bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lentiviral vectors can be used for full-length dystrophin gene therapy
Authors: Counsell John R. , Asgarian Zeinab , Meng Jinhong , Ferrer Veronica , Vink Conrad A. , Howe Steven J. , Waddington Simon N. , Thrasher Adrian J. , Muntoni Francesco , Morgan Jennifer E. , Danos Olivier 
Published: February 2017

AbstractDuchenne Muscular Dystrophy (DMD) is caused by a lack of dystrophin expression in patient muscle fibres. Current DMD gene therapy strategies rely on the expression of internally deleted forms of dystrophin, missing important functional domains. Viral gene transfer of full-length dystrophin could restore wild-type functionality, although this approach is restricted by the limited capacity of recombinant viral vectors. Lentiviral vectors can package larger transgenes than adeno-associated viruses, yet lentiviral vectors remain largely unexplored for full-length dystrophin delivery. In our work, we have demonstrated that lentiviral vectors can package and deliver inserts of a similar size to dystrophin. We report a novel approach for delivering large transgenes in lentiviruses, in which we demonstrate proof-of-concept for a ‘template-switching’ lentiviral vector that harnesses recombination events during reverse-transcription. During this work, we discovered that a standard, unmodified lentiviral vector was efficient in delivering full-length dystrophin to target cells, within a total genomic load of more than 15,000 base pairs. We have demonstrated gene therapy with this vector by restoring dystrophin expression in DMD myoblasts, where dystrophin was expressed at the sarcolemma of myotubes after myogenic differentiation. Ultimately, our work demonstrates proof-of-concept that lentiviruses can be used for permanent full-length dystrophin gene therapy, which presents a significant advancement in developing an effective treatment for DMD.
Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma
Authors: Neel Dana S. , Bivona Trever G. 
Published: February 2017

AbstractThe advent of genomics has led to the identification of specific “driver” mutations in oncogenic kinases, and the development of targeted small molecule inhibitors to block their tumor-driving functions. These specific inhibitors have been a clinical success, and often significantly prolong the lives of individuals with cancer. Inevitably, however, the treated tumors recur as resistance to these targeted therapies develops. Here, we review the major mechanisms by which a cancer cell can evade targeted therapy, focusing on mechanisms of resistance to kinase inhibitors in lung cancer. We discuss the promising concept of rational upfront polytherapy in lung cancer, which involves concurrently targeting multiple proteins in critical signaling pathways in a cancer cell to prevent or delay resistance.
High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex
Authors: Lauridsen J K , Olesen R H , Vendelbo J , Hyde T M , Kleinman J E , Bibby B M , Brock B , Rungby J , Larsen A 
Published: February 2017

AbstractSeveral studies link increasing body mass index (BMI) to cognitive decline both as a consequence of obesity per se and as a sequela of obesity-induced type 2 diabetes. Obese individuals are prone to a chronic low-grade inflammation as the metabolically active visceral fat produces proinflammatory cytokines. Animal studies indicate that these cytokines can cross the blood–brain barrier. Such crossover could potentially affect the immune system in the brain by inducing gene expression of proinflammatory genes. The relationship between obesity and neuroinflammation in the human brain is currently unknown. Therefore we aim to examine the relationship between BMI and gene expression of central inflammatory markers in the human frontal cortex. Microarray data of 141 neurologically and psychiatrically healthy individuals were obtained through the BrainCloud database. A simple linear regression analysis was performed with BMI as variable on data on IL10, IL1β, IL6, PTGS2 (COX2) and NOS2 (iNOS). Increasing BMI is associated with a decrease in the mRNA expression of IL10 (P=0.014) and an increase in the expression of NOS2 (iNOS; P=0.040). Expressions of IL10 and NOS2 (iNOS) were negatively correlated (P<0.001). The expression of IL10 was mostly affected by individuals with BMI ⩾40. Multiple linear regression analyses with BMI, age, sex and race as variables were performed in order to identify potential confounders. In conclusion, increasing BMI could affect the IL10-mediated anti-inflammatory defense in the brain and induce iNOS-mediated inflammatory activity.
Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach
Authors: Abdallah C G , Wrocklage K M , Averill C L , Akiki T , Schweinsburg B , Roy A , Martini B , Southwick S M , Krystal J H , Scott J C 
Published: February 2017

AbstractThe anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.
Frequency Dependence Hearing Loss Evaluation in Perforated Tympanic Membrane
Authors: Dawood Mohammed 
Published: February 2017

