bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-Scale Screening and Identification of Novel Pathogenic Staphylococcus aureus Genes Using a Silkworm Infection Model
Authors: Paudel Atmika , Hamamoto Hiroshi , Panthee Suresh , Matsumoto Yasuhiko , Sekimizu Kazuhisa
Published: January 2020

The regulatory network of virulence factors produced by the opportunistic pathogen Staphylococcus aureus is unclear and the functions of many uncharacterized genes in its genome remain to be elucidated. In this study, we screened 380 genes whose function was unassigned, utilizing gene-disrupted transposon mutants of the community-acquired methicillin-resistant S. aureus USA300 for pathogenicity in silkworms. We identified 10 strains with reduced silkworm killing ability. Among them, 8 displayed reduced virulence in a mouse model as evidenced by reduced colony-forming units in organs of infected mice. The role of each gene in pathogenicity was further confirmed by complementation and pathogenicity tests in silkworms, where we found that the phenotype was not restored in 1 strain. Additionally, some of the mutants displayed reduced hemolysis, proteolysis, pigment production, and survival in murine RAW 264.7 monocyte-macrophage cells. These newly identified genes involved in virulence will enhance our understanding of the pathogenicity of S. aureus.
Evaluation of penicillin G susceptibility testing methods for Staphylococcus lugdunensis
Authors: Hagstrand Aldman Malin , Påhlman Lisa I
Published: January 2020

Background

Staphylococcus lugdunensis belongs to the CoNS group, but is regarded to be more virulent than most other CoNS. It is also remarkably susceptible to antibiotics, including penicillin G.

Objectives

To evaluate different methods for penicillin susceptibility testing, to assess penicillin susceptibility rates among S. lugdunensis and to describe the clinical presentation including antibiotic treatment.

Methods

Clinical isolates of S. lugdunensis were tested for penicillin susceptibility using disc diffusion according to CLSI (10 U disc) and EUCAST (1 U disc), assessment of zone-edge appearance, nitrocefin test and Etest for MIC determination. PCR of the blaZ gene was used as a reference method.

Results

Of the 112 isolates included in the study, 67% were susceptible to penicillin G according to blaZ PCR. The EUCAST disc diffusion test had 100% sensitivity, whereas the CLSI method had one very major error with a false-susceptible isolate. When zone-edge appearance was included in the assessment, the false-susceptible isolate was correctly classified as resistant. Foreign-body infection was the most common focus of infection, affecting 49% of the participants. Only 4% of the patients were treated with penicillin G.

Conclusions

Penicillin susceptibility is common in S. lugdunensis and the disc diffusion method according to EUCAST had a higher sensitivity than that of CLSI. Assessment of zone-edge appearance could increase the sensitivity of the disc diffusion test. Penicillin susceptibility testing and treatment should be considered in S. lugdunensis infections.
OmpC regulation differs between ST131 and non-ST131 Escherichia coli clinical isolates and involves differential expression of the small RNA MicC
Authors: Suelter Corey S , Hanson Nancy D
Published: January 2020

Background

Virulence genes and the expression of resistance mechanisms undoubtedly play a role in the successful spread of the pandemic clone Escherichia coli ST131. Porin down-regulation is a chromosomal mechanism associated with antibiotic resistance. Translation of porin proteins can be impacted by modifications in mRNA half-life and the interaction among small RNAs (sRNAs), the porin transcript and the sRNA chaperone Hfq. Modifications in the translatability of porin proteins could impact the fitness and therefore the success of E. coli ST131 isolates in the presence of antibiotic.

Objectives

To identify differences in the translatability of OmpC and OmpF porins for different STs of E. coli by comparing steady-state RNA levels, mRNA half-life, regulatory sRNA expression and protein production.

Methods

RNA expression was evaluated using real-time RT–PCR and OmpC mRNA half-life by northern blotting. OmpC, OmpF and Hfq protein levels were evaluated by immunoblotting.

Results

Differences between ST131 and non-ST131 isolates included: (i) the level of OmpC RNA and protein produced with mRNA expression higher for ST131 but OmpC protein levels lower compared with non-ST131 isolates; (ii) OmpC mRNA half-life (21–30 min for ST131 isolates compared with <2–23 min for non-ST131 isolates); and (iii) levels of the sRNA MicC (2- to 120-fold for ST131 isolates compared with −4- to 70-fold for non-ST131 isolates).

Conclusions

Mechanisms involved in the translatability of porin proteins differed among different STs of E. coli. These differences could provide a selective advantage to ST131 E. coli when confronted with an antibiotic-rich environment.
Extract-and-Inject Analysis of Veterinary Drug Residues in Catfish and Ready-to-Eat Meats by Ultrahigh-Performance Liquid Chromatography – Tandem Mass Spectrometry
Authors: Lehotay Steven J , Lightfield Alan R
Published: January 2020

Background

Validated analytical methods are needed to conduct regulatory monitoring of ready-to-eat meats and fish for food safety, risk assessment, and other purposes. The methods should be cost-effective, high-throughput, and meet acceptable performance standards for a wide scope of drugs and matrixes.

