Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of cadmium on osteoclast differentiation during bone injury in female mice

Cadmium (Cd) is a toxic heavy metal that represents an occupational hazard and environmental pollutant toxic heavy metal, which can cause osteoporosis following accumulation in the body. The purpose of this study was to investigate the effect of Cd on bone tissue osteoclast differentiation in vivo. Female BALB/c mice were randomly divided into three groups and given drinking water with various concentrations of Cd (0, 5, and 25 mg/L) for 16 weeks, after which the mice were sacrificed after collecting urine and blood. The level of Cd, calcium (Ca), phosphorus (P), trace elements, and some biochemical indicators were measured, and the bone was fixed in a 4% formaldehyde solution for histological observation. Bone marrow cells were isolated to determine the expression of osteoclast‐associated mRNA and proteins. Cd was increased in the blood, urine, and bone in response to Cd in drinking water in a dose‐dependent manner. The content of iron (Fe), manganese (Mn), and zinc (Zn) was significantly increased, whereas Ca and P were decreased in bone compared to the control group. Cd affected the histological structure of the bone, and induced the upregulation and downregulation of tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and estradiol in the serum, respectively. Cd had no significant effect on the alkaline phosphatase activity in the serum. The expression of osteoclast marker proteins, including TRACP, cathepsin K, matrix metalloprotein 9, and carbonic anhydrases were all increased in the Cd‐treated bone marrow cells. Cd significantly increased the expression of receptor activator of nuclear factor kappa B ligand (RANKL), but had lower effect on the expression of osteoprotegerin (OPG) in both bone marrow cells and bone tissue. Thus, Cd exposure destroyed the bone microstructure, promoted the formation of osteoclasts in the bone tissue, and accelerated bone resorption, in which the OPG/RANKL pathway may play an important role.
Injury Incidence and Workloads during congested Schedules in Football

This study compared injury incidence and training loads be tween single and multi-match weeks, and seasons with and without congested scheduling. Measures of internal (session-Rating of Perceived Exertion × duration for training/match and % maximal heart rate) and external load (total, low-, high-, and very high-intensity running distances) along with injury incidence rates were determined from 42 players over 3 seasons; including 1 without and 2 (season 2 and 3) with regular multi-match weeks. Within-player analyses compared 1 (n = 214) vs. 2-match (n = 86) weeks ( > 75min in matches), whilst team data was compared between seasons. Total injury rates were increased during multi-match weeks (p = 0.001), resulting from increased match and training injuries (50.3, 16.9/1000h). Between-season total injury rates were highest when congested scheduling was greatest in season 3 (27.3/1000h) and season 2 (22.7/1000h) vs. season 1 (14.1/ 1000h; p = 0.021). All external load measures were reduced in multi-match weeks (p < 0.05). Furthermore, all internal and external training loads were lowest in seasons with congestion (p < 0.05). In conclusion, increased injury rates in training and matches exist. Total loads remain comparable between single and multi-match weeks, though reduce in congested seasons. Whether injuries result from reduced recovery, increased match analyses showed a significant difference for total (IRR: 1.89 [95 % CI 1.4–11.2]; p < 0.05), match (IRR: 1.92 [95 % CI 1.4–11.2]; p < 0.05) and training injury risk (IRR: 1.72 [95 % CI 1.3–4.7]; p > 0.05) between seasons 2 and
First‐line R‐CVP versus R‐CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4

R‐CVP (cyclophosphamide, vincristine, prednisone) and R‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non‐Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression‐free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R‐CVP to R‐CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa‐associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R‐CVP or R‐CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m2 q 2 months for 12 cycles. Primary endpoint was event‐free survival (EFS). Two‐hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R‐CHOP: 127, R‐CVP: 123). Median age was 56 years (21–85), 44% were male, 90% were in stage III–IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R‐CHOP and R‐CVP groups (P = 0·218) respectively. After a median follow‐up of 67, 66, and 70 months, five‐year EFS was 61% vs. 56% (not significant), progression‐free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R‐CHOP vs. the R‐CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients. , in the R‐CHOP and the R‐CVP groups respectively. This multicentre randomized study with >five‐year follow‐up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R‐CVP or R‐CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R‐CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second‐line therapy.
Awakening the regenerative potential of the mammalian retina

