Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of neuropeptide drugs that cross the blood-brain barrier

SummaryIn recent years, there have been several important advancements in the development of neuropeptide therapeutics. Nevertheless, the targeting of peptide drugs to the CNS remains a formidable obstacle. Delivery of peptide drugs is limited by their poor bioavailability to the brain due to low metabolic stability, high clearance by the liver, and the presence of the blood brain barrier (BBB). Multiple strategies have been devised in an attempt to improve peptide drug delivery to the brain, with variable results. In this review, we discuss several of the strategies that have been used to improve both bioavailability and BBB transport, with an emphasis on antibody based vector delivery, useful for large peptides/small proteins, and glycosylation, useful for small peptides. Further development of these delivery methods may finally enable peptide drugs to be useful for the treatment of neurological disease states.
Effects of network topology on the conditional distributions of surrogated generalized coherence estimates

Coherence estimation is an established approach in multiple-channel detection and estimation, providing optimal solutions in many cases. Recent work has considered the use of maximum-entropy matrix completion when elements are missing from the gram matrix from which the coherence statistics are formed. This is desirable in sensor network settings, for example, where direct communication is not available between every pair of nodes in the network. This paper examines the role of network topology in determining the conditional distributions of the statistic obtained by the matrix completion process under both signal-present and signal-absent hypotheses.
The VWF-GPIb axis in ischaemic stroke: lessons from animal models

Summary Stroke is a leading cause of death and long-term disability worldwide. Ischaemic stroke is caused by a blood clot that obstructs cerebral blood flow. Current treatment mainly consists of achieving fast reperfusion, either via pharmacological thrombolysis using tissue plasminogen activator or via endovascular thrombectomy. Unfortunately, reperfusion therapy is only available to a limited group of patients and reperfusion injury can further aggravate brain damage. Hence, there is an urgent need for better understanding of ischaemic stroke pathophysiology in order to develop novel therapeutic strategies. In recent years, the pathophysiological importance of von Willebrand factor (VWF) in ischaemic stroke has become clear from both clinical and experimental studies. In particular, binding of VWF to platelet glycoprotein Ib (GPIb) has become an interesting target for ischaemic stroke therapy. Recent insights show that inhibting the VWF-GPIb interaction could result in a pro-thrombolytic activity improving cerebral reperfusion rates and concurrently reducing cerebral ischaemia/reperfusion damage. This review gives an overview of the experimental evidence that illustrates the crucial role of the VWF-GPIb axis in ischaemic stroke.
Video Classification and Shot Detection for Video Retrieval Applications

Appropriate organization of video databases is essential for pertinent indexing and retrieval of visual information. This paper proposes a new feature called Block Intensity Comparison Code (BICC) for video classification and an unsupervised shot change detection algorithm to detect the shot changes in a video stream using autoassociative neural network (AANN) which makes retrieval problems much simpler. BICC represents the average block intensity difference between blocks of a frame. A novel AANN misclustering rate (AMR) algorithm is used to detect the shot transitions. The experiments demonstrate the effectiveness of the proposed methods.
RORγT, a thymus‐specific isoform of the orphan nuclear receptor RORγ / TOR, is up‐regulated by signaling through the pre‐T cell receptor and binds to the TEA promoter

TEA (T early alpha) is a genetic element located upstream of the TCR‐Jα cluster. Thymocytes from mice carrying a targeted deletion of TEA do not rearrange their TCRα locus on a window spanning the first nine Jα segments. This led us to the hypothesis of TEA having a “rearrangement focusing” activity on the 5′ side of the TCR‐Jα region. We analyzed DNAseI and “phylogenetic” footprints within the TEA promoter in an attempt to identify trans‐acting factors that could account for its regulatory function on DNA accessibility. One of these footprints corresponded to a putative DNA‐binding site for an orphan nuclear receptor of the ROR / RZR family. The RORγT cDNA clone was isolated from a thymus library using a probe corresponding to the DNA‐binding domain of RORγ / TOR. RORγT is a thymus‐specific isoform of RORγ, expressed almost exclusively in immature double‐positive thymocytes. RORγT binds, to the TEA promoter in vitro. Lastly, the expression of RORγT is stimulated in two situations that mimic activation through the pre‐TCR and in which the thymocytes have their TCR‐α locus in an “open”, yet unrearranged DNA configuration. We propose that the expression of RORγT may be part of the pre‐TCR activation cascade leading to the maturation of α / β T cells and may participate in the regulation of DNA accessibility in the TCR‐Jα locus.
Oncological Outcomes of Stage II Endometrial Cancer: A Retrospective Analysis of 250 Cases