Objective

The goal of this study was to demonstrate the validity for possible implementation in the US National Residue Program of an efficient method for qualitative and quantitative analysis of 176 targeted drugs at levels as low as 10 ng/g in hot dogs, catfish and swai (Siluriformes), chicken tenders, fried bacon, and sausage using ultrahigh-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS).

Methods

Sample preparation simply involved a 5 min extraction by shaking 2 g comminuted samples with 10 mL of 4/1 (v/v) acetonitrile/water followed by centrifugation and UHPLC-MS/MS analysis of 2 μL injections. For cleanup comparison purposes only, sausage extracts were also prepared using a cartridge-based EMR-Lipid method prior to analysis.

Results

Acceptable validation of 70–120% recoveries with <25% RSDs was met for 156–176 out of 186 drugs and quality control analytes without cleanup depending on the matrix. The EMR-Lipid method for sausage improved results for some analytes, such as mectin anthelmintics, due to reduction of indirectly interfering fats in the final extracts, but it also led to significantly worse results for several other drugs, resulting in 32 fewer analytes meeting the given validation criteria than without cleanup.

Conclusions

The simple, high-throughput method was demonstrated to be valid to meet routine regulatory and other monitoring needs for many diverse targeted drugs in fish and ready-to-eat meat matrixes.
Evaluation of the 3M™ Petrifilm™ Rapid E. coli/Coliform Count Plate for the Enumeration of E. coli and Coliforms: Collaborative Study, First Action: 2018.13
Authors: Bird Patrick , Bastin Benjamin , Klass Nicole , Crowley Erin , Agin James , Goins David , Bakken Hannah , Lingle Cari , Schumacher April ,   Collaborators, Calle A , Suntharesan K , Gohil V , Donkers A , Smith R , Wood D , Diederich S , Kuchenberg S , Satoshi I , Brown M , Alvarez N , Corti S , Hochreuter M
Published: January 2020

Background

The 3M™ Petrifilm™ Rapid E. coli/Coliform Count Plate is a selective and differential sample-ready-culture medium designed for the rapid enumeration of Escherichia coli (E. coli) and coliforms in the food and beverage industries.

Objective

The 3M Petrifilm Rapid E. coli/Coliform Count Plate was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM) Chapter 4 Enumeration of Escherichia coli and the Coliform Bacteria, the International Organization of Standards (ISO) 4832:2006 Microbiology of food and animal feeding stuffs — Horizontal method for the enumeration of coliforms—Colony-count technique, and ISO 16649-2:2017 Microbiology of food and animal feeding stuffs—Horizontal method for the enumeration of beta-glucuronidase-positive Escherichia coli—Part 2 Colony-count technique at 44 degrees C using bromo-4-chloro-3- indolyl beta-D-glucuronide methods for the enumeration of E. coli and coliforms in dry dog kibble.

Method

The candidate method was evaluated using two diluents, Butterfield's phosphate buffered diluent and peptone salt solution, in a paired study design with each reference method in a multi-laboratory collaborative study following the current AOAC Validation Guidelines. Three target contamination levels and an uninoculated control level were evaluated.

Results

The candidate and reference methods were not statistically different at each contamination level. Reproducibility values obtained during the collaborative study were similar between the candidate and reference methods.

Conclusion

These results demonstrate that the candidate method is equivalent to the reference methods.

Highlight

3M Petrifilm Rapid E. coli/Coliform Count Plate was recommended for Official First Action status for enumeration of E. coli and coliforms in a broad range of foods and environmental surfaces.
Immune system stimulation increases the irreversible loss of cysteine to taurine, but not sulfate, in starter pigs
Authors: Rakhshandeh Anoosh , de Lange Cornelis F M , Htoo John K , Rakhshandeh Amanda R
Published: January 2020

An isotope tracer study was conducted to evaluate the effects of immune system stimulation (ISS) on the irreversible loss of cysteine (Cys) to taurine (Tau) and sulfate (SO4), as well as glutathione (GSH) synthesis, during the fed state in pigs. We previously have reported that ISS increases plasma Cys flux and the GSH synthesis rate at the tissue and whole-body levels in growing pigs. Thus, the current article presents the data on the irreversible loss of Cys during ISS in pigs. Ten gilts (BW: 7.0 ± 0.12 kg) were feed restricted a sulfur amino acids (SAA) limiting diet and injected twice with either saline (n = 4) or increasing amounts of E. coli lipopolysaccharide (n = 6). The day after the second injection, a 5-h primed continuous intravenous infusion of 35S-Cys was conducted. ISS reduced plasma Cys and total SAA concentrations (16% and 21%, respectively; P < 0.05). However, ISS had no effect on the plasma concentrations of Tau and SO4, nor did it affect the appearance of 35S in plasma Tau, plasma SO4, urinary Tau, or urinary SO4 (P > 0.19). On a whole-body basis and including urinary excretion, ISS increased the appearance of 35S in Tau by 67% (P < 0.05), but tended to decrease the appearance of 35S in SO4 by 22% (P < 0.09). Overall, the current findings indicate that during ISS, decreased plasma SAA concentrations and increased plasma Cys flux are attributed in part to increased rates of Cys conversion to Tau, but not Cys catabolism to SO4. Thus, increased utilization of Cys for the synthesis of immune system metabolites, such as GSH and Tau, is likely the main contributor to increased Cys flux during ISS in pigs. In addition, the irreversible loss of Cys during ISS is small and has a minimal impact on the daily SAA requirements of starter pigs.
Regulation of growth in Drosophila melanogaster: the roles of mitochondrial metabolism
Authors: Jacobs Howard T , George Jack , Kemppainen Esko
Published: January 2020

