Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacterial Ligase D preternary-precatalytic complex performs efficient abasic sites processing at double strand breaks during nonhomologous end joining

Abstract Abasic (AP) sites, the most common DNA lesions are frequently associated with double strand breaks (DSBs) and can pose a block to the final ligation. In many prokaryotes, nonhomologous end joining (NHEJ) repair of DSBs relies on a two-component machinery constituted by the ring-shaped DNA-binding Ku that recruits the multicatalytic protein Ligase D (LigD) to the ends. By using its polymerization and ligase activities, LigD fills the gaps that arise after realignment of the ends and seals the resulting nicks. Here, we show the presence of a robust AP lyase activity in the polymerization domain of Bacillus subtilis LigD (BsuLigD) that cleaves AP sites preferentially when they are proximal to recessive 5′-ends. Such a reaction depends on both, metal ions and the formation of a Watson–Crick base pair between the incoming nucleotide and the templating one opposite the AP site. Only after processing the AP site, and in the presence of the Ku protein, BsuLigD catalyzes both, the in-trans addition of the nucleotide to the 3′-end of an incoming primer and the ligation of both ends. These results imply that formation of a preternary-precatalytic complex ensures the coupling of AP sites cleavage to the end-joining reaction by the bacterial LigD.
Effectiveness and safety of the switch from Remicade to CT-P13 in patients with inflammatory bowel disease.

AIMS To evaluate the clinical outcomes in patients with IBD after switching from Remicade to CT-P13 in comparison with patients who maintain Remicade . METHODS Patients under Remicade who were in clinical remission with standard dosage at study entry were included. The switch cohort (SC) comprised patients who made the switch from Remicade to CT-P13, and the "non-switch" cohort (NC) patients kept under Remicade . RESULTS Four hundred seventy-six patients were included: 199 (42%) in the SC and 277 (58%) in the NC. Median follow-up was 18 months in the SC and 23 months in the NC (p<0.01). Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR=3.5, 95%CI=2-6). Thirteen percent of patients had adverse events in the NC and 6% in the SC (p<0.05). CONCLUSIONS Switching from Remicade to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. Nocebo effect might have influenced this result. Switching from Remicade to CT-P13 was safe.
Comparison of the effect of advanced platelet-rich fibrin and leukocyte- and platelet-rich fibrin on outcomes after removal of impacted mandibular third molar: A randomized split-mouth study

Aim: In this study, it was aimed to investigate and compare the postoperative effects of leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) in terms of pain, swelling, and trismus after mandibular third molar surgery. Subjects and Methods: The study included a total of 27 patients with bilateral impacted mandibular third molar, which surgically operated at different times. Patients were evaluated in two randomly separated groups. For the first and second group, A-PRF and L-PRF were applied into the tooth socket, respectively. The outcome variables were pain, swelling, the number of analgesics taken, and trismus. These variables were also assessed based on first, second, third, and seventh days following the operation. Statistical Analysis Used: The data were collected and analyzed with unpaired Student's t-test and Mann–Whitney U test. Results: The study was conducted with 27 patients, consisting of 15 females and 12 males between ages of 18–26. The visual analog scale pain scores of the L-PRF group during first (P < 0.05), second, and third days and total values (P < 0.01); the number of analgesics on days 2 (P < 0.01) and 3; and their total values (P < 0.05) were significantly higher than the A-PRF group. There was no significant difference between swelling, trismus, and the duration of operation (P > 0.05). Conclusion: The results of this study showed that the use of A-PRF after mandibular third molar extraction significantly reduces postoperative pain and the patients need to take analgesics of A-PRF group compared to L-PRF group.
Hepatitis E: an underestimated emerging threat

Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.
Evaluation and path-coefficient analysis of some sugarcane clones under Upper Egypt region conditions