Introduction Tympanic membrane perforation is a relatively common problem that predisposes patients to varying degrees of conductive hearing loss.
Objective The objective of this study is to evaluate and analyze the frequency dependence hearing loss in tympanic membrane perforation based on the size and the site of perforation.
Methods For the study, I selected 71 patients' (89) ears for the cross-sectional study with tympanic membrane perforations; I examined the size and the site of perforations under the microscope and classified them into small, moderate, large, and subtotal perforations, and into anterior central, posterior central, malleolor central, and big central perforations. I measured mean level of speech frequencies hearing loss, and its relation with the site and the size of the perforation analyzed.
Results The mean hearing loss at different sizes of the perforation at all speech frequencies was 37.4 dB, with ABG of 26.6 dB, and its maximum loss was detected in subtotal perforation of 42.3 dB, with ABG of 33.7 dB, at 500 Hz frequency, while in relation to the sites, it was 38.2 dB, with ABG of 26.8 dB, and its maximum loss was detected in big central site perforation of 42.1 dB, with ABG of 33.6 dB, at 500 Hz frequency.
Conclusions The hearing loss was proportionally related with the sizes of the perforations, and the posterior site had greater impact on the hearing than anterior site perforations. This was also applied to the frequency dependence hearing level, as was detected to be worse at lower frequencies as 500 Hz, than those of 1000–2000 Hz.
Simultaneous Incidental Parathyroid Carcinoma and Intrathyroid Parathyroid Gland in Suspected Renal Failure Induced Hyperparathyroidism
Authors: Pappa Andrew , Hackman Trevor 
Published: February 2017

AbstractHyperparathyroidism is a common disorder affecting more than hundreds of thousands of people annually. While most commonly secondary to an adenoma, it may also arise from four-gland hyperplasia or malignancy. In the case of primary hyperparathyroidism, the number of glands involved may be unknown prior to surgery. In contrast, the metabolic disorder associated with renal failure induced hyperparathyroidism ensures a hyperplasia picture. Despite the uniform hyperplasia seen in tertiary disease and the preoperative expectation for four-gland exploration, our case demonstrates the continued need for a surgeon's vigilance during dissection to identify all glands and appropriately use intraoperative parathyroid hormone (PTH) testing. In addition, while intraoperative PTH assessment is an effective method for confirming adequacy of treatment for hyperparathyroidism, only surgical pathology can confirm malignancy, which should be considered with PTH levels > 1,000. The case also underscores the importance of comprehensive surgery management and mindful interpretation of intraoperative PTH levels in the management of hyperparathyroidism. Standard surgical technique includes complete exploration of the central compartment, and thyroid lobectomy when the aforementioned exploration fails to reveal the necessary parathyroid tissue, especially with a persistently elevated PTH. Without a standardized progressive compartment exploration and judicious use of intraoperative hormone testing, intrathyroidal parathyroid glands can be missed.
Geometric localization of thermal fluctuations in red blood cells
Authors: Evans Arthur A. , Bhaduri Basanta , Popescu Gabriel , Levine Alex J. 
Published: February 2017

Significance
Cell shapes are related to their biological function. More generally, membrane morphology plays a role in the segregation and activity of transmembrane proteins. Here we show geometric implications regarding how cellular mechanics plays a role in localizing thermal fluctuations on the membrane. We show theoretically that certain geometric features of curved shells control the spatial distribution of membrane undulations. We experimentally verify this theory using discocyte red blood cells and find that geometry alone is sufficient to account for the observed spatial distribution of fluctuations. Our results, based on statistical physics and membrane elasticity, have general implications for the use of membrane shape to control thermal undulations in a variety of nanostructured materials ranging from cell membranes to graphene sheets.
Surgical Treatment of a Double Origin Posterior Inferior Cerebellar Artery Aneurysm and Insights From Embryology: Case Report and Literature Review
Authors: Silva Michael A. , See Alfred P. , Aziz-Sultan Mohammad A. , Patel Nirav J. 
Published: February 2017

Abstract

BACKGROUND AND IMPORTANCE: Aneurysms affecting double origin (DO) posterior inferior cerebellar artery (PICA) variants are rare. Most reports describe endovascular occlusion of the affected branch to treat the aneurysm, but we describe a patient in which open surgical sacrifice of 1 branch resulted in insufficient perfusion.
This case and our review of PICA embryology provide insight into treatment of aneurysms affecting duplicated intracranial vessels.

CLINICAL PRESENTATION: We report the only case of open surgical treatment of an aneurysm affecting a leg of a DOPICA. A 42-year-old woman presenting with the worst headache of her life was found to have a DOPICA aneurysm and initially treated by trapping the aneurysm. Intraoperative indocyanine green imaging revealed insufficient perfusion through the caudal branch, which was remediated by end-to-end anastomosis to preserve flow through both origins. The patient made a full recovery.

CONCLUSION: Treating a DOPICA aneurysm by sacrificing 1 of the origins is not possible for all patients. This first report of open surgical treatment of a DOPICA leg aneurysm suggests that 1 or both branches may be required for sufficient perfusion, and the unique embryology of DOPICA development suggests a possible mechanism.
Unexpected Complication of Cocaine-Associated Anti-Neutrophil Cytoplasmic Antibody Vasculitis Related to Persistent In-Hospital Cocaine Use
Authors: Olives Travis D. , Kornas Rebecca L. , Fujisawa Russell , Cole Jon B. 
Published: February 2017

Introduction:
Levamisole-adulterated cocaine has been implicated in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. We present a case of spontaneous intraperitoneal hemorrhage, an unexpectedly severe complication of cocaine-related ANCA vasculitis, developing late during hospitalization.

Case Report:
An adult male with a history of hepatitis C, distant cocaine use, and limited health care presented to a local emergency department (ED) with volume overload, renal failure, hyperkalemia and non-anion gap metabolic acidosis. An extensive workup ensued, followed by pulse-dose methylprednisolone and plasma exchange for ANCA vasculitis with crescentic glomerulonephritis. Tachycardia and hypertension persisted throughout hospitalization despite treatment. On hospital day (HD) 13, his abdomen became distended and tender. Mental status and blood pressure declined, and he was emergently intubated. Paracentesis revealed frank blood; hemoglobin declined from 10.6 to 4.6 g/dL during 10 hours. Laparotomy revealed 3.5 L of intraperitoneal blood and a bleeding omental vessel. Histopathology revealed necrotic aneurysmal dilatation diagnostic of systemic vasculitis. Urine cocaine metabolite was positive on HD #13, consistent with the patient's report of in-hospital cocaine use. He was discharged on HD #28 without further complications with plans for outpatient hemodialysis.

Discussion:
ANCA vasculitis is widely reported following levamisole-adulterated cocaine use. Catastrophic in-hospital hemorrhage due to ANCA vasculitis and vascular necrosis, though previously unreported, may occur with ongoing cocaine use.
Maternal Mortality & Injustice
Authors: Patton Cheryl M. 
Published: February 2017

ABSTRACT:
The incidence of maternal mortality rates (MMRs) is grossly higher in developing countries than in wealthier regions. Multiple factors are involved in the MMR. Much of the attention to lower deaths was given to biomedical causes. However, socioeconomic, healthcare availability, and cultural issues often impede a woman's chance of healthy maternal outcomes. Most maternal deaths are preventable. This article discusses the injustices that occur as a result of global maternal health disparities, and highlights organizations that are working to end preventable maternal deaths.
Benign Atrophic Papulosis (Degos Disease) With Lymphocytic Vasculitis and Lichen Sclerosus-Like Features
Authors: Kim Esther , Motaparthi Kiran 
Published: February 2017

Abstract:
Degos disease manifests as 2 distinct clinical variants, malignant atrophic papulosis and benign atrophic papulosis, which are distinguished by the presence or absence of systemic disease. Both forms feature cutaneous involvement typified by erythematous papules with scar-like centers, and the classic histologic picture is described as wedge-shaped dermal necrosis overlying thrombotic vasculopathy. However, the histopathology of early lesions is distinct and more variable. A case of benign atrophic papulosis with lymphocytic vasculitis and lichen sclerosus–like features is described, and the spectrum of histologic findings in Degos disease is reviewed.
Prospective Cohort Comparison of Visual Acuity and Contrast Sensitivity Between Femto Laser In Situ Keratomileusis and Orthokeratology for Low-to-Moderate Myopia
Authors: Tian Mingxia , Ma Ping , Mu Guoying 
Published: February 2017

Purpose:
To compare the visual acuity and contrast sensitivity (CS) after femto laser in situ keratomileusis (fLASIK) and orthokeratology (OK) in patients with low-to-moderate myopia.

Methods:
A total of 68 patients were enrolled in this prospective cohort study. Of these, 40 eyes from 40 patients with low-to-moderate myopia underwent fLASIK and 28 eyes from 28 patients underwent OK. In addition to uncorrected distance visual acuity and corrected distance visual acuity, photopic and mesopic CS (with CSV-1000E) were tested before treatment and at 1, 3, and 6 months after treatment.

Results:
The preoperative refraction and CS were not significantly different between the groups (P>0.05). Postoperative visual acuity and refraction were similar (P>0.05). The photopic CS of the fLASIK group was better than that of the OK group (P<0.01). The fLASIK mesopic CS was better than the OK at 3 c/d (P=0.023). In the fLASIK group, only the photopic CS of postoperