bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis
Authors: Huang Jing , Fan Huizhen , Qiu Qi , Liu Kunpeng , Lv Shuang , Li Jiang , Yang Hui , Shu Xiaoming , Xu Yuan , Lu Xiangchen , Lu Cheng , Zhang Yunnan , Xiao Cheng 
Published: April 2020

Aims: We performed an updated meta-analysis to verify correlations between gene polymorphisms and adverse events in methotrexate (MTX)-treated rheumatoid arthritis (RA) patients. Then, we conducted a retrospective cohort study of Han Chinese in China. Methods: Relevant studies were collected from the PubMed database and the EMBASE database until December 2017. Pre-allele, dominant, recessive, codominant, and homozygotic models were applied. In addition, a retrospective cohort study enrolling 162 RA patients treated with MTX was conducted. Single nucleotide polymorphism (SNP) genotyping was analyzed by PCR and product sequencing. Results: A total of 39 studies were included in 20 meta-analyses; meta-analysis showed a significant association between MTX-related toxicity and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T(rs1801133) polymorphism in East Asian RA patients, and significant associations were observed between MTX-related toxicity and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) 347C>G (rs2372536), reduced folate carrier 1 (RFC-1) 80G>A (rs1051266), and adenosine triphosphate-binding cassette B1 (ABCB1) 3435C>T(rs1045642) polymorphisms in European RA patients but not in East Asian RA patients. Moreover, in our retrospective cohort study, ATIC 347C>G(rs2372536) and ABCB1 3435C>T(rs1045642) polymorphisms were not associated with MTX-related toxicity. However, a significant association was observed between MTX-related toxicity and RFC-1 80G>A (rs1051266) polymorphism in Chinese Han RA patients. Conclusion: Evidence-based results suggest that the MTHFR 677C>T(rs1801133), ATIC 347C>G(rs2372536), RFC-1 80G>A (rs1051266), ABCB1 3435C>T(rs1045642) polymorphisms are associated with MTX-related toxicity. Larger and more stringent study designs may provide more accurate findings for the effects of these SNPs on MTX-related toxicity, and larger sample-size studies of the Chinese Han population should be conducted for further validation.
Adhering to antiretroviral therapy: A qualitative analysis of motivations for and obstacles to consistent use of antiretroviral therapy in people living with HIV
Authors: Fleischer Lisa , Avery Ann 
Published: April 2020

Objectives: Based on the 2015 U.S. Centers for Disease Control and Prevention data, 40% of people living with HIV in the United States with an HIV diagnosis and 18.5% of people living with HIV in HIV care in the United States are not virally suppressed. Many HIV care clinics have implemented recommendations to improve the percentage of people living with HIV on antiretroviral therapy. To understand what more could be done, we examine patients’ motivations and obstacles to maintaining adherence to antiretroviral therapy. Methods: We conducted qualitative analysis using a qualitative description framework of in-depth interviews with people living with HIV receiving care at an urban HIV care clinic in the midwestern United States. Results: We found that while many traditional barriers to care have been addressed by existing programs, there are key differences between those consistent with antiretroviral therapy and those inconsistent with antiretroviral therapy. In particular, self-motivation, diagnosis acceptance, treatment for depression, spiritual beliefs, perceived value of the HIV care team, and prior experience with health care distinguish these two groups. Most significantly, we found that people living with HIV consistent with antiretroviral therapy describe their main motivation as coming from themselves, whereas people living with HIV inconsistent with antiretroviral therapy more often describe their main motivation as coming from the HIV care team. Conclusion: Our results highlight the importance of the HIV care team’s encouragement of maintaining antiretroviral adherence, as well as encouraging treatment for depression.
Radiographic scoring systems for psoriatic arthritis are insufficient for psoriatic arthritis mutilans: results from the Nordic PAM Study
Authors: Laasonen Leena , Lindqvist Ulla , Iversen Lars , Ejstrup Leif , Jonmundsson Thorarinn , Ståhle Mona , Gudbjornsson Bjorn 
Published: April 2020

