Miracle-dz/UniFAR-FTUs huggingface dataset:
Bilevel Construction Site Layout Optimization Based on Hazardous-Material Transportation

AbstractConstruction site layout optimization (CSLO) involves many important issues vital for the success of construction projects. One of the most important is the hazardous-material transportation (HT) problem. This paper concurrently considers CSLO and HT, namely the CSLO-HT problem, and proposes a bilevel multiobjective decision-making model (BMDMM). In this model, the upper-level decision-maker is the project manager, who aims to minimize site layout costs and economic losses from potential HT accidents. The lower-level decision-maker is the carrier, to whom the HT work is subcontracted, and whose goal is to reduce transportation costs. To solve the proposed bi-level multiobjective model, a fuzzy random simulation–based bilevel multiobjective genetic algorithm (frs-BLMOGA) is proposed. The approach is then applied to a hydropower construction project to illustrate the performance of the proposed methodology. The results and further analyses of the methodology prove that both the project manager and t.
Inhibition of Human UDP-Glucuronosyltransferases1A1–Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice

Bilirubin-related adverse drug reactions (ADRs) or malady (e.g., jaundice) induced by some herbs rich in certain flavonoids have been widely reported. However, the causes and mechanisms of the ADRs are not well understood. The aim of this paper was to explore the mechanism of Shuang-huang-lian (SHL) injections and its major constituents-induced jaundice via inhibiting human UDP-glucuronosyltransferases1A1 (hUGT1A1)-mediated bilirubin glucuronidation. The inhibitory effects of SHL and its major constituents in the herbal medicine, including baicalein (BAI), baicalin (BA), and hyperoside (HYP), on bilirubin glucuroBBREVInidation were investigated. This study indicated that the average formation rates of bilirubin glucuronides [i.e., mono-glucuronide 1 (BMG1), BMG2, and bilirubin diglucuronide] displayed significant differences (P < 0.05). Specifically, the formation of BMGs was favored regardless of whether an inhibitor was absent or present. SHL, BAI, BA, and HYP dose-dependently inhibit bilirubin glucuronidation, showing the IC50 values against total bilirubin glucuronidation were in the range of (7.69 ± 0.94)–(37.09 ± 2.03) μg/ml, (4.51 ± 0.27)–(20.84 ± 1.99) μM, (22.36 ± 5.74)–(41.35 ± 2.40) μM, and (15.16 ± 1.12)–(42.80 ± 2.63) μM for SHL, BAI, BA, and HYP, respectively. Both inhibition kinetics assays and molecular docking simulations suggested that SHL, BAI, BA, and HYP significantly inhibited hUGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibition. Collectively, some naturally occurring flavonoids (BAI, BA, and HYP) in SHL have been identified as the inhibitors against hUGT1A1-mediated bilirubin glucuronidation, which well explains the bilirubin-related ADRs or malady triggered by SHL in clinical settings. SIGNIFICANCE STATEMENT Herbal products and their components (e.g., flavonoids), which been widely used across the entire world, may cause liver injury. As a commonly used herbal products rich in flavonoids, SHL injections easily lead to symptoms of liver injury (e.g., jaundice) owing to significant inhibition of hUGT1A1-mediated bilirubin glucuronidation by its flavonoid components (i.e., baicalein, baicalin, and hyperoside). Herb-induced bilirubin-related ADRs and the associated clinical significance should be seriously considered.
Activities of Daily Living-Based Rehabilitation System for Arm and Hand Motor Function Retraining After Stroke

