bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)
Authors: El Hasbani Georges , Jawad Ali , Uthman Imad 
Published: October 2019

AbstractBackgroundFamilial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians.Main bodyLike many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations.ConclusionSince carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.
A randomised controlled trial exploring the impact of a dedicated health and social care professionals team in the emergency department on the quality, safety, clinical and cost-effectiveness of care for older adults: a study protocol
Authors: Cassarino Marica , Robinson Katie , O’Shaughnessy Íde , Smalle Eimear , White Stephen , Devlin Collette , Quinn Rosie , Trépel Dominic , Boland Fiona , Ward Marie E. , McNamara Rosa , O’Connor Margaret , McCarthy Gerard , Ryan Damien , Galvin Rose 
Published: October 2019

Abstract

Background
Older people are frequent emergency department (ED) users who present with complex issues that are linked to poorer health outcomes following the index visit, often have increased ED length of stay, and tend to have raised healthcare costs. Encouraging evidence suggests that ED teams involving health and social care professionals (HSCPs) can contribute to enhanced patient flow and an improved patient experience by improving care decision-making and thus promoting timely and effective care. However, the evidence supporting the impact of HSCP teams assessing and intervening with older adults in the ED is limited and identifies important methodological limitations, highlighting the need for more robust and comprehensive investigations of this model of care. This study aims to evaluate the impact of a dedicated ED-based HSCP team on the quality, safety, and clinical- and cost-effectiveness of care of older adults when compared with usual care.

Methods
The study is a single-site randomised controlled trial whereby patients aged ≥65 years who present to the ED of a large Irish hospital will be randomised to the experimental group (ED-based HSCP assessment and intervention) or the control group (usual ED care). The recruitment target is 320 participants. The HSCP team will provide a comprehensive functional assessment as well as interventions to promote a safe discharge for the patient. The primary outcome is ED length of stay (from arrival to discharge). Secondary outcomes include: rates of hospital admissions from the ED, ED re-visits, unplanned hospital admissions and healthcare utilisation at 30 days, and 4 and 6 months of follow-up; patient functional status and quality of life (at baseline and follow-up); patient satisfaction; cost-effectiveness in terms of costs associated with ED-based HSCP compared with usual care; and perceptions on implementation by ED staff members.

Discussion
This is the first randomised controlled trial testing the impact of HSCPs working in teams in the ED on the quality, safety, and clinical- and cost-effectiveness of care for older patients. The findings of this study will provide important information on the effectiveness of this model of care for future implementation.

Trial registration
ClinicalTrials.gov, NCT03739515. Registered on 12 November 2018.
Single mutation at a highly conserved region of chloramphenicol acetyltransferase enables isobutyl acetate production directly from cellulose by Clostridium thermocellum at elevated temperatures
Authors: Seo Hyeongmin , Lee Jong-Won , Garcia Sergio , Trinh Cong T. 
Published: October 2019

Abstract

Background
Esters are versatile chemicals and potential drop-in biofuels. To develop a sustainable production platform, microbial ester biosynthesis using alcohol acetyltransferases (AATs) has been studied for decades. Volatility of esters endows high-temperature fermentation with advantageous downstream product separation. However, due to the limited thermostability of AATs known, the ester biosynthesis has largely relied on use of mesophilic microbes. Therefore, developing thermostable AATs is important for ester production directly from lignocellulosic biomass by the thermophilic consolidated bioprocessing (CBP) microbes, e.g., Clostridium thermocellum.

Results
In this study, we engineered a thermostable chloramphenicol acetyltransferase from Staphylococcus aureus (CATSa) for enhanced isobutyl acetate production at elevated temperatures. We first analyzed the broad alcohol substrate range of CATSa. Then, we targeted a highly conserved region in the binding pocket of CATSa for mutagenesis. The mutagenesis revealed that F97W significantly increased conversion of isobutanol to isobutyl acetate. Using CATSa F97W, we demonstrated direct conversion of cellulose into isobutyl acetate by an engineered C. thermocellum at elevated temperatures.