Evaluation of sugarcane clones is an important step to choose selection criteria for improvement of cane yield. This study was carried at Kom-Ombo Agric. Res., Station, Aswan governorate, ARC, Egypt to study the performance, phenotypic correlation and path-coefficient analysis of some sugarcane clones. Twenty four clones of sugarcane along with their parents and the check variety (G-T-54-9) were investigated in a Randomized Complete Block Design with three replicates for the two years; 2018/2019 and 2019/2020. In each season and over seasons, the differences were highly significant among clones for all the studied traits; stalk length, stalk diameter, cane yield, brix, sucrose, purity, sugar recovery and sugar yield. In addition, mean squares due to years and years × clones interactions were significant (p˂0.01) for all the studied traits, except brix. The combined mean demonstrated that the clone No. 281 produced the highest cane yield and sugar yield compared to the check variety (G-T-54-9). This clone is promising and could be take steps as new sugarcane clone for Upper Egypt based on cane yield and sugar yield. All studied traits were high in broad sense heritability except sucrose percent was moderate. Cane yield recorded positive correlation with stalk length, stalk diameter and sugar yield, and it was negative with the other traits under study. Path analysis exhibited that sugar yield and brix were the two important traits for cane yield improvement.
Kindness begins with yourself: The role of self-compassion in adolescent body satisfaction and eating pathology.

OBJECTIVE A wealth of evidence indicates that self-compassion is linked with positive psychological outcomes; however, little is known about the process through which self-compassion exerts its effect. The primary purpose of this research was to investigate the direct and indirect impact of self-compassion on body satisfaction and eating pathology in adolescents. METHOD Two hundred and thirty-eight students were recruited from three local high schools (Mage = 16.49, 43.7% boys). All participants completed the Self-Compassion Scale (SCS), Hopkins Symptom Checklist (SCL-5), Body Areas Satisfaction Scale (BASS), and Eating Disorder Examination Questionnaire - Adolescent Version (EDE-Q) at baseline. The SCL-5, BASS, and EDE-Q were completed 4 months later. RESULTS Self-compassion was positively associated with body satisfaction and negatively associated with psychological distress and eating pathology in boys and girls at both time points. Longitudinal conditional process analyses revealed that self-compassion predicted changes in body satisfaction and eating pathology through changes in psychological distress for girls only. Notably, self-compassion was higher in boys than in girls. DISCUSSION Results underscore how self-compassion may be an important factor to target in fostering a positive body image and preventing disordered eating in adolescents.
Lymphocyte Counts and Multiple Sclerosis Therapeutics: Between Mechanisms of Action and Treatment-Limiting Side Effects

Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common side effect of nearly every MS therapeutic agent is lymphopenia, which can be both beneficial and, in some cases, treatment-limiting. A sound knowledge of the underlying mechanism of action of the selected agent is required in order to understand treatment-associated changes in white blood cell counts, as well as monitoring consequences. This review is a comprehensive summary of the currently available DMTs with regard to their effects on lymphocyte count. In the first part, we describe important general information about the role of lymphocytes in the course of MS and the essentials of lymphopenic states. In the second part, we introduce the different DMTs according to their underlying mechanism of action, summarizing recommendations for lymphocyte monitoring and definitions of lymphocyte thresholds for different therapeutic regimens.
Designer Stem Cells: Genome Engineering and the Next Generation of Cell‐Based Therapies

Stem cells provide tremendous promise for the development of new therapeutic approaches for musculoskeletal conditions. In addition to their multipotency, certain types of stem cells exhibit immunomodulatory effects that can mitigate inflammation and enhance tissue repair. However, the translation of stem cell therapies to clinical practice has proven difficult due to challenges in intradonor and interdonor variability, engraftment, variability in recipient microenvironment and patient indications, and limited therapeutic biological activity. In this regard, the success of stem cell‐based therapies may benefit from cellular engineering approaches to enhance factors such as purification, homing and cell survival, trophic effects, or immunomodulatory signaling. By combining recent advances in gene editing, synthetic biology, and tissue engineering, the potential exists to create new classes of “designer” cells that have prescribed cell‐surface molecules and receptors as well as synthetic gene circuits that provide for autoregulated drug delivery or enhanced tissue repair. Published by Wiley Periodicals, Inc. J Orthop Res 37:1287–1293, 2019.
Novel Polymeric Thin-Film Composite Membranes for High-Temperature Gas Separations

