Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Contributing to Pedestrian and Bicycle Crashes on Rural Highways

Approximately 25% of pedestrian and bicycle fatal and injury accidents occur on rural highways. In contrast to urban highways, rural highways have certain characteristics that can be more hazardous to pedestrians and bicyclists, such as higher average vehicle speeds and a lack of sidewalk provisions. The objectives of this study were first, to compare and contrast rural and urban pedestrian and bicyclist crashes in North Carolina; and second, to identify problem areas (specific crash types and crash locations) on rural highways that are of high priority for safety treatment and treatment development. Rural pedestrian and bicyclist crashes were found to be characterized by higher percentages of fatalities, higher percentages of alcohol consumption, higher vehicles speeds, unpaved shoulders, and midblock-related crash types. Eleven pedestrian problem areas were identified, of which the most prevalent were "walking along roadway" on rural two-lane roads, "pedestrian failed to yield, midblock" on rural two-lane roads, and "midblock dart/dash" on rural two-lane roads. Five bicycle problem areas were identified, of which the most common were "bicyclist turn/merge into path of motorist, midblock" on rural two-lane roads and "motorist overtaking, midblock" on rural two-lane roads. Potential countermeasures for these problem areas were discussed in view of their potential safety effectiveness and feasibility for rural areas. Countermeasures that rated highly for both criteria included improvements in roadway lighting, addition of paved shoulders, education of pedestrians and motorists, and increase in marked space for bicyclists on the existing roadway.
REVIEW Japanese Salmon Research in the Ocean: A Review and Future Issues

This paper provided a review on the results of Japanese salmon research conducted in 1993-2000 under the Science Plan decided by the North Pacific Anadromous Fish Commission (NPAFC). Recent developments of stock identification techniques and high-seas salmon population surveys provided new information for the ocean distribution of chum salmon: Japanese chum salmon inhabit the Okhotsk Sea in the early ocean life, pass the first winter in the western North Pacific Ocean, and then migrate to the Bering Sea by the next summer. Coastal surveys suggested that major salmon mortalities occur in the early ocean life, but the causes of juvenile mortalities have not been well understood. Scale pattern analysis suggested that Japanese chum salmon suffer from growth reduction in the Bering Sea, resulting in increase of age at maturity. A long term biological monitoring in the subarctic North Pacific Ocean found a negative relationship between macro- zooplankton and pink salmon biomass. A similar biological monitoring should be necessary in the Bering Sea. The extremely low lipid contents in the muscle of overwintering salmon indicated a great difficulty for them to survive in winter. Future research issues are (1) juvenile salmon studies in the Okhotsk Sea, (2) winter salmon studies in the North Pacific Ocean, (3) salmon ecology studies in the Bering Sea, and (4) monitoring of major salmon stocks. These issues are indispensable for the sustainable stock management of Pacific salmon.
Applications of fast and accurate summation in computational geometry

In this paper, we present a recent algorithm given by Ogita, Rump and Oishi [39] for accurately computing the sum of n floating point numbers. They also give a computational error bound for the computed result. We apply this algorithm in computing determinant and more particularly in computing robust geometric predicates used in computational geometry. We improve existing results that use either a multiprecision libraries or extended large accumulators.
Leishmania (L.) amazonensis LaLRR17 increases parasite entry in macrophage by a mechanism dependent on GRP78

Abstract Abstract Leishmaniases affect 12 million people worldwide. They are caused by Leishmania spp. , protozoan parasites transmitted to mammals by female phlebotomine flies. During the life cycle, promastigote forms of the parasite live in the gut of infected sandflies and convert into amastigotes inside the vertebrate macrophages. The parasite evades macrophage's microbicidal responses due to virulence factors that affect parasite phagocytosis, survival and/or proliferation. The interaction between Leishmania and macrophage molecules is essential to phagocytosis and parasite survival. Proteins containing leucine-rich repeats (LRRs) are common in several organisms, and these motifs are usually involved in protein–protein interactions. We have identified the LRR17 gene, which encodes a protein with 6 LRR domains, in the genomes of several Leishmania species. We show here that promastigotes of Leishmania (L.) amazonensis overexpressing LaLRR17 are more infective in vitro. We produced recombinant LaLRR17 protein and identified macrophage 78 kDa glucose-regulated protein (GRP78) as a ligand for LaLRR17 employing affinity chromatography followed by mass spectrometry. We showed that GRP78 binds to LaLRR17 and that its blocking precludes the increase of infection conferred by LaLRR17. Our results are the first to report LRR17 gene and protein, and we hope they stimulate further studies on how this protein increases phagocytosis of Leishmania.
Adjunctive MRI in the diagnosis of placenta accreta spectrum in major placenta previa: incidence, risk factors, and maternal morbidity

BACKGROUND: Antenatal assessment of maternal risk factors and imaging evaluation can help in diagnosis and treatment of placenta accreta spectrum (PAS) in major placenta previa (PP). Recent evidence suggests that magnetic resonance imaging (MRI) could complement ultrasonography (US) in the PAS diagnosis. OBJECTIVES: Evaluate the incidence, risk factors, and maternal morbidity related to the MRI diagnosis of PAS in major PP. DESIGN: A 10-year retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS AND METHODS: We report on patients with major PP who had cesarean delivery in Abha Maternity and Children's Hospital (AMCH) over a 10-year period (2012-2021). They were evaluated with ultrasonography (US) and color Doppler for evidence of PAS. Antenatal MRI was ordered either to confirm the diagnosis (if equivocal US) or to assess the depth of invasion/extra-uterine extension (if definitive US). MAIN OUTCOME MEASURES: Risk factors for PAS in major PP and maternal complications. SAMPLE SIZE: 299 patients RESULTS: Among 299 patients, MRI confirmed the PAS diagnosis in 91/299 (30.5%) patients. The independent risk factors for MRI diagnosis of PAS in major PP included only repeated cesarean sections and advanced maternal age. The commonest maternal morbidity in major PP with PAS was significantly excessive intraoperative bleeding. CONCLUSION: MRI may be a valuable adjunct in the evaluation of PAS in major PP, but not as a substitute for US. MRI may be suitable in major PP/PAS patients who are older and have repeated cesarean deliveries with equivocal results or suspected deep/extra-uterine extension on US. LIMITATION: Single center, small sample size, lack of complete histopathological diagnosis. CONFLICT OF INTEREST: None.
On selection of semiparametric spatial regression models

In this paper, we focus on variable selection techniques for a class of semiparametric spatial regression models, which allow one to study effects of explanatory variables in the presence of spatial information. The spatial smoothing problem in the nonparametric part is tackled by means of bivariate splines over triangulation, which is able to deal efficiently with data distributed over irregularly shaped regions. In addition, we develop a unified procedure for variable selection to identify significant covariates under a double penalization framework, and we show that the penalized estimators enjoy the “oracle” property. The proposed method can simultaneously identify nonzero spatially distributed covariates and solve the problem of “leakage” across complex domains of the functional spatial component. To estimate the standard deviations of the proposed estimators for the coefficients, a sandwich formula is developed as well. In the end, Monte Carlo simulation examples and a real data example are provided to illustrate the proposed methodology.
Hearing Aids Reduce Self-Perceived Difficulties in Noise for Listeners With Normal Audiograms

Objectives: This study assessed hearing aid benefits for people with a normal audiogram but hearing-in-noise problems in everyday listening situations. Design: Exploratory double-blinded case-control study whereby participants completed retrospective questionnaires, ecological momentary assessments, speech-in-noise testing, and mental effort testing with and without hearing aids. Twenty-seven adults reporting speech-in-noise problems but normal air conduction pure-tone audiometry took part in the study. They were randomly separated into an experimental group that trialed mild-gain hearing aids with advanced directional processing and a control group fitted with hearing aids with no gain or directionality. Results: Self-reports showed mild-gain hearing aids reduce hearing-in-noise difficulties and provide a better hearing experience (i.e., improved understanding, participation, and mood). Despite the self-reported benefits, the laboratory tests did not reveal a benefit from the mild-gain hearing aids, with no group differences on speech-in-noise tests or mental effort measures. Further, participants found the elevated cost of hearing aids to be a barrier for their adoption. Conclusions: Hearing aids benefit the listening experience in some listening situations for people with normal audiogram who report hearing difficulties in noise. Decreasing the price of hearing aids may lead to greater accessibility to those seeking remediation for their communication needs.
De novo network analysis reveals autism causal genes and developmental links to co-occurring traits

In this study, we provide a biological argument for looking at an autistic individual’s phenotype as being related to their combined genetic risk for different clusters of traits. Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other conditions, such as attention-deficit/hyperactivity disorder and schizophrenia, which can complicate diagnosis and management. Although research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this, we conducted a two-sample Mendelian randomisation analysis and identified four genes located at the 17q21.31 locus that are putatively causal for autism in fetal cortical tissue (LINC02210, LRRC37A4P, RP11-259G18.1, and RP11-798G7.6). LINC02210 was also identified as putatively causal for autism in adult cortical tissue. By integrating data from expression quantitative trait loci, genes and protein interactions, we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits in fetal cortical tissue. We also identified a distinct cluster of co-occurring traits, including cognition and worry, linked to the genetic loci at 3p21.1. Our findings provide insights into the relationship between autism and co-occurring traits, which could be used to develop predictive models for more accurate diagnosis and better clinical management.
Associations between polygenic risk scores and accelerated brain ageing in smokers

Abstract Background Smoking contributes to a variety of neurodegenerative diseases and neurobiological abnormalities, suggesting that smoking is associated with accelerated brain aging. However, the neurobiological mechanisms affected by smoking, and whether they are genetically influenced, remain to be investigated. Methods Using structural magnetic resonance imaging data from the UK Biobank (n = 33 293), a brain age predictor was trained on non-smoking healthy groups and tested on smokers to obtain the BrainAge Gap (BAG). The cumulative effect of multiple common genetic variants associated with smoking was then calculated to acquire a polygenic risk score (PRS). The relationship between PRS, BAG, total gray matter volume (tGMV), and smoking parameters was explored and further genes included in the PRS were annotated to identify potential molecular mechanisms affected by smoking. Results The BrainAge in smokers was predicted with very high accuracy (r = 0.725, MAE = 4.16). Smokers had a greater BAG (Cohen's d = 0.074, p < 0.0001) and higher PRS (Cohen's d = 0.63, p < 0.0001) than non-smokers. A higher PRS was associated with increased amount of smoking, mediated by BAG and tGMV. Several neurotransmitters and ion channel pathways were enriched in the group of smoking-related genes involved in addiction, brain synaptic plasticity, and some neurological disorders. Conclusion By using a simplified single indicator of the entire brain (BAG) in combination with the PRS, this study highlights the greater BAG in smokers and its linkage with genes and smoking behavior, providing insight into the neurobiological underpinnings and potential features of smoking-related aging.
CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing

The long-term success rate of dental implants can be improved by establishing a favorable biological sealing with a high-quality epithelial attachment. The application of mesenchymal stem cells (MSCs) holds promise for facilitating the soft tissue integration around implants, but the molecular mechanism is still unclear and the general application of MSC sheet for soft tissue integration is also relatively unexplored. We found that gingival tissue–derived MSC (GMSC) sheet treatment significantly promoted the expression of hemidesmosome (HD)–related genes and proteins in gingival epithelial cells (GECs). The formation of HDs played a key role in strengthening peri-implant epithelium (PIE) sealing. Further, high-throughput transcriptome sequencing showed that GMSC sheet significantly upregulated the PI3K/AKT pathway, confirming that cell adhesion and HD expression in GECs were regulated by GMSC sheet. We observed that the expression of transcription factor CREB3L2 in GECs was downregulated. After treatment with PI3K pathway inhibitor LY294002, CREB3L2 messenger RNA and protein expression levels were upregulated. Further experiments showed that overexpression or knockdown of CREB3L2 could significantly inhibit or promote HD-related genes and proteins, respectively. We confirmed that CREB3L2 was a transcription factor downstream of the PI3K/AKT pathway and participated in the formation of HDs regulated by GMSC sheet. Finally, through the establishment of early implant placement model in rats, we clarified the molecular function of CREB3L2 in PIE sealing as a mechanical transmission molecule in GECs. The application of GMSC sheet–implant complex could enhance the formation of HDs at the implant–PIE interface and decrease the penetration distance of horseradish peroxidase between the implant and PIE. Meanwhile, GMSC sheet reduced the length of CREB3L2 protein expression on PIE. These findings elucidate the potential function and molecular mechanism of MSC sheet regulating the epithelial sealing around implants, providing new insights and ideas for the application of stem cell therapy in regenerative medicine.
AAV1.NT‐3 gene therapy in the SOD1KO mouse model of accelerated sarcopenia

Sarcopenia, an age‐related loss of muscle mass, is a critical factor that affects the health of the older adults. The SOD1KO mouse is deficient of Cu/Zn superoxide dismutase, used as an accelerated aging model. We previously showed that NT‐3 improves muscle fibre size by activating the mTOR pathway, suggesting a potential for attenuating age‐related muscle loss. This study assessed the therapeutic efficacy of AAV1.NT‐3 in this accelerated aging model.
Quantitative increases of extracellular vesicles in prolonged cold storage of platelets increases the potential to enhance fibrin clot formation

Platelet derived extracellular vesicles (EVs) display a pro‐coagulant phenotype and are generated throughout platelet concentrate (PC) storage. Cold storage (CS) of PCs is thought to provide a superior haemostatic advantage over room temperature (RT) storage and could prolong the storage time. However, the effect of storage conditions on EV generation and PC function is unknown. We investigated EV production under CS and RT conditions and assessed whether these EVs exhibited a more pro‐coagulant phenotype in model experiments.
Emergency department patient‐centred care perspectives from deaf and hard‐of‐hearing patients

Deaf and hard‐of‐hearing (DHH) patients are a priority population for emergency medicine health services research. DHH patients are at higher risk than non‐DHH patients of using the emergency department (ED), have longer lengths of stay in the ED and report poor patient–provider communication. This qualitative study aimed to describe ED care‐seeking and patient‐centred care perspectives among DHH patients.
Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles

Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one‐directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs‐derived conditioned medium (CM) was harvested from different time intervals (Day 0−2: CM‐D2 and Day 5−7: CM‐D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM‐D2 significantly induced the inflammatory phenotype in KCs, but not CM‐D7. Neither CM‐D2 nor CM‐D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs‐derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV‐depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll‐like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.
High sensitivity c-reactive protein and circulating biomarkers of endothelial dysfunction in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors

Abstract Tyrosine kinase inhibitors (TKIs) have revolutionized the management of patients with chronic myelogenous leukemia (CML); however, they may cause cardiovascular (CV) toxicities. In this cross-sectional study, we explored whether high-sensitivity C-reactive protein (hsCRP) and novel markers of vascular dysfunction were associated with exposure to specific TKIs, in 262 CML patients. Hs-CRP level was not associated with CML disease activity or treatment with a specific TKI. Body mass index (OR: 1.15, 95% CI: 1.108–1.246; p < 0.001) and CML duration (OR: 1.004, 95% CI: 1.001–1.008; p = 0.024) were independently associated with higher hs-CRP. In exploratory analyses, novel endothelial-centric markers (e.g. ET-1 and VCAM-1) were differential across the various TKIs, particularly amongst nilotinib- and ponatinib-treated patients. While Levels of hs-CRP do not appear to be correlated with specific TKIs, circulating markers of vascular dysfunction were altered in patients treated with specific TKIs and should be explored as potential markers of TKI-associated CV risk.
SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models

ABSTRACT SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for Omicron in a monkey kidney cell line, experiments with protease inhibitors showed that Omicron (BA.1 and XBB1.5) did not use cathepsins for entry into human airway organoids and instead utilized TTSPs. Likewise, CRISPR-edited intestinal organoids showed that entry of Omicron BA.1 relied on the expression of the serine protease TMPRSS2 but not cathepsin L or B. Together, these data force us to rethink the concept that Omicron has adapted to cathepsin-mediated entry and indicate that TTSP inhibitors should not be dismissed as prophylactic or therapeutic antiviral strategy against SARS-CoV-2. IMPORTANCE Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human in vitro cell models. Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human in vitro cell models.
Toward Sub‐Terahertz: Space‐Time Coding Metasurface Transmitter for Wideband Wireless Communications

A space‐time coding metasurface (STCM) operating in the sub‐terahertz band to construct new‐architecture wireless communication systems is proposed. Specifically, a programmable STCM is designed with varactor‐diode‐tuned metasurface elements, enabling precise regulation of harmonic amplitudes and phases by adjusting the time delay and duty cycle of square‐wave modulation signal loaded on the varactor diodes. Independent electromagnetic (EM) regulations in the space and time domains are achieved by STCM to realize flexible beam manipulations and information modulations. Based on these features, a sub‐terahertz wireless communication link is constructed by employing STCM as a transmitter. Experimental results demonstrate that the STCM supports multiple modulation schemes including frequency‐shift keying, phase‐shift keying, and quadrature amplitude modulations in a wide frequency band. It is also shown that the STCM is capable of realizing wide‐angle beam scanning in the range of ±45o, which offers an opportunity for user tracking during the communication. Thus, the STCM transmitter with high device density and low power consumption can provide low‐complexity, low‐cost, low‐power, and low‐heat solutions for building the next‐generation wireless communication systems in the sub‐terahertz frequency and even terahertz band.