Mitochondrial functions are often considered purely from the standpoint of catabolism, but in growing cells they are mainly dedicated to anabolic processes, and can have a profound impact on the rate of growth. The Drosophila larva, which increases in body mass ∼200-fold over the course of ∼3 days at 25°C, provides an excellent model to study the underlying regulatory machinery that connects mitochondrial metabolic capacity to growth. In this review, we will focus on several key aspects of this machinery: nutrient sensing, endocrine control of feeding and nutrient mobilization, metabolic signalling, protein synthesis regulation and pathways of steroid biosynthesis and activity. In all these aspects, mitochondria appear to play a crucial role.
Population Genomics Training for the Next Generation of Conservation Geneticists: ConGen 2018 Workshop
Authors: Stahlke Amanda , Bell Donavan , Dhendup Tashi , Kern Brooke , Pannoni Samuel , Robinson Zachary , Strait Jeffrey , Smith Seth , Hand Brian K , Hohenlohe Paul A , Luikart Gordon
Published: January 2020

The increasing availability and complexity of next-generation sequencing (NGS) data sets make ongoing training an essential component of conservation and population genetics research. A workshop entitled “ConGen 2018” was recently held to train researchers in conceptual and practical aspects of NGS data production and analysis for conservation and ecological applications. Sixteen instructors provided helpful lectures, discussions, and hands-on exercises regarding how to plan, produce, and analyze data for many important research questions. Lecture topics ranged from understanding probabilistic (e.g., Bayesian) genotype calling to the detection of local adaptation signatures from genomic, transcriptomic, and epigenomic data. We report on progress in addressing central questions of conservation genomics, advances in NGS data analysis, the potential for genomic tools to assess adaptive capacity, and strategies for training the next generation of conservation genomicists.
Solar cycle variation of νmax in helioseismic data and its implications for asteroseismology
Authors: Howe Rachel , Chaplin William J , Basu Sarbani , Ball Warrick H , Davies Guy R , Elsworth Yvonne , Hale Steven J , Miglio Andrea , Nielsen Martin Bo , Viani Lucas S
Published: January 2020

The frequency, νmax, at which the envelope of pulsation power peaks for solar-like oscillators is an important quantity in asteroseismology. We measure νmax for the Sun using 25 yr of Sun-as-a-star Doppler velocity observations with the Birmingham Solar-Oscillations Network (BiSON), by fitting a simple model to binned power spectra of the data. We also apply the fit to Sun-as-a-star Doppler velocity data from Global Oscillation Network Group and Global Oscillations at Low Frequency, and photometry data from VIRGO/SPM on the ESA/NASA SOHO spacecraft. We discover a weak but nevertheless significant positive correlation of the solar νmax with solar activity. The uncovered shift between low and high activity, of $\simeq 25\, \rm \mu Hz$, translates to an uncertainty of 0.8 per cent in radius and 2.4 per cent in mass, based on direct use of asteroseismic scaling relations calibrated to the Sun. The mean νmax in the different data sets is also clearly offset in frequency. Our results flag the need for caution when using νmax in asteroseismology.
Uncovering tissue-specific binding features from differential deep learning
Authors: Phuycharoen Mike , Zarrineh Peyman , Bridoux Laure , Amin Shilu , Losa Marta , Chen Ke , Bobola Nicoletta , Rattray Magnus
Published: January 2020

Transcription factors (TFs) can bind DNA in a cooperative manner, enabling a mutual increase in occupancy. Through this type of interaction, alternative binding sites can be preferentially bound in different tissues to regulate tissue-specific expression programmes. Recently, deep learning models have become state-of-the-art in various pattern analysis tasks, including applications in the field of genomics. We therefore investigate the application of convolutional neural network (CNN) models to the discovery of sequence features determining cooperative and differential TF binding across tissues. We analyse ChIP-seq data from MEIS, TFs which are broadly expressed across mouse branchial arches, and HOXA2, which is expressed in the second and more posterior branchial arches. By developing models predictive of MEIS differential binding in all three tissues, we are able to accurately predict HOXA2 co-binding sites. We evaluate transfer-like and multitask approaches to regularizing the high-dimensional classification task with a larger regression dataset, allowing for the creation of deeper and more accurate models. We test the performance of perturbation and gradient-based attribution methods in identifying the HOXA2 sites from differential MEIS data. Our results show that deep regularized models significantly outperform shallow CNNs as well as k-mer methods in the discovery of tissue-specific sites bound in vivo.
Presumed Nonalcoholic Fatty Liver Disease Among Medicare Beneficiaries With HIV, 2006–2016
Authors: Paik James M , Henry Linda , Golabi Pegah , Alqahtani Saleh A , Trimble Gregory , Younossi Zobair M
Published: January 2020

Background

Newer treatments for HIV and hepatitis C virus (HCV) have decreased mortality in HIV/HCV patients. Nonalcoholic fatty liver disease (NAFLD) has increased globally; therefore, the prevalence and mortality of NAFLD among HIV (+) patients was assessed.