ABSTRACT As with all glial cells, the major role of retinal Müller glia (MG) is to provide essential neuronal support. However, the MG of some non-mammalian species have the additional ability to generate new retinal neurons capable of sight restoration. Unfortunately, mammalian MG do not possess this ability. However, if we could understand the reasons why, we may be able to devise strategies to confer regenerative potential. The recent discovery that the Hippo signaling pathway acts as an intrinsic block to mammalian MG proliferation, along with reports of adeno-associated virus (AAV)-based MG reprogramming and functional photoreceptor differentiation, may indicate a watershed moment in the field of mammalian retinal regeneration. However, as researchers delve deeper into the cellular and molecular mechanisms, and further refine MG reprogramming strategies, we should recall past misinterpretations of data in this field and proceed with caution. Here, we provide a summary of these emerging data and a discussion of technical concerns specific to AAV-mediated reprogramming experiments that must be addressed in order for the field to move forward. Summary: This Spotlight discusses strategies that can be used to unlock the endogenous regenerative potential of the mammalian retina, highlighting potential technical pitfalls and important considerations.
A biomechanical comparison of different tying techniques of a double-stranded looped suture

Purpose: This study aims to assess the biomechanical performance of different tying techniques of a double-stranded looped suture (DSLS). Methods: Loop and knot security of DSLS tying techniques (nice knot (NK), modified nice knot (MNK), double-twist knot (DTK), and double-barrel knot (DBK)) were compared. The square knot of DSLS (SKD) and the square knot of single-stranded suture (SKS) had been used as references. Twenty-four loops of each configuration were created using No. 2 Fiberwire (Arthrex, Naples, Florida, USA) and tested with a material testing machine. Samples were loaded with 10 N preloads for loop security assessment. Knot security was subsequently evaluated. Twelve loops of each knot were loaded to failure. The rest were subjected to cyclic load testing and the elongation at the 50th and 1000th cycles were measured. Knot bulkiness was determined by measuring knot height before testing. Data were compared with analysis of variance and post hoc tests. Statistical significance was p < 0.05. Results: All knots showed no statistically significant difference in displacement with preload. The load-to-failure was highest in NK, followed by MNK, DTK, DBK, SKD, and SKS. The cyclic loading test at the 50th cycle and the 1000th cycle demonstrated that NK has significantly less displacement than the others except MNK. DTK provided a minimal average knot height followed by NK, SKS, DBK, MNK, and SKD. Conclusion: The different tying techniques in DSLS provided the similar loop security but different knot security and knot bulkiness. NK and MNK are biomechanically superior to the other knots, whereas DTK is the least bulky. The findings in the present study may help set the guide for the surgeons to select the tying technique of DSLS to best suit their requirement.
Bifenthrin Induces Fat Deposition by Improving Fatty Acid Uptake and Inhibiting Lipolysis in Mice.

Chemical residues in the environment are considered to be important factors that cause obesity. Bifenthrin is one of the pyrethroid pesticides and is widely used worldwide. However, its effect on adipose tissue is ill defined. Here, we administered bifenthrin/corn oil to adult C57BL/6 mice by gavage. After six weeks, the bifenthrin treatment significantly increased body weight (P = 0.015) and fat mass (P < 0.001). Then, we identified 246 differently expressed proteins by proteomic analysis and they highly involved in fatty acid uptake and lipid metabolism process. Interestingly, protein hormone-sensitive lipase (HSL) and adipose triacylglyceride lipase (ATGL) were down-regulated while lipoprotein lipase (LPL) is up-regulated after bifenthrin treatment. Similar effects in 3T3-L1 cells treated with bifenthrin validated the in vivo results. Thus, this study suggests that long-term exposure to low-dose bifenthrin induces fat deposition in mice by improving fatty acid uptake and inhibiting lipolysis, and it may cause obesity in human.
Quantitative Interpretation of Genetic Toxicity Dose‐Response Data for Risk Assessment and Regulatory Decision‐Making: Current Status and Emerging Priorities

