bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the Prognosis of Osgood-Schlatter Poorer Than Anticipated? A Prospective Cohort Study With 24-Month Follow-up
Authors: Holden Sinead , Olesen Jens Lykkegaard , Winiarski Lukasz M. , Krommes Kasper , Thorborg Kristian , Hölmich Per , Rathleff Michael Skovdal 
Published: August 2021

Background: Osgood-Schlatter disease (OSD), an apophyseal injury of the tibial tuberosity, affects up to 1 in 10 adolescents. This condition has previously been assumed to be innocuous and to self-resolve with limited intervention. Purpose: To investigate the 24-month prognosis of OSD and examine if ultrasound (US) classification is associated with outcomes. Study Design: Case series; Level of evidence, 4. Methods: This study included a preregistered prospective cohort of 51 adolescents (aged 10-14 years) diagnosed with OSD who were evaluated for 24 months. The primary outcome at 24-month follow-up was whether participants continued to experience OSD-related knee pain. Baseline US scans were collected and characterized by OSD type (De Flaviis classification) as well as maturation of the tibial tuberosity. Secondary outcomes included sports participation, Knee injury and Osteoarthritis Outcome Score (KOOS) Sport/Recreation subscale, and health-related quality of life (European Quality of Life–5 Dimensions–Youth [EQ-5D-Y]). All participants were invited for re-examination by US at follow-up. Results: A total of 51 patients preregistered for the study, with 90% (n = 46) available at follow-up. Of these 46 participants, 37% (n = 17) still reported knee pain due to OSD. In this subgroup, the median duration since symptom onset was 42 months (interquartile range, 38-51 months). More than 1 in 5 participants reported stopping sport due to knee pain, and those who continued to experience knee pain reported significantly worse KOOS Sport/Recreation scores at follow-up compared with patients with no knee pain (mean 74 [95% CI, 63-84] vs 91 [95% CI, 85-97]). Participants with continued OSD-related pain also had lower health-related quality of life (mean difference in EQ-5D-Y, 0.11 [95% CI, 0.06-0.13]). Higher De Flaviis classification at baseline was significantly associated with an increased risk of knee pain at 2 years. Diagnostic US at follow-up demonstrated primarily tendon changes (thickening, positive Doppler signal), as well as an ununited ossicle in 32% of participants who underwent US scanning at follow-up. Conclusion: Over one-third of the study participants had knee pain at 2-year follow-up, which was associated with lower sports related function and health related quality of life. This questions the assumption that all patients with OSD experience quick recovery. Participants without any changes on imaging at baseline were less likely to report pain at follow-up.
Dutch Mental Health Patients’ and Significant Others’ Perspectives on Compulsory Treatment at Home: One Size Does Not Fit All
Authors: de Waardt DA , Meijnckens D , Wierdsma AI , Widdershoven GAM , Mulder CL 
Published: August 2021

On January 1, 2020, the Compulsory Mental Health Care Act took effect in the Netherlands. It contains provisions for compulsory community treatment (CCT) and compulsory treatment at home (CTH). In this study, we collected the opinions of patients and their significant others on CTH and on their preferences regarding compulsory care in their homes. Patients and their significant others were involved in the experience-based co-design of a purpose-built online questionnaire. This questionnaire was completed by 624 patients and 531 significant others. Sixty-one percent of the patients and 62% of the significant others did not want compulsory treatment to take place at home but in hospital or elsewhere. Patients’ and significant others’ opinion showed few differences, except with regard to the involvement of the significant others in CTH. As the respective views of patients and significant others were mixed, we recommend that crisis plans and compulsory treatment plans should be individually tailored to the needs and wishes of patients and their significant others regarding CTH.
RARγ activation sensitizes human myeloma cells to carfilzomib treatment through the OAS-RNase L innate immune pathway
Authors: Wang Qiang , Lin Zhijuan , Wang Zhuo , Ye Lingqun , Xian Miao , Xiao Liuling , Su Pan , Bi Enguang , Huang Yung-hsing , Qian Jianfei , Liu Lintao , Ma Xingzhe , Yang Maojie , Xiong Wei , Zu Youli , Pingali Sai Ravi , Xu Bing , Yi Qing 
Published: August 2021

