Miracle-dz/UniFAR-FTUs huggingface dataset:
Dihydropyrimidine derivatives as MDM2 inhibitors

One of the chief pathways to regulate p53 levels is MDM2 protein, which negatively controls p53 by direct inhibition. Many cancers overproduce MDM2 protein to interrupt p53 functions. Therefore, impeding MDM2's binding to p53 can reactivate p53 in tumor cells may suggest an effective approach for tumor therapy. Here, some Monastrol derivatives were designed in silico as MDM2 inhibitors, and their initial cytotoxicity was evaluated in vitro on MFC‐7 and MDA‐MB‐231 cells. A small library of Monastrol derivatives was created, and virtual screening (VS) was performed on them. The first‐ranked compound, which was extracted from VS, and the other six compounds 5a‐5f were selected to carry out the single‐docking and docking with explicit waters. The compound with the best average results was then subjected to molecular dynamic (MD) simulation. Compounds 5a‐5f were chemically synthesized and evaluated in vitro for their initial cytotoxicity on MFC‐7 and MDA‐MB‐231 cells by MTT assay. The best compound was compound 5d with ΔGave = −10.35 kcal/mol. MD simulation revealed a median potency in comparison with Nutlin‐3a. The MTT assay confirmed the docking and MD experiments. 5d has an IC50 of 60.09 μM on MCF‐7 cells. We attempted to use Monastrol scaffold as a potent inhibitor of MDM2 rather than an Eg5 inhibitor using in silico modification. The results obtained from the in silico and in vitro evaluations were noteworthy and warranted much more effort in the future.
Cortical gray to white matter signal intensity ratio as a sign of neurodegeneration and cognition independent of β‐amyloid in dementia

Cortical gray to white matter signal intensity ratio (GWR) measured from T1‐weighted magnetic resonance (MR) images was associated with neurodegeneration and dementia. We characterized topological patterns of GWR during AD pathogenesis and investigated its association with cognitive decline. The study included a cross‐sectional dataset and a longitudinal dataset. The cross‐sectional dataset included 60 cognitively healthy controls, 61 mild cognitive impairment (MCI), and 63 patients with dementia. The longitudinal dataset included 26 participants who progressed from cognitively normal to dementia and 26 controls that remained cognitively normal. GWR was compared across the cross‐sectional groups, adjusted for amyloid PET. The correlation between GWR and cognition performance was also evaluated. The longitudinal dataset was used to investigate GWR alteration during the AD pathogenesis. Dementia with β‐amyloid deposition group exhibited the largest area of increased GWR, followed by MCI with β‐amyloid deposition, MCI without β‐amyloid deposition, and controls. The spatial pattern of GWR‐increased regions was not influenced by β‐amyloid deposits. Correlation between regional GWR alteration and cognitive decline was only detected among individuals with β‐amyloid deposition. GWR showed positive correlation with tau PET in the left supramarginal, lateral occipital gyrus, and right middle frontal cortex. The longitudinal study showed that GWR increased around the fusiform, inferior/superior temporal lobe, and entorhinal cortex in MCI and progressed to larger cortical regions after progression to AD. The spatial pattern of GWR‐increased regions was independent of β‐amyloid deposits but overlapped with tauopathy. The GWR can serve as a promising biomarker of neurodegeneration in AD.
Nutrient Removal and Physical, Chemical Properties in Samany Date Palm as Influenced by Different Pruning Treatments

This study was carried out for two successive seasons (2004 and 2005) at El-Kanater El-Khairia, El-Kaliobia Governorate, Egypt, Samany cultivar were subjected to four pruning treatments concerning the leaf/bunch ratio; (A) control (without pruning); (B) 12:1 (Slight pruning); (C) 10:1 (moderate pruning) and (D) 6:1 (Heavy pruning). The moderate pruning gave the highest bunch weight, yield, fruit weight, flesh weight, fruit volume and fruit dimensions in both seasons. The same pruning treatment gave the highest increase non-reducing sugars percentage in both seasons. The slight pruning increasing total sugars and total soluble solids percentage. Total acidity increased with moderate pruning in the first season, but increased with slight pruning in the second season. Moderate pruning improved nutrient contents of different parts of palm. Nutrients removed by the palm annually under moderate pruning were: 1049 g K; 694 g N; 298.2 g Ca; 158.1g Mg, 136.1g P; 27.2 g Na; 19.1g Fe; 1.28 g Mn; 1.06g Zn and 0.53 g Cu. in the first season and in the second season were: 1386 g K; 857 g N; 372 g Ca; 286.7g Mg, 196.4g P; 34.5 g Na; 18.6 Fe; 1.42 g Mn; 1.23 g Zn and 0.77g Cu.
Highlighting the limitations of static microplate biofilm assays for industrial biocide effectiveness compared to dynamic flow conditions

