Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine Learning–Derived Acetabular Dysplasia and Cam Morphology Are Features of Severe Hip Osteoarthritis: Findings From UK Biobank

The contribution of shape changes to hip osteoarthritis (HOA) remains unclear, as is the extent to which these vary according to HOA severity. In the present study, we used statistical shape modeling (SSM) to evaluate relationships between hip shape and HOA of different severities using UK Biobank DXA images. We performed a cross‐sectional study in individuals with left hip dual‐energy X‐ray absorptiometry (DXA) scans. Statistical shape modeling (SSM) was used to quantify hip shape. Radiographic HOA (rHOA) was classified using osteophyte size and number and joint space narrowing. HOA outcomes ranged in severity from moderate (grade 2) to severe (grade ≥3) rHOA, hospital‐diagnosed HOA, and subsequent total hip replacement (THR). Confounder‐adjusted logistic regression between the top 10 hip shape modes (HSMs) and OA outcomes was performed. Further models adjusted for alpha angle (AA) and lateral center‐edge angle (LCEA), reflecting acetabular dysplasia and cam morphology, respectively. Composite HSM figures were produced combining HSMs associated with separate OA outcomes. A total of 40,311 individuals were included (mean 63.7 years, 47.8% male), of whom 5.7% had grade 2 rHOA, 1.7% grade ≥3 rHOA, 1.3% hospital‐diagnosed HOA, and 0.6% underwent THR. Composite HSM figures for grade 2 rHOA revealed femoral neck widening, increased acetabular coverage, and enlarged lesser and greater trochanters. In contrast, grade ≥3 rHOA, hospital‐diagnosed HOA, and THR were suggestive of cam morphology and reduced acetabular coverage. Associations between HSMs depicting cam morphology and reduced acetabular coverage and more severe HOA were attenuated by AA and LCEA adjustment, respectively. Relationships between hip shape and HOA differed according to severity. Notably, cam morphology and acetabular dysplasia were features of severe HOA, but unrelated to moderate disease, suggesting possible prognostic utility. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Mitotic checkpoint gene expression is tuned by codon usage bias

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half‐lives and long protein half‐lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+, their short mRNA half‐lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1+ mRNA has a short half‐life despite a higher frequency of optimal codons, and despite the lack of known RNA‐destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co‐translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine‐tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.
Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations

Abstract Background CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. Aim The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. Subjects and methods Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. Results In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. Conclusion In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.
Mouse Bestrophin-2 Is a Bona ﬁde Cl (cid:2) Channel: Identiﬁcation of a Residue Important in Anion Binding and Conduction

Bestrophins have recently been proposed to comprise a new family of Cl (cid:2) channels. Our goal was to test whether mouse bestrophin-2 (mBest2) is a bona ﬁde Cl (cid:2) channel. We expressed mBest2 in three different mammalian cell lines. mBest2 was trafﬁcked to the plasma membrane as shown by biotinylation and immunoprecipitation, and induced a Ca 2 (cid:3) -activated Cl (cid:2) current in all three cell lines (EC 50 for Ca 2 (cid:3) (cid:4) 230 nM). The permeability sequence was SCN (cid:2) : I (cid:2) : Br (cid:2) : Cl (cid:2) : F (cid:2) (8.2: 1.9: 1.4: 1: 0.5). Although SCN (cid:2) was highly permeant, its conductance was (cid:2) 10% that of Cl (cid:2) and SCN (cid:2) blocked Cl (cid:2) conductance (IC 50 (cid:4) 12 mM). Therefore, SCN (cid:2) entered the pore more easily than Cl (cid:2) , but bound more tightly than Cl (cid:2) . Mutations in S79 altered the relative permeability and conductance for SCN (cid:2) as expected if S79 contributed to an anion binding site in the channel. P SCN /P Cl (cid:4) 8.2 (cid:5) 1.3 for wild-type and 3.9 (cid:5) 0.4 for S79C. G SCN /G Cl (cid:4) 0.14 (cid:5) 0.03 for wild-type and 0.94 (cid:5) 0.04 for S79C. In the S79 mutants, SCN (cid:2) did not block Cl (cid:2) conductance. This suggested that the S79C mutation altered the afﬁnity of an anion binding site for SCN (cid:2) . Additional evidence that S79 was located in the conduction pathway was provided by the ﬁnding that modiﬁcation of the sulfhydryl group in S79C with MTSET (cid:3) or MTSES (cid:2) increased conductance signiﬁcantly. Because the effect of positively and negatively charged MTS reagents was similar, electrostatic interactions between the permeant anion and the channel at this residue were probably not critical in anion selectivity. These data provide strong evidence that mBest2 forms part of the novel Cl (cid:2) conduction pathway in mBest2-transfected cells and that S79 plays an important role in anion binding in the pore of the channel. ﬁde (a) mBest2 expression must produce identical Cl currents when expressed in different cell types. (b) The mBest2 protein must be expressed on the cell surface. (c) Mutations in putative pore domains of mBest2 must alter the conduction of anions through the expressed channels. Here we report that these three conditions are met. Most interestingly, we describe a mutation that produces signiﬁcant changes in ion the The nature of these changes suggests that this the pore. These data provide idea
The Association: Early Adoption of IFRS and Value Relevance of Accounting Information

The objective of this article is to analyze the impact of the early adoption of IFRS on the value relevance of accounting information among the CAC 40 listed companies.In our study we adopted the Ohlson (1995) models in order to study the value relevance of accounting information. Our data was collected manually . The period 2002-2004 was used as the pre anticipation of the IFRS and the period 2004-2006 was used as the post anticipation of the IFRS . The problem therefore of our research is the following is: What is the effect of the early adoption of IFRS on the quality of the accounting information? In the study, our estimates focused on two panels: panel A and panel B. After analyzing the various estimates we found that the early adoption of IFRS has enabled companies in panel A, companies which adopted IFRS in an anticipated manner, to provide investors with accounting information with greater value relevance compared to the companies of panel B.Thanks to this study we can confirm that the early adoption of IFRS significantly enhanced the quality of accounting information for panel A.
Detecting and Tracking Pseudo Base Stations in GSM Signal Hijacking and Frauds: a Visualized Approach

Pseudo base station (PBS), sometimes called fake base station, refers to cellular base stations that are employed for malicious and usually illegal purposes. Through the pitfalls of the GSM protocol, PSBs can hijack GSM signals of cellphones close by. Most PBSes are portable, for example hidden in vans or even carried in backpacks, and are deployed in densely populated regions. Then they can steal personal information from neighboring smartphones, or send intriguing messages to them that would ultimately lead to telecom frauds. In recent years, there has been a terrifying increase in the number of telecom frauds and the smartphones infected by viruses sent from PBSes. This urgently calls for methods and systems that can effectively identify and track PBSes. In this study, we designed and implemented a PBS detecting and tracking system, by conducting topic analysis of messages received by cellphones and analyzing their temporal and spatial distribution patterns. Using the system, we could perform a variety of exploratory analysis, including categorizing PBSes into either stationary or moving PBSes, discovering and visualizing their behavior patterns, and identifying districts that tend to suffer from a particular type of fraud messages.
Analgesic effect of gastrin-releasing peptide in the dorsal horn

Itch and pain are both unpleasant, but they are discrete sensations. Both of these sensations are transmitted by C-fibers and processed in laminae I-II of the dorsal horn. To examine whether pruriception modulates pain, we first confirmed the activation of cells in the itch-related circuits that were positive for gastrin-releasing peptide (GRP) and GRP receptor (GRPR) using a paw formalin injection model. This pain model with typical biphasic pain behavior increased c-Fos but did not affect the expressions of GRP and GRPR mRNAs in the dorsal horn. Using c-Fos expression as a marker for activated cells, we confirmed that formalin injection increased the number of cells double-labeled for c-Fos and GRP or GRPR in the dorsal horn. The emergence of these neurons indicates the activation of itch-related circuits by acute pain signals. The effect of an antagonist for a GRPR was examined in the paw formalin injection model. Intrathecal chronic antagonization of spinal GRPR enhanced the onset of phase II of paw formalin injection-induced pain behavior. Exogenous intrathecal GRP infusion to the paw-formalin injection model not only showed significant reduction of pain behavior but also increased c-Fos in the inhibitory neurons in the dorsal horn. The anti-nociceptive effect of spinal GRP infusion was observed in the peripheral inflammation model (complete Freund’s adjuvant injection model). In this study we suggest that painful stimuli activated itch-related neuronal circuits and uncovered the spinal activation of the itch-induced analgesic effect on acute and established inflammatory pain.
The X-linked helicase DDX3X is required for lymphoid differentiation and MYC-driven lymphomagenesis.