Methods

Using Medicare denominator, inpatient, and outpatient files (random 5% sample per year), serial cross-sectional analysis (2006 to 2016) was performed. Joinpoint trend analysis evaluated prevalence and mortality with average annual percent change (AAPC). HIV (+) patients and liver diseases (LDs) were identified using International Classification of Diseases 9/10 codes. NAFLD was presumed using diagnosis codes or codes for metabolic dysfunction and obesity in absence of other LDs. Liver-related HIV (+) indicated HIV (+) patients with LDs.

Results

Among 28 675 887 Medicare beneficiaries, 47 062 were HIV (+) (mean [SD] age, 51.4 [11.3] years); 11 920 had liver diseases (6923 HCV, 2019 hepatitis B virus [HBV], 2472 presumed NAFLD, 278 alcoholic liver disease [ALD], and 1653 other LDs); 2882 HIV (+) patients died; 1260 had LDs. The prevalence and mortality for non-liver-related HIV (+) decreased (AAPC, –1.1% and –9.1%). Liver-related HIV (+) increased (AAPC, 1.7%; P = .007); mortality leveled off. Prevalence and mortality worsened for presumed NAFLD (AAPC, 9.7% and 10.0%) and improved for HBV and HCV (HBV: AAPC, –3.5% and –8.8%; HCV: AAPC, –0.7% and –4.9%). After adjustments, HCV (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.24–172), HBV (OR, 2.40; 95% CI, 2.09–2.77), ALD (OR, 5.70; 95% CI, 4.34–7.48), and presumed NAFLD (OR, 1.46; 95% CI, 1.24–1.72) increased 1-year mortality.

Conclusions

Among HIV (+) subjects, viral hepatitis remains the leading LD for increased 1-year mortality, but the prevalence and mortality with presumed NAFLD are increasing.
‘Everybody in Nigeria is a doctor…’: a qualitative study of stakeholder perspectives on lay diagnosis of malaria and pneumonia in Nigeria
Authors: Elimian Kelly O , Myles Puja R , Phalkey Revati , Sadoh Ayebo , Pritchard Catherine
Published: January 2020

Background

Lay diagnosis is a widely used diagnostic approach for home management of common illnesses in Nigeria. This study aimed to explore the perspectives of caregivers and healthcare professionals on lay diagnosis of childhood malaria and pneumonia. Aligned to this, the study sought to explore the feasibility of training caregivers in the Integrated Management of Childhood Illness (IMCI) guidelines for improved recognition and treatment of these diseases.

Methods

A qualitative study using individual face-to-face semi-structured interviews was conducted in Benin City, Nigeria. Participants included 13 caregivers with children under 5 years and 17 healthcare professionals (HPs). An inductive approach to thematic analysis was used to generate themes and analyses.

Results

Caregivers relied on lay diagnosis but recognised its limitations. The perceived severity of malaria and pneumonia significantly influenced caregivers’ preference for reliance on lay diagnosis practices, health-seeking behaviour and willingness to undertake training in IMCI guidelines for home management of diseases. Safety and potential unintended misuse of medications were recognised by caregivers and HPs as the main challenges.

Conclusions

The high level of acceptance among caregivers to receive IMCI training could help improve effective management of childhood malaria and pneumonia at the community level through early recognition and prompt treatment.
Engaging Religion in a Contested Age: Contestations, Postmodernity, and Social Change
Authors: Nesbitt Paula D
Published: January 2020

Both secular and religious contestations have threatened the character of contemporary civic discourse, signifying underlying issues needing to be addressed. Postmodern and globalization influences have contributed to their scope and intensity, adding underlying complexities to the presenting issues. Drawing upon case examples of a secular plant closure in a racially and ethnically diverse company town and strife threatening organizational viability in the cross-cultural Anglican Communion, I argue first that religion either directly influences or indirectly serves as a latent resource within secularized morality, and second that cross-cultural contestations involving religion typically contain underlying societal concerns; both need to be addressed in analyzing meaning and hope for change. Sociologists of religion have opportunity to explore how religion is deployed as a moral basis of contestation, and how it might interact with postcolonial and other cultural dynamics, with implications for solutions in building social cohesion across worldviews and cultures.
A metanalysis on cabozantinib and bone metastases: true story or commercial gimmick?
Authors: Bersanelli Melissa , Buti Sebastiano , Ghidini Antonio , Tiseo Marcello , Petrelli Fausto
Published: January 2020

Is it true that cabozantinib should be the preferred option treating patients with bone metastases? Are there any reliable comparisons between this drug and other standard options in this subgroup? To address the issue, we performed a systematic review and metanalysis of randomized trials with cabozantinib, to assess its effectiveness, in terms of overall survival, according to the presence of bone metastases. We included (a) randomized controlled trials; (b) any solid tumors and therapeutic line; and (c) overall survival data available according to the site of disease. Cabozantinib improved overall survival both for the group with bone metastases, with risk of death decreased by 53% (hazard ratio, 0.47; 95% confidence interval, 0.26–0.87; P=0.02) and for the group without bone metastases, decreasing the risk of death by 44% (hazard ratio, 0.56; 95% confidence interval, 0.40–0.79; P=0.001) over the standard of care. The difference was not significantly different between the two groups. Despite cabozantinib can be undoubtedly listed as a good therapeutic option for cancer patients with bone metastases, it seems that its preclinical profile against bone remodeling does not translate into an actual clinical relevance, preventing from considering the presence of bone metastases as principal criterion for the choice of this drug.
Beta-Blocker Dose Stratifies Mortality Risk in a Racially Diverse Heart Failure Population
Authors: Lteif Christelle , Arwood Meghan J. , Kansal Mayank , Cavallari Larisa H. , Desai Ankit A. , Duarte Julio D.
Published: January 2020

Heart failure (HF) is highly prevalent and a major cause of death in the United States. The effect of HF medications on survival has been predicted by validated models studied in populations predominantly of European descent. This study aimed to identify medications associated with survival in a racially diverse HF population. Patients with HF were recruited and followed from 2001 to 2015. Data were collected from electronic health records and the Social Security Death Index. The primary analysis tested the association between medication dose and all-cause mortality, with a secondary analysis assessing the composite outcome of death or cardiac-related hospitalization. Circulating concentration of the fibrotic marker procollagen type III N-terminal peptide (PIIINP) was also compared with medication doses in patients with concentrations available. The study population consisted of 337 patients, of which 25.2% died and 46% were hospitalized. Increased beta-blocker (BB) dose was significantly associated with survival in the base model [hazard ratio (HR) = 0.71, P = 0.017] and marginally associated in the comprehensive model (HR = 0.75, P = 0.068). BB dose was also associated with decreased risk of the composite end point in the base model (HR = 0.80, P = 0.029) and to a lesser extent in the comprehensive model (HR = 0.83, P = 0.085). Furthermore, increased BB dose was inversely associated with circulating PIIINP concentration (P = 0.041). In conclusion, our study highlights the importance of BB dose escalation for survival and decreased hospitalization in patients with HF, regardless of race or HF type. It also suggests that benefits observed with high-dose BBs could be mediated, at least in part, by decreased cardiac fibrosis.
A Report of Intracranial Meningioma Recurring as Ectopic Orbital Meningioma Associated With Basal Encephalocele
Authors: Satija Celine E. , Mehta Viraj J. , Maltry Amanda C. , Nussbaum Eric , Nussbaum Leslie , Harrison Andrew R.
Published: January 2020

The authors describe a rare case of recurrent ectopic meningioma associated with sphenoid encephalocele in the medial anterior orbit of a 52-year-old man with a history of a resected intracranial meningioma. Typical features of ectopic meningioma are reviewed as well as potential etiologies of this very rare recurrence of intracranial meningioma in the orbit. Treatment is typically surgical excision.

The authors report a rare case of recurrent orbital ectopic meningioma in the right medial canthus of a 52-year-old man.
The serum interleukin-26 level is a potential biomarker for chronical hepatitis B
Authors: Luo Liwen , Jiang Li , Tian Zhiqiang , Zhang Xinqi
Published: January 2020

Proinflammatory interleukin-26 (IL-26) is involved in chronic inflammation; however, the role of IL-26 in chronic hepatitis B (CHB) remains unknown.

In this study, serum IL-26 was quantified in a cohort of CHB patients at baseline and during telbivudine (LdT) treatment.

Our results showed that the serum IL-26 level was significantly elevated in CHB patients compared with that in healthy controls and was time-dependently decreased during LdT treatment, accompanying hepatitis B e antigen (HBeAg) seroconversion and reduced serum levels of hepatitis B virus (HBV) DNA, aspartate transaminase, and alanine transaminase across baseline and treatment. In addition, the serum level of IL-26 exhibited a similar declining trend to that of T helper 17 (Th17) cell-secreted IL-17 during LdT treatment in CHB patients. The percentage of IL-26-expressing CD4+ cells was significantly higher than that of IL-26-expressing CD4- cells isolated from the peripheral blood mononuclear cells of CHB patients, suggesting that serum IL-26 might be mainly released from CD4+ T cells. Furthermore, the baseline mRNA levels of IL-26 and orphan nuclear receptor RORγt—an important transcription factor expressed by Th17 cells—were positively correlated and displayed the same declining trend across the baseline and LdT treatment in CHB patients, suggesting that Th17 cells could be a possible cellular source of the increased serum IL-26 in CHB patients.

Taken together, our results suggest that serum IL-26, possibly produced by Th17 CD4+ cells, is a novel and potential biomarker for CHB prognosis and treatment.
Clinical nutrition for the gastroenterologist: bedside strategies for feeding the hospitalized patient
Authors: McClave Stephen A. , Omer Endashaw
Published: January 2020

Purpose of review

The timing, advancement, and use of appropriate monitors determine whether the hospitalized patient experiences the full benefit of nutritional therapy. This article reviews management strategies in delivering the optimal nutrition regimen capable of improving outcomes in the hospitalized patient.

Recent findings

Enteral nutrition should be initiated in the first 24–36 h after admission. Determination of nutritional risk helps guide the urgency with which nutritional therapy is provided and predicts the likelihood for difficulties in delivering the prescribed regimen. Feeds should be advanced slowly over 3–4 days to meet 70–80% of goal for calories (20 kcal/kg/day) and 100% for protein (2.0 gm/kg/day). Reaching protein goals early on may be more important than achieving energy goals. Patients should be monitored for hemodynamic stability, evidence of refeeding syndrome, and tolerance in the setting of gastrointestinal dysfunction. Parenteral nutrition should be utilized in select high-risk patients where the feasibility of full enteral nutrition is questioned.

Timing with early initiation of enteral nutrition, avoidance of overfeeding, and step-wise advancement of feeds are required to safely realize the benefits of such therapy.
Mini Osteoplastic Flap Through Supra-Eyebrow Incision for Primary Frontal Sinus Squamous Cell Carcinoma
Authors: Lee Yu-Mi , Park Hye-Jin , Kim Sung-Dong , Cho Kyu-Sup
Published: January 2020

Primary carcinoma of the frontal sinus is very rare, with an incidence of 0.3% to 1.0% of all paranasal sinus carcinomas. Although complete resection with a clear margin is definitely essential to achieve tumor control, radical surgery with osteoplastic flap using bicoronal incision has significant postoperative morbidities including scalp numbness, hair loss, and frontalis palsy. This article reports a rare case of primary frontal sinus squamous cell carcinoma extending to the orbit, which was treated successfully by mini osteoplastic flap through supra-eyebrow incision combined transnasal endoscopic approach.
Interactive web application for plotting personalized prognosis prediction curves in allogeneic hematopoietic cell transplantation using machine learning
Authors: Okamura Hiroshi , Nakamae Mika , Koh Shiro , Nanno Satoru , Nakashima Yasuhiro , Koh Hideo , Nakane Takahiko , Hirose Asao , Hino Masayuki , Nakamae Hirohisa
Published: January 2020

Background

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for malignant hematological disorders. Transplant clinicians estimate patient-specific prognosis empirically in clinical practice based on previous studies on similar patients. However, this approach does not provide objective data. The present study primarily aimed to develop a tool capable of providing accurate personalized prognosis prediction after allo-HCT in an objective manner.

Methods

We developed an interactive web application tool with a graphical user interface capable of plotting the personalized survival and cumulative incidence prediction curves after allo-HCT adjusted by eight patient-specific factors, which are known as prognostic predictors, and assessed their predictive performances. A random survival forest model using the data of patients who underwent allo-HCT at our institution was applied to develop this application.

Results

We succeeded in showing the personalized prognosis prediction curves of 1-year overall survival (OS), progression-free survival (PFS), relapse/progression, and non-relapse mortality (NRM) interactively using our web application (https://predicted-os-after-transplantation.shinyapps.io/RSF_model/). To assess its predictive performance, the entire cohort (363 cases) was split into a training cohort (70%) to develop the predictive model and test cohort (30%) to confirm its performance time-sequentially. The areas under the receiver-operating characteristic curves for 1-year OS, PFS, relapse/progression, and NRM in test cohort were 0.70, 0.72, 0.73, and 0.77, respectively.

Conclusions

The new web application could allow transplant clinicians to inform a new allo-HCT candidate of the objective personalized prognosis prediction and facilitate decision-making.
Glacier ice archives fifteen-thousand-year-old viruses
Authors: Zhong Zhi-Ping , Solonenko Natalie E. , Li Yueh-Fen , Gazitúa Maria C. , Roux Simon , Davis Mary E. , Van Etten James L. , Mosley-Thompson Ellen , Rich Virginia I. , Sullivan Matthew B. , Thompson Lonnie G.
Published: January 2020

While glacier ice cores provide climate information over tens to hundreds of thousands of years, study of microbes is challenged by ultra-low-biomass conditions, and virtually nothing is known about co-occurring viruses. Here we establish ultra-clean microbial and viral sampling procedures and apply them to two ice cores from the Guliya ice cap (northwestern Tibetan Plateau, China) to study these archived communities. This method reduced intentionally contaminating bacterial, viral, and free DNA to background levels in artificial-ice-core control experiments, and was then applied to two authentic ice cores to profile their microbes and viruses. The microbes differed significantly across the two ice cores, presumably representing the very different climate conditions at the time of deposition that is similar to findings in other cores. Separately, viral particle enrichment and ultra-low-input quantitative viral metagenomic sequencing from ∼520 and ∼15,000 years old ice revealed 33 viral populations (i.e., species-level designations) that represented four known genera and likely 28 novel viral genera (assessed by gene-sharing networks).In silicohost predictions linked 18 of the 33 viral populations to co-occurring abundant bacteria, includingMethylobacterium,Sphingomonas, andJanthinobacterium, indicating that viruses infected several abundant microbial groups. Depth-specific viral communities were observed, presumably reflecting differences in the environmental conditions among the ice samples at the time of deposition. Together, these experiments establish a clean procedure for studying microbial and viral communities in low-biomass glacier ice and provide baseline information for glacier viruses, some of which appear to be associated with the dominant microbes in these ecosystems.

