bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease
Authors: Tahmaz Volkan , Wiesen Martin H. J. , Gehlsen Uta , Sauerbier Laura , Stern Michael E. , Holtick Udo , Gathof Birgit , Scheid Christof , Müller Carsten , Steven Philipp 
Published: August 2020

Abstract
Purpose
Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients’ morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED. Since these patients often receive systemic immunosuppressant therapy from their oncologists, a topical re-administration of these drugs via ASED with potentially beneficial or harmful effects is possible. The purpose of the study was to determine whether and to which extent systemic immunosuppressants are detectable in ASED.

Methods
A total of 34 samples of ASED from 16 patients with hemato-oncological malignancies after allo-SCT were collected during the manufacturing process and screened for levels of cyclosporine, mycophenolic acid, everolimus, and tacrolimus via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study followed the tenets of the Declaration of Helsinki and informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study.

Results
Cyclosporine was found in 18 ASED samples in concentrations ranging from 6.5–105.0 ng/ml (32.0 ± 22.8 ng/ml, mean ± SD). The concentration range of mycophenolic acid in 19 samples was 0.04–25.0 mg/l (4.0 ± 5.4 mg/l, mean ± SD). Everolimus and tacrolimus concentrations were well below the respective limits of quantification (< 0.6 and < 0.5 ng/ml) of the established LC-MS/MS method in all samples.

Conclusions
Our study suggests that orally administered cyclosporine and mycophenolic acid for the treatment of systemic GvHD, but not everolimus and tacrolimus, are distinctly detectable in ASED in relevant concentrations. It is highly likely that these agents affect topical therapy of ocular GvHD. However, the extent of this effect needs to be evaluated in further studies.
The probability of intransitivity in dice and close elections
Authors: Hązła Jan , Mossel Elchanan , Ross Nathan , Zheng Guangqu 
Published: August 2020

AbstractWe study the phenomenon of intransitivity in models of dice and voting. First, we follow a recent thread of research forn-sided dice with pairwise ordering induced by the probability, relative to 1/2, that a throw from one die is higher than the other. We build on a recent result of Polymath showing that three dice with i.i.d. faces drawn from the uniform distribution on$$\{1,\ldots ,n\}$${1,…,n}and conditioned on the average of faces equal to$$(n+1)/2$$(n+1)/2are intransitive with asymptotic probability 1/4. We show that if dice faces are drawn from a non-uniform continuous mean zero distribution conditioned on the average of faces equal to 0, then three dice are transitive with high probability. We also extend our results to stationary Gaussian dice, whose faces, for example, can be the fractional Brownian increments with Hurst index$$H\in (0,1)$$H∈(0,1). Second, we pose an analogous model in the context of Condorcet voting. We considernvoters who rankkalternatives independently and uniformly at random. The winner between each two alternatives is decided by a majority vote based on the preferences. We show that in this model, if all pairwise elections are close to tied, then the asymptotic probability of obtaining any tournament on thekalternatives is equal to$$2^{-k(k-1)/2}$$2-k(k-1)/2, which markedly differs from known results in the model without conditioning. We also explore the Condorcet voting model where methods other than simple majority are used for pairwise elections. We investigate some natural definitions of “close to tied” for general functions and exhibit an example where the distribution over tournaments is not uniform under those definitions.
Virtual Observations: a software tool for contextual observation and assessment of user’s actions in virtual reality
Authors: Howie Scott , Gilardi Marco 
Published: August 2020

AbstractIn this paper, we present ‘Virtual Observation’ (VO) a software tool for contextual observation and assessment of user’s directly from within the virtual reality (VR) simulation framework. Unlike other recording systems, the VO system described in this paper focuses on recording and reconstructing VR user’s positional, rotational and input data to recreate the same experience the user had with a VR simulation. Different from animation-based approaches, VO records user inputs and reconstructs the simulation from them and the user positional data. Moreover, the system allows the broadcast of this information to a remote machine enabling remote live observation of the simulation. Datasets recorded by the system can be shared by exporting them as XML files or, optionally, into a standalone online application, such as browser WebGL, allowing researchers, developers and educators to share and review a VR user simulation through a free-moving camera using a web browser. In this paper, the consistency of the data generated from the software by the client, server and reconstructed datasets acquired during real-time live observations was evaluated. We conclude that this Virtual Observation software offers detailed reconstruction of low-level information and visual information of user actions during simulations for both live and offline observations. We envision that our system will be of benefit for researchers, developers and educators that work with VR applications.
Double-endoscope assisted endoscopic submucosal dissection for treating tumors in rectum and distal colon by expert endoscopists: a feasibility study
Authors: Ebigbo A. , Tziatzios G. , Gölder S. K. , Probst A. , Messmann H. 
Published: August 2020

Abstract
Background
Colorectal endoscopic submucosal dissection (ESD) is an effective but challenging procedure. To facilitate ESD, several methods that apply traction are available; however, the optimal one remains to be established. The aim of this study was to evaluate the feasibility and safety of the double-endoscope assisted ESD (DEA-ESD) by improving traction to treat complex colorectal lesions.

Methods
Naïve or previously treated lesions in the rectum and sigmoid colon were included. A grasping forceps advanced through a small-caliber endoscope (GIF-XP190N, Olympus Medical Systems, Tokyo, Japan, 5.4 mm outer diameter) was used to apply traction to the mucosal flap. Lesions were deemed complex when they exceeded a total of nine points on the SMSA scoring system (size, morphology, site, and access) and recurrent when they were previously treated with endoscopic mucosal resection (EMR). Outcome measures included procedural success, total procedure time, complications, and recurrence rate at 3-month follow-up.

Results
Nine patients (mean age 62.3 ± 14.5 years) were included; five had rectal and four had tumors in the sigmoid colon. The median SMSA score was 14 (SMSA Level IV—complex polyp), while three patients were pre-treated with EMR. DEA-ESD was technically feasible in all cases. En bloc resection and R0 resection rates were 100%, respectively, with a mean procedure time of 128.4 ± 54.1 min. No immediate or delayed complications occurred.

Conclusions
DEA-ESD is a feasible and safe method for treating complex or recurrent tumors in the rectum and distal colon.
Contents, vehicles, and complex data analysis in neuroscience
Authors: Burnston Daniel C. 
Published: August 2020

AbstractThe notion of representation in neuroscience has largely been predicated on localizing the components of computational processes that explain cognitive function. On this view, which I call “algorithmic homuncularism,” individual, spatially and temporally distinct parts of the brain serve as vehicles for distinct contents, and the causal relationships between them implement the transformations specified by an algorithm. This view has a widespread influence in philosophy and cognitive neuroscience, and has recently been ably articulated and defended by Shea (2018). Still, I am skeptical about algorithmic homuncularism, and I argue against it by focusing on recent methods for complex data analysis in systems neuroscience. I claim that analyses such as principle components analysis and linear discriminant analysis prevent individuating vehicles as algorithmic homuncularism recommends. Rather, each individual part contributes to a global state space, trajectories of which vary with important task parameters. I argue that, while homuncularism is false, this view still supports a kind of “vehicle realism,” and I apply this view to debates about the explanatory role of representation.
Physicochemical characteristics of the Dombrovska pit lake (Ukraine) formed in an opencast potassium salt mine and the genome response of Chironomus salinarius Kieffer (Chironomidae, Diptera) to these conditions
Authors: Michailova Paraskeva , Szarek-Gwiazda Ewa , Kownacki Andrzej 
Published: August 2020

AbstractThis study focuses on the Dombrovska pit lake, near the city of Kalush in Ukraine, which is a former potassium salt mine filled with brine and freshwater. The water level is still increasing and as a result the salinity is decreasing. We analyzed the benthic fauna communities and the genome instability by assessing the rearrangements in the polytene chromosomes of Chironomus salinarius and the physicochemical parameters of the near-bottom water (pH, conductivity, mineralization, major ions, NO3−, NH4+, metals Cd, Pb, Cu, Mn, and Fe) and sediment (pH, organic matter and metals Cd, Pb, Cu, Zn, Mn, and Fe) at four sites. The water mineralization ranged from 17.3 to 26.2 g dm−3 which are classified as mesohaline and polyhaline waters, respectively. The biodiversity of the benthic fauna was low, and the dominant species was C. salinarius. The density of C. salinarius varied spatially and changed from 637 ind./m2 at a depth of 5 m to 8167 ind./m2 at a depth of 2.5 m. The genome instability was analyzed by examining the structural and functional changes in the salivary gland chromosomes of C. salinarius. The exposure of C. salinarius damaged the chromosomes and the activities of key structures, such as the Balbiani ring and nucleolar organizer, were partially or completely suppressed.
Metabolic profile of the synthetic drug 4,4′-dimethylaminorex in urine by LC–MS-based techniques: selection of the most suitable markers of its intake
Authors: Chieffi Claudia , Camuto Cristian , De-Giorgio Fabio , de la Torre Xavier , Diamanti Francesca , Mazzarino Monica , Trapella Claudio , Marti Matteo , Botrè Francesco 
Published: August 2020

Abstract
Purpose
In this study, the phase I and II metabolic pathways of 4,4′-dimethylaminorex were characterized to select the marker(s) of intake allowing the unequivocal identification of this novel psychoactive substance in urine samples.

Methods
The metabolic profile of 4,4′-dimethylaminorex was characterized using both in vitro and in vivo models. In detail, for the in vitro experiments, either pooled human liver microsomes or recombinant cytochrome P450 isoforms were selected, whereas the in vivo investigation was performed on male mice ICR (CD-1®). Sample preparation included enzymatic hydrolysis followed by liquid/liquid extraction. The instrumental analysis was performed by ultra-high-performance liquid chromatography coupled to either high- or low-resolution tandem mass spectrometry.

Results
Five metabolic products were isolated only for the cis-isomer: the phase I metabolic reactions included hydrolysis, carboxylation, hydroxylation, and carbonylation. CYP2D6 was the principal isoenzyme involved, and the incubation in the presence of different allelic variants showed significant alteration on the metabolic profile. Once formed, the phase I metabolites underwent extensive conjugation. Not only the most abundant compounds detected, but also those with the most extended window of detection, were the carboxylated and the hydroxylated metabolites. These analytes together with the parent compound were selected as the most suitable markers of intake.

Conclusions
Knowledge of the metabolic profiles of the new drugs is essential for their fast identification. Phase I and phase II metabolites of 4,4′-dimethylaminorex were identified and selected as markers of intake, to be considered as the most suitable analytical targets in forensic toxicology.
Revision of failed reverse shoulder arthroplasty—a point of no return?
Authors: Gohlke Frank , Abdelkawi Ayman A. , Eltair Hani , Aboalata Mohamed , Hussein Walid , Abdrabo Mohamed S. , Jasper Tina 
Published: August 2020

Abstract
Background
The rate of complications after revision of reverse shoulder arthroplasty (RSA) is higher than it is in primary RSA, depending on the type of surgical intervention, the follow-up time, the preoperative condition of the patient, and the experience of the surgeon.

Objective
The current article represents an evaluation of the authors’ experiences with revisions of RSA and a review of literature, in order to define prognostic parameters and surgical options for the most common modes of failure.

Materials and methods
Between 2010 and 2019, 136 revisions of RSA were performed. Mean age of the patients at surgery was 68.3 years (29–88 years). The main indication was instability in 24 patients and chronic infection in 34. Aseptic loosening of the stem was the main indication in 15 and aseptic loosening of the baseplate in 23 patients. Periprosthetic fractures were present in 21 patients. Fractures of the scapular spine were operated on in 6 and surgery was performed for progressive notching due to malposition of the glenosphere in 4 patients.

Results
Staged procedures, use of allografts, and custom-made implants are common, especially for chronic infections and severe bone loss. Most of the patients (88.2%) were treated successfully. Two salvage procedures and two retentions of spacers occurred. We identified risk groups for re-revision: chronic dislocations, chronic infections, advanced bone loss, and scapular spine fractures. We observed a shift of indications and techniques, often related to the design of the implants.

Conclusion
These results confirm that careful preoperative planning, special implants, and a high level of experience are mandatory. With time, the authors developed an algorithm for certain indications because it was recognized that failures are often of multifactorial origin. Today, numerous implant designs which differ considerably in biomechanical features and failure modes are available. This makes revisions of RSA more complex than it was in the past.
Survivorship care for cancer patients in primary versus secondary care: a systematic review
Authors: Vos J. A. M. , Wieldraaijer T. , van Weert H. C. P. M. , van Asselt K. M. 
Published: August 2020

Abstract
Background
Cancer survivorship care is traditionally performed in secondary care. Primary care is often involved in cancer management and could therefore play a more prominent role.

Purpose
To assess outcomes of cancer survivorship care in primary versus secondary care.

Methods
A systematic search of MEDLINE and EMBASE was performed. All original studies on cancer survivorship care in primary versus secondary care were included. A narrative synthesis was used for three distinctive outcomes: (1) clinical, (2) patient-reported, and (3) costs.

Results
Sixteen studies were included: 7 randomized trials and 9 observational studies. Meta-analyses were not feasible due to heterogeneity. Most studies reported on solid tumors, like breast (N = 7) and colorectal cancers (N = 3). Clinical outcomes were reported by 10 studies, patient-reported by 11, and costs by 4. No important differences were found on clinical and patient-reported outcomes when comparing primary- with secondary-based care. Some differences were seen relating to the content and quality of survivorship care, such as guideline adherence and follow-up tests, but there was no favorite strategy. Survivorship care in primary care was associated with lower societal costs.

Conclusions
Overall, cancer survivorship care in primary care had similar effects on clinical and patient-reported outcomes compared with secondary care, while resulting in lower costs.

Implications for cancer survivors
Survivorship care in primary care seems feasible. However, since the design and outcomes of studies differed, conclusive evidence for the equivalence of survivorship care in primary care is still lacking. Ongoing studies will help provide better insights.
Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin
Authors: Juhlin Carl Christofer , Zedenius Jan , Höög Anders 
Published: August 2020

AbstractNeuroendocrine neoplasms (NENs) have traditionally been identified via expression of proteins associated to the regulation of secretory vesicles and granules. We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogranin A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immunoreactivity was noted for ISL1 in 91/139 NENs (65%) and in 6/22 (27%) non-NENs, for INSM1 in 76/85 NENs (89%) and in 2/5 (40%) non-NENs, and for SECG in 49 out of 64 NENs (77%) and in 0/5 non-NENs (0%). Generally, ISL1, INSM1, and SECG exhibited sensitivities in line with or slightly below that of CGA and SYP—largely attributable to tissue-specific patterns regarding tumoral origin. Moreover, for pancreatic and small intestinal NENs, the two largest subgroups, ISL1 staining results were consistent irrespectively of tumor source and WHO grade. We verify previously suggested immunohistochemical schemes of neuroendocrine markers of first- and second-generations to facilitate the diagnostic process for NENs and confirm that the second-generation neuroendocrine markers display tissue-specific patterns. We therefore recommend their implementation in tertiary endocrine pathology centers, not least to aid in the identification of primary tumors when analyzing metastases.
Avoiding Rice-Based Cadmium and Inorganic Arsenic in Infant Diets Through Selection of Products Low in Concentration of These Contaminants
Authors: Shi Zhengyu , Carey Manus , Davidson Emily , Meharg Caroline , Meharg Andrew A. 
Published: August 2020

AbstractCadmium in the diet is of concern as it is a renal toxicant and a carcinogen, with a half-life in the body measured in decades. Inorganic arsenic is a chronic carcinogen. For many subpopulations, rice and rice products may be the dominate source of cadmium and inorganic arsenic. In particular, rice porridge, cereal and cake are widely used to feed infants (children < 4.5 years old). In the EU standards for cadmium infant foods in general has been set at 40 μg/kg w.wt., and for inorganic arsenic in rice-based infant foods the standard is 100 μg/kg w.wt.. Here we report cadmium and inorganic arsenic concentrations in rice products marketed for infants, and rice containing products that infants may eat but that are not specifically designated for infants. It was found that while rice-based infant foods conformed to the standards, their non-infant food (generic) analogues did not. Non-infant rice crackers and puffed rice cereals, in particular, had concentrations above these standards for both cadmium and inorganic arsenic. Polished pure rice grain purchased in the UK, but sourced from different countries, was also problematic. Basmati, Italian, Spanish and Thai rice, either exceeded one or the other of the cadmium and inorganic arsenic safety thresholds for infants, or both. Egyptian rice grain was particularly low for both toxins. Therefore, if those responsible for infants want to lower exposure to cadmium and inorganic arsenic, they should stick to foods specifically labeled for infants, or carefully source low cadmium and inorganic arsenic rice-based products that are not specifically labeled as being for infant consumption, or minimize exposure to rice-based foods.
In-silico identification and differential expression of putative disease resistance-related genes within the collinear region of Brassica napus blackleg resistance locus LepR2’ in Brassica oleracea
Authors: Hossain Mohammad Rashed , Ferdous Mostari Jahan , Park Jong-In , Robin Arif Hasan Khan , Natarajan Sathishkumar , Jung Hee-Jeong , Kim Hoy-Taek , Nou Ill-Sup 
Published: August 2020

AbstractBlackleg disease, caused by Leptosphaeria maculans, greatly affects the production of cabbage (Brassica oleracea). However, definitive R-gene(s) are yet to be identified in this crop. In contrast, a number of R-loci have been identified in A- or B-genome crops. Identification of few resistant cabbage genotypes indicates the presence of R-genes in this C-genome crop. High ancestral synteny between Brassica genomes suggests that the collinear regions of known A- or B-genome R-loci may also contain functional R-genes in the C-genome. Strong resistance was observed in the cotyledons of cabbage inbred line SCNU-98 against two L. maculans isolates, 03–02 s and 00–100 s. We investigated the collinear region of the Brassica napus blackleg resistance locus LepR2’ in B. oleracea since both isolates of L. maculans contain corresponding avirulence genes. The locus was collinear to a 5.8 Mbp genomic segment of B. oleracea chromosome C09 containing 13 genes that have putative disease resistance-related domains. High expression of genes Bo9g117290 and Bo9g111510 against isolate 00–100 s, and high expression of genes Bo9g126150 and Bo9g111490 against both isolates in the resistant-line SCNU-98 indicate their putative roles in blackleg resistance, which remained to be functionally verified. This work enhances our understanding of R-gene-mediated resistance to blackleg in cabbage.