check board technique.

Results:

The highest concentration of vitamin D3 [83.3 μg/mL] demonstrated a complete eradication
of the tested microorganisms. Conversely, omega-3 had a lower effect on them. The
highest concentration of combining vitamin D3 and omega-3 with/without gentamicin resulted
in a complete eradication of the S. aureus, E. coli and P. aeruginosa with a 6.8 to 7 log reduction.
On the other hand, C. albicans was inhibited when using vitamin D3 [83.3 μg/mL] or when
this concentration is combined with 100mg/mL of omega-3. However, when these two concentrations
were added to amphotericin B the log reduction dropped to 0.45 suggesting antagonistic
effect.

result:

The highest concentration of vitamin D3 (83.3 μg/mL) demonstrated a complete eradication of the tested microorganisms. Conversely, omega-3 had a lower effect on them. The highest concentration of combining vitamin D3 and omega-3 with/without gentamicin resulted in a complete eradication of the S. aureus, E. coli and P. aeruginosa with a 6.8 to 7 log reduction. On the other hand, C. albicans was inhibited when using vitamin D3 (83.3 μg/mL) or when this concentration is combined with 83.3 μg/mL vitamin D3 and 100mg/mL of omega-3. However, when these two concentrations were added to amphotericin B the log reduction dropped to 0.45 suggesting antagonistic effect.

Conclusion:

These findings suggested that, unlike omega 3, vitamin D3 possesses good antimicrobial
effects against pathogenic microorganisms. The combination of the studied food supplement
showed enhanced microbial inhibition at high concentration, while they had antagonistic
effect when combined with amphotericin B and applied on C. albicans combined. Further
studies on the exact antimicrobial mechanism are still required to understand the measured data
here.
Pharmacophore Optimization using Pharmacophore Mapping, QSAR, Docking, and ADMET Screening of Novel Pyrimidines Derivatives as Anticancer DNA Inhibitors
Authors: Patil Shital M. , Randive Vrushali , Mahadik Indrani , Bhandari Shashikant , Asgonkar Kalyani , Nikalje Piyush
Published: May 2024

Cancer is a global health issue, and cancer cells' resistance to existing treatments has
prompted a search for new anticancer drugs. The DNA of cancer cells is regarded as the primary
target for developing new molecules. In-silico studies aid in the optimization of current pharmacophores
and the development of new molecules. This study aimed to optimize the pharmacophore
utilizing QSAR studies and pharmacophore mapping to generate novel chemical entities (NCEs) of
pyrimidine derivatives as DNA inhibitors for cancer treatment. Furthermore, these NCEs were subjected
to molecular docking and Absorption, Distribution, Metabolism, Excretion, and Toxicity
(ADMET) screening to determine their drug-likeness. This study used Schrodinger's Maestro (13.4)
software for pharmacophore mapping, QSAR, molecular docking, and ADME. Toxicity was determined
using the Pro Tox II online tool. Pharmacophore mapping was performed using the phase
module. The QSAR model was generated using an atom-based QSAR approach. The Qik prop module
was utilized for ADME prediction. Molecular docking was done in Standard precision mode. In
pharmacophore mapping, we discovered that the DHHRR_1 hypothesis fitted best, with a survival
score of 5.4408. The optimal atom-based QSAR model produced correlation coefficients of R2 =
0.9487 and Q2 = 0.8361. Based on QSAR research, a new set of 43 derivatives was generated. These
compounds pass all ADMET requirements. In molecular docking investigations, three compounds
demonstrated binding with key amino acids with a significant dock score comparable to the standard.
Considering docking data and pharmacokinetic behavior of newly developed compounds, molecules
NC10, NC9, and NC43 have the highest DNA binding capability.
Anti-carcinogenic Potential of Nano-curcumin -“Killing Cancerous Cells”
Authors: Khan Mohsin Ali , Khan Anwar , Khan Akhlak Ahmed , Simrah  , Mirza Mohd. Aamir , Javed Naquvi Kamran , Kumar Devendra
Published: May 2024

Nowadays, cancer treatment is currently limited to surgery, chemotherapy, and radiation,
which carry the risk of damaging the normal tissue of the body and incomplete removal of
the cancerous cells from the body. Thus, the Nano technique offers a great means to target therapies
directly on cancerous cells and neoplasm. Moreover, because nano-based formulations of
polyphenolic curcumin show a major effect on cancer and tumour cells, nanoparticles have a tendency
to overcome the hydrophobic nature of curcumin to improve its stability and bioavailability
in vitro and in vivo. It is apparent from the studies that Curcumin has shown anticancer effects by
regulating various immunomodulators, which include cytokines, reactive oxygen species, and
cyclooxygenase-2 (COX-2). It also takes part in the downregulation of growth factors, protein
kinases, oncogenic molecules, and various signalling pathways, such as nuclear factor kappalight-
chain enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and signal
transducer and activator of transcription 3 (STAT3) signalling. According to recent studies and
clinical trials, nano curcumin shows a major effect on cancerous cells. In this article, the authors
summarised the mechanism of nano curcumin in various metastatic cancers and the most recent
clinical trials performed.