bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Study of Community-Based HIV/AIDS Prevention Interventions, Programs, and Projects for Rural and Remote Regions in Canada: Implementation Challenges and Lessons Learned
Authors: Worthington Catherine , Mollison Ashley , Herman Tamara , Johnston Christine , Masching Renée , Pooyak Sherri , Lee Rebecca , Loutfy Mona
Published: November 2018

Context:

Fifteen percent to 20% of the Canadian and American populations live outside urban areas, and despite growing regional HIV/AIDS–related health disparities, there is little published research specific to rural or remote (rural/remote) HIV/AIDS prevention programming.

Objective:

To document implementation challenges, lessons learned, and evaluation approaches of promising and proven HIV/AIDS prevention programs and interventions developed and delivered by organizations with rural/remote catchment areas in Canada to provide a foundation for information sharing among agencies.

Design:

Qualitative study design, using a community-based participatory research approach. We screened Canadian community-based organizations with an HIV/AIDS prevention mandate to determine whether they offered services for rural/remote populations and invited organizational representatives to participate in semistructured telephone interviews. Interviews were audio-recorded and transcribed. Content analysis was used to identify categories in the interview data.

Setting:

Canada, provinces (all except Prince Edward Island), and territories (all except Nunavut).

Participants:

Twenty-four community-based organizations.

Results:

Screening calls were completed with 74 organizations, of which 39 met study criteria. Twenty-four (62%) interviews were conducted. Populations most frequently served were Indigenous peoples (n = 13 organizations) and people who use drugs (n = 8 organizations) (categories not mutually exclusive). Key lessons learned included the importance of involving potential communities served in program development; prioritizing community allies/partnerships; building relationships; local relevancy and appropriateness; assessing community awareness or readiness; program flexibility/adaptability; and addressing stigma. Evaluation activities were varied and used for funder reporting and organizational learning.

Conclusions:

Rural/remote HIV/AIDS programs across Canada expressed similar challenges and lessons learned, suggesting that there is potential for knowledge exchange, and development of a community of practice. Top-down planning and evaluation models may fail to capture program achievements in rural/remote contexts. The long-term engagement practices that render rural/remote programs promising do not always conform to planning and implementation requirements of limited funding.
Assessing the Burden of Neonatal Abstinence Syndrome: Validation of ICD-9-CM Data, Florida, 2010-2011
Authors: Phillips-Bell Ghasi S. , Holicky Abigail , Lind Jennifer N. , Sappenfield William M. , Hudak Mark L. , Petersen Emily , Anjorhin Suzanne , Watkins Sharon M. , Creanga Andreea A. , Correia Jane A.
Published: November 2018

Context:

On October 1, 2015, the United States transitioned from using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM. Continuing to monitor the burden of neonatal abstinence syndrome (NAS) after the transition presently requires use of data dependent on ICD-9-CM coding to enable trend analyses. Little has been published on the validation of using ICD-9-CM codes to identify NAS cases.

Objective:

To assess the validity of hospital discharge data (HDD) from selected Florida hospitals for passive NAS surveillance, based on ICD-9-CM codes, which are used to quantify baseline prevalence of NAS.

Design:

We reviewed infant and maternal data for all births at 3 Florida hospitals from 2010 to 2011. Potential NAS cases included infants with ICD-9-CM discharge codes 779.5 and/or 760.72 in linked administrative data (ie, HDD linked to vital records) or in unlinked HDD and infants identified through review of neonatal intensive care unit admission logs or inpatient pharmacy records. Confirmed infant cases met 3 clinician-proposed criteria. Sensitivity and positive predictive value were calculated to assess validity for the 2 ICD-9-CM codes, individually and combined.

Results:

Of 157 confirmed cases, 134 with 779.5 and/or 760.72 codes were captured in linked HDD (sensitivity = 85.4%) and 151 in unlinked HDD (sensitivity = 96.2%). Positive predictive value was 74.9% for linked HDD and 75.5% for unlinked HDD. For either HDD types, the single 779.5 code had the highest positive predictive value (86%), lowest number of false positives, and good to excellent sensitivity.

Conclusions:

Passive surveillance using ICD-9-CM code 779.5 in either linked or unlinked HDD identified NAS cases with reasonable validity. Our work supports the use of ICD-9-CM code 779.5 to assess the baseline prevalence of NAS through 2015.
Analysis of Cell Viability and Gene Expression After Continuous Ultrasound Therapy in L929 Fibroblast Cells
Authors: Bertin Larissa Dragonetti , Poli-Frederico Regina Célia , Pires Oliveira Deise Aparecida Almeida , Oliveira Priscila Daniele , Pires Flávia Beltrão , Silva Ana Flávia Spadaccini , Oliveira Rodrigo Franco
Published: November 2018

Objective

This study aimed to analyze cell viability and gene expression interleukin 6 and vascular endothelial growth factor after continuous ultrasound therapy of 1 and 3 MHz in L929 fibroblast cells.

