bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydration of Glaucophane in the System Na2O–MgO–Al2O3–SiO2–H2O and the Effects of NaCl-, CO2- and Silicate-bearing Aqueous Fluids
Authors: Cheng Nanfei , Jenkins David M , Huang Fang
Published: February 2020

Arc magmas are thought to be generated by partial melting of the mantle wedge above the subduction slab, which is triggered by the fluids from the dehydration of subducting oceanic crust. Among the dehydration reactions, those occurring at the depths of the blueschist-to-eclogite transition are considered to be very important. The sodium amphibole glaucophane (□Na2Mg3Al2Si8O22(OH)2, where □ represents a vacancy) is characteristic of blueschists, so that determining the higher-temperature stability of end-member glaucophane helps constrain the maximum temperature of the transition between blueschists and eclogites. A reversed determination of the dehydration reaction 2 glaucophane = 4 jadeite + 3 enstatite + 2 quartz + 2 H2O was done in the system Na2O–MgO–Al2O3–SiO2–H2O over the pressure-temperature (P–T) range of 2·5–3·3 GPa and 760–900 °C for durations of 24–96 hours, using synthetic phases as starting materials. The reaction was bracketed at 830–850 °C at 2·5 GPa and at 810–830 °C at 2·9 GPa in the presence of water. In addition to pure water, 5 molality H2O–NaCl (mole fraction XNaCl = 0·08) and 5 molality H2O–CO2 (XCO2 = 0·08) fluids were used to check the effects of NaCl and CO2, respectively, on the dehydration reaction. The H2O–NaCl fluid shifts the reaction boundary at 2·5 GPa from 840 °C to a lower T (800 °C), while the CO2–H2O fluid shifts the boundary to a higher T (860 °C). At these high P–T conditions, the fluid, even without any added NaCl or CO2, is a silicate-bearing aqueous fluid. The different effects of NaCl and CO2 are attributed to differences in their capabilities to inhibit the solubility of silicates, such as quartz in water, and in changing the activity of water at such P–T conditions. The difference can shift the depth of dehydration by 6 km for an average low dT/dP geothermal gradient of 325 °C/GPa. The shift in the boundary could be considerably larger for shallower dT/dP slab-top geothermal gradients. The experimental results show a good fit with those from thermodynamic modelling and aqueous geochemical calculation.
Polyphase Zircon Growth during Slow Cooling from Ultrahigh Temperature: an Example from the Archean Pikwitonei Granulite Domain
Authors: Guevara Victor E , MacLennan Scott A , Dragovic Besim , Caddick Mark J , Schoene Blair , Kylander-Clark Andrew R C , Couëslan Chris G
Published: February 2020

Quantifying the timescales of Archean ultrahigh temperature (UHT) metamorphism is essential for constraining the style of plate tectonics on the early Earth. However, such timescales can be difficult to quantify, due to the antiquity of Archean rocks and the extreme thermal conditions of UHT metamorphism. We constrain the timescales of Archean UHT metamorphic processes recorded by a single rock sample from the Pikwitonei granulite domain (northwestern Superior Province), through the integration of two U–Pb zircon petrochronologic techniques. In this study we combine: (1) high-spatial resolution laser ablation split-stream inductively coupled mass spectrometry (LASS) on in situ zircon (in thin section) and hand-picked zircon; and (2) high-precision isotope dilution thermal ionization mass spectrometry (ID-TIMS) analyses on microsampled fragments from the same hand-picked zircon analysed by LASS. Phase equilibria modelling and Zr-in-rutile thermometry suggest the rock followed a P–T path characterized by decompression at > 960 °C, followed by near-isobaric cooling at ∼0·8 GPa. In situ LASS zircon analyses could be interpreted to record zircon growth at broadly ∼2665 Ma, though the large uncertainties on isotopic dates make potentially distinct growth episodes difficult to distinguish. ID-TIMS U–Pb dates of zircon fragments reveal a polyphase zircon growth history over a 24 Ma duration, from 2673 to 2649 Ma. Zircon trace element compositions, textures, and microstructural relationships, as well as evaluation of zircon-garnet equilibrium, suggest zircon grew during melt crystallization, after UHT decompression and garnet resorption. Variable Ti concentrations within zircon domains indicate: (1) zircon crystallized through the temperature interval of ∼875 °C to ∼730 °C, potentially in isolated rock domains with variable zircon saturation temperature; and/or (2) zircon crystallized over a narrower temperature interval in isolated rock domains with variable aTiO2 and/or aSiO2. Collectively, the data suggest the west-central Pikwitonei granulite domain reached peak UHT conditions prior to 2673 Ma, after which suprasolidus conditions in the lower crust persisted for at least 24 Ma. Such an interpretation would be impossible if based on either the LASS or ID-TIMS zircon data alone, which highlights the utility of applying both techniques in tandem to constrain metamorphic timescales in ancient UHT terranes.
On Non-Eliminative Structuralism. Unlabeled Graphs as a Case Study, Part A†
Authors: Leitgeb Hannes
Published: February 2020

This is Part A of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A summarizes the general attractions of non-eliminative structuralism. Afterwards, it motivates an understanding of unlabeled graphs as structures sui generis and develops a corresponding axiomatic theory of unlabeled graphs. As the theory demonstrates, graph theory can be developed consistently without eliminating unlabeled graphs in favour of sets; and the usual structuralist criterion of identity can be applied successfully in graph-theoretic proofs. Part B will turn to the philosophical interpretation and assessment of the theory.
Trichoderma Isolates Inhibit Fusarium virguliforme Growth, Reduce Root Rot, and Induce Defense-Related Genes on Soybean Seedlings
Authors: Pimentel Mirian F. , Arnão Erika , Warner Amanda J. , Subedi Arjun , Rocha Leonardo F. , Srour Ali , Bond Jason P. , Fakhoury Ahmad M.
Published: February 2020

Sudden death syndrome (SDS) caused by Fusarium virguliforme is among the most important diseases affecting soybean in the United States. The use of biological control agents (BCAs) such as Trichoderma spp. can be a valuable resource to suppress F. virguliforme populations. Therefore, this research focused on screening possible BCAs against F. virguliforme and evaluating mycoparasitism and the induction of systemic resistance as mechanisms underlying the antagonistic activity of selected BCAs against F. virguliforme. In total, 47 potential BCAs, including 41 Trichoderma isolates and 6 Mortierella isolates, were screened in a dual-plate assay. The most effective isolates belonged to the Trichoderma harzianum species and were able to inhibit F. virguliforme radial growth by up to 92%. Selected Trichoderma isolates were tested in the greenhouse and in a microplot study. They reduced root rot caused by F. virguliforme when the plants were coinoculated with the pathogen and the BCA. The tested BCA’s ability to reduce F. virguliforme growth may be related to several mechanisms of action, including mycoparasitism and induction of defense-related genes in plants, as revealed by monitoring the expression of defense-related genes in soybean. Our results highlight the potential of native Trichoderma isolates to inhibit F. virguliforme growth and reduce SDS severity, providing the basis for future implementation of biological control in soybean production. More efforts are needed to implement the use of these approaches in production fields, and to deepen the current knowledge on the biology of these highly antagonistic isolates.
Pathogenicity, Symptom Development, and Colonization ofMetrosideros polymorphabyCeratocystis lukuohia
Authors: Hughes Marc A. , Juzwik Jennifer , Harrington Thomas C. , Keith Lisa M.
Published: February 2020

Extensive mortality of Metrosideros polymorpha (`ōhi`a) trees has been associated with Ceratocystis spp. on Hawai`i Island and was named rapid `ōhi`a death (ROD). Both C. lukuohia and C. huliohia have been associated with ROD, although C. lukuohia appears to be the more important pathogen. Crown observations and dissections of forest trees either wound-inoculated with, or naturally infected by, C. lukuohia were conducted to confirm pathogenicity and document patterns of host colonization. In pathogenicity trials, one of three and two of three trees inoculated with the fungus in February and August, respectively, exhibited crown wilt symptoms at 92 and 69 days after inoculation. Extensive, radial, black staining of the sapwood was found in main stems, while no crown wilt or xylem staining was found in control trees. Xylem staining, necrotic phloem, and fungus presence was noted in six trees inoculated in May to June and harvested 37 to 42 days later, and these observations were compared with those in two naturally infected trees felled in early August. Contiguous xylem staining was found in the main stems and into crowns of all diseased trees, while discontinuous streaks of xylem staining extended into the main forks and side branches. Necrotic phloem associated with xylem staining occurred on the lower stems of inoculated trees. Aside from the necrotic phloem and radial staining of the sapwood, symptom development in `ōhi`a infected with C. lukuohia is similar to other systemic wilt diseases on hardwood trees. We propose Ceratocystis wilt of `ōhi`a as the official name of the disease.
Listening Difficulties of Children With Cochlear Implants in Mainstream Secondary Education
Authors: Krijger Stefanie , Coene Martine , Govaerts Paul J. , Dhooge Ingeborg
Published: February 2020

Objectives:

Previous research has shown that children with cochlear implants (CIs) encounter more communication difficulties than their normal-hearing (NH) peers in kindergarten and elementary schools. Yet, little is known about the potential listening difficulties that children with CIs may experience during secondary education. The aim of this study was to investigate the listening difficulties of children with a CI in mainstream secondary education and to compare these results to the difficulties of their NH peers and the difficulties observed by their teachers.

Design:

The Dutch version of the Listening Inventory for Education Revised (LIFE-R) was administered to 19 children (mean age = 13 years 9 months; SD = 9 months) who received a CI early in life, to their NH classmates (n = 239), and to their teachers (n = 18). All participants were enrolled in mainstream secondary education in Flanders (first to fourth grades). The Listening Inventory for Secondary Education consists of 15 typical listening situations as experienced by students (LIFEstudent) during class activities (LIFEclass) and during social activities at school (LIFEsocial). The teachers completed a separate version of the Listening Inventory for Secondary Education (LIFEteacher) and Screening Instrument for Targeting Educational Risk.

Results:

Participants with CIs reported significantly more listening difficulties than their NH peers. A regression model estimated that 75% of the participants with CIs were at risk of experiencing listening difficulties. The chances of experiencing listening difficulties were significantly higher in participants with CIs for 7 out of 15 listening situations. The 3 listening situations that had the highest chance of resulting in listening difficulties were (1) listening during group work, (2) listening to multimedia, and (3) listening in large-sized classrooms. Results of the teacher’s questionnaires (LIFEteacher and Screening Instrument for Targeting Educational Risk) did not show a similar significant difference in listening difficulties between participants with a CI and their NH peers. According to teachers, NH participants even obtained significantly lower scores for staying on task and for participation in class than participants with a CI.

Conclusions:

Although children with a CI seemingly fit in well in mainstream schools, they still experience significantly more listening difficulties than their NH peers. Low signal to noise ratios (SNRs), distortions of the speech signal (multimedia, reverberation), distance, lack of visual support, and directivity effects of the microphones were identified as difficulties for children with a CI in the classroom. As teachers may not always notice these listening difficulties, a list of practical recommendations was provided in this study, to raise awareness among teachers and to minimize the difficulties.
Prognostic effect of implementation of the mass low-dose computed tomography lung cancer screening program: a hospital-based cohort study
Authors: Wu Fu-Zong , Huang Yi-Luan , Wu Yun-Ju , Tang En-Kuei , Wu Ming-Ting , Chen Chi-Shen , Lin Yun-Pei
Published: February 2020

Low-dose computed tomography lung cancer screening aims to detect early-stage lung cancers in order to decrease the incidence of advanced-stage lung cancers and to reduce lung cancer mortality. We analyzed the time trends of lung cancer stage distribution and mortality rates after the gradual implementation of the low-dose computed tomography lung cancer screening in a hospital-based cohort. Using the hospital-based cancer registry data on lung cancer number and death from 2007 to 2014, we aim to evaluate the trends in stage distribution and mortality rate after the gradual implementation of low-dose computed tomography lung cancer screening program over recent years. From 2007 to 2014, overall 2542 cases of lung cancers were diagnosed according to hospital-based cancer registry. For the 1-year mortality rate, the mortality rate decreased gradually from 48.16 to 37.04% between 2007 and 2014. For the 5-year mortality rate, the mortality rate decreased gradually from 88.49 to 69.44% between 2007 and 2014. There was a gradual decrease in stage IV lung cancer with the corresponding sharp increase in stage I early lung cancer after following the implementation of the large volume of the low-dose computed tomography examination between the years 2011 and 2014. In conclusion, these results suggest that the gradual implementation of low-dose computed tomography lung screening program could lead to a remarkable decrease in lung cancer mortality and a remarkable stage shift in the trend over time in this hospital-based cohort.
All-trans retinoic acid suppressed GES-1 cell proliferation induced by exosomes from patients with precancerous lesions by arresting the cell cycle in S-phase
Authors: Gao Lei , He Yue , Wang Kexin , Wang Chen , Wu Hanhan , Hu Anla , Ruan Liang , Bo Qingli , Chen Wenjun , Hu Chuanlai , Li Li , Zhang Daoming , Xia Tao , Qian Shiqing , Liu Zhining , Yang Yi , Yang Wanshui , Wang Hua , Zhao Qihong
Published: February 2020

We aimed to detect the expression of specific LncRNAs in exosomes isolated from the serum of patients with precancerous lesions and to study the effect of these serum exosomes on the activity of GES-1 cells in patients with precancerous lesions, as well as the activity of all-trans retinoic acid on GES-1 cells with or without the exosomes. Exosomes were extracted from the serum of patients with precancerous lesions and normal controls. Based on our previous sequencing results, quantitative real time-PCR was used to detect differentially expressed LncRNAs. Exosomes from the serum of patients with precancerous lesions were cocultured with GES-1 cells, and 5 μM all-trans retinoic acid was added as an intervention. Changes in cell viability and expression of LncHOXA10 were observed. Compared with the blank group, the proliferation activity of GES-1 cells cocultured with exosomes derived from the serum of patients with precancerous lesions was increased (P < 0.01), the proportion of cells in S phase was increased (P < 0.05). After adding 5 μM all-trans retinoic acid, the viability of cells decreased significantly (P < 0.01), the proportion of cells in S phase decreased significantly (P < 0.05). The expression of LncHOXA10 was decreased (P < 0.05). All-trans retinoic acid can conduct its chemopreventive effects by inhibiting the expression of LncHOXA10, thereby reducing the activity of LncHOXA10 in GES-1 cells cocultured with serum exosomes from patients with precancerous lesions.
International Consensus Definition of Low Anterior Resection Syndrome
Authors: Keane Celia , Fearnhead Nicola S. , Bordeianou Liliana G. , Christensen Peter , Basany Eloy Espin , Laurberg Søren , Mellgren Anders , Messick Craig , Orangio Guy R. , Verjee Azmina , Wing Kirsty , Bissett Ian
Published: February 2020

BACKGROUND:

Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience.

OBJECTIVE:

The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders.

DESIGN:

This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting.

PARTICIPANTS:

Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish).

MAIN OUTCOME MEASURE:

The primary outcome measured was the priorities for the definition of low anterior resection syndrome.

RESULTS:

Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome.

LIMITATIONS:

Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this.

CONCLUSIONS:

This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention.
Pulmonary Delivery of Antiarrhythmic Drugs for Rapid Conversion of New-Onset Atrial Fibrillation
Authors: Verrier Richard L. , Belardinelli Luiz
Published: February 2020

Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.
Urinary Tract Infections With Extended-spectrum-β-lactamase-producing Bacteria
Authors: Amin Omayma , Prestel Christopher , Gonzalez Mark D. , Lyon Tabitha , Shane Andi , Jaggi Preeti , Tippett Ashley , Yildirim Inci
Published: February 2020

Background:

Urinary tract infections (UTI) are the most common bacterial infections among infants and young children with fever without a source. Extended-spectrum β-lactamases (ESBLs) have emerged as emerging cause of UTI globally; however, data about risk factors and clinical features of children with ESBL-UTI have been scarce.

Objective:

To describe the predisposing risk factors, clinical and microbiologic features associated with pediatric UTIs caused by ESBL-producing bacteria (ESBL-PB).

Methods:

Our nested case-control study ran from January 1, 2012 to December 31, 2016. Pediatric patients with ESBL-PB UTI were compared with patients with non-ESBL-PB UTI matched for age and year of diagnosis.

Results:

A total of 720 children were enrolled (240 cases and 480 controls). Patients with ESBL-PB UTI were more likely to have a history of prior intensive care unit (ICU) admission (22.5% vs. 12.3%, P < 0.001), at least one underlying comorbidity (19.2% vs. 5.8%, P < 0.001), prior hospitalization (47.1% vs. 32.9%, P < 0.001), exposure to a cephalosporin antibiotic within 30 days before culture (7.5% vs. 4.2%, P = 0.035), and to have cystostomy (7.9% vs. 1.5%, P < 0.001) compared with those with non-ESBL-PB UTI. Patients with ESBL-PB UTI were more likely to present with hypothermia (48.8% vs. 38.5%, P = 0.009); had significantly longer average hospital stays {8.7 days [95% confidence interval (CI): 3.2–14.3] vs. 4.0 days (95% CI: 2.5–5.5)} and were more likely to be admitted to the ICU [odds ratio (OR) 1.8; 95% CI: 1.1-2.9). Multivariate analysis determined that only having cystostomy (OR 3.7; 95% CI: 1.4–9.4] and at least one underlying comorbidity (OR 2.4; 95% CI: 1.3–4.3) were the independent risk factors for ESBL-PB UTI. All ESBL-PB isolates tested against meropenem were susceptible, majority were resistant to multiple non-beta-lactam antibiotics.

Conclusions:

Children with underlying comorbidities and cystostomy are at higher risk for ESBL-PB UTI, but majority of ESBL cases were patients without any known risk factors. Clinical signs/symptoms and commonly used biochemical markers were unreliable to differentiate cases caused by ESBL-PB from those caused by non-ESBL-PB. Further research is needed to elucidate the conditions most associated with ESBL-PB UTIs among children to properly guide empirical therapy in patients at-risk for these infections, to improve the outcomes, and finally, to determine strategies for rational antimicrobial use.
Neonatal Outcomes Following Culture-negative Late-onset Sepsis Among Preterm Infants
Authors: Jiang Siyuan , Yang Zuming , Shan Ruobing , Zhang Yi , Yan Weili , Yang Yi , Shah Prakesh S. , Lee Shoo K. , Cao Yun
Published: February 2020

Background:

Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants.

Methods:

We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) ≥ stage 3 or bronchopulmonary dysplasia (BPD).

Results:

Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5–2.1]}, PVL [aOR: 2.0 (95% CI: 1.4–2.8)] and BPD [aOR: 1.8 (95% CI: 1.5–2.2)] relative to the absence of LOS.

Conclusion:

Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.
Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis
Authors: Berkhout Daniel J.C. , Niemarkt Hendrik J. , Andriessen Peter , Vijlbrief Daniel C. , Bomers Marije K. , Cossey Veerle , Hulzebos Christian V. , van Kaam Anton H. , Kramer Boris W. , van Lingen Richard A. , Wicaksono Alfian N. , Covington James A. , van Weissenbruch Mirjam M. , Benninga Marc A. , de Boer Nanne K.H. , de Meij Tim G.J.
Published: February 2020

Background:

Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC.

Methods:

In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter–related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry.

Results:

In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter–related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11).

Conclusions:

Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.
Bedaquiline and Delamanid in Children With XDR Tuberculosis: What is prolonged QTc?
Authors: Shah Ira , Gandhi Srushti , Shetty Naman S.
Published: February 2020

Bedaquiline and delamanid used to treat extensively drug-resistant tuberculosis are known to cause prolonged QTc. Two children with extensively drug-resistant tuberculosis were put on bedaquiline and delamanid and had prolonged QTc on the Bazett formula but normal QTc by the Fridericia formula. Both had no adverse effects. Correct formula for monitoring QTc should be used thereby preventing unnecessary withholding of medicines.
Burden of Injury and Illness in the Road Race Medical Tent: A Narrative Review
Authors: Breslow Rebecca G. , Giberson-Chen Carew C. , Roberts William O.
Published: February 2020

Objective:

To summarize the literature relating to prehospital care at 5 km through marathon distance road races and present the epidemiology of common medical encounters, significant medical complications, and medical outcomes.

Data Sources:

We searched PubMed and Google Scholar for the published literature pertaining to road race medical tent encounters at 5 km through marathon distance road races from 2000 to 2018. We included English-language, original articles reporting on injury and illness incidence.

Main Results:

Standard medical encounter definitions have recently been formulated in response to the previous lack of uniform definitions. The incidence of medical complications at road races may be influenced by environmental conditions and race distance. Minor and moderate medical encounters, such as dermatologic injuries, musculoskeletal injuries, and exercise-associated collapse, are common. Serious and life-threatening medical complications, including exertional heat stroke, exercise-associated hyponatremia, and cardiac arrest, are less frequent. Fatalities are also rare, with rates of 0.3 to 5 per 100 000 participants reported at marathons. The ratio of hospital transports to medical encounters is low.

Conclusions:

On-site medical services play a key role in the safety of both runners and the community. Future research and care initiatives in this field should focus on optimizing treatment protocols, promoting injury prevention efforts and reducing host community costs.
Short-Term Outcome Predictors in Patients With Primary Adhesive Capsulitis Treated With Ultrasound-Guided Hydrodilatation With Corticosteroids
Authors: Yang Chen-Ya , Fu Li-Heng , Lee Chao-Chung , Wang Kevin A. , Chou Chen-Liang , Wang Jia-Chi
Published: February 2020

Objective

Glenohumeral joint hydrodilatation with corticosteroids has been proposed as an effective secondary therapeutic procedure for primary adhesive capsulitis. However, little is known about which subgroup of patients would benefit from this procedure. This study aimed to identify covariates associated with improved prognosis in patients receiving ultrasound-guided hydrodilatation with corticosteroid injection.

Design

This was a cohort study. Data on baseline demographic characteristics, disease status, past medical conditions, and initial ultrasonographic findings were collected. Linear and logistic regression analyses were performed to determine the prognostic factors associated with better clinical outcomes.

Results

Fifty-three patients (54 shoulders) were included. Linear regression analysis showed that coracohumeral ligament thickness of less than 3 mm, use of analgesics before hydrodilatation, and female sex were associated with good improvement in the Shoulder Pain and Disability Index score. Multivariate logistic regression analysis showed that coracohumeral ligament thickness of less than 3 mm on ultrasound was associated with a strong tendency (P = 0.054) of reaching the minimal detectable change. In addition, capsule rupture did not play a role in determining the clinical efficacy of hydrodilatation.

Conclusions

In patients with primary adhesive capsulitis, coracohumeral ligament thickness of less than 3 mm is correlated with greater short-term improvement in the Shoulder Pain and Disability Index score after ultrasound-guided hydrodilatation with steroid injection is performed.
Persistent Immune Activation in HIV-1–Infected Ex Vivo Model Tissues Subjected to Antiretroviral Therapy: Soluble and Extracellular Vesicle-Associated Cytokines
Authors: Mercurio Vincenzo , Fitzgerald Wendy , Molodtsov Ivan , Margolis Leonid
Published: February 2020

Background:

Residual immune activation after successful antiretroviral therapy (ART) in HIV-1–infected patients is associated with the increased risk of complications. Cytokines, both soluble and extracellular vesicle (EV)-associated, may play an important role in this immune activation.

Setting:

Ex vivo tissues were infected with X4LAI04 or R5SF162 HIV-1. Virus replicated for 16 days, or tissues were treated with the anti-retroviral drug ritonavir.

Methods:

Viral replication and production of 33 cytokines in soluble and EV-associated forms were measured with multiplexed bead-based assays.

Results:

Both variants of HIV-1 efficiently replicated in tissues and triggered upregulation of soluble cytokines, including IL-1β, IL-7, IL-18, IFN-γ, MIP-1α, MIP-1β, and RANTES. A similar pattern was observed in EV-associated cytokine release by HIV-infected tissues. In addition, TNF-α and RANTES demonstrated a significant shift to a more soluble form compared with EV-associated cytokines. Ritonavir treatment efficiently suppressed viral replication; however, both soluble and EV-associated cytokines remained largely upregulated after 13 days of treatment. EV-associated cytokines were more likely to remain elevated after ART. Treatment of uninfected tissues with ritonavir itself did not affect cytokine release.

Conclusions:

We demonstrated that HIV-1 infection of ex vivo lymphoid tissues resulted in their immune activation as evaluated by upregulation of various cytokines, both soluble and EV-associated. This upregulation persisted despite inhibition of viral replication by ART. Thus, similar to in vivo, HIV-1–infected human tissues ex vivo continue to be immune-activated after viral suppression, providing a new laboratory model to study this phenomenon.
Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn's Disease: The SuPREMe-CD Study - A Randomized Clinical Trial
Authors: Luglio Gaetano , Rispo Antonio , Imperatore Nicola , Giglio Mariano Cesare , Amendola Alfonso , Tropeano Francesca Paola , Peltrini Roberto , Castiglione Fabiana , De Palma Giovanni Domenico , Bucci Luigi
Published: February 2020

Objective:

This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and stapled ileocolic side-to-side anastomosis.

Background:

Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence score and surgical recurrence rate in Crohn disease (CD).

Methods:

Randomized controlled trial (RCT) at a tertiary referral institution. Primary endpoint: endoscopic recurrence (ER) (Rutgeerts score ≥i2) after 6 months. Secondary endpoints: clinical recurrence (CR) after 12 and 24 months, ER after 18 months, and surgical recurrence (SR) after 24 months.

Results:

In all, 79 ileocolic CD patients were randomized in Kono group (36) and Conventional group (43). After 6 months, 22.2% in the Kono group and 62.8% in the Conventional group presented an ER [P < 0.001, odds ratio (OR) 5.91]. A severe postoperative ER (Rutgeerts score ≥i3) was found in 13.8% of Kono versus 34.8% of Conventional group patients (P = 0.03, OR 3.32). CR rate was 8% in the Kono group versus 18% in the Conventional group after 12 months (P = 0.2), and 18% versus 30.2% after 24 months (P = 0.04, OR 3.47). SR rate after 24 months was 0% in the Kono group versus 4.6% in the Conventional group (P = 0.3). Patients with Kono-S anastomosis presented a longer time until CR than patients with side-to-side anastomosis (hazard ratio 0.36, P = 0.037). On binary logistic regression analysis, the Kono-S anastomosis was the only variable significantly associated with a reduced risk of ER (OR 0.19, P < 0.001). There were no differences in postoperative outcomes.

Conclusions:

This is the first RCT comparing Kono-S anastomosis and standard anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and clinical recurrence rate for patients who underwent Kono-S anastomosis, and no safety issues.

ClinicalTrials.gov ID NCT02631967.
The Implications of B-lineage Cells in Kidney Allografts
Authors: Filippone Edward J. , Farber John L.
Published: February 2020

The majority of cells comprising the inflammatory infiltrates in kidney allografts undergoing acute and/or chronic rejection are typically T cells and monocyte/macrophages with B cells, plasma cells, and eosinophils accounting for <5%. In a significant minority of biopsies, B lineage cells (B cells and/or plasma cells) may be found more abundantly. Although plasma cell infiltrates tend to be more diffuse, B cells tend to aggregate into nodules that may mature into tertiary lymphoid organs. Given the ability to target B cells with anti-CD20 monoclonal antibodies and plasma cells with proteasome inhibitors and anti-CD38 monoclonal antibodies, it is increasingly important to determine the significance of such infiltrates. Both cell types are potential effectors of rejection, but both also have a tolerizing potential. B cell infiltrates have been associated with steroid resistance and reduced graft survival in some studies but not in others, and their presence should not prompt automatic depletional therapy. Plasma cell–rich infiltrates tend to occur later, may be associated with cell-mediated and/or antibody-mediated rejection, and portend an adverse outcome. Viral infection and malignancy must be ruled out. Randomized controlled trials are needed to determine the appropriateness of specific therapy when B cells and/or plasma cells are found. No strong therapeutic recommendations can be made at this time.
Lateralised cerebral processing of abstract linguistic structure in clear and degraded speech
Authors: Meng Qingqing , Hegner Yiwen Li , Giblin Iain , McMahon Catherine , Johnson Blake W
Published: February 2020

Providing a plausible neural substrate of speech processing and language comprehension, cortical activity has been shown to track different levels of linguistic structure in connected speech (syllables, phrases and sentences), independent of the physical regularities of the acoustic stimulus. In the current study, we investigated the effect of speech intelligibility on this brain activity as well as the underlying neural sources. Using magnetoencephalography (MEG), brain responses to natural speech and noise-vocoded (spectrally-degraded) speech in nineteen normal hearing participants were measured. Results showed that cortical MEG coherence to linguistic structure changed parametrically with the intelligibility of the speech signal. Cortical responses coherent with phrase and sentence structures were lefthemisphere lateralized, whereas responses coherent to syllable/word structure were bilateral. The enhancement of coherence to intelligible compared to unintelligible speech was also left lateralized and localized to the parasylvian cortex. These results demonstrate that cortical responses to higher level linguistics structures (phrase and sentence level) are sensitive to speech intelligibility. Since the noise-vocoded sentences simulate the auditory input provided by a cochlear implant, such objective neurophysiological measures have potential clinical utility for assessment of cochlear implant performance.
Parallel lemniscal and non-lemniscal sources control auditory responses in the orbitofrontal cortex (OFC)
Authors: Srivastava Hemant K , Bandyopadhyay Sharba
Published: February 2020

The orbitofrontal cortex (OFC), controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown, in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure deviance detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed deviance detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or the amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus the baseline sensory responses allow the behavioral requirement based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurological disorders can lead to behavioral deficits.
Translational control of methionine and serine metabolic pathways underpin the paralog-specific phenotypes of Rpl22 ribosomal protein mutants in cell division and replicative longevity
Authors: Maitra Nairita , He Chong , Blank Heidi M. , Tsuchiya Mitsuhiro , Schilling Birgit , Kaeberlein Matt , Aramayo Rodolfo , Kennedy Brian K. , Polymenis Michael
Published: February 2020

A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Some may reflect general effects due to lower growth rate and ribosome levels, but a number of diverse phenotypes cannot be explained through this mechanism. Yeast and other organisms live longer when they lack specific ribosomal proteins, especially of the large 60S subunit of the ribosome. However, longevity is neither associated with the generation time of RP deletion mutants nor with bulk inhibition of protein synthesis. Here, we comprehensively queried actively dividing RP paralog mutants through the cell cycle. Our data link transcriptional, translational, and metabolic changes to phenotypes associated with the loss of paralogous RPs. We uncovered specific translational control of transcripts encoding enzymes of methionine and serine metabolism, which are part of one-carbon (1C) pathways. Cells lacking Rpl22Ap, which are long-lived, have lower levels of metabolites associated with 1C metabolism. Loss of 1C enzymes, such as the serine hydroxymethyltransferase Shm2p increased the longevity of wild type cells. These results provide a molecular basis for paralog-specific phenotypes in ribosomal mutants and underscore the significance of 1C metabolic pathways in mechanisms of cell division and cellular aging. 1C pathways exist in all organisms, including humans, and targeting the relevant enzymes could represent longevity interventions.
A hierarchical transcriptional network controls appressorium-mediated plant infection by the rice blast fungus Magnaporthe oryzae
Authors: Oses-Ruiz Miriam , Martin-Urdiroz Magdalena , Soanes Darren M , Kershaw Michael J , Cruz-Mireles Neftaly , Valdovinos-Ponce Guadalupe , Molinari Camilla , Littlejohn George R , Derbyshire Paul , Menke Frank , Valent Barbara , Talbot Nicholas J
Published: February 2020

Rice blast is a pervasive and devastating disease that threatens rice production across the world. In spite of its importance to global food security, however, the underlying biology of plant infection by the blast fungus Magnaporthe oryzae remains poorly understood. In particular, it is unclear how the fungus elaborates a specialised infection cell, the appressorium, in response to surface signals from the rice leaf. Here, we report the identification of a network of temporally co-regulated transcription factors that act downstream of the Pmk1 mitogen-activated protein kinase pathway to regulate gene expression during appressorium-mediated plant infection. We have functionally characterised this network of transcription factors and demonstrated the operation of a hierarchical transcriptional control system. We show that this tiered regulatory mechanism involves Pmk1-dependent phosphorylation of the Hox7 homeobox transcription factor, which represses hyphal-associated gene expression and simultaneously induces major physiological changes required for appressorium development, including cell cycle arrest, autophagic cell death, turgor generation and melanin biosynthesis. Mst12 then regulates gene functions involved in septin-dependent cytoskeletal re-organisation, polarised exocytosis and effector gene expression necessary for plant tissue invasion.
Pharmacological inhibition of longevity regulator PAPP-A restrains mesenchymal stromal cell activity
Authors: Mohrin Mary , Liu Justin , Zavala-Solorio Jose , Bhargava Sakshi , Trumble John Maxwell , Brito Alyssa , Hu Dorothy , Brooks Daniel , Bouxsein Mary L. , Baron Roland , Kutskova Yuliya , Freund Adam
Published: February 2020

Reducing insulin-like growth factor (IGF) signaling is one of the best conserved and characterized mechanisms to extend longevity. Pregnancy associated plasma protein A (PAPP-A) is a secreted metalloprotease that increases IGF availability by cleaving IGF binding proteins. PAPP-A inhibition reduces local IGF signaling, limits the progression of multiple age-related diseases, and extends lifespan, but the mechanisms behind these pleiotropic effects remains unknown. Here, we developed and utilized a PAPP-A neutralizing antibody to discover that adulthood inhibition of this protease reduced collagen and extracellular matrix (ECM) gene expression in multiple tissues in mice. Using bone marrow to explore this effect, we identified mesenchymal stromal cells (MSCs) as the source of PAPP-A and primary responders to PAPP-A inhibition. Short-term treatment with anti-PAPP-A reduced IGF signaling in MSCs, altered MSC expression of collagen/ECM, and decreased MSC number. This affected MSC-dependent functions, decreasing myelopoiesis and osteogenesis. Our data demonstrate that PAPP-A inhibition reduces the activity and number of IGF-dependent mesenchymal progenitor cells and their differentiated progeny, and that this reduction leads to functional changes at the tissue level. MSC-like cells are present in virtually all tissues, and aberrant collagen and ECM production from mesenchymal cells drives aspects of aging and age-related diseases, thus this may be a mechanism by which PAPP-A deficiency enhances lifespan and healthspan.

Inhibition of PAPP-A, a regulator of IGF signaling, decreases multi-tissue collagen and extracellular matrix gene expression and modulates mesenchymal stromal cell activity in murine bone marrow.
Dynamic control of visually-guided locomotion through cortico-subthalamic projections
Authors: Adam Elie M. , Johns Taylor , Sur Mriganka
Published: February 2020

Goal-directed locomotion requires control signals that propagate from higher-order areas to regulate spinal mechanisms. The cortico-subthalamic hyperdirect pathway offers a short route for cortical information to reach locomotor centers in the brainstem. We developed a task where head-fixed mice run to a visual landmark then stop and wait to collect reward, and examined the role of secondary motor cortex (M2) projections to the subthalamic nucleus (STN) in controlling locomotion. Our modeled behavioral strategy indicates a switching point in behavior or a sudden change from running to stopping, suggesting a critical neuronal control signal at stop locations. Optogenetic activation of M2 axons in STN leads the animal to stop prematurely. By imaging M2 neurons projecting to STN, we find neurons that are active at the onset of stops when executed at the landmark but not when executed spontaneously elsewhere. Our results suggest that the M2-STN pathway can be recruited during visually-guided locomotion to rapidly and precisely control the mesencephalic locomotor region (MLR) through the basal ganglia. By capturing the physiological dynamics through a feedback control model and analyzing neuronal signals in M2, MLR and STN, we find that the cortico-subthalamic projections potentially control MLR activity by differentiating an M2 error signal to ensure fast input-output dynamics.