Most stroke survivors have difficulties completing activities of daily living (ADLs) independently. However, few rehabilitation systems have focused on ADLs-related training for gross and fine motor function together. We propose an ADLs-based serious game rehabilitation system for the training of motor function and coordination of both arm and hand movement where the user performs corresponding ADLs movements to interact with the target in the serious game. A multi-sensor fusion model based on electromyographic (EMG), force myographic (FMG), and inertial sensing was developed to estimate users’ natural upper limb movement. Eight healthy subjects and three stroke patients were recruited in an experiment to validate the system’s effectiveness. The performance of different sensor and classifier configurations on hand gesture classification against the arm position variations were analyzed, and qualitative patient questionnaires were conducted. Results showed that elbow extension/flexion has a more significant negative influence on EMG-based, FMG-based, and EMG+FMG-based hand gesture recognition than shoulder abduction/adduction does. In addition, there was no significant difference in the negative influence of shoulder abduction/adduction and shoulder flexion/extension on hand gesture recognition. However, there was a significant interaction between sensor configurations and algorithm configurations in both offline and real-time recognition accuracy. The EMG+FMG-combined multi-position classifier model had the best performance against arm position change. In addition, all the stroke patients reported their ADLs-related ability could be restored by using the system. These results demonstrate that the multi-sensor fusion model could estimate hand gestures and gross movement accurately, and the proposed training system has the potential to improve patients’ ability to perform ADLs.
Long-term follow-up of patients treated with pyrocarbon disc implant for thumb carpometacarpal osteoarthritis: the effect of disc position on outcomes measures

Abstract Pyrocarbon disc interposition arthroplasty is an effective treatment for thumb base osteoarthritis. However, as with all implant techniques, the disc can (sub)luxate over time. The relationship between disc position, the experienced pain, and the necessity for revision surgery is not known. This study evaluated the effect of radiographic pyrocarbon disc position on the Michigan Hand Questionnaire (MHQ) outcome measurement. In addition, the correlation between disc position and other factors, including pain intensity, thumb strength, and occupation, was assessed. In this retrospective study, we included 136 patients (161 thumbs) with a mean follow-up of 6.7 years (range 3.3–11). Radiographs were scored on disc position and classified as ‘well aligned’ (Grade 1) up to ‘luxated’ (Grade 4). A database used for outcome measures included MHQ scores, pain intensity, satisfaction, thumb strength, range of motion, occupation, and hand dominance. In bivariate analyses, we assessed any association between disc position and outcome measurements. Eighty of the 136 implants (59%) were well-positioned (not displaced), 41% were (slightly) displaced (grade 2–3). No relationship existed between the degree of disc displacement and MHQ scores. Manual labor occupation was the only factor that correlated with more severe disc displacement. We could not detect any association between disc position and other outcome variables including pain intensity, thumb strength, or hand dominance. In conclusion, our study suggests that radiographic disc displacement has little clinical consequences. Future studies must assess if there is a causality between heavy mechanical stress to the CMC1 joint and luxation of the pyrocarbon disc over time. Level of evidence: IV Therapeutic—Retrospective case series.
In Pursuit of the Quadruple Aim: A Geriatric Prescribing Context’s Impact on Clinician Workflows and Alert Fatigue

The impact of a novel Geriatric Prescribing Context (GPC) on hospital clinicians’ prescribing workflows is still unknown. A cross-sectional survey was distributed to 346 inpatient pharmacists, physicians, and advance practice providers employed at three pilot site hospitals affected by the GPC to assess awareness and impact to usual workflow. The GPC, a set of medication default doses and frequencies for patients 75 years and older, was unnoticed by 74% of survey respondents (n = 119) with pharmacists more likely to be aware of the context than prescribers. The impact of the GPC on clinicians’ workflow differed by setting, with academic respondents reporting no change or decreased time to write or verify orders, and community respondents reporting no change or increased time to write or verify orders. The GPC has smoothly integrated into usual prescribing workflows for both prescribers and pharmacists and both overall reported positive responses to the implementation.
Accuracy of transcranial Doppler in detecting intracranial stenosis in patients with sickle cell anemia when compared to magnetic resonance angiography

Stroke, the most devastating consequence of sickle cell anemia (SCA), is associated with endothelial damage and intracranial artery stenosis. We aimed to assess transcranial Doppler (TCD) ultrasound accuracy in detecting intracranial stenosis when compared to magnetic resonance angiography (MRA).
Formation of Au, Pt, and bimetallic Au–Pt nanostructures from thermal dewetting of single-layer or bilayer thin films

Formation of Au, Pt, and bimetallic Au–Pt nanostructures by thermal dewetting of single-layer Au, Pt and bilayer Au–Pt thin films on Si substrates was systematically studied. The solid-state dewetting of both single-layer and bilayer metallic films was shown to go through heterogeneous void initiation followed by void growth via capillary agglomeration. For the single-layer of Au and Pt films, the void growth started at a temperature right above the Hüttig temperature, at which the atoms at the surface or at defects become mobile. Uniformly distributed Au (7 ± 1 nm to 33 ± 8 nm) and Pt (7 ± 1 nm) NPs with monodispersed size distributions were produced from complete dewetting achieved for thinner 1.7−5.5 nm thick Au and 1.4 nm thick Pt films, respectively. The NP size is strongly dependent on the initial thin film thickness, but less so on temperature and time. Thermal dewetting of Au–Pt bilayer films resulted in partial dewetting only, forming isolated nano-islands or large particles, regardless of sputtering order and total thin film thickness. The increased resistance to thermal dewetting shown in the Au–Pt bilayer films as compared to the individual Au or Pt layer is a reflection of the stabilizing effect that occurs upon adding Pt to Au in the bimetallic system. Energy dispersive x-ray spectroscopic analysis showed that the two metals in the bilayer films broke up together instead of dewetting individually. According to the x-ray diffraction analysis, the produced Au–Pt nanostructures are phase-segregated, consisting of an Au-rich phase and a Pt-rich phase.
Neurofilament light chain and retinal layers' determinants and association: A population‐based study

Both retinal atrophy measured through optical coherence tomography and plasma neurofilament light chain (NfL) levels are markers of neurodegeneration, but their relationship is unknown. Therefore, we assessed their determinants and association in 4369 participants of a population‐based study. Both plasma NfL levels and inner retinal atrophy increased exponentially with age. In the presence of risk factors for neurodegeneration (including age, smoking, and a history of neurological disorders), plasma NfL levels were associated with inner retinal atrophy and outer retinal thickening. Our findings indicate that inner retinal atrophy can reflect neuroaxonal damage as mirrored by rising plasma NfL levels.
Electrical stimulation waveform‐dependent osteogenesis on PVDF/BaTiO3 composite using a customized and programmable cell stimulator

Directing cellular functionalities using biomaterial‐based bioelectronic stimulation remains a significant constraint in translating research outcomes to address specific clinical needs. Electrical stimulation is now being clinically used as a therapeutic treatment option to promote bone tissue regeneration and to improve neuromuscular functionalities. However, the nature of the electrical waveforms during the stimulation and underlying biophysical rationale are still not scientifically well explored. Furthermore, bone‐mimicking implant‐based bioelectrical regulation of osteoinductivity has not been translated to clinics. The present study demonstrates the role of the electrical stimulation waveform to direct differentiation of stem cells on an electroactive polymeric substrate, using monophasic direct current (DC), square waveform, and biphasic waveform. In this regard, an in‐house electrical stimulation device has been fabricated for the uninterrupted delivery of programmed electrical signals to stem cells in culture. To provide a functional platform for stem cells to differentiate, barium titanate (BaTiO3, BT) reinforced poly(vinylidene difluoride) (PVDF) has been developed with mechanical properties similar to bone. The electrical stimulation of human mesenchymal stem cells (hMSCs) on PVDF/BT composite inhibited proliferation rate at day 7, indicating early commitment for differentiation. The phenotypical characteristics of DC stimulated hMSCs provided signatures of differentiation towards osteogenic lineage, which was subsequently confirmed using alkaline phosphatase assay, collagen deposition, matrix mineralization, and genetic expression. Our findings suggest that DC stimulation induced early osteogenesis in hMSCs with a higher level of intracellular reactive oxygen species (ROS), whereas the stimulation with square wave directed late osteogenesis with a lower ROS regeneration. In summary, the present study critically analyzes the role of electrical stimulation waveforms in regulating osteogenesis, without external biochemical differentiation inducers, on a bone‐mimicking functional biomaterial substrate. Such a strategy can potentially be adopted to develop orthopedic implant‐based bioelectronic medicine for bone regeneration.
The role of thrombin in haemostasis

Thrombin is a multifunctional serine protease generated in injured cells. The generation of thrombin in coagulation plays a central role in the functioning of haemostasis. The last enzyme in the coagulation cascade is thrombin, with the function of cleaving fibrinogen to fibrin, which forms the fibrin clot of a haemostatic plug. Although thrombin primarily converts fibrinogen to fibrin, it also has many other positive regulatory effects on coagulation. Thrombin has procoagulant, inflammatory, cellular proliferation and anticoagulant effects. In coagulation system, thrombin has two very distinct roles. Firstly, it acts as a procoagulant when it converts fibrinogen into an insoluble fibrin clot, activates factor (F) XIII, activates thrombin activatable fibrinolysis inhibitor (TAFI) and activates FV, FVIII and FXI. Thrombin also enhances platelet adhesion by inactivating a disintegrin and metalloprotease with thrombospondin type1 motif (ADAMTS13). However, when thrombin activates protein C, it acts as an anticoagulant. A natural anticoagulant pathway that supplies regulation of the blood coagulation system contains protein C, which is the key component. This is accomplished by the specific proteolytic inactivation of FV and FVIII. In this review, the multiple roles of thrombin in the haemostatic response to injury are studied in addition to the cofactors that determine thrombin activity and how thrombin activity is thought to be coordinated.
KDM5-mediated redistribution of H3K4me3 is required for oocyte-to-embryonic transition in cattle

Abstract Reprogramming of histone modifications is critical to safeguard correct gene expression profile during preimplantation development. Of interest, trimethylation of lysine 4 on histone 3 (H3K4me3) exhibits a unique and dynamic landscape with a potential species-specific feature. Here, we address how it is reprogrammed and its functional significance during oocyte maturation and early embryonic development in cows. Notably, the overall signal of H3K4me3 decreased sharply during embryonic genome activation (EGA). By using low input ChIP-seq, we find widespread broad H3K4me3 domains in oocytes and early cleaved embryos. The broad domains are gradually removed after fertilization, which is obviously seen during EGA. Meanwhile, H3K4me3 becomes enriched at promoter regions after the removal of broad H3K4me3. Interestingly, the gene expression level displays a positive correlation with the relative H3K4me3 signal of their promoters when embryos reach 16-cell stage. Importantly, disruption of KDM5 (H3K4me3 demethylases) increases H3K4me3 level, decreases the embryonic developmental rate, and results in dysregulation of over a thousand genes. Meanwhile, KDM5 deficiency causes a redistribution of H3K4me3 across genome. In particular, H3K4me3 in gene body or intergenic regions cannot be removed, and H3K4me3 in promoter regions is aberrantly reduced. Besides, the positive correlation between promoter H3K4me3 enrichment and gene expression level disappears. Overall, we describe the genomic reprogramming of H3K4me3 with a greater resolution during bovine preimplantation development and propose that KDM5-mediated redistribution of H3K4me3 plays an important role in modulating oocyte-to-embryonic transition. Summary Sentence KDM5-mediated redistribution of H3K4me3 plays an important role in modulating oocyte-to-embryonic transition.
Characterising acute ischaemic stroke thrombi: insights from histology, imaging and emerging impedance-based technologies

Treatment of acute ischaemic stroke (AIS) focuses on rapid recanalisation of the occluded artery. In recent years, advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retrieved during the endovascular thrombectomy procedure. Despite ongoing developments and progress in AIS imaging techniques, it is not yet possible to conclude definitively regarding thrombus characteristics that could advise on the probable efficacy of thrombolysis or thrombectomy in advance of treatment. Intraprocedural devices with dignostic capabilities or new clinical imaging approaches are needed for better treatment of AIS patients. In this review, what is known about the composition of the thrombi that cause strokes and the evidence that thrombus composition has an impact on success of acute stroke treatment has been examined. This review also discusses the evidence that AIS thrombus composition varies with aetiology, questioning if suspected aetiology could be a useful indicator to stroke physicians to help decide the best acute course of treatment. Furthermore, this review discusses the evidence that current widely used radiological imaging tools can predict thrombus composition. Further use of new emerging technologies based on bioimpedance, as imaging modalities for diagnosing AIS and new medical device tools for detecting thrombus composition in situ has been introduced. Whether bioimpedance would be beneficial for gaining new insights into in situ thrombus composition that could guide choice of optimum treatment approach is also reviewed.
Novel mutations of the calcium-sensing receptor impede differential diagnosis of primary hyperparathyroidism and familial hypocalciuric hypercalcemia.

Background Familial hypocalciuric hypercalcemia 1 (FHH1) is an autosomal dominant disorder caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene, commonly leading-in contrast to primary hyperparathyroidism (PHPT)-to asymptomatic hypercalcemia. It is important to establish the correct diagnosis, as surgery may be curative in PHPT, but most likely ineffective in FHH. The study aims to evaluate patients with FHH1, initially misinterpreted as PHPT and some even undergone surgery. Methods CaSR-genotyping was conducted, various biochemical parameters including twenty-four-hour urinary Ca excretion (24hU CE) and the calculated relation of urinary Ca clearance to creatinine clearance (CCCR), type of surgery and 1-year follow-up data of fourteen patients with proven FHH1 were evaluated retrospectively. Results Genetic analysis revealed a total of nine novel heterozygous variants in the CaSR gene in our study population. Six of fourteen patients (42.9%) underwent surgery for initially suspected PHPT, showing normalized biochemical parameters immediately after surgery. In 1-year follow-up, however, five of six operated patients (83.3%) showed normal parathyroid hormone (PTH), but elevated serum calcium levels. In contrast, only one of the operated patients (16.7%) presented both PTH and serum calcium in the normal range. Histology showed adenoma in three (50%), hyperplasia in two (33.3%), and normal parathyroid tissue in one (16.7%) of the patients. Conclusions We discovered novel heterozygous variants in the CaSR gene, which considerably impede differential diagnosis of PHPT and FHH1. Furthermore, our results indicate that parathyroid surgery fails to provide long-term benefits for patients with FHH1 and suspected PHPT, even though this coincidence seems to exist.
Oxidative Stress: Meeting Multiple Targets in Pathogenesis of Vascular Endothelial Dysfunction.

Vascular endothelium is the innermost lining of blood vessels, which maintains vasoconstriction and vasodilation. Loss of vascular tone is a hallmark for cardiovascular disorders. Though there are numerous factors, such as over activation of renin angiotensin aldosterone system, kinases, growth factors, etc. play crucial role in induction and progression of vascular abrasion. Interestingly, dysregulation of these pathways either enhances the intensity of oxidative stress, or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered a key culprit in the progression of vascular endothelial dysfunction. Oxidative stress induced by reactive oxygen and nitrogen species causes abnormal gene expression, alteration in signal transduction, and the activation of pathways leading to induction and progression of vascular injury. In addition, numerous antioxidants have been noted to possess promising therapeutic potential in preventing the development of vascular endothelial dysfunction. Therefore, we have focused on current perspectives in oxidative stress signalling to evaluate common biological processes whereby oxidative stress plays a crucial role in the progression of vascular endothelial dysfunction.
Attention to audiovisual speech does not facilitate language acquisition in infants with familial history of autism.

BACKGROUND Due to familial liability, siblings of children with ASD exhibit elevated risk for language delays. The processes contributing to language delays in this population remain unclear. METHODS Considering well-established links between attention to dynamic audiovisual cues inherent in a speaker's face and speech processing, we investigated if attention to a speaker's face and mouth differs in 12-month-old infants at high familial risk for ASD but without ASD diagnosis (hr-sib; n = 91) and in infants at low familial risk (lr-sib; n = 62) for ASD and whether attention at 12 months predicts language outcomes at 18 months. RESULTS At 12 months, hr-sib and lr-sib infants did not differ in attention to face (p = .14), mouth preference (p = .30), or in receptive and expressive language scores (p = .36, p = .33). At 18 months, the hr-sib infants had lower receptive (p = .01) but not expressive (p = .84) language scores than the lr-sib infants. In the lr-sib infants, greater attention to the face (p = .022) and a mouth preference (p = .025) contributed to better language outcomes at 18 months. In the hr-sib infants, neither attention to the face nor a mouth preference was associated with language outcomes at 18 months. CONCLUSIONS Unlike low-risk infants, high-risk infants do not appear to benefit from audiovisual prosodic and speech cues in the service of language acquisition despite intact attention to these cues. We propose that impaired processing of audiovisual cues may constitute the link between genetic risk factors and poor language outcomes observed across the autism risk spectrum and may represent a promising endophenotype in autism.