julilili42/papers huggingface dataset:
Spectral domain optical coherence tomography interpretation – Response to Blacklaws et al
2018-05-16

We appreciate the interest in our review on intraocular lymphoma published in this Journal in 2016 (Fend et al, 2016). In their letter to the Editor, Blacklaws and colleagues point out that in our Fig. 2B, which shows the Optical Coherence Tomography (OCT) of a patient with choroidal marginal B-cell lymphoma, the findings are described incorrectly, and that the hyporeflective areas highlighted by the arrows do not represent a retinal detachment. After discussion with the consultant ophthalmologist who provided us with this clinical image, we agree with Blacklaws and colleagues’ interpretation and are grateful to them for pointing out this mistake, for which we apologize. As mentioned by Blacklaws and colleagues, enhanced depth imaging OCT (EDI-OCT) is necessary to assess the thickness of the choroid, which is essential for diagnosing this rare lymphoma type (Aronow et al, 2014; Shields et al, 2014).
Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis
2018-05-17

Abstract Purpose: Peritoneal carcinomatosis is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Because current therapies are mostly ineffective, new therapeutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and antitumor activity of intraperitoneal administration of oncolytic vaccinia virus GL-ONC1 in advanced stage peritoneal carcinomatosis patients. Patients and Methods: GL-ONC1 was administered intraperitoneally every 4 weeks for up to four cycles at three different dose levels (107–109 pfu) following a standard 3+3 dose escalation design. GL-ONC1 was infused via an indwelling catheter that enabled repetitive analyses of peritoneal fluid biopsies. The primary study objective was safety of GL-ONC1 according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.0). Results: Patients with advanced-stage peritoneal carcinomatosis (n = 7) or advanced peritoneal mesothelioma (n = 2) received 24 doses of GL-ONC1. Adverse events were limited to grades 1–3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported, and the MTD was not reached. Furthermore, no signs of viral shedding were observed. Importantly, in 8 of 9 study patients, effective intraperitoneal infections, in-patient replication of GL-ONC1, and subsequent oncolysis were demonstrated in cycle 1. All patients developed neutralizing activities against GL-ONC1. Conclusions: GL-ONC1 was well tolerated when administered into the peritoneal cavity of patients with advanced stage peritoneal carcinomatosis. Efficient tumor cell infection, in-patient virus replication, and oncolysis were limited to treatment cycle 1 (ClinicalTrials.gov number, NCT01443260). Clin Cancer Res; 24(18); 4388–98. ©2018 AACR.
Astrophysical Black Holes: A Compact Pedagogical Review
2018-05-17

Abstract Black holes are among the most extreme objects that can be found in the Universe and an ideal laboratory for testing fundamental physics. Here, the basic properties of black holes as expected from general relativity, the main astronomical observations, and the leading astrophysical techniques to probe the strong gravity region of these objects are reviewed. The main intention is to provide a compact introductory overview on astrophysical black holes to new students entering this research field, as well as to senior researchers working in general relativity and alternative theories of gravity, who wish to quickly learn the state of the art of astronomical observations of black holes.
Stem cell-based retina models
2018-05-17

From the early days of cell biological research, the eye-especially the retina-has evoked broad interest among scientists. The retina has since been thoroughly investigated and numerous models have been exploited to shed light on its development, morphology, and function. Apart from various animal models and human clinical and anatomical research, stem cell-based models of animal and human cells of origin have entered the field, especially during the last decade. Despite the observation that the retina of different species comprises endogenous stem cells, most stem cell-related research in the human retina is now based on pluripotent stem cell models. Herein, systems of two-dimensional (2D) cultures and co-cultures of distinctly differentiated retinal subtypes revealed a variety of cellular aspects but have in many aspects been replaced by three-dimensional (3D) structures-the so-called retinal organoids. These organoids not only contain all major retinal cell subtypes compared to the physiological situation, but also show a distinct layering in close proximity to the in vivo morphology. Nevertheless, all these models have inherent advantages and disadvantages, which are expounded and summarized in this review. Finally, we discuss current application aspects of stem cell-based retina models and the specific promises they hold for the future.
Plasmonic trapping potentials for cold atoms
2018-05-17

This paper reports on conceptual and experimental work towards the realization of plasmonic surface traps for cold atoms. The trapping mechanism is based on the combination of a repulsive and an attractive potential generated by evanescent light waves that are plasmonically enhanced. The strength of enhancement can be locally manipulated via the thickness of a metal nanolayer deposited on top of a dielectric substrate. Thus, in principle the trapping geometry can be predefined by the metal layer design. We present simulations of a plasmonic lattice potential using a gold grating with sinusoidally modulated thickness. Experimentally, a first plasmonic test structure is presented and characterized. Furthermore, the surface potential landscape is detected by reflecting ultracold atom clouds from the test structure revealing the influence of both evanescent waves. A parameter range is identified where stable traps can be expected.
Signal sequence‐independent targeting of MID2mRNA to the endoplasmic reticulum by the yeast RNA‐binding protein Khd1p
2018-05-17

Localization of mRNA s depends on specific RNA‐binding proteins ( RBP s) and critically contributes not only to cell polarization but also to basal cell function. The yeast RBP Khd1p binds to several hundred mRNA s, the majority of which encodes secreted or membrane proteins. We demonstrate that a subfraction of Khd1p associates with artificial liposomes and endoplasmic reticulum ( ER ), and that Khd1p endomembrane association is partially dependent on its binding to RNA . ER targeting of at least two mRNA s, MID 2 and SLG 1 / WSC 1 , requires KHD 1 but is independent of their translation. Together, our results suggest interdependence of Khd1p and mRNA for their targeting to the ER and presents additional evidence for signal sequence‐independent, RBP ‐mediated mRNA targeting.
Custom-made Stent Grafts for the Treatment of Pseudoaneurysms after Childhood Coarctation Surgery
2018-05-17

Background Post-coarctation of the aorta (CoA) pseudoaneurysms is a complication of open repair. Thoracic endovascular repair (TEVAR) is feasible but complicated by proximity to the supra-aortic trunks and severe arch angulation. Methods We describe three cases of post-CoA pseudoaneurysms treated with custom-made Relay stent grafts (Vascutek, Scotland). Results Technical and clinical success was achieved in all three cases with no mortality, morbidity, endoleaks, or complications. In all three, pseudoaneurysm sac shrinkage was observed at the follow-ups; in one case, there was complete resolution. Conclusion Redo open surgery is challenging because of adhesions of the thoracic cavity and associated morbidity and mortality. TEVAR is less invasive and offers fewer complications. Custom-made modifications overcome difficult anatomies including short landing zones and diameter variability.
RNA-antimicrobial peptide LL-37 complexes fuel a TLR- and NET-mediated inflammatory cycle of neutrophil activation in psoriasis
2018-05-17

Abstract Psoriasis is an inflammatory autoimmune disease characterized by skin lesions showing strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37, but the role of PMNs in this context remains unclear. We here show that primary human PMNs, especially PMNs from psoriasis patients, not only respond via TLR8 to human and bacterial RNA in complexed with LL37 by cytokine-, chemokine- and neutrophil extracellular trap (NET)-release; they also actively release additional RNA and LL37 in response to stimulation by the same complex and both RNA and LL37 were found to be highly abundant in psoriatic skin. Moreover, RNA-LL37-induced NETs propagated PMN activation and could thus fuel a PMN-mediated and self-sustaining inflammatory loop that may represent an unexpected early initiator or amplifying event in psoriasis. Given that TLR inhibitory oligodeoxynucleotides prevented the cytokine production and NETosis of PMNs by RNA-LL37 complexes in vitro , our study also highlights TLR blockade as a potential therapeutic intervention strategy in psoriasis. Summary Human and bacterial RNA in complex with LL37 activates neutrophils via TLR8 to release cytokines, chemokines and neutrophil extracellular traps (NETs). NETs and neutrophil-rich areas in psoriatic skin contain RNA and LL37, suggesting RNA-LL37 may fuel a PMN-mediated and self-sustaining inflammatory cycle in psoriasis.
Frontispiece: Metal‐Catalyzed Synthesis and Use of Thioesters: Recent Developments
2018-05-17

Thioesters are valuable building blocks not only in nature, but also in organic synthesis. They can undergo oxidative addition or single-electron transfer with suitable homogeneous catalysts. This Minireview looks at the most significant discoveries using thioesters as substrates in metal-catalyzed reactions, as well as at noteworthy methods available for their synthesis. For more details, see I. Fleischer et al. on page 7092 ff.
Social support, violence exposure and mental health among young South African adolescents
2018-05-18

The stress-buffering effects of social support may not be maintained in contexts of high exposure to violence. Implications for interventions to enhance youth safety and resilience in high-violence contexts are considered.
How Confidence in Prior Attitudes, Social Tag Popularity, and Source Credibility Shape Confirmation Bias Toward Antidepressants and Psychotherapy in a Representative German Sample: Randomized Controlled Web-Based Study (Preprint)
2018-05-18

<sec> <title>BACKGROUND</title> In health-related, Web-based information search, people should select information in line with expert (vs nonexpert) information, independent of their prior attitudes and consequent confirmation bias. </sec> <sec> <title>OBJECTIVE</title> This study aimed to investigate confirmation bias in mental health–related information search, particularly (1) if high confidence worsens confirmation bias, (2) if social tags eliminate the influence of prior attitudes, and (3) if people successfully distinguish high and low source credibility. </sec> <sec> <title>METHODS</title> In total, 520 participants of a representative sample of the German Web-based population were recruited via a panel company. Among them, 48.1% (250/520) participants completed the fully automated study. Participants provided prior attitudes about antidepressants and psychotherapy. We manipulated (1) confidence in prior attitudes when participants searched for blog posts about the treatment of depression, (2) tag popularity —either psychotherapy or antidepressant tags were more popular, and (3) source credibility with banners indicating high or low expertise of the tagging community. We measured tag and blog post selection, and treatment efficacy ratings after navigation. </sec> <sec> <title>RESULTS</title> Tag popularity predicted the proportion of selected antidepressant tags (beta=.44, SE 0.11; P&lt;.001) and blog posts (beta=.46, SE 0.11; P&lt;.001). When confidence was low (−1 SD), participants selected more blog posts consistent with prior attitudes (beta=−.26, SE 0.05; P&lt;.001). Moreover, when confidence was low (−1 SD) and source credibility was high (+1 SD), the efficacy ratings of attitude-consistent treatments increased (beta=.34, SE 0.13; P=.01). </sec> <sec> <title>CONCLUSIONS</title> We found correlational support for defense motivation account underlying confirmation bias in the mental health–related search context. That is, participants tended to select information that supported their prior attitudes, which is not in line with the current scientific evidence. Implications for presenting persuasive Web-based information are also discussed. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT03899168; https://clinicaltrials.gov/ct2/show/NCT03899168 (Archived by WebCite at http://www.webcitation.org/77Nyot3Do) </sec>
Sleep divergently affects cognitive and automatic emotional response in children
2018-05-19

Sleep enhances memory for emotional experiences, but its influence on the emotional response associated with memories is elusive. Here, we compared the influence of nocturnal sleep on memory for negative and neutral pictures and the associated emotional response in 8-11-year-old children, i.e., an age group with heightened levels of emotional memory-related sleep features. During all sessions, emotional responses as measured by subjective ratings, the late positive potential of the EEG (LPP) and heart rate deceleration (HRD) were recorded. Sleep enhanced picture memory. Compared to dynamics across wakefulness, sleep decreased the emotional response in ratings and the LPP, while increasing the emotional response in HRD. We conclude that sleep consolidates immediate emotional meaning by enhancing more automatic emotional responses while concurrently promoting top-down control of emotional responses, perhaps through strengthening respective neocortical representations.
Complement Factor H as a potential atherogenic marker in chronic Chagas’ disease
2018-05-19

Summary We aimed to investigate the association between plasma levels of complement Factor H ( FH ) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas’ disease ( CD ). FH plasmatic levels were determined in 80 chronic CD patients. Glycaemic index, lipidogram (high‐density lipoprotein cholesterol HDL ‐C, low‐density lipoprotein cholesterol LDL ‐C, triglycerides and total cholesterol) and Ultrasensitive C‐Reactive Protein ( uCRP ) values were obtained from medical records. Height, weight, body mass index ( BMI ) blood pressure and left ventricular ejection fraction ( LVEF ) were obtained from echocardiography examinations. Comparisons between chronic CD clinical forms were performed using Mann‐Whitney test and correlation Spearman’s test. FH levels were correlated positively with triglycerides ( P = .001, r = .39), LDL ‐C ( P = .009, r = .3), cholesterol ( P = .02, r = .28), uCRP ( P = .029, r = .31) and BMI ( P = .008, r = .34); and negatively with HDL ‐C ( P = .03, r = −.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels was observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD.
Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study
2018-05-19

Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C<sub>0</sub>) while area under the concentration vs time curve (AUC) is used in solid organ transplant. AUC potentially has an important relationship with the development of acute graft-versus-host-disease (aGVHD). We conducted a prospective study to describe the relationship between severe (grade III-IV) aGVHD and cyclosporine AUC in pediatric HSCT recipients. Pediatric patients who underwent allogeneic myeloablative HSCT and scheduled to receive cyclosporine for aGVHD prophylaxis participated in this multicenter study. Cyclosporine doses were adjusted based on C<sub>0</sub> according to each center's standard of care. Cyclosporine AUC was determined weekly until neutrophil engraftment or Day +42, whichever was later. Associations between severe aGVHD and cyclosporine AUC and other patient and treatment-related factors were evaluated. Of the 110 children enrolled, 97 were evaluable. Thirty-seven (38%) children developed aGVHD; 13 (13.4%) had severe aGVHD. On univariate analysis, there was no association between severe aGVHD and cyclosporine AUC at any time point before engraftment. Future research should focus on refinement of C<sub>0</sub> targets for cyclosporine therapeutic drug monitoring in HSCT.
Active sensing with light improves predator detection in a diurnal fish
2018-05-19

Abstract Active sensing by means of light is rare. In vertebrates, it is known only from chemiluminescent fish with light organs below their pupils, an anatomical arrangement that is ideal to generate eyeshine in the pupils of nearby organisms. Here, we test whether diurnal fish can achieve the same by redirecting sunlight through reflection instead. We recently showed that small (&lt; 5 cm), benthic, marine triplefin fish actively redirect downwelling light using their iris. We hypothesized that this mechanism allows triplefins to improve detection of a cryptic organism by generating eyeshine in its pupil. Here, we tested this by attaching small dark hats to triplefins to shade their iris from downwelling light. Two controls consisted of triplefins with a clear or no hat. These treatments test the prediction that light redirection increases the visual detection ability of triplefins. To this end, we placed treated fish in a tank with a display compartment containing either a stone as the control stimulus, or a scorpionfish, i.e. a cryptic, motionless triplefin predator with retroreflective eyes. After overnight acclimatization, we determined the average distance triplefins kept from the display compartment over two days. Both in the laboratory ( n = 15 replicates per treatment) and in a similar field experiment at 15 m depth ( n = 43 replicates per treatment) fish kept longer distances from the scorpionfish than from the stone. This response varied between hat treatments: shaded triplefins stayed significantly closer to the scorpionfish in the laboratory and in one of two orientations tested in the field. A follow-up field experiment at 10 m depth revealed the immediate response of triplefins to a scorpionfish. At first, many individuals ( n = 80) moved towards it, with shaded triplefins getting significantly closer. All individuals then gradually moved to a safer distance at the opposite half of the tank. Visual modelling supported the experimental results by showing that triplefins can redirect enough light with their iris to increase a scorpionfish’s pupil brightness above detection threshold at a distance of 7 cm under average field conditions and at more than 12 cm under favorable conditions. We conclude that triplefins are generally good in the visual detection of a cryptic predator, but can significantly improve this ability when able to redirect downwelling light with their iris and induce eyeshine in the predator’s pupil. We discuss the consequences of “diurnal active photolocation” for visual detection and camouflage among fish species.
Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC).
2018-05-20

104 Background: Combining immune-checkpoint inhibitors with chemotherapy yielded high response rates in patients (pts) with metastatic TNBC. Therefore, we evaluated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor, to standard neoadjuvant chemotherapy in pts with primary TNBC. Methods: GeparNuevo randomized pts to durvalumab (D) 1.5 g i.v. or placebo every 4 weeks (wks). D/placebo monotherapy (0.75 g i.v.) was given for the first 2 wks (window phase), followed by a biopsy and D/placebo plus nab-paclitaxel (nP) 125 mg/m2 weekly for 12 wks, followed by D/placebo plus epirubicin/cyclophosphamide (EC) q2 wks for 4 cycles. Randomization was stratified by stromal tumor infiltrating lymphocyte (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). Pts with primary cT1b-cT4a-d disease, centrally confirmed TNBC and sTILs status were included. Primary objective compares pCR (ypT0 ypN0) rates. Secondary objectives are pCR rates in stratified subpopulations and according to other pCR definitions; response rates; breast conservation rate; toxicity; compliance and survival. Sample size was planned assuming a pCR rate of 48% for placebo based on the GeparSepto results and 66% for D (as clinically meaningful benefit), requiring 158 pts to show superiority of D (2-sided α=0.2, 80% power). Assuming a 10% drop-out rate, randomization of 174 pts was planned. Results: A total of 174 pts were enrolled between June 2016 and September 2017 and all pts had completed treatment. Median age was 49.5 years [range 23.0-76.0]; 44.5% of pts had cT1, 49.7% cT2, 3.5% cT3, 2.3% cT4; 83.3% G3 and 31.4% cN-positive tumors assessed by sonography; sTILs categories were 37.9% low, 47.7% intermediate, and 14.4% high; median Ki67 was 49.0% [range 3.0%-96.0%]. A total of 86 SAEs and 65 immune related AEs of special interest (irAESI) were reported; 34.5% of pts had at least one SAE and 27.6% had at least one irAESI. Overall, 84 of 174 pts (48.3% 95%CI [40.7-56.0]) had a pCR. Conclusions: Combination of chemotherapy with durvalumab/placebo yielded a high pCR rate in TNBC. Treatment was feasible. Unblinded results will be presented at the meeting. Funding and drug was provided by AstraZeneca and Celgene. Clinical trial information: NCT02685059.