Design

The L929 cells were cultivated in 12-well plates and divided into the following five groups: Group 1 (G1), nonirradiated; G2, 0.2 W/cm2–1 MHz; G3, 0.5 W/cm2–1 MHz; G4, 0.2 W/cm2–3 MHz; and G5, 0.5 W/cm2–3 MHz. The cells were irradiated at 24 and 48 hrs. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The gene expression analysis was assessed using real-time polymerase chain reaction.

Results

The G2 and G3 showed a decrease in cell viability when compared with the G1 at 48 hrs (P < 0.01). The G4 and G5 presented an increase in viability (P = 0.01 and P = 0.03, respectively) in 24 to 48 hrs. The cells irradiated at an intensity of 0.5 W/cm2–3 MHz at 48 hrs showed a 0.21-fold decrease in interleukin-6 gene transcripts and a 1.67-fold increase in vascular endothelial growth factor gene transcripts.

Conclusions

Continuous ultrasound therapy with a frequency of 3 MHz at an intensity of 0.5 W/cm2 stimulates cell proliferation, decreases interleukin-6 gene expression, and increases vascular endothelial growth factor gene expression in L929 fibroblast cells.
Evolving Trends in Textured Implant Use for Cosmetic Augmentation in the United States
Authors: Tandon Vickram J. , DeLong Michael R. , Ballard Tiffany N. , Clemens Mark W. , Brandt Keith E. , Kenkel Jeffrey M. , Cederna Paul S.
Published: November 2018

Background:

Breast implants have evolved for decades. In 2011, the U.S. Food and Drug Administration identified an association between textured breast implants and breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). The purpose of this study was to identify the trends of textured implant use since that time.

Methods:

Maintenance of Certification tracer data were queried between 2011 and 2015 for cosmetic breast augmentation cases submitted by American Board of Plastic Surgery diplomates. A nested random effects logistic regression analysis was used to identify associations between variables.

Results:

Eleven thousand seven hundred sixteen breast augmentations were performed by 880 unique surgeons. The overall proportion of cases using textured implants increased steadily from 2.3 percent in 2011 to 13.0 percent in 2015 (p < 0.001). The proportion of surgeons whose cases included both textured and smooth implants increased (from 6.2 percent to 24.3 percent), as did those using only textured implants (from 0.4 percent to 4.4 percent) (p < 0.001). Significance remained after controlling for form-stable implants, suggesting an alternative motivation for use of textured implants. Subglandular cases (20.5 percent) were more likely to use a textured implant than submuscular (8.4 percent) or dual-plane (7.8 percent) (p < 0.001) cases.

Conclusions:

Maintenance of Certification tracer data represent a random sampling of American Board of Plastic Surgery–certified plastic surgeons spanning the gamut of practice settings. Despite ongoing education regarding the association of BIA-ALCL with textured implants, American Board of Plastic Surgery diplomates have trended toward increased use of textured implants for cosmetic breast augmentation since 2011. This finding does not appear to be driven by the introduction of anatomical implants during the study period.
Medical Tourism and Postoperative Infections: A Systematic Literature Review of Causative Organisms and Empiric Treatment
Authors: Padilla Pablo , Ly Priscilla , Dillard Rachel , Boukovalas Stefanos , Zapata-Sirvent Ramon , Phillips Linda G.
Published: November 2018

Background:

Medical tourism has become increasingly globalized as individuals travel abroad to receive medical care. Cosmetic patients in particular are more likely to seek surgery abroad to defray costs. Unfortunately, not all procedures performed abroad adhere to strict hygienic regulations, and bacterial flora vary. As a result, it is not uncommon for consumers to return home with difficult-to-treat postoperative infections.

Methods:

A systematic literature review of PubMed, Ovid, Web of Science, and Cumulative Index to Nursing and Allied Health Literature databases was performed to assess the microbiology patterns and medical management of patients with postoperative infections after undergoing elective surgery abroad.

Results:

Forty-two cases of postoperative infections were reported among patients who underwent elective surgery abroad. Most cases were reported from the Dominican Republic, and the most common elective procedures were abdominoplasty, mastopexy, and liposuction. Rapidly growing mycobacteria such as Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae were among the most common causes of postoperative infection, with M. abscessus involving 74 percent of cases. Most cases were treated with surgical débridement and a combination of antibiotics. Clarithromycin, amikacin, and moxifloxacin were the most common drugs used for long-term treatment.

Conclusions:

When encountering a patient with a history of medical tourism and treatment-refractory infection, rapidly growing mycobacteria must be considered. To increase the likelihood of yielding a diagnostic organism, multiple acid-fast bacilli cultures from fluid and débridement content should be performed. There has been reported success in treating rapidly growing mycobacterial infections with a combination of antibiotics including clarithromycin, amikacin, and moxifloxacin.
68Ga-PSMA PET/CT Urachus Metastases in Recurrent Prostate Cancer With Very Low PSA Level
Authors: Le Thiec Maëlle , Rusu Daniela , Fleury Vincent , Kraeber-Bodéré Francoise , Rousseau Caroline
Published: November 2018

