Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased Function of Delayed Recall in Non-demented Elderly Subjects With Apolipoprotein E ε4 Allele

Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD). Inconsistent results about the role of APOE ε4 alleles on cognitive decline of community non-dementia elderly have been reported. This study aimed to examine the relationship between APOE ε4 allele and cognitive abilities in the subjects aged 60 years or above from a community in Shanghai, China. A total of 1445 participants voluntarily accepted the analysis of APOE genotype and global cognitive assay using the Mini Mental Status Evaluation (MMSE). There were no significant differences in total MMSE scores between APOE ε4 carriers and non-carriers. In addition, the performances of orientation, registration, attention, calculation, and language had no significant differences between subjects with and without APOE ε4 allele. However, stratified analysis showed that the performance of delayed recall in subjects with APOE ε4 allele was inferior to that in non-ε4 carriers (p = 0.041). Further, the multiple linear regression analysis showed the significant correlations between the presence of APOE ε4 allele and the scores of the delayed memory subdomain if age, gender, and education were adjusted but no significant correlations if the related factors were not adjusted. The results indicate that significant impact of APOE ε4 allele only on the delay memory but not on global or other sub-domains of cognitive abilities.
ECG R-wave peaks marking with simultaneously recorded continuous blood pressure

Background and objectives ECG signal is relatively weak and vulnerable to various noise interferences, such as electromyography. There will be robustness problems when detecting the instantaneous heart rate independently. In some cases, multiple human physiologic parameters are monitored to help in heart rate detection. Methods In this paper, an algorithm that marks the R-wave peaks with the help of simultaneously recorded continuous blood pressure is proposed and tested on two databases. One database, called the challenge database, is provided by the PhysioNet/Computing in Cardiology Challenge 2014, and the other is the MGH/MF waveform database. Results The final scores of the proposed algorithm are 97.3% for the challenge database and 96.6% for the MGH/MF waveform database. Conclusions The experimental results show that this algorithm has high detection accuracy and a relatively strong robustness.
Exploratory Factor Analysis: Millennial Generations Intention To Search Job Vacancies Using Social Media

The purpose of this research is to identify the factors that influence millennial generations intention to search job vacancies using social media. This study is quantitative research with explorative descriptive approach and non-probability purposive sampling was used to select participants. The data was collected using questionnaire. The total sample size of this research is 259 millennial generations who works in the capital city of Indonesia or surrounding areas and had experience searching or applying jobs using social media. To analyze the data, this research uses exploratory factor analysis technique using SPSS 20 software. The results of this study indicate that there are 3 factors that influence millennial generations intention to search job vacancies using social media.
Effects of buried grain boundaries in multilayer MoS2

Two-dimensional transition metal dichalcogenides have been the focus of intense research for their potential application in novel electronic and optoelectronic devices. However, growth of large area two-dimensional transition metal dichalcogenides invariably leads to the formation of grain boundaries that can significantly degrade electrical transport by forming large electrostatic barriers. It is therefore critical to understand their effect on the electronic properties of two-dimensional semiconductors. Using MoS2 as an example material, we are able to probe grain boundaries in top and buried layers using conductive atomic force microscopy. We find that the electrical radius of the grain boundary extends approximately 2 nm from the core into the pristine material. The presence of grain boundaries affects electrical conductivity not just within its own layer, but also in the surrounding layers. Therefore, electrical grain size is always smaller than the physical size, and decreases with increasing thickness of the MoS2. These results signify that the number of layers in synthetically grown 2D materials must ideally be limited for device applications.
Effect of fasting and subsequent refeeding on the transcriptional profiles of brain in juvenile Spinibarbus hollandi

Starvation is a common stress in fish. The underlying molecular mechanisms associated with growth depression caused by feeding restriction and compensatory growth are not well understood. We investigated the effect of fasting and refeeding on the transcriptome profiles of brain in juvenile S. hollandi using RNA-seq. A total of 4.73 × 108 raw reads were obtained from nine brain samples. De novo transcriptome assembly identified 387,085 unigenes with 2.1×109 nucleotides. A total of 936 annotated unigenes showed significantly differential expression among the control, fasting, and fasting-refeeding groups. The down-regulated differentially expressed genes (DEGs) during fasting were mainly associated with cell cycle, DNA replication, and mitosis. The up-regulated DEGs were mainly related to glucose and lipid metabolism, material transportation, and transcription factors. Most decreased DEGs during fasting were restored to normal levels after refeeding. Comparing with the control group, genes associated with protein synthesis, stimulus response, and carbohydrate metabolism were significantly over-expressed and pro-opio melanocortin (POMC) was down-regulated during the refeeding period. In conclusion, fish mobilized stored energetic materials and reduced energy consumption to prolong survival during fasting. After refeeding, the down-regulation of DEGs, e.g., POMC may be associated with compensatory growth. Up-regulation of DEGs related to ribosomal protein, stimulus response, and carbohydrate metabolism may contribute to eliminate negative effect of starvation on brain. This study provided the first transcriptome data related with impact of short-time starvation and refeeding in S. hollandi brains.
Risk factors analysis of nosocomial pneumonia in elderly patients with acute cerebral infraction

Abstract To investigate the risk factors of nosocomial pneumonia (NP) in elderly patients with acute cerebral infarction (ACI). In this study, 324 aged 70 years and over patients with ACI who were admitted to the inpatient department of TianJin First Hospital (China) from January 2012 to February 2018 were retrospectively analyzed. The patients were divided into NP group (80 patients) and non-NP group (244 patients) according to whether NP was occurred 48 hours after hospitalization. Baseline profiles and biochemical analyses were compared between 2 groups. Information regarding risk factors for NP in elderly patients with ACI was collected from all patients. Associations with NP and outcome were evaluated. Among the total patients, NP occurred in 80 (24.69%) patients. There were no statistically significant differences between risk of NP and sex, current drinking, diabetes mellitus, stroke history, and levels of serum UA, TG, HDL-C, LDL-C, Glucose, chloride, potassium. Multivariate logistic regression analysis showed that the independent risk factors for NP were living alone (OR 4.723; CI 1.743∼12.802; P = .002), initial NIHSS score (OR 1.441; CI 1.191∼1.743; P = .000), NRS2002 score (OR 0.139; CI 0.087∼0.223; P = .000), BMI (OR 1.586; CI 1.353∼1.858; P = .000), a past pneumonia history (OR 0.073; CI 0.017∼0.321; P = .001), atrial fibrillation (AF) (OR 0.129; CI 0.033∼0.499; P = .003), CRP (OR 1.050; CI 1.017∼1.085; P = .003), BUN (OR 0.603; CI 0.448∼0.812; P = .001) and Cr (OR 1.036; CI 1.015∼1.057; P = .001). Level of albumin was an independent protective factor of NP in elderly patients with ACI (OR 0.865; CI 0.750∼0.999; P = .048). Furthermore, elderly patients with ACI who had NP had worse clinical outcomes both during hospitalization and after discharge (P < .05). We identified significant risk factors for NP in elderly patients with ACI, including living alone, initial NIHSS score, malnutrition, a past pneumonia history, AF, CRP, and Renal function were associated with NP in elderly patients with ACI. The clinical course was worse and the duration of hospital stay was longer in NP patients than in non-NP patients.
Cell transfection of purified cytolethal distending toxin B subunits allows comparing their nuclease activity while plasmid degradation assay does not

The Cytolethal Distending Toxin (CDT) is produced by many pathogenic bacteria. CDT is known to induce genomic DNA damage to host eukaryotic cells through its catalytic subunit, CdtB. CdtB is structurally homologous to DNase I and has a nuclease activity, dependent on several key residues. Yet some differences between various CdtB subunit activities, and discrepancies between biochemical and cellular data, have been observed. To better characterise the role of CdtB in the induction of DNA damage, we affinity-purified wild-type and mutants of CdtB, issued from E. coli and H. ducreyi, under native and denaturing conditions. We then compared their nuclease activity by a classic in vitro assay using plasmid DNA, and two different eukaryotic assays–the first assay where host cells were transfected with a plasmid encoding CdtB, the second assay where host cells were directly transfected with purified CdtB. We show here that in vitro nuclease activities are difficult to quantify, whereas CdtB activities in host cells can be easily interpreted and confirmed the loss of function of the catalytic mutant. Our results highlight the importance of performing multiple assays while studying the effects of bacterial genotoxins, and indicate that the classic in vitro assay should be complemented with cellular assays.
Trauma and Relationship Strain: Oral Histories With World Trade Center Disaster Responders

Existing models of couple functioning after trauma are primarily based on the experiences of returning military veterans. In this study, we conducted thematic analysis of a purposive sample of 49 oral histories of responders to the 9/11/01 terrorist attacks to understand how they navigated life with their spouses after the response experience. Use of multiple coders and analytic matrices increased analytic rigor. In the sample, 34.7% disclosed a posttraumatic stress disorder (PTSD) diagnosis and another 22.7% mentioned experiencing at least one trauma symptom. Most responders had not sought mental health intervention, relying instead on their spouses’ caregiving. Responders reported limited disclosure to their spouses about the details of their 9/11/01 response work, which may have helped them cope emotionally with repeated 9/11/01 clean-up duties. Shared values regarding the common good and patriotism were important for maintaining an intimate relationship after 9/11/01, and helping partners understand and feel understood by each other.
Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial.

PURPOSE Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM. METHODS After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy. RESULTS Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. [%]: 6 [3.2] v 10 [5.3], respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86; P = .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0). CONCLUSION There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM.
The nature and intensity of mechanical stimulation drive different dynamics of MRTF-A nuclear redistribution after actin remodeling in myoblasts

Serum response factor and its cofactor myocardin-related transcription factor (MRTF) are key elements of muscle-mass adaptation to workload. The transcription of target genes is activated when MRTF is present in the nucleus. The localization of MRTF is controlled by its binding to G-actin. Thus, the pathway can be mechanically activated through the mechanosensitivity of the actin cytoskeleton. The pathway has been widely investigated from a biochemical point of view, but its mechanical activation and the timescales involved are poorly understood. Here, we applied local and global mechanical cues to myoblasts through two custom-built set-ups, magnetic tweezers and stretchable substrates. Both induced nuclear accumulation of MRTF-A. However, the dynamics of the response varied with the nature and level of mechanical stimulation and correlated with the polymerization of different actin sub-structures. Local repeated force induced local actin polymerization and nuclear accumulation of MRTF-A by 30 minutes, whereas a global static strain induced both rapid (minutes) transient nuclear accumulation, associated with the polymerization of an actin cap above the nucleus, and long-term (hours) accumulation, with a global increase in polymerized actin. Conversely, high strain induced actin depolymerization at intermediate times, associated with cytoplasmic MRTF accumulation.
Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus

The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.
Fuzzing: on the exponential cost of vulnerability discovery

We present counterintuitive results for the scalability of fuzzing. Given the same non-deterministic fuzzer, finding the same bugs linearly faster requires linearly more machines. For instance, with twice the machines, we can find all known bugs in half the time. Yet, finding linearly more bugs in the same time requires exponentially more machines. For instance, for every new bug we want to find in 24 hours, we might need twice more machines. Similarly for coverage. With exponentially more machines, we can cover the same code exponentially faster, but uncovered code only linearly faster. In other words, re-discovering the same vulnerabilities is cheap but finding new vulnerabilities is expensive. This holds even under the simplifying assumption of no parallelization overhead. We derive these observations from over four CPU years worth of fuzzing campaigns involving almost three hundred open source programs, two state-of-the-art greybox fuzzers, four measures of code coverage, and two measures of vulnerability discovery. We provide a probabilistic analysis and conduct simulation experiments to explain this phenomenon.
Tissue-specific mosaicism in a patient with Rubinstein-Taybi syndrome and CREBBP exon 1 duplication.

Medical Faculty Skopje, Skopje, Macedonia, Macedonian Academy of Sciences and Arts (MASA), Skopje, Macedonia and Institute of Human Genetics, University Medical Centre of the Johannes Gutenberg University, Mainz, Mainz, Germany Correspondence to Zoran S. Gucev, Medical Faculty Skopje, University Children’s Hospital, 1000, Skopje, Macedonia Tel: +389 70 279 742; fax; +389 23 229 156; e-mail: gucevz@gmail.com
An Efficient Model For Measuring Maintainability From Code Cloning And Refactoring Using Regression

: SPL has been developed to control variability and commonality among the system. Object Oriented paradigm suffers with the problem of Code Clones which adversely affects the software qualities especially Maintainability. Literature survey reveals that this problem persists in FOP too. As the Software Product Line expands, unknowingly lot of Code Clones is introduced in the source code. Code Clones are the codes which are repeated or duplicated in other parts of the source code as the functionality of program increases. Thus Code Clones deteriorates the performance and functionality and introduces errors which adversely affects the Software Product Lines. In the existent literature, we have found that Feature Oriented Programming was able to remove Object Oriented Code Clones but in effect it introduced Feature Oriented Programming related Code Clones. Till now, no such evidence has been found in the literature which has justified the occurrence of Code Clones in Delta Oriented Programming. Hence, the focus here is on the Code Clones in Feature Oriented Programming. Maintainability is an important factor which we are considering here since the more Code Clones are found in the source code for any Software Product Lines, the more difficult it becomes to maintain Software Product Lines which in turn leads to higher cost and increased lines of source code. Thus, it becomes crucial to address the code clones as the SPL evolves, since as the SPL grows, its maintainability also becomes important and cost factor can considerably be reduced if the clones are nipped at the early stages.
Does the use of proton pump inhibitors increase the risk of hypomagnesemia

Background: Proton pump inhibitors (PPIs) are commonly used in the treatment of acid-related diseases; however, the association between the use of PPIs and potential risk of hypomagnesemia is controversial. Methods: In the present study, databases including PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the Cochrane Library, and 4 Chinese databases were searched since the inception until April 2018. Previous observational studies on the incidence of hypomagnesemia in individuals exposed to PPIs were included. Results: This systematic review involved 15 studies including 129,347 participants, and the sample size varied from 52 to 95,205. Meta-analysis of 14 studies indicated that the use of PPIs increased the risk of hypomagnesemia [RR, 1.44, 95% CI, 1.13–1.76; I2, 85.2%]. Subgroup analysis revealed that the use of PPI was not associated with the incidence of hypomagnesemia in outpatients [RR, 1.49; 95% CI, 0.83–2.14; I2, 41.4%] and hospitalized patients [RR, 1.05; 95% CI, 0.81–1.29; I2, 62.1%], respectively. The use of PPIs was not related to the risk of hypomagnesemia based on the cut-off values of 1.8 mg/dL [RR, 1.73; 95% CI, 0.87–2.58; I2, 65.2%], 1.7 mg/dL [RR, 1.48; 95% CI, 0.90–2.06; I2, 87.6%], and 1.6 mg/dL [RR, 0.98; 95% CI, 0.69–1.27; I2, 67.9%]. Conclusion: The association between the exposure to PPI and the incidence of hypomagnesemia remained unclear. Due to the remarkable heterogeneity in previous studies, a definitive conclusion could not be drawn. Further research should be conducted to investigate the relationship between the use of individual PPI and potential risk of hypomagnesemia, and a dose-response analysis may be required.
TOP: Time-to-Event Bayesian Optimal Phase II Trial Design for Cancer Immunotherapy.

BACKGROUND Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more appropriate in some trials. These new features of immunotherapy make conventional phase II trial designs, which assume a single binary endpoint that is quickly ascertainable, inefficient and dysfunctional. METHODS We propose a flexible and efficient time-to-event Bayesian optimal phase II (TOP) design. The TOP design is efficient in that it allows real-time "go/no-go" interim decision making in the presence of late-onset responses by using all available data, and maximizes statistical power for detecting effective treatments. TOP is flexible in the number of interim looks and capable of handling simple and complicated endpoints under a unified framework. We conduct simulation studies to evaluate the operating characteristics of the TOP design. RESULTS In the considered trial settings, compared to some existing Bayesian designs, the TOP design shortens the trial duration by 4-10 months, and improves the power to detect effective treatment up to 90%, with well controlled type I errors. CONCLUSION The TOP design is transparent and easy to implement, as its decision rules can be tabulated and included in the protocol prior to the conduct of the trial. The TOP design provides a flexible, efficient and easy-to-implement method to accelerate and improve the development of immunotherapies.