Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the Impact of Non-Differential Genotyping Errors on Rare Variant Tests of Association

Background/Aims: We aim to quantify the effect of non-differential genotyping errors on the power of rare variant tests and identify those situations when genotyping errors are most harmful. Methods: We simulated genotype and phenotype data for a range of sample sizes, minor allele frequencies, disease relative risks and numbers of rare variants. Genotype errors were then simulated using five different error models covering a wide range of error rates. Results: Even at very low error rates, misclassifying a common homozygote as a heterozygote translates into a substantial loss of power, a result that is exacerbated even further as the minor allele frequency decreases. While the power loss from heterozygote to common homozygote errors tends to be smaller for a given error rate, in practice heterozygote to homozygote errors are more frequent and, thus, will have measurable impact on power. Conclusion: Error rates from genotype-calling technology for next-generation sequencing data suggest that substantial power loss may be seen when applying current rare variant tests of association to called genotypes.
Lymphatics in the Brain?!

ards of care for treatment of recurrent glioblastoma: are we there yet? Neuro Oncol. 2013;15(1):4-27. 3. Hundsberger T, Hottinger AF, Roelcke U, et al. Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes [published online ahead of print October 12, 2015]. J Neuro Oncol. doi: 10.1007/ s11060-015-1957-0. Available at: http://link.springer. com/article/10.1007%2Fs11060-015-1957-0.
Design of unequal error protection for MIMO-OFDM systems with hierarchical signal constellations

In multimedia communication systems, efficient trans- mission system design should incorporate the use of matching unequal error protection (UEP), since source coders exhibit unequal bit error sensitivity. In this paper, we present UEP schemes which exploit differences in bit error protection levels in orthogonal frequency division multiplexing (OFDM) systems over frequency selective fading channels. We introduce an UEP scheme which improves the link performance with multiple transmit and receive antennas. Especially, we propose a new receiver structure based on two stage Maximum Likelihood detection (MLD) schemes which can approach the performance of a full search MLD receiver with much reduced computational complexity. In the performance analysis, we derive a generalized pairwise error probability expression for the proposed UEP schemes. Simulation results show that the proposed schemes achieve a significant performance gain over the conventional equal error protection (EEP) scheme.
Fine Temporal Properties of Center–Surround Interactions in Motion Revealed by Reverse Correlation

Center–surround interactions are a key property of visual motion mechanisms. Using a temporal reverse correlation method with human observers, we investigated perceptual interactions between a brief center motion (∼20 ms) and a surround that moved up–down with a new direction chosen randomly every 5 ms. The aim was to reveal interactions between center and surround motions and their dependency on relative direction, contrast, and timing. Hypothesizing that surround computation involves different neural circuitry than the center response, we manipulated surround contrast to affect the relative timing of center and surround signals. The reverse correlation analysis yielded temporal profiles of surround influence indicating, in 5 ms steps, the time course of the effect of the surround on the discriminability of center motion. The resulting temporal profiles varied systematically with contrast: as surround contrast decreased, both the latency and duration of its influence increased. This finding, consistent with longer and variable neural response latencies at low contrast, psychophysically reveals fine-scale temporal interactions between center and surround signals. Additionally, the strength of surround influence was correlated with psychophysical thresholds for discriminating center motion. The directionality of this relationship, however, depended only on center contrast. When center motion was high contrast, poor direction discrimination was associated with an increased probability of same-direction surround motions. Low-contrast center motion, however, was more discriminable when surrounded by motion in the same direction, regardless of surround contrast. This suggests that the previously reported adaptive nature of center–surround interactions in motion is driven primarily by the visibility of the center motion signals.
Ionotropic Glutamate Receptor GluR1 in the Visual Cortex of Hamster: Distribution and Co-Localization with Calcium-Binding Proteins and GABA

The subunit composition of the AMPA receptor is critical to its function. AMPA receptors that display very low calcium permeability include the GluR2 subunit, while AMPA receptors that contain other subunits, such as GluR1, display high calcium permeability. We have studied the distribution and morphology of neurons containing GluR1 in the hamster visual cortex with antibody immunocytochemistry. We compared this labeling to that for calbindin D28K, parvalbumin, and GABA. Anti-GluR1-immunoreactive (IR) neurons were located in all layers. The highest density of GluR1-IR neurons was found in layers II/III. The labeled neurons were non-pyramidal neurons, but were varied in morphology. The majority of the labeled neurons were round or oval cells. However, stellate, vertical fusiform, pyriform, and horizontal neurons were also labeled with the anti-GluR1 antibody. Two-color immunofluorescence revealed that many of the GluR1-IR neurons in the hamster visual cortex were double-labeled with either calbindin D28K (31.50%), or parvalbumin (22.91%), or GABA (63.89%). These results indicate that neurons in the hamster visual cortex express GluR1 differently according to different layers and selective cell types, and that many of the GluR1-IR neurons are limited to neurons that express calbindin D28K, parvalbumin, or GABA. The present study elucidates the neurochemical structure of GluR1, a useful clue in understanding the differential vulnerability of GluR1-containing neurons with regard to calcium-dependent excitotoxic mechanisms.
How the ExpertFit distribution-fitting software can make your simulation models more valid

The authors discuss the critical role of simulation input modeling in a successful simulation study. Two pitfalls in simulation input modeling are then presented and we explain how any analyst, regardless of their knowledge of statistics, can easily avoid these pitfalls through the use of the ExpertFit distribution-fitting software. We use a set of real-world data to demonstrate how the software automatically specifies and ranks probability distributions, and then tells the analyst whether the "best" candidate distribution is actually a good representation of the data. If no distribution provides a good fit, then ExpertFit can define an empirical distribution. In either case, the selected distribution is put into the proper format for direct input to the analyst's simulation software.
Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates

The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs. m1A947 is conserved in humans and all vertebrates having adenine at the corresponding mtDNA position (90% of vertebrates). However, this mtDNA base is a thymine in 10% of the vertebrates and a guanine in the 23S rRNA of 95% of bacteria, suggesting alternative evolutionary solutions. m1A, uridine, or guanine may stabilize the local structure of mitochondrial and bacterial ribosomes. Experimental assessment of genome-edited Escherichia coli showed that unmodified adenine caused impaired protein synthesis and growth. Our findings revealed a conserved mechanism of rRNA modification that has been selected instead of DNA mutations to enable proper mitochondrial ribosome function.
Measured capacity of an Ethernet: myths and reality

Ethernet, a 10 Mbit/sec CSMA/CD network, is one of the most successful LAN technologies. Considerable confusion exists as to the actual capacity of an Ethernet, especially since some theoretical studies have examined operating regimes that are not characteristic of actual networks. Based on measurements of an actual implementation, we show that for a wide class of applications, Ethernet is capable of carrying its nominal bandwidth of useful traffic, and allocates the bandwidth fairly. We discuss how implementations can achieve this performance, describe some problems that have arisen in existing implementations, and suggest ways to avoid future problems.
Suicide in Parkinson's Disease Patients Treated With Levodopa‐Carbidopa Intestinal Gel

Fernandez et al. presented results of a 12-month followup study concerning safety and efficacy of levodopacarbidopa intestinal gel (LCIG) in Parkinson’s disease (PD). Two among 272 treated patients committed suicide, both with history of depression. The researchers did not consider suicide to be treatment related. However, suicide percentage in their study is higher than expected for PD. Owing to the short follow-up period, the suicide risk could have even been underestimated. In our experience, suicide may be more common in LCIG-treated patients, because we have witnessed 2 cases of suicide among 53 PD patients treated with LCIG in Slovenia from 2006 to 2014. Patients’ characteristics are given in Table 1. The first patient was a 67-year-old male without a history of depression who was started on LCIG only 3 years after PD onset, as necessitated by poor symptoms control and motor complications on combination of L-dopa and dopamine agonist (DA). Notably, DA was withdrawn on LCIG initiation. The patient did not display any signs of depression or suicidal ideation. Within 3 weeks, LCIG dosage was optimized, allowing good motor function. During temporary weekend discharge, he committed suicide by hanging. The second patient was a 72-year-old male with a 15-year history of PD and no history of depression before LCIG. LCIG resulted in excellent motor response; however, he immediately developed psychosis and visual hallucinations. Psychiatric symptoms resolved with medical treatment. During the subsequent 5 years, the patient had stable motor response, but experienced cognitive decline and reappearance of visual hallucinations. One year before death, he was noticed to be depressed and venlafaxine 75 mg was started. At the last follow-up visit, he had no obvious signs of depression. He committed suicide 2 months later by shooting himself in the head. Both families were unaware of the patients’ intentions. Most, but not all, studies found that suicide rate in PD is equivalent or lower than in the general population, despite a high prevalence of comorbid risk factors, such as depresT A B L E 1 . P a ti e n ts ’ c h a ra c te ri s ti c s
Local Transplantation of Granulocyte Colony-Stimulating Factor-Mobilized Human Peripheral Blood Mononuclear Cells for Unhealing Bone Fractures

We previously reported the therapeutic potential of human peripheral blood (hPB) CD34+ cells for bone fracture healing via vasculogenesis/angiogenesis and osteogenesis. Transplantation of not only hPB CD34+ cells but also hPB total mononuclear cells (MNCs) has shown their therapeutic efficiency for enhancing ischemic neovascularization. Compared with transplantation of purified hPB CD34+ cells, transplantation of hPB MNCs is more attractive due to its simple method of cell isolation and inexpensive cost performance in the clinical setting. Thus, in this report, we attempted to test a hypothesis that granulocyte colony-stimulating factor-mobilized (GM) hPB MNC transplantation could also contribute to fracture healing via vasculogenesis/angiogenesis and osteogenesis. Nude rats with unhealing fractures received local administration of the following materials with atelocollagen: 1 × 107 GM hPB MNCs (Hi group), 1 × 106 GM hPB MNCs (Lo group), or PBS (PBS group). Immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated human cell-derived vasculogenesis and osteogenesis in the Hi and Lo groups, but not in the PBS group at week 1. Intrinsic angiogenesis and osteogenesis assessed by rat capillary, osteoblast density, and real-time RT-PCR analysis was significantly enhanced in the Hi group compared to the other groups. Blood flow assessment by laser doppler perfusion imaging showed a significantly higher blood flow ratio at week 1 in the Hi group compared with the other groups. Morphological fracture healing was radiographically and histologically confirmed in about 30% of animals in the Hi group at week 8, whereas all animals in the other groups resulted in nonunion. Local transplantation of GM hPB MNCs contributes to fracture healing via vasculogenesis/angiogenesis and osteogenesis.
Near-Lossless Multichannel EEG Compression Based on Matrix and Tensor Decompositions

A novel near-lossless compression algorithm for multichannel electroencephalogram (MC-EEG) is proposed based on matrix/tensor decomposition models. MC-EEG is represented in suitable multiway (multidimensional) forms to efficiently exploit temporal and spatial correlations simultaneously. Several matrix/tensor decomposition models are analyzed in view of efficient decorrelation of the multiway forms of MC-EEG. A compression algorithm is built based on the principle of “lossy plus residual coding,” consisting of a matrix/tensor decomposition-based coder in the lossy layer followed by arithmetic coding in the residual layer. This approach guarantees a specifiable maximum absolute error between original and reconstructed signals. The compression algorithm is applied to three different scalp EEG datasets and an intracranial EEG dataset, each with different sampling rate and resolution. The proposed algorithm achieves attractive compression ratios compared to compressing individual channels separately. For similar compression ratios, the proposed algorithm achieves nearly fivefold lower average error compared to a similar wavelet-based volumetric MC-EEG compression algorithm.
Hydrogel Interferometry for Ultrasensitive and Highly Selective Chemical Detection

Developing ultrasensitive chemical sensors with small scale and fast response through simple design and low‐cost fabrication is highly desired but still challenging. Herein, a simple and universal sensing platform based on a hydrogel interferometer with femtomol‐level sensitivity in detecting (bio)chemical molecules is demonstrated. A unique local concentrating effect (up to 109 folds) in the hydrogel induced by the strong analyte binding and large amount of ligands, combined with the signal amplification effect by optical interference, endows this platform with an ultrahigh sensitivity, specifically 10−14m for copper ions and 1.0 × 10−11 mg mL−1 for glycoprotein with 2–4 order‐of‐magnitude enhancement. The specific chemical reactions between selected ligands and target analytes provide high selectivity in detecting complex fluids. This universal principle with broad chemistry, simple physics, and modular design allows for high performance in detecting wide customer choices of analytes, including metal ions and proteins. The scale of the sensor can be down to micrometer size. The nature of the soft gel makes this platform transparent, flexible, stretchable, and compatible with a variety of substrates, showing high sensing stability and robustness after 200 cycles of bending or stretching. The outstanding sensing performance grants this platform great promise in broad practical applications.
Prevalence of Human Papillomavirus Genotypes in Women from Cozumel, Mexico

Background: Human papillomavirus (HPV) subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 have been implicated in the development of cervical cancer (CC). These 13 high risk HPV types have been shown to be present in up to 99.7% of CC samples. In Mexico, this cancer is the leading cause of death from malignancy among women. The aim of this study was to determine the prevalence of different HPV genotypes and investigate epidemiological aspects associated with HPV infection in women from Cozumel. Material and methods: We performed an epidemiological, prospective and cross sectional study with 1,187 who accepted participation in a campaign of screening for CC, during the period 2014 to 2015. Data on epidemiological and socio-economic variables were obtained. Cervical cells were collected for detection of HPV DNA and typing of HPV-positive samples by Multiplex PCR, using a commercial kit for 16 viral genotypes. Results: The overall prevalence of HPV in women from Cozumel was 15.8 % (188/1,187), either single (13.6%) or multiple (2.19 %). The most common HPV types , in descending order of frequency, were 58 (24.5 %), 59 (13.3 %), 39 (12.2 %) and 66 (9.6 %). The most frequent high risk types were HPV-58 and -59 and of low risk HPV types the most common was HPV-6. Number of sexual partners (OR=4.78; 95% CI= 2.73-8.37; P=<0.0001) and age of first coitus (OR=0.51; 95% CI=0.32-0.81; P=<0.0011) were significantly associated with HPV infection. Conclusions: Our data indicate that the overall incidence of high risk HPV infection in Cozumel is low as compared to other studies worldwide, with a different profile of subtypes. However, as expected, risky sexual behavior was found associated with positive cases of HPV. These results highlight the need for establish strategies to prevent HPV acquisition and evaluate the impact of a vaccine application in the Cozumel population.
Ibrutinib Resistance Is Reduced by an Inhibitor of Fatty Acid Oxidation in Primary CLL Lymphocytes

Chronic Lymphocytic Leukemia (CLL) is an incurable disease, characterized by the accumulation of malignant B-lymphocytes in the blood stream (quiescent state) and homing tissues (where they can proliferate). In CLL, the targeting of B-cell receptor signaling through a Burton's tyrosine kinase inhibitor (ibrutinib) has rendered outstanding clinical results. However, complete remission is not guaranteed due to drug resistance or relapse, revealing the need for novel approaches for CLL treatment. The characterization of metabolic rewiring in proliferative cancer cells is already being applied for diagnostic and therapeutic purposes, but our knowledge of quiescent cell metabolism—relevant for CLL cells—is still fragmentary. Recently, we reported that glutamine metabolism in primary CLL cells bearing the del11q deletion is different from their del11q negative counterparts, making del11q cells especially sensitive to glutaminase and glycolysis inhibitors. In this work, we used our primary CLL lymphocyte bank and compounds interfering with central carbon metabolism to define metabolic traits associated with ibrutinib resistance. We observe a differential basal metabolite uptake linked to ibrutinib resistance, favoring glutamine uptake and catabolism. Upon ibrutinib treatment, the redox balance in ibrutinib resistant cells is shifted toward NADPH accumulation, without an increase in glutamine uptake, suggesting alternative metabolic rewiring such as the activation of fatty acid oxidation. In accordance to this idea, the curtailing of fatty acid oxidation by CPT1 inhibition (etomoxir) re-sensitized resistant cells to ibrutinib. Our results suggest that fatty acid oxidation could be explored as a target to overcome ibrutinib resistance.
Opioid use disorder: A public health emergency

ABSTRACT The treatment of patients with acute and chronic pain not attributed to cancer or end-of-life conditions is a challenge for many clinicians. Although CDC guidelines that focus on the primary care setting have provided critical recommendations, evidence-based guidance is lacking on optimal duration of opioid treatment for postoperative and acute care in specialty settings. Over the last 2 decades, the liberal use of opioids has resulted in many unintended consequences, including dependence and abuse, illicit distribution of legally and illegally prescribed opioid medication, progression to IV heroin and an epidemic of overdoses, and most recently an increase in the incidence of HIV among patients sharing syringes, frequently in communities with historically low HIV rates. This article analyzes these complex issues and proposes strategies to help clinicians improve patient care through education and responsible prescribing.
Genotypic diversity of Pasteurella multocida isolates from pigs and poultry in Australia

OBJECTIVE To investigate the genotype and diversity of Pasteurella multocida present in pig herds and to determine the extent of overlap with isolates from poultry flocks in Australia. METHODS A total of 43 isolates from pigs from different farms and regions of Australia were used in this study. A diverse collection of 41 poultry isolates, with 31 being previously characterised, was also used. The pig isolates and 10 poultry isolates were identified by species-specific PCR assay, serotyped by the Heddleston scheme and genotyped by a multiplex PCR based on the lipopolysaccharide (LPS) outer core biosynthesis locus, repetitive element PCR fingerprinting (rep-PCR) and multilocus sequence typing (MLST), with the latter being used on a subset of the isolates based on the rep-PCR results. RESULTS Only 4 out of 8 recognised LPS genotypes were found in the pig isolates, with each isolate assigned to an LPS genotype. In contrast, 77% of the isolates were non-typable or cross-reacting in the Heddleston serotyping scheme. The rep-PCR analysis recognised 20 patterns, yet only 16 sequence types (STs) were found and 4 were new STs. There were 5 STs (STs 7, 11, 20, 24 and 58) shared among the pig and poultry isolates. CONCLUSIONS Although only limited numbers of isolates have been examined, there is evidence of a sharing of genotypes between Australian pigs and chickens. These findings have major implication for biosecurity measures with regard to minimising both direct (e.g. animal to animal) and in-direct (e.g. shared staff or cross-visitors) contact between poultry and pigs.
An approximate dual subgradient algorithm for multi-agent non-convex optimization

We consider a multi-agent optimization problem where agents aim to cooperatively minimize a sum of local objective functions subject to a global inequality constraint and a global state constraint set. In contrast to existing papers, we do not require the objective, constraint functions, and state constraint sets to be convex. We propose a distributed approximate dual subgradient algorithm to enable agents to asymptotically converge to a pair of approximate primal-dual solutions over dynamically changing network topologies. Convergence can be guaranteed provided that the Slater's condition and strong duality property are satisfied.