Peritoneal carcinomatosis in prostate cancer is extremely rare and has been described in only few cases with high PSA level, androgen deprivation, or in symptomatic patients. To date, 2 cases of 68Ga-PSMA PET positive peritoneal metastases have been reported. We report a case of urachus metastases showed on 68Ga-PSMA PET/CT performed for biochemical recurrence with a very low PSA level at 0.50 ng/mL.
Pharmacological Inhibition of PTEN Restores Remote Ischemic Postconditioning Cardioprotection in Hypercholesterolemic Mice: Potential Role of PTEN/AKT/GSK3β SIGNALS
Authors: Hong Jun , Ge Hong-Wei , Liu Jing-Quan , Sun Ren-Hua , Kong Fei-Juan
Published: November 2018

Although remote ischemic postconditioning (RIPC) was shown to confer cardioprotection against myocardial ischemia/reperfusion (I/R) injury in normal animals, whether RIPC-induced cardioprotection is altered in the presence of hypercholesterolemia, a comorbidity with acute myocardial infarction (AMI) patients has yet to be determined. Normal or 2% cholesterol chow was fed to male C57BL/6J mice for 12 weeks to induce hypercholesterolemia, then normal or hypercholesterolemic murine hearts were exposed to AMI by coronary artery ligation. RIPC was induced by four episodes of 5 min femoral artery occlusion followed by 5 min reperfusion immediately after myocardial reperfusion in mice. Following I/R, RIPC significantly attenuated postischemic infarct size, hindered cardiomyocyte apoptosis, improved cardiac systolic function, decreased phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, and further increased Akt and GSK-3β phosphorylation in non-hypercholesterolemic, but not in hypercholesterolemic mice. Application of the PTEN inhibitor bisperoxovanadium (BpV) (1.0 mg/kg) reduced postischemic infarct size, attenuated cardiomyocyte apoptosis, and improved cardiac dysfunction in normal, but not in hypercholesterolemic mice. Further, increased dose of BpV (2 mg/kg or 10 mg/kg) failed to rescue the detrimental effects of hypercholesterolemia on I/R in mice following I/R. Especially important, we demonstrated that the combination BpV and RIPC exerted marked cardioprotective effects both in normal and hypercholesterolemic mice with I/R, indicating that PTEN inhibition restores RIPC-elicited myocardial protection in the presence of hypercholesterolemia. Our results demonstrated that hypercholesterolemia attenuated RIPC-induced cardioprotection against I/R injury by alteration of PTEN/Akt/GSK3β signals, and inhibition of PTEN rescued RIPC-induced cardioprotection in the presence of hypercholesterolemia.
Modulation of Peroxynitrite Reduces Norepinephrine Requirements in Ovine MRSA Septic Shock
Authors: Fukuda Satoshi , Ihara Koji , Andersen Clark R. , Randolph Anita C. , Nelson Christina L. , Zeng Yaping , Kim Jisoo , DeWitt Douglas S. , Rojas Jose D. , Koutrouvelis Aristides , Herndon David N. , Prough Donald S. , Enkhbaatar Perenlei
Published: November 2018

Vascular hypo-responsiveness to vasopressors during septic shock is a challenging problem. This study is to test the hypothesis that reactive nitrogen species (RNS), such as peroxynitrite, are major contributing factors to vascular hypo-responsiveness in septic shock. We hypothesized that adjunct therapy with peroxynitrite decomposition catalyst (PDC) would reduce norepinephrine requirements in sepsis resuscitation. Fourteen female Merino sheep were subjected to a “two-hit” injury (smoke inhalation and endobronchial instillation of live methicillin-resistant Staphylococcus aureus [1.6–2.5 × 1011 CFUs]). The animals were randomly allocated to control: injured, fluid resuscitated, and titrated norepinephrine, n = 7; or PDC: injured, fluid resuscitated, titrated norepinephrine, and treated with PDC, n = 7. One-hour postinjury, an intravenous injection of PDC (0.1 mg/kg) was followed by a continuous infusion (0.04 mg/kg/h). Titration of norepinephrine started at 0.05 mcg/kg/min based on their mean arterial pressure. All animals were mechanically ventilated and monitored in the conscious state for 24 h. The mean arterial pressure was well maintained in the PDC with significantly less norepinephrine requirement from 7 to 23 h after injury compared with control. Total norepinephrine dose, the highest norepinephrine rate, and time on norepinephrine support were also significantly lower in PDC. Modified sheep organ failure assessment scores at 6 to 18 h postinjury were significantly lower in PDC compared with control. PDC improved survival rate at 24 h (71.4% vs. 28.6%). PDC treatment had no adverse effects. In conclusion, the modulation of RNS may be considered an effective adjunct therapy for septic shock, in the case of hypo-responsiveness to norepinephrine.
Modulation of Endoplasmic Reticulum Stress Influences Ischemia-Reperfusion Injury After Hemorrhagic Shock
Authors: Obert David Peter , Wolpert Alexander Karl , Korff Sebastian
Published: November 2018

Background:

Impaired function of the endoplasmic reticulum (ER) results in ER stress, an accumulation of proteins in the ER lumen. ER stress is a major contributor to inflammatory diseases and is part of the pathomechanism of ischemia-reperfusion injury (IRI). Since severe traumatic injury is often accompanied by remote organ damage and immune cell dysfunction, we investigated the influence of ER stress modulation on the systemic inflammatory response and liver damage after hemorrhagic shock and reperfusion (HS/R).

