bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor-derived CAR-T Cells Serve as a Reduced-intensity Conditioning Regimen for Haploidentical Stem Cell Transplantation in Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: Case Report and Review of the Literature
Authors: Zhang Cheng , Kong Pei-Yan , Li Shiqi , Chen Ting , Ni Xun , Li Yunyan , Wang Meiling , Liu Yao , Gao Lei , Gao Li , Peng Xian-Gui , Sun Ai-Hua , Wang Ping , Yang Zhi , Zhang Xi , Qian Cheng
Published: June 2018

Background:

Reduced-intensity conditioning (RIC) regimens with low tolerable toxicities have been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relapse rate by this treatment is high. Treatment of CD19+ B-cell relapsed/refractory acute lymphoblastic leukemia (r/r ALL) with allogeneic chimeric antigen receptor-modified T (CAR-T) cells is safe and effective. Use of allogeneic CD19-CAR-T cells as a part of RIC regimens for treatment of r/r ALL patients with haploidentical HSCT has not been investigated yet.

Case Presentation:

A 12-year-old girl with CD19+ r/r ALL underwent haploidentical HSCT. The patient received fludarabine, busulfan, and cyclophosphamide combined with haploidentical donor-derived CD19-CAR-T cells as the conditioning regimen. Granulocyte colony-stimulating factor–mobilized peripheral blood stem cells and granulocyte colony-stimulating factor–mobilized bone marrow were infused on days 1 and 2, respectively. Mycophenolate mofetil and tacrolimus were administered on day 1, antithymocyte globulin was administered on days +14 and +15, and a short course of methotrexate was administered to prevent graft-versus-host disease. The time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The patient’s engraftment and full-donor cell engraftment were established. The disease was in complete remission with minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease or serious cytokine-release syndrome was found.

Conclusions:

Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT.
The Prevalence of Traumatic Brain Injury and On-Campus Service Utilization Among Undergraduate Students
Authors: Meske Sam , Hazzard Joseph B. , Ni Meng , Hanson Tyler , Van Horn Lucas , Smith Josh
Published: June 2018

Objective:

(1) To examine the prevalence of college-aged students on campus who had a history of concussion(s) or traumatic brain injury (TBI) and associated symptoms and (2) to evaluate the rate of campus service utilization among students who had a TBI.

Setting:

A representative sampling, randomly selected campus-wide e-mail was sent out with a Qualtrics online survey.

Participants:

College-aged students (N= 466,n= 429) at a northeastern US university responded and consented to participate in the online survey.

Design:

Descriptive study using an online survey to evaluate the prevalence of TBI and subsequent utility of campus services.

Main Outcome Measures:

The survey assessed concussion history and the diagnosing clinician, activity in which it occurred, level of consciousness, associated symptoms, and utilization of campus services for academic accommodation.

Results:

Prevalence of concussion/TBI in the study population (51.7%) is notably higher than previous reporting in adult and college populations (∼10%-25%). Campus disability and accommodative services were underutilized (10%-13%) and were accessed more readily by the female population. In addition, there were reportable increases in symptom prevalence and service utilization with a greater number of previous concussions.

Conclusions:

Awareness and utilization of accommodative services, especially with a history of concussions, need to be improved in order to ensure academic and occupational success of students.
Efficiency of intraoperative frozen section analysis of central neck lymph node dissection in patients with papillary thyroid carcinoma
Authors: Kim Mi Jin , Kim Cheol Seung , Kim Je Roung , Park Young Sam
Published: June 2018

Background and Objective:

Because of the high survival rate and low recurrence rate of thyroid carcinoma, the therapeutic process is changing from aggressive treatment to submissive treatment. Currently, choosing central node dissection (CND) as a treatment option is considered controversial since. This approach has been shown to have poor outcomes. Therefore, we conducted this study to confirm whether the intraoperative frozen section analysis (IFSA) of CND during surgery affects treatment outcomes of patients with this type of cancer.

Materials and Methods:

First, we collected the medical records of 265 patients who underwent surgery for papillary thyroid cancer at the Presbyterian Medical Center from 2014 to 2016. The patients were divided into 2 groups: IFSA and non-IFSA. The outcomes of treatment options were then assessed. We analyzed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IFSA of CND.

Results:

Of the 265 patients in the study, 74 patients (89%) in the IFSA group and 95 patients (52.2%) in the non-IFSA group were treated appropriately (P-value=0.000). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IFSA of CND were 93.5%, 100%, 100%, 96.3%, and 97.5%, respectively.

Conclusions:

The IFSA of CND is a useful method to confirm central node metastasis during surgery. Determining the range of surgery required for each patient using this method is useful for ensuring minimal complications and for providing a successful, effective oncologic surgery.
Novel Leukocyte Modulator Device Reduces the Inflammatory Response to Cardiopulmonary Bypass
Authors: Johnston Kimberly A. , Westover Angela J. , Rojas-Pena Alvaro , Haft Jonathan W. , Toomasian John M. , Johnson Thomas , Buffington Deborah A. , Humes H. David
Published: June 2018

Leukocyte (LE) activation during cardiopulmonary bypass (CPB) promotes a systemic inflammatory response that contributes to organ injury and postoperative organ dysfunction. A leukocyte modulatory device (L-MOD) for use during (and after) CPB to limit leukocyte-mediated organ injury was tested in a preclinical model. Twenty-two pigs underwent 180 minutes of CPB and 5 hours postoperative observation. Pigs received no intervention (group 1, n = 9), 3 hours of therapy by incorporation of L-MOD into the CPB circuit (group 2, n = 6), or 8 hours of therapy using a femoral venovenous L-MOD circuit during and after CPB (group 3, n = 7). Leukocyte activation was increased at the end of CPB and leukocyte counts, namely neutrophils, increased postoperatively in most animals. These indices trended much lower in group 3. Systemic vascular resistance was not as reduced post-CPB for the L-MOD-treated pigs, and urine output was significantly greater for group 3 (p < 0.01). At 5 hours post-CPB, group 3 had a lower troponin-I (1.59 ± 0.68 ng/ml) than group 1 or group 2 (3.97 ± 2.63 and 3.55 ± 2.04 ng/ml, respectively, p < 0.05) and a lower urine neutrophil gelatinase-associated lipocalin (7.57 ± 3.59 ng/ml) than the average of the other groups (50.71 ± 49.17, p < 0.05). These results demonstrate the therapeutic potential of L-MOD therapy to mitigate the inflammatory response to CPB. Eight hours of venovenous L-MOD resulted in less organ injury and post-op organ dysfunction in this model.
Real-Time Measurement of Polyvinylpyrrolidone Eluted from Polysulfone Membrane Dialyzers Based on the Ultraviolet Spectrum
Authors: Shimamoto Yoshimasa , Matsushita Seigo , Yamamoto Takatoshi , Nakamura Yuki , Kamada Aki , Miyata Masahiro , Umimoto Koichi
Published: June 2018

The objective of this study was to develop a new method for measuring polyvinylpyrrolidone (PVP) eluted from polysulfone (PSu) membrane dialyzers. The Müller method is generally used for the measurement of PVP, in which the PVP concentration is determined by measuring the absorbance after a red color is generated by the formation of PVP-iodine complexes when iodine is added to a sample. In contrast, our method does not require any reagents and allows real-time measurement of PVP by the ultraviolet absorption spectrum (UV-s method). In this study, the UV-s method and the Müller method were used to measure PVP eluted from two types of PSu membrane dialyzer (PS-1.6UW sterilized by autoclaving [n = 10] and APS-15SA sterilized by gamma radiation [n = 10]). Polyvinylpyrrolidone concentrations measured by the two methods showed a significant positive correlation (r
s = 0.99, p = 0.0006). The PVP concentration (median [25th–75th percentiles]) in PS-1.6UW dialyzer washings obtained by rinsing with physiologic saline was 2.0 (1.18–4.85) mg/L with the Müller method and 3.35 (2.38–4.23) mg/L with the UV-s method, showing no significant difference. However, the PVP concentration in APS-15SA dialyzer washings was 0 (0–0.35) mg/L by the Müller method and 0.95 (0.45–2.58) mg/L by the UV-s method, and there was a significant difference between the two methods. In conclusion, the low concentration of PVP eluted from a PSu dialyzer sterilized by gamma radiation was hardly detected by the Müller method but could be clearly detected by the new UV-s method. These findings suggest that the UV-s method could be used for real-time measurement of PVP eluted from PSu membrane dialyzers.
The Human Microbiota
Authors: Berdanier Carolyn D.
Published: June 2018

Humans exist and other species coexist with a variety of microorganisms called the microbiota. Some of these produce needed nutrients such as vitamin K and short-chain fatty acids. The majority of the microorganisms are harmless, yet some of these organisms may play a role in chronic degenerative and other diseases. We do not know the identity of all of the microbiota that coexist with our bodies, yet we are beginning to learn that they can have far-reaching effects on our health and well-being. They may be involved in eliciting the inflammatory state, may be responsible for certain injuries, and may elicit signals that travel to the immune system that in turn serve as “triggers for the autoimmune response. The microbiotia can also generate signals to the brain that in turn may explain their associations with the development of obesity, heart disease, and diabetes. Research continues to describe the identity, location, and function of the microbiota. Strategies to enhance the favorable roles of the microbiota while suppressing the deleterious effects are being studied.
Mazabraud’s Syndrome Mimicking Metastases on FDG PET/CT in a Patient With Colon Cancer
Authors: Mahajan Sonia , Goel Reema , Riedl Christopher , Ulaner Gary A.
Published: June 2018

Mazabraud’s, a syndrome consisting of fibrous dysplasia and soft tissue myxomas, is a rare disorder with less than 100 cases reported in the literature. Appearance of lesions in Mazabraud’s syndrome on FDG PET/CT scan in an oncological scenario can be misinterpreted as malignancy. We present the case of a 69-year-old woman, diagnosed with metastatic colon carcinoma and suspected osseous as well as soft tissue metastases, who was later found to have concomitant Mazabraud’s syndrome. This case describes the diagnostic dilemma associated with this unusual entity and importance of differentiating benign and malignant etiologies on FDG PET/CT scan.
Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients
Authors: Engen Rachel M. , Park Giulia E. , Schumacher Cooper S. , Gimferrer Idoia , Warner Paul , Finn Laura S. , Weiss Noel S. , Smith Jodi M.
Published: June 2018

Background

The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear.

Methods

One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection.

Results

Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA.

Conclusions

The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.
Insights into the evolution of oxygenic photosynthesis from a phylogenetically novel, low-light cyanobacterium
Authors: Grettenberger Christen L. , Sumner Dawn Y. , Wall Kate , Brown C. Titus , Eisen Jonathan , Mackey Tyler J. , Hawes Ian , Jungblut Anne D.
Published: June 2018

Atmospheric oxygen level rose dramatically around 2.4 billion years ago due to oxygenic photosynthesis by the Cyanobacteria. The oxidation of surface environments permanently changed the future of life on Earth, yet the evolutionary processes leading to oxygen production are poorly constrained. Partial records of these evolutionary steps are preserved in the genomes of organisms phylogenetically placed between non-photosynthetic Melainabacteria, crown-group Cyanobacteria, andGloeobacter, representing the earliest-branching Cyanobacteria capable of oxygenic photosynthesis. Here, we describe nearly complete, metagenome assembled genomes of an uncultured organism phylogenetically placed between the Melainabacteria and crown-group Cyanobacteria, for which we propose the name CandidatusAurora vandensis {au.roraLatin noundawnandvand.ensis, originating from Vanda}.

The metagenome assembled genome ofA. vandensiscontains homologs of most genes necessary for oxygenic photosynthesis including key reaction center proteins. Many extrinsic proteins associated with the photosystems in other species are, however, missing or poorly conserved. The assembled genome also lacks homologs of genes associated with the pigments phycocyanoerethrin, phycoeretherin and several structural parts of the phycobilisome. Based on the content of the genome, we propose an evolutionary model for increasing efficiency of oxygenic photosynthesis through the evolution of extrinsic proteins to stabilize photosystem II and I reaction centers and improve photon capture. This model suggests that the evolution of oxygenic photosynthesis may have significantly preceded oxidation of Earth’s atmosphere due to low net oxygen production by early Cyanobacteria.
Local Polyploidy Phenomenon inEscherichia coliand its significance in genetic engineering
Authors: Yang Fayu , Guo Liwei , Lyu Kenao , Zhang Jiao , Yang Yunpeng , Wang Huiyan , Yu Huan , Guo Dele , Ding Tingting , Huang Chaoyong , Ren Huiyong , Ma Xiaoyan , Yang Yu , Huo Yi-xin
Published: June 2018

Classic Helmstetter & Cooper model asserted that the multifork phenomenon in the process of replication. However, the impacts of the multifork on the evolution and genetic engineering are still vague. Here, we employed CRISPR/Cas9 technology to knock-out eighteenEscherichia colichromosomal fragments (over 50 kb) that represent all areas of the chromosome. We demonstrated that a single cell could have wild-type, color-reporter, and antibiotic-resistant genes simultaneously in the same locus of the different branches of the duplication forks after multiple rounds of deletions and replacements. This phenomenon that a single cell had different genotypes in its local polyploid chromosomes, which was similar to eukaryotic heterozygote, was named as local polyploidy. Under a defined selective pressure condition, offspring cells containing at least a copy of conditionally beneficial mutation could be enriched, and other alleles could be kept silently and peacefully in the duplication fork(s) of the same cell. The significance of this phenomenon in the genetic engineering was discussed.
Profiling of bacterial and fungal microbial communities in cystic fibrosis sputum using RNA
Authors: Grahl Nora , Dolben Emily L. , Filkins Laura M. , Crocker Alex W. , Willger Sven D. , Morrison Hilary G. , Sogin Mitchell L. , Ashare Alix , Gifford Alex H. , Jacobs Nicholas J. , Schwartzman Joseph D. , Hogan Deborah A.
Published: June 2018

Here, we report an approach to detect diverse bacterial and fungal taxa in complex samples by direct analysis of community RNA in one step using NanoString probe sets. We designed rRNA-targeting probe sets to detect forty two bacterial and fungal genera or species common in cystic fibrosis (CF) sputum, and demonstrated taxon-specificity of these probes as well as a linear response over more than three logs of input RNA. Culture-based analyses correlated qualitatively with relative abundance data on bacterial and fungal taxa obtained by NanoString and the analysis of serial samples demonstrated the use of this method to simultaneously detect bacteria and fungi and to detect microbes at low abundance without an amplification step. The relative abundances of bacterial taxa detected by analysis of RNA correlated with the relative abundances of the same taxa as measured by sequencing of the V4V5 region of the 16S rRNA gene amplified from community DNA from the same sample. We propose that this method may complement other methods designed to understand dynamic microbial communities, may provide information on bacteria and fungi in the same sample with a single assay, and, with further development, may provide quick and easily-interpreted diagnostic information on diverse bacteria and fungi at the genus or species level.

Importance

Here we demonstrate the use of an RNA-based analysis of specific taxa of interest, including bacteria and fungi, within microbial communities. This multiplex method may be useful as a means to identify samples with specific combinations of taxa and to gain information on how specific populations vary over time and space or in response to perturbation. A rapid means to measure bacterial and fungal populations may aid in the study of host response to changes in microbial communities.
Rapid Isolation of Yeast DNA
Authors: Green Michael R. , Sambrook Joseph
Published: June 2018

This method is used to isolate yeast genomic DNA or shuttle plasmids that replicated both in Saccharomyces cerevisiae and in E. coli.
Analysis of Cell Viability by the Lactate Dehydrogenase Assay
Authors: Kumar Priti , Nagarajan Arvindhan , Uchil Pradeep D.
Published: June 2018

A common method for determining cytotoxicity is based on measuring the activity of cytoplasmic enzymes released by damaged cells. Lactate dehydrogenase (LDH) is a stable cytoplasmic enzyme that is found in all cells. LDH is rapidly released into the cell culture supernatant when the plasma membrane is damaged, a key feature of cells undergoing apoptosis, necrosis, and other forms of cellular damage. LDH activity can be easily quantified by using the NADH produced during the conversion of lactate to pyruvate to reduce a second compound in a coupled reaction into a product with properties that are easily quantitated. This protocol measures the reduction of a yellow tetrazolium salt, INT, by NADH into a red, water-soluble formazan-class dye by absorbance at 492 nm. The amount of formazan is directly proportional to the amount of LDH in the culture, which is, in turn, directly proportional to the number of dead or damaged cells.
Model-free reconstruction of magnetic correlations in frustrated magnets
Authors: Roth Nikolaj , May Andrew F. , Ye Feng , Chakoumakos Bryan C. , Iversen Bo Brummerstedt
Published: June 2018

Frustrated magnetic systems exhibit extraordinary physical properties, but quantification of their magnetic correlations poses a serious challenge to experiment and theory. Current insight into frustrated magnetic correlations relies on modelling techniques such as reverse Monte-Carlo methods, which require knowledge about the exact ordered atomic structure. Here, we present a method for direct reconstruction of magnetic correlations in frustrated magnets by three-dimensional difference pair distribution function analysis of neutron total scattering data. The methodology is applied to the disordered frustrated magnet bixbyite, (Mn1−xFex)2O3, which reveals nearest-neighbor antiferromagnetic correlations for the metal sites up to a range of approximately 15 Å. Importantly, this technique allows for magnetic correlations to be determined directly from the experimental data without any assumption about the atomic structure.
I shall, we shall, and all others will: paradoxical information security behaviour
Authors: Snyman Dirk P. , Kruger Hennie , Kearney Wayne D.
Published: June 2018

Purpose

The purpose of this paper is to investigate the lemming effect as a possible cause for the privacy paradox in information security.

Design/methodology/approach

Behavioural threshold analysis is used to test for the presence of the lemming effect in information security behaviour. Paradoxical behaviour may be caused by the influential nature of the lemming effect. The lemming effect is presented as a possible cause of the privacy paradox.

Findings

The behavioural threshold analysis indicates that the lemming effect is indeed present in information security behaviour and may lead to paradoxical information security behaviour.

Practical implications

The analysis of the lemming effect can be used to assist companies in understanding the way employees influence each other in their behaviour in terms of security. By identifying possible problem areas, this approach can also assist in directing their information security education endeavours towards the most relevant topics.

Originality/value

This research describes the first investigation of the lemming effect in information security by means of behavioural threshold analysis in practice.
Mild hyperbaric oxygen activates the proliferation of epidermal basal cells in aged mice
Authors: Nishizaka Takahiro , Nomura Tomoko , Higuchi Kazuhiko , Takemura Ai , Ishihara Akihiko
Published: June 2018

The proliferation of epidermal basal cells decreases with age. This study examined the effects of exposure to mild hyperbaric oxygen on the proliferative activity of epidermal basal cells in aged mouse skin. Hairless mice aged 5, 34 and 55 weeks were exposed to mild hyperbaric oxygen at 1266 hPa with 36% oxygen for 6 h/day for 1 or 2 weeks. Skin samples were then collected from the back area to evaluate epidermal thickness and the number and proliferative activity of epidermal basal cells. Exposure to mild hyperbaric oxygen had no effect on the epidermal thickness, irrespective of age, but accelerated the proliferative activity of epidermal basal cells in aged mouse skin.
Male clients of Thai transgender sex workers in Europe
Authors: PRAVATTIYAGUL JUTATHORN
Published: June 2018

Academic approaches to the topic of Thai transgender women (kathoey) working in the sex industry have hitherto typically focused on their sociocultural background and economic motivations. These have relied heavily on feminist theories. Meanwhile, such studies have typically also treated their clients as products of heteropatriarchy or as deviants. This article presents fresh insights into Thai kathoey sex workers' European clients in the UK, the Netherlands, Denmark and Belgium. This is a neglected field in sexual behaviour that involves fetishism and the reality of European men who prefer to buy sex from Thai transgender sex workers. With an anthropological understanding of power relations, the article questions the notion, common in studies of prostitution, that the entire story is one of vile human degradation and violence against transgender sex workers.
The wires crossed: What dowsing reveals about environmental knowledge in Britain
Authors: WOOLLEY JONATHAN
Published: June 2018

Dowsing is a customary means of finding hidden things – especially water and minerals – and is found across northern Europe and the Americas. It recently became the subject of some controversy after a scientist revealed that 10 out of the 12 British water companies stated on Twitter that they used the practice, despite a lack of scientific evidence for its efficacy. In this article, the author analyzes the contours of this controversy in order to identify underlying cultural attitudes towards knowledge and the landscape it reveals. He concludes by sounding two notes of caution regarding the critical posture adopted by scientists who are rushing to condemn this customary practice, stressing the importance of understanding the nature of dowsing as a cultural form regardless of its efficacy and the need for scientists to be mindful of their own biases and preconceptions.
Suture Embolism of the Left Superior Lobar Pulmonary Artery
Authors: Ahn Janice Seulgy , Grise Joy , DelTondo Joseph A.
Published: June 2018

Endogenous pulmonary thromboemboli are a common cause of noncardiac sudden natural death. Embolism of exogenous material is a rare but potential finding in autopsies following surgeries, medical procedures, penetrating trauma, and nonparenteral drug abuse. This report describes the first case of a suture embolism of the left superior lobar pulmonary artery following complicated abdominal surgery.
XCL1‐XCR1 pathway promotes trophoblast invasion at maternal‐fetal interface by inducing MMP‐2/MMP‐9 activity
Authors: Zhang Si‐Ming , Tian Fu‐Ju , Zeng Wei‐Hong , Ma Xiao‐Ling , Ren Jia‐Bin , Lin Yi
Published: June 2018

Problem

Certain chemokines with their receptors can promote or inhibit trophoblast cell migration and invasion in human first‐trimester placenta. Whether the lymphotactin (Lptn; XCL1)—XC chemokine receptor 1 (XCR1) chemokine pathway affects trophoblast cell migration and invasion in human first‐trimester placenta remains unclear.

Method of study

The expression pattern of chemokine XCL1 and its receptor XCR1 was detected in human first‐trimester by qRT‐PCR, and the effect of recombinant human XCL1 (rhXCL1) on trophoblast cell function was tested by wound healing and Transwell assays. Matrix metalloproteinase (MMP) activity in trophoblast cells treated with rhXCL1 was assessed via qRT‐PCR and gelatin zymography.

Results

Abundant XCR1 mRNA was expressed in the first‐trimester decidua and villi. XCL1 and XCR1 mRNA were expressed at a higher level in the first‐trimester than in the term placenta. RhXCL1 promoted trophoblast cell migration and invasion by increasing MMP‐9 and MMP‐2 activity and that of the MMP‐2/tissue inhibitor of metalloproteinases 2 (TIMP‐2) complex via the phosphatidylinositol 3‐kinase (PI3K)/AKT kinase (AKT), mitogen‐activated protein kinase (MEK), and JUN N‐terminal kinase (JNK) signaling pathways.

Conclusion

XCL1‐XCR1 chemokine pathway promotes trophoblast invasion by increasing matrix metalloproteinase activity in human first‐trimester placenta.
Comparison of ranibizumab versus dexamethasone for macular oedema following retinal vein occlusion: 1‐year results of the COMRADE extension study
Authors: Feltgen Nicolas , Hattenbach Lars‐Olof , Bertelmann Thomas , Callizo Josep , Rehak Matus , Wolf Armin , Berk Hüsnü , Eter Nicole , Lang Gabriele E. , Pielen Amelie , Schmitz‐Valckenberg Steffen , Quiering Claudia , Rose Uwe , Hoerauf Hans ,   the COMRADE Study Group
Published: June 2018

Purpose

The COMRADE studies are the first randomized controlled head‐to‐head trials comparing the efficacy and safety of intravitreal ranibizumab versus dexamethasone (DEX) in patients with macular oedema secondary to retinal vein occlusion (RVO). The COMRADE extension trial was designed to provide additional 6‐month data of patients who completed the core studies.

Methods

In this open‐label, phase IV study patients who completed the COMRADE core studies were prospectively enrolled. Overall, 92 branch RVO (BRVO) patients (ranibizumab 52, DEX 40) and 83 central RVO (CRVO) patients (ranibizumab 61, DEX 22) were treated, and 94.6% of BRVO patients and 97.6% of CRVO patients completed the extension study. Patients were assigned to the same treatment group as in the core studies. Patients were monitored monthly and received either 0.5 mg ranibizumab or a 0.7 mg DEX implant as needed.

Results

Over the course of the extension, treatment‐emergent adverse events (TEAEs) of the study eye occurred in 55.8% of BRVO patients on ranibizumab and in 62.5% of those on DEX. Among CRVO patients, 65.5% in the ranibizumab group and 59.1% in the DEX group developed TEAEs. Overall, elevated intraocular pressure (IOP) was more frequent with DEX than ranibizumab treatment. Mean average change in best‐corrected visual acuity (BCVA) in BRVO patients was significantly better for ranibizumab than DEX (p = 0.0249). The CRVO results were consistent with BRVO's, although not significant (p = 0.1119).

Conclusion

When used according to the European labels, ranibizumab revealed a better ocular safety profile and produced greater average BCVA gains than DEX. By the end of the additional 6‐month study period, this difference in BCVA was more pronounced in BRVO as in CRVO patients. The main limitation of the COMRADE studies was that DEX patients received only a single intravitreal treatment during the first 6 months, which is presumably not adequate. However, frequent DEX implants could lead to more steroid‐related side effects, especially to an increased intraocular pressure.
Choroidal vascularity index changes after vitreomacular surgery
Authors: Rizzo Stanislao , Savastano Alfonso , Finocchio Lucia , Savastano Maria Cristina , Khandelwal Neha , Agrawal Rupesh
Published: June 2018

Purpose

To study the structural changes in the choroid using swept‐source (SS) optical coherence tomography (OCT), a tool for the choroidal vascularity index (CVI) following epiretinal membrane removal.

Methods

Fifty‐two eyes of 26 patients were evaluated in this prospective, single‐centre, observational study. Twenty‐six eyes underwent vitrectomy for epiretinal membrane removal (VT‐group), and the control group consisted of 26 corresponding fellow eyes (F‐group). All patients were evaluated at baseline, 30 and 90 days postsurgery. Using a modified image binarization algorithm for SS‐OCT scans, the subfoveal choroidal area was segmented into the luminal and stromal areas, and the CVI was measured by calculating the proportion of the luminal area (LA) to the cross‐sectional choroid area.

Results

The mean CVI in the VT‐group was 63.86 ± 4.04% at the baseline, 62.45 ± 4.21% at 30 days postsurgery and 61.06 ± 3.79% at 90 days (p < 0.001). The F‐group had a mean CVI of 61.12 ± 2.29% at the baseline, 60.91 ± 2.25% at 30 days postsurgery and 61.05 ± 2.28% at 90 days (p = 0.29).

Conclusion

The CVI decreases following epiretinal membrane removal when compared to the fellow eyes, which suggests structural changes in the vascular layers of the choroid. The implication of these results may be that secondary inflammation resulting from mechanical traction induces choroidal thickness by way of increased vascularization of the choroid.
Randomised clinical trial: Tong‐Xie‐Yao‐Fang granules versus placebo for patients with diarrhoea‐predominant irritable bowel syndrome
Authors: Chen M. , Tang T.‐C. , Wang Y. , Shui J. , Xiao X.‐H. , Lan X. , Yu P. , Zhang C. , Wang S.‐H. , Yao J. , Zheng H. , Huang D.‐Q.
Published: June 2018

Background

Tong‐Xie‐Yao‐Fang (TXYF) is a Chinese herbal formula for treating chronic diarrhoea accompanied by abdominal pain. The results were inconsistent in previous trials examining its effect.

Aim

To study the efficacy of TXYF granules for treating diarrhoea‐predominant irritable bowel syndrome (IBS‐D).

Methods

We performed a double‐blind, placebo‐controlled randomised trial and enrolled 160 participants with IBS‐D. The participants had VAS scores ≥3 cm in IBS‐D global symptoms and ≥2 days in a week with abdominal pain and loose stools (Bristol score 5, 6 or 7). They were randomly assigned to received TXYF or placebo during a treatment period of 4 weeks, and they were followed up for 8 weeks after treatment. The primary outcome was adequate relief of IBS‐D global symptoms for at least 2 of 4 weeks during weeks 1‐4. Secondary outcomes included mean weekly VAS scores of IBS‐D major symptoms, mean weekly stool frequency, mean weekly Bristol score, and adverse events.

Results

155 of 160 patients completed the trial. We found a significantly higher rate of adequate relief of global symptoms in TXFY group during weeks 1 to 4 (57.5% vs 37.5%, χ2 = 5.6391, P = 0.017); logistic regression analysis showed a similar result (OR 2.2, 95% CI 1.2‐4.4, P = 0.016). Most of the secondary outcomes showed superiority of TXYF over placebo in weekly assessment from week 3 to week 7. The adverse event rate was low in both groups (3.8% vs 3.8%, P = 1.000).

Conclusion

During a 4 week trial, TXFY granules were superior to placebo in controlling symptoms of IBS‐D.
Usefulness of a novel, slim long syringe‐like device for applying surgical mesh through a 5‐mm trocar
Authors: Nakase Yuen , Nakamura Kei , Sougawa Akira , Nagata Tomoyuki , Mochizuki Satoshi , Kitai Shouzo , Inaba Seishirou
Published: June 2018

We developed a device for introducing surgical mesh through a 5‐mm trocar during transabdominal preperitoneal hernia repair. This device is like a slim long syringe; it has a polypropylene outer sheath (outer diameter, 5.8 mm; inner diameter, 5.6 mm; length, 2500 mm) and inner rod, and is made in a similar manner to a drinking straw. Therefore, the manufacturing costs are low. To use the device, folded mesh is placed inside it with a grasper before surgery. The device is then inserted through the trocar, and the mesh is pushed out by the inner rod and applied. The folded mesh extrudes smoothly pubis side to lateral side along the inguinal curve. It reinforces the area without any contamination and expands in a manner that makes it easy for the surgeon to place and fix the mesh. Our device allows mesh to be applied smoothly, comfortably, and economically, and it may reduce the risk of infection.
Transanal minimally invasive surgery for local excision of early rectal tumor
Authors: Yoshitomi Mami , Hasegawa Suguru , Takahashi Ryo , Hida Koya , Kawada Kenji , Sakai Yoshiharu
Published: June 2018

Introduction

Local excision (LE) is used in early rectal cancer and other pathologies for diagnostic purposes and curative treatment, as well as for palliative surgery in patients who are medically unfit for radical resection. Recently, transanal minimally invasive surgery (TAMIS) has been increasingly accepted as a means for performing LE. Here, we present a TAMIS technique for LE to which endoscopic submucosal dissection was applied.

Materials and Surgical Technique

We used conventional laparoscopic instruments, including a 10‐mm 30° camera. A GelPOINT Path® was introduced into the anal canal to maintain stable pneumorectum and valve‐free access. After injecting MucoUp® (SI‐4404) into the submucosal layer at the edge of the tumor, we marked dots on the mucosa with cautery using the point of the monopolar diathermy L‐hook; we then performed circumferential mucosal incision and submucosal dissection. The remaining defects do not always have to be sutured.

Discussion

TAMIS for LE was performed for seven patients with no postoperative complication and mortality. One lesion required full‐thickness resection, one lesion required partial full‐thickness resection, and five lesions were dissected completely beneath the submucosal layer. Based on the pathological results, three patients underwent conventional radical resections. One patient had local recurrence at the 8‐month follow‐up and underwent endoscopic mucosal resection. TAMIS may be a promising option for LE that provides acceptable oncological outcomes and benefits to quality of life.
Framing the ethical and legal issues of human artificial gametes in research, therapy, and assisted reproduction: A German perspective
Authors: Advena‐Regnery Barbara , Dederer Hans‐Georg , Enghofer Franziska , Cantz Tobias , Heinemann Thomas
Published: June 2018

Recent results from studies on animals suggest that functional germ cells may be generated from human pluripotent stem cells, giving rise to three possibilities: research with these so‐called artificial gametes, including fertilization experiments in vitro; their use in vivo for therapy for the treatment of human infertility; and their use in assisted reproductive technologies in vitro. While the legal, philosophical, and ethical questions associated with these possibilities have been already discussed intensively in other countries, the debate in Germany is still at its beginning. A systematic and detailed analysis of the legal framework in Germany is provided with regard to the three possibilities, including the applicable statutory laws as well as the constitutional law. The question emerges as to whether the statutory laws as well as the constitution justify a distinction to be made between embryos of artificial and natural origin. This question is subject to philosophical analysis, discussing the distinction between person and thing, dignity and price, personality and property, and nature and technique. As a result, the criterion of naturalness alone may not be sufficient to differentiate between embryos of natural and artificial origin, and other criteria need to be identified.
The emerging alliance of sphingosine‐1‐phosphate signalling and immune cells: from basic mechanisms to implications in hypertension
Authors: Don‐Doncow Nicholas , Zhang Yun , Matuskova Hana , Meissner Anja
Published: June 2018

The immune system plays a considerable role in hypertension. In particular, T‐lymphocytes are recognized as important players in its pathogenesis. Despite substantial experimental efforts, the molecular mechanisms underlying the nature of T‐cell activation contributing to an onset of hypertension or disease perpetuation are still elusive. Amongst other cell types, lymphocytes express distinct profiles of GPCRs for sphingosine‐1‐phosphate (S1P) – a bioactive phospholipid that is involved in many critical cell processes and most importantly majorly regulates T‐cell development, lymphocyte recirculation, tissue‐homing patterns and chemotactic responses. Recent findings have revealed a key role for S1P chemotaxis and T‐cell mobilization for the onset of experimental hypertension, and elevated circulating S1P levels have been linked to several inflammation‐associated diseases including hypertension in patients. In this article, we review the recent progress towards understanding how S1P and its receptors regulate immune cell trafficking and function and its potential relevance for the pathophysiology of hypertension.

Linked Articles

This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Feature Curve Co‐Completion in Noisy Data
Authors: Gehre Anne , Lim Isaak , Kobbelt Leif
Published: June 2018

Feature curves on 3D shapes provide important hints about significant parts of the geometry and reveal their underlying structure. However, when we process real world data, automatically detected feature curves are affected by measurement uncertainty, missing data, and sampling resolution, leading to noisy, fragmented, and incomplete feature curve networks. These artifacts make further processing unreliable. In this paper we analyze the global co‐occurrence information in noisy feature curve networks to fill in missing data and suppress weakly supported feature curves. For this we propose an unsupervised approach to find meaningful structure within the incomplete data by detecting multiple occurrences of feature curve configurations (co‐occurrence analysis). We cluster and merge these into feature curve templates, which we leverage to identify strongly supported feature curve segments as well as to complete missing data in the feature curve network. In the presence of significant noise, previous approaches had to resort to user input, while our method performs fully automatic feature curve co‐completion. Finding feature reoccurrences however, is challenging since naïve feature curve comparison fails in this setting due to fragmentation and partial overlaps of curve segments. To tackle this problem we propose a robust method for partial curve matching. This provides us with the means to apply symmetry detection methods to identify co‐occurring configurations. Finally, Bayesian model selection enables us to detect and group re‐occurrences that describe the data well and with low redundancy.
Repairing Inconsistent Curve Networks on Non‐parallel Cross‐sections
Authors: Huang Z. Y. , Holloway M. , Carr N. , Ju T.
Published: June 2018

In this work we present the first algorithm for restoring consistency between curve networks on non‐parallel cross‐sections. Our method addresses a critical but overlooked challenge in the reconstruction process from cross‐sections that stems from the fact that cross‐sectional slices are often generated independently of one another, such as in interactive volume segmentation. As a result, the curve networks on two non‐parallel slices may disagree where the slices intersect, which makes these cross‐sections an invalid input for surfacing. We propose a method that takes as input an arbitrary number of non‐parallel slices, each partitioned into two or more labels by a curve network, and outputs a modified set of curve networks on these slices that are guaranteed to be consistent. We formulate the task of restoring consistency while preserving the shape of input curves as a constrained optimization problem, and we propose an effective solution framework. We demonstrate our method on a data‐set of complex multi‐labeled input cross‐sections. Our technique efficiently produces consistent curve networks even in the presence of large errors.
PointProNets: Consolidation of Point Clouds with Convolutional Neural Networks
Authors: Roveri Riccardo , Öztireli A. Cengiz , Pandele Ioana , Gross Markus
Published: June 2018

With the widespread use of 3D acquisition devices, there is an increasing need of consolidating captured noisy and sparse point cloud data for accurate representation of the underlying structures. There are numerous algorithms that rely on a variety of assumptions such as local smoothness to tackle this ill‐posed problem. However, such priors lead to loss of important features and geometric detail. Instead, we propose a novel data‐driven approach for point cloud consolidation via a convolutional neural network based technique. Our method takes a sparse and noisy point cloud as input, and produces a dense point cloud accurately representing the underlying surface by resolving ambiguities in geometry. The resulting point set can then be used to reconstruct accurate manifold surfaces and estimate surface properties. To achieve this, we propose a generative neural network architecture that can input and output point clouds, unlocking a powerful set of tools from the deep learning literature. We use this architecture to apply convolutional neural networks to local patches of geometry for high quality and efficient point cloud consolidation. This results in significantly more accurate surfaces, as we illustrate with a diversity of examples and comparisons to the state‐of‐the‐art.
Terrain Super‐resolution through Aerial Imagery and Fully Convolutional Networks
Authors: Argudo O. , Chica A. , Andujar C.
Published: June 2018

Despite recent advances in surveying techniques, publicly available Digital Elevation Models (DEMs) of terrains are low‐resolution except for selected places on Earth. In this paper we present a new method to turn low‐resolution DEMs into plausible and faithful high‐resolution terrains. Unlike other approaches for terrain synthesis/amplification (fractal noise, hydraulic and thermal erosion, multi‐resolution dictionaries), we benefit from high‐resolution aerial images to produce highly‐detailed DEMs mimicking the features of the real terrain. We explore different architectures for Fully Convolutional Neural Networks to learn upsampling patterns for DEMs from detailed training sets (high‐resolution DEMs and orthophotos), yielding up to one order of magnitude more resolution. Our comparative results show that our method outperforms competing data amplification approaches in terms of elevation accuracy and terrain plausibility.
A Physically Consistent Implicit Viscosity Solver for SPH Fluids
Authors: Weiler Marcel , Koschier Dan , Brand Magnus , Bender Jan
Published: June 2018

In this paper, we present a novel physically consistent implicit solver for the simulation of highly viscous fluids using the Smoothed Particle Hydrodynamics (SPH) formalism. Our method is the result of a theoretical and practical in‐depth analysis of the most recent implicit SPH solvers for viscous materials. Based on our findings, we developed a list of requirements that are vital to produce a realistic motion of a viscous fluid. These essential requirements include momentum conservation, a physically meaningful behavior under temporal and spatial refinement, the absence of ghost forces induced by spurious viscosities and the ability to reproduce complex physical effects that can be observed in nature. On the basis of several theoretical analyses, quantitative academic comparisons and complex visual experiments we show that none of the recent approaches is able to satisfy all requirements. In contrast, our proposed method meets all demands and therefore produces realistic animations in highly complex scenarios. We demonstrate that our solver outperforms former approaches in terms of physical accuracy and memory consumption while it is comparable in terms of computational performance. In addition to the implicit viscosity solver, we present a method to simulate melting objects. Therefore, we generalize the viscosity model to a spatially varying viscosity field and provide an SPH discretization of the heat equation.
Hair Modeling and Simulation by Style
Authors: Jung Seunghwan , Lee Sung‐Hee
Published: June 2018

As the deformation behaviors of hair strands vary greatly depending on the hairstyle, the computational cost and accuracy of hair movement simulations can be significantly improved by applying simulation methods specific to a certain style. This paper makes two contributions with regard to the simulation of various hair styles. First, we propose a novel method to reconstruct simulatable hair strands from hair meshes created by artists. Manually created hair meshes consist of numerous mesh patches, and the strand reconstruction process is challenged by the absence of connectivity information among the patches for the same strand and the omission of hidden parts of strands due to the manual creation process. To this end, we develop a two‐stage spectral clustering method for estimating the degree of connectivity among patches and a strand‐growing method that preserves hairstyles. Next, we develop a hairstyle classification method for style‐specific simulations. In particular, we propose a set of features for efficient classifications and show that classifiers trained with the proposed features have higher accuracy than those trained with naive features. Our method applies efficient simulation methods according to the hairstyle without specific user input, and thus is favorable for real‐time simulation.