Background Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis (PsA). Purpose To describe the radiological features in PAM and explore whether existing scoring systems for radiological damage in psoriatic arthritis are applicable for PAM. Material and Methods Radiographs were scored according to the modified Sharp-van der Heijde (mSvdH) and the Psoriatic Arthritis Ratingen Score (PARS) systems for PsA. Results At inclusion, 55 PAM patients (49% women, mean age 58 ± 12 years) had conventional radiographs of both hands and feet. A total of 869 PAM joints were detected and 193 joints with ankylosis. The mean total mSvdH score was 213.7 ± 137.8 (41% of maximum) with a higher score for hands than for feet: 136.6 ± 90.1 vs. 79.1 ± 60.9. However, the total score was relatively higher in the feet than in the hands when compared to the highest possible scoring (47% vs. 38% of max). The mean total PARS score was 126.3 ± 79.6 (35% of max). Scoring for joint destruction was higher than for proliferation (22% vs. 11% of max). Strong correlation was found between mSvdH and PARS (r2 = 0.913). A significant correlation was found between scoring and duration of arthritis and the Health Assessment Questionnaire. History of smoking, BMI, and gender did not influence the scoring values. Conclusions The two scoring systems studied may not be ideal to indicate progression of PAM in advanced disease since they reach ceiling effects rather early. Therefore, reporting early signs suggestive of PAM, e.g. signs of pencil-in-cup deformities or osteolysis, is crucial. This would reveal the presence of PAM and might lead to improved treatment in order to minimize joint damage.
Comparison between hook plate fixation with and without coracoclavicular ligament suture for acute acromioclavicular joint dislocations
Authors: Seo Joong-Bae , Kim Seong-Jun , Ham Hee-Jung , Yoo Jae-Sung 
Published: April 2020

Background: Hook plates are widely used for repair of acromioclavicular joint (ACJ) dislocations. However, it is unclear whether repair of torn coracoclavicular (CC) ligament is necessary. The purpose of this study was to evaluate the outcomes of the hook plate fixation with direct CC ligament repair for acute ACJ dislocation in comparison with the hook plate fixation without direct CC ligament repair. Methods: The study included 120 patients with acute ACJ dislocations who underwent surgery. The patients were divided into 73 patient groups with Arbeitsgemeinschaft für Osteosynthesefragen (AO) hook plate fixation and direct CC ligament repair and 47 patient groups without direct CC ligament repair. For clinical assessments, the American Shoulder and Elbow Surgeons score, constant score, and time for implant removal were recorded. The corcoclavicular distance (CCD) and the CCD ratio were used for the evaluation of reduction. Typical reported complications, such as secondary dislocation, implant failure or loosening, peri-implant fracture, acromion osteolysis, and postoperative ACJ arthrosis, were also analyzed. Results: There were no differences in the clinical outcomes between the two groups. There was no difference in the timing of implant removal between the two groups. The last follow-up CCD was not statistically significant between group with direct CC ligament repair and without repair (9.1 ± 3.3 vs. 9.0 ± 2.8, respectively, p > 0.05). The last follow-up CCD ratio showed significant differences between the two groups (12.6 ± 25.5% vs. 26.3 ± 39.7, respectively, p < 0.05). There was no statistically significant difference in the complication rate between the two groups. Conclusion: The hook plate fixation with direct CC ligament repair group was better for maintenance of reduction than that of the hook plate fixation without direct CC ligament repair group. Although, there were no differences of clinical outcomes and complications between two groups. Level of Evidence: Level III, Retrospective Study.
Comparison of medial and lateral tibial tunnel in pullout repair of posterior root tear of medial meniscus: Radiologic, clinical, and arthroscopic outcomes
Authors: Kwon Sai-Won , Kim Jun Bum , Kim Chang Hyun , Hong Si John , Hong Yong Cheol , Jang Byung-Woong 
Published: April 2020

Purpose: Medial meniscus posterior root tear (MMPRT) should be repaired to the correct position as possible to maintain hoop tension of the meniscus. In this study, we propose a comparison of the outcome between the medial tunnel and the lateral tunnel in the pullout suture technique using the tibial tunnel for anatomical repair of posterior root tear of medial meniscus. Methods: From April 2010, of patients who underwent pullout suture, 51 cases (24 medial tunnel group (MTG) and 27 lateral tunnel group (LTG)) were able to follow-up with second look arthroscopy. Original Coronal Ratio of Root Attachment (CRORA) was defined as the ratio of the distance from the medial edge of the tibial plateau to the root attach site divided by the entire tibial medial–lateral width on preoperative computed tomography. Error between postoperative CRORA and original CRORA was calculated. We compared this error, clinical outcome, and arthroscopic finding between MTG and LTG. Results: The mean error ratio of postoperative CRORA divided by original CRORA was 0.86 ± 0.11 in MTG, which was significantly ( p = 0.001) lower than that (1.02 ± 0.06) in LTG. The mean value of the root attach point in the MTG with a post/original CRORA value of 0.86 ± 0.11 means statistically significant medialization after the operation. There was no statistically significant difference in changes of International Knee Documentation Committee (IKDC) and Lysholom score between MTG and LTG. The difference between the two groups of arthritis progression was not statistically significant. Conclusion: In patients with MMPRT, CRORA may provide a basis for coronal assessment of root repair position before and after surgery, and lateral tibial tunnel technique can help anatomical repair by reducing technical error due to guide pin slip medially compared to medial tibial tunnel technique.
Anterior knee pain after total knee arthroplasty: A multifactorial analysis
Authors: Laubach Markus , Hellmann Julian TR , Dirrichs Timm , Gatz Matthias , Quack Valentin , Tingart Markus , Betsch Marcel 
Published: April 2020

