bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Outcomes of an All-Arthroscopic Biceps Tenodesis Using the Anterolateral Anchor During Concomitant Double-Row Rotator Cuff Repair
Authors: Meghpara Mitchell B. , Schulz William , Buerba Rafael A. , Golan Elan J. , Vyas Dharmesh 
Published: October 2020

Background: Pathology of the long head of the biceps tendon frequently occurs concomitantly with rotator cuff tears, necessitating a surgical treatment, often in the form of a tenodesis procedure. Many techniques for a tenodesis exist; however, they often require additional implants or a separate incision. Purpose: To report an average of 2-year outcomes of an all-arthroscopic biceps tenodesis employing the stay sutures from the anterolateral anchor during concomitant double-row rotator cuff repair (RCR). Study Design: Case series; Level of evidence, 4. Methods: Data were prospectively collected and retrospectively reviewed for all patients who underwent an all-arthroscopic biceps tenodesis during concomitant double-row RCR by the senior author between January 2014 and May 2018. Patients were included if they underwent this procedure and had baseline preoperative patient-reported outcomes (PROs) with a minimum of 1 year of postoperative PROs for the American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) for pain score. Additionally, patient data, surgical history, postoperative complications, and satisfaction were reported. Results: Fifteen patients were eligible for the study. There were 12 (80%) men and 3 (20%) women with a mean age of 50.0 years (range, 35-64 years). The mean follow-up time was 25.2 months (range, 13-63 months). Six of 15 (40%) patients also had an arthroscopic subscapularis repair performed. ASES shoulder scores improved from 37.1 preoperatively to 94.1 postoperatively ( P < .001), and VAS scores improved from 6.4 preoperatively to 0.5 postoperatively ( P < .001). One patient who underwent concomitant subscapularis repair reported continued anterior groove pain. No patients experienced biceps cramping, developed a deformity, or required a repeat operation at the final follow-up. Overall, 93.3% of the patients reported being highly satisfied with their surgery. Conclusion: This study presents the clinical results of an all-arthroscopic technique for concomitant double-row RCR and biceps tenodesis, which resulted in high rates of patient satisfaction and significant improvement in reported shoulder outcome and pain scores. Additionally, this technique offers the potential benefits of avoiding a secondary incision, which may decrease surgical morbidity while also decreasing cost by eliminating the need for an extra, tenodesis-specific implant.
DNA Methylation of Endoglin Pathway Genes in Pregnant Women With and Without Preeclampsia
Authors: Rietze Allison H , Conley Yvette P , Ren Dianxu , Anderson Cindy M , Roberts James M , Jeyabalan Arun , Hubel Carl A , Schmella Mandy J 
Published: October 2020

Objective: We compared blood-based DNA methylation levels of endoglin ( ENG) and transforming growth factor beta receptor 2 ( TGFβR2) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies. Methods: We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [( ENG subset: n = 20 (9 cases, 11 controls); TGFβR2 subset: n = 28 (15 cases, 13 controls)]. Results: The majority of the preeclampsia cases delivered at ⩾34 weeks’ gestation (83%). Average methylation levels for ENG ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; P = .102) and TGFβR2 (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; P = .695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the ENG analytic subset revealed a trend between levels of ENG methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; P = .062). Conclusion: Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology.
Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169
Authors: Gemenetzi Katerina , Psomopoulos Fotis , Carriles Alejandra A. , Gounari Maria , Minici Claudia , Plevova Karla , Sutton Lesley-Ann , Tsagiopoulou Maria , Baliakas Panagiotis , Pasentsis Kostas , Anagnostopoulos Achilles , Sandaltzopoulos Raphael , Rosenquist Richard , Davi Frederic , Pospisilova Sarka , Ghia Paolo , Stamatopoulos Kostas , Degano Massimo , Chatzidimitriou Anastasia 
Published: October 2020

Abstract
Chronic lymphocytic leukemia (CLL) major stereotyped subset 2 (IGHV3-21/IGLV3-21, ∼2.5% of all cases of CLL) is an aggressive disease variant, irrespective of the somatic hypermutation (SHM) status of the clonotypic IGHV gene. Minor stereotyped subset 169 (IGHV3-48/IGLV3-21, ∼0.2% of all cases of CLL) is related to subset 2, as it displays a highly similar variable antigen-binding site. We further explored this relationship through next-generation sequencing and crystallographic analysis of the clonotypic B-cell receptor immunoglobulin. Branching evolution of the predominant clonotype through intraclonal diversification in the context of ongoing SHM was evident in both heavy and light chain genes of both subsets. Molecular similarities between the 2 subsets were highlighted by the finding of shared SHMs within both the heavy and light chain genes in all analyzed cases at either the clonal or subclonal level. Particularly noteworthy in this respect was a ubiquitous SHM at the linker region between the variable and the constant domain of the IGLV3-21 light chains, previously reported as critical for immunoglobulin homotypic interactions underlying cell-autonomous signaling capacity. Notably, crystallographic analysis revealed that the IGLV3-21–bearing CLL subset 169 immunoglobulin retains the same geometry and contact residues for the homotypic intermolecular interaction observed in subset 2, including the SHM at the linker region, and, from a molecular standpoint, belong to a common structural mode of autologous recognition. Collectively, our findings document that stereotyped subsets 2 and 169 are very closely related, displaying shared immunoglobulin features that can be explained only in the context of shared functional selection.
Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma
Authors: Locke Frederick L. , Rossi John M. , Neelapu Sattva S. , Jacobson Caron A. , Miklos David B. , Ghobadi Armin , Oluwole Olalekan O. , Reagan Patrick M. , Lekakis Lazaros J. , Lin Yi , Sherman Marika , Better Marc , Go William Y. , Wiezorek Jeffrey S. , Xue Allen , Bot Adrian 
Published: October 2020

Abstract
ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216.
State-of-art review of traffic signal control methods: challenges and opportunities
Authors: Qadri Syed Shah Sultan Mohiuddin , Gökçe Mahmut Ali , Öner Erdinç 
Published: October 2020

Abstract
Introduction
Due to the menacing increase in the number of vehicles on a daily basis, abating road congestion is becoming a key challenge these years. To cope-up with the prevailing traffic scenarios and to meet the ever-increasing demand for traffic, the urban transportation system needs effective solution methodologies. Changes made in the urban infrastructure will take years, sometimes may not even be feasible. For this reason, traffic signal timing (TST) optimization is one of the fastest and most economical ways to curtail congestion at the intersections and improve traffic flow in the urban network.

Purpose
Researchers have been working on using a variety of approaches along with the exploitation of technology to improve TST. This article is intended to analyze the recent literature published between January 2015 and January 2020 for the computational intelligence (CI) based simulation approaches and CI-based approaches for optimizing TST and Traffic Signal Control (TSC) systems, provide insights, research gaps and possible directions for future work for researchers interested in the field.

Methods
In analyzing the complex dynamic behavior of traffic streams, simulation tools have a prominent place. Nowadays, microsimulation tools are frequently used in TST related researches. For this reason, a critical review of some of the widely used microsimulation packages is provided in this paper.

Conclusion
Our review also shows that approximately 77% of the papers included, utilizes a microsimulation tool in some form. Therefore, it seems useful to include a review, categorization, and comparison of the most commonly used microsimulation tools for future work. We conclude by providing insights into the future of research in these areas.
Raman2imzML converts Raman imaging data into the standard mass spectrometry imaging format
Authors: Iakab Stefania Alexandra , Sementé Lluc , García-Altares María , Correig Xavier , Ràfols Pere 
Published: October 2020

AbstractBackgroundMultimodal imaging that combines mass spectrometry imaging (MSI) with Raman imaging is a rapidly developing multidisciplinary analytical method used by a growing number of research groups. Computational tools that can visualize and aid the analysis of datasets by both techniques are in demand.ResultsRaman2imzMLwas developed as an open-source converter that transforms Raman imaging data into imzML, a standardized common data format created and adopted by the mass spectrometry community. We successfully converted Raman datasets to imzML and visualized Raman images using open-source software designed for MSI applications.ConclusionRaman2imzMLenables both MSI and Raman images to be visualized using the same file format and the same software for a straightforward exploratory imaging analysis.
Optimal designs for phase II/III drug development programs including methods for discounting of phase II results
Authors: Erdmann Stella , Kirchner Marietta , Götte Heiko , Kieser Meinhard 
Published: October 2020

Abstract
Background
Go/no-go decisions after phase II and sample size chosen for phase III are usually based on phase II results (e.g., the treatment effect estimate of phase II). Due to the decision rule (only promising phase II results lead to phase III), treatment effect estimates from phase II that initiate a phase III trial commonly overestimate the true treatment effect. Underpowered phase III trials are the consequence. Optimistic findings may then not be reproduced, leading to the failure of potentially expensive drug development programs. For some disease areas these failure rates are described to be quite high: 62.5%.

Methods
We integrate the ideas of multiplicative and additive adjustment of treatment effect estimates after go decisions in a utility-based framework for optimizing drug development programs. The design of a phase II/III program, i.e., the “right amount of adjustment”, the allocation of the resources to phase II and III in terms of sample size, and the rule applied to decide whether to stop or to proceed with phase III influences its success considerably. Given specific drug development program characteristics (e.g., fixed and variable per patient costs for phase II and III, probable gain in case of market launch), optimal designs with respect to the maximal expected utility can be identified by the proposed Bayesian-frequentist approach. The method will be illustrated by application to practical examples characteristic for oncological studies.

Results
In general, our results show that the program set-ups with adjusted treatment effect estimate used for phase III planning are superior to the “naïve” program set-ups with respect to the maximal expected utility. Therefore, we recommend considering an adjusted phase II treatment effect estimate for the phase III sample size calculation. However, there is no one-fits-all design.

Conclusion
Individual drug development planning for a specific program is necessary to find the optimal design. The optimal choice of the design parameters for a specific drug development program at hand can be found by our user friendly R Shiny application and package (both assessable open-source via [1]).
Training improves the handling of inhaler devices and reduces the severity of symptoms in geriatric patients suffering from chronic-obstructive pulmonary disease
Authors: Luley Marie-Christine , Loleit Tobias , Knopf Elmar , Djukic Marija , Criée Carl-Peter , Nau Roland 
Published: October 2020

Abstract
Purpose
Elderly patients with impaired vision, cognitive decline or motor/sensory disturbances of their fingers suffering from chronic-obstructive pulmonary disease (COPD) encounter difficulties in handling inhaler devices used as the cornerstones of treatment of pulmonary obstruction. Many elderly patients make severe mistakes which impede adequate drug delivery to the bronchioles. This multimodal training program was designed to reduce the number of handling mistakes of inhaler devices.

Methods
From October 1, 2016 to September 30, 2017, a prospective intervention study was conducted in 38 in-patients > 65 years (median age 79 years) with previously diagnosed COPD. The effect of an 8-day intervention comprising daily counselling and video demonstration according to the recommendations of the German Airway League on the frequency of mistakes during handling of inhaler devices, the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC) and the perception of symptoms (COPD Assessment Test, CAT) were studied. Measurements on days 1 and 8 were compared by Wilcoxon signed rank test.

Results
The number of handling mistakes per patient decreased as a consequence of the intervention from 3.0 (0–7) to 0.5 (0–6) [median (minimum-maximum; p < 0.0001)]. The CAT Score decreased from 19.5 (14/24) to 14.5 (10.75/21) [median (25./75. percentile; p < 0.0001) indicating a substantial reduction of clinical symptoms. Conversely, FEV1 and FVC only slightly increased (difference statistically not significant). At study entry, the number of handling mistakes was inversely correlated with the Mini Mental Status Test (MMST) score (p = 0.01). The reduction of the number of handling mistakes during the intervention was not correlated with the MMST.

Conclusion
In COPD, intensive training for 8 days improved the handling of inhalers and reduced clinical symptoms in geriatric patients. Patients with cognitive abnormalities also benefitted from this intervention.

Trial registration
German Clinical Trials Registry DRKS00023196, date of registration September 29, 2020 (retrospectively registered).
Frequency of thrombophilia associated genes variants: population-based study
Authors: Wawrusiewicz-Kurylonek Natalia , Krętowski Adam Jacek , Posmyk Renata 
Published: October 2020

Abstract
Background
Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations.

Methods
All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay.

Results
The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G > A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects.

Conclusion
The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).
The IL-6 rs12700386 polymorphism is associated with an increased risk of developing osteoarthritis in the knee in the Chinese Han population: a case-control study
Authors: Yang Hui , Zhou Xindie , Xu Dongmei , Chen Gang 
Published: October 2020

Abstract
Background
This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population.

Methods
We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism.

Results
We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥55 years old or with BMI ≥ 25 kg/m2. The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients.

Conclusion
These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.
The personal and clinical impact of screen-detected maternal rheumatic heart disease in Uganda: a prospective follow up study
Authors: Voleti Sonia , Okello Emmy , Murali Meghna , Sarnacki Rachel , Majwala Albert , Ssembatya Renny , Bakka Olivia , Namisanvu Henriator , Njeri Angela , Matovu Alphonsus , DeStigter Kristen , Sable Craig , Beaton Andrea 
Published: October 2020

Abstract
Background
Pre-existing maternal cardiac disease is a significant contributor to adverse maternal, fetal, and neonatal outcomes. In 2015–2017, our team conducted the first community-based study of maternal rheumatic heart disease (RHD) in sub-Saharan Africa and identified RHD in 88% of those with pre-existing heart disease.
Here we conducted a follow up investigation of women previously identified with RHD, describing clinical and echocardiographic outcomes, identifying barriers to medical adherence and evaluating the personal impact of RHD.

Methods
A 2 week prospective follow up was completed at sites in Central and Eastern Uganda. Participants underwent a three-step mixed methods study comprising of 1) direct structured interview targeting clinical history and medication adherence, 2) echocardiogram to evaluate left-sided heart valves, and 3) semi-structured guideline interview to elicit personal impacts of RHD.

Results
The team evaluated 40 (80%) of the original 51 mothers with RHD at a median post-partum time of 2.5 years after delivery (IQR 0.5). Echocardiographic data showed improvement in nine women with the remaining 31 women showing stable echocardiographic findings. Adherence to Benzathine penicillin G (BPG) prophylaxis was poor, with 70% of patients either poorly adherent or non-adherent.
Three major themes emerged from interviews: 1) social determinants of health (World Health Organization, Social determinants of health, 2019) negatively affecting healthcare, 2) RHD diagnosis negatively affecting female societal wellbeing, 3) central role of spouse in medical decision making.

Conclusions
Screening echocardiography can identify women with pre-existing rheumatic heart disease during pregnancy, but long-term follow-up in Uganda reveals adherence to medical care following diagnosis, including BPG, is poor. Additionally, mothers diagnosed with RHD may experience unintended consequences such as social stigmatization. As identification of occult RHD is critical to prevent adverse pregnancy outcomes, further research is needed to determine how to best support women who face a new diagnosis of RHD, and to determine the role of screening echocardiography in high-risk settings.