Material and Methods:

Male C56BL/6-mice were subjected to hemorrhagic shock with a mean arterial pressure of 30 ± 5 mm Hg. After 90 min mice were resuscitated with Ringer solution. Either the ER stress inductor tunicamycin (TM), its drug vehicle (DV), or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) were added to reperfusion solution. Animals were sacrificed 14 h after shock induction and plasma concentrations of liver transaminases as well as inflammatory cytokines were measured. In addition, liver tissue sections were embedded in paraffin. For the quantification of hepatocellular damage hematoxylin and eosin stained tissue sections were analyzed. Furthermore, the topographic patterns of ER stress marker proteins were evaluated using immunohistochemistry.

Results:

ER stress modulation influenced the topographic pattern of ER stress marker proteins. The alterations were particularly seen in the transition zone between vital liver parenchyma and cell death areas. Furthermore, the application of tunicamycin during reperfusion inhibited the secretion of pro-inflammatory cytokines and increased the hepatocellular damage significantly. However, the injection of TUDCA resulted in a significantly reduced liver damage, as seen by lower transaminases and smaller cell death areas.

Conclusion:

ER stress modulation influences post-hemorrhagic IRI. Moreover, the ER stress inhibitor TUDCA diminished the hepatocellular damage following HS/R significantly. This may help to provide a therapeutic target to ameliorate the clinical outcome after trauma-hemorrhage.
Population Level Analysis of Adhesive Small Bowel Obstruction
Authors: Udelsman Brooks V. , Chang David C. , Parina Ralitza , Talamini Mark A. , Lillemoe Keith D. , Witkowski Elan R.
Published: November 2018

Objective:

The objective of this study was to determine the effects of open versus laparoscopic surgery on the development of adhesive small bowel obstruction (aSBO).

Summary Background Data:

aSBO is a significant contributor to short and long-term postoperative morbidity. Laparoscopy has demonstrated a protective effect in colorectal surgery, but these effects have not been generalized to other abdominal procedures.

Methods:

Population level California state data (1995–2010) was analyzed. We identified patients who underwent Roux-en-Y gastric bypass (RYGB), cholecystectomy, partial colectomy, appendectomy, and hysterectomy. The primary outcome was aSBO. Clinical, patient, and hospital characteristics were assessed using Kaplan–Meir methodology and Cox regression analysis adjusting for demographics, comorbidities, and operative approach.

Results:

We included 1,612,629 patients with a median follow-up of 6.3 years. The 5-year incidence rate of aSBO was higher after open surgery compared with laparoscopic surgery for each procedure (RYGB 2.1% vs. 1.5%, P < 0.001; cholecystectomy 2.2% vs. 0.65%, P < 0.001; partial colectomy 5.5% vs. 2.8%, P < 0.001; appendectomy 0.58% vs. 0.35%, P < 0.001; and hysterectomy 0.89% vs. 0.54%, P < 0.001). The period of greatest risk for aSBO formation was within the first 2-years. In multivariate analysis, an open approach was associated with an increased risk of aSBO for each procedure [RYGB hazard ratio (HR) 1.24, P < 0.001; cholecystectomy HR 1.89, P < 0.001; partial colectomy HR 1.49, P < 0.001; appendectomy HR 1.45, P < 0.001; and hysterectomy HR 1.16, P < 0.001).

Conclusions:

Laparoscopy is associated with a significant and sustained reduction in the rate of aSBO. The period of greatest risk for aSBO is within the first 2 years after surgery.
Management of adhesive small bowel obstruction: A distinct paradigm shift in the United States
Authors: Matsushima Kazuhide , Sabour Andrew , Park Caroline , Strumwasser Aaron , Inaba Kenji , Demetriades Demetrios
Published: November 2018

BACKGROUND

Recent studies show that early operative intervention in patients who fail nonoperative management of adhesive small bowel obstruction (ASBO) is associated with improved outcomes. The purpose of this study was to determine the trend in practice pattern and outcomes of patients with ASBO in the United States.

METHODS

Data from the National Inpatient Sample data (2003–2013) were extracted for analysis and included patients (age ≥18 years) who were discharged with primary diagnosis codes consistent with ASBO. We analyzed the data to examine changes in mortality and hospital length of stay in addition to any trends in rate and timing of operative interventions.

RESULTS

During the study period, 1,930,289 patients were identified with the diagnosis of ASBO. Over the course of the study period, the rate of operative intervention declined (46.10–42.07%, p = 0.003), and the timing between admission and operative intervention was significantly shortened (3.09–2.49 days, p < 0.001). In addition, in-hospital mortality rate decreased significantly (5.29–3.77%, p < 0.001). In the multiple logistic regression analysis, the relative risk of mortality decreased by 5.6% per year (odds ratio, 0.944; 95% confidence interval, 0.937–0.951; p < 0.001). Hospital length of stay decreased from 10.39 to 9.06 days (p < 0.001).