Abstract The minimal inhibitory concentration of an antimicrobial required to inhibit the growth of planktonic populations (minimum inhibitory concentration [MIC]) remains the ‘gold standard’ even though biofilms are acknowledged to be recalcitrant to concentrations that greatly exceed the MIC. As a result, most studies focus on biofilm tolerance to high antimicrobial concentrations, whereas the effect of environmentally relevant sub‐MIC on biofilms is neglected. The effect of the MIC and sub‐MIC of an isothiazolinone biocide on a microbial community isolated from an industrial cooling system was assessed under static and flow conditions. The differential response of planktonic and sessile populations to these biocide concentrations was discerned by modifying the broth microdilution assay. However, the end‐point analysis of biofilms cultivated in static microplates obscured the effect of sub‐MIC and MIC on biofilms. A transition from batch to the continuous flow system revealed a more nuanced response of biofilms to these biocide concentrations, where biofilm‐derived planktonic cell production was maintained despite an increase in the frequency and extent of biofilm sloughing. A holistic, ‘best of both worlds’ approach that combines the use of static and continuous flow systems is useful to investigate the potential for the development of persistent biofilms under conditions where exposure to sub‐MIC and MIC may occur.
Structural Color from Cellulose Nanocrystals or Chitin Nanocrystals: Self-Assembly, Optics, and Applications

Widespread concerns over the impact of human activity on the environment have resulted in a desire to replace artificial functional materials with naturally derived alternatives. As such, polysaccharides are drawing increasing attention due to offering a renewable, biodegradable, and biocompatible feedstock for functional nanomaterials. In particular, nanocrystals of cellulose and chitin have emerged as versatile and sustainable building blocks for diverse applications, ranging from mechanical reinforcement to structural coloration. Much of this interest arises from the tendency of these colloidally stable nanoparticles to self-organize in water into a lyotropic cholesteric liquid crystal, which can be readily manipulated in terms of its periodicity, structure, and geometry. Importantly, this helicoidal ordering can be retained into the solid-state, offering an accessible route to complex nanostructured films, coatings, and particles. In this review, the process of forming iridescent, structurally colored films from suspensions of cellulose nanocrystals (CNCs) is summarized and the mechanisms underlying the chemical and physical phenomena at each stage in the process explored. Analogy is then drawn with chitin nanocrystals (ChNCs), allowing for key differences to be critically assessed and strategies toward structural coloration to be presented. Importantly, the progress toward translating this technology from academia to industry is summarized, with unresolved scientific and technical questions put forward as challenges to the community.
Workload, nurse turnover, and patient mortality: Test of a hospital-level moderated mediation model

Background Hospitals are often tasked with improving patient care while simultaneously increasing operational efficiency. Although efficiency may be gained by maintaining higher patient volume per nurse (higher workload), high-quality patient care requires low levels of nurse turnover, which might be adversely affected by an increase in workload. Purpose Drawing upon job demands–resources theory, we hypothesized that hospital-level workload will predict nurse turnover and that nurse turnover will predict patient mortality, and that registered nurse hiring rates and human resource management practices will moderate (buffer) the positive relationship between nurse workload and nurse turnover, whereas quality care structures will moderate (buffer) the positive relationship between nurse turnover and patient mortality. Methods We tested this model utilizing multiple sources of time-lagged data collected from a sample of 156 hospitals in the United States. Results Our findings suggest that (a) nurse workload is associated with higher nurse turnover, (b) nurse turnover is positively associated with patient mortality, (c) nurse staffing buffers the workload–turnover relationship as a first-stage moderator, and (d) quality care structures act as a second-stage moderator that mitigates the effects of turnover on mortality. Conclusions/Practice Implications The reduction of nurse turnover and patient mortality requires investments in adequate levels of nurse staffing and implementation of quality care structures.
Seasonal variation of groundwater quality in a part of Vadodara District for irrigation, Gujarat, India