Purpose: Dissatisfaction and an impaired quality of life after total knee arthroplasty (TKA) is often associated with postsurgical anterior knee pain (AKP). The underlying pathological mechanisms are not yet fully understood. Therefore, a multifactorial approach encompassing clinical and radiological parameters seemed reasonable and promising to investigate postsurgical AKP. Methods: In this cross-sectional study, 25 patients without and 25 patients with postsurgical AKP after unilateral TKA were randomly recruited from a larger cohort of patients. Multiple clinical and radiological parameters—including real-time shear wave elastography (SWE) to measure the patellar and quadriceps tendon elasticity—were acquired and subsequently associated with AKP. For statistical analysis, SPSS (IBM, version 25) was used. Results: In total 50 participants (58.0% men, mean age 63.42 years, mean body mass index 29.75 kg/m2), having different prosthetic designs implanted, were included. Independently of key covariates, the strength of the quadriceps muscle ( p = 0.021), a thinner inlay ( p = 0.041), and a lower position of the patella ( p = 0.041) were associated with AKP. Although no correlation with AKP was found ( p = 0.346, resp. p = 0.154), we observed significantly decreased Young’s modulus of the patellar and quadriceps tendons for the involved knee compared to the uninvolved knee ( p < 0.001). Conclusion: In conclusion, quadriceps muscle strength, inlay thickness, and the patella position might be of particular relevance in avoiding postsurgical AKP. Future studies with larger sample sizes are needed to clarify the impact of quadriceps muscle strength and the postoperative patella position as well as the role of SWE as a personalized modifiable prediction marker.
Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography
Authors: Roh Miin , Miller Joan W. , Jeng-Miller Karen W. , Wang Jay C. , Laíns Inês , Silverman Rebecca F. , Loewenstein John I. , Husain Deeba , Vavvas Demetrios G. , Miller John B. 
Published: April 2020

Purpose: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). Methods: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. Results: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of 1 to 10 years. Conclusions: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.
Systematic review of observational studies reporting antiphospholipid antibodies in patients with solid tumors
Authors: Abdel-Wahab Noha , Tayar Jean H. , Fa'ak Faisal , Sharma Gaurav , Lopez-Olivo Maria A. , Yousif Abdelrahman , Shagroni Tasneam , Al-Hawamdeh Sami , Rojas-Hernandez Cristhiam M. , Suarez-Almazor Maria E. 
Published: April 2020

Abstract
This review summarizes the evidence on antiphospholipid (aPL) antibodies and related thromboembolic events in patients with solid tumors. Data sources included Medline, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through August 2019 without restrictions. Observational studies that evaluated patients with solid tumors for the presence of aPL antibodies were included. Data were extracted and quality was assessed by one reviewer and cross-checked by another. Thirty-three studies were identified. Gastrointestinal (GI) and genitourinary (GU) cancers were the most frequently reported. Compared with healthy patients, patients with GI cancer were more likely to develop anticardiolipin antibodies (risk ratio [RR], 5.1; 95% confidence interval [CI], 2.6-9.95), as were those with GU (RR, 7.3; 95% CI, 3.3-16.2) and lung cancer (RR, 5.2; 95% CI, 1.3-20.6). The increased risk for anti-β2-glycoprotein I or lupus anticoagulant was not statistically significant. Patients with lung cancer who had positive aPL antibodies had higher risk of developing thromboembolic events than those who had negative antibodies (RR, 3.8%; 95% CI, 1.2-12.2), while the increased risk in patients with GU cancer was not statistically significant. Deaths due to thromboembolic events were more common among patients with lung cancer who had elevated aPL antibodies. A limitation of this review is that the results are contingent on the reported information. We found an increased risk of developing aPL antibodies in patients with GI, GU, and lung cancers resulting in thromboembolic events and death. Further studies are needed to better understand the pathogenesis and development of aPL antibodies in cancer.
Pulmonary arterial hypertension with below threshold pulmonary vascular resistance
Authors: Ratwatte Seshika , Anderson James , Strange Geoffrey , Corrigan Carolyn , Collins Nicholas , Celermajer David S. , Dwyer Nathan , Feenstra John , Keating Dominic , Kotlyar Eugene , Lavender Melanie , Whitford Helen , Whyte Ken , Williams Trevor , Wrobel Jeremy P. , Keogh Anne , Lau Edmund M. 
Published: April 2020

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25–30 mmHg), PAWP 13 mmHg (IQR 11–14 mmHg) and PVR 2.2 Wood units (IQR 1.9–2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280–416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7–96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32–101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and “borderline” PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.
Maternal smoking during pregnancy affects adult onset of asthma in offspring: a follow up from birth to age 46 years
Authors: Toppila-Salmi Sanna , Luukkainen Annika T. , Xu Baizhuang , Lampi Jussi , Auvinen Juha , Dhaygude Kishor , Järvelin Marjo-Riitta , Pekkanen Juha 
Published: April 2020

RationaleEnvironmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma.ObjectivesTo determine the association between prenatal ETS and adult onset asthma.Measurements and main resultsThe questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04–2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28–40.67) or past cough with wheeze (3.21, 95% CI 1.71–6.05). A significant association was detected between gestational smoke exposure and the offspring's forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA ofRUNX1, gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11–14.52, adjusted p-value for interaction 0.10).ConclusionMaternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV1/FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring's airways to ETS and its putative long-term effects.
Vertical pons hyperintensity and hot cross bun sign in cerebellar-type multiple system atrophy and spinocerebellar ataxia type 3
Authors: Sugiyama Atsuhiko , Yokota Hajime , Yamanaka Yoshitaka , Mukai Hiroki , Yamamoto Tatsuya , Hirano Shigeki , Koide Kyosuke , Ito Shoichi , Kuwabara Satoshi 
Published: April 2020

Abstract
Background
The “hot cross bun” (HCB) sign, a cruciform hyperintensity in the pons on magnetic resonance imaging (MRI), has gradually been identified as a typical finding in multiple system atrophy, cerebellar-type (MSA-C). Few reports have evaluated the sensitivity of an HCB, including a cruciform hyperintensity and vertical line in the pons, which precedes a cruciform hyperintensity, in the early stages of MSA-C. Moreover, the difference in frequency and timing of appearance of an HCB between MSA-C and spinocerebellar ataxia type 3 (SCA3) has not been fully investigated.

Methods
This study investigated the time at which an HCB and orthostatic hypotension (OH) appeared in 41 patients with MSA-C, based on brain MRI and head-up tilt test. The MRI findings were compared with those of 26 patients with SCA3. The pontine signal findings on T2-weighted MRI were graded as 0 (no change), 1 (a vertical T2 high-intensity line), or 2 (a cruciform T2 high-intensity line), with grades 1 or 2 considered as an HCB. OH 30/15 was defined as a decrease in systolic blood pressure of > 30 mmHg or diastolic blood pressure of > 15 mmHg.

Results
Among the 24 patients with MSA-C within 2 years from the onset of motor symptoms, an HCB was detected in 91.7%, whereas OH 30/15 was present in 60.0%. Among the 36 patients with MSA-C within 3 years from the onset of motor symptoms, a grade 2 HCB was detected in 66.7% of those with MSA-C but in none of those with SCA-3.

Conclusions
HCB is a highly sensitive finding for MSA-C, even in the early stages of the disease. A grade 2 HCB in the early stage is an extremely specific finding for differentiating MSA-C from SCA-3.
Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy
Authors: Lu Yuanjun , Chan Yau-Tuen , Tan Hor-Yue , Li Sha , Wang Ning , Feng Yibin 
Published: April 2020

AbstractEpigenetics is dynamic and heritable modifications to the genome that occur independently of DNA sequence. It requires interactions cohesively with various enzymes and other molecular components. Aberrant epigenetic alterations can lead to inappropriate onset of genetic expressions and promote tumorigenesis. As the epigenetic modifiers are susceptible to extrinsic factors and reversible, they are becoming promising targets in multiple cancer therapies. Recently, various epi-drugs have been developed and implicated in clinical use. The use of epi-drugs alone, or in combination with chemotherapy or immunotherapy, has shown compelling outcomes, including augmentation of anti-tumoral effects, overcoming drug resistance, and activation of host immune response.