CONCLUSION

Over the last decade, fewer patients with ASBO were managed operatively, whereas those requiring an operation underwent one earlier in their hospitalization. Although further studies are warranted, our results suggest that recent changes in practice pattern may have contributed to improved outcomes.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
Hemophagocytic Lymphohistiocytosis Due to Primary HHV-8 Infection in a Liver Transplant Recipient
Authors: Cohen Gabriel M. , Langer Arielle L. , Sima Hamid , Chang Charissa , Troy Kevin , Taimur Sarah
Published: November 2018

Human herpesvirus-8 (HHV-8) remains best known as an oncogenic virus, but nonneoplastic disease manifestations, such as bone marrow failure or hemophagocytic lymphohistiocytosis (HLH) have gained greater recognition in recent years. In organ transplantation, HHV-8 infection commonly occurs with reactivation of latent virus among recipients from endemic regions of the world or due to transmission from the organ donor. We describe a case of HHV-8–associated HLH in a liver transplant recipient at increased risk for primary infection. Our case highlights the risk of non–donor-derived, posttransplant primary HHV-8 infection, and demonstrates that HLH can be a life-threatening complication of this infection.
Bupropion-Related Exacerbation of Tic Disorder in an Adult: A Case Report
Authors: Lurie Ido , Ganor Ori , Mayer Gad
Published: November 2018

Bupropion is antidepressant and a smoking cessation aid medication related to dopaminergic activity. We report for the first time a case of an older adult with a known tic disorder, which was in remission but exacerbated during treatment with bupropion. It has been reported that other dopaminergic compounds such as methylphenidate can exacerbate tic disorder. Clinicians should be aware of this potential adverse effect when prescribing bupropion to adults with tic and other motor disorders.
Widespread changes in firing rate and functional connectivity across the fronto-parietal network during rule guided working memory
Authors: Salazar RF
Published: November 2018

Flexible rule-based behavior is an integral component of our daily lives. Rule dependent changes in the activity and functional connectivity of neurons in the frontoparietal network may underlie this flexibility. To test this idea, we simultaneously recorded neural activity from multiple areas in prefrontal and posterior parietal cortices of macaque monkeys while they performed a delayed match-to-sample task involving a non-instructed switch between location and identity matching rules. Our analysis revealed rule-dependent differences in firing rates during all phases of the task and marked task-dependent increases in spike count correlations with only weak differences between rules. These effects were widespread with a high incidence occurring within and between the dorsolateral prefrontal cortex, the lateral intraparietal area and area PG. We conclude that rule based visual working memory is associated with widespread modifications in excitability and functional connectivity across the frontoparietal network.
Collection of Sixteen High-Quality Human Head CAD Models Generated with SimNIBS 2.1 Using Connectome Subject Data within MATLAB® Platform
Authors: Htet Aung Thu , Noetscher Gregory M. , Burnham Edward H. , Nummenmaa Aapo , Makarov Sergey N.
Published: November 2018

The goal of this study is to introduce a collection of sixteen high-resolution, 2-manifold CAD compatible head models within the MATLAB platform available to all interested parties for electromagnetic and acoustic simulations. Each model contains skin, skull, CSF, GM, cerebellum, WM, and ventricles head compartments and possesses an “onion” topology: the grey matter shell is a container for white matter, ventricles, and cerebellum objects, the CSF shell contains the grey matter shell, the skull shell contains the CSF shell, and finally the skin or scalp shell contains the skull shell. The models are fully compatible with ANSYS ED FEM software, CST Studio Suite, Sim4Life/SEMCAD software, and other electromagnetic software packages.

The collection is based on MRI data from the Human Connectome Project (HCP) segmented using the SimNIBS 2.1/2.1.1 processing pipeline. The average number of triangular surface facets in a model is 866,000, the average triangle quality is 0.25, the average edge length is 1.48 mm, and the average surface mesh density or resolution is 0.57 points per mm2. If necessary, a finer model mesh can be created for every head using available MATLAB tools.
Repeat expansion and methylation state analysis with nanopore sequencing
Authors: Gießelmann Pay , Brändl Björn , Raimondeau Etienne , Bowen Rebecca , Rohrandt Christian , Tandon Rashmi , Kretzmer Helene , Assum Günter , Galonska Christina , Siebert Reiner , Ammerpohl Ole , Heron Andrew , Schneider Susanne A. , Ladewig Julia , Koch Philipp , Schuldt Bernhard M. , Graham James E. , Meissner Alexander , Müller Franz-Josef
Published: November 2018

Expansions of short tandem repeats are genetic variants that have been implicated in neuropsychiatric and other disorders but their assessment remains challenging with current molecular methods. Here, we developed a Cas12a-based enrichment strategy for nanopore sequencing that, combined with a new algorithm for raw signal analysis, enables us to efficiently target, sequence and precisely quantify repeat numbers as well as their DNA methylation status. Taking advantage of these single molecule nanopore signals provides therefore unprecedented opportunities to study pathological repeat expansions.
A Meta-Analysis of Alzheimer’s Disease Brain Transcriptomic Data
Authors: Patel Hamel , Dobson Richard J.B , Newhouse Stephen J
Published: November 2018

Background

Microarray technologies have identified imbalances in the expression of specific genes and biological pathways in Alzheimer’s disease (AD) brains. However, there is a lack of reproducibility across individual AD studies, and many related neurodegenerative and mental health disorders exhibit similar perturbations. We are yet to identify robust transcriptomic changes specific to AD brains.