The area in Vadodara district, Gujarat, India, is selected to discuss the impact of seasonal variation of groundwater quality on irrigation, where the agriculture is the main livelihood of rural people and the groundwater is the main source for irrigation and drinking. Groundwater samples collected seasonally, pre and post-monsoons, during three years from Twenty five wells in the area were analyzed for pH, EC, TDS, TH, Ca 2+ , Mg 2+ , Na + , K + , CO3 2− , HCO3 − , Cl − , SO4 2− , NO3 − and F − . Various tools such as Electrical conductivity (EC), Sodium Absorption Ratio (SAR), United States Salinity Laboratory (USSL) were used to evaluate the quality of water and its suitability for irrigation purposes. Results of SAR shows that many of the wells during premonsoon illustrate high values indicating the unsuitable nature of groundwater for irrigation but during post monsoon, SAR values found to be decreased due to the dilution effect of precipitation by monsoon.
Principles and Properties of Artificial Trough Rainfall Simulator

Many researches on soil erosion and soil and water conservation under various conditions can be conducted using artificial rainfall simulation.The research period can be greatly shortened with the aid of the technique.Rainfall simulation has already become an important technique for laboratory and filed experi- ments and an efficient approach to collecting data of soil erosion,soil and water conservation benefits,and soil erosion modeling.Based on the discussion of basic requirements and types of artificial rainfall simulator, the structure,principles,advantages,and disadvantages of trough rainfall simulator are analyzed in detail. The objective is to stimulate the processes of research and manufacture on rainfall simulator and to promote the progress of related researches in our country.
A center-based, ambulatory care concept for hidradenitis suppurativa improves patient outcomes and is also cost-effectiveness

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the population. The patient journey through the German health care system leads to high disease burden and substantial treatment costs. The EsmAiL study showed that an innovative, interprofessional, multimodal care-concept reduces disease activity and burden of HS compared to standard care. This paper examines the costs of treating HS in Germany and compares them with those of the innovative care concept implemented in EsmAiL. Methods EsmAiL was a two-arm, multicenter, prospective randomized controlled trial including 553 adults with HS. The study was registered in the German Clinical Trials Registry (DRKS00022135). The control group (CG) remained in standard care, whereas the intervention group (IG) was referred to specialized so-called ‘acne-inversa-centres (AiZ)’ where patients were treated with a structured, interdisciplinary approach. The present paper analyses the treatment costs for a subpopulation based on health insurance cost data from the two largest German health insurers. Quality-Adjusted Life Years (QALY) was assessed based on Dermatology Life Quality Index (DLQI). Results Total annual treatment costs per patient were €3,966.07 in standard care (n = 89) and €3,974.37 in the innovative care (n = 93). The costs per additional QALY amounted to €12,698.72 in the IG. Given the conventional and established threshold of €22,600 to €33,900 per QALY, the innovative treatment in AiZ proved to be cost-effective. Conclusion Treatment costs of HS are substantial and increase with disease severity. The new form of care is cost-effective and is expected to decrease costs in the long run. KEY MESSAGE A structured, multimodal form of care reduces costs in the treatment of Hidradenitis suppurativa compared to standard care.
Whole exome sequencing reveals novel candidate variants for endometriosis utilizing multiple affected members in a single family

