Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Somatic Mutation in Exon 12 of DNA Polymerase β in Ovarian Cancer Tissue Samples

Background DNA polymerase β (pol β) is a key enzyme of base excision repair pathway. It is a 1-kb gene consisting of 14 exons. Its catalytic part lies between exon 8 and exon 14. Exon 12 has a role in deoxyribonucleotide triphosphate selection for nucleotide transferase activity. Methods Genomic DNA was isolated from ovarian carcinoma samples. Single strand conformation polymorphism method was used to detect mutation in genomic DNA. Results: Twenty-four patients of the 152 pair of tumor samples (15.8%) exhibited a point mutation (C→G) in position 725 in exon 12, which shifts proline to arginine (P242R). Statistical analysis showed a significant (p < 0.001) relationship between pol β mutation and the age of detection. Conclusion This is a newly reported somatic mutation of pol β in ovarian carcinoma patients from India.
The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines

Abstract Background: This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity. Methods: The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines. Results: The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option. Conclusion: The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper.
Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy.

BACKGROUND Community-acquired respiratory viruses, such as influenza virus, are thought to be major causes of morbidity and mortality in patients who had undergone hematopoietic stem cell transplantation (HSCT). Risk factors for acquisition, progression to pneumonia, and the effect of antiviral therapy are unknown. METHODS We reviewed records from patients with documented influenza over 12 consecutive respiratory-virus infection seasons at a single transplantation center. RESULTS From 1 September 1989 through 31 March 2002, influenza virus was isolated from 62 of 4797 persons undergoing HSCT (1.3%); 44 patients had upper respiratory tract infections (URIs) alone, and 18 developed pneumonia. Among patients with influenza virus infection, pneumonia developed more commonly among those infected earlier after transplantation (median, 36 vs. 61 days, P=.04) and those with concurrent lymphopenia. Of the 51 cases that were initially diagnosed as URIs, 17 were treated with antivirals, and 34 were not treated. Six untreated patients (18%) developed pneumonia, whereas 1 (13%) of 8 patients treated with rimantadine and 0 of 9 treated with oseltamivir developed pneumonia. The duration of influenza virus shedding was longer in patients treated with steroid doses of >1 mg/kg than among those treated with doses of <1 mg/kg (mean, 15 vs. 9 days); there was a trend towards decreased shedding with oseltamivir therapy (but not rimantadine therapy) after controlling for steroid use (P<.08). The 30-day mortality rate was highest among patients who had progression to pneumonia (5 [28%] of 18 patients); pulmonary copathogens (such as Aspergillus fumigatus) were commonly isolated. CONCLUSIONS Influenza virus infection is an important cause of mortality early after HSCT. Our nonrandomized data suggest that early antiviral therapy with neuraminidase inhibitors may prevent progression to pneumonia and decrease viral shedding, which may prevent both influenza-related death in index patients and nosocomial transmission to others.
Adaptive Fuzzy Control for Synchronization of Coronary Artery System With Input Nonlinearity

In this paper, we propose a parametric adaptive control strategy for synchronization of Takagi–Sugeno (T-S) fuzzy coronary artery system. We use the T-S fuzzy model to represent the coronary artery system, because the coronary artery system has complicated nonlinear characteristic in reality. Based on the new model, a fuzzy parametric adaptive output feedback controller is designed to achieve the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> synchronization of coronary artery system with input nonlinearity and parameter perturbations. Some simulation results are given to illustrate the effectiveness of our control strategy.
Prevention of Axonal Degeneration by Perineurium Injection of Mitochondria in a Sciatic Nerve Crush Injury Model

Background Axon degeneration leads to cytoskeletal disassembly, metabolism imbalance, and mitochondrial dysfunction during neurodegeneration or nerve injury. Objective In this study, we assess the possibility of mitigating axon degeneration by local injection of mitochondria in a crushed sciatic nerve. Methods Sciatic nerve explants cocultured with mitochondria were assessed for the optimal dosage in local injection and nerve regeneration potential. The left sciatic nerve was crushed in Sprague-Dawley rats and then local injection of mitochondria into the distal end of the injured nerve was conducted for further assessment. Results Mitochondrial coculture attenuated cytoskeletal loss and oxidative stress in isolated nerve explants. In Vivo analyses also showed that mitochondrial transplantation improved animal neurobehaviors, electrophysiology of nerve conduction, and muscle activities. Mitochondria injection significantly attenuated the oxidative stress and increased the expression of neurotrophic factors both in injured nerves and denervated muscles, as well as restored muscular integrity, and increased the pool of muscular progenitor cells and total muscle weight. Conclusion Mitochondria injection can protect injured nerves from axonal degeneration both in Vitro and in Vivo. This improvement was accompanied with the expression of neurotrophic factors as well as the reduction of oxidative stress, which may account for the functional recovery of both injured nerves and denervated muscles.
Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy

Prion-like, trans-neuronal spread of tau pathology in humans is controversial. By evaluating tau burden and functional connectivity in living patients, Cope et al. demonstrate relationships consistent with this in Alzheimer's disease but not progressive supranuclear palsy. Tau distribution in the latter is better explained by metabolic demand and trophic support.
The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.
Knowledge of diabetes mellitus and safe practices during Ramadan fasting among Muslim patients with diabetes mellitus in Singapore.

INTRODUCTION This study aimed to explore the level of knowledge of Muslim patients with diabetes mellitus (DM) regarding DM and the self-management of DM when fasting during Ramadan. METHODS Muslim patients with DM attending the Diabetes Centre of Singapore General Hospital, Singapore, were surveyed on their knowledge of DM and self-management of DM when fasting during Ramadan. Data on patient demographics, DM history and management of DM during the previous Ramadan was also collected. RESULTS A total of 92 patients (34 male, 58 female) were surveyed. The mean age of the patients was 53.4 ± 13.3 years. The patients were either Malay (91.3%) or Indian (8.7%), and most (66.3%) had at least a secondary school education. Most (89.1%) had Type 2 DM. The mean duration of DM was 8.7 ± 5.1 years and mean pre-Ramadan haemoglobin A1c was 8.4% ± 1.8%. DM treatment consisted of insulin therapy (37.0%), oral glucose-lowering drugs (35.9%) and combined therapy (22.8%). The mean DM knowledge score was 58.8% for general knowledge and 75.9% for fasting knowledge. During the previous Ramadan, although 71.4% of the patients consulted their physicians, 37.3% did not monitor their blood glucose levels and 47.0% had hypoglycaemic episodes. Among those who had hypoglycaemia, 10.8% continued to fast. CONCLUSION Unsafe self-management practices were observed among DM patients who fasted during Ramadan. Efforts should be made to bridge the gap between knowledge of DM and self-management of DM.
Continuous, robust hand gesture recognition for embedded devices

Gestures are gaining significant demand in embedded devices to provide enhanced user experience through natural communication. This paper presents a robust approach of Hand Gesture Recognition to detect gestures in real time without the need of a delimiter. The method represents the gestures with trajectory strings and matches them with stored trajectory strings of pre-defined gestures. The proposed method employs an enhanced matching scheme using a custom edit distance metric that enables finding of the closest gesture in the database with speed invariance, position invariance and length invariance without the need of a delimiter.
Antimicrobial Stewardship in Inpatient Settings in the Asia Pacific Region: A Systematic Review and Meta-analysis.

Background An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. Methods We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. Results Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. Conclusions ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region.
Trajectories of cardiorespiratory fitness in patients with juvenile dermatomyositis

Objectives Previous research demonstrated decreased cardiorespiratory fitness (CRF) in patients with JDM during active disease and remission. However, longitudinal data regarding trajectories of CRF are currently lacking. The objective of this study was to determine trajectories of CRF in patients with both monocyclic and chronic JDM, and to identify potential predictors of these trajectories. Methods Thirty-six patients with JDM [median age (interquartile range) at diagnosis: 8.3 (6.3-15.4) years] treated in our paediatric rheumatology outpatient clinic were included. All patients performed multiple cardiopulmonary exercise tests between 2003 and 2016. Relevant CRF parameters were analysed, including peak oxygen uptake, maximal workload, mechanical efficacy and oxygen uptake at ventilatory anaerobic threshold. We analysed trajectories up to 10 years after diagnosis and determined predictors of CRF outcome parameters by multilevel analyses. Results Trajectories demonstrated significant declines in CRF during the active phase of the disease with subsequent improvement in CRF during the initial years after diagnosis. However, hereafter no further improvements, and even a decrease, in CRF were observed over time in both monocyclic and chronic subtypes of JDM. We found that a longer disease duration, younger age of onset and higher prednisone dose negatively influence CRF. Conclusion Patients with both monocyclic and chronic JDM show decreases in long-term CRF trajectories. Longer disease duration, younger age of onset and higher prednisone dose negatively influence CRF. This study stresses the need for regular evaluation of CRF and implementation of (exercise) interventions to improve CRF in patients with JDM, even in monocyclic patients.
The Past and Future of Tuberculosis Research

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB's epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB.
New Crambescidin-Type Alkaloids from the Indonesian Marine Sponge Clathria bulbotoxa

A crude methanolic extract of the Indonesian sponge Clathria bulbotoxa showed a potent cytotoxic activity against the human epidermoid carcinoma A431 cells. An investigation of the active components led to the isolation of three new compounds named crambescidins 345 (1), 361 (2), and 373 (3), together with the known related metabolites crambescidins 359 (4), 657 (5), and 800 (6). The structures of the compounds were determined by spectroscopic analysis. These compounds 1–4 that possess a simple pentacyclic guanidine core exhibited moderate cytotoxicity against the A431 cells with the IC50 values of 7.0, 2.5, 0.94, and 3.1 μM, respectively, while the known compounds 5 and 6 that possess a long aliphatic side chain were found to be significantly cytotoxic. On the other hand, in an anti-oomycete activity test against the fungus-like plant pathogen Phytophthora capsici, 1–4 showed a higher activity than that of 5 and 6, suggesting that the long aliphatic side chain plays a significant role for cytotoxicity, but is not effective or suppressive for anti-oomycete activity.
Clocked Definitions in HOL

Many potentially non-terminating functions cannot be directly defined in a logic of total functions, such as HOL. A well-known solution to this is to define non-terminating functions using a clock that forces termination at a certain depth of evaluation. Such clocked definitions are often frowned upon and avoided, since the clock is perceived as extra clutter. In this short paper, we explain that there are different ways to add a clock, some less intrusive than others. Our contribution is a technique by which termination proofs are kept simple even when minimising the use of the clock mechanism. Our examples are definitions of semantic interpreters for programming languages, so called functional big-step semantics.
Analysis of the adoption of security headers in HTTP

With the increase in the number of threats within web-based systems, a more integrated approach is required to ensure the enforcement of security policies from the server to the client. These policies aim to stop man-in-the-middle attacks, code injection, and so on. This study analyses some of the newest security options used within HTTP responses, and scans the Alexa Top 1 Million sites for their implementation within HTTP responses. These options scanned for include: content security policy, public key pinning extension for HTTP, HTTP strict transport security, and HTTP header field X-frame-options, in order to understand the impact that these options have on the most popular websites. The results show that, while the implementation of the parameters is increasing, it is still not implemented on many of the top sites. Along with this, the study shows the profile of adoption of Let's Encrypt digital certificates across the one million sites, along with a way of assessing the quality of the security headers.
Proteomic expression profile of injured rat peripheral nerves revealed biological networks and processes associated with nerve regeneration

Peripheral nerve regeneration is regulated through the coordinated spatio‐temporal activation of multiple cellular pathways. In this work, an integrated proteomics and bioinformatics approach was employed to identify differentially expressed proteins at the injury‐site of rat sciatic nerve at 20 days after damage. By a label‐free liquid chromatography mass‐spectrometry (LC‐MS/MS) approach, we identified 201 differentially proteins that were assigned to specific canonical and disease and function pathways. These include proteins involved in cytoskeleton signaling and remodeling, acute phase response, and cellular metabolism. Metabolic proteins were significantly modulated after nerve injury to support a specific metabolic demand. In particular, we identified a group of proteins involved in lipid uptake and lipid storage metabolism. Immunofluorescent staining for acyl‐CoA diacylglycerol acyltransferase 1 (DGAT1) and DAGT2 expression provided evidence for the expression and localization of these two isoforms in Schwann cells at the injury site in the sciatic nerve. This further supports a specific local regulation of lipid metabolism in peripheral nerve after damage.
Resolution Limits for Detecting Community Changes in Multilayer Networks

Multilayer networks capture pairwise relationships between the components of complex systems across multiple modes or scales of interactions. An important meso-scale feature of these networks is measured though their community structure, which defines groups of strongly connected nodes that exist within and across network layers. Because interlayer edges can describe relationships between different modalities, scales, or time points, it is essential to understand how communities change and evolve across layers. A popular method for detecting communities in multilayer networks consists of maximizing a quality function known as modularity. However, in the multilayer setting the modularity function depends on an interlayer coupling parameter, $\omega$, and how this parameter affects community detection is not well understood. Here, we expose an upper bound for $\omega$ beyond which community changes across layers can not be detected. This upper bound has non-trivial, purely multilayer effects and acts as a resolution limit for detecting evolving communities. Further, we establish an explicit and previously undiscovered relationship between the single layer resolution parameter, $\gamma$, and interlayer coupling parameter, $\omega,$ that provides new understanding of the modularity parameter space. Our findings not only represent new theoretical considerations but also have important practical implications for choosing interlayer coupling values when using multilayer networks to model real-world systems whose communities change across time or modality.
The Association Between Health Changes and Cessation of Alcohol Consumption

Abstract Aims To assess whether health changes affect cessation of alcohol consumption and to compare the health status of former drinkers and abstainers. Methods Cohort data from 9001 Korean participants aged 40–69 years old were analyzed. Alcohol consumption was assessed every 2 years for 10 years. Participant age, sex, marital status, education level, employment status, smoking, chronic disease, perceived health and changes in these variables were analyzed to identify factors associated with quitting alcohol drinking. The number of diseases and perceived health of former drinkers and people who at baseline were lifetime abstainers were compared. Results Among 4037 drinkers at baseline, 673 (16.7%) were classed as quitters and 3364 (83.3%) were classed as non-quitters. Sex, age and worsened perception of health were significantly associated with cessation of drinking. Women and individuals >60 years were more likely to cease drinking. There was a significant association between disease onset or treatment and alcohol cessation for cancer cases, but not for cardiovascular disease or chronic disease cases. There was no significant difference in number of diseases or perceived health between former drinkers and people who at baseline were lifetime abstainers. Conclusions The effect of disease onset or treatment on alcohol consumption cessation depended on disease type. Former drinkers did not show significantly worse health than people who at baseline were lifetime abstainers. Further studies of alcohol consumption and its effects on health are needed to consider disease occurrence and changes in alcohol consumption. Short summary Disease onset or treatment significantly affected alcohol consumption cessation for cancer cases, but not for cardiovascular disease or other chronic disease cases. There was no significant difference in health status between former drinkers and lifetime abstainers.