AbstractProteasome inhibitors (PIs) such as bortezomib (Btz) and carfilzomib (Cfz) are highly efficacious for patients with multiple myeloma (MM). However, relapses are frequent, and acquired resistance to PI treatment emerges in most patients. Here, we performed a high-throughput screen of 1855 Food and Drug Administration (FDA)-approved drugs and identified all-trans retinoic acid (ATRA), which alone has no antimyeloma effect, as a potent drug that enhanced MM sensitivity to Cfz-induced cytotoxicity and resensitized Cfz-resistant MM cells to Cfz in vitro. ATRA activated retinoic acid receptor (RAR)γ and interferon-β response pathway, leading to upregulated expression of IRF1. IRF1 in turn initiated the transcription of OAS1, which synthesized 2-5A upon binding to double-stranded RNA (dsRNA) induced by Cfz and resulted in cellular RNA degradation by RNase L and cell death. Similar to ATRA, BMS961, a selective RARγ agonist, could also (re)sensitize MM cells to Cfz in vitro, and both ATRA and BMS961 significantly enhanced the therapeutic effects of Cfz in established MM in vivo. In support of these findings, analyses of large datasets of patients’ gene profiling showed a strong and positive correlation between RARγ and OAS1 expression and patient’s response to PI treatment. Thus, this study highlights the potential for RARγ agonists to sensitize and overcome MM resistance to Cfz treatment in patients.
Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis
Authors: Semenza Gregg L. 
Published: August 2021

Abstract
Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcriptional activity, respectively. Mutations in genes encoding components of the O2-sensing pathway cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcomes in these disorders.
Incidence and mortality rates of intracranial hemorrhage in hemophilia: a systematic review and meta-analysis
Authors: Zwagemaker Anne-Fleur , Gouw Samantha C. , Jansen Julie S. , Vuong Caroline , Coppens Michiel , Hu Qun , Feng Xiaoqin , Kim Soon K. , Van der Bom Johanna G. , Fijnvandraat Karin 
Published: August 2021

Abstract
Intracranial hemorrhage (ICH) is a severe complication that is relatively common among patients with hemophilia. This systematic review aimed to obtain more precise estimates of ICH incidence and mortality in hemophilia, which may be important for patients, caregivers, researchers, and health policy makers. PubMed and EMBASE were systematically searched using terms related to “hemophilia” and “intracranial hemorrhage” or “mortality.” Studies that allowed calculation of ICH incidence or mortality rates in a hemophilia population ≥50 patients were included. We summarized evidence on ICH incidence and calculated pooled ICH incidence and mortality in 3 age groups: persons of all ages with hemophilia, children and young adults younger than age 25 years with hemophilia, and neonates with hemophilia. Incidence and mortality were pooled with a Poisson-Normal model or a Binomial-Normal model. We included 45 studies that represented 54 470 patients, 809 151 person-years, and 5326 live births of patients with hemophilia. In persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval [CI], 1.2-4.8) and 0.8 (95% CI 0.5-1.2) per 1000 person-years, respectively. In children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births. ICH was classified as spontaneous in 35% to 58% of cases. Our findings suggest that ICH is an important problem in hemophilia that occurs among all ages, requiring adequate preventive strategies.
CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro
Authors: Cheng Xiaoqiang , Lin Jiayi , Chen Zhanghuan , Mao Yubo , Wu Xiexin , Xu Congxin , Du Jiacheng , Dong Zhongchen , Yang Huilin , Zhou Feng , Geng Dechun 
Published: August 2021

Abstract
Background
Nucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity.

Method
In Vitro, H2O2 was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model.

Result
In vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (H2O2) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3.

Conclusions
The experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by H2O2 could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.
Incidence of incidental cancer in transurethral resection of prostate specimens: a 10-year retrospective analysis
Authors: Nergiz Döndü , Yıldırım Hülya Tosun , Yıldırım Şenay 
Published: August 2021

Abstract
Background
Prostate cancer can be detected incidentally in patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia. Therefore, it is very important that the transurethral resection of the prostate specimen is evaluated carefully for accurate grading and staging. The aim of this study was to investigate the frequency of incidental prostate cancer and its relationship with clinicopathological findings.

Methods
The study included a total of 900 patients, who underwent transurethral resection of the prostate for benign prostatic hyperplasia treatment between June 2010 and June 2020. Patient age, prostate-specific antigen (PSA) levels and resected prostate weight were assessed, and the tumor stage, Gleason grade group, lymphovascular and perineural invasion status were also evaluated in the incidental prostate cancer group. The association between these parameters and prostate cancer detection was analyzed.

Results
Incidental detection of prostate cancer was determined at the rate of 13.3%. The incidental prostate cancer group had a significantly higher mean age and PSA levels compared to the benign prostatic hyperplasia group. The weight of the resected specimen had no impact on the incidence of incidental prostate cancer. Of the total 120 incidental prostate cancer cases, 59 (49.2%) were stage T1a and 61 (50.8%) were stage T1b. No significant difference was determined between the T1 stages and age distribution, but a statistically significant difference was determined in the other clinicopathological parameters.