Abstract Background Endometriosis is an estrogen‐dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants. Thus, necessity of identifying rare variants for the missing heritability is implicated in the literature. Therefore, our study aimed to identify novel rare genetic variants involved in the pathogenesis of endometriosis utilizing a family of multiple affected members. Methods A family composed of four affected women along with their two unaffected mothers were recruited at a single gynecology and infertility clinic specialized in endometriosis. All patients presented with endometriomas, which was visualized by transvaginal ultrasonography. Two affected individuals had received laparoscopic endometrioma excision and therefore were diagnosed with recurrent disease. One mother had a history of endometrial serous adenocarcinoma (ESC) for which she underwent hysterectomy with bilateral oophorectomy. Three endometriosis cases were whole exome sequenced on Illumina NextSeq 550 platform with an average of 90% coverage. Candidate genes were confirmed by Sanger sequencing and followed‐up with family segregation. Results Novel rare variants were identified in TNFRSF1B (NM_001066.3: c.1072G>A, p.(Ala358Thr)) and GEN1 (NM_001130009.3: c.1574C>T, p.(Ser525Leu)) as possible genetic causes of endometriosis. A third novel rare variant was identified in CRABP1 (NM_004378.3:c.54G>C, p.(Glu18Asp)) only on the mother with ESC history and her daughters. Conclusion Novel candidate genetic variants that might contribute to endometriosis were suggested that need replication through independent cohorts or validation by functional studies. The family has also received genetic counseling and that the affected daughters are on clinical follow‐up, accordingly.
The Importance of Siliceous Radiolarian-Bearing Mudstones in the Formation of Sediment-Hosted Zn-Pb ± Ba Mineralization in the Selwyn Basin, Yukon, Canada

Sediment-hosted massive sulfide (SHMS) mineralization occurred in three main episodes during the evolution of the Selwyn Basin, Yukon, and Northwest Territories, Canada. In the Macmillan Pass district (Tom and Jason deposits), the Upper Devonian strata of the Earn Group host the youngest, least deformed examples of SHMS mineralization. The Earn Group comprises gray to black, homogeneous mudstones, which have been deformed in the Cordilleran fold-and-thrust belt, are weathered and poorly exposed; this makes stratigraphic correlations and the recognition of prospective units very challenging. The host rock (siliceous mudstone) and mineralized intervals at the Tom and Jason Zn-Pb ± Ba deposits have been sampled from drill core. Major element chemistry and total organic carbon (TOC) data are presented for the host-rock samples from two drill holes (TYK-5, n = 18; 76-17, n = 19). All mudstones contain between 2 and 5 wt % TOC and 67 to 83 wt % SiO2. Subtle alteration, marked by potassium loss (K2O/Al2O3 50% radiolarians by volume) within the mineralized horizons and in barren, time equivalent strata, and therefore are a useful stratigraphic marker unit in otherwise homogeneous, featureless fine-grained mudstones. The presence of highly siliceous, carbonaceous mudstone units (with preserved radiolarians) suggests that in the Late Devonian there is a link between biological productivity in the water column, the resultant sedimentation, and the SHMS deposits. These biosiliceous lithologies may be particularly favorable host rocks to SHMS mineralization for the following reasons: (1) high porosities during early diagenesis preserve volume and enhance permeabilities in partially lithified sediments, which are important parameters for subseafloor replacement mineralization; (2) these units are rich in organic materials due to their deposition in productive settings, and have a high capacity for the generation of sulfide via sulfate reduction. Therefore, we suggest there is a link between times of high biological activity and productivity in oceans, sediments derived from those processes, and SHMS deposits.
AI-Based Decision-Support System for Diagnosing Acanthamoeba Keratitis Using In Vivo Confocal Microscopy Images

Purpose In vivo confocal microscopy (IVCM) of the cornea is a valuable tool for clinical assessment of the cornea but does not provide stand-alone diagnostic support. The aim of this work was to develop an artificial intelligence (AI)-based decision-support system (DSS) for automated diagnosis of Acanthamoeba keratitis (AK) using IVCM images. Methods The automated workflow for the AI-based DSS was defined and implemented using deep learning models, image processing techniques, rule-based decisions, and valuable input from domain experts. The models were evaluated with 5-fold-cross validation on a dataset of 85 patients (47,734 IVCM images from healthy, AK, and other disease cases) collected at a single eye clinic in Sweden. The developed DSS was validated on an additional 26 patients (21,236 images). Results Overall, the DSS uses as input raw unprocessed IVCM image data, successfully separates artefacts from true images (93% accuracy), then classifies the remaining images by their corneal layer (90% accuracy). The DSS subsequently predicts if the cornea is healthy or diseased (95% model accuracy). In disease cases, the DSS detects images with AK signs with 84% accuracy, and further localizes the regions of diagnostic value with 76.5% accuracy. Conclusions The proposed AI-based DSS can automatically and accurately preprocess IVCM images (separating artefacts and sorting images into corneal layers) which decreases screening time. The accuracy of AK detection using raw IVCM images must be further explored and improved. Translational Relevance The proposed automated DSS for experienced specialists assists in diagnosing AK using IVCM images.
Assessment of Stabilization, Temporal Variation and Leachate Contamination Potential of Municipal Solid Waste Dumpsites in

