bluuebunny/crossref_metadata_2025 huggingface dataset:
The True Effect of a Lumbar Dural Tear on Complications and Cost
Authors: Alluri Ram , Kang H. Paco , Bouz Gabriel , Wang Jeffrey , Hah Raymond J.
Published: September 2019

Study Design.

Retrospective database analysis.

Objective.

The aim of this study was to match risk factors for complications in patients who did and did not sustain a dural tear while undergoing posterior lumbar spine surgery and compare local and systemic complications.

Summary of Background Data.

Current data do not adequately define whether the event of sustaining an isolated dural tear increases the risk for postoperative complications while controlling for other confounding risk factors.

Methods.

The PearlDiver Database was queried for patients who underwent posterior lumbar spine decompression and/or fusion for degenerative pathology. Patients with and without dural tears were 1:2 matched based on demographic variables and comorbidities. Complications, cost, length of stay (LOS), and readmission rates were analyzed.

Results.

The 1:2 matched cohort included 9038 patients with a dural tear and 17,340 patients without a dural tear. All complications assessed were significantly higher in the dural tear group (P < 0.03). Venothromboembolic (VTE) events occurred in 1.3% of patients with a dural tear and 0.9% of patients without a dural tear (odds ratio [OR] 1.46, P < 0.0001). Meningitis occurred in 25 patients (0.3%) with a dural tear and eight patients (<0.1%) without a dural tear (OR 6.0, P < 0.0001). Patients with a dural tear had 120% higher medical costs, 200% greater LOS, and were two times more likely to be readmitted (P < 0.0001).

Conclusion.

Sustaining a dural tear while undergoing posterior lumbar spinal decompression and/or fusion for degenerative pathology significantly increased the risk of complications and increased length of stay, risk of readmission, and overall 90-day hospital cost. Dural tears specifically increased the risk of a VTE complication by 1.46 times and meningitis by six times; these are important complications to have a high degree of suspicion for in the setting of durotomy, as they can lead to significant morbidity for the patient.

Level of Evidence: 3
Body Mass Index and Modified Glasgow Prognostic Score Are Useful Predictors of Surgical Site Infection After Spinal Instrumentation Surgery
Authors: Kobayashi Yutaka , Inose Hiroyuki , Ushio Shuta , Yuasa Masato , Hirai Takashi , Yoshii Toshitaka , Okawa Atsushi
Published: September 2019

Study Design.

Retrospective observational study.

Objective.

To analyze a large consecutive cohort of patients who had undergone spinal instrumentation surgery, to characterize a patient population with surgical site infections (SSI), and to identify preoperative risk factors associated with SSI.

Summary of Background Data.

Malnutrition is a risk factor for SSI in many health conditions; however, the evidence connecting preoperative malnutrition with SSI in spinal instrumentation surgery is limited because of the small number of retrospective studies. While the modified Glasgow prognostic score (mGPS), C-Reactive protein (CRP)–albumin ratio (CAR), controlling nutritional status index (CONUT), prognostic nutritional index (PNI), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) are established methods for evaluating nutritious status, little has been reported on the predictive value of these indicators with respect to postoperative spinal infection.

Methods.

We retrospectively investigated 384 patients who underwent spinal instrumentation surgery. We evaluated the significance of risk factors, including mGPS, CAR, CONUT, PNI, PLR, and NLR. We then performed stepwise logistic regression analysis to analyze the concurrent effects of various factors on the prevalence of SSI.

Results.

Of the 384 patients analyzed, 14 were diagnosed with SSIs. Univariate analysis showed that preoperative BMI, lymphocyte count, albumin, erythrocyte sedimentation rate, CRP, CONUT, mGPS, CAR, and PNI were risk factors for SSI. Stepwise logistic regression analysis revealed that higher mGPS and lower BMI before surgery were independent risk factors for SSI. A receiver operating characteristic curve showed that the cut-off values of mGPS and BMI were 1 and 20.39, respectively.

Conclusion.

The risk factors for SSI after spinal instrumentation surgery were mGPS more than or equal to 1 and BMI less than or equal to 20.39 kg/m2. These findings could help to identify patients at higher risk of SSI after spinal instrumentation surgery.

Level of Evidence: 4
Should Sagittal Spinal Alignment Targets for Adult Spinal Deformity Correction Depend on Pelvic Incidence and Age?
Authors: Protopsaltis Themistocles S. , Soroceanu Alexandra , Tishelman Jared C. , Buckland Aaron J. , Mundis Gregory M. , Smith Justin S. , Daniels Alan , Lenke Lawrence G. , Kim Han Jo , Klineberg Eric O. , Ames Christopher P. , Hart Robert A. , Bess Shay , Shaffrey Christopher I. , Schwab Frank J. , Lafage Virginie
Published: September 2019

Study Design.

Retrospective analysis.

Objective.

Determine whether deformity corrections should vary by pelvic incidence (PI).

Summary of Background Data.

Alignment targets for deformity correction have been reported for various radiographic parameters. The T1 pelvic-angle (TPA) has gained in applications for adult spinal deformity (ASD) surgical-planning since it directly measures spinal alignment separate from pelvic- and lower-extremity compensation. Recent studies have demonstrated that ASD corrections should be age specific.

Methods.

A prospective database of consecutive ASD patients was analyzed in conjunction with a normative spine database. Clinical measures of disability included the Oswestry Disability Index (ODI) and Short Form 36 Survey (SF-36) Physical Component Score (PCS). Baseline relationships between TPA, age, PI, and ODI/SF-36 PCS scores were analyzed in the ASD and asymptomatic patients. Linear regression modeling was used to determine alignment targets based on PI and age-specific normative SF-36-PCS values.

Results.

Nine hundred three ASD patients (mean 53.7 yr) and 111 normative subjects (mean 50.7 yr) were included. Patients were subanalyzed by PI: low, medium, high (<40, 40–75, >75); and age: elderly (>65 yr, n = 375), middle age (45–65 yr, n = 387), and young (18–45 yr, n = 141). TPA and SRS-Schwab parameters correlated with age and PI in ASD and normative subjects (r = 0.42, P < 0.0001). ODI correlated with PCS (r = 0.71, P < 0.0001). Linear regression analysis using age-normative SF-36-PCS values demonstrated that ideal spinopelvic alignment is less strict with increasing PI and age.

Conclusion.

Targets for ASD correction should vary by age and PI. This is demonstrated in both asymptomatic and ASD subjects. Using age-normative SF-36 PCS values, alignment targets are described for different age and PI categories. High-PI patients do not require as rigorous realignments to attain age-specific normative levels of health status. As such, sagittal spinal alignment targets increase with increasing age as well as PI.

Level of Evidence: 3
Measles and Vaccination
Authors: Schmidt Karen
Published: September 2019

As the increasingly fierce debate about vaccines grows, so do the number of measles cases. Personal choice, inaccurate understanding, and legislative action are fueling vaccine refusal for this previously eradicated, highly contagious viral infection. In August 2019, measles cases had spread to 30 U.S. states and were spreading globally, endangering mainly young children and those unable to be vaccinated. Herd immunity is being eroded as parents refuse vaccinations or choose alternate vaccine schedules. Nurses are in a prime position to educate and advocate for vaccinations that safeguard public health.
Hand-Crafted Endoluminal Vacuum-Assisted Drainage for Anastomotic Leak After IPAA
Authors: Okkabaz Nuri , Esen Eren , Schwartzberg David M. , Remzi Feza H. , Kirat Hasan T.
Published: September 2019

INTRODUCTION:

The vacuum-assisted drainage has many applications in managing complex wound healing. It quickens the recovery period by its hyperemic effect on the exposed zone, decreasing bacterial colonization, preventing tissue edema, and promoting granulation of the wound. However, its use in anastomotic leak after IPAA is scarcely studied, especially because a proprietary endoluminal vacuum-assisted closure system was removed from the US market.

TECHNIQUE:

We applied a hand-crafted endoluminal vacuum-assisted closure system using the existing standard wound vacuum-assisted closure supplies to 2 patients who developed an anastomotic leak with a presacral abscess after completion proctectomy with J-pouch construction.

RESULTS:

We changed the endoluminal vacuum-assisted closure drain every 2 to 3 days, and both patients had substantial improvements in their abscess cavity after the seventh and ninth applications.

CONCLUSIONS:

Anastomotic leak at the IPAA traditionally takes up to a year to heal, which causes a significant toll on the psychosocial life of the patient and delayed stoma closure. Therefore, we believe that facilitating the healing process by using our hand-crafted endoluminal vacuum-assisted closure drain might provide a great value to patients’ quality of life.
Evaluation of Gastroesophageal Reflux in Children Born With Esophageal Atresia Using pH and Impedance Monitoring
Authors: Vergouwe Floor W.T. , van Wijk Michiel P. , Spaander Manon C.W. , Bruno Marco J. , Wijnen René M.H. , Schnater Johannes M. , IJsselstijn Hanneke
Published: September 2019

Objectives:

The aim of the study was to evaluate acid and nonacid gastroesophageal reflux in infants and school‐aged children with esophageal atresia (EA) using pH‐impedance (pH‐MII) monitoring.

Methods:

Between 2012 and 2017, all 24‐hour pH‐MII studies performed in infants (⩽18 months) and 8‐year olds with EA were included. Antiacid therapy was discontinued before study. Exclusion criteria were: isolated tracheoesophageal fistula; esophageal replacement therapy; tube feeding; and monitoring <18 hours. Automatically detected retrograde bolus movements (RBM) were manually reviewed and modified/deleted if necessary.

Results:

We included 57 children (51% boys; 2% isolated EA; 44% thoracoscopic EA repair): 24 infants (median age 0.6 years) and 33 school‐aged children (median age 8.2 years). Of the automatically detected 3313 RBM, 1292 were manually deleted from the tracings: 52% of nonacid RBM and 8% of acid RBM (mainly misinterpreted swallows or 1 event recognized as several events). In infants, median reflux index (RI; pH <4) was 2.6% (abnormal in n = 2), median RBM was 61 (62% nonacid, 58% mixed), and median of the mean BCT was 11 seconds. In older children, median RI was 0.3% (abnormal in n = 4), median RBM was 21 (64% nonacid; 75% mixed), and median of the mean BCT was 13 seconds.

Conclusions:

Most children with EA off medication have a normal RI, yet experience a significant number of nonacid RBM. After manual revision of the tracings, a high percentage of RBM was deleted. Our data show that automated impedance analysis software needs refinement for use in infants and children with EA and question the need for standard antiacid therapy in these patients.
CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis
Authors: Mougey Edward B. , Williams Andre , Coyne Ashlan J. Kunz , Gutiérrez‐Junquera Carolina , Fernández‐Fernández Sonia , Cilleruelo Maria Luz , Rayo Ana , Echeverría Luis , Román Enriqueta , González Lois Carmen , Chao Montserrat , Al‐Atrash Hadeel , Lima John J. , Franciosi James P.
Published: September 2019

Objective:

Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI‐REE, PPI‐nonresponsive EoE).

Methods:

Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high‐dose PPI therapy for esophageal eosinophilia in children.

Results:

Of the 92 patients examined, 57 (62%) were PPI‐REE and 35 (38%) were PPI‐nonresponsive EoE. Forty‐six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C19*17 (P = 0.35). In children who received a PPI dose between ≥1.54 and ⩽2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C19*17 associated with PPI‐nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI‐REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C19*17 to predict PPI‐nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C19*17 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023).

Conclusions:

Common variants in CYP2C19 and STAT6 associate with a PPI‐nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype‐guided approach to PPI dosing.
Gastric Hepatoid Adenocarcinoma: Differentiation From Gastric Adenocarcinoma With Dynamic Contrast-Enhanced Computed Tomographic Findings
Authors: Fu Yi , Zhu Hui , Peng Wei-jun
Published: September 2019

Purpose

This study aimed to describe the computed tomographic (CT) findings of gastric hepatoid adenocarcinoma (GHA) and determine features distinguishing it from gastric adenocarcinoma (GA).

Methods

Computed tomographic images of pathologically verified GHA (n = 11) and GA (n = 38) were retrospectively reviewed. α-Fetoprotein (AFP), carcinoembryonic antigen (CEA), and CT findings were assessed in our study. Computed tomographic findings included the location, distribution, growth pattern, ulceration, thickness of gastric wall, enhancement pattern, and the ratio of lesion attenuation to aorta CT attenuation. Short diameter of the metastatic lymph nodes, mean short diameter of metastatic lymph nodes, and the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically were measured and calculated. Data were compared using the χ2 and Student t tests; significant CT criteria were identified using receiver operating characteristic curve.

Results

α-Fetoprotein, CEA, and CT findings, including the longest short diameter, the mean short diameter, the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically, the lesion in arterial phase minus portal venous phase, and the lesion/aorta ratio, were statistically significant predictors for the differentiation of GHA from GA (P < 0.05). When only the aforementioned CT findings were used as criteria, the sensitivity and specificity for diagnosing GHA were 82.86% and 90.91%, respectively. When AFP, CEA, and CT findings were used as criteria, sensitivity of 97.14% and specificity of 90.91% were achieved.

Conclusions

Elevated serum AFP level and CT findings could distinguish GHA and GA with a high degree of accuracy.
Use of a Virtual Reality Device for Basic Life Support Training
Authors: Bench Suzanne , Winter Colin , Francis Gary
Published: September 2019

Introduction

Immediate initiation of cardiopulmonary resuscitation significantly increases the chances of survival after a cardiac arrest. Virtual reality devices allow the integration of features of real patients into training to facilitate interaction and feedback, thus improving performance. However, its use as a training tool remains underexplored. The aims of this study were to undertake initial testing of a virtual reality basic life support prototype and to explore users' views and experiences.

Methods

We recruited 23 adult staff members working at a Central London University in England and exposed them to a 5-minute virtual reality experience. Each participant completed a prequestionnaire and postquestionnaire and took part in a focus group discussion. Quantitative data were descriptively analyzed, whereas qualitative data underwent thematic analysis.

Results

Regardless of prior experience of using virtual reality and/or performing basic life support, most participants scored more than 90% for chest compressions and reported an increase in confidence and competence after the experience. Focus group discussions identified the following 4 key themes: experience and expectations; performance and feedback; interaction and immersion; and potential.

Conclusions

Our study suggests that virtual reality is an enjoyable method by which to teach basic life support. Although concerns over the accuracy of the tracking system and the small sample size weaken our conclusions regarding its ability to assess performance, our exploratory data are of value to educators, researchers, and policy makers. Future work needs to address our study limitations, consider how virtual reality fits into the broader context of training, and attend to accreditation and resource issues.
Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse
Authors: Lee Daniel D. , Wasson Megan , Hallock Jennifer L. , Heredia-Melero Gerardo , Kinman Casey , Maldonado Pedro A. , Pilkinton Marjorie L. , Sammel Mary D. , Greer Joy A. , Arya Lily A.
Published: September 2019

Objective

The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older.

Methods

This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis.

Results

A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status.

Conclusions

Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.
Prevalence of Pelvic Floor Disorders in Female CrossFit Athletes
Authors: High Rachel , Thai Kim , Virani Hina , Kuehl Thomas , Danford Jill
Published: September 2019

Objectives

This study aimed to estimate the prevalence of pelvic floor disorders by symptoms in female CrossFit athletes in the United States and characterize subjects reporting pelvic organ prolapse symptoms, urinary incontinence, and fecal incontinence.

Methods

A 27-question anonymous questionnaire was distributed to owners of CrossFit-affiliated gyms. Select questions from validated questionnaires were used to define symptoms. Positive responses with “moderate, or quite a bit” bother defined the presence of urinary incontinence (with stress or urgency). A response of “yes” to “having a bulge or something falling out” defined the presence of pelvic organ prolapse. A response of “yes” to “lose stool beyond your control” questions defined the presence of fecal incontinence.

Results

Three hundred fourteen respondents had mean age of 36 ± 10 years and a mean body mass index of 25.2 ± 4 kg/m2. Forty-four percent reported ≥1 vaginal delivery. For each workout, respondents reported lifting mean weights of 91 to 217 lb, and 90% reported participation in ≥3 CrossFit workouts per week. Pelvic floor disorder symptoms reported included the following: pelvic organ prolapse, 3.2% (10/314); urinary incontinence, 26.1% (82/314); and fecal incontinence, 6% (19/314). Higher age, parity, and number of vaginal deliveries were associated with urinary incontinence. Higher parity and number of vaginal deliveries were associated with prolapse. Fecal incontinence was not associated with age, body mass index, or obstetric history.

Conclusion

The prevalence of pelvic floor symptoms in female CrossFit athletes from the general population is likely similar to the general population; however, the prevalence of bothersome urinary incontinence is higher than the general population in women younger than 40 years.
CVRMS: Cross-validated Rank-based Marker Selection for Genome-wide Prediction of Low Heritability
Authors: Jeong Seongmun , Kim Jae-Yoon , Kim Namshin
Published: September 2019

CVRMS is an R package designed to extract marker subsets from repeated rank-based marker datasets generated from genome-wide association studies or marker effects for genome-wide prediction (https://github.com/lovemun/CVRMS). CVRMS provides an optimized genome-wide biomarker set with the best predictability of phenotype by implemented ridge regression using genetic information. Applying our method to human, animal, and plant datasets with wide heritability (zero to one), we selected hundreds to thousands of biomarkers for precise prediction.
A precision virtual crossmatch decision support system for interpretation of ambiguous molecular HLA typing data
Authors: Kaur Navchetan , Pinelli David , Kransdorf Evan P. , Pando Marcelo J , Smith Geoffrey , Murphey Cathi L , Kamoun Malek , Bray Robert A , Tambur Anat , Gragert Loren
Published: September 2019

Virtual crossmatch (VXM) compares a transplant candidate’s unacceptable antigens to the HLA typing of the donor before an organ offer is accepted and, in selected cases, supplant a prospective physical crossmatch. However, deceased donor typing can be ambiguous, leading to uncertainty in compatibility prediction. We have developed a web application that utilizes ambiguous HLA molecular typing data to assist in VXM assessments. The application compares a candidate’s listed unacceptable antigens to computed probabilities of all possible two-field donor HLA alleles and UNOS antigens. The VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) tool can be accessed at http://www.transplanttoolbox.org/victor. We reanalyzed historical VXM cases where a transplant center’s manual interpretation of molecular typing results influenced offer evaluation. We found that VICTOR’s automated interpretation of ambiguous donor molecular typing data would influence VXM decisions. Standardized interpretation of molecular typing data, if applied to the match run, could also change which offers are made. HLA typing ambiguity has been an underappreciated source of immunological risk in organ transplantation. The VICTOR tool can serve as a testbed for development of allocation policies with the aim of decreasing offers refused due to HLA incompatibility.
Adaptive-Resolution Multi-Orientation Analysis of Complex Filamentous Network Images
Authors: Kittisopikul Mark , Vahabikashi Amir , Shimi Takeshi , Goldman Robert D. , Jaqaman Khuloud
Published: September 2019

Microscopy images of cytoskeletal, nucleoskeletal, and other filamentous structures contain complex junctions where multiple filaments with distinct orientations overlap, yet state-of-the-art software generally uses single orientation analysis to segment these structures. We describe an image analysis approach to simultaneously segment both filamentous structures and their intersections in microscopy images, based on analytically resolving coincident multiple orientations upon image filtering in a manner that balances orientation resolution and spatial localization.
Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization
Authors: Rosoff Daniel B. , Smith George Davey , Mehta Nehal , Clarke Toni-Kim , Lohoff Falk W.
Published: September 2019

Alcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.
Protein Design and Variant Prediction Using Autoregressive Generative Models
Authors: Shin Jung-Eun , Riesselman Adam J. , Kollasch Aaron W. , McMahon Conor , Simon Elana , Sander Chris , Manglik Aashish , Kruse Andrew C. , Marks Debora S.
Published: September 2019

The ability to design functional sequences and predict effects of variation is central to protein engineering and biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments are not robust. Such applications include the prediction of variant effects of indels, disordered proteins, and the design of proteins such as antibodies due to the highly variable complementarity determining regions. We introduce a deep generative model adapted from natural language processing for prediction and design of diverse functional sequences without the need for alignments. The model performs state-of-art prediction of missense and indel effects and we successfully design and test a diverse 105-nanobody library that shows better expression than a 1000-fold larger synthetic library. Our results demonstrate the power of the ‘alignment-free’ autoregressive model in generalizing to regions of sequence space traditionally considered beyond the reach of prediction and design.
The histone demethylase KDM6B fine-tunes the host response toStreptococcus pneumoniae
Authors: Connor Michael G. , Camarasa Tiphaine Marie-Noelle , Patey Emma , Rasid Orhan , Barrio Laura , Weight Caroline M. , Miller Daniel P. , Heyderman Robert S. , Lamont Richard J. , Enninga Jost , Hamon Melanie A.
Published: September 2019

Streptococcus pneumoniaeis a natural colonizer of the human upper respiratory tract and an opportunistic pathogen. After colonization, bacteria either remain in the human upper respiratory tract, or may progress to cause pneumococcal disease. Although epithelial cells are among the first to encounter pneumococci, the cellular processes and contribution of epithelial cells to the host response are poorly understood. Here, we show aS. pneumoniaeserotype 6B ST90 strain, which does not cause disease in a murine infection model, induces a unique NF-κB signature response distinct from an invasive disease causing isolate of serotype 4 (TIGR4). This signature is characterized by activation of p65 (RelA) and requires a histone demethylase, KDM6B. At the molecular level, we show that interaction of the 6B strain with epithelial cells leads to chromatin remodeling within the IL-11 promoter in a KDM6B dependent manner, where KDM6B specifically demethylates histone H3 lysine 27 di-methyl. Chromatin remodeling of the IL-11 locus facilitates p65 access to three NF-κB sites, which are otherwise inaccessible when stimulated by IL-1β or TIGR4. Finally, we demonstrate through chemical inhibition of KDM6B, with GSK-J4 inhibitor, and through exogenous addition of IL-11 that the host responses to 6B ST90 and TIGR4 strains can be interchanged bothin vitroand in a murine model of infectionin vivo. Our studies hereby reveal how a chromatin modifier governs cellular responses during infection.
Neuroprotective effects of crocin I and II in an ischemia-reperfusion injury model
Authors: Lv Baowei , Yin Junyan , Feng Chunqing , Li Yanhui
Published: September 2019

Background

Crocin I and II are derived from the medicinal plantCrocus sativusL. (Saffron), and their neuroprotective effects have been attracting more and more attention. However, their protective effect against cerebral apoplexy induced by hypoxia has not been reported. In this study, we aimed to clarify the roles of crocin I and II in protecting against ischemic injury.

Materials/Methods

We generated a rat cerebral ischemia-reperfusion injury model using a reversible cerebral artery occlusion suture method and found changes in amino acid neurotransmitters in the frontal cortex after drug administration. We also identified changes in mRNA expression ofBcl2, Bax, Casp3, P38, andNFkb1in the frontal cortex and changes in antioxidant indices in the brain.

Results

Crocin I and II both had protective effects on ischemic/anoxic injuryin vivoby downregulating the expression ofCasp3andNfkb1mRNA and the steady-state levels of excitatory amino acids/inhibitory amino acids during ischemia and reperfusion and by improving the total antioxidant capacity and total superoxide dismutase activities during ischemia. We also found that crocin I and II had synergistic effects when used together.

Conclusions

These findings displayed that crocin I and II could protect animal model against ischemic and anoxic injury and provided new evidence for both molecules’ potential medicinal value.
Evolution under pH stress and high population densities leads to increased density-dependent fitness in the protistTetrahymena thermophila
Authors: Moerman Felix , Arquint Angelina , Merkli Stefanie , Wagner Andreas , Altermatt Florian , Fronhofer Emanuel A.
Published: September 2019

Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist speciesTetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r0). Overall, evolution at low pH led to the convergence ofr0and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation betweenr0andα, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase inr0, or decrease ofα, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress.
Exploration of social spreading reveals behavior is prevalent amongPedobacterandP. fluorescensisolates, and shows variations in induction of phenotype
Authors: McCully Lucy M. , Graslie Jasmine , Bitzer Adam S. , Sigurbjörnsdóttir Auður M. , Vilhelmsson Oddur , Silby Mark W.
Published: September 2019

Within soil, bacteria are naturally found in multi-species communities, where interactions can lead to emergent community properties. It is critical that we study bacteria in a social context to investigate community-level functions. We previously showed that when co-cultured,Pseudomonas fluorescensPf0-1 andPedobactersp. V48 engage in interspecies social spreading on a hard agar surface, a behavior which required close contact and was dependent on the nutritional environment. In this study, we investigate whether the ability to participate in social spreading is widespread amongP. fluorescensandPedobacterisolates, and whether the requirements for interaction vary. We find that this phenotype is not restricted to the interaction betweenP. fluorescensPf0-1 andPedobactersp. V48, but is a more prevalent behavior found in one clade in theP. fluorescensgroup and two clades in thePedobactergenus. We also discovered that the interaction with certainPedobacterisolates occurred without close contact, indicating induction of spreading by a putative diffusible signal. As is the case for ISS by Pf0-1+V48, motility of all interacting pairs is influenced by the environment, with no spreading behaviors observed under high nutrient conditions. While Pf0-1+V48 require low nutrient but high NaCl conditions, in the broader range of interacting pairs this requirement for low nutrient and high salt was variable. The prevalence of motility phenotypes observed in this study and found within the literature indicates that community-induced locomotion in general, and social spreading in particular, is likely important within the environment. It is crucial that we continue to study microbial interactions and their emergent properties to gain a fuller understanding of the functions of microbial communities.
B cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis
Authors: Okurut Samuel , Meya David B. , Bwanga Freddie , Olobo Joseph , Eller Michael A. , Cham-Jallow Fatim , Bohjanen Paul R. , Pratap Harsh , Palmer Brent E. , Hullsiek Katharine H. , Manabe Yukari C. , Boulware David R. , Janoff Edward N.
Published: September 2019

Background

Activated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during HIV and cryptococcal meningitis co-infection are ill defined.

Methods

We characterized clinical parameters, mortality and B cell phenotypes in blood and CSF by flow cytometry in HIV-infected adults with cryptococcal (n=31), and non-cryptococcal meningitis (n=12), and heathy control subjects with neither infection (n=10).

Results

Activation of circulating B cells (CD21low) was significantly higher in blood of subjects with HIV infection compared with healthy controls, and greater yet in matched CSF B cells (p<0.001). Among B cell subsets, elevated frequencies of memory and plasmablasts/plasma cells most clearly distinguished the CSF from blood compartments. With cryptococcal meningitis, lower frequencies of expression of the regulatory protein PD-1 on plasmablasts/plasma cells in blood (median 7%) at presentation was associated with significantly decreased 28-day survival (29% (4/14 subjects)), whereas higher PD-1 expression (median 46%) characterized subjects with higher survival (88% (14/16 subjects)).

Conclusion

With HIV infection, B cell differentiation and regulatory markers are discrete elements of the circulating and CSF compartments with clinical implications for cryptococcal disease outcome, potentially due to their effects on the fungus and other local immune cells.
Parameter fitting using time-scale analysis for vector-borne diseases with spatial dynamics
Authors: Sartori Larissa M. , Pereira Marcone C. , Oliva Sergio M.
Published: September 2019

Vector-borne diseases are becoming increasingly widespread in a growing number of countries and it has the potential to invade new areas and habitats, either associated to changes in vectors habitats, human circulation or climate changes. From the dynamical point of view, the spatial-temporal interaction of models that try to adjust to such events are rich and challenging. The first challenges are to address the dynamics of the vectors (very fast and local) and the dynamics of humans (very heterogeneous and non-local). The objective of the present paper is to use the well-known Ross-Macdonald models, incorporating spatial movements, identifying different times scales and estimate in a suitable way the parameters. We will concentrate in a practical example, a simplified space model, and apply to Dengue’s spread in the state of Rio de Janeiro, Brazil.
Tuber yield and processing quality response of French fried potatoes to nitrogen fertilization
Authors: Jiang Lili , Wang Ziquan , Jin Guanghui , Zhang Guizhi , Zhang Chunyu
Published: September 2019

Nitrogen (N) is an important factor that influences potato production; appropriate N fertilizer management can optimize tuber yield and quality and thus reduce the risk of environmental N losses. The present study aimed to evaluate the effects of different nitrogen (N) application rates (0, 75, 150, 225, 300, and 375 kg ha−1) on the total tuber yield, marketable yield, dry matter content, reducing sugar content, sucrose content of tuber, and fry color index of two potato cultivars (Kennebec and Shepody) in 2016 and 2017. N supply significantly affected tuber yield and processing quality, but these effects depended on the year and/or cultivar. The results indicated that low (75 kg ha−1) and medium-N application rates (150 or 225 kg ha−1) had a positive effect on tuber yield and processing quality; however, high-N application rates (300 and 375 kg ha−1) resulted in lower yield and poor quality. Total and marketable yields responded quadratically to N, and they were optimized at 150 kg ha−1for Kennebec and 225 kg ha−1for Shepody in both the years. The processing quality of tubers also responded quadratically with increasing N application rates. The optimal range of N application was approximately 145–185.83 kg ha−1for Kennebec and approximately 93.44–288.67 kg ha−1for Shepody according to the processing quality standards of French fried potatoes in China. To achieve the goals of high yield and high quality, N application rates should be 150 kg ha−1for Kennebec and 225 kg ha−1for Shepody.
Cardiac competence of the paraxial head mesoderm fades concomitant with a shift towards the head skeletal muscle programme
Authors: Alzamrooni Afnan , Vieira Petra Mendes , Murciano Nicoletta , Wolton Matthew , Schubert Frank R. , Robson Samuel C. , Dietrich Susanne
Published: September 2019

The vertebrate head mesoderm provides the heart, the great vessels, some smooth and most head skeletal muscle, in addition to parts of the skull. It has been speculated that the ability to generate cardiac and smooth muscle is the evolutionary ground-state of the tissue. However, whether indeed the entire head mesoderm has generic cardiac competence, how long this may last, and what happens as cardiac competence fades, is not clear.

Bone morphogenetic proteins (Bmps) are known to promote cardiogenesis. Using 41 different marker genes in the chicken embryo, we show that the paraxial head mesoderm that normally does not engage in cardiogenesis has the ability to respond to Bmp for a long time. However, Bmp signals are interpreted differently at different time points. Up to early head fold stages, the paraxial head mesoderm is able to read Bmps as signal to engage in the cardiac programme; the ability to upregulate smooth muscle markers is retained slightly longer. Notably, as cardiac competence fades, Bmp promotes the head skeletal muscle programme instead. The switch from cardiac to skeletal muscle competence is Wnt-independent as Wnt caudalises the head mesoderm and also suppresses Msc-inducing Bmp provided by the prechordal plate, thus suppressing both the cardiac and the head skeletal muscle programmes.

Our study for the first time suggests a specific transition state in the embryo when cardiac competence is replaced by skeletal muscle competence. It sets the stage to unravel the cardiac-skeletal muscle antagonism that is known to partially collapse in heart failure.

Summary statement

The head mesoderm has generic cardiac competence until early head fold stages. Thereafter, cardiac competence fades in the paraxial region, and Bmp promotes head skeletal muscle programmes instead of cardiac programmes.
Diagnosing and predicting mixed culture fermentations with unicellular and guild-based metabolic models
Authors: Scarborough Matthew J. , Hamilton Joshua J. , Erb Elizabeth A. , Donohue Timothy J. , Noguera Daniel R.
Published: September 2019

Multi-species microbial communities determine the fate of materials in the environment and can be harnessed to produce beneficial products from renewable resources. In a recent example, fermentations by microbial communities have produced medium-chain fatty acids (MCFAs). Tools to predict, assess, and improve the performance of these communities, however, are limited. To provide such tools, we constructed two metabolic models of MCFA-producing microbial communities based on available genomic, transcriptomic and metabolomic data. The first model is a unicellular model (iFermCell215), while the second model (iFermGuilds789) separates fermentation activities into functional guilds. Ethanol and lactate are fermentation products known to serve as substrates for MCFA production, while acetate is another common co-metabolite during MCFA production. Simulations with iFermCell215 predict that low molar ratios of acetate-to-ethanol favor MCFA production, whereas the products of lactate and acetate co-utilization are less dependent on the acetate-to-lactate ratio. In simulations of an MCFA-producing community fed a complex organic mixture derived from lignocellulose, iFermGuilds789 predicted that lactate was an extracellular co-metabolite that served as a substrate for butyrate (C4) production. Extracellular hexanoic (C6) and octanoic acids (C8) were predicted by iFermGuilds789 to be from community members that directly metabolize sugars. Modeling results provide several hypotheses that can improve our understanding of microbial roles in a MCFA-producing microbiome and inform strategies to increase MCFA production. Further, these models represent novel tools for exploring the role of mixed microbial communities in carbon recycling in the environment, as well as on beneficial reuse of organic residues.

IMPORTANCE

Microbiomes are vital to human health, agriculture, and protecting the environment. Predicting behavior of self-assembled or synthetic microbiomes, however, remains a challenge. In this work, we used unicellular and guild-based metabolic models to investigate production of medium-chain fatty acids by a mixed microbial community that is fed multiple organic substrates. Modeling results provided insights into metabolic pathways of three medium-chain fatty acid-producing guilds and identified potential strategies to increase production of medium-chain fatty acids. This work demonstrates the role of metabolic models in augmenting multi-omic studies to gain greater insights into microbiome behavior.
Correlated evolution of large DNA fragments in the 3D genome of Arabidopsis thaliana
Authors: Yan Yubin , Li Zhaohong , Li Ye , Wu Zefeng , Yang Ruolin
Published: September 2019

In eukaryotes, the three-dimensional (3D) conformation of the genome is far from random, and this nonrandom chromatin organization is strongly correlated with gene expression and protein function, which are two critical determinants of the selective constraints and evolutionary rates of genes. However, whether genes and other elements that are located close to each other in the 3D genome evolve in a coordinated way has not been investigated in any organism. To address this question, we constructed chromatin interaction networks (CINs) in Arabidopsis thaliana based on high-throughput chromosome conformation capture (Hi-C) data and demonstrated that adjacent large DNA fragments in the CIN indeed exhibit more similar levels of polymorphism and evolutionary rates than random fragment pairs. Using simulations that account for the linear distance between fragments, we proved that the 3D chromosomal organization plays a role in the observed correlated evolution. Spatially interacting fragments also exhibit more similar mutation rates and functional constraints in both coding and noncoding regions than the random expectations, indicating that the correlated evolution between 3D neighbors is a result of combined evolutionary forces. A collection of 39 genomic and epigenomic features can explain much of the variance in genetic diversity and evolutionary rates across the genome. Moreover, features that have a greater effect on the evolution of regional sequences tend to show higher similarity between neighboring fragments in the CIN, suggesting a pivotal role of epigenetic modifications and chromatin organization in determining the correlated evolution of large DNA fragments in the 3D genome.
Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018-Impact and Lessons Learned
Authors: Zhu YanChun , O’Brien Brittany , Leach Lynn , Clark Alexandra , Bates Marian , Adams Eleanor , Ostrowsky Belinda , Quinn Monica , Dufort Elizabeth , Southwick Karen , Erazo Richard , Haley Valerie B. , Bucher Coralie , Chaturvedi Vishnu , Limberger Ronald J. , Blog Debra , Lutterloh Emily , Chaturvedi Sudha
Published: September 2019

Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, spread, environmental survival, and drug resistance. Colonization on both biotic and abiotic surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in NY from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of ribosomal genes for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia Clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.