Methods and Results

Twenty-two AD, eight Schizophrenia, five Bipolar Disorder, four Huntington's disease, two Major Depressive Disorder and one Parkinson’s disease dataset totalling 2667 samples and mapping to four different brain regions (Temporal lobe, Frontal lobe, Parietal lobe and Cerebellum) were analysed. Differential expression analysis was performed independently in each dataset, followed by meta-analysis using a combining p-value method known as Adaptively Weighted with One-sided Correction. This identified 323, 435, 1023 and 828 differentially expressed genes specific to the AD temporal lobe, frontal lobe, parietal lobe and cerebellum brain regions respectively. Seven of these genes were consistently perturbed across all AD brain regions with SPCS1 gene expression pattern replicating in RNA-seq data. A further nineteen genes were perturbed specifically in AD brain regions affected by both plaques and tangles, suggesting possible involvement in AD neuropathology. Biological pathways involved in the “metabolism of proteins” and viral components were significantly enriched across AD brains.

Conclusion

This study solely relied on publicly available microarray data, which too often lacks appropriate phenotypic information for robust data analysis and needs to be addressed by future studies. Nevertheless, with the information available, we were able to identify specific transcriptomic changes in AD brains which could make a significant contribution towards the understanding of AD disease mechanisms and may also provide new therapeutic targets.
A Biomechanical Model of Tumor-induced Intracranial Pressure and Edema in Brain Tissue
Authors: Sorribes I. C. , Moore M. N. J. , Byrne H. M. , Jain H. V.
Published: November 2018

Brain tumor growth and tumor-induced edema result in increased intracranial pressure (ICP), which, in turn, is responsible for conditions as benign as headaches and vomiting, or as severe as seizures, neurological damage, or even death. Therefore, it has been hypothesized that tracking ICP dynamics may offer improved prognostic potential in terms of early detection of brain cancer and better delimitation of the tumor boundary. However, translating such theory into clinical practice remains a challenge, in part, due to an incomplete understanding of how ICP correlates with tumor grade. Here, we propose a multiphase mixture model that describes the biomechanical response of healthy brain tissue – in terms of changes in ICP and edema – to a growing tumor. The model captures ICP dynamics within the diseased brain and accounts for the ability/inability of healthy tissue to compensate for this pressure. We propose parameter regimes that distinguish brain tumors by grade thereby providing critical insight into how ICP dynamics vary by severity of disease. In particular, we offer an explanation for clinically observed phenomena such as lack of symptoms in low grade glioma patients versus a rapid onset of symptoms in those with malignant tumors. Our model also takes into account the effects tumor-derived proteases may have on ICP levels and extent of tumor invasion. This work represents an important first step towards understanding the mechanisms that underlie the onset of edema and ICP in cancer-afflicted brains. Continued modeling effort in this direction has the potential to make an impact in the field of brain cancer diagnostics.
Transcriptional landscape of soybean (Glycine max) embryonic axes during germination in the presence of paclobutrazol, a gibberellin biosynthesis inhibitor
Authors: Gazara Rajesh K. , de Oliveira Eduardo A. G. , A. Oliveira Antônia Elenir , Venancio Thiago M.
Published: November 2018

Gibberellins (GA) are key positive regulators of seed germination. Although the GA effects on seed germination have been studied in a number of species, little is known about the transcriptional reprogramming modulated by GA during this phase in species other than Arabidopsis thaliana. Here we report the transcriptome analysis of soybean embryonic axes during germination in the presence of paclobutrazol (PBZ), a GA biosynthesis inhibitor. We found a number of differentially expressed cell wall metabolism genes, supporting their roles in cell expansion during germination. Several genes involved in the biosynthesis and signaling of other phytohormones were also modulated, indicating an intensive hormonal crosstalk at the embryonic axis. We have also found 26 photosynthesis genes that are up-regulated by PBZ at 24 hours of imbibition (HAI) and down-regulated at 36 HAI, which led us to suggest that this is part of a strategy to implement an autotrophic growth program in the absence of GA-driven mobilization of reserves. Finally, 30 transcription factors (mostly from the MYB, bHLH and bZIP families) that are down-regulated by PBZ and are likely downstream GA targets that will drive transcriptional changes during germination.
A macaque connectome for large-scale network simulations in TheVirtualBrain
Authors: Shen Kelly , Bezgin Gleb , Schirner Michael , Ritter Petra , Everling Stefan , McIntosh Anthony R.
Published: November 2018

Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing connectome data using diffusion-based tractography in macaques. We illustrate the utility of the connectome as an extension of TheVirtualBrain by simulating resting-state BOLD-fMRI data and fitting it to empirical resting-state data.
E-ChRPs: Engineered Chromatin Remodeling Proteins for Precise Nucleosome Positioning
Authors: Donovan DA , Crandall JG , Banks OGB , Jensvold ZD , McKnight LE , McKnight JN
Published: November 2018