One of the biggest problems associated with the dumping of solid waste is managing leachate that is formed when water passes through the deposited waste. It contains products of decomposition of organic matter and soluble ions which present a potential pollution threat for the surrounding soil, surface and ground waters. The knowledge of the composition of leachate helps to ascertain the contamination potential it poses to the immediate ecosystem and also aids to design an effective treatment technology and appropriate liners to contain the leachate. In this paper, leachate pollution index has been used to quantify the contamination potential that the dumping sites pose to the environment. This study also demonstrates the influence of various stabilization stages of the dumping sites on the composition of the leachate season wise.
Standardized Comparison of Voice-Based Information and Documentation Systems to Established Systems in Intensive Care: Crossover Study

Background The medical teams in intensive care units (ICUs) spend increasing amounts of time at computer systems for data processing, input, and interpretation purposes. As each patient creates about 1000 data points per hour, the available information is abundant, making the interpretation difficult and time-consuming. This data flood leads to a decrease in time for evidence-based, patient-centered care. Information systems, such as patient data management systems (PDMSs), are increasingly used at ICUs. However, they often create new challenges arising from the increasing documentation burden. Objective New concepts, such as artificial intelligence (AI)–based assistant systems, are hence introduced to the workflow to cope with these challenges. However, there is a lack of standardized, published metrics in order to compare the various data input and management systems in the ICU setting. The objective of this study is to compare established documentation and retrieval processes with newer methods, such as PDMSs and voice information and documentation systems (VIDSs). Methods In this crossover study, we compare traditional, paper-based documentation systems with PDMSs and newer AI-based VIDSs in terms of performance (required time), accuracy, mental workload, and user experience in an intensive care setting. Performance is assessed on a set of 6 standardized, typical ICU tasks, ranging from documentation to medical interpretation. Results A total of 60 ICU-experienced medical professionals participated in the study. The VIDS showed a statistically significant advantage compared to the other 2 systems. The tasks were completed significantly faster with the VIDS than with the PDMS (1-tailed t59=12.48; Cohen d=1.61; P<.001) or paper documentation (t59=20.41; Cohen d=2.63; P<.001). Significantly fewer errors were made with VIDS than with the PDMS (t59=3.45; Cohen d=0.45; P=.03) and paper-based documentation (t59=11.2; Cohen d=1.45; P<.001). The analysis of the mental workload of VIDS and PDMS showed no statistically significant difference (P=.06). However, the analysis of subjective user perception showed a statistically significant perceived benefit of the VIDS compared to the PDMS (P<.001) and paper documentation (P<.001). Conclusions The results of this study show that the VIDS reduced error rate, documentation time, and mental workload regarding the set of 6 standardized typical ICU tasks. In conclusion, this indicates that AI-based systems such as the VIDS tested in this study have the potential to reduce this workload and improve evidence-based and safe patient care.
A Coupled Model for Highly Accurate Calculation of Storm Surge Occurring in Inner Bay

Storm surges occurring in inner bays are strongly influenced by inflow rates of seawater from offshore and sea surface winds affected by complicated coastlines and landforms surrounding inner bays. A coupled model that employs the ocean model CCM with a multi-sigma coordinate system and a meteorological model MM5 performing 4DDABS was developed for accurate reproduction of the inflow rates of seawater from offshore and the sea surface winds. Its validity and utility were verified by comparing the observed results of the storm surge in Ise Bay generated by typhoon MELOR (2009) with the computed results. Results demonstrated that tidal levels calculated with the coupled model agree well with those observed at all locations in Ise Bay.