The screen‐and‐bin approach for interpretation of genotoxicity data is predicated on three false assumptions: that genotoxicants are rare, that genotoxicity dose–response functions do not contain a low‐dose region mechanistically characterized by zero‐order kinetics, and that genotoxicity is not a bona fide toxicological endpoint. Consequently, there is a need to develop and implement quantitative methods to interpret genotoxicity dose–response data for risk assessment and regulatory decision‐making. Standardized methods to analyze dose–response data, and determine point‐of‐departure (PoD) metrics, have been established; the most robust PoD is the benchmark dose (BMD). However, there are no standards for regulatory interpretation of mutagenicity BMDs. Although 5–10% is often used as a critical effect size (CES) for BMD determination, values for genotoxicity endpoints have not been established. The use of BMDs to determine health‐based guidance values (HBGVs) requires assessment factors (AFs) to account for interspecies differences and variability in human sensitivity. Default AFs used for other endpoints may not be appropriate for interpretation of in vivo mutagenicity BMDs. Analyses of published dose–response data showing the effects of compensatory pathway deficiency indicate that AFs for sensitivity differences should be in the range of 2–20. Additional analyses indicate that the AF to compensate for short treatment durations should be in the range of 5–15. Future work should use available data to empirically determine endpoint‐specific CES values; similarly, to determine AF values for BMD adjustment. Future work should also evaluate the ability to use in vitro dose–response data for risk assessment, and the utility of probabilistic methods for determination of mutagenicity HBGVs. Environ. Mol. Mutagen. 61:66–83, 2020. © 2019 Her Majesty the Queen in Right of Canada
Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

ABSTRACT Pluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development is its expression restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation. This article has an associated First Person interview with the joint first authors of the paper. Summary: Nanog is a key factor for pluripotency, but we show that it has further roles during gastrulation by regulating lineage determinants such as Pou3f1.
Description and phylogeny of a new species of Liolaemus (Iguania: Liolaemidae) endemic to the south of the Plurinational State of Bolivia

The Liolaemus montanus group is a diverse group of lizards that ranges from central Peru to southwestern Mendoza, Argentina, including much of the Plurinational State of Bolivia (“Bolivia”) and Chile. The species of this group mainly inhabit high elevation areas with cold temperatures. In the last years, several species of this group have been described, mostly in Argentina and Chile. In Bolivia, there are at least thirteen valid species belonging to the L. montanus group. In this study, we describe a new species of the L. montanus group with a marked endemism in the Cordillera de Sama of the Tarija Department, Bolivia, and a combination of unique character states that allows its formal description as a new species. The phylogenetic relationships based on analysis of 159 morphological characters suggest that it belongs to the L. montanus group, and that it is closest to Liolaemus pulcherrimus, which is found allopatrically in a small area of the Jujuy Province, Argentina. The multivariate analyses of 66 morphological characters support the phylogenetic relationships. Statistical analyses of inter-species comparisons of morphological characters are not considered the only methods due to the non-independence of some characters states among species; thus, a phylogenetic analysis is recommended. The detailed revision of specimens of the L. montanus group held in the collections of Bolivia is filling major geographic gaps and improving our understanding of the phylogenetic and biogeographic relationships of this widely distributed group of South American lizards.
Evaluation of knowledge level related to obstructive sleep apnea syndrome

Objective: Our aim in this study is to evaluate the knowledge level of outpatients about obstructive sleep apnea syndrome (OSAS). Subjects and Methods: This cross-sectional analytical study included 1651 patients and patient relatives who applied to Konya Training and Research Hospital outpatient clinics. Sociodemographic data form and OSAS knowledge level questionnaire were applied to participants. SPSS 21 package program was used for the statistical analysis of the data. It was accepted that p value was <0.05. Results: The average knowledge score in the knowledge level questionnaire was 15.1 (3-33). 61% of the participants had never heard of OSAS before. Those who are married, those living in the city center and women have a higher level of knowledge. When age, education level and income level increased, the score of information also increased. Most of the participants' information source was the social media with 56.5% (n = 364) and least were health workers with 19.8% (n = 127). The knowledge level of people whose information sources were doctors, were significantly higher than other information sources such as nurses, friends, internet and television as. There was no significant difference between the other groups. Conclusion: In our study, it was concluded that the level of knowledge about OSAS in the society was not sufficient and that the society had to be informed about this disease which has serious complications and awareness should be established.
Emotional Responses to Stressors in Everyday Life Predict Long-Term Trajectories of Depressive Symptoms.

BACKGROUND Individuals' emotional responses to stressors in everyday life are associated with long-term physical and mental health. Among many possible risk factors, the stressor-related emotional responses may play an important role in future development of depressive symptoms. PURPOSE The current study examined how individuals' positive and negative emotional responses to everyday stressors predicted their subsequent changes in depressive symptoms over 18 months. METHODS Using an ecological momentary assessment approach, participants (n = 176) reported stressor exposure, positive affect (PA), and negative affect (NA) five times a day for 1 week (n = 5,483 observations) and provided longitudinal reports of depressive symptoms over the subsequent 18 months. A multivariate multilevel latent growth curve model was used to directly link the fluctuations in emotions in response to momentary stressors in everyday life with the long-term trajectory of depressive symptoms. RESULTS Adults who demonstrated a greater difference in stressor-related PA (i.e., relatively lower PA on stressor vs. nonstressor moments) reported larger increases in depressive symptoms over 18 months. Those with greater NA responses to everyday stressors (i.e., relatively higher NA on stressor vs. nonstressor moments), however, did not exhibit differential long-term changes in depressive symptoms. CONCLUSIONS Adults showed a pattern consistent with both PA and NA responses to stressors in everyday life, but only the stressor-related changes in PA (but not in NA) predicted the growth of depressive symptoms over time. These findings highlight the important-but often overlooked-role of positive emotional responses to everyday stressors in long-term mental health.
Crystal structures and calorimetry reveal catalytically relevant binding mode of coproporphyrin and coproheme in coproporphyrin ferrochelatase

Coproporphyrin ferrochelatases (CpfCs, EC 4.99.1.9 ) insert ferrous iron into coproporphyrin III yielding coproheme. CpfCs are utilized by prokaryotic, mainly monoderm (Gram‐positive) bacteria within the recently detected coproporphyrin‐dependent (CPD) heme biosynthesis pathway. Here, we present a comprehensive study on CpfC from Listeria monocytogenes (LmCpfC) including the first crystal structure of a coproheme‐bound CpfC. Comparison of crystal structures of apo‐LmCpfC and coproheme‐LmCpfC allowed identification of structural rearrangements and of amino acids involved in tetrapyrrole macrocycle and Fe2+ binding. Differential scanning calorimetry of apo‐, coproporphyrin III‐, and coproheme‐LmCpfC underline the pronounced noncovalent interaction of both coproporphyrin and coproheme with the protein (ΔTm = 11 °C compared to apo‐LmCpfC), which includes the propionates (p2, p4, p6, p7) and the amino acids Arg29, Arg45, Tyr46, Ser53, and Tyr124. Furthermore, the thermodynamics and kinetics of coproporphyrin III and coproheme binding to apo‐LmCpfC is presented as well as the kinetics of insertion of ferrous iron into coproporphyrin III‐LmCpfC that immediately leads to formation of ferric coproheme‐LmCpfC (kcat/KM = 4.7 × 105 m−1·s−1). We compare the crystal structure of coproheme‐LmCpfC with available structures of CpfCs with artificial tetrapyrrole macrocycles and discuss our data on substrate binding, iron insertion and substrate release in the context of the CPD heme biosynthesis pathway.
A Clinicoradiological and Functional Evaluation of Lapidus Surgery for Moderate to Severe Bunion Deformity Shows Excellent Stable Correction and High Long-Term Patient Satisfaction

Background. Lapidus surgery involving arthrodesis of the first metatarsocuneiform (MTC) joint is an effective procedure for the correction of moderate to severe hallux valgus. The aim of this study was to collect and analyze radiographic data from our institution and determine the extent of first metatarsal shortening associated with the Lapidus procedure. Materials and Methods. A total of 53 patients (54 feet) who underwent arthrodesis of the first MTC joint combined with modified McBride bunionectomy for correction of moderate to severe hallux valgus deformity, between 2010 and 2015 were included in this study. Complete radiographic evaluation and AOFAS (American Orthopaedic Foot and Ankle Surgery) scoring was available for 54 feet. The average preoperative hallux valgus angulation (HVA) was 32° and the average intermetatarsal angle (IMA) was 16°. Results. Excluding 2 patients with postoperative hallux varus the average postoperative HVA correction at last follow-up was 14°. Average postoperative IMA was 9°. Although there was minimal bone resection during preparation of the MTC joint, no significant shortening of the first metatarsal was observed with this procedure. The relative length of the first metatarsal to the second metatarsal changed only 1.3%. Nonunion of the first MTC joint occurred in 10.3%, but only 1 foot was symptomatic requiring revision. The average postoperative hallux AOFAS score was 80.8. In sum, 63% of patients were very satisfied, 27% satisfied with reservations, and 10% were dissatisfied. Conclusion. The Lapidus bunion procedure offers excellent stable correction of moderate to severe hallux valgus deformity with minimal shortening of the first metatarsal and thereby higher patient satisfaction. Levels of Evidence: Level IV: Retrospective case series