bluuebunny/crossref_metadata_2025 huggingface dataset:
Airflow Patterns around Obstacles with Large‐Span Shallow Shell Roof: Wind Tunnel Measurements and Direct Simulation
Authors: Jia Hongying , Dang Huixue , Ma Qianying , Zhao Jun-Hai
Published: November 2019

Wind tunnel tests on the rigid model of large‐span shallow spherical shell roof structure were carried out. The variation rule and the calculation method for the average shape coefficient of the fluctuating wind pressure under six different typical wind directions were obtained. The wind pressure distribution of the node deflection and cross section stress was numerically investigated and analyzed. Meanwhile, the effect of mechanics‐flow form of the typical spherical shell structure on the wind pressure distribution was analyzed quantitatively. In this study, it is found that the results of numerical simulation agree well with the wind tunnel test data. The study on the mechanical characteristics, as well as the wind vibration research, of the spherical shell structure in different working conditions provides a reliable theoretical basis for the mechanical index of the wind vibration.
Hepatocyte Growth Factor in Blood and Gastric Cancer Risk: A Nested Case–Control Study
Authors: Jang Jieun , Ma Seung Hyun , Ko Kwang-Pil , Choi Bo Yul , Yoo Keun-Young , Park Sue K.
Published: November 2019

Background:

Potential of hepatocyte growth factor (HGF)–stimulating signaling pathways related to cytotoxin-associated gene A (CagA) to predict gastric cancer development has not been fully investigated.

Methods:

We conducted a nested case–control study consisting of 238 gastric cancer cases and 238 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF concentrations were measured with a human HGF ELISA. Odds ratios (OR) and 95% confidence intervals (CI) for gastric cancer development according to HGF level were calculated using conditional logistic regression model.

Results:

Sequential elevation of gastric cancer risk according to HGF level increase was observed (OR, 10.99; 95% CI, 4.91–24.62) for highest quartile HGF (≥364 pg/mL) versus lowest quartile HGF (<167 pg/mL). A significantly increased gastric cancer risk associated with high HGF level measured even 6 or more years prior to cancer diagnosis was also found. The group with both high risk of HGF and CagA-related genetic variants was associated with highest gastric cancer risk compared with the group with both low risk of HGF and genetic variants (Pinteraction = 0.05). Model performance using HGF and CagA-related genetic variants to discriminate gastric cancer was fair [area under the curve of receiver operating characteristic (AUC-ROC), 0.71; 95% CI, 0.64–0.78] and significantly higher than that of model not including those biomarkers.

Conclusions:

Our results suggest HGF as a potential biomarker to predict gastric cancer development.

Impact:

These findings suggest HGF as a useful biomarker to predict gastric cancer risk. Further research to assess gastric cancer risk based on useful biomarkers, including HGF, may contribute to primary prevention of gastric cancer.
Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research
Authors: Lubas Margaret M. , Lu Yan , Gehr Aaron W. , Ghabach Bassam , Tanna Bhavna , Narra Kalyani , Brinkman Tara M. , Ojha Rohit P.
Published: November 2019

Background:

Limited information is available about the representativeness of survivors engaging in patient-centered research, despite the potential for threats to generalizability. We thus aimed to assess the representativeness of survivors engaged or interested in research development.

Methods:

We used data from the Health Information National Trends Survey, a nationally representative survey, to identify survivors of adult cancers. Our outcomes of interest were based on responses to questions about engagement or interest in developing patient-centered research. We estimated the ratio of relative frequencies (RRF) and corresponding 95% confidence limits (CL) of sociodemographic and survivorship characteristics between survivors engaged or interested in patient-centered research and the overall survivor population.

Results:

Our study population comprised 934 survivors, of whom 5% reported being engaged in patient-centered research and 26% reported an interest in participating. Relative frequencies of characteristics were discordant for engaged survivors but largely similar for interested survivors compared with all survivors. In particular, engaged survivors had a higher relative frequency of individuals ages 50 to 64 years (RRF = 1.7; 95% CL, 1.1–2.5), Hispanic (RRF = 2.9; 95% CL, 1.2–6.9), non-Hispanic Black (RRF = 2.9; 95% CL, 1.1–2.5), and unemployment (RRF = 4.7; 95% CL, 1.4–16).

Conclusions:

We observed several meaningful differences in the characteristics of survivors engaged in patient-centered research compared with all survivors, which raises concerns about the generalizability of findings from such studies.

Impact:

Patient-centered research may not benefit the broader survivor community if survivors engaging in research development are not representative of all survivors. Greater attention to recruiting mechanisms is necessary to avoid creating disparities.
Endobronchial Ultrasound for the Diagnosis of Centrally Located Lung Tumors: A Systematic Review and Meta-Analysis
Authors: Kuijvenhoven Jolanda C. , Leoncini Fausto , Crombag Laurence C. , Spijker René , Bonta Peter I. , Korevaar Daniël A. , Annema Jouke T.
Published: November 2019

Introduction: Obtaining a tissue diagnosis of centrally located lung tumors in patients presenting without endobronchial abnormalities is challenging, and therefore a considerable diagnostic problem. Objective: The objective of this study was to evaluate the performance of linear endobronchial ultrasound guided-transbronchial-needle aspiration (EBUS-TBNA) for the diagnosis of centrally located lung tumors. Methods: We performed a systematic review (PROSPERO, CRD42017080968) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science till November 18, 2018 for studies that evaluated the yield and/or sensitivity of EBUS-TBNA for diagnosing centrally located lung tumors. We assessed the study quality using QUADAS-2 and performed random-effects meta-analysis. Results: A total of 5,657 manuscripts were identified; of these 14 were considered for the study, including 1,175 patients who underwent EBUS-TBNA for diagnosing an intrapulmonary tumor. All studies had a high risk of bias or applicability concerns, predominately regarding patient selection. The average yield of EBUS-TBNA for diagnosing centrally located lung tumors was 0.89 (95% CI 0.84–0.92) and average sensitivity for diagnosing malignant tumors was 0.91 (95% CI 0.88–0.94). Among studies reporting this information, EBUS-related complications occurred in 5.4% of patients (42/721). Conclusion: EBUS-TBNA has a high yield and sensitivity for diagnosing centrally located lung tumors and is safe in selected patients. Prospective studies are recommended to evaluate the routine use of this procedure for diagnosing intrapulmonary tumors.
Incidence and Predictors of Permanent Pacemaker Implantation in Patients Who Underwent Transcatheter Aortic Valve Replacement: Observation of a Chinese Population
Authors: Du Fang , Zhu Qifeng , Jiang Jubo , Chen Han , Liu Xianbao , Wang Jian’an
Published: November 2019

Aims: Permanent pacemaker (PPM) implantation is one of the most common complications after transcatheter aortic valve replacement (TAVR). We studied the incidence of PPM implantation and identified the predictors in patients who underwent TAVR in a Chinese population. Methods and Results: A total of 256 patients who underwent TAVR with self-expandable valves were included. The incidence of PPM implantation in our study population was 14.8%. In patients who received PPM implantation, the proportion of bicuspid aortic valve (BAV) patients was much lower compared to tricuspid aortic valve (TAV) patients (18.4 vs. 81.6%, p < 0.05). Patients with BAV were associated with a significantly lower PPM implantation rate and shallower implantation depth compared to patients with TAV (6.4 vs. 21.7% and 4.2 ± 4.4 vs. 6.2 ± 5.0 mm, respectively, p < 0.05 for both). In the multivariable logistic regression analysis, prior right bundle branch block (RBBB; OR 8.3, 95% CI 2.2–32.1, p < 0.05), implantation depth (OR 1.3, 95% CI 1.1–1.5, p = 0.01), and TAV (OR 4.7, 95% CI 1.5–14.4, p < 0.05) were independent predictors of PPM implantation after TAVR. There was no difference in 30-day and 1-year all-cause mortality between the 2 groups. Conclusions: The incidence of PPM implantation in patients with self-expandable valves after TAVR was 14.8% in our cohort study. Independent predictors of PPM implantation included prior RBBB, TAV, and implantation depth at the noncoronary sinus side. TAVR in BAV with a supra-annular structure-based sizing strategy might decrease the risk of PPM implantation.
Anomalous Experience of Self and World: Administration of the EASE and EAWE Scales to Four Subjects with Schizophrenia
Authors: Englebert Jérôme , Monville François , Valentiny Caroline , Mossay Françoise , Pienkos Elizabeth , Sass Louis
Published: November 2019

The aim of this paper was to study anomalies of self- and world experience in schizophrenia from a phenomenological perspective through the use of the Examination of Anomalous Self-Experience (EASE) and Examination of Anomalous World Experience (EAWE) interviews. Four patients with diagnoses of schizophrenia were interviewed with both the EASE and the EAWE. A qualitative analysis of these interviews was carried out on all the data; quantitative scores were also assigned, based on the frequency and intensity of the items endorsed by the subjects. In the EASE, the subjects endorsed an average frequency of 45% of all items. In the EAWE, the subjects endorsed an average frequency of 26% of all items. Furthermore, the EAWE data indicated more heterogeneous profiles of experience than the EASE data. This heterogeneity is not surprising, given that the EAWE was designed to be a more broad-based or less targeted exploration of various changes likely to be associated with the schizophrenia spectrum (but also with certain other conditions). Our data suggest that although disturbances of world experience may always be present in schizophrenia, they may take numerous and varied forms. Because the experience of the world occurs across many different modalities, disturbances of this experience would be fundamentally less unitary, whereas the experience of the self presents a more coherent and unitary gestalt. These results show a certain overlapping between the scales while also indicating the potential value of a combined use of the two instruments. Finally, we discuss the relationship between experiential description and behavioral observation, and their potentially complementary value in exploring the first-person perspective, particularly in the case of experiences that occur at a more prereflective level.
Changes in CD4+CD25+FoxP3+ Regulatory T Cells and Serum Cytokines in Sublingual and Subcutaneous Immunotherapy in Allergic Rhinitis with or without Asthma
Authors: Xian Mo , Feng Mulin , Dong Yan , Wei Nili , Su Qiujuan , Li Jing
Published: November 2019

Background: Few studies have directly compared the immunologic responses to specific subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Objective: We aimed to directly compare clinical efficacy and immunological responses between SLIT and SCIT in allergic rhinitis (AR) sensitized to house dust mites. Methods: Sixty-seven patients (age 5–55 years) with moderate-severe Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae AR with or without asthma were randomized (2:2:1) into SLIT (n = 27), SCIT (n = 26) and placebo (n = 14) groups. Symptom and medication scores, visual analogue score, serum Der-p specific immunoglobulin G4 (Der-p-sIgG4), CD4+CD25+FoxP3+ regulatory T cells (Tregs) and serum cytokines were measured. Results: After 1-year treatment, a significant improvement of total rhinitis score (TRS), total rhinitis medication score (TRMS) and visual analogue score occurred in both SLIT and SCIT. There were no differences in clinical efficacy except for TRMS (p = 0.026) when SLIT and SCIT were directly compared. CD4+CD25+FoxP3+ Tregs had a trend towards upregulation in the 2 modes and inversely correlated with TRS (p = 0.024) only in SLIT. Der-p-sIgG4 significantly increased in SLIT and SCIT (p < 0.05), and it was 30 times higher in SCIT than SLIT after the treatment (p < 0.05). Serum interferon-γ significantly increased only in SCIT after 1 (p = 0.008), 6 (p = 0.007) and 12 (p = 0.008) months of treatment and inversely correlated with TRS (p = 0.032). Conclusion: While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4+CD25+Foxp3+ Tregs, sIgG4 and cytokines.
Vocal and Nonvocal Habits among Vedic Chanters
Authors: Ramani Sai Aishwarya , Kumar Balasubramanium Radish , Gunjawate Dhanshree R.
Published: November 2019

Objectives: The objective of the present study was to explore the voice concerns and vocal and nonvocal habits of Vedic chanters. Participants and Method: A cross-sectional design was used to study 200 Vedic chanters using a 36-item questionnaire. This questionnaire was developed and administered to explore their voice concerns and vocal and nonvocal habits. Descriptive statistics were used to summarize the findings and K-means cluster analysis was carried out to identify clusters concerning voice quality and influence of habits. Results: The majority of Vedic chanters were involved in certain vocal habits such as use of loud voice while chanting and frequent throat clearing. Further, approximately half of the chanters expressed a concern towards their voice, while a vast majority experienced vocal fatigue. Cluster analysis helped in identification of 4 clusters: Vedic chanters with (1) good lifestyle and good voice characteristics (n = 107), (2) good lifestyle but bad voice characteristics (n = 15), (2) poor lifestyle and good voice characteristics (n = 51), and (4) poor lifestyle leading to bad voice characteristics (n = 27). Conclusion: The findings of the present study provide useful information on voice concern and vocal and nonvocal habits among a unique population of individuals. The current study of Vedic chanters highlights the need to have a detailed understanding of their specific voice usage, demands, and voice characteristics.
18F-Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma as a Useful Predictor of an Extremely Rapid Response to Lenvatinib
Authors: Kawamura Yusuke , Kobayashi Masahiro , Shindoh Junichi , Kobayashi Yuta , Kasuya Kayoko , Sano Tomoya , Fujiyama Shunichiro , Hosaka Tetsuya , Saitoh Satoshi , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Ikeda Kenji , Arase Yasuji , Hashimoto Masaji , Kumada Hiromitsu
Published: November 2019

Background and Aims: This study aimed to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of the response of hepatocellular carcinoma (HCC) to lenvatinib. Methods: We evaluated 28 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT. The tumor-to-normal liver standardized uptake value ratio (TLR) of the target tumor was measured before treatment using 18F-FDG-PET/CT, with a TLR ≥2 classified as a high potential for malignant HCC. The treatment response was evaluated 2 weeks after the initiation of lenvatinib using modified Response Evaluation Criteria in Solid Tumors. Results: Of the 28 patients, 12 (43%) presented with a TLR ≥2. Evaluation of the treatment response at 2 weeks in these 12 patients revealed that 2 (17%) exhibited a complete response, 8 (67%) a partial response, 2 (17%) stable disease, and none with progressive disease. Therefore, 10 of the 12 patients (83%) experienced an objective response to lenvatinib. On the other hand, 7 of the 16 patients with a TLR <2 (44%) experienced an objective response. Thus, the objective response rate was higher in patients with a TLR ≥2 than in those with a TLR <2. Multivariate logistic regression analysis revealed that a TLR ≥2 (odds ratio 10.53; p = 0.028) is a useful predictor of an early objective response at 2 weeks. Conclusion: Patients with unresectable HCC showed a good early treatment response to lenvatinib. High TLR (≥2) may be a useful predictor of an extremely rapid treatment response.
Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy
Authors: Avendaño-Estrada Arturo , Velasco Francisco , Velasco Ana Luisa , Cuellar-Herrera Manola , Saucedo-Alvarado Pablo E. , Marquez-Franco Rene , Rivera-Bravo Belen , Ávila-Rodríguez Miguel A.
Published: November 2019

Background: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. Methods: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2’-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. Results: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. Conclusion: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.
Dynamics Is Not Enough: An Interactivist Perspective
Authors: Bickhard Mark H.
Published: November 2019

An underlying process metaphysics is, arguably, necessary, but it is not sufficient for understanding the world, and, in particular, for understanding the mind and its development. It is necessary for both logical and empirical reasons, but we also need to account, within such a dynamic framework, for emergent normativity, adaptability, and cognition, among other phenomena, in order to model development. I will sketch these arguments, and then outline a model of development within that framework, with a brief introduction to how these processes are realized in the brain.
Correlation between Diabetic Retinopathy Severity and Oxygen Metabolism in Patients with Diabetic Macular Edema during Treatment with Intravitreal Aflibercept
Authors: Blindbæk Søren Leer , Peto Tunde , Grauslund Jakob
Published: November 2019

Purpose: To attribute data on changes in diabetic retinopathy (DR) severity during treatment of diabetic macular edema (DME) with vascular endothelial growth factor inhibitors (anti-VEGF), this study aimed to (1) examine the correlation between oxygen saturations in retinal vessels and the number of DR lesions on ultra-wide field color fundus photographs prior to anti-VEGF treatment and (2) compare changes in oxygen saturations in retinal vessels with changes in the number of DR lesions after a loading dose of three monthly intravitreal injections of 2.0 mg of aflibercept. Methods: This 3-month prospective study included 37 eyes of patients with DME and varying severity of peripheral DR lesions. DR lesions were graded on wide field images and retinal oxygen saturations were evaluated by retinal oximetry. Patients were then treated with three monthly intravitreal injections of 2 mg aflibercept and wide field imaging and retinal oximetry were repeated 4 weeks after the last injection. Patients with proliferative DR or previous panretinal photocoagulation were excluded. Results: Baseline retinal arteriolar oxygen saturation increased with increasing DR severity and numbers of microaneurysms, hemorrhages, and cotton wool spots (p = 0.03, 0.01, 0.03, and <0.001), while no correlation between the severity of DR lesions and retinal venular oxygen saturation was found. After treatment with intravitreal aflibercept, the severity of DR lesions significantly reduced, while retinal arteriolar and venular oxygen saturation as well as the arteriolar-venular difference remained unchanged (95.5 vs. 95.8%, p = 0.44; 62.9 vs. 64.5%, p = 0.08; 32.5 vs. 31.4%, p = 0.33). Conclusion: This study demonstrated that structural DR lesions correlate with retinal arteriolar oxygen saturation in patients with DME prior to anti-VEGF treatment and that improvement in the severity of DR lesions can occur without corresponding changes in retinal oxygen metabolism during intravitreal therapy. Our results suggest that DR severity on color fundus photographs should be interpreted with caution once intravitreal therapy is initiated.
Efficacies and Related Issues of Ustekinumab in Japanese Patients with Crohn’s Disease: A Preliminary Study
Authors: Miyazaki Takako , Watanabe Kenji , Kojima Kentaro , Koshiba Ryoji , Fujimoto Koji , Sato Toshiyuki , Kawai Mikio , Kamikozuru Koji , Yokoyama Yoko , Hida Nobuyuki , Nakamura Shiro
Published: November 2019

Introduction: Ustekinumab (UST) is an antibody to the p40 subunit of interleukins 12 and 23 in Crohn’s disease (CD) patients. Few reports are available on CD in the Asian scenario. Objective: We evaluated UST’s efficacy in inducing remission and its maintenance in Japanese CD patients. Methods: This retrospective study was conducted in UST-treated CD patients at our center. The primary endpoint was the clinical remission rate at week 8; the major secondary endpoints were the clinical remission rate at week 24 or 48, change in CD activity index (CDAI) and biomarkers, endoscopic efficacy, and cumulative remission maintenance rate. Results: The clinical remission rates at weeks 8, 24, and 48 were 44.4, 66.7, and 50.0%, respectively. Delayed response was shown by 22.2% of the patients; they achieved remission by week 24. The baseline CDAI was significantly lower in the remission group than in the nonremission group at week 8 (95% CI 0.89–0.99; p = 0.03). The cumulative remission maintenance rates at 6 and 12 months were 82.4 and 49.8%, respectively. Loss of response (LOR) was noted in 22.2% of the patients within 1 year. The endoscopic response and mucosal healing rate were 52.6 and 5.3%, respectively. Rapid improvements in serum albumin levels were observed at weeks 8 (p = 0.06), 24 (p < 0.01), and 48 (p = 0.01) from the baseline in active cases at baseline. Conclusions: UST is effective for remission induction and maintenance, especially in those with lower CD activity, however, may result in delayed response or LOR.
Survey of Mast Cell Mediator Levels from Patients Presenting with Symptoms of Mast Cell Activation
Authors: Butterfield Joseph H.
Published: November 2019

Introduction: Although 4 mast cell mediators can be routinely measured, the results of initial testing to evaluate symptoms of mast cell activation have not been widely reported. Objective: We examined the results of mast cell mediator tests used to assess patients with mast cell activation symptoms during a 5-year time span. Methods: After excluding patients with alternative diagnoses, records of 108 patients were reviewed for initial mediator test results. Mediators included serum tryptase plus urinary N-methyl histamine (N-MH), leukotriene (LT)E4, and 11β-prostaglandin (PG) F2α or 2,3-dinor-11β-PGF2α (BPG). Results: Most commonly, either a single measured elevation of 1 mediator (48.1%) or elevations of 2 (33.3%) mediators was found at baseline, during symptoms or at both time points. Elevated levels of a single mediator in order of frequency were: BPG > tryptase > LTE4 > N-MH, and for two mediators: BPG + tryptase (n = 16 cases) > BPG + LTE4 (n = 9) > BPG + N-MH (n = 6). Elevations in 3 mediators (n = 8) or 4 mediators (n = 2) were much less frequent. Monoclonal mast cell activation syndrome (n = 6), and systemic and cutaneous mastocytosis (n = 4) were also infrequent. Baseline plus symptom-associated tryptase values were obtained in only 7 patients. Conclusions: This survey suggests that elevations of 1 or 2 mediators are the most common (total 81.4% of cases) findings from initial tests for mast cell activation. Elevated levels of BPG were most commonly found both singly and in combination with other mediators, followed by the finding of elevated levels of tryptase. Baseline plus symptom-associated tryptase levels were measured in only a minority of patients.
Reducing Perioperative Risks of Surgery in Crohn’s Disease
Authors: Reindl Wolfgang , Thomann Anne Kerstin , Galata Christian , Kienle Peter
Published: November 2019

Background: Approximately one-third of all patients suffering from Crohn’s disease (CD) undergo surgery within the first 10 years after diagnosis and another 20% will have a second operation in the 10 years after their first operation. Surgery will remain an essential part of managing CD and therefore it is crucial to prevent perioperative complications by optimizing perioperative management. Methods: We reviewed the current literature on managing immunomodulating therapy, nutritional support, and thromboembolic prophylaxis in the perioperative situation. Results: CD patients with serious nutritional deficits (weight loss >10% in the last 3–6 months, body mass index <18.5 kg/m2, or albumin levels <30 g/L) benefit from intensive enteral or parenteral nutritional support, thereby reducing the risk of surgical-site infections and post-operative septic complications. Immunosuppressive therapy with prednisolone doses >20 mg should be avoided. The risk of therapy with anti-TNFα agents, vedolizumab, and ustekinumab for surgical complications has not been fully established. Analysis of currently available data suggests that an interval of 4–8 weeks is prudent to avoid complications and reduce risk by performing protective ostomy in the emergency setting. Finally, due to the high risk of venous thromboembolism, prophylactic therapy with heparin is recommended. Conclusion: As most cases of CD-related surgery are performed in a non-emergency setting, careful planning and risk management can reduce the rate of surgical complications, increase quality of life, and also reduce costs.
Nusinersen Administration Via an Intrathecal Port in a 16-Year-Old Spinal Muscular Atrophy Patient with Profound Scoliosis
Authors: Flotats-Bastardas Marina , Linsler Stefan , Zemlin Michael , Meyer Sascha
Published: November 2019

Introduction: Spinal muscular atrophy (SMA) is a genetic disease affecting the second motor neuron, causing progressive muscle atrophy and weakness due to decreased expression of the survival motor neuron. Different subtypes exist, type 2 being one of the most frequent ones. These patients show a high incidence of scoliosis requiring surgery. In 2016 and 2017, the Federal Drug Administration and European Medical Agency approved nusinersen for all types of SMA. It is a splicing modifier that enhances the expression of survival motor neuron and it has to be administered intrathecally. In patients with profound scoliosis, intrathecal administration can be challenging. Here, we present our experience with the implantation of an intrathecal port in a patient with SMA type 2. Case Presentation: A 16-year-old girl with SMA type 2 was referred for intrathecal nusinersen therapy. Because of severe scoliosis, spondylodesis of the segments TH7-S1 was performed at 14 years of age. The first two loading doses were given by spinal tap under sedation and computed tomography guidance, but we were unable to administer the following dose because of severe scoliotic spinal deformation. To ensure further drug therapy, an intrathecal port catheter (Celsite® Safety; Braun, Germany) was implanted via microsurgical hemilaminectomy L4. Further intrathecal nusinersen administration was uneventful. Conclusion: We conclude that the implantation of an intrathecal port system in patients with SMA and profound scoliosis is a safe and feasible procedure and allows the administration of nusi­nersen while reducing the need for sedation and exposure to radiation.
Bilateral Calcification of Basal Ganglia in a Patient with Duplication of Both 11q13.1q22.1 and 4q35.2 with New Phenotypic Features
Authors: Zaki Maha S. , Eid Ola M. , Eid Maha M. , Mohamed Amal M. , Sayed Inas S.M. , Abdel-Hamid Mohamed S. , Abdel-Salam Ghada M.H.
Published: November 2019

We report on a female patient who presented with severe intellectual disability and autistic behavior, dysmorphic features, orodental anomalies, and bilateral calcification of basal ganglia. Using a high-density oligonucleotide microarray, we have identified a de novo duplication of 11q13.1q22.1 involving the dosage sensitive genes FGF3 and FGF4, genes related to autosomal dominant disorders KMT5B, GAL, SPTBN2, and LRP5, susceptibility loci SCZD2, SLEH1, and SHANK2, mitochondrial genes NDUFV1, NDUFS8, and TMEM126B, and many loss of function genes, including PHOX2A, CLPB, MED17, B3GNT1, LIPT2, and CLPB. However, the duplication did not involve Ribonuclease H2, subunit C (RNASEH2C) which is considered to be located in the critical region for Aicardi-Goutières syndrome. In combination with the duplication at 11q13.1, a 1.849-Mb heterozygous duplication at 4q35.2 was also identified. Although this duplicated region does not contain causative genes related to brain calcification, the duplication at 4q35 was reported previously in a patient with basal ganglia calcification, coats' like retinopathy, and glomerulosclerosis. Our patient's presentation and genomic findings indicate that duplication of 4q35.2 could be a novel genetic cause of calcification of basal ganglia. Our report also underscores the clinical significance of rearrangements in 11q13.1q22.1 in the pathogenesis of basal ganglia calcification.
Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer
Authors: Mochizuki Satsuki , Ao Tadakazu , Sugiura Takumi , Yonemura Keisuke , Shiraishi Takehiro , Kajiwara Yoshiki , Okamoto Koichi , Shinto Eiji , Okada Yasunori , Ueno Hideki
Published: November 2019

Background: Cancer tissues consist of cancer cells and stroma, the latter of which dictates cancer tissue microenvironment. We recently reported that the desmoplastic reaction (DR) pattern at the invasive front in colorectal cancer (CRC) is a promising prognostic indicator. However, the molecular mechanisms of DR formation and contribution to patients’ prognosis remain unclear. Summary: The tumor tissue microenvironment composed of extracellular matrix (ECM), soluble factors (growth factors/cytokine/cytokine), and stromal cells controls tumor growth and spread. Among stromal cells, cancer-associated fibroblasts (CAFs) play a key role in development of the cancer tissue microenvironment, and they are responsible for DR formation. CAFs express a disintegrin and metalloproteinases (ADAMs), which modulate cancer tissue microenvironmental factors. We isolated CAFs and normal fibroblasts from colon tissues of patients with CRC and characterized them. CAFs showed the increased expression of several ADAM species including ADAM9, ADAM10, ADAM12, and ADAM17, and the expression was further increased on the ECM-coated plates. Our in vitro and in vivo studies using CAFs and CRC cells suggest that ADAM expression is associated with the morphological DR category, and ADAMs may affect cancer malignancy through tumor proliferation in CRC. Key Message: This review summarizes the present knowledge on ADAMs in cancer and describes our recent findings regarding the molecular biological background of DR mainly by focusing on ADAMs.
Effectiveness of Cytapheresis for Ulcerative Colitis in Special Situations: Delayed Onset of Optimum Efficacy in Elderly Patients
Authors: Shibuya Tomoyoshi , Nomura Osamu , Nomura Kei , Okahara Koki , Haga Keiichi , Ishikawa Dai , Sakamoto Naoto , Ogihara Tatsuo , Osada Taro , Nagahara Akihito
Published: November 2019

Background: Cytapheresis is a non-pharmacologic treatment option in which depleting elevated/activated leucocytes is known to exacerbate and perpetuate ulcerative colitis (UC) by releasing inflammatory cytokines. Therefore, it is a relevant treatment for elderly patients who wish to avoid pharmacologicals. Methods: The efficacy of Cytapheresis for remission induction in 72 patients who received Cytapheresis for active UC at our hospital was retrospectively evaluated. Patients included 11 elderly cases, patients on steroids, biologics, calcineurin inhibitor, and 13 with extra-intestinal complications. Lichtiger’s UC clinical activity index ≤4 meant remission was assessed at the end of therapy and then 1 month later. The efficacy on extra-intestinal manifestations meant improvement of the main morbidity. Results: At the end of Cytapheresis therapy, the remission rate in the elderly was 36.4%, and 54.2% in the non-elderly patients. One-month post Cytapheresis, the remission rate in the elderly had increased to 72.7% (p = 0.042), but to 58.3% in the non-elderly, suggesting a delayed response phenomenon in the elderly. The efficacy of Cytapheresis in 4 cases with loss of response to biologics was 75%, and 84.6% in the 13 patients with extra-intestinal complications, indicating a dramatic efficacy on dermatitis and arthralgia. Conclusions: Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.
The Uncanny of the Illness Experience: Can Phenomenology Help?
Authors: Madeira Luís , Leal Beatriz , Filipe Teresa , Rodrigues Madalena Ferro , Figueira Maria Luísa
Published: November 2019

The illness experience encompasses not only several changes in bodily processes but also the very feeling of becoming ill. This seemingly non-scientific aspect of being sick is characterized by forms of uncanny body experiences and an unhomelike being-in-the-world. Both include disconcerting phenomena, feelings of fear, restlessness, and inexplicability. In this paper we discuss some contributions aiming to understand the illness experience, focusing on the concept of the uncanny. This life event brings changes in the familiarity of our world, revelation of what previously was and should have remained hidden, loss of control, and the certainty of mortality. The experience of uncanniness is here conceptualized as a psychopathological phenomenon that should be regarded as a general symptom of diseases and should be identified and approached. We discuss the impact of these considerations on medical practice, focusing on the role of physicians and ultimately on the purpose of medicine.
Expression and Clinical Significance of POLR1D in Colorectal Cancer
Authors: Tian Yong , Sun Fan , Zhong Yong , Huang Wenhua , Wang Guowu , Liu Chaoqing , Xiao Yujie , Wu Jiangdong , Mu Lati
Published: November 2019

Purpose: RNA polymerase I subunit D (POLR1D) is involved in the synthesis of ribosomal RNA precursors and small RNAs, but its mechanism in the development and progression of colorectal cancer (CRC) remains ambiguous. Thus, this research aimed to investigate POLR1D’s expression and significance in human CRC patients and evaluate its association with clinicopathological characteristics. Methods: Matched fresh-frozen cancerous and non-cancerous tissues were collected from 100 patients diagnosed with CRC. Immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction analyses were adopted to validate the correlation between POLR1D expression and clinicopathological parameters in CRC tissues and adjacent normal tissues (ANTs). Results: POLR1D expression in CRC tissues was significantly higher than in the ANTs. χ2 test and Spearman’s correlative analysis showed that a high POLR1D expression is significantly associated with clinical stage, Dukes stage, tumor differentiation, depth of invasion, and metastasis (p < 0.05). It is not correlated with gender, age, and tumor location and size (p > 0.05). Kaplan-Meier survival curves show that the overall survival (OS) time for the low expression group is remarkably longer than for the high expression group (p < 0.0015). Univariate and multivariate analyses indicate that a high POLR1D expression is an independent prognostic factor for poor OS (p = 0.000). Conclusion: The findings of this study strongly indicate that POLR1D plays a pivotal role in the occurrence and progression of CRC. It might be an independent adverse prognostic factor for CRC patients and could serve as a potential therapeutic target for clinical diagnosis in CRC and anticancer drug development.
The Gut Microbiome in Bipolar Disorder and Pharmacotherapy Management
Authors: Flowers Stephanie A. , Ward Kristen M. , Clark Crystal T.
Published: November 2019

The gut microbiome is a complex and dynamic community of commensal, symbiotic, and pathogenic microorganisms that exist in a bidirectional relationship with the host. Bacterial functions in the gut play a critical role in healthy host functioning, and its disruption can contribute to many medical conditions. The relationship between gut microbiota and the brain has gained attention in mental health due to the mounting evidence supporting the association of gut bacteria with mood and behavior. Patients with bipolar disorder exhibit an increased frequency of gastrointestinal illnesses such as inflammatory bowel disease, which mechanistically has been linked to microbial community function. While the heterogeneity in microbial communities between individuals might be associated with disease risk, it may also moderate the efficacy or adverse effects associated with the use of medication. The following review highlights published evidence linking the function of gut microbiota both to bipolar disorder risk and to the effect of medications that influence microbiota, inflammation, and mood symptoms.
Evidence for Prenatal Exposure to Thyroid Disruptors and Adverse Effects on Brain Development
Authors: Demeneix Barbara A.
Published: November 2019

Thyroid hormone regulates vital processes in early brain development such as neuronal stem cell proliferation, migration, and myelination. The fetal thyroid is not fully functional until mid-pregnancy (18–20 weeks), so placental transfer of maternal thyroid hormones during early pregnancy is crucial, as is the maternal iodine status. The volume of chemical production has increased 300-fold since the 1970s. Thus, chemical exposure is ubiquitous; every child born today has dozens of man-made xenobiotic compounds in its blood. Increasing evidence from both epidemiological and animal or in vitro studies demonstrates that many of these chemicals have the potential to interfere with thyroid hormone availability and action at different physiological levels. These chemicals are found in numerous consumer products and include certain plastics, pesticides, perfluorinated compounds, and flame retardants. The last decades have seen exponential increases in neurodevelopmental disease including autism spectrum disorder and attention deficit/hyperactivity disorder. We hypothesize that prenatal exposure to mixtures of thyroid hormone-disrupting chemicals, with iodine deficiency potentially exacerbating the situation, has a strong probability of contributing to this increased incidence of neurodevelopmental disease, but could also entail a surreptitious, but socio-economically consequential, loss of IQ. Thyroid hormone receptor actions can modulate gene transcription, most often through epigenetic mechanisms. Thus, interference with epigenetic regulations is increasingly thought to link neurodevelopmental disease and IQ loss to thyroid hormone disruption.
Multimodality Imaging in Infective Endocarditis
Authors: Erba Paola A. , Pizzi Maria N. , Roque Albert , Salaun Erwan , Lancellotti Patrizio , Tornos Pilar , Habib Gilbert
Published: November 2019

Infective endocarditis (IE) is a complex disease with cardiac involvement and multiorgan complications. Its prognosis depends on prompt diagnosis that leads to an aggressive therapeutic management combining antibiotic therapy and early cardiac surgery when indicated. However, IE diagnosis always poses a challenge, and echocardiography remains diagnostically imperfect in cases of prosthetic valve IE or cardiac implantable electronic device infection. In recent years, other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) have experienced significant technical improvements, and their application to the detection of cardiac and extracardiac IE-related lesions seems to be a strategic way forward in the management of patients with suspected IE. However, the scientific evidence in the literature remains limited; current guidelines address the use of the multimodality imaging in the field of IE with caution; the incremental value of each technique and their combinations is debated; and their use varies across countries. Despite these limitations, healthcare providers and surgeons should be aware of the possibilities offered by the multimodal imaging approach when appropriate. Here, we emphasize the value of a multidisciplinary heart valve team, the endocarditis team, underlining the importance of cardiac and extracardiac imaging experts in playing a key role in informing the diagnosis and management of patients with IE. Illustrative cases, critical appraisal of contemporary data, and conceptual and practical suggestions for clinicians that may help to improve the prognosis of patients with IE are provided in this review article.
Investigation and Treatment of High Blood Pressure in Young People
Authors: Hinton Thomas C. , Adams Zoe H. , Baker Richard P. , Hope Katrina A. , Paton Julian F.R. , Hart Emma C. , Nightingale Angus K.
Published: November 2019

Hypertension among young people is common, affecting 1 in 8 adults aged between 20 and 40 years. This number is likely to increase with lifestyle behaviors and lowering of hypertension diagnostic thresholds. Early-life factors influence blood pressure (BP) although the mechanisms are unclear; BP tracks strongly within individuals from adolescence through to later life. Higher BP at a young age is associated with abnormalities on heart and brain imaging and increases the likelihood of cardiovascular events by middle age. However, diagnosis rates are lower, and treatment is often delayed in young people. This reflects the lack of high-quality evidence that lowering BP in young adults improves cardiovascular outcomes later in life. In this review, we evaluate the current evidence regarding the association between BP in young adult life and adverse cardiovascular outcomes later in life. Following this, we discuss which young people with raised BP should be investigated for secondary causes of hypertension. Third, we assess the current models to assess cardiovascular risk and show a lack of validation in the younger age group. Fourth, we evaluate the evidence for lifestyle interventions in this age group and demonstrate a lack of persistence in BP lowering once the initial intervention has been delivered. Fifth, we address the pros and cons of drug treatment for raised BP in young people. Finally, there are unique life events in young people, such as pregnancy, that require specific advice on management and treatment of BP.
Ektaphelenchoides shiroodensis n. sp. (Rhabditida: Ektaphelenchinae) a new member of the genus
Authors: Aliramaji Farzad , Pourjam Ebrahim , Pedram Majid
Published: November 2019

Ektaphelenchoides shiroodensis n. sp. is described and illustrated based upon morphological, morphometric and molecular data. It was recovered from the bark samples of a dead alder tree (Alnus sp.) from countryside around Shirood city, Mazandaran province, in the north of Iran. The new species is characterised by 768-985 μm long females, its lip region separated from the body contour by constriction, lateral field with three barely visible lines, forming two weak bands, 26-29 μm long stylet with wide lumen without conophore and basal swellings, excretory pore always at the level with median bulb, post-vulval uterine sac (PUS) 43-76 μm long, elongate conoid posterior body region ending to a long filiform part with pointed tip, males common with dorsally convex conical tail ending to a short narrower region with pointed tip, seven precloacal + cloacal + caudal papillae and arcuate spicules with wide condylus, blunt rostrum and simple end. Based upon the similar posterior body region (‘tail’) and comparable PUS length, the new species was compared to three known species, viz., E. attenuata, E. hunti and E. pini. Comparisons with the aforementioned species and similar species under the genus Seinura are discussed. The phylogenetic affinities of the new species, based upon two partial small and large subunit ribosomal DNA (SSU and LSU rDNA D2-D3) sequences, are discussed. Furthermore, several ektaphelenchid and seinurid species previously described from Iran were recovered in the present study, sequenced for their aforementioned genomic markers, and included in the phylogenetic analyses.
Neobartsia matuy (Orobanchaceae), a new species from the Colombian Andes

Authors: MALAGON MARIA DEL PILAR , MENDOZA-CIFUENTES HUMBERTO , GÓMEZ-PARRA SOFIA , URIBE-CONVERS SIMON
Published: November 2019

A new species of Neobartsia endemic to the eastern Andes of Colombia is described, illustrated, and compared with related species. This species belongs to section Orthocarpiflorae and morphologically it is characterized by having floral bracts light green with glandular hairs, corolla yellowish green, the galea cucullate, longer than the lip, retrorsely glandular-puberulous, the lip three-lobed, glabrous and the corolla tube decurved. Currently, it is only known from two localities in the Colombian department of Boyacá, where it grows in the páramo ecosystem between 3528 and 3639 meters above sea level on rocky soil with grassy vegetation.
Festuca devesae (Poaceae), a new species from northern Spain

Authors: MARTÍNEZ-SAGARRA GLORIA
Published: November 2019

Festuca devesae (Poaceae), a new species from the low mountains of northern Iberian Peninsula (Burgos and Álava provinces, Spain), is described. According to its morphology, it belongs to Festuca subsect. Festuca, the most diverse group within the genus. The new species differs from other known consectional taxa by having a continuous layer of abaxial subepidermal sclerenchyma in the leaf cross-sections, and by the leaf sheaths closed to the mouth. Both traits are found together only in F. segimonensis and F. hystrix, from which F. devesae clearly differs in the leaf apex shape, the size of the auricles, and the leaf anatomy in cross-section, among other traits. A detailed morphometric description, photographs, and data on leaf anatomy, phenology, ecology, and distribution are given. A comparison with morphologically similar species and an identification key are also provided.