Importance

This study establishes ultra-clean microbial and viral sampling procedures for glacier ice, which complements priorin silicodecontamination methods and expands, for the first time, the clean procedures to viruses. Application of these methods to glacier ice confirmed prior common microbiological findings for a new ice core climate record, and provides a first window into viral genomes and their ecology from glacier ice across two time horizons, and emphasizes their likely impact on abundant microbial groups. Together these efforts provide clean sampling approaches and foundational datasets that should enable simultaneous access to an archived virosphere in glacier ice.
Mapping Trends in Insecticide Resistance Phenotypes in African Malaria Vectors
Authors: Hancock PA , Hendriks CJM , Tangena J-A , Gibson H , Hemingway J , Coleman M , Gething PW , Cameron E , Bhatt S , Moyes CL
Published: January 2020

Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from theAnopheles gambiaecomplex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across Sub-Saharan Africa from 2005-2017 as well as substantial spatial variation in resistance trends.
Brain signatures of surprise in EEG and MEG data
Authors: Mousavi Zahra , Kiani Mohammad Mahdi , Aghajan Hamid
Published: January 2020

The brain is constantly anticipating the future of sensory inputs based on past experiences. When new sensory data is different from predictions shaped by recent trends, neural signals are generated to report this surprise. Existing models for quantifying surprise are based on an ideal observer assumption operating under one of the three definitions of surprise set forth as the Shannon, Bayesian, and Confidence-corrected surprise. In this paper, we analyze both visual and auditory EEG and auditory MEG signals recorded during oddball tasks to examine which temporal components in these signals are sufficient to decode the brain’s surprise based on each of these three definitions. We found that for both recording systems the Shannon surprise is always significantly better decoded than the Bayesian surprise regardless of the sensory modality and the selected temporal features used for decoding.

Author summary

A regression model is proposed for decoding the level of the brain’s surprise in response to sensory sequences using selected temporal components of recorded EEG and MEG data. Three surprise quantification definitions (Shannon, Bayesian, and Confidence-corrected surprise) are compared in offering decoding power. Four different regimes for selecting temporal samples of EEG and MEG data are used to evaluate which part of the recorded data may contain signatures that represent the brain’s surprise in terms of offering a high decoding power. We found that both the middle and late components of the EEG response offer strong decoding power for surprise while the early components are significantly weaker in decoding surprise. In the MEG response, we found that the middle components have the highest decoding power while the late components offer moderate decoding powers. When using a single temporal sample for decoding surprise, samples of the middle segment possess the highest decoding power. Shannon surprise is always better decoded than the other definitions of surprise for all the four temporal feature selection regimes. Similar superiority for Shannon surprise is observed for the EEG and MEG data across the entire range of temporal sample regimes used in our analysis.
Electrochemical carbon fiber-based technique for simultaneous recordings of brain tissue PO2, pH, and extracellular field potentials
Authors: Hosford Patrick S. , Wells Jack A. , Christie Isabel N. , Lythgoe Mark , Millar Julian , Gourine Alexander V.
Published: January 2020

A method for simultaneous electrochemical detection of brain tissue PO2(PtO2) and pH changes together with neuronal activity using a modified form of fast cyclic voltammetry with carbon fiber electrodes is described. This technique has been developed forin vivoapplications and recordings from discrete brain nuclei in experimental animals. The small size of the carbon fiber electrode (⍰7μm, length <100μm) ensures minimal disruption of the brain tissue and allows recordings from small brain areas. Sample rate (up to 4 Hz) is sufficient to resolve rapid changes in PtO2and pH that follow changes in neuronal activity and metabolism. Rapid switching between current and voltage recordings allows combined electrochemical detection and monitoring of extracellular action potentials. For simultaneous electrochemical detection of PtO2and pH, two consecutive trapezoidal voltage ramps are applied with double differential-subtraction of the background current. This enables changes in current caused by protons and oxygen to be detected separately with minimal interference between the two. The profile of PtO2changes evoked by increases in local neuronal activity recorded using the described technique was similar to that of blood oxygen level dependent responses recorded using fMRI. This voltammetric technique can be combined with fMRI and brain vessel imaging to study the metabolic mechanisms underlying neurovascular coupling response with much greater spatial and temporal resolution than is currently possible.
Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria
Authors: Adolph Kenneth W.
Published: January 2020

Metaxin 1 and 2 genes, previously investigated in vertebrates, are shown to be widely distributed among invertebrates. But metaxin 3 is absent. The predicted proteins of the invertebrate metaxins were initially identified by homology with human metaxin 1 and 2 proteins, and by the presence of characteristic GST_Metaxin protein domains. Invertebrate metaxins were revealed for a variety of phyla, including Echinodermata, Cnidaria, Porifera, Chordata, Arthropoda, Mollusca, Brachiopoda, Placozoa, and Nematoda. Metaxins were also found in insects (Arthropoda) of different taxonomic orders: Diptera, Coleoptera, Lepidoptera, Hymenoptera, and Blattodea. Invertebrate and human metaxin 1 proteins have about 41% identical amino acids, while metaxin 2 proteins have about 49% identities. Invertebrate and vertebrate metaxins share the same characteristic protein domains, further strengthening the identification of the invertebrate proteins as metaxins. The domains are, for metaxin 1, GST_N_Metaxin1_like, GST_C_Metaxin1_3, and Tom37. For metaxin 2, they are GST_N_Metaxin2, GST_C_Metaxin2, and Tom37. Phylogenetic trees show that invertebrate metaxin 1 and metaxin 2 proteins are related, but form separate groups. The invertebrate proteins are also closely related to vertebrate metaxins, though forming separate clusters. These phylogenetic results indicate that all metaxins likely arose from a common ancestral sequence. The neighboring genes of the invertebrate metaxin 1 and 2 genes are largely different for different invertebrate species. This is unlike the situation with vertebrate metaxin genes, where, for example, the metaxin 1 gene is adjacent to the thrombospondin 3 gene. The dominant secondary structures predicted for the invertebrate metaxins are alpha-helical segments, with little beta-strand. The conserved pattern of helical segments is the same as that found for vertebrate metaxins 1, 2, and 3.
Genetic characterization of stem cell-like cancer cell in the peri-tumoral regions and proliferative lymphocyte in the peripheral blood of patients with glioblastoma
Authors: Yang Runwei , Huang Guanglong , Guo Jinglin , Li Yaomin , Song Haimin , Li Kaishu , Yi Guozhong , Lin Zhiying , Wang Xiran , Xie Sidi , Liu Zhifeng , Shi Xiaofeng , Li Ke , Qi Songtao , Liu Yawei
Published: January 2020