Objective The aim of this study was to investigate the effect of different surgical approaches, adjuvant therapy, and pathological characteristics on oncological outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer (EC). Methods A multicenter, retrospective department database review was performed to identify patients with FIGO 2009 stage II EC who underwent surgical staging between 2002 and 2015 at 5 gynecologic oncology centers in Turkey. Results Original pathology reports of 4867 patients who underwent surgical treatment for EC were analyzed. The study group consisted of 250 FIGO stage II patients. Of these patients, 203 (81.2%) had endometrioid and 47 (18.8%) had nonendometrioid histologic subtype of EC. Whereas 199 patients (79.6%) underwent type I hysterectomy, the remaining 51 patients (20.4%) underwent radical hysterectomy. Of the 250 patients, 208 patients (83.2%) had adjuvant therapy including radiotherapy (pelvic external beam radiotherapy and/or vaginal brachytherapy [VBT]) and/or platinum-based chemotherapy. Disease recurred in 29 patients (11.6%). The 5-year disease-free survival (DFS) and overall survival (OS) for the entire cohort were 82% and 85%, respectively. Multivariate analysis showed that only adjuvant treatment (P = 0.001; hazard ratio, 4.02; 95% confidence interval, 1.72–9.36) was significantly associated with DFS. According to multivariate analysis, only age older than 60 years (P = 0.01; hazard ratio, 3.03; 95% confidence interval, 1.3–7.04) was identified as an independent risk factor for OS. However, there were no differences in OS when evaluated by grade, histology, tumor size, type of hysterectomy, or adjuvant treatment. Conclusions In stage II EC, adjuvant external beam radiotherapy ± VBT were associated with increased DFS but not OS. However, the benefit of VBT alone on DFS could not be demonstrated. Only age was an independent risk factor for OS. Type of hysterectomy and histologic subtype of the tumor for patients with uterus-confined disease improved neither DFS nor OS in our study group.
Extragonadal oocytes residing in the mouse ovarian hilum contribute to fertility†

Abstract The observation of pups born from recipient and donor mice after ovariectomy followed by ovarian transplant poses the interesting possibility of an extraovarian source of oocytes. However, whether mammalian adult oocytes reside in extragonadal tissues remains elusive. Using transgenic fluorescent reporter mice and transplantation surgeries, we demonstrate the presence of both donorand recipient-derived corpora lutea and recovery of both donor- and recipient-derived offspring from ovariectomized mice after transplantation of donor ovaries. A potential region for extraovarian oocytes is the hilum, a ligament-like structure between the ovary and the reproductive tract. Immunofluorescent confocal microscopy of mouse ovaries and reproductive tracts revealed that a population of primordial follicles resides outside the ovary within the hilum. Ovariectomy-only controls confirmed that oocytes remain in the recipient hilum after surgery. These results provide evidence that the hilum is a reserve source of follicles, which likely return to the ovary for maturation and ovulation. By identifying a new follicle reservoir, our study addresses a long-standing question in reproductive biology and contributes to new conceptual knowledge about ovarian function and fertility. Summary Sentence An extraovarian source of oocytes exists within the mouse ovarian hilum, amuscular structure that connects the ovary to the reproductive tract; these oocytes reside within primordial and primary follicles and may contribute to female fertility.
Cell therapy for stroke

SummaryIncreasing experimental evidence suggests that cell transplantation can enhance recovery from stroke in animal models of focal cerebral ischemia. Clinical trials have been investigating the effects of a human immortalized neuronal cell line and porcine fetal neurons in stroke victims with persistent and stable deficits. Preclinical studies are focusing on the effects of human stem cells from various sources including brain, bone marrow, umbilical cord, and adipose tissue. This review presents an overview of preclinical and clinical studies on cell therapy for stroke. We emphasize the current, limited knowledge about the biology of implant sources and discuss special conditions in stroke that will impact the potential success of neurotransplantation in clinical trials.
On-Field Signs Predict Future Acute Symptoms After Sport-Related Concussion: A Structural Equation Modeling Study

Abstract Objectives: This study investigated the relationship between on-field, objective signs immediately following sport-related concussion and self-reported symptom endorsement within 1 day post injury. Methods: A retrospective case series of 237 concussed high school athletes was performed. On-field signs were evaluated immediately post injury. Self-reported symptoms (2 clusters) were collected within 1 day post injury. A two-step structural equation model and follow-up bivariate regression analyses of significant on-field signs and symptom clusters were performed. Results: Signs of immediate memory, β=0.20, p=. 04, and postural instability, β=0.19, p < . 01, significantly predicted a greater likelihood of endorsing the cognitive-migraine-fatigue symptom cluster within 1 day post injury. Regarding signs correlated with specific symptoms, immediate memory was associated with symptoms of trouble remembering, χ 2 =37.92, p < . 001, odds ratio (OR)=3.89 (95% confidence interval (CI) [2.47, 6.13]), and concentration difficulties, χ 2 =10.84, p=. 001, OR=2.13 (95% CI [1.37, 3.30]). Postural instability was associated with symptom endorsement of trouble remembering, χ 2 =12.08, p < . 001, OR=1.76 (95% CI [1.29, 2.40]). Conclusions: Certain post-concussion on-field signs exhibited after injury were associated with specific symptom endorsement within 1 day post injury. Based on these associations, individualized education-based interventions and academic accommodations may help reduce unanticipated worry from parents, students, and teachers following a student-athlete’s sport-related concussion, especially in cases of delayed onset symptoms. (JINS, 2018, 24, 476–485)
Risk of preterm birth following late pregnancy exposure to NSAIDs or COX-2 inhibitors

Abstract Pregnant women may take nonsteroidal antiinflammatory drugs (NSAIDs), selective cyclooxygenase (COX)-2 inhibitors, or biological agents to relieve symptoms or manage disease flares in late pregnancy. We aimed to quantify the risk of prematurity associated with late pregnancy exposure to nonselective NSAIDs, selective COX-2 inhibitors, and biological agents. Using data from Quebec Pregnancy Cohort, we performed a population-based cohort study. We included all women who were covered by the Quebec Drug Plan and had a singleton live birth between January 1, 1998 and December 31, 2009. Late pregnancy exposure was defined as having filled at least 1 prescription for nonselective NSAIDs, selective COX-2 inhibitors, or biological agents in the 3 months before delivery. Prematurity was defined as <37 weeks of gestation. Crude and adjusted odds ratios (OR) were obtained using generalized estimation equation models. Covariates included maternal autoimmune diseases, demographics, concomitant drug use, history of pregnancy complications, and other comorbidities. A total of 156,531 pregnancies met inclusion criteria and were considered for analyses. In the 3 months before delivery, 391 pregnancies were exposed to nonselective NSAIDs, 55 to COX-2 inhibitors, and 12 to biological agents. After adjustment for maternal autoimmune diseases, concomitant medication use, and other risk factors, COX-2 inhibitor use in late pregnancy was associated with a 2.46-fold increased risk of prematurity (adjusted OR, 2.46; 95% confidence interval, 1.28-4.72) compared to nonuse; only late pregnancy exposure to celecoxib was found to increase the risk (adjusted OR, 3.41; 95% confidence interval, 1.29-9.02). In conclusion, celecoxib use during late pregnancy may increase the risk of prematurity.
Hierarchical evaluation of electrical stimulation protocols for chronic wound healing: An effect size meta‐analysis

Electrical stimulation (ES) has been tested for decades to improve chronic wound healing. However, uncertainty remains on the magnitude of the efficacy and on the best applicable protocol. We conducted an effect size meta‐analysis to assess the overall efficacy of ES on wound healing, to compare the efficacy of the different modalities of electrical stimulation, and to determine whether efficacy differs depending on the wound etiology, size, and age of the chronic wound. Twenty‐nine randomized clinical trials with 1,510 patients and 1,753 ulcers were selected. Overall efficacy of ES on would healing was a 0.72 SMD (95% CI: 0.48, 1) corresponding to a moderate to large effect size. We found that unidirectional high voltage pulsed current (HVPC) with the active electrode over the wound was the best evidence‐based protocol to improve wound healing with a 0.8 SMD (95% CI: 0.38, 1.21), while evaluation of the efficacy of direct current was limited by the small number of studies. ES was more effective on pressure ulcers compared to venous and diabetic ulcers, and efficacy trended to be inversely associated with the wound size and duration. This study confirms the overall efficacy of ES to enhance healing of chronic wounds and highlights the superiority of HVPC over other type of currents, which is more effective on pressure ulcers, and inversely associated with the wound size and duration. This will enable to standardize future ES practices.
The use of the R6 transgenic mouse models of Huntington’s disease in attempts to develop novel therapeutic strategies

SummaryHuntington’s disease (HD) is a genetic neurodegenerative disorder. Since identification of the disease-causing gene in 1993, a number of genetically modified animal models of HD have been generated. The first transgenic mouse models, R6/1 and R6/2 lines, were established 8 years ago. The R6/2 mice have been the best characterized and the most widely used model to study pathogenesis of HD and therapeutic interventions. In the present review, we especially focus on the characteristics of R6 transgenic mouse models and, in greater detail, describe the different therapeutic strategies that have been tested in these mice. We also, at the end, critically assess the relevance of the HD mouse models compared with the human disease and discuss how they can be best used in the future.
A New Low Computational Complexity Sphere Decoding Algorithm

The complexity of sphere decoding (SD) has been widely studi ed in that the algorithm is vital in providing the optimal Maximum Likelihood performance with low comple xity. In this paper, we propose a proper tree search technique that reduces overall SD computational complexit y without sacrificing performance. We build a check-table to pre-calculate and store some terms, temporally store som e mid-stage terms, and take advantage of a new lattice representation of our previous work. This method allows sig nificant reduction for the number of operations required to decode the transmitted symbols. We consider 2x2 and 4x4 sy stems employing 4-QAM and 64-QAM, and show that this approach achieves large gains for average number o f r al multiplications and real additions, which range from 70% to 90% and40% to 75% respectively, depending on the number of antennas and the co nstellation size of modulation schemes. We also show that these complexity ga ins become greater when the system dimension and the modulation levels become larger.
Kin recognition is a nutrient-dependent inducible phenomenon

ABSTRACT Recognition and response to prospective competitors are crucial variables that must be considered in resource distribution and utilization in plant communities. Associated behaviors are largely mediated through the exchange of low-molecular weight exudates. These cues can significantly alter the root system architecture (RSA) between neighboring plants and are routinely sensitive enough to distinguish between plants of the same or different accessions, a phenomenon known as kin recognition (KR). Such refined discrimination of identity, based on the composition and detection of patterns of exudate signals is remarkable and provides insight into the chemical ecology of plant-plant interactions. The discovery that KR occurs in Arabidopsis thaliana provides a model system to resolve many of the mechanistic questions associated with this process. We hypothesized that the low-molecular weight cues which direct changes to the RSA during KR was driven by nutrient availability. Here we present evidence in support of a nutrient-inducible model for KR. Our findings underscore how exudate production and detection are influenced by nutrient availability as well as how this information is integrated into ‘decisions’ about competition and root system architecture which may have broader impacts on community composition.
Statistically modelling the relationships between Type D personality and social support, health behaviors and symptom severity in chronic illness groups

Objective: The study aimed to develop a predictive model of how Type D personality influences health behaviours, social support and symptom severity and assess its generalisability to a range of chronic illnesses. Design: Participants were classified as either healthy (n = 182) or having a chronic illness (n = 207). Participants completed an online survey measuring Type D and a range of health-related variables. Chronic illness participants were classified as having either a functional somatic syndrome (i.e. chronic fatigue syndrome or fibromyalgia), where the underlying pathological processes were unclear, or illnesses such as type 2 diabetes, osteoarthritis or rheumatoid arthritis, where the causes are well understood. Main Outcome Measures: Outcome measures were health behaviours, social support and both physical and psychological symptoms. Results: The rate of Type D was higher in chronic illness participants (53%) than in healthy controls (39%). Negative affectivity (NA) and social inhibition (SI) both correlated with outcome measures, although NA was generally the stronger predictor. Using NA and SI as independent subscales led to superior prediction of health outcomes than using categorical or continuous representations. Conclusion: Findings suggest that the relationship between Type D and health outcomes may generalise across different chronic illnesses.
Hepatic damage exacerbates cisplatin-induced acute kidney injury in Sprague-Dawley rats

ABSTRACT The objective of this study was to elucidate the effect of hepatic damage on cisplatin (CDDP)-induced acute kidney injury (AKI). Thioacetamide (TAA, 150 mg/kg), a hepatotoxicant, was intraperitoneally (i.p.) injected to male Sprague-Dawley rats for 3 d prior to CDDP (5 mg/kg, i.p.) injection. All animals were sacrificed 5 d after CDDP treatment, and urine or blood was obtained to measure various parameters. No significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were observed after CDDP treatment. However, pretreatment with TAA significantly elevated ALT and AST activity. Serum blood urea nitrogen and creatinine levels significantly increased in CDDP-treated group compared to control. In addition, urinary excretion of novel protein-based biomarkers such as neutrophil gelatinase-associated lipocalin, vascular endothelial growth factor, kidney injury molecule-1, and tissue inhibitor of metalloproteinase-1 rose markedly in the CDDP-treated group. In particular, pretreatment with TAA markedly elevated CDDP-induced urinary excretion of protein-based nephrotoxic biomarkers compared with CDDP alone. Hematoxylin and eosin staining demonstrated that pretreatment with TAA following CDDP injection led to more severe tubular damage and apoptosis in rats compared with CDDP alone. Antioxidant status was significantly reduced in kidneys following pretreatment with TAA prior to CDDP. These findings indicate that liver injury enhanced the vulnerability of kidney to CDDP-induced AKI and this phenomenon may be associated with severe apoptotic damage.
Performance Analysis of a Cognitive Radio Network Using Network Calculus

In this paper, we consider a multi-channel cognitive radio system serving a primary network and a secondary network, and analyze the quality of service and delay-constrained capacity of the secondary network. Specifically, by assuming that a certain amount of resource is exclusively reserved and used on each channel by the primary network, we derive the traffic transportation capacity that is guaranteed to the secondary network. Based on this, we analyze the traffic delay distribution in the secondary network and derive an upper bound on it, which allows us to further obtain a guaranteed capacity of the secondary network in serving traffic with probabilistic delay requirement. Both numerical and simulation results are presented for an example where the secondary network traffic follows a model taken from 3GPP LTE. The delay distribution, average delay and delay-constrained capacity of the secondary network are compared. The excellent match between analytical results and simulation results validates the theoretical analysis.
Trajectory-Based Road-Geometry and Crash-Risk Estimation with Smartphone-Assisted Sensor Networks

As mobile devices came into wide use, it became practical to collect travel data in personal logs. Many studies have been conducted to extract meaningful information from this trend. In this study, we present a system for monitoring road-geometry and crash-risk estimation, based on trajectories created using a smartphone-aided sensor network. The proposed system consists of a number of node vehicles with smartphone applications for GPS data collection and a map server which aggregates the collected GPS trajectories and estimates road conditions. In order to estimate road geometry and crash risk information, the trajectories were segmented and categorized into groups according to their headings. Based on the processed trajectories, the geometry of the road section was estimated using the principal curve method. The crash risk of the road section was estimated from the constructed road geometry and the density map of the trajectories. Our system was evaluated using bicycle trajectories collected from segregated bicycle tracks in Seoul, Korea. Constructed geometry and crash-risk information of the track was compared with real track geometry and crash data. As a result, the estimated road geometry showed over 74% similarity and the calculated crash risk (61%) matched the real crash data.