Conclusions
The results of this study demonstrated that the incidence of incidental prostate cancer detection was related to age and PSA levels and increased, especially in those aged ≥ 60 years and/or PSA level ≥ 4 ng/mL. To avoid overlooking incidental prostate cancer in these patients, it can be recommended that material is sufficiently sampled and carefully evaluated, and when necessary, all resected specimens are examined. Although no significant correlation was determined between specimen weight and the incidence of incidental prostate cancer, as a significant difference was determined in T1 stages, this suggests that the amount of material evaluated could change the sub-stage.
Greater morphological and primary metabolic adaptations in roots contribute to phosphate-deficiency tolerance in the bread wheat cultivar Kenong199
Authors: Zheng Lu , Karim Mohammad Rezaul , Hu Yin-Gang , Shen Renfang , Lan Ping 
Published: August 2021

Abstract
Background
Phosphate (Pi) deficiency severely affects crop growth and productivity, including wheat, therefore it is necessary to develop cultivars with enhanced Pi-deficiency tolerance. However, the underlying mechanism of Pi-deficiency tolerance in wheat is still elusive. Two contrasting wheat cultivars, low-Pi tolerant Kenong199 (KN199) and low-Pi sensitive Chinese Spring (CS) were used to reveal adaptations in response to Pi deficiency at the morphological, physiological, metabolic, and molecular levels.

Results
KN199 was more tolerant to Pi deficiency than CS with significantly increased root biomass and R/S ratio. Root traits, the total root length, total root surface area, and total root volume, were remarkably enhanced by Pi deficiency in KN199. The shoot total P and soluble Pi concentrations of KN199 were significantly higher than those of CS, but not in roots. In KN199, high Pi level in shoots is a higher priority than that in roots under Pi deficiency. It was probably due to differentially regulation in the miR399-mediated signaling network between the shoots of the two cultivars. The Pi deficiency-induced root architecture adaptation in KN199 was attributed to the regulation of the hormone-mediated signaling (ethylene, gibberellin, and jasmonates). The expression of genes associated with root development and Pi uptake was enhanced in KN199. Some primary metabolites (amino acids and organic acids) were significantly accumulated in roots of KN199 under Pi deficiency.

Conclusions
The low-Pi tolerant wheat cultivar KN199 possessed greater morphological and primary metabolic adaptations in roots than CS under Pi deficiency. The adaption and the underlying molecular mechanisms in wheat provide a better understanding of the Pi-deficiency tolerance and the strategies for improving Pi efficiency in wheat.
Exosomal circEIF3K from cancer-associated fibroblast promotes colorectal cancer (CRC) progression via miR-214/PD-L1 axis
Authors: Yang Kaihua , Zhang Jie , Bao Chuanqing 
Published: August 2021

AbstractBackgroundTumor microenvironment (e.g., cancer-associated fibroblast) plays a key role in cancer tumorigenesis and metastasis. However, the detailed mechanism of whether hypoxia promotes CRC progression via tumor microenvironment remains unclear.MethodsIn this study, circEIF3K exosome was examined by NanoSight Tracking Analysis and RT-qPCR. We used cell colony formation assay, transwell assay and tube formation assay to determine proliferation, invasion and metastasis of HCT116 or SW620 cells. Xenograft tumor assay was employed to show in vivo tumor growth of HCT116 cells.ResultsWe found that hypoxia could induce secretion of circEIF3K exosome. Conditioned medium (CM) and exosome from circEIF3K knockdown CAF significantly attenuated proliferation, invasion and tube formation of HCT116 or SW620 cells, which could be reverted by miR-214 under hypoxia treatment. Besides, we observed that circEIF3K knockdown evidently impaired tumor growth in mice. TCGA dataset analysis showed that low expression of circEIF3K was observed in normal tissues and associated with prolonged survival time. Finally, PD-L1 was confirmed as important target for miR-214 in CRC.ConclusionIn conclusion, our study reveals that a novel axis circEIF3K/miR-214/PD-L1 mediates hypoxia-induced CRC progression via CAF, providing the rationale for developing new targeted therapeutics to treat CRC.
Prevalence of bone fractures among children and adolescents with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis
Authors: Seens Hoda , Modarresi Shirin , MacDermid Joy C , Walton David M , Grewal Ruby 
Published: August 2021

AbstractBackgroundAttention-deficit/hyperactivity disorder (ADHD) is a significant neurodevelopment disorder among children and adolescents, with 5 % prevalence. Bone fractures account for 25 % of accidents and injuries among all children and adolescents. Considering the characteristics of inattention, hyperactivity, and impulsivity in children with ADHD, it is critical to examine bone fractures among these children. The objective of our meta-analysis was to determine the prevalence of bone fractures among children and adolescents with ADHD.MethodsWe completed a systematic review and meta-analysis using an electronic search of the following databases: CINAHL, EMBASE, PsycINFO, PubMed, and Scopus. The search terms used were: “attention deficit hyperactivity disorder OR attention deficit disorder” and “bone fracture*.” We included studies examining patients 18 years or younger who were diagnosed with ADHD and tracked (prospectively or retrospectively) for five or more years. Effect size (es), using a random effects model, was calculated. We registered the review protocol with PROSPERO (CRD42019119527).ResultsFrom 445 records retrieved, 31 full text articles were reviewed and 5 articles met inclusion criteria for meta-analysis. The summary es revealed the prevalence of bone fractures among children and adolescents with ADHD to be 4.83 % (95 % CI: 3.07–6.58 %). The location of bone fractures, using a subset of data, showed a distribution of 69.62 %, 22.85 %, and 7.53 % in the upper limbs, lower limbs, and other anatomical regions, respectively. Another subset of studies revealed a 2.55-fold increase in the prevalence of fractures among the children with ADHD compared to their counterparts.ConclusionsAwareness of these findings is critical to physicians, parents, and policy makers to create safe environments and provide supports in order to optimize the health and safety of children and adolescents with ADHD.
Rural-urban determinants of vitamin a deficiency among under 5 children in Bangladesh: Evidence from National Survey 2017–18
Authors: Hossain Md. Moyazzem , Yeasmin Sabina , Abdulla Faruq , Rahman Azizur 
Published: August 2021

AbstractBackgroundVitamin A supplementation reduces child morbidity, mortality, and blindness of people, especially in developing countries like Bangladesh. This study explores significant determinants of vitamin A deficiency among preschool children in rural and urban areas of Bangladesh.MethodsThe data set was extracted from a nationally representative survey based on a cross-sectional study, the BDHS-2017-18. The base survey was conducted using a two-stage stratified sample of households. A sample of 8364 (urban 2911, rural 5453) children under-5 years old was analyzed using bivariate and multivariate statistical techniques.ResultsResults have demonstrated that 73.9 and 73.2% of children have had a vitamin A supplementation from urban and rural areas, respectively. Logistic regression analysis showed that parents’ education plays a vital role in consuming vitamin A supplements in urban and rural areas. Children whose mothers have secondary (OR: 1.17, CI: 0.76–1.81) and higher (OR: 1.21, CI: 0.72–2.04) education were more likely to consume vitamin A supplementation than children whose mothers were illiterate in urban areas. However, in rural areas, children whose mothers have secondary education were about 24% and higher education with 60% more likely to consume vitamin A supplementation than children whose mothers were illiterate. Child’s age, regional variation and wealth index also contributing factors for vitamin A deficiency in Bangladesh.ConclusionsThese findings indicated that the consumption of vitamin A does not cover the target of sustainable development goals. Thus special national and community level efforts are required to ensure the coverage of the national vitamin A program is increased adequately to the most vulnerable groups of children in Bangladesh.
Oral health-related quality of life among a group of patients with substance use disorders in rehabilitation treatment: a cross-sectional study
Authors: Amiri Saeed , Shekarchizadeh Hajar 
Published: August 2021

Abstract
Background
Little is known about the effect of illicit drugs on oral health-related quality of life. Our aim was to investigate oral health-related quality among patients with substance use disorders, and its association with dental caries experience and drug use profile.

Methods
Applying a stratified cluster random sampling method, we conducted a cross-sectional study on 267 in-treatment patients with substance use disorders in Isfahan, Iran in 2016. Self-administered questionnaires requested participants’ demographics and drug use profile. A trained dental student carried out personal interviews utilizing Oral Impact on Daily Performance (OIDP) instrument. Clinical examinations were conducted to record dental caries experience. T test, ANOVA, pearson and spearman correlation coefficient, and linear regression model served for statistical analysis (p < 0.05).

Results
A great majority of the participants reported past use of opium (85%) followed by heroin (42.7%) and amphetamines (20.2%). The most common routes of drug administration were combined routes (44.6%) followed by smoking (36.7%). The mean score of OIDP was 22.4 ± 8.6. As high as 74.1% of the participants reported at least one OIDP impact. The most prevalent OIDP impact was “difficulty eating” (64.8%). The most prevalent cause of the impacts were “dental decay” and “tooth loss”. No significant association revealed between OIDP and patients’ demographics and drug use profile (p > 0.05). Participants with higher caries experience, reported greater OIDP (p < 0.05).

Conclusions
There is an oral impact on the daily performance of patients with substance use disorders. Patients with higher caries experience reported greater OIDP. Thus, in addition to normative assessment of oral health, clinicians should consider the patients’ self-reported oral problems, and the social and mental aspects of oral conditions.