The glioblastoma (GBM) recurrence rate is high, despite multimodal treatment including surgery, radiotherapy, chemotherapy, and immunotherapy. Most recurrences occur at the resection margin that is located outside the GBM contrast-enhancing region (C region) of magnetic resonance imaging. However, the nature of the GBM cells that lie outside the C region is unclear. We used single-cell RNA sequencing (scRNA-seq) to compare 12 samples taken from inside and outside the C region from four patients with GBM and identified a cluster of GBM cells outside the C region that exhibited fragmented CNVs in chromosomes such as 1, 10, 12 and 19 (herein termed CNV 4). A transcription factor–transcription cofactor interaction network was constructed to uncover the transcriptional regulatory mechanism of these CNV 4 GBM cells that had prognostic significance (p < 0.05). Furthermore, a sub-cluster of these CNV 4 GBM cells possessed stem cell-like properties and had tumorigenic potential. In parallel, we analyzed peripheral blood mononuclear cells (PBMCs) from four patients with GBM, three patients with epilepsy and three healthy volunteers by scRNA-seq. We identified a novel subtype of proliferative immune cells only in patients with GBM. Overall, our findings indicate that CNV 4 cells might contribute to GBM recurrence and proliferative circulating immune cells are specific to patients with GBM. This study sheds light on a neglected aspect of GBM, and opens new avenues to explore GBM recurrence and immunotherapy.

Significance

We show that a subset of GBM cells outside the C region possess the properties of stem cell and tumorigenesis potential, which might be responsible for cancer recurrence. Besides, proliferative lymphocytes are specific to the PBMCs of patients with GBM, which could help to develop novel immunotherapy.
Improving the sensitivity of cluster-based statistics for fMRI data
Authors: Geerligs Linda , Maris Eric
Published: January 2020

Because of the high dimensionality of neuroimaging data, identifying a statistical test that is both valid and maximally sensitive is an important challenge. Here, we present a combination of two approaches for fMRI data analysis that together result in substantial improvements of the sensitivity of cluster-based statistics. The first approach is to create novel cluster definitions that are sensitive to physiologically plausible effect patterns. The second is to adopt a new approach to combine test statistics with different sensitivity profiles, which we call the min(p) method. These innovations are made possible by using the randomization inference framework. In this paper, we report on a set of simulations that demonstrate (1) that the proposed methods control the false-alarm rate, (2) that the sensitivity profiles of cluster-based test statistics vary depending on the cluster defining thresholds and cluster definitions, and (3) that the min(p) method for combining these test statistics results in a drastic increase of sensitivity (up to five-fold), compared to existing fMRI analysis methods. This increase in sensitivity is not at the expense of the spatial specificity of the inference.
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at Chr16q11.2 and on the MAPT H1 allele
Authors: Soutar Marc P.M. , Melandri Daniela , O’Callaghan Benjamin , Annuario Emily , Monaghan Amy E. , Welsh Natalie J. , D’Sa Karishma , Guelfi Sebastian , Zhang David , Pittman Alan , Trabzuni Daniah , Pan Kylie S. , Kia Demis A. , Bictash Magda , Gandhi Sonia , Houlden Henry , Cookson Mark R. , Wood Nicholas W , Singleton Andrew B. , Hardy John , Whiting Paul J. , Blauwendraat Cornelis , Whitworth Alexander J. , Manzoni Claudia , Ryten Mina , Lewis Patrick A. , Plun-Favreau Hélène
Published: January 2020

Parkinson’s disease (PD) is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies (GWAS) has considerably advanced our understanding of the PD genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Impaired mitophagy is a key causative pathway in familial PD, but its relevance to idiopathic PD is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through GWAS. We identified two new regulators of PINK1-mitophagy, KAT8 and KANSL1, previously shown to modulate lysine acetylation. We show that KAT8 and KANSL1 modulatePINK1gene expression and subsequent PINK1-mitophagy. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic PD.KANSL1is located on chromosome 17q21 where the risk associated gene has long been considered to beMAPT. While our data does not exclude a possible association between theMAPTgene and PD, it provides strong evidence thatKANSL1plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration.