bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn’s Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial
Authors: Matar Manar , Shamir Raanan , Turner Dan , Broide Efrat , Weiss Batia , Ledder Oren , Guz-Mark Anat , Rinawi Firas , Cohen Shlomi , Topf-Olivestone Chani , Shaoul Ron , Yerushalmi Baruch , Ben-Horin Shomron , Assa Amit
Published: December 2019

Background

The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction.

Methods

Participants were children 6–17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies.

Results

Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group.

Conclusions

Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).
Inhibitory Control of Basolateral Amygdalar Transmission to the Prefrontal Cortex by Local Corticotrophin Type 2 Receptor
Authors: Yarur Hector E , Vega-Quiroga Ignacio , González Marcela P , Noches Verónica , Thomases Daniel R , Andrés María E , Ciruela Francisco , Tseng Kuei Y , Gysling Katia
Published: December 2019

Background

Basolateral amygdalar projections to the prefrontal cortex play a key role in modulating behavioral responses to stress stimuli. Among the different neuromodulators known to impact basolateral amygdalar-prefrontal cortex transmission, the corticotrophin releasing factor (CRF) is of particular interest because of its role in modulating anxiety and stress-associated behaviors. While CRF type 1 receptor (CRFR1) has been involved in prefrontal cortex functioning, the participation of CRF type 2 receptor (CRFR2) in basolateral amygdalar-prefrontal cortex synaptic transmission remains unclear.

Methods

Immunofluorescence anatomical studies using rat prefrontal cortex synaptosomes devoid of postsynaptic elements were performed in rats with intra basolateral amygdalar injection of biotinylated dextran amine. In vivo microdialysis and local field potential recordings were used to measure glutamate extracellular levels and changes in long-term potentiation in prefrontal cortex induced by basolateral amygdalar stimulation in the absence or presence of CRF receptor antagonists.

Results

We found evidence for the presynaptic expression of CRFR2 protein and mRNA in prefrontal cortex synaptic terminals originated from basolateral amygdalar. By means of microdialysis and electrophysiological recordings in combination with an intra-prefrontal cortex infusion of the CRFR2 antagonist antisauvagine-30, we were able to determine that CRFR2 is functionally positioned to limit the strength of basolateral amygdalar transmission to the prefrontal cortex through presynaptic inhibition of glutamate release.

Conclusions

Our study shows for the first time to our knowledge that CRFR2 is expressed in basolateral amygdalar afferents projecting to the prefrontal cortex and exerts an inhibitory control of prefrontal cortex responses to basolateral amygdalar inputs. Thus, changes in CRFR2 signaling are likely to disrupt the functional connectivity of the basolateral amygdalar-prefrontal cortex pathway and associated behavioral responses.
Eigenvector Convergence for Minors of Unitarily Invariant Infinite Random Matrices
Authors: Najnudel Joseph
Published: December 2019

In [10], Pickrell fully characterizes the unitarily invariant probability measures on infinite Hermitian matrices. An alternative proof of this classification is given by Olshanski and Vershik in [9], and in [3] Borodin and Olshanski deduce from this proof that under any of these invariant measures, the extreme eigenvalues of the minors, divided by the dimension, converge almost surely. In this paper, we prove that one also has a weak convergence for the eigenvectors, in a sense that is made precise. After mapping Hermitian to unitary matrices via the Cayley transform, our result extends a convergence proven in our paper with Maples and Nikeghbali [6], for which a coupling of the circular unitary ensemble of all dimensions is considered.
Transcriptomic Profiles of Confirmed Pediatric Tuberculosis Patients and Household Contacts Identifies Active Tuberculosis, Infection, and Treatment Response Among Indian Children
Authors: Tornheim Jeffrey A , Madugundu Anil K , Paradkar Mandar , Fukutani Kiyoshi F , Queiroz Artur T L , Gupte Nikhil , Gupte Akshay N , Kinikar Aarti , Kulkarni Vandana , Balasubramanian Usha , Sreenivasamurthy Sreelakshmi , Raja Remya , Pradhan Neeta , Shivakumar Shri Vijay Bala Yogendra , Valvi Chhaya , Hanna Luke Elizabeth , Andrade Bruno B , Mave Vidya , Pandey Akhilesh , Gupta Amita ,   CTRIUMPh RePORT India Study Team
Published: December 2019

Background

Gene expression profiling is emerging as a tool for tuberculosis diagnosis and treatment response monitoring, but limited data specific to Indian children and incident tuberculosis infection (TBI) exist.

Methods

Sixteen pediatric Indian tuberculosis cases were age- and sex-matched to 32 tuberculosis-exposed controls (13 developed incident TBI without subsequent active tuberculosis). Longitudinal samples were collected for ribonucleic acid sequencing. Differential expression analysis generated gene lists that identify tuberculosis diagnosis and tuberculosis treatment response. Data were compared with published gene lists. Population-specific risk score thresholds were calculated.

Results

Seventy-one genes identified tuberculosis diagnosis and 25 treatment response. Within-group expression was partially explained by age, sex, and incident TBI. Transient changes in gene expression were identified after both infection and treatment. Application of 27 published gene lists to our data found variable performance for tuberculosis diagnosis (sensitivity 0.38–1.00, specificity 0.48–0.93) and treatment response (sensitivity 0.70–0.80, specificity 0.40–0.80). Our gene lists found similarly variable performance when applied to published datasets for diagnosis (sensitivity 0.56–0.85, specificity 0.50–0.85) and treatment response (sensitivity 0.49– 0.86, specificity 0.50–0.84).

Conclusions

Gene expression profiles among Indian children with confirmed tuberculosis were distinct from adult-derived gene lists, highlighting the importance of including distinct populations in differential gene expression models.
Teaching International Relations through the Format of a Massive Open Online Course (MOOC)
Authors: Kaempf Sebastian , Finn Carrie
Published: December 2019

Since the early twenty-first century, tertiary education has witnessed a dramatic shift with the rise of massive open online courses (MOOCs). Celebrated by some as the ultimate “democratization” of education, this development has not been without controversy. The main purpose of this article is neither to confirm nor dispel the controversies rather it seeks to critically examine one MOOC to encourage more nuanced reflections about teaching international relations through this new format. The case study presented here is of “MEDIAWARx,” a MOOC offered on edX in the IR field since 2017. This article provides an in-depth view into the pedagogical aims and design as well as the response to and experience of one specific MOOC.
Probing the ionosphere by the pulsar B0950+08 with help of RadioAstron ground-space baselines
Authors: Zhuravlev Vladimir I , Yermolaev Yu I , Andrianov A S
Published: December 2019

The ionospheric scattering of pulses emitted by PSR B0950+08 is measured using the 10-mRadioAstron Space Radio Telescope, the 300-m Arecibo Radio Telescope, and the 14 x 25-m Westerbork Synthesis Radio Telescope (WSRT) at a frequency band between 316 and 332 MHz. We analyse this phenomenon based on a simulated model of the phase difference obtained between antennas that are widely separated by nearly 25 Earth diameters. We present a technique for processing and analysing the ionospheric total electron content (TEC) at the ground stations of the ground-space interferometer. This technique allows us to derive almost synchronous half-hour structures of the TEC in the ionosphere at an intercontinental distance between the Arecibo and WSRT stations. We find that the amplitude values of the detected structures are approximately twice as large as the values for the TEC derived in the international reference ionosphere (IRI) project. Furthermore, the values of the TEC outside these structures are almost the same as the corresponding values found by the IRI. According to a preliminary analysis, the detected structures were observed during a geomagnetic storm with a minimum Dst index of ∼75 nT generated by interplanetary disturbances, and may be due to the influence of interplanetary and magnetospheric phenomena on ionospheric disturbances. We show that the Space Very Long Baseline Interferometry provides us with new opportunities to study the TEC, and we demonstrate the capabilities of this instrument to research the ionosphere.
Globular clusters in the stellar stream surrounding the Milky Way analogue NGC 5907
Authors: Alabi Adebusola B , Forbes Duncan A , Romanowsky Aaron J , Brodie Jean P
Published: December 2019

We study the globular clusters (GCs) in the spiral galaxy NGC 5907 well-known for its spectacular stellar stream – to better understand its origin. Using wide-field Subaru/Suprime-Cam gri images and deep Keck/DEIMOS multi-object spectroscopy, we identify and obtain the kinematics of several GCs superimposed on the stellar stream and the galaxy disc. We estimate the total number of GCs in NGC 5907 to be 154 ± 44, with a specific frequency of 0.73 ± 0.21. Our analysis also reveals a significant, new population of young star cluster candidates found mostly along the outskirts of the stellar disc. Using the properties of the stream GCs, we estimate that the disrupted galaxy has a stellar mass similar to the Sagittarius dwarf galaxy accreted by the Milky Way, i.e. $\sim 10^8~\rm M_\odot$.
Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes
Authors: Ávila-Arcos María C , McManus Kimberly F , Sandoval Karla , Rodríguez-Rodríguez Juan Esteban , Villa-Islas Viridiana , Martin Alicia R , Luisi Pierre , Peñaloza-Espinosa Rosenda I , Eng Celeste , Huntsman Scott , Burchard Esteban G , Gignoux Christopher R , Bustamante Carlos D , Moreno-Estrada Andrés
Published: December 2019

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico’s Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations.
Predicting occupational allergy in culinary and hairdressing apprentices
Authors: Lipińska-Ojrzanowska A , Walusiak-Skorupa J , Nowakowska-Świrta E , Wiszniewska M
Published: December 2019

Background

Apprentices are usually exposed to the same workplace agents as qualified professionals. There is therefore a risk of the development of occupational allergy in apprentices exposed to high (HMW-A) and low molecular inhalant allergens (LMW-A).

Aims

To evaluate and compare the occurrence of work-related allergy-like symptoms in apprentices exposed to HMW-A and LMW-A in a culinary and hairdressing school during the first and second year of vocational training.

Methods

We asked culinary and hairdressing apprentices in their first and second year of vocational training to complete a questionnaire about work-related allergy-like symptoms. In first-year apprentices, we undertook spirometry, skin prick tests for occupational allergens and blood tests for allergen-specific Immunoglobulin E (IgE) antibodies.

Results

Hypersensitivity to occupational allergens was more frequent in first-year apprentices exposed to HMW-A compared to LMW-A (P < 0.05). Apprentices exposed to LMW-A reported increasing occurrence of skin disorders and upper respiratory tract symptoms between the first and second years of training. First-year apprentices exposed to HMW-A more frequently reported rhino-conjunctivitis and dyspnoea (approximately P < 0.001 and P < 0.05) and those exposed to LMW-A more often reported skin symptoms (P < 0.05).

Conclusions

Periodic skin and respiratory health surveillance for apprentices exposed to LMW-A or HMW-A might help with early identification and management of occupational allergy.
Provider perspectives on a clinical demonstration project to transition patients with stable mental health conditions to primary care
Authors: Fletcher Terri L , Johnson Adrienne L , Kim Bo , Yusuf Zenab , Benzer Justin , Smith Tracey
Published: December 2019

Research to improve access to mental healthcare often focuses on increasing timely referrals from primary care (PC) to specialty mental health (SMH). However, timely and appropriate transitions back to PC are indispensable for increasing access to SMH for new patients. We developed and implemented a formalized process to identify patients eligible for transition from SMH to PC. The FLOW intervention was piloted at a Veterans Health Administration community-based outpatient clinic. Qualitatively examine provider perspectives regarding patient transitions at initiation and termination of the FLOW project. Sixteen mental health providers and three PC staff completed qualitative interviews about the benefits and drawbacks of FLOW at initiation. Ten mental health providers and one PC staff completed interviews at 12-month follow-up. Primary benefits anticipated at initiation were that FLOW would increase access to SMH, provide acknowledgment of veterans’ recovery, and differentiate between higher and lower intensity mental health services. SMH providers reported additional perceived benefits at 12-month follow-up, including decreased stress over their caseloads and increased ability to deliver efficient, effective treatment. Anticipated drawbacks at initiation were that veterans would get inconsistent care, PC could not offer the same level of care as SMH, and veterans might view transition as a rejection by their SMH provider. Perceived drawbacks were similar at 12-month follow-up, but there was less frequent endorsement. Findings highlight need for sustained and frequent provider education regarding (i) the appropriate characteristics of individuals eligible for transition and (ii) established procedures to ensure care coordination during and after transition.
Sustainability of a biobehavioral intervention implemented by therapists and sustainment in community settings
Authors: Ryba Marlena M , Lo Stephen B , Andersen Barbara L
Published: December 2019

The ultimate aim of dissemination and implementation of empirically supported treatments (ESTs) in behavioral medicine is (a) sustainability of the therapist/provider’s EST usage and (b) sustainment of EST delivery in the setting. Thus far, sustainability has been understudied, and the therapist and setting variables that may be influential are unclear. The purpose of the study was to test the therapists’ sustainability of a cancer-specific EST using a prospective longitudinal design and examine its predictors. Oncology mental health therapists (N = 134) from diverse settings (N = 110) completed training in the biobehavioral intervention (BBI) and were provided with 6 months of support for implementation, with no support thereafter. BBI usage (percent of patients treated) was reported at 2, 4, 6, and 12 months. Using a generalized estimating equation with a logistic link function, 12-month sustainability (a nonsignificant change in usage from 6 to 12 months) was studied along with therapist, supervisor, and setting variables as predictors. BBI usage increased through 6 months and, importantly, usage was sustained from 6 (68.4% [95% CI = 62.2%–73.9%]) to 12 months (70.9% [95% CI = 63.6%–77.3%]), with sustainment in 66 settings (60.0%). Predictors of implementation-to-sustainability usage were therapists’ early intentions to use the BBI (p < .001) and from the setting, supervisors’ positive attitudes toward ESTs (p = .016). Adding to the DI literature, a health psychology intervention was disseminated, implemented, and found sustainable across diverse therapists and settings. Therapists and setting predictors of usage, if modified, might facilitate future sustainability/sustainment of ESTs.
Transcription-independent Induction of ERBB1 through Hypoxia-inducible Factor 2A Provides Cardioprotection during Ischemia and Reperfusion
Authors: Lee Jae W. , Koeppen Michael , Seo Seong-Wook , Bowser Jessica L. , Yuan Xiaoyi , Li Jiwen , Sibilia Maria , Ambardekar Amrut V. , Zhang Xu , Eckle Tobias , Yoo Seung-Hee , Eltzschig Holger K.
Published: December 2019

Background

During myocardial ischemia, hypoxia-inducible factors are stabilized and provide protection from ischemia and reperfusion injury. Recent studies show that myocyte-specific hypoxia-inducible factor 2A promotes myocardial ischemia tolerance through induction of epidermal growth factor, amphiregulin. Here, the authors hypothesized that hypoxia-inducible factor 2A may enhance epidermal growth factor receptor 1 (ERBB1) expression in the myocardium that could interface between growth factors and its effect on providing tolerance to ischemia and reperfusion injury.

Methods

Human myocardial tissues were obtained from ischemic heart disease patients and normal control patients to compare ERBB1 expression. Myocyte-specific Hif2a or ErbB1 knockout mice were generated to observe the effect of Hif2a knockdown in regulating ERBB1 expression and to examine the role of ERBB1 during myocardial ischemia and reperfusion injury.

Results

Initial studies of myocardial tissues from patients with ischemic heart disease showed increased ERBB1 protein (1.12 ± 0.24 vs. 13.01 ± 2.20, P < 0.001). In contrast, ERBB1 transcript was unchanged. Studies using short hairpin RNA repression of Hif2A or Hif2a

loxP/loxP
Myosin Cre+ mice directly implicated hypoxia-inducible factor 2A in ERBB1 protein induction during hypoxia or after myocardial ischemia, respectively. Repression of RNA-binding protein 4 abolished hypoxia-inducible factor 2A–dependent induction of ERBB1 protein. Moreover, ErbB1

loxP/loxP
Myosin Cre+ mice experienced larger infarct sizes (22.46 ± 4.06 vs. 46.14 ± 1.81, P < 0.001) and could not be rescued via amphiregulin treatment.

Conclusions

These findings suggest that hypoxia-inducible factor 2A promotes transcription-independent induction of ERBB1 protein and implicates epidermal growth factor signaling in protection from myocardial ischemia and reperfusion injury.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury
Authors: Mathis Michael R. , Naik Bhiken I. , Freundlich Robert E. , Shanks Amy M. , Heung Michael , Kim Minjae , Burns Michael L. , Colquhoun Douglas A. , Rangrass Govind , Janda Allison , Engoren Milo C. , Saager Leif , Tremper Kevin K. , Kheterpal Sachin ,   on behalf of the Multicenter Perioperative Outcomes Group Investigators
Published: December 2019

Background

Despite the significant healthcare impact of acute kidney injury, little is known regarding prevention. Single-center data have implicated hypotension in developing postoperative acute kidney injury. The generalizability of this finding and the interaction between hypotension and baseline patient disease burden remain unknown. The authors sought to determine whether the association between intraoperative hypotension and acute kidney injury varies by preoperative risk.

Methods

Major noncardiac surgical procedures performed on adult patients across eight hospitals between 2008 and 2015 were reviewed. Derivation and validation cohorts were used, and cases were stratified into preoperative risk quartiles based upon comorbidities and surgical procedure. After preoperative risk stratification, associations between intraoperative hypotension and acute kidney injury were analyzed. Hypotension was defined as the lowest mean arterial pressure range achieved for more than 10 min; ranges were defined as absolute (mmHg) or relative (percentage of decrease from baseline).

Results

Among 138,021 cases reviewed, 12,431 (9.0%) developed postoperative acute kidney injury. Major risk factors included anemia, estimated glomerular filtration rate, surgery type, American Society of Anesthesiologists Physical Status, and expected anesthesia duration. Using such factors and others for risk stratification, patients with low baseline risk demonstrated no associations between intraoperative hypotension and acute kidney injury. Patients with medium risk demonstrated associations between severe-range intraoperative hypotension (mean arterial pressure less than 50 mmHg) and acute kidney injury (adjusted odds ratio, 2.62; 95% CI, 1.65 to 4.16 in validation cohort). In patients with the highest risk, mild hypotension ranges (mean arterial pressure 55 to 59 mmHg) were associated with acute kidney injury (adjusted odds ratio, 1.34; 95% CI, 1.16 to 1.56). Compared with absolute hypotension, relative hypotension demonstrated weak associations with acute kidney injury not replicable in the validation cohort.

Conclusions

Adult patients undergoing noncardiac surgery demonstrate varying associations with distinct levels of hypotension when stratified by preoperative risk factors. Specific levels of absolute hypotension, but not relative hypotension, are an important independent risk factor for acute kidney injury.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Outcomes of Scleral Contact Lens Use in Veteran Population
Authors: Kanakamedala Amritha , Salazar Humberto , Campagna Giovanni , Chamberlain Paul , Vadapalli Sangita , Orengo-Nania Silvia , Khandelwal Sumitra
Published: December 2019

Objectives:

To document outcomes associated with use of scleral contact lenses (SL) in the veteran population and analyze the medical and demographic factors that affect these outcomes, specifically those involved in contact lens discontinuation.

Methods:

A retrospective study of consecutive patients first fitted with Jupiter Scleral lenses at the Michael E. DeBakey Veterans Affairs Medical Center between 2010 and 2018. The primary outcome was continuation of SL use at 1 year. Demographic factors and variables such as presence of comorbid diseases, improvement in visual acuity, and daily lens wear time were compared. Logistic regression analysis was used to determine which factors were associated with SL discontinuation.

Results:

One hundred twenty patients with a mean age of 56.7±15.1 years were fitted with SL during the study period. The most common diagnosis was corneal ectasia (55.8%). Sixty-six (55.0%) patients had difficulty with wear, the most common being ocular irritation (20.0%) and mid-day fogging or bubbles (15.8%). Forty-one patients (34.2%) discontinued SL use with a median time from fitting to discontinuation of 5.2 months. The most common reason for SL discontinuation was difficulty with insertion and removal (53.7%). Comorbid neurologic disease had a statistically significant association with discontinuation (odds ratio 4.6, 95% confidence interval 1.3–17, P=0.022). There were statistically significant differences in mean visual acuity improvement (P=0.003) and daily wear time (P<0.001) but not age (P=0.70) between patients who continued and discontinued lens use.

Conclusions:

Scleral contact lenses are effective for treating a wide variety of ocular diseases and have positive outcomes in veterans. This study aids in understanding patient factors that affect outcomes of SL use in veterans. Further prospective studies are needed to make formal recommendations regarding candidate selection.
Associations between recent thymic emigrants and CD4+ T-cell recovery after short-term antiretroviral therapy initiation
Authors: Briceño Olivia , Chávez-Torres Monserrat , Peralta-Prado Amy , Garrido-Rodríguez Daniela , Romero-Mora Karla , Pinto-Cardoso Sandra , Reyes-Terán Gustavo
Published: December 2019

Objective:

Around 20–30% of HIV-infected individuals (HIV+) on successful antiretroviral therapy (ART) fail to normalize their CD4+ T-cell counts. Various factors could contribute to the lack of immune reconstitution, one of them being thymic insufficiency. We aimed to explore associations between recent thymic emigrants (RTEs) and CD4+ T-cell recovery.

Design:

ART-naive HIV+ individuals who started ART with advanced AIDS were selected. Good versus poor immune reconstitution was defined by CD4+ gains above or below 100 CD4+ T cells/μl. The follow-up period was 6 months.

Methods:

Peripheral blood mononuclear cells were isolated and flow cytometry was used to characterize RTEs as the fraction of naive CD4+ T cells expressing CD31+, the platelet endothelial cell adhesion molecule. Markers of cellular activation, senescence, exhaustion and cycling were also assessed.

Results:

After 6 months on ART, HIV+ individuals with good immune reconstitution had higher absolute numbers of RTEs, compared with those with poor immune reconstitution, and these strongly correlated with CD4+ gains in those individuals with good immune reconstitution but not with poor immune reconstitution. We also found that CD8+ T-cell immune activation decreased as early as 2 months post-ART initiation in individuals with good immune reconstitution, but only at month 6 post-ART in individuals with poor immune reconstitution. Levels of immune activation were inversely correlated with the absolute numbers of RTEs in both groups, but more strongly so in individuals with poor immune reconstitution.

Conclusion:

We show that RTEs are linked to CD4+ T-cell recovery and that the degree of immune reconstitution is not directly linked to persistent immune activation.
Surgical Outcomes of Bony Batten Grafting Through Endonasal Septoplasty in the Correction of Caudal Septum Deviation
Authors: Aksakal Ceyhun
Published: December 2019

Objective:

The aim of the present study was to evaluate the efficiency and usefulness of bony batten grafts through endonasal septoplasty in the correction of caudal septum deviations.

Method:

In this case-controlled retrospective study, 65 patients who had bony batten graft procedure for the correction of caudal septum deviation using endonasal septoplasty with complete pre-operative and post-operative questionnaire information and complete post-operative follow-up data (an average follow-up period of 24.1 months) in our hospital in September 2013 and August 2018 period were evaluated. Nasal Obstruction Symptoms Evaluation (NOSE) scores of the patients before and after the operation were compared. Besides, severity of nasal symptoms (mouth dryness, hyposmia, rhinorrhea, epistaxis and snoring) before and after the operation was compared using visual analog scale (VAS). Complications which developed in post-operative period were also analyzed.

Findings:

Average age of the 65 patients (14 female and 51 male) was 27.6 ± 11.3. A straight septum was achieved in 57 patients (87.6%) in post-operative period while 8 patients (12.4%) had residual deviation. Average pre-operative NOSE score was 79.8 ± 22.3 while average post-operative NOSE score was 21.4 ± 4.6 and the difference was significant (P < 0.0001). Significant improvements were observed in VAS scores of all evaluated symptoms in post-operative period. Two patients developed septal hematoma in post-operative period.

Conclusion:

Bony batten graft procedure through endonasal septoplasty is an efficient and useful method with low complication rate for the correction of deviation of caudal septum.
Anaerosphaera multitolerans sp. nov., a salt-tolerant member of the family Peptoniphilaceae isolated from a mesophilically operated biogas fermenter fed with maize silage
Authors: Rettenmaier Regina , Liebl Wolfgang , Zverlov Vladimir V.
Published: December 2019

In this work, we succeeded in the isolation of a novel species out of a mesophilically operated biogas fermenter fed with maize silage. Strains GS7-6-2T, GS-7K2 and GS-0K3 were isolated from three individual enrichment cultures. 16S rRNA gene sequence comparisons indicated that the isolates had 100 % sequence identity and were most closely related to Anaerosphaera amininiphila WN036T, with which they shared a 16S rRNA gene sequence similarity of 93.1 %. As a representative, strain GS7-6-2T was further characterized. Strain GS7-6-2T was mesophilic with its growth optimum at 30 °C and a pH range from pH 5.5 to 9.5 (optimum, pH 6.0–8.5). Cells were spherical and sometimes arranged into short chains. Growth was possible with up to 3.6 % (w/v) NaCl, but best without additional NaCl. Strain GS7-6-2T produced butyric acid and acetic acid as main fermentation products while growing on GS2 medium. The major cellular fatty acids were C18 : 1ω7c, C16 : 0 and C16 : 1ω9c. The Gram-stain result was negative. The DNA G+C content was 32.8 mol%. Strain GS7-6-2T was able to ferment 16 (comprising four carbohydrates, five amino acids, four organic acids and three nucleotides) out of the 95 tested substrates. Due to the ecological, genetic and phenotypic differences from the most closely affiliated and validly named organism, A. amininiphila WN036T, the isolates represent a novel species within the genus

Anaerosphaera

, family

Peptoniphilaceae

, for which the name Anaerosphaera multitolerans sp. nov. is proposed. The type strain is GS7-6-2T (=DSM 107952T=CECT 9705T).
The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria
Authors: Bharwani Aadil , West Christine , Champagne-Jorgensen Kevin , Neufeld Karen-Anne McVey , Ruberto Joseph , Kunze Wolfgang A. , Bienenstock John , Forsythe Paul
Published: December 2019

There is accumulating evidence that certain gut microbes modulate brain chemistry and have antidepressant-like behavioural effects. However, it is unclear which brain regions respond to bacteria-derived signals or how signals are transmitted to distinct regions. We investigated the role of the vagus in mediating neuronal activation following oral treatment withLactobacillus rhamnosus(JB-1).

Male Balb/c mice were orally administered a single dose of saline or a live or heat-killed preparation of a physiologically active bacterial strain,Lactobacillus rhamnosus(JB-1). 165 minutes later, c-Fos immunoreactivity in the brain was mapped, and mesenteric vagal afferent fibre firing was recorded. Mice also underwent sub-diaphragmatic vagotomy to investigate whether severing the vagus prevented JB-1-induced c-Fos expression. Finally, we examined the ΔFosB response following acute versus chronic bacterial treatment.

While a single exposure to live and heat-killed bacteria altered vagal activity, only live treatment induced rapid neural activation in widespread but distinct brain regions, as assessed by c-Fos expression. Sub-diaphragmatic vagotomy abolished c-Fos immunoreactivity in most, but not all, previously responsive regions. Chronic, but not acute treatment induced a distinct pattern of ΔFosB expression, including in previously unresponsive brain regions.

These data identify that specific brain regions respond rapidly to gut microbes via vagal-dependent and independent pathways, but suggest long-term exposure is required for the chronic brain activity associated with behavioural changes.
Characterization of the Key Region and Phosphorylation Sites of EcaICE1 for its Molecular Interaction with EcaHOS1 Protein from Eucalyptus camaldulensis
Authors: Cheng Ling , Zhang Weihua , Hu Jianlin , Zhang Ziyang , Liu Yan , Lin Yuanzhen
Published: December 2019

ICE1 (inducer of CBF expression 1), a MYC-like bHLH transcriptional activator, plays an important role in plant under cold stress via regulating transcriptional expression of downstream cold-responsive genes. Ubiquitination-proteasome pathway mediated by high expression of osmotically responsive gene1 (HOS1) can effectively induce the degradation of ICE1 and decrease the expression of expression of CBFs and their downstream genes under cold stress response in Arabidopsis, but the knowledge about ubiquitination regulation of ICE1 by HOS1 is still limited in woody plants. In this study, a complete open reading frame of EcaICE1 gene and EcaHOS1 was amplified from the tissue culture seedlings of Eucalyptus camaldulensis. Yeast two-hybrid (Y2H) and BiFC assay results showed that EcaICE1 can interact with EcaHOS1 protein in the nucleus, and further Y2H assay demonstrated that the 126-185 amino acid region at the N-terminus of EcaICE1 protein was indispensable for its interaction with EcaHOS1 protein. Moreover, we found that the amino acids at positions 143, 145, 158 and 184 within the key interaction region were the potential phosphorylation sites of EcaICE1 based on bioinformatics analysis, and that only the substitution of Serine (Ser) 158 by Alanine (Ala) blocked the protein-protein interactions between EcaICE1 and EcaHOS1 by Y2H and β-galactosidase assays using site-direct mutagenesis. In summary, we first reported that EcaICE1 could interact with EcaHOS1 protein in Eucalyptus, and identified Ser 158 of EcaICE1 as the key phosphorylation site for its interaction with EcaHOS1 protein.
Complementation between pathological prion protein subassemblies to cross existing species barriers
Authors: Igel-Egalon Angélique , Laferrière Florent , Tixador Philippe , Moudjou Mohammed , Herzog Laetitia , Reine Fabienne , Torres Juan Maria , Laude Hubert , Rezaei Human , Béringue Vincent
Published: December 2019

Background

prion replication results from the autocatalytic templated assisted conversion of the host-encoded prion protein PrPCinto misfolded, polydisperse PrPSc conformers. Structurally distinct PrPScconformers can give rise to multiple prion strains. Within and between prion strains, the biological activity (replicative efficacy and specific infectivity) of PrPScassemblies is size-dependent and thus reflects an intrinsic structural heterogeneity. The contribution of such PrPScheterogeneity across species prion adaptation, - which is believed to be based on fit-adjustment between PrPSctemplate(s) and host PrPC-, has not been explored.

Methods

to define the structural-to-fitness PrPSclandscape, we measured the relative capacity of size-fractionated PrPScassemblies from different prion strains to cross mounting species barriers in transgenic mice expressing foreign PrPc.

Results

in the absence of a transmission barrier, the relative efficacy of the isolated PrPScassemblies to induce the disease is superimposable to the efficacy observed in the homotypic context. However, in the presence of a transmission barrier, size fractionation overtly delays and even abrogates prion pathogenesis in both neural and extraneural, prion-permissive tissues, for reason independent of the infectivity load of the isolated assemblies. This suggests that a synergy between structurally distinct PrPScassemblies in the inoculum is requested for crossing the species barrier. We further strengthen this hypothesis by showing that altering, by serial dilution, PrPScassemblies content of unfractionated inocula reduce their specific infectivity in an aberrant manner, solely in the presence of a transmission barrier.

Conclusions

our data support a mechanism whereby overcoming prion species barrier requires complementation between structurally distinct PrPScassemblies. This work provides key insight into the “quasi-species” concept applied to prions, which would not necessarily rely on prion sub-strains as constituent but on structural PrPScheterogeneity within prion population.
Nearest-neighbor Projected-Distance Regression (NPDR) for detecting network interactions with adjustments for multiple tests and confounding
Authors: Le Trang T. , Dawkins Bryan A. , McKinney Brett A.
Published: December 2019

Machine learning feature selection methods are needed to detect complex interaction-network effects in complicated modeling scenarios in high-dimensional data, such as GWAS, gene expression, eQTL, and structural/functional neuroimage studies for case-control or continuous outcomes. In addition, many machine learning methods have limited ability to address the issues of controlling false discoveries and adjusting for covariates. To address these challenges, we develop a new feature selection technique called Nearest-neighbor Projected-Distance Regression (NPDR) that calculates the importance of each predictor using generalized linear model (GLM) regression of distances between nearest-neighbor pairs projected onto the predictor dimension. NPDR captures the underlying interaction structure of data using nearest-neighbors in high dimensions, handles both dichotomous and continuous outcomes and predictor data types, statistically corrects for covariates, and permits statistical inference and penalized regression. We use realistic simulations with interactions and other effects to show that NPDR has better precision-recall than standard Relief-based feature selection and random forest importance, with the additional benefit of covariate adjustment and multiple testing correction. Using RNA-Seq data from a study of major depressive disorder (MDD), we show that NPDR with covariate adjustment removes spurious associations due to confounding. We apply NPDR to eQTL data to identify potentially interacting variants that regulate transcripts associated with MDD and demonstrate NPDR’s utility for GWAS and continuous outcomes.
A Novel LysR-Type Global Regulator RpvA Controls Persister Formation and Virulence inStaphylococcus aureus
Authors: Han Jian , Liu Zhe , Xu Tao , Shi Wanliang , Xu Xiaogang , Wang Sen , Ji Lei , Xu Yuanyuan , Peng Qi , Li Weiping , Zhang Ying
Published: December 2019

Staphylococcus aureusis the leading cause of wound and nosocomial infections. Persister formation and virulence factors play crucial roles duringS. aureusinfection. However, the mechanisms of persister formation and its relationship to virulence inS. aureusare poorly understood. In this study, we screened a transposon mutant library and identified a LysR-type global transcriptional regulator NWMN_0037, which we called RpvA, for regulator of persistence and virulence, whose mutation leads to higher susceptibility to antibiotics ampicillin and norfloxacin and various stresses including oxidative stress, heat, and starvation in late exponential and early stationary phase. Interestingly, therpvAmutant was highly attenuated for virulence compared with the parentS. aureusNewman strain as shown by a much higher lethal dose, reduced ability to survive in macrophages and to form abscess in the mouse model. Transcriptional profiling and metabolomic analysis revealed that RpvA could repress multiple genes includinggapR,gapA,tpi,pgm,eno,glpD, andacsexpression and enhance production of numerous intermediate metabolites including dihydroxyacetone phosphate, 2-phosphoglycerate, acetyl-CoA, glycerol 3-phosphate, L-glutamate in the cells. The differentially expressed genes and altered production of metabolites are distributed in global metabolism including carbohydrate metabolism, amino acid metabolism, energy metabolism and metabolism of cofactors and vitamins. These metabolic adjustments could cause the cell to go into dormancy, thus promotingS. aureusto convert to persisters. In addition, RpvA could upregulate the expression of virulence genes includinghla,hlgA,hlgB,hlgC,lukF,lukS,lukD,seaandcoa, and carotenoid biosynthesis genes (crtI,crtM,crtN). Gel shift assay confirmed that RpvA could bind to the promoters of candidate target geneshla,hlgBandcrtM, thus promotingS. aureusvirulence. Because of the important functions of the RpvA, it may serve as an attractive target for developing new drugs and vaccines to more effectively controlS. aureusinfections.
ACPT gene is inactivated in mammalian lineages that lack enamel and teeth
Authors: Mu Yuan , Huang Xin , Liu Rui , Gai Yulin , Liang Na , Yin Daiqing , Shan Lei , Xu Shixia , Yang Guang
Published: December 2019

Loss of tooth or enamel is widespread in multiple mammal lineages. Although several studies have been reported, the evolutionary mechanisms of tooth / enamel loss are still unclear. Most previous studies have found that some tooth-related genes have been inactivated in toothless and / or enamel-less mammals, such as ENAM, ODAM, C4orf26, AMBN, AMTN, DSPP, etc. Here, we conducted evolutionary analyses on ACPT plays a key role in amelogenesis, to interrogate the mechanisms. We obtained the ACPT sequences from 116 species, including edentulous and enamel-less mammals, then evolutionary analyses were implemented. The results showed that variant ORF-disrupting mutations have been detected in ACPT coding region among nine edentulous baleen whales and three enamel-less taxa (pygmy sperm whale, aardvark, nine-banded armadillo). Furtherly, selective pressure uncovered that the selective constraints have been relaxed among all toothless and enamel-less lineages. Moreover, our results support the hypothesis that mineralized teeth were lost or degenerated in the common ancestor of crown Mysticeti through two shared single-base sites deletion in exon 4 and 5 of ACPT among all living baleen whales. DN / dS values on transitional branches were used to estimate ACPT inactivation times. In the case of aardvark, inactivation of ACPT was estimated at ~23.60-28.32 Ma, which is earlier than the oldest pangolin fossil time (Orycteropus minutus, ~19Ma), suggesting that ACPT inactivation may result in degeneration or loss of enamel. Conversely, the inactivation time of ACPT estimated in armadillo (~10.18-11.30 Ma) is later than the oldest fossil time, suggesting that inactivation of ACPT may result from degeneration or loss of enamel in these mammals. Our findings suggested that different mechanisms of degeneration of tooth / enamel might exist among toothless and enamel-less lineages during evolution. Our study further considered that ACPT is a novel gene for studying tooth evolution.
Different detection capabilities by mycological media for Candida isolates from mono- or dual-species cultures
Authors: Angelis Giulia De , Menchinelli Giulia , Torelli Riccardo , Carolis Elena De , Posteraro Patrizia , Sanguinetti Maurizio , Posteraro Brunella
Published: December 2019

Objectives

The aim of this study was to compare the Candida bromcresol green (BCG) medium with the chromogenic (CHROM) Brilliance Candida agar and Sabouraud dextrose agar (SDA) media in regard to their capability of detecting Candida isolates from mono-or dual-species cultures.

Methods

We prepared Candida isolates’ suspensions to obtain mono-species (n = 18) or dual-species (n = 153) culture plates per each medium, and three readers independently observed 513 plates at 24-h, 48-h and 72-h incubation time. We scored reading results as correct, over or under detection compared to the expected species number(s).

Results

BCG showed significantly higher correct-detection and lower under-detection rates for all Candida species when observed by at least one reader. At 24-h reading, 12 mono-species cultures had correct (or over) detections in all media, whereas 106, 60 and 78 dual-species cultures had correct (or over) detections in BCG, CHROM or SDA, respectively.

Conclusion

BCG provides the basis for an accurate laboratory diagnosis of Candida infections.
Neural habituation enhances novelty detection: an EEG study of rapidly presented words
Authors: Jacob Len P. L. , Huber David E.
Published: December 2019

Huber and O’Reilly (2003) proposed that neural habituation aids perceptual processing, separating neural responses to currently viewed objects from recently viewed objects. However, synaptic depression has costs, producing repetition deficits. Prior work confirmed the transition from repetition benefits to deficits with increasing duration of a prime object, but the prediction of enhanced novelty detection was not tested. The current study examined this prediction with a same/different word priming task, using support vector machine (SVM) classification of EEG data, ERP analyses focused on the N400, and dynamic neural network simulations fit to behavioral data to provide a priori predictions of the ERP effects. Subjects made same/different judgements to a response word in relation to an immediately preceding brief target word; prime durations were short (50ms) or long (400ms), and long durations decreased P100/N170 responses to the target word, suggesting that this manipulation increased habituation. Following long duration primes, correct “different” judgments of primed response words increased, evidencing enhanced novelty detection. An SVM classifier predicted trial-by-trial behavior with 66.34% accuracy on held-out data, with greatest predictive power at a time pattern consistent with the N400. The habituation model was augmented with a maintained semantics layer (i.e., working memory) to generate behavior and N400 predictions. A second experiment used response-locked ERPs, confirming the model’s assumption that residual activation in working memory is the basis of novelty decisions. These results support the theory that neural habituation enhances novelty detection, and the model assumption that the N400 reflects updating of semantic information in working memory.