bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and Radiological Outcome Analysis of Osteoperiosteal Decortication Flap in Nonunion of Tibia
Authors: Kumar Vineet , Waliullah Shah , Avasthi Sachin , Mahapatra Swagat , Singh Ajai , Ali Sabir
Published: July 2021

Introduction. The treatment of long bone shaft nonunions is challenging. The technique of osteoperiosteal decortications flap for approaching the nonunion site coupled with fixation modalities was first described by Judet in 1963. Despite promising clinical and radiological union, this technique is not popular among orthopaedic surgeons. Our study aimed to evaluate the radiological union and functional results of shaft tibia nonunions treated by the osteoperiosteal decortication approach. Methods. This retrospective study included all the cases with established tibial shaft nonunion following stringent inclusion and exclusion criteria and operated upon by following the principle of osteoperiosteal flap technique from April 2015 to July 2019. Further subgroups were made based on nonunions complexity based on nonunion scoring system (NUSS) score. The outcome measures included radiological union scale in tibial fractures (RUST) and lower extremity functional scale (LEFS). The preoperative scores for union and function were recorded, and the subsequent scores were obtained at three, six, and nine months and one year. Appropriate statistical analysis of the data was done. Results. Thirty-four cases were shortlisted for analysis, fulfilling our inclusion and exclusion criteria. There were 22 males (64.7%) and 12 females (35.3%) with a mean age of 34.17 ± 10.3 years. Subgroup analysis based on the complexity of nonunion (NUSS score) revealed 14 cases in group A, 10 cases in group B, 10 cases in group C, and 0 cases in group D. The average time from fracture to surgery in these cases was 14.6 months. The average time to achieve union was 9.6 months, with patients in groups A, B, and C, having a mean duration of 9, 10.5, and 12 months, respectively. Statistically, significant improvement was seen in both RUST scores and LEFS score. Complications included infection in seven cases, wound dehiscence in two cases, and four cases of persistent nonunion. Conclusion. Osteoperiosteal decortication remains a highly effective surgical technique in the management of nonunion of long bones. NUSS scoring is an essential tool for prognosticating nonunion cases. This score is inversely related to the radiological union (RUST score) of the bone and functional recovery (LEFS score) of the patient.
Novel Bee Colony Optimization with Update Quantities for OFDMA Resource Allocation
Authors: Sun Ming , Huang Yujing , Wang Shumei , Xu Yaoqun
Published: July 2021

In recent years, large usage of wireless networks puts forward challenge to the utilization of spectrum resources, and it is significant to improve the spectrum utilization and the system sum data rates in the premise of fairness. However, the existing algorithms have drawbacks in efficiency to maximize the sum data rates of orthogonal frequency division multiple access (OFDMA) systems in the premise of fairness threshold. To address the issue, a novel artificial bee colony algorithm with update quantities of nectar sources is proposed for OFDMA resource allocation in this paper. Firstly, the population of nectar sources is divided into several groups, and a different update quantity of nectar sources is set for each group. Secondly, based on the update quantities of nectar sources set for these groups, nectar sources are initialized by a greedy subcarrier allocation method. Thirdly, neighborhood searches and updates are performed on dimensions of nectar sources corresponding to the preset update quantities. The proposed algorithm can not only make the initialized nectar sources maintain high levels of fairness through the greedy subcarrier allocation but also use the preset update quantities to reduce dimensions of the nectar sources to be optimized by the artificial bee colony algorithm, thereby making full use of both the local optimization of the greedy method and the global optimization of the artificial bee colony algorithm. The simulation results show that, just in the equal‐power subcarrier allocation stage, the proposed algorithm can achieve the required fairness threshold and effectively improve the system sum data rates.
A Treatment Technology for Optimizing the Stress State of Railway Tunnel Bottom Structure
Authors: Han Zili , Ma Weibin , Chai Jinfei , Zhu Zhenyu , Lin Chuannian , An Zeli , Ma Chaofeng , Xu Xueliang , Xu Tianyuan
Published: July 2021

With the continuous increase of railway transportation volume, the aging problem of railway tunnel bottom structure is becoming more and more serious, which seriously threatens the safe operation of trains. Based on the cause analysis and field detection of the defects at the railway tunnel bottom structure, the “Anchor‐Grouting‐Drainage” treatment technology of the railway tunnel bottom structure is summarized. The research shows that (1) the technology is simple and can effectively repair the defects of railway tunnel bottom structure under the conditions of the narrow site, short time of maintenance skylight, strict requirements of track size variation, and no interference with the normal operation of the train, which has great significance and broad application prospect. (2) The drainage system of the existing railway tunnel bottom structure can be applied to the reconstruction of the railway tunnel bottom structure. The high‐strength transverse diversion structure at the bottom of the tunnel has the advantages of strong bearing capacity, large drainage capacity, and corrosion resistance, which can provide a reference for the subsequent implementation of the reconstruction project at the railway tunnel bottom structure.
Competition Analysis on Industry Populations Based on a Three-Dimensional Lotka–Volterra Model
Authors: Wang Sheng-Yuan , Chen Wan-Ming , Wu Xiao-Lan
Published: July 2021

The classical Lotka–Volterra model is mainly a two-dimensional configuration. The two-dimensional form limits the application scenarios of the Lotka–Volterra model. The research objective of this paper is to develop a feasible three population equilibrium model to analyze the industry competition. In order to expand the Lotka–Volterra model to empirical analysis, this paper proposes a symbiosis model of enterprise population based on a three-dimensional Lotka–Volterra model. This paper analyzes the symbiotic system from two aspects: the balanced development of three species and the competitive evolution of the three species, taking the sales volume of three local automobile enterprises in China as the sample for empirical analysis. The symbiotic optimization under the equilibrium state of three populations indicates that there is the possibility of equilibrium and reciprocity in the growth of three automobile product populations. The empirical analysis fully explains the feasibility of this research paradigm. The analysis of competition evolution shows that cooperative action is better than competitive strategy and that comprehensive cooperation is the ideal state of a three-population symbiotic system.
Identification of New Biomarker for Prediction of Hepatocellular Carcinoma Development in Early-Stage Cirrhosis Patients
Authors: Ning Gang , Li Yongqiang , Chen Wenji , Tang Wenjuan , Shou Diwen , Luo Qingling , Chen Huiting , Zhou Yongjian
Published: July 2021

Background. Liver cirrhosis is one of the major drivers of hepatocellular carcinoma (HCC). In the present study, we aimed to identify and validate new biomarker for early prediction of HCC development in early-stage cirrhosis patients. Methods. mRNA expression and clinical parameters of GSE63898, GSE89377, GSE15654, GSE14520, and TCGA-HCC cohort and ICGC-HCC cohort were downloaded for analysis. Wilcoxon test was performed to identify DEGs. Univariate and multivariate Cox regression analysis were used to develop the risk signature, and ROC analysis was performed to analyze the predictive accuracy and sensitivity of the risk signature. Results. There were 42 DEGs (including 28 upregulated genes and 14 downregulated genes) found in early-stage liver cirrhosis patients before developing HCC from GSE1565442. Then, a risk signature consisting of 8 DEGs could effectively classify early-stage cirrhosis patients into high-risk group with shorter HCC development time and low-risk group with longer HCC development time from GSE15654. Multivariate Cox analysis indicated that the risk signature was an independent prognostic factor for the prediction of HCC development and ROC analysis showed that the signature exhibited good predictive efficiency in predicting 2-, 5-, and 10-year HCC development. Mechanistically, significantly higher proportions of CD8 T cells were found to be enriched in cirrhosis patients with low risk score, and higher CD8 T cells were associated with longer HCC development time. Besides, the signature was an independent prognostic factor for poorer prognosis of early-stage liver cirrhosis patients of GSE15654. Moreover, the signature could also separate HCC patients from healthy controls and was also associated with the poorer prognosis of HCC patients from three HCC cohorts. Finally, we also identified HDAC inhibitors, such as trichostatin A, to be a potential chemopreventive treatment for the prevention of HCC development by targeting risk signature based on CMap analysis. Conclusion. A risk signature was developed and validated for early prediction of HCC development, which may be a useful tool to set up individualized follow-up interval schedules.
Research on PMF Model Based on BP Neural Network Ensemble Learning Bagging and Fuzzy Clustering
Authors: Zhang Zhengjin , Huang Guilin , Zhang Yong , Wei Siwei , Shi Baojin , Jiang Jiabao , Liang Baohua
Published: July 2021

Probability matrix factorization model can be used to solve the problem of high‐dimensional sparsity of user and rating data in the recommender systems. However, most of the existing methods use the user to model the item rating, ignoring the relationship between the user and the item, so the accuracy of user‐item rating prediction is still low. Therefore, this paper proposes a probabilistic matrix factorization model based on BP neural network ensemble learning, bagging, and fuzzy clustering. Firstly, the membership function of fuzzy clustering and the selection of cluster center are used to calculate the user‐item rating matrix; secondly, BP neural network trains the user‐item scoring matrix after clustering, further improving the accuracy of scoring prediction; finally, the bagging method in ensemble learning is introduced, which takes the number of user‐item scores as the base learner, trains the base learner through BP neural network, and finally obtains the score prediction through the voting results, which improves the stability of the model. Compared with the existing PMF models, the root mean square error of the PMF model after fuzzy clustering is increased by 9.27% and 3.95%, and the average absolute error is increased by 21.14% and 1.11%, respectively; then, the performance of the first mock exam is introduced. The root mean square error of the ensemble method is increased by 4.02% and 0.42%, respectively, compared with the existing single model. Finally, the weights of BP neural network training based learner are introduced to improve the accuracy of the model, which also verifies the universality of the model.
Targeting c-Myc to Overcome Acquired Resistance of EGFR Mutant NSCLC Cells to the Third-Generation EGFR Tyrosine Kinase Inhibitor, Osimertinib
Authors: Zhu Lei , Chen Zhen , Zang Hongjing , Fan Songqing , Gu Jiajia , Zhang Guojing , Sun Kevin D.-Y. , Wang Qiming , He Yong , Owonikoko Taofeek K. , Ramalingam Suresh S. , Sun Shi-Yong
Published: July 2021

Osimertinib (AZD9291 or TAGRISSO) is a promising and approved third-generation EGFR tyrosine kinase inhibitor (TKI) for treating patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR-activating mutations or the resistant T790M mutation. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A fuller understanding of the mechanism of action of osimertinib and its linkage to acquired resistance will enable the development of more efficacious therapeutic strategies. Consequently, we have identified a novel connection between osimertinib or other EGFR-TKIs and c-Myc. Osimertinib rapidly and sustainably decreased c-Myc levels primarily via enhancing protein degradation in EGFR-mutant (EGFRm) NSCLC cell lines and xenograft tumors. c-Myc levels were substantially elevated in different EGFRm NSCLC cell lines with acquired resistance to osimertinib in comparison with their corresponding parental cell lines and could not be reduced any further by osimertinib. Consistently, c-Myc levels were elevated in the majority of EGFRm NSCLC tissues relapsed from EGFR-TKI treatment compared with their corresponding untreated baseline c-Myc levels. Suppression of c-Myc through knockdown or pharmacologic targeting with BET inhibitors restored the response of resistant cell lines to osimertinib. These findings indicate that c-Myc modulation mediates the therapeutic efficacy of osimertinib and the development of osimertinib acquired resistance. Furthermore, they establish c-Myc as a potential therapeutic target and warrant clinical testing of BET inhibition as a potential strategy to overcome acquired resistance to osimertinib or other EGFR inhibitors.

Significance:

This study demonstrates a critical role of c-Myc modulation in mediating therapeutic efficacy of osimertinib including osimertinib acquired resistance and suggests targeting c-Myc as a potential strategy to overcome osimertinib acquired resistance.
Fighting Liver Metastasis by Activating MAIT Cells
Authors: Lantz Olivier
Published: July 2021

In this issue, Ruf and colleagues show that antigen stimulation of mucosal-associated invariant T (MAIT) cells in the presence of the TLR9 ligand CpG decreases intrahepatic tumor growth, suggesting that MAIT cells could be used as an antitumor tool.

See related article by Ruf et al., p. 1024 (3).
Impact of the COVID-19 Pandemic on Gastroenterology Department Activity: The Gastroenterologist’s Perspective Nationwide and the Real Impact in a Portuguese Center
Authors: Ribeiro Gomes Ana Catarina , Pinho Rolando , Silva João Carlos , Afecto Edgar , Correia João P. , Carvalho João
Published: July 2021

Background: Several gastroenterology societies have created recommendations in order to reduce nonessential exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Our aim is to evaluate the national gastroenterologists’ perspective on the impact of COVID-19 and the impact of reorganization of a gastroenterology department during the COVID-19 pandemic. Methods: For the first purpose, an online survey was distributed to gastroenterologists nationwide. For the second purpose, the authors conducted an analysis of some endoscopic procedures performed at the Gastroenterology Department of the Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E) between March 16 and May 8 during the years 2019 and 2020. Results: Sixty-seven gastroenterologists answered our survey. Only 14.9% were residents and 86.6% worked in a hospital with COVID-19 patients, with 16.4% assigned to assist those patients. All of the departments suffered modifications. Ninety percent of the residents affirmed that their activity had changed. Ninety-four percent declared having nonessential endoscopic procedures postponed, and 85.1% maintained in-person medical visits, 88.1% were already having remote consultations, and 11.9% did not have any clinical visit. In our gastroenterology unit, the number of endoscopic procedures decreased by 73.1% from 2019 to 2020. In 2020, the proportion of urgent procedures was higher compared to 2019. Conclusion: The advent of COVID-19 has led to important changes in gastroenterology activities in Portugal, and national gastroenterology units are complying with the recommendations. Furthermore, Portuguese gastroenterologists believed that the decrease in endoscopic activity can compromise residents’ education and training. The gastroenterology department at CHVNG/E has shown a significant reduction in the number of endoscopic procedures.
Cholangiocarcinoma: An Emerging Target for Molecular Therapy
Authors: Tsimafeyeu Ilya , Temper Mark
Published: July 2021

Background: Cholangiocarcinoma has been traditionally considered a tumor with poor prognosis. Until now, surgical treatment has been the only more or less effective approach. Summary: Over 10 years, chemotherapy with a combination of gemcitabine and cisplatin remains the standard first-line therapy for patients with locally advanced or metastatic cholangiocarcinoma, which leads to a median overall survival of 11.7 months. Several inhibitors of HER (ERBB), HGF/c-MET, Hedgehog, KRAS-BRAF-MEK-ERK, and PI3K/AKT/mTOR signaling pathways did not show their superiority to standard chemotherapy. The rise of hope is associated with the emergence of novel fibroblast growth factor receptors and isocitrate dehydrogenase inhibitors as well as immune checkpoint inhibitors.
Early Revision after Artificial Urinary Sphincter Implantation Does Not Impair the Long-Term Treatment Success
Authors: Sayedahmed Khalid , Rosenhammer Bernd , Burger Maximilian , Goßler Christopher
Published: July 2021

Introduction: After implantation of an artificial urinary sphincter (AUS) due to stress urinary incontinence, in some cases revision procedures may be necessary. This is mostly due to device infection or cuff erosion in the long term. The aim of this study was to evaluate the impact of early revision procedures (prior to or immediately after AUS activation) on the long-term outcome. Methods: We retrospectively evaluated patients who underwent primary AUS implantation between 2006 and 2019. Patients with previous radiotherapy, urethroplasty, urethral stent placement, or repeat AUS implantation were excluded. Early revision was defined as prior to or immediately after AUS activation and comprised pump repositioning or cuff size adaptation due to difficulties in using the pump, persistent urinary incontinence, or urinary retention. Patients were compared with regard to complication rates, functional outcome, and patient satisfaction. Univariable and multivariable logistic regression analyses were performed to analyze risk factors for early AUS revision. Kaplan-Meier analysis evaluated explantation-free survival. Results: A total of 250 patients were included. Twenty patients (8%) required early revision (pump repositioning in 15 cases [75%], cuff downsizing in 3 cases [15%], and cuff upsizing in 2 cases [10%]). Mean follow-up was 78.6 months. 96.4% of all patients were objectively continent at the time of last follow-up without differences between both groups, and patient satisfaction was high in both groups. No differences with regard to mechanical implant failure, tissue atrophy, and AUS explantation due to cuff erosion or implant infection were observed. Explantation-free survival was comparable in both groups. On univariable logistic regression analysis, coronary artery disease and transcorporal cuff placement were associated with early AUS revision. Conclusion: Early revision after AUS implantation can be performed without negative impact on the long-term outcome.
Atraumatic Insertion of a Cochlear Implant Pre-Curved Electrode Array by a Robot-Automated Alignment with the Coiling Direction of the Scala Tympani
Authors: Torres Renato , Hochet Baptiste , Daoudi Hannah , Carré Fabienne , Mosnier Isabelle , Sterkers Olivier , Ferrary Evelyne , Nguyen Yann
Published: July 2021

Introduction: Electrode array translocation is an unpredictable event with all types of arrays, even using a teleoperated robot in a clinical scenario. We aimed to compare the intracochlear trauma produced by the HiFocus™ Mid-Scala (MS) electrode array (Advanced Bionics, Valencia, CA, USA) using a teleoperated robot, with an automated robot connected to a navigation system to align the pre-curved tip of the electrode array with the coiling direction of the scala tympani (ST). Methods: Fifteen freshly frozen temporal bones were implanted with the MS array using the RobOtol® (Collin, Bagneux, France). In the first group (n = 10), the robot was teleoperated to insert the electrode array into the basal turn of the ST under stereomicroscopic vision, and then the array was driven by a slow-speed hydraulic insertion technique with an estimated placement of the pre-curved electrode tip. In the second group (n = 5), 3 points were obtained from the preoperative cone-beam computed tomography: the 2 first defining the ST insertion axis of the basal turn and a third one at the center of the ST at 270°. They provided the information to the automated system (RobOtol® connected with a navigation system) to automatically align the electrode array with the ST insertion axis and to aim the pre-curved tip toward the subsequent coiling of the ST. After this, the electrode array was manually advanced. Finally, the cochleae were obtained and fixed in a crystal resin, and the position of each electrode was determined by a micro-grinding technique. Results: In all cases, the electrode array was fully inserted into the cochlea and the depth of insertion was similar using both techniques. With the teleoperated robotic technique, translocations of the array were observed in 7/10 insertions (70%), but neither trauma nor array translocation occurred with automated robotic insertion. Conclusion: We have successfully tested an automated insertion system (robot + navigation) that could accurately align a pre-curved electrode array to the axis of the basal turn of the ST and its subsequent coiling, which reduced intracochlear insertion trauma and translocation.
KDM6A Lysine Demethylase Directs Epigenetic Polarity of MDSCs during Murine Sepsis
Authors: Bah Isatou , Alkhateeb Tuqa , Youssef Dima , Yao Zhi Q. , McCall Charles E. , El Gazzar Mohamed
Published: July 2021

Sepsis-induced myeloid-derived suppressor cells (MDSCs) increase mortality risk. We previously identified that long non-coding RNA Hotairm1 supports myeloid precursor shifts to Gr1+CD11b+ MDSCs during mouse sepsis. A major unanswered question is what molecular processes control Hotairm1 expression. In this study, we found by a genetic deletion that a specific PU.1-binding site is indispensable in controlling Hotairm1 transcription. We then identified H3K4me3 and H3K27me3 at the PU.1 site on the Hotairm1 promoter. Controlling an epigenetic switch of Hotairm1 transcription by PU.1 was histone KDM6A demethylase for H3K27me3 that derepressed its transcription with possible contributions from Ezh2 methyltransferase for H3K27me3. KDM6A knockdown in MDSCs increased H3K27me3, decreased H3K4me3, and inhibited Hotairm1 transcription activation by PU.1. These results enlighten clinical translation research of PU.1 epigenetic regulation as a potential sepsis immune-checkpoint treatment site.
Predicting the Risk of Ischemic Stroke in Patients Treated with Novel Oral Anticoagulants: A Machine Learning Approach
Authors: Kostev Karel , Wu Tong , Wang Yue , Chaudhuri Kal , Reeve Russel , Tanislav Christian
Published: July 2021

Introduction: The aim of this cohort study was to estimate the predictors of ischemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) in a large database containing data from general practitioners in Germany using machine learning methods. Methods: This retrospective cohort study included 39,652 patients with a diagnosis of atrial fibrillation (AF) and an initial prescription of NOAC in 1,278 general practices in Germany between January 2011 and December 2018. Of 39,652 patients, 2,310 (5.8%) receive the first stroke or TIA diagnosis during the follow-up time (average follow-up time 2.5 [SD: 1.8] years). Sub-Population Optimization and Modeling Solutions (SOMS) tool was used to identify subgroups at a higher risk of stroke compared to the overall population receiving NOAC based on 37 different variables. Results: Using SOMS, a total of 9 variables were considered important for the stroke prediction. Age had 59.1% of prediction importance, following by ischemic heart diseases (10.6%), urinary tract infections (4.6%), dementia (3.5%), and male sex (3.5%). Further variables with less importance were dizziness (2.2%), dorsalgia (1.5%), shoulder lesions (1.1%), and diabetes mellitus (1.1%). Discussion/Conclusions: The stroke risk in AF patients treated with NOAC could be predicted based on comorbidities like ischemic heart diseases, urinary tract infections, and dementia additionally to age and male sex. Knowing and addressing these factors may help reduce the risk of stroke in this patient population.
Perioperative Outcomes of Transurethral Resection, Open Prostatectomy, and Laser Therapy in the Surgical Treatment of Benign Prostatic Obstruction: A “Real-World” Data Analysis from the URO-Cert Prostate Centers
Authors: Herden Jan , Ebert Thomas , Schlager Daniel , Pretzer Jana , Porres Daniel , Schafhauser Wolfgang , Kriegmair Martin , Schürmann Miguel Garcia , Distler Florian , Oberpenning Frank , Reimann Michael , Haupt Gerald , Schmidt Sebastian , Laabs Sven , Planz Bernhard , Cohausz Maximilian , Gronau Eckart , Platz Guido , Buse Stephan , Jones Jon , Waldner Michael , Heidenreich Axel , Ruebben Herbert , Zumbe Juergen , Goell Alexander , Khaljani Ehsan , Czempiel Winfried , Schultze-Seemann Wolfgang , Weib Peter
Published: July 2021

Introduction: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). Methods: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. Results: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4–7) for TUR-P, 9 days (IQR: 7–11) for OP, and 5 days (IQR: 4–6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27–8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12–22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03–3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74–3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56–7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66–2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. Conclusion: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.
Nemaline Myopathy: A Case Report
Authors: Mubaraki Adnan A.
Published: July 2021

Generalized weakness in the pediatric and adolescent population is caused by many disorders that affect the neuromuscular axis. As next-generation sequencing (NGS) is becoming of high yield in replacing more invasive procedures, that is, muscle and nerve biopsy, more previously undiagnosed diseases of the muscles are now labeled with specific pathogenicity. A 16-year-old-girl diagnosed with nemaline myopathy but previously was misdiagnosed with congenital myasthenia and put-on unnecessary medications. Clinicians should be aware of congenital diseases that affect the muscles and know the importance of the NGS in reaching the correct diagnosis more so when there is a history of consanguinity.
Unusual Presentation of a Gastrointestinal Stromal Tumor in a Small Intestine Diverticulum
Authors: Senti Mackenna , Torres Tania A. , Espinosa Jairo , Shebrain Saad
Published: July 2021

A 50-year-old female with no significant medical history initially presented to an urgent care center with symptoms of acute onset abdominal pain, nausea, and emesis. Chest and abdominal X-ray revealed free air under the diaphragm, prompting immediate transfer to the emergency department. Continued abdominal tenderness and pain were concerning for perforated viscus. The patient was transferred to the operating room, and diagnostic laparoscopy was performed. Inflammation and contamination were discovered in the right side of the abdomen and pelvis secondary to a small bowel (SB) perforation. Segmental SB resection revealed a perforated diverticulum. Pathological examination confirmed a diagnosis of gastrointestinal stromal tumor (GIST) at the perforated segment. On postoperative day 5, the patient was discharged home, and at 30-month follow-up, the patient continued to do well. Although rare, SB diverticula are commonly false (i.e., pseudodiverticula). The concomitant presence of a GIST in a true SB diverticulum presenting with perforation has not yet been reported.
Rücken und Schmerz: Nicht immer nur entzündlich!
Authors: Adler Sabine
Published: July 2021

Objectives: The main purpose of this retrospective cohort study was to provide an evaluation of Ankylosing spondylitis (AS) patients’ fibromyalgia risk in different age and sex subgroups by analyzing large study samples. Methods: Datasets from the National Taiwan Insurance Research Database (NHIRD) were retrieved in this retrospective cohort study. This study was approved by the Institutional Review Board of Chung Shan Medical University (IRB permit number CS15134). Within the Longitudinal Health Insurance Database (LHID), and the subset of NHIRD, we identified AS patients to explore the risk of further fibromyalgia. The exposure cohort included patients with newly-diagnosed AS (ICD-9-CM:720.0) during 2000–2013. After 1:4 age-sex matching and 1:2 propensity score matching, and adjusting potential confounders, individuals without AS were identified as a comparison cohort. The adjusted hazard ratio of subsequent development of fibromyalgia in people with AS was evaluated. Further stratification analyses of different ages and genders were then undertaken to validate the results. Results: In total, 17 088 individuals were included in the present study, including 5,696 patients with AS and 11,392 individuals without AS. Respective incidence rates (per 1,000 person-months) of fibromyalgia was 0.52 (95% CI, 0.46–0.59) in the AS cohort and 0.39 (95% CI, 0.35–0.44) in the non-AS cohort. Compared with the non-AS cohort, aHR of developing fibromyalgia was 1.32 (95% CI, 1.12–1.55) in people with AS. This association was consistent in both statistical models of 1:4 age-sex matching and 1:2 propensity score matching. Conclusion: Patients with AS were associated with a higher risk of fibromyalgia, especially those over 65 years old. In managing patients with AS, clinicians should be aware of this association, which could impact diagnosis, disease activity evaluation, and treatment.
Einsatz von Secukinumab bei Patienten mit Psoriasis und Psoriasis-Arthritis – Ergebnisse einer nichtinterventionellen Studie unter Praxisbedingungen (SERENA-Studie)
Authors: Sticherling Michael
Published: July 2021

Introduction: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. Methods: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. Results: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N =  460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89–1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n =  1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. Conclusion: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.
Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post–Cardiac Arrest
Authors: Hoiland Ryan L. , Ainslie Philip N. , Wellington Cheryl L. , Cooper Jennifer , Stukas Sophie , Thiara Sonny , Foster Denise , Fergusson Nicholas A. , Conway Edward M. , Menon David K. , Gooderham Peter , Hirsch-Reinshagen Veronica , Griesdale Donald E. , Sekhon Mypinder S.
Published: July 2021

Rationale:

Secondary brain hypoxia portends significant mortality in ischemic brain diseases; yet, our understanding of hypoxic ischemic brain injury (HIBI) pathophysiology in humans remains rudimentary.

Objective:

To quantify the impact of secondary brain hypoxia on injury to the neurovascular unit in patients with HIBI.

Methods and Results:

We conducted a prospective interventional study of invasive neuromonitoring in 18 post–cardiac arrest patients with HIBI. The partial pressures of brain tissue O
2
(PbtO
2
) and intracranial pressure were directly measured via intraparenchymal microcatheters. To isolate the cerebrovascular bed, we conducted paired sampling of arterial and jugular venous bulb blood and calculated the transcerebral release of biomarkers of neurovascular injury and inflammation in the patients with HIBI and 14 healthy volunteers for control comparisons. Ten patients with HIBI exhibited secondary brain hypoxia (PbtO
2
<20 mmHg), while 8 exhibited brain normoxia (PbtO
2
≥20 mmHg). In the patients with secondary brain hypoxia, we observed active cerebral release of glial fibrillary acidic protein (−161 [−3695 to −75] pg/mL;
P
=0.0078), neurofilament light chain (−231 [−370 to −11] pg/mL;
P
=0.010), total tau (−32 [−310 to −3] pg/mL;
P
=0.0039), neuron-specific enolase (−14 890 [−148 813 to −3311] pg/mL;
P
=0.0039), and ubiquitin carboxy-terminal hydrolase L1 (−14.7 [−37.7 to −4.1] pg/mL;
P
=0.0059) indicating de novo neuroglial injury. This injury was unrelated to the systemic global ischemic burden or cerebral endothelial injury but rather was associated with cerebral release of IL-6 (interleukin-6; −10.3 [−43.0 to −4.2] pg/mL;
P
=0.0039). No cerebral release of the aforementioned biomarkers was observed in patients with HIBI with brain normoxia or the healthy volunteers. Hyperosmolar therapy in the patients with secondary brain hypoxia reduced the partial pressure of jugular venous O
2
-to-PbtO
2
gradient (39.6 [34.1–51.1] versus 32.0 [24.5–39.2] mm Hg;
P
=0.0078) and increased PbtO
2
(17.0 [9.1–19.7] versus 20.2 [11.9–22.7] mm Hg;
P
=0.039) suggesting improved cerebrovascular-to-parenchymal O
2
transport.

Conclusions:

Secondary brain hypoxia is associated with de novo neuroglial injury and cerebral release of IL-6. Mitigating cerebrovascular-to-parenchymal limitations to O
2
transport is a promising therapeutic strategy for patients with HIBI with secondary brain hypoxia.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03609333.
Breastfeeding in the First Days of Life Is Associated With Lower Blood Pressure at 3 Years of Age
Authors: Miliku Kozeta , Moraes Theo J. , Becker Allan B. , Mandhane Piushkumar J. , Sears Malcolm R. , Turvey Stuart E. , Subbarao Padmaja , Azad Meghan B.
Published: July 2021

Background

Breastfeeding in infancy is associated with lower cardiovascular disease risk in adulthood; however, the amount of breastfeeding required to achieve this benefit is unknown.