Novel selective polymeric thin-film composite membranes (TFCMs) for applications at elevated temperatures were developed. Thin selective layers of the polyimides Matrimid 5218® and 6FDA-6FpDA were cast on a developed polybenzimidazole (PBI) porous support prepared by a phase inversion process. The TFCM properties were investigated with different gases in a wide temperature range, including temperatures up to 270 °C. The membranes showed very high thermal stability and performed well at the elevated temperatures. The development of highly thermally resistant polymeric membranes such as these TFCMs opens opportunities for application in high-temperature integrated processes, such as catalytic membrane reactors for the water-gas shift reaction in order to maximize H2 yield.
The myth of LGBTQ mobilities: framing the lives of gender- and sexually diverse Australians between regional and urban contexts

Abstract Gender- and sexually diverse youth are often represented in popular discourses through concepts of movement and mobility. Conceptual stories of LGBTQ youth transitions to adulthood in particular are marked by narratives of movement from regional (rural and/or small towns) to major urban areas. Although not wholly outside lived experience, a cultural myth that portrays the experience of gender- and sexually diverse young people entering into ‘adulthood’ via such mobility continues to circulate in scholarship, popular media, personal accounts of coming out, support resources and self-help guidance documents. This paper draws on a recent study of gender and sexual diversity, support and belonging to examine instances of LGBTQ youth mobility in relation to participant interviews and focus groups undertaken in an Australian project examining two generations of sexually diverse subjects’ views on growing up, support and belonging. Participants differed generationally in how they experienced mobility from regional to urban settings, demonstrating that contemporary real-world accounts of such mobility are complex, nuanced and diverse and that the felt ‘expectation’ that one should migrate to a city in order to live a full gender- or sexually diverse life has waned among young people in the more recent generation.
Catabolic activity of osteoblast lineage cells contributes to osteoclastic bone resorption in vitro

ABSTRACT Osteoblast lineage cells in human bone were recently shown to colonize eroded bone surfaces and to closely interact with osteoclasts. They proved to be identical to reversal cells and are believed to differentiate into bone-forming osteoblasts thereby coupling resorption and formation. However, they also exert catabolic activity that contributes to osteoclastic bone resorption, but this has not received much attention. Herein, we used co-cultures of primary human osteoblast lineage cells and human osteoclasts derived from peripheral blood monocytes to investigate whether a catabolic activity of osteoblast lineage cells could impact on osteoclastic bone resorption. Through a combination of immunofluorescence, in situ hybridization and time-lapse experiments, we show that MMP-13-expressing osteoblast lineage cells are attracted to and closely interact with bone-resorbing osteoclasts. This close interaction results in a strong and significant increase in the bone resorptive activity of osteoclasts – especially those making trenches. Importantly, we show that osteoclastic bone resorption becomes sensitive to inhibition of matrix metalloproteinases in the presence, but not in the absence, of osteoblast lineage cells. We propose that this may be due to the direct action of osteoblast-lineage-derived MMP-13 on bone resorption. Summary: Osteoblast lineage cells directly stimulate osteoclastic bone resorption and promote the aggressive trench-resorption mode by exerting a matrix metalloproteinase-dependent catabolic activity.
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion

Significance The vesicular membrane protein synaptobrevin-2 (syb-2) plays an important role in vesicular membrane fusion at the neuronal synapse by participating in the dynamic formation of the SNARE complex. Here, by a combination of solution-state NMR and fluorescence spectroscopy, we find that syb-2 in its prefusion form, before forming the SNARE complex, shows high internal flexibility, characteristic for an intrinsically disordered protein (IDP). But it also reveals an increasing rigidity from the N to C terminus that correlates with an observed increase in lipid binding affinity as well as the known increased rate for C-terminal compared with N-terminal SNARE zippering. This provides a mechanistic perspective on how an IDP and its lipid interactions can lower the energy barrier for membrane fusion. Intrinsically disordered proteins (IDPs) and their conformational transitions play an important role in neurotransmitter release at the neuronal synapse. Here, the SNARE proteins are essential by forming the SNARE complex that drives vesicular membrane fusion. While it is widely accepted that the SNARE proteins are intrinsically disordered in their monomeric prefusion form, important mechanistic aspects of this prefusion conformation and its lipid interactions, before forming the SNARE complex, are not fully understood at the molecular level and remain controversial. Here, by a combination of NMR and fluorescence spectroscopy methods, we find that vesicular synaptobrevin-2 (syb-2) in its monomeric prefusion conformation shows high flexibility, characteristic for an IDP, but also a high dynamic range and increasing rigidity from the N to C terminus. The gradual increase in rigidity correlates with an increase in lipid binding affinity from the N to C terminus. It could also explain the increased rate for C-terminal SNARE zippering, known to be faster than N-terminal SNARE zippering. Also, the syb-2 SNARE motif and, in particular, the linker domain show transient and weak membrane binding, characterized by a high off-rate and low (millimolar) affinity. The transient membrane binding of syb-2 may compensate for the repulsive forces between the two membranes and/or the SNARE motifs and the membranes, helping to destabilize the hydrophilic-hydrophobic boundary in the bilayer. Therefore, we propose that optimum flexibility and membrane binding of syb-2 regulate SNARE assembly and minimize repulsive forces during membrane fusion.
Treatment of Wide-Neck Intracranial Aneurysms with the Woven EndoBridge Device Associated with Stenting: A Single-Center Experience

BACKGROUND AND PURPOSE: The intrasaccular flow disruptor, the Woven EndoBridge device, is increasingly used for the treatment of wide-neck intracranial aneurysms. Due to unfavorable anatomy, additional stent placement is sometimes required to avoid Woven EndoBridge protrusion into bifurcation branches. We report our experience with the Woven EndoBridge associated with stent placement for the treatment of complex intracranial aneurysms. MATERIALS AND METHODS: Patients with aneurysms treated with the Woven EndoBridge Single-Layer plus stent placement were evaluated retrospectively with prospectively maintained data. The technical feasibility, procedural complications, aneurysm occlusion, and clinical outcome were studied. RESULTS: Seventeen patients and aneurysms treated with the Woven EndoBridge plus stent placement were included. The mean aneurysm size was 7 ± 3.1 mm. Aneurysm locations were the following: MCA (10 patients), anterior communicating artery (3 patients), basilar tip (3 patients), and posterior communicating artery (1 patient). Two lesions were ruptured and treated in the acute phase. The Woven EndoBridge and stent placement were successfully delivered in all cases. There were no permanent/major complications. Among the 2 patients with SAH, minor and completely reversible in-stent thrombosis occurred during treatment. An asymptomatic occlusion of the angular artery with a distal nonbifurcation aneurysm was discovered during the angiographic follow-up. Long-term (10.4 months) angiographic complete (Raymond-Roy I) and near-complete (Raymond-Roy II) occlusion was obtained in 11 (69%) and 2 (12.5%) aneurysms, respectively. The mean sizes of aneurysms showing Raymond-Roy I/Raymond-Roy II and Raymond-Roy III occlusion were 5.5 ± 2.1 mm and 10 ± 1 mm, respectively (P = .003). The mean fluoroscopy time was 35 ± 14 minutes. CONCLUSIONS: Aneurysm embolization with the Woven EndoBridge device associated with stent placement appears technically feasible and effective for the treatment of lesions with unfavorable anatomy. In our study, this strategy was relatively safe with a low rate of relevant procedure-related adverse events.
Factors Associated with Free Medicine Use in Patients with Hypertension and Diabetes: A 4-Year Longitudinal Study on Full Coverage Policy for Essential Medicines in Taizhou, China

Full coverage policies for medicines have been implemented worldwide to alleviate medicine cost burden and promote access to medicines. However, few studies have explored the factors associated with free medicine use in patients with chronic diseases. This study aimed to analyze the utilization of free medicines by patients with hypertension and diabetes after the implementation of the full coverage policy for essential medicines (FCPEM) in Taizhou, China, and to explore the factors associated with free medicine use. We conducted a descriptive analysis of characteristics of patients with and without free medicine use and performed a panel logit model to examine factors associated with free medicine use, based on an electronic health record database in Taizhou from the baseline year (12 months in priori) to three years after FCPEM implementation. After FCPEM implementation, the proportion of patients without any free medicine use decreased from 31.1% in the baseline year to 28.9% in the third year, while that of patients taking free medicines rose from 11.0% to 22.8%. Patients with lower income or education level, those with agricultural hukou, patients aged 65 and above, married patients, and patients in the Huangyan district were more likely to take free medicines. In conclusion, FCPEM contributed to improved medicine access, especially in vulnerable populations. Local policy makers should consider expanding the coverage of FCPEM to other types of medicines and cultivate the potential of social supports for patients to enhance the effectiveness of FCPEM policies.