Regulation of chromatin structure is essential for controlling the access of DNA to factors that require association with specific DNA sequences. The ability to alter chromatin organization in a targeted manner would provide a mechanism for directly manipulating DNA-dependent processes and should provide a means to study direct consequences of chromatin structural changes. Here we describe the development and validation of engineered chromatin remodeling proteins (E-ChRPs) for inducing programmable changes in nucleosome positioning by design. We demonstrate that E-ChRPs function both in vivo and in vitro to specifically reposition target nucleosomes and entire nucleosomal arrays, and possess the ability to evict native DNA-binding proteins through their action. E-ChRPs can be designed with a range of targeting modalities, including the SpyCatcher and dCas9 moieties, resulting in high versatility and enabling diverse future applications. Thus, engineered chromatin remodeling proteins represent a simple and robust means to probe regulation of DNA-dependent processes in different chromatin contexts.
The modular mechanism of chromocenter formation in Drosophila
Authors: Jagannathan Madhav , Cummings Ryan , Yamashita Yukiko M.
Published: November 2018

A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. In our previous study (Jagannathan et al., 2018), we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus. Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a ‘modular’ network, where interactions between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that interactions between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.
Factors Associated with Risk Of HIV-Infection Among Pregnant Women in Cameroon: Evidence from the 2016 National Sentinel Surveillance Survey of HIV and syphilis
Authors: Anoubissi Jean de Dieu , Gabriel Ekali Loni , Nde Cyprien Kengne , Fokam Joseph , Tseuko Dorine Godelive , Messeh Arlette , Moussa Yasmine , Nkenfou Celine Nguefeu , Bonono Leonard , Billong Serge-Clotaire , Nfetam Jean-Bosco Elat
Published: November 2018

Background

Human Immunodeficiency Virus infection (HIV) remains a public health concern in Cameroon that requires regular surveillance for informed policy-making to guide programmatic interventions. Using data from the 2016 HIV national sentinel survey in Cameroon, we ascertained HIV prevalence and factors associated with risk of infection among pregnant women

Methods

A cross-sectional study was conducted throughout 2016 in the 10 regions of Cameroon, targeting 7000 first antenatal care (ANC-1) attendees (4000 from urban and 3000 from rural areas) in 60 sentinel health facilities. HIV serological test was performed using the national serial algorithm at the National Reference Laboratory (NRL). Prevalence was determined, and multivariate logistic regression was used to assess determinants of HIV infection, with p-value<0.05 considered statistically significant.

Results

Of the 7000 targeted participants, a total of 6859 first ANC-1 attendees were enrolled (98.0% sampling coverage). Median age was 26 [IQR: 21-30] years and 47,40% had a secondary school level of education. The national prevalence of HIV was 5.70% (95% CI: 4.93 – 6.40) and range from 9.7% in East region to 2.6% in North region. The prevalence was 5.58% (95% CI: 95%: 4.88 – 6.35) in urban and 5.87% (95% CI: 5.04 – 6.78) in rural settings. Factors that were associated with HIV infection included marital status, women who were married or living with their partner are less likely to be infected than singles women (aOR=0.60; 95% CI: 0.46 – 0.78), multiparity [aOR=1.5(95%CI:1.0-2.2)] and been living in the Centre, East, North-west and South-west regions. HIV infection was also significantly associated with age, with the risk of being infected increasing with age.

Conclusion

Pregnant women in Cameroon are still disproportionately infected with HIV compared with the general population (prevalence 4.3%). Preventive actions to curb the epidemic amongst pregnant women should prioritize interventions targeting single pregnant women, who are older, and residing particularly in the Centre, East, North West and South West regions of the country.
A critical role of the T3SS effector EseJ in intracellular trafficking and replication ofEdwardsiella piscicidain non-phagocytic cells
Authors: Zhang Lingzhi , Jiang Jiatiao , Hu Tianjian , Zhang Jin , Liu Xiaohong , Yang Dahai , Zhang Yuanxing , Liu Qin
Published: November 2018

Edwardsiella piscicida(E. piscicida) is an intracellular pathogen within a broad spectrum of hosts. Essential toE. piscicidavirulence is its ability to survive and replicate inside host cells, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here, we characterized its intracellular lifestyle in non-phagocytic cells and showed that intracellular replication ofE. piscicidain non-phagocytic cells is dependent on its type III secretion system. Following internalization,E. piscicidais contained in vacuoles that transiently mature into early endosomes, but subsequently bypasses the classical endosome pathway and fusion with lysosomes which depends on its T3SS. Following a rapid escape from the degradative pathway,E. piscicidawas found to create a specialized replication-permissive niche characterized by endoplasmic reticulum (ER) markers. We also found that a T3SS effector EseJ is responsible for intracellular replication ofE. piscicidaby preventing endosome/lysosome fusion. Furthermore,in vivoexperiments confirmed that EseJ is necessary for bacterial colonization ofE. piscicidain both mice and zebrafish. Thus, this work elucidates the strategies used byE. piscicidato survive and proliferate within host non-phagocytic cells.

Author summary

E. piscicidais a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. The present study is the first comprehensive characterization ofE. piscicida’s intracellular life-style in host cells. Upon internalization,E. piscicidais transiently contained in Rab5-positive vacuoles, but the pathogen prevents further endosome maturation and fusion with lysosomes by utilizing an T3SS effector EseJ. In addition, the bacterium creates an specialized replication niche for rapid growth via an interaction with the ER. Our study provides new insights into the strategies used byE. piscicidato successfully establishes an intracellular lifestyle that contributes to its survival and dissemination during infection.
An inexpensive system for imaging the contents of multi-well plates
Authors: Bohm Andrew
Published: November 2018

An inexpensive system for automated imaging of the contents of 12-, 24- and 96-well plates has been built. The xyz stage is constructed from parts from a light-duty computer numerical control wood-carving/engraving machine, and the Arduino-based board was wired so that it can trigger still images or movies though a microscope-mounted digital camera. The translation stage provides reproducible three-dimensional movement of the sample over a volume of 160 mm in x, 100 mm in y and 40 mm in z. A Python script generates the G-code command file that scans the plate and collects a series of z-stacked images of each sample. A second Python script automates the calculation of images with a digitally enhanced depth of field. The imaging system is currently being used to facilitate screening for protein crystals, but it could be used to automate the imaging of many other types of samples in multi-well plates.
Leveraging interactive social media communication for organizational success
Authors: Chen Feifei
Published: November 2018

Purpose

The purpose of this paper is to examine how microblog communication enabled a new form of hybrid net-roots third-sector organization that rely heavily on the internet to achieve multiple organizational successes in civil society, social movement and service providing in China, where the government holds predominating power over the third sector.

Design/methodology/approach

A qualitative inductive analysis was conducted to analyze two successful organizations’ Sina tweets sent from their Weibo debuts to the dates when they achieved their first milestone successes. In the analysis, the author iteratively alternated between emic data coding and etic reference to literature on social movement rhetoric and nonprofits’ microblog communication.

Findings

This study developed an indigenous communication framework featuring three key communication strategies: changing perceptions, mobilizing action, and building and maintaining relationships, each associated with specific tactics. These strategies and tactics allowed both organizations to tap into social media’s interactive features to engage publics and construct legitimacy.

Research limitations/implications

This paper enriches social media-based communication research and classic social movement rhetoric, and further illustrates strategic communication’s active role in reacting to and reforming institutional contexts. Findings from study might be extended to address similar problems experienced by nonprofits across countries, especially within those that operate in a context where institutional separation from a predominant government is unavailable.

Originality/value

This original communication framework developed in this study crystalizes strategic microblog use by a nascent type of nonprofit when fulfilling functions reflects civil society, social movements and traditional nonprofit organizations in an understudied political and social context.
Top government hands-on megaproject management: the case of Istanbul’s grand airport
Authors: Eren Fatih
Published: November 2018

Purpose

The purpose of this paper is to explore top government hands-on megaproject management model applied to Istanbul’s new airport megaproject. The study aims to find an answer to this research question: “How is the organizational design and management of a megaproject that has been alive in a confrontational socio-political environment and whose national strategic importance is high?”

Design/methodology/approach

Organizational theory and critical theory perspectives are used in this study. Istanbul’s grand airport is chosen as the case study. Interview, focus group and document analysis methods are used together. The research yields data from qualitative resources. Verbal and written materials are organized into three major themes and 27 key subjects for content analysis.

Findings

A top level of organizational management can be attained in the state in order for the mega projects with high national strategic importance to survive without problems and with high performance. The top government-level organizational structure implemented at Istanbul’s new airport has reduced complexity, risk and uncertainty; increased performance and product quality; and strenghtened inter-organizational compatibility and communication within the megaproject organization. However, this structuring also increased centralization, reduced transparency and direct public participation in the decision-making process.

Research limitations/implications

The megaproject is run in strict confidence and limited information is shared gradually in a controlled way with public by the megaproject organization. Therefore, a qualitative methodology is followed and the usage of quantitative data remained limited in the research.

Practical implications

The study presents an exemplary top government-level megaproject management model for countries experiencing strong socio-political conflicts and aiming to perform megaprojects with high national strategic importance.

Social implications

The organization of Istanbul’s new airport megaproject offers an exemplary, flexible and innovative organizational management model for countries that want to realize mega projects with high national strategic importance and experience strong socio-political conflicts. The questions of how to cope with challenges, how to build management capabilities and how to improve the cooperation and coordination within megaprojects have found some answers with this study. In addition, this study provides an insight into how to make more effective objections to wrong megaproject practices and the right strategies that the opposing organizations can follow.

Originality/value

This empirical research widens and deepens the theoretical foundations of top government hands-on megaproject management. The study, which includes a process analysis, allows to better understand the philosophy, nature, success, planning process, social organization and dynamics of megaprojects and to explain them through the values and strategies of organizations.