Conclusions
This study highlights that CAT is a potential thermostable AAT that can be harnessed to develop the thermophilic CBP microbial platform for biosynthesis of designer bioesters directly from lignocellulosic biomass.
Genetically encoded biosensors for lignocellulose valorization
Authors: Alvarez-Gonzalez Guadalupe , Dixon Neil 
Published: October 2019

Abstract
Modern society is hugely dependent on finite oil reserves for the supply of fuels and chemicals. Moving our dependence away from these unsustainable oil-based feedstocks to renewable ones is, therefore, a critical factor towards the development of a low carbon bioeconomy. Lignin derived from biomass feedstocks offers great potential as a renewable source of aromatic compounds if methods for its effective valorization can be developed. Synthetic biology and metabolic engineering offer the potential to synergistically enable the development of cell factories with novel biosynthetic routes to valuable chemicals from these sustainable sources. Pathway design and optimization is, however, a major bottleneck due to the lack of high-throughput methods capable of screening large libraries of genetic variants and the metabolic burden associated with bioproduction. Genetically encoded biosensors can provide a solution by transducing the target metabolite concentration into detectable signals to provide high-throughput phenotypic read-outs and allow dynamic pathway regulation. The development and application of biosensors in the discovery and engineering of efficient biocatalytic processes for the degradation, conversion, and valorization of lignin are paving the way towards a sustainable and economically viable biorefinery.
Transfection of Culicoides sonorensis biting midge cell lines with Wolbachia pipientis
Authors: Ghosh Arnab , Jasperson Dane , Cohnstaedt Lee W. , Brelsfoard Corey L. 
Published: October 2019

AbstractBackgroundBiting midges of the genusCulicoidesvector multiple veterinary pathogens and are difficult to control. Endosymbionts particularlyWolbachia pipientismay offer an alternative to control populations ofCulicoidesand/or impact disease transmission in the form of population suppression or replacement strategies.MethodsCulicoides sonorensiscell lines were transfected with aWolbachiainfection using a modified shell vial technique. Infections were confirmed using PCR and cell localization using fluorescentin situhybridization (FISH). The stability ofWolbachiainfections and density was determined by qPCR. qPCR was also used to examine immune genes in the IMD, Toll and JACK/STAT pathways to determine ifWolbachiawere associated with an immune response in infected cells.ResultsHere we have transfected twoCulicoides sonorensiscell lines (W3 and W8) with aWolbachiainfection (walbB) from donorAedes albopictusAa23 cells. PCR and FISH showed the presence ofWolbachiainfections in bothC. sonorensiscell lines. Infection densities were higher in the W8 cell lines when compared to W3. In stably infected cells, genes in the immune Toll, IMD and JAK/STAT pathways were upregulated, along with Attacin and an Attacin-like anti-microbial peptides.ConclusionsThe successful introduction ofWolbachiainfections inC. sonorensiscell lines and the upregulation of immune genes, suggest the utility of usingWolbachiafor a population replacement and/or population suppression approach to limit the transmission ofC. sonorensisvectored diseases. Results support the further investigation ofWolbachiainduced pathogen inhibitory effects inWolbachia-infectedC. sonorensiscell lines and the introduction ofWolbachiaintoC. sonorensisadultsviaembryonic microinjection to examine for reproductive phenotypes and host fitness effects of a novelWolbachiainfection.
A novel cooperative spectrum signal detection algorithm for underwater communication system
Authors: Xiaolin Jiang , Zhengyu Tang , Ronghui Wang 
Published: October 2019

Abstract
In order to further improve the spectrum resource detection probability and increase the spectrum utilization rate in underwater wireless communication systems, this paper designs a novel multi-layer cooperative spectrum sensing algorithm based on compressed sensing, which uses compressed sensing technology to estimate the spectrum to reduce the sampling rate and the overhead of sonar signals. This new algorithm seeks the optimal hyper-parameter through Bayesian model. The multi-layer Bayesian model is introduced into the Dirichlet process to realize the automatic grouping of compressed perceptual data with the information from the non-parametric grouping mechanism, and the optimal super-parameters are selected through the fusion center to determine the spectrum. Simulation results show that the proposed algorithm fully considers the temporal correlation of compressed perceptual data and effectively improves spectral sensing performance of underwater communication system.
Stationary distribution of a stochastic SIRD epidemic model of Ebola with double saturated incidence rates and vaccination
Authors: Wang Panpan , Jia Jianwen 
Published: October 2019

Abstract
In this paper, a stochastic SIRD model of Ebola with double saturated incidence rates and vaccination is considered. Firstly, the existence and uniqueness of a global positive solution are obtained. Secondly, by constructing suitable Lyapunov functions and using Khasminskii’s theory, we show that the stochastic model has a unique stationary distribution. Moreover, the extinction of the disease is also analyzed. Finally, numerical simulations are carried out to portray the analytical results.
Numerical treatment of stochastic heroin epidemic model
Authors: Rafiq M. , Raza Ali , Iqbal M. Usman , Butt Zubair , Naseem Hafiza Anum , Akram M. Ali , Butt M. Kamran , Khaliq Adil , Qurat-ul-Ain  , Azam Shamrash 
Published: October 2019

Abstract
We have presented the numerical analysis of a stochastic heroin epidemic model in this paper. The mean of stochastic heroin model is itself a deterministic solution. The effect of reproduction number has also been observed in the stochastic heroin epidemic model. We have developed some stochastic explicit and implicitly driven explicit methods for this model. But stochastic explicit methods have flopped for certain values of parameters. In support, some theorems and graphical illustrations are presented.
Detection of Pan drug resistance OXA-48 producing Providencia in an ICU patient for the first time in Nepal
Authors: Sah Ranjit , Khadka Shusila , Shrestha Gentle Sunder , Acharya Subhash , Aryal Diptesh , Shrestha Pramesh , Kattel Hari Prasad , Shah Niranjan Prasad , Pokhrel Bharat Mani , Singh Yogendra Prasad , Rijal Basista , Erdem Hakan 
Published: October 2019

Abstracts

Background
Resistance to antimicrobial agents of pathogenic bacteria has become a major problem in routine medical practices. Carbapenem resistance has long been increasing. The production of carbapenem- hydrolysing β-lactamases (carbapenamases), which include NDM, KPC, OXA-48, IMP-1 and VIM is the most common mechanism.

Case presentation
A 56 years old male presented with fever and mental changes with progressively decreasing sensorium for the last 3 days. He was admitted to Intensive care unit (ICU) with a diagnosis of meningoencephalitis. On day seven, he developed ventilator associated pneumonia due Klebsiella pnemoniae and Acinetobacter baumannii. He was on meropenem, but the isolates were susceptible to colistin, tigecyclin and amikacin solely. Hence, amikacin was started with addition of intravenous and nebulized colistin. Subsequently, vital signs improved with resolution of fever. However, on day 18, he developed fever once again with a drop in blood pressure. Inotropic support was maintained, and echinocandins and tigecycline were added to the regimen.
Repeat blood and urine culture grew Providencia species, which were resistant to most of the drugs on phenotypic Kirby-Bauer disk diffusion method and are intrinsically resistant to colistin and tigecycline. Phenotypic detection of ESBL (combined disk method), MBL, KPCs, AmpC and co-producer were tested according to updated CLSI guideline and all were negative. But the Modified Hodges test was found to be positive. Consequenty, OXA-48 drug resistance pattern was brought into action by blank disc method according to A Tsakris et al., which revealed indentation of growth toward both EDTA and EDTA/PBA disk indicating production of OXA-48 carbapenamase. To confirm the resistance pattern we processed the isolated colonies for Xpert Carba-R (Cepheid) assay, which detected blaOXA-48 gene and confirmed the OXA-48 drug resistance pattern. Hence, the infecting organism was not susceptible to any of the antibiotics. The patient was kept under isolation and on 31th day of admission, he died of septic shock.

Conclusions
Carbapenamase production along with intrinsic colistin resistance in infecting bacterial pathogens can cause fatal outcomes in the resource limited countries like Nepal where new antibiotic combinations ceftazidime+ Avibactam, or aztreonam +avibactam are not available. Drug resistance patterns including OXA 48 producer should be characterized in all cases by standard phenotypic methods or by Xpert Carba-R assay and larger studies are required to know the exact burden of OXA 48 producer in Nepal.
Development of a telegenetics program in the Asia-Pacific/Middle East region.
Authors: Dawood Shaheenah S. , Dhar Aparna , Sharma Poonam , Kini Lata 
Published: October 2019

15 Background: BRCA mutations is emerging as an agnostic marker for PARPi. Accessibility to genetic counselling is limited due to shortage of manpower and access to institutions that provide it. Our aim was to look at the incidence of pathogenic germline mutations in India/UAE and develop a virtual pathway, aimed at increasing accessibility to genetic counselling. Methods: 864 patients(pts) were tested in the UAE and India for germline mutations. Based on discussion between physicians and patients, an urgent need for genetic counseling was identified. A virtual platform (telegenetics) was constructed for those who sought genetic counseling due to a personal or family history of malignancies. Referral of pts was either self-based or through a treating physician. Primary goals included 1) ease of access for pts, 2) increase comprehension of the indications, implications and consequences of genetic testing, 3) decrease physician time in the clinic. 10 questions were developed determine pt and physician satisfaction. Results: 241(28.9%)pts had a pathogenic variant in BRCA1/BRCA. 115pts were enrolled in the pilot phase of the tele genetics program; all physician referred. Counselling was by a dedicated trained genetic counsellor through voice-call(43.5%), video-conferencing(47.8%) or in person when requested (8.7%). All pts completed a satisfaction survey. Majority of pts were comfortable sharing information on a virtual platform(80%), were happy with the quality of virtual connection(85%), and felt comfortable connecting with the genetic counselor(90%). Information is currently being collected from referring physicians. Conclusions: Our ongoing pilot phase reveals improved pt satisfaction and understanding of the information provided. A mobile application has been developed to enhance pt accessibility/convenience and physician connectivity with the testing phase of the app currently on going. To our knowledge this is the first tele genetics program to target the middle east/Asia pac region that is targeted to cope with increase in pt volumes, expand appropriate referrals, starting with pts who have a personal or family history of cancers, expanding to more complex high risk diseases over time.
What Filipinos, the world’s number one Internet users, want to know about cancer: A Google search analysis from 2015 to 2019.
Authors: Catedral Lance Isidore Garcenila , Leones Louis Mervyn Banua , Berba Carlo Miguel 
Published: October 2019

23 Background: Filipinos were the world’s heaviest Internet users in 2018. It has been shown that they use the Internet to actively search for health-related information, but it has not yet been determined what kinds of information are sought. There is a gap in our present understanding of the information needs of the Filipino population in relation to cancer. The study assessed the cancer-related information needs of Filipinos using Internet search data from March 2015 to May 2019. Methods: A retrospective longitudinal study was done using Google AdWords Keyword Planner to identify search terms related to cancer from Internet users from the Philippines from June 2015 to May 2019. The identified search terms were assessed descriptively using Microsoft Excel version 16.26. The search terms were qualitatively categorized and described. Results: A total of 806 cancer-related search terms were identified, with 13,632,890 Google web searches, during the period under review. The top ten search terms with the highest monthly search volume in the Philippines (n=4,741,600, 34.78%) were “cancer,” “breast cancer,” “cervical cancer,” “prostate cancer,” “colon cancer,” “breast cancer symptoms,” “lung cancer,” “lung cancer symptoms,” “colon cancer symptoms,” and “lungs.” In this time period, Filipinos sought information on cancer-related signs and symptoms (n=3,307,640, 24.26%) and cancer treatment (n=604,070, 4.43%). Filipinos also searched for alternative, herbal, and natural cancer treatments, but the search volume accounted for a low percentage of the total searches (n=8,710, 0.06%). Searches for the search term, “cancer,” were highest on January to February, a trend observed from January 2016 to 2019. Conclusions: Our study provides insight into the cancer-related information needs of the Filipino population. This information may inform the development of targeted, cost-effective awareness campaigns through the Internet, which may be more effective if launched at the beginning of each year.
Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA).
Authors: Oxnard Geoffrey R. , Klein Eric A. , Seiden Michael , Hubbell Earl , Venn Oliver , Jamshidi Arash , Zhang Nan , Beausang John F. , Gross Samuel , Kurtzman Kathryn N. , Fung Eric T. , Yecies Jessica , Shaknovich Rita , Fields Alexander P. , Sekeres Mikkael A. , Richards Donald A. , Yu Peter Paul , Aravanis Alex , Hartman Anne-Renee , Liu Minetta C. 
Published: October 2019

44 Background: A noninvasive cfDNA blood test detecting multiple cancers at earlier stages could decrease cancer mortality. In earlier discovery work, whole-genome bisulfite sequencing outperformed whole-genome and targeted sequencing approaches for multi-cancer detection across stages at high specificity. Here, multi-cancer detection and TOO localization using bisulfite sequencing of plasma cfDNA to identify methylomic signatures was evaluated in preparation for clinical validation, utility, and implementation studies. Methods: 2301 analyzable participants (1422 cancer [ > 20 tumor types, all stages], 879 non-cancer) were included in this prespecified substudy from the Circulating Cell-free Genome Atlas (CCGA) (NCT02889978) study - a prospective, multi-center, observational, case-control study with longitudinal follow-up. Plasma cfDNA was subjected to a targeted methylation sequencing assay using high-efficiency methylation chemistry to enrich for methylation targets, and a machine learning classifier determined cancer status and tissue of origin (TOO). Observed methylation fragments characteristic of cancer and TOO were combined across targeted regions and assigned a relative probability of cancer and of a specific TOO. Results: Performance is reported at 99% specificity (ie, a combined false positive rate across all cancer types of 1%), a level required for population-level screening. Across cancer types, sensitivity ranged from 59 to 86%. Combined cancer detection (sensitivity [95% CI]) was 34% (27-43%) in stage I (n = 151), 77% (70-83%) in stage II (n = 171), 84% (79-89%) in stage III (n = 204), and 92% (88-95%) in stage IV (n = 281). TOO was provided for 94% of all cancers detected; of these, TOO was correct in > 90% of cases. Conclusions: Detection of multiple deadly cancers across stages using methylation signatures in plasma cfDNA was achieved with a single, fixed, low false positive rate, and simultaneously provided accurate TOO localization. This targeted methylation assay is undergoing validation in preparation for prospective clinical investigation as a cancer detection diagnostic. Clinical trial information: NCT02889978.
A phase I study of MR-HIFU hyperthermia (HT) with radiation (RT) and chemotherapy (CT) for recurrent rectal cancer.
Authors: Chu William , Huang Yuexi , Pichardo Samuel , Staruch Robert , Partanen Ari , McGuffin Merrylee , Chan Kelvin K. , Wong Shun , Czarnota Gregory J. , Hynynen Kullervo 
Published: October 2019

78 Background: HT may improve cancer control and quality of life by sensitizing tumors to RT and CT. Inoperable recurrent rectal cancer has marginal outcomes with current retreatment regimens. We report the results from a first-in-human phase I study of MR-HIFU hyperthermia combined with RT and CT for recurrent rectal cancer. Methods: This ethics-approved study enrolled 6 patients fit for re-irradiation and chemotherapy; and with a MRI-visible and HIFU-accessible lesion. Patients received 30.6 Gy (17 fractions) and daily oral capecitabine, plus MR-HIFU HT immediately before RT on days 1, 8, and 15. Primary objectives were safety (acute toxicity) and treatment feasibility. Secondary objectives included late toxicity, pain palliation, quality of life, and radiologic response. HT was delivered with the Sonalleve MR-HIFU system on a 3T MRI. MR-based feedback control parameters were prescribed to achieve a mean temperature of 42.5°C in an 18 mm diameter target region for 30 minutes without exceeding 45°C. Results: One patient withdrew after completing 1/3 HT sessions due to scheduling and sedation difficulties. Five patients completed HT, RT and CT. There were no intraoperative complications, no adverse events or unintended tissue damage attributable to HT, RT, or CT. Table shows the best single continuous HT and mean temperatures (T90, T10), cumulative time in range (TIR), cumulative number of equivalent minutes at 43oC(CEM43) and day 90 imaging response. Sonication and MRI suite times were 36±13 and 226±78min. Conclusions: MR-HIFU HT was safely delivered in patients with recurrent rectal cancer. Treatment planning and patient set-up times decreased while beam-on time increased with experience. MR-HIFU HT combined with RT and CT appears feasible for primary tumours. Clinical trial information: NCT02528175. [Table: see text]