The X-linked gene DDX3X encodes an RNA helicase that is mutated at high frequencies in several types of human B-cell lymphoma. Females have two active DDX3X alleles and males carry a DDX3Y homolog on the Y chromosome. We show here that pan-hematopoietic, homozygous deletion of Ddx3x in female mice perturbs erythropoiesis, causing early developmental arrest. However, both hemizygous male and heterozygous female embryos develop normally, suggesting that one Ddx3x allele is sufficient for fetal hematopoietic development in females and that the Ddx3y allele can compensate for the loss of Ddx3x in males. In adult mice, DDX3X deficiency altered hematopoietic progenitors, early lymphoid development, marginal zone and germinal center B-cells, and lymphomagenesis in a sex-dependent manner. Loss of both Ddx3x alleles abrogated MYC-driven lymphomagenesis in females, while Ddx3x-deletion in males did not affect the formation of B-cell lymphoma in both mouse models. Moreover, tumors that appeared in male mice lacking DDX3X showed upregulated expression of DDX3Y, indicating a critical requirement for DDX3 activity for lymphomagenesis. These data reveal sex-specific roles of DDX3X in erythro- and lymphopoiesis as well as in MYC-driven lymphomagenesis.
‘Student tutors go online’ - Investigation of cognitive and social congruence in online student tutorials - a longitudinal study

ABSTRACT The concept of peer-assisted learning (PAL) has been implemented at many medical faculties. Due to the Covid-19 pandemic, parts of the medical education experience transitioned to digital formats. However, little is known about PAL and online student tutorials. PAL is effective due to cognitive and social congruence. This study aims to investigate these concepts in an online student tutorial on taking a patient’s medical history. This longitudinal study took place in a preclinical communication course on how to take a patient’s medical history. In an online student tutorial, the students learned how to take a patient’s psychosocial medical history. Using standardised questionnaires, cognitive and social congruence were assessed. T-tests of independent samples were performed for data comparison. The participants included 128 second-year medical students and 5 student tutors. Cognitive congruence (Mstudent = 4.19 ± 0.56; Mstudenttutor = 4.04 ± 0.57) and social congruence (MStudent = 4.25 ± 0.56; MStudenttutor = 4.06 ± 0.57) were high for both students and student tutors in the online setting. In comparison to the face-to-face group, students in the online setting considered the student tutors to be significantly (p < .05) more socially congruent. Learning success increased during the course; however, it was not influenced by cognitive congruence. Cognitive and social congruence are high in an online setting. The students’ learning success increased during the online tutorial. Based on the higher level of social congruence, student tutors might be very motivated to be open and approachable in an online setting. Simultaneously, students might pay more attention and participate actively in the online setting. Social and cognitive congruence contribute to the effectiveness of online student tutorials and, thus, online student tutorials should be integrated into medical training.
Changing incidence and survival of intrahepatic cholangiocarcinoma based on Surveillance, Epidemiology, and End Results Database (2000-2017)

Backgrounds/Aims Historically, the incidence and prognosis of patients diagnosed with intrahepatic cholangiocarcinoma (ICC) have been inadequately understood. Survival analysis in ICC has yet to be investigated in a population-based study. Methods We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program (SEER) 18 Registry. Risk ratios were estimated via Poisson regression. Hazard ratios for 5-year survival were estimated using hierarchical Cox regression models. Results Males show a higher rate of age-adjusted ICC incidence. Blacks carried a decreased risk of ICC diagnosis than Whites, while Asians revealed a higher risk of ICC diagnosis when compared with Whites. The observed survival rates at 12, 36, and 60 months were 36.3%, 12.8%, and 8.1%, respectively. Compared with Whites, Blacks showed an increased risk of death (p < 0.01). Lymph node resection during surgery was associated with a 64.1% reduced risk of mortality (p < 0.01). A higher T stage at diagnosis was associated with poor survival (p < 0.01). Surgery combined with chemoradiotherapy, radiotherapy, or chemotherapy was associated with a reduced risk of mortality compared with nonsurgical interventions (p < 0.01). Conclusions ICC incidence has been increasing since 2000, especially in White males. The risk of ICC rises with age. Lymph node removal is associated with better survival. In recent years, survival had worsened, and surgical intervention improved survival compared with nonsurgical management.
Orthology-based analysis helps map evolutionary diversification and predict substrate class use of BAHD acyltransferases.

Large enzyme families catalyze metabolic diversification by virtue of their ability to use diverse chemical scaffolds. How enzyme families attain such functional diversity is not clear. Furthermore, duplication and promiscuity in such enzyme families limits their functional prediction, which has produced a burgeoning set of incompletely annotated genes in plant genomes. Here, we address these challenges using BAHD acyltransferases as a model. This fast-evolving family expanded drastically in land plants, increasing from 1-5 copies in algae to ~100 copies in diploid angiosperm genomes. Compilation of >160 published activities helped visualize the chemical space occupied by this family and define eight different classes based on structural similarities between acceptor substrates. Using orthologous groups (OGs) across 52 sequenced plant genomes, we developed a method to predict BAHD acceptor substrate class utilization as well as origins of individual BAHD OGs in plant evolution. This method was validated using 6 novel and 28 previously characterized enzymes and helped improve putative substrate class predictions for BAHDs in the tomato genome. Our results also revealed that while cuticular wax and lignin biosynthetic activities were more ancient, anthocyanin acylation activity was fixed in BAHDs later near the origin of angiosperms. The OG-based analysis enabled identification of signature motifs in anthocyanin-acylating BAHDs, whose importance was validated via molecular dynamic simulations, site-directed mutagenesis and kinetic assays. Our results not only describe how BAHDs contributed to evolution of multiple chemical phenotypes in the plant world but also propose a biocuration-enabled approach for improved functional annotation of plant enzyme families.
Modelling Japanese encephalitis virus transmission dynamics and human exposure in a Cambodian rural multi-host system

Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving wild birds as reservoirs and pigs as amplifying hosts. JE is endemic in Cambodia, where it circulates in areas with low pig densities (<70 pigs per km2), and could be maintained in a multi-host system composed of pigs, but also poultry as competent hosts, and dogs, cattle and humans as non-competent hosts. We used a mathematical model representing Japanese encephalitis virus (JEV) transmission in a traditional Cambodian village that we calibrated with field data collected in 3 districts of Kandal province, Cambodia. First, R0 calculations allowed us to assess the capacity of the epidemiological system to be invaded by JEV and sustain virus transmission in villages in the 3 districts, and we predicted human exposure at the epidemiological equilibrium, based on simulations. Changes in spatial density of livestock, in agricultural practices, and epizootics (e.g., African swine fever), can profoundly alter the composition of host communities, which could affect JEV transmission and its impact on human health. In a second step, we then used the model to analyse how host community composition affected R0 and the predicted human exposure. Lastly, we evaluated the potential use of dog JE seroprevalence as an indicator of human exposure to JEV. In the modeled villages, the calculated R0 ranged from 1.07 to 1.38. Once the equilibrium reached, predicted annual probability of human exposure ranged from 9% to 47%, and predicted average age at infection was low, between 2 and 11 years old, highlighting the risk of severe forms of JEV infection and the need to intensify child immunization. According to the model, increasing the proportion of competent hosts induced a decrease in age at infection. The simulations also showed that JEV could invade a multi-host system with no pigs, reinforcing the assumption of poultry acting as reservoirs. Finally, the annual human exposure probability appeared linearly correlated with dog seroprevalence, suggesting that in our specific study area, dog seroprevalence would be a good proxy for human exposure.
A Study on the Design and Performance Test of Side Thruster

In this paper, we present a study concerning the design of a 400 N class side thruster for small ships. The side thrusters used in Korea are imported from abroad. The performance and durability of the imported products employed in Korea are not adequate, therefore the side thrusters which will be suitable for Korean domestic needs to be re-designed. The strength calculation of the side thruster was performed by KS standard. Strength calculation and design were made to meet design requirements. Structural analysis and safety factor analysis were carried out to confirm the validity of strength calculations and design. After manufacturing the bevel gear, a back lash test was conducted. We also conducted a no-load test, a rated load, and an overload test for a performance test and a durability test of the design while satisfying the design conditions.
Deuterium MRSI of tumor cell death in vivo following oral delivery of 2H‐labeled fumarate

There is an unmet clinical need for direct and sensitive methods to detect cell death in vivo, especially with regard to monitoring tumor treatment response. We have shown previously that tumor cell death can be detected in vivo from 2H MRS and MRSI measurements of increased [2,3‐2H2]malate production following intravenous injection of [2,3‐2H2]fumarate. We show here that cell death can be detected with similar sensitivity following oral administration of the 2H‐labeled fumarate.
AP‐3 complex subunit delta gene, ap3d1, regulates melanogenesis and melanophore survival via autophagy in zebrafish (Danio rerio)

Zebrafish are an emerging model organism to study the syndromic albinism disorder, Hermansky–Pudlak syndrome (HPS), due to visible pigment development at 24 hours postfertilization, and conserved melanogenesis mechanisms. We describe crasher, a novel HPS type 10 (HPS10) zebrafish model, with a mutation in AP‐3 complex subunit delta gene, ap3d1. Exon 14 of ap3d1 is overexpressed in crasher mutants, while the expression of ap3d1 as a whole is reduced. ap3d1 knockout in *AB zebrafish recapitulates the mutant crasher phenotype. We show ap3d1 loss‐of‐function mutations cause significant expression changes in the melanogenesis genes, dopachrome tautomerase (dct) and tyrosinase‐related protein 1b (tyrp1b), but not tyrosinase (tyr). Last, Generally Applicable Gene‐set Enrichment (GAGE) analysis suggests autophagy pathway genes are upregulated together in crasher. Treatment with autophagy‐inhibitor, bafilomycin A1, significantly decreases melanophore number in crasher, suggesting ap3d1 promotes melanophore survival by limiting excessive autophagy. crasher is a valuable model to explore the regulation of melanogenesis gene expression and pigmentation disease.