Methods and Results

In the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study, we analyzed 2382 children with complete data on early life feeding and blood pressure. Infant feeding was documented from hospital records in the first few days of life and reported by mothers throughout infancy. Blood pressure was measured at 3 years of age. Analyses controlled for birth weight, gestational age, socioeconomic status, maternal body mass index, and other potential confounders. We found that nearly all children (2333/2382; 97.9%) were ever breastfed, of whom 98 (4.2%) only briefly received breast milk during their birth hospitalization (“early limited breastfeeding”). At 3 years of age, blood pressure was higher in children who were never breastfed (mean systolic/diastolic 103/60 mm Hg) compared with those who were ever breastfed (99/58 mm Hg), including those who received only early limited breastfeeding (99/57 mm Hg). These differences in systolic blood pressure persisted in adjusted models (ever breastfed: −3.47 mm Hg, 95% CI, −6.14 to −0.80; early limited breastfeeding: −4.24 mm Hg, 95% CI, −7.45 to −1.04). Among breastfed children, there was no significant dose‐response association according to the duration or exclusivity of breastfeeding. Associations were not mediated by child body mass index.

Conclusions

Although the benefits of sustained and exclusive breastfeeding are indisputable, this study indicates any breastfeeding, regardless of duration or exclusivity, is associated with lower blood pressure at 3 years of age. Further research examining the bioactive components of early breast milk, underlying mechanisms, and long‐term associations is warranted.
Conspecific aggression strategies are conditioned by environmental, social and intrinsic variables in breeding blue tits Cyanistes caeruleus
Authors: Velasco Adara C. , Ferrer Esperanza S. , Sanz Juan José
Published: July 2021

Territorial behaviour arises as a strategy of ensuring individuals’ access to a variety of potentially limiting resources. While aggressiveness is a well-studied widespread trait across taxa, the mechanisms that allow for a range of aggressive phenotypes to coexist in the wild remains unclear. In this study, we analyse environmental, social and intrinsic variables that can modulate the expression of different strategies of male–male aggressiveness. Furthermore, through network analysis we explore the role of this trait in the establishment of territories during the breeding season as the intensity of different aggressiveness strategies may limit or grant access to resources. Simulating territorial intrusions during the early incubation period, we assessed the aggressiveness of breeding male blue tits (Cyanistes caeruleus). We defined three types of conspecific aggressiveness (nonconfrontational intimidating, nonconfrontational cautious and confrontational) and analysed the effect of habitat structure, territory quality, presence of other breeding species and male condition on the type and intensity of the aggressive display. The results obtained suggest that yearling males rely on intimidating behaviour more than older males, that perform more cautious displays. Furthermore, smaller and heavier males opted for confrontational strategies. The density and nature of neighbours, as well as the territory quality and the habitat structure, also conditioned the intensity and type of display. Surprisingly, the network analysis revealed that the intensity of male–male aggressive displays did not condition the establishment of breeding territories. Our results suggest that aggressiveness is a context-specific trait shaped by a complex array of environmental and intrinsic parameters.
Phylogenetic analysis and trait evolution of ant cocoons
Authors: Greer Jordan A. , Moreau Corrie S.
Published: July 2021

Most ant species have lost the ability to spin cocoons. To explore the evolution of cocoon loss within Formicidae, we perform an ancestral state reconstruction of cocooned pupae across a genus-level phylogeny and use a sister clade analysis to determine the impact of cocoon evolution on ant speciation. Then, we fit models of correlated evolution between cocoon status and several other organismal traits. We find that the re-emergence of cocoons is rare and that “naked” lineages display an increased rate of speciation in 5 out of 9 sister group comparisons. Models of correlated evolution with cocoon status were favored for metapleural gland and worker polymorphism. Metapleural gland favored rates of evolution were inconclusive, while worker polymorphism displayed a higher transition rate towards polymorphism coupled with cocoon loss. These results suggest that cocoon loss may allow for other complex traits to develop and may represent a novel example of relaxed selection.
History as Antidote to Wounded National Pride: Politics of History in Kemal Tahir’s Devlet Ana
Authors: Erdem Servet
Published: July 2021

This article analyses Devlet Ana, Kemal Tahir’s novel on the rise of the Ottomans, within the scope of the politics of history. Through an analysis of Tahir’s novel, the article reveals the political and ideological forces that brought about a reactionary, monolithic, and totalising understanding of history and historiography in the Turkish literary institution. The article argues that despite Tahir’s allegedly Marxist framing, his understanding of history—driven by an inferiority complex and Westophobia—hardly goes beyond an ethical binarism in which absolute good or evil racial and civilisational nature determines everything.
Turkey’s Candidature to the UN Security Council Seat in 1948: Why the West’s ‘Favorite’ Candidate Lost
Authors: Balcı Ali , Duman Talha İsmail
Published: July 2021

Following the Second World War, Turkey vigorously pursued a policy of effective participation in international institutions. As part of this policy, Turkish diplomats campaigned for a non-permanent seat in the UN Security Council in the year 1948. This article aims to provide descriptive information about this campaign and explain why Turkey lost the election in the UN General Assembly for the seat reserved for the Near East region. In doing so, the article primarily uses historical documents from the Foreign Relations of the United States (frus) series because they provide very detailed information about backstage diplomacy, motivations of candidate countries, and opinions of the US diplomats about candidates. The article concludes that it was the US Cold War policies that influenced the outcome of the 1948 election. Although it was publicly known that the US supported Turkey in this election, a closer examination of the American diplomatic documents reveals that the US voted for Egypt in order to keep it in the Western camp.
Profane Illuminations: Robert Anton Wilson’s Hedonic Ascesis
Authors: Davis Erik
Published: July 2021

The writer Robert Anton Wilson (1932–2007) played a significant intellectual role in the American counterculture in the late 1970s, 1980s, and 1990s. Drawing from a wide range of discourses, as well as his own occultural fictions and personal experiments in “hedonic engineering,” Wilson presented a pluralistic view of reality that combined a pragmatic skepticism with a creative and esoteric embrace of the “meta-programming” possibilities of altered states of consciousness. In his 1975 Illuminatus! trilogy, written with Robert Shea, Wilson wove anarchist, psychedelic, and occult themes into a prophetic conspiracy fiction written with a satiric and willfully pulp sensibility. Ritually experimenting with psychedelic drugs and sexual magic – experiences related in his 1977 book Cosmic Trigger – Wilson developed a wayward if deeply self-reflexive theory and dialectical method of visionary practice, one that, amidst the paranoia, presented its own deconstructive and libertarian vision of gnosis. This essay contextualizes and unpacks Wilson’s visionary pragmatism in terms of Foucault’s roughly contemporaneous notion of “technologies of self,” later elaborated by Peter Sloterdijk as “anthropotechnics.” It also traces the specific debts that Wilson owed to other esoteric and psychedelic technologists of the self, including Aleister Crowley, Timothy Leary, and John Lilly.
Lectotypification of three names in Cicer (Fabaceae)
Authors: KRIVENKO DENIS , TATANOV IVAN
Published: July 2021

Cicer Linnaeus (1753: 738), as currently established, includes about 50 species distributed from north to south from the Altai Mountains (C Asia) to the East African Rift (E Africa), and from west to east from the Canary Islands (W Africa) to the upper Irtysh River in Dzungaria (C Asia) (van der Maesen et al. 2007, Dönmez 2011, Toker et al. 2021). In the course of our revisionary work on this genus for Caucasian flora conspectus (Takhtajan 2003), we found the name C. anatolicum Alefeld (1861: 349) and its synonym C. glutinosum Alefeld (1861: 349), also the name C. minutum Boiss. & Hohen. in Boissier (1849: 130) that warrant lectotypification in accordance with the Shenzhen Code (Turland et al. 2018). The second-step lectotypification is made for C. anatolicum and C. minutum, while the lectotype is selected for C. glutinosum based on the analysis of their protologues and original herbarium material deposited in C, BM, G, LE, M, MO, P and WAG. Herbarium acronyms mentioned here follow Thiers (2021-onward).
A fresh look at Cosmetus Perty, 1833 (Opiliones: Cosmetidae), with new synonymies and description of two new species from Colombia
Authors: MEDRANO MIGUEL , KURY ADRIANO B. , MARTINEZ LEONEL
Published: July 2021

Cosmetus Perty, 1833 is the type genus of the most diverse subfamily of Laniatores, Cosmetinae. The genus currently includes 22 valid species with a disconnected distribution, including coastal forests of NE Brazil, dry forests of the Ecuadorian Pacific, Chocó-Darien moist forests and the Venezuelan Andes. The morphology among species in the genus is quite variable, but they share almost exclusively the fused spine in area III. The type species Cosmetus varius is little known due to few, poor quality illustrations, a vague type locality, and lost type material, and was misidentified by Koch in 1840, making it difficult to define or even taxonomically revise the genus. Herein we: (1) provide distribution maps for nominal Cosmetus species; (2) recognize the poorly defined type species C. varius as a species occurring in central-eastern Bahia, agreeing with the itinerary of Spix and von Martius; (3) synonymize three other species from central-eastern Bahia with C. varius; (4) provide images of the external morphology of three Brazilian species of the genus; and (5) describe two new sympatric species from the Colombian Pacific region (Chocó-Darien moist forest), thus representing the first report of the genus for the country. Both Colombian species, Cosmetus acanti sp. nov. and Cosmetus villarreali sp. nov., have similar external morphology but are remarkably different in genital morphology. Morphological evidence indicates that Cosmetus may be an artificial group. However, given the chaotic taxonomy of the family Cosmetidae, and the deep intertwining of nomenclature, we do not know at the moment where each of those species should be classified.