bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRX3 and IRX5 Inhibit Adipogenic Differentiation of Hypertrophic Chondrocytes and Promote Osteogenesis
Authors: Tan Zhijia , Kong Mingpeng , Wen Songjia , Tsang Kwok Yeung , Niu Ben , Hartmann Christine , Chan Danny , Hui Chi-chung , Cheah Kathryn S.E. 
Published: July 2020

ABSTRACTMaintaining the correct proportions of different cell types in the bone marrow is critical for bone function. Hypertrophic chondrocytes (HCs) and osteoblasts are a lineage continuum with a minor contribution to adipocytes, but the regulatory network is unclear. Mutations in transcription factors, IRX3 and IRX5, result in skeletal patterning defects in humans and mice. We found coexpression of Irx3 and Irx5 in late-stage HCs and osteoblasts in cortical and trabecular bone. Irx3 and Irx5 null mutants display severe bone deficiency in newborn and adult stages. Quantitative analyses of bone with different combinations of functional alleles of Irx3 and Irx5 suggest these two factors function in a dosage-dependent manner. In Irx3 and Irx5 nulls, the amount of bone marrow adipocytes was increased. In Irx5 nulls, lineage tracing revealed that removal of Irx3 specifically in HCs exacerbated reduction of HC-derived osteoblasts and increased the frequency of HC-derived marrow adipocytes. β-catenin loss of function and gain of function specifically in HCs affects the expression of Irx3 and Irx5, suggesting IRX3 and IRX5 function downstream of WNT signaling. Our study shows that IRX3 and IRX5 regulate fate decisions in the transition of HCs to osteoblasts and to marrow adipocytes, implicating their potential roles in human skeletal homeostasis and disorders.AbstractFate decision of hypertrophic chondrocyte is controlled by Irx3 and Irx5. With normal expression of Irx3 and Irx5, hypertrophic chondrocytes preferentially differentiate into Col1a1+ osteoblasts, and few are differentiated into Perilipin+ adipocytes. Upon deletion of Irx3 and Irx5, osteogenesis of hypertrophic chondrocyte is inhibited and adipogenesis is promoted, which causes repaired bone formation and increased bone marrow adipose tissue amount. © 2020 American Society for Bone and Mineral Research.
Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative
Authors: Hayes Kaleen N , Giannakeas Vasily , Wong Andy Kin On 
Published: July 2020

ABSTRACT
Antiresorptive medications have been explored for treating knee osteoarthritis (OA); however, little data exist on the effects of today's more potent nitrogen-containing oral bisphosphonates on radiographic disease-progression in patients with varying disease-severity, especially those who are not overweight. The primary objective of this cohort study was to determine if the use of bisphosphonates is protective against 2-year radiographic-progression of knee OA in Osteoarthritis Initiative (OAI) participants, stratified by baseline radiographic disease status. Secondary objectives were to examine effects in non-overweight participants (body mass index [BMI] &lt; 25 kg/m2) and cumulative bisphosphonate exposure effects. We identified female OAI participants aged ≥50 years and excluded those missing baseline radiograph readings, bisphosphonate use information, or all clinical questionnaire information at baseline. Participants reporting bisphosphonate use (69% alendronate) were propensity-matched 1:1 to non–bisphosphonate users and followed until first radiographic knee OA progression (1-unit increase in Kellgren and Lawrence [KL] grade) or data were censored (first missed visit or end of 2-year follow-up). Discrete-time logistic regression models estimated hazard ratios (HRs) between bisphosphonate users versus nonusers, with an interaction term for baseline KL grade (KL &lt;2 or KL ≥2). We identified 1977 eligible women (n = 346 bisphosphonate users). Propensity-matched results indicated that bisphosphonate users with KL grade &lt;2 were protected against progression (HRKL&lt;2 0.53; 95% CI, 0.35 to 0.79), while bisphosphonate use was not associated with radiographic progression in those with KL grade ≥2 (HRKL≥2 1.06; 95% CI, 0.83 to 1.35). When restricting analyses to those with BMI &lt;25 kg/m2, effects were strengthened (HRKL&lt;2 0.49 [95% CI, 0.26 to 0.92]; HRKL≥2 0.69 [95% CI, 0.33 to 1.26]). Duration of bisphosphonate use had no effect on progression, though sample size was limited. Bisphosphonate therapy may be protective against radiographic knee OA progression in early-stage patients, particularly those who are non-overweight, but less so for those with more advanced disease or more weight-bearing joint stress. © 2020 American Society for Bone and Mineral Research (ASBMR).
Alpha‐lipoic acid prevents brain injury in rats administered with valproic acid
Authors: Turkyilmaz Ismet Burcu , Bilgin Sokmen Bahar , Yanardag Refiye 
Published: July 2020

AbstractValproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures. Nonetheless, VPA has many life‐threatening side effects associated with free radical production. Alpha‐lipoic acid (ALA) is a powerful antioxidant, which can scavenge reactive oxygen species (ROS). The effects of ALA against VPA‐stimulated brain injury were investigated. In this study, Sprague‐Dawley rats were divided as four groups: Group I, control rats; Group II, ALA‐administered rats (50 mg/kg/d); Group III, VPA‐administered rats (0.5 g/kg/d); Group IV: VPA‐ and ALA‐administered rats at the same dose and time. According to the results, VPA increased lipid peroxidation, protein carbonyl, advanced oxidation protein products, total oxidant status, nitric oxide levels and glutathione‐S‐transferase, adenosine deaminase, xanthine oxidase activities, decreased glutathione, total antioxidant capacity levels, catalase, superoxide dismutase, glutathione peroxidase, sodium‐potassium ATPase, and paraoxonase activities. Treatment with ALA reversed these effects. In conclusion, we may suggest that ALA may be a good candidate for prevention of VPA‐induced brain injury.
How much therapy is enough? The dose–response effect and its moderators in a psychology training clinic
Authors: Chen Belinda , Keenan‐Miller Danielle 
Published: July 2020

AbstractObjectiveThe current study aims to sharpen the understanding of the psychotherapy dose–response effect and its moderators in a psychology training clinic.MethodData were extracted from 58 client records. Weekly Patient Health Questionnaire‐9 and Generalized Anxiety Disorder‐7, as well as Outcomes Questionnaire‐45.2, administered every fifth session, assessed whether clients achieved reliable change (RC) and clinically significant and reliable change (CSR) during treatment. Survival analyses were conducted to determine the sessions required for 50% of the sample to achieve these outcomes. Multilevel Cox frailty regressions were used to investigate client‐and‐therapy‐based moderators.ResultsThe median time for 50% of the sample to achieve RC was 8–10 sessions and 11 sessions to achieve initial CSR. Past treatment history was a significant moderator of time to achieve RC.ConclusionsFrom a population perspective, psychotherapy is most beneficial to patients early in treatment. Sharper understanding of the number of sessions required to achieve meaningful change can inform practice in training settings.
Psychometric properties of the Italian version of the Interpersonal Needs Questionnaire‐15 (INQ‐15‐I)
Authors: Iliceto Paolo , D'Antuono Laura , Fino Emanuele , Carcione Antonino , Candilera Gabriella , Silva Caroline , Joiner Thomas E. 
Published: July 2020

AbstractObjective:The Interpersonal Needs Questionnaire (INQ‐15) is a self‐report measure of thwarted belongingness and perceived burdensomeness, two constructs associated with suicidal ideation. The objective of the current study was to translate the INQ‐15 from English to Italian (INQ‐15‐I) and to test its factor structure, reliability, and validity in Italian samples.Method:We examined (a) whether the components of the hypothesized two‐factor measurement model are invariant across a community sample (N = 510) and a clinical sample (N = 259); (b) the relations between the INQ‐15‐I factors and measures of depression (Beck Depression Inventory‐II), hopelessness (Beck Hopelessness Scale), and suicidal ideation (Beck Scale for Suicide Ideation); (c) the reliability and psychometric properties of the INQ‐15‐I.Results:Results from multigroup confirmatory factor analyses supported the adequacy of the two‐factor model to represent thwarted belongingness and perceived burdensomeness. The model is invariant across community and clinical groups, showing excellent fit. The two INQ‐15‐I scales measure highly intercorrelated constructs. Both significantly correlate with depression, hopelessness, and suicidal ideation, and correlations are high in the clinical sample.Conclusion:The INQ‐15‐I is a valid and reliable measure of thwarted belongingness and perceived burdensomeness. Implications for research, assessment, and intervention in suicidal ideation are discussed.
Characteristics of nonsuicidal self‐injury among veterans
Authors: Lear Mary K. , Penzenik Molly E. , Forster Jeri E. , Starosta Amy , Brenner Lisa A. , Nazem Sarra 
Published: July 2020

AbstractObjectiveThe current study aimed to (a) assess basic nonsuicidal self‐injury (NSSI) characteristics using a validated clinical interview among a sample of veterans not recruited for specific diagnostic or environmental criteria and (b) examine the relation between NSSI and medical severity of prior suicide attempts (SAs) among veterans.DesignWe conducted secondary data analyses among a combined sample of veterans (N = 165) from two parent studies conducted at a large VA Medical Center that implemented identical recruitment protocols. No psychiatric criteria were utilized for inclusion or exclusion purposes.ResultsApproximately 16% of participants reported NSSI history and almost 21% reported SA history. NSSI history was associated with probability of prior SA but not the medical severity of prior SA.ConclusionsNSSI is a prevalent concern among veterans and is associated with probability of SA. It remains unclear whether prior NSSI is associated with more medically serious SA in this population.
FoxO1a mediated cadmium‐induced annulus fibrosus cells apoptosis contributes to intervertebral disc degeneration in smoking
Authors: Jing Doudou , Wu Wei , Deng Xiangyu , Peng Yizhong , Yang Wenbo , Huang Donghua , Shao Zengwu , Zheng Dong 
Published: July 2020

AbstractCadmium (Cd), a type of heavy metal that accumulates in the body because of smoking, mediates the toxic effect of smoking in many diseases, such as cardiovascular disease, osteoarthritis, and osteoporosis. However, the toxic effect of Cd on intervertebral disc tissues have not been reported. In the current study, we demonstrated that Cd induced the apoptosis of annulus fibrosus (AF) cells, which contributed to intervertebral disc degeneration (IVDD). Specifically, Cd induced the nuclear translocation of FoxO1a, which drives AF cells apoptosis through mitochondrial‐related pathway. Phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) signal pathway is also involved in this process. The combined use of LY29002, an inhibitor of PI3K, and small interfering RNA‐targeting FoxO1a confirmed the relationship between the PI3K/AKT signal pathway and FoxO1a. In summary, present research explores the mechanism behind the contribution of smoking to IVDD and finds a new feasible target for preventing IVDD in smoking.
Vitamin C alleviates the senescence of periodontal ligament stem cells through inhibition of Notch3 during long‐term culture
Authors: Yang Yan , Wang Tao , Zhang Sicheng , Jia Sixun , Chen Hong , Duan Yufeng , Wang Shikai , Chen Guoqing , Tian Weidong 
Published: July 2020

AbstractPeriodontal ligament stem cells (PDLSCs), as potential “seed cells” for periodontal tissue repair and regeneration, require to be expanded in vitro for a large scale. Senescence of PDLSCs occurred during long‐term culture may compromise the therapeutic effects of PDLSCs. Medium supplements may be useful in antisenescence. However, the effects and mechanisms of vitamin C (Vc) treatment on PDLSCs during long‐term culture are still unclear. In this study, we identified that Vc‐treated PDLSCs cells maintained a slender morphology, higher growth rate and migration capacity, stemness, and osteogenic differentiation capability during a long‐term culture. Moreover, we also identified that Notch3 was significantly upregulated during the cell senescence, and Vc treatment alleviated the senescence of PDLSCs through inhibition of Notch3 during long‐term culture. In summary, Vc treatment suppressed PDLSCs senescence by reducing the expression of Notch3 and might be a simple and useful strategy to inhibit cellular senescence during the cell long‐term culture.
Filamentous nestin and nonmuscle myosin IIB are associated with a migratory phenotype in neonatal rat cardiomyocytes
Authors: Bergeron Alexandre , Brezai Andra , Shukr Rami , Villeneuve Louis , Allen Bruce G. , Qureshi Wasay M. S. , Hentges Kathryn E. , Calderone Angelino 
Published: July 2020

AbstractCardiomyocyte migration represents a requisite event of cardiogenesis and the regenerative response of the injured adult zebrafish and neonatal rodent heart. The present study tested the hypothesis that the appearance of the intermediate filament protein nestin in neonatal rat ventricular cardiomyocytes (NNVMs) was associated in part with the acquisition of a migratory phenotype. The cotreatment of NNVMs with phorbol 12,13‐dibutyrate (PDBu) and the p38α/β mitogen‐activated protein kinase inhibitor SB203580 led to the de novo synthesis of nestin. The intermediate filament protein was subsequently reorganized into a filamentous pattern and redistributed to the leading edge of elongated membrane protrusions translating to significant lengthening of NNVMs. PDBu/SB203580 treatment concomitantly promoted the reorganization of nonmuscle myosin IIB (NMIIB) located predominantly at the periphery of the plasma membrane of NNVMs to a filamentous phenotype extending to the leading edge of elongated membrane protrusions. Coimmunoprecipitation assay revealed a physical interaction between NMIIB and nestin after PDBu/SB203580 treatment of NNVMs. In wild‐type and heterozygous NMIIB embryonic hearts at E11.5–E14.5 days, nestin immunoreactivity was identified in a subpopulation of cardiomyocytes elongating perpendicular to the compact myocardium, at the leading edge of nascent trabeculae and during thickening of the compact myocardium. In mutant embryonic hearts lacking NMIIB protein expression, trabeculae formation was reduced, the compact myocardium significantly thinner and nestin immunoreactivity undetectable in cardiomyocytes at E14.5 days. These data suggest that NMIIB and nestin may act in a coordinated fashion to facilitate the acquisition of a migratory phenotype in neonatal and embryonic cardiomyocytes.
Enhanced protection against lipopolysaccharide‐induced acute lung injury by autologous transplantation of adipose‐derived stromal cells combined with low tidal volume ventilation in rats
Authors: Liang Zuodi , Yin Xiuru , Sun Wenchong , Zhang Shuo , Chen Xiaohuan , Pei Ling , Zhao Ning 
Published: July 2020

AbstractAdipose‐derived stromal cells (ADSCs) showed excellent capacity in regeneration and tissue protection. Low tidal volume ventilation (LVT) strategy demonstrates a therapeutic benefit on the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study, therefore, aimed to undertaken determine whether the combined LVT and ADSCs treatment exerts additional protection against lipopolysaccharide (LPS)‐induced ALI in rats. The animals were randomized into seven groups: Group I (control), Group II (instillation of LPS at 10 mg/kg intratracheally), Group III (LPS+LVT 6 ml/kg), Group IV (LPS+intravenous autologous 5 × 106 ADSCs which were pretreated with a scrambled small interfering RNA [siRNA] of keratinocyte growth factor [KGF] negative control), Group V (LPS+ADSCs which were pretreated with a scrambled siRNA of KGF, Group VI (LPS+LVT and ADSCs as in the Group IV), and Group VII (LPS+LVT and ADSCs as in the Group V). We found that levels of tumor necrosis factor‐α, transforming growth factor‐β1, and interleukin (IL)‐1β and IL‐6, the proinflammatory cytokines, were remarkably increased in LPS rats. Moreover, the expressions of ENaC, activity of Na, K‐ATPase, and alveolar fluid clearance (AFC) were obviously reduced by LPS‐induced ALI. The rats treated by ADSCs showed improved effects in all these changes of ALI and further enhanced by ADSCs combined with LVT treatment. Importantly, the treatment of ADSCs with siRNA‐mediated knockdown of KGF partially eliminated the therapeutic effects. In conclusion, combined treatment with ADSCs and LVT not only is superior to either ADSCs or LVT therapy alone in the prevention of ALI. Evidence of the beneficial effect may be partly due to improving AFC by paracrine or systemic production of KGF and anti‐inflammatory properties.
Numbers and Units Affect Goal Pursuit Organization and Motivation
Authors: Lembregts Christophe , Pena‐Marin Jorge 
Published: July 2020

Goals are one of the most ubiquitous drivers of behavior. Despite the wealth of research on goal pursuit, less is known about how individuals organize their goal pursuit in the first place. This manuscript represents one of the first studies to provide insight into quantitative goal organization, proposing that the unit/numerical value in which a goal is described influences goal pursuit organization. Specifying a superordinate goal in units with larger numbers (e.g., studying for an examination for 120 min per week), rather than with smaller numbers (2 hr per week), leads to a goal pursuit structure that consists of more, but smaller subgoals. We also find that units with larger compared to smaller numbers tend to have a positive effect on goal motivation (i.e., more likely to start the goal earlier and to finish it). Finally, this positive effect on goal motivation is attenuated when consumers focus is on the number of subgoals left (rather than completed) while pursuing the overarching goal. We believe that changing units may be an easy‐to‐implement nudge for anyone (e.g., marketers, managers, public policymakers, behavioral therapists) who wants to increase the likelihood that individuals use a particular goal pursuit structure.
Predictive values of blood urea nitrogen/creatinine ratio and other routine blood parameters on disease severity and survival of COVID‐19 patients
Authors: Ok Fesih , Erdogan Omer , Durmus Emrullah , Carkci Serkan , Canik Aggul 
Published: July 2020

AbstractWe aimed to examine independent predictive factors for the severity and survival of COVID‐19 disease, from routine blood parameters, especially the blood urea nitrogen (BUN)/creatinine (Cr) ratio. A total of 139 patients with COVID‐19 were investigated at Siirt State Hospital. According to the disease severity, the patients were categorized as three groups (moderate: 85, severe: 54, and critical: 20). Then, patients were divided into two groups: nonsevere (moderate) and severe (severe and critical). Demographic, clinical data, and routine blood parameters were analyzed. In multivariate model adjusted for potential confounders BUN/Cr ratio (odds ratio [OR] = 1.70; 95% confidence interval [CI]: 1.20‐2.40; P = .002) and neutrophil to lymphocyte ratio (NLR) (OR = 2.21; 95% CI: 1.20‐4.30; P < .001) were independent predictive factors for disease severity. In multivariate Cox proportional hazard model BUN/Cr ratio (hazard ratio [HR] = 1.02; 95% CI: 1.01‐1.05; P = .030), and NLR (HR = 1.17; 95% CI: 1.06‐1.30; P = .020) were independent predictors for survival of COVID‐19 disease. The optimal thresholds of the BUN/Cr ratio at 33.5 and 51.7 had the superior possibility for severe disease and mortality, area under the curve (AUC) were 0.98 and 0.95, respectively. The optimal thresholds of NLR at 3.27 and 5.72 had a superior possibility for severe disease and mortality, AUC were 0.87 and 0.85, respectively. BUN/Cr and NLR are independent predictors for COVID‐19 patient severity and survival. Routine evaluation of BUN/Cr and NLR can help identify high‐risk cases with COVID‐19.
Type 2 Diabetes Metabolic Improvement After Roux‐en‐Y Gastric Bypass May Include a Compensatory Mechanism That Balances Fatty Acid β and ω Oxidation
Authors: Mendonça Machado Natasha , Torrinhas Raquel Susana , Sala Priscila , Ishida Robson Kiyoshi , Guarda Ismael Francisco Mota Siqueira , Moura Eduardo Guimarães Hourneaux de , Sakai Paulo , Santo Marco Aurélio , Linetzky Waitzberg Dan 
Published: July 2020

AbstractBackgroundMore than half of patients who undergo Roux‐en‐Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal (GI) metabolic mechanisms of this improvement are still elusive.MethodsPaired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18), and ileum (n = 18), collected by double‐balloon enteroscopy.ResultsAfter RYGB, improvements in body composition and weight‐related and glucose homeostasis parameters were observed. Plasma‐enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid (TCA) cycles, gluconeogenesis, malate‐aspartate shuttle, and carnitine synthesis. In GI tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the TCA cycle were enriched, particularly in plasma, jejunum, and ileum. Fluctuations of dicarboxylic acids (DCAs) were relevant in several metabolomic tests, and metabolite alterations included aminomalonate and fumaric, malic, oxalic, and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism.ConclusionsRYGB was associated with systemic and GI metabolic reprogramming. DCA alterations link ω and β fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement.
Bone sarcoma surgery in times of COVID‐19 pandemic lockdown‐early experience from a tertiary centre in India
Authors: Kumar Venkatesan Sampath , Banjara Roshan , Thapa Sushma , Majeed Abdul , Kapoor Love , Janardhanan Ritvik , Bakhshi Sameer , Kumar Vijay , Malhotra Rajesh , Khan Shah Alam 
Published: July 2020

AbstractBackground and ObjectivesCoronavirus disease 2019 (COVID‐19) lockdown has presented a unique challenge for sarcoma care. The purpose of this study is to evaluate the early results and feasibility of surgeries for bone sarcomas during the COVID‐19 lockdown.MethodsOur prospectively collected orthopaedic oncological database was reviewed to include two groups of patients‐ those who underwent surgery in the immediate 4 weeks before lockdown (non‐lockdown group) and those operated in the first 4 weeks of lockdown (lockdown group). All patients were followed‐up clinically and telephonically to collect the outcome data.ResultsOut of the 91 patients who qualified for inclusion, fifty were classified into the non‐lockdown group while 41 patients formed the lockdown group. Both the groups were comparable with respect to baseline demographic parameters. However, during the lockdown period 37 patients (90%) had undergone a major surgical intervention as against 24 patients (48%) in the non‐lockdown group (P < .001). There was no significant difference in type of anaesthesia, median estimated blood loss and procedure duration. None of the patients/health care workers had evidence of severe acute respiratory syndrome‐coronavirus 2 infection at 15 days follow‐up.ConclusionOur study results suggest that appendicular bone tumours can be safely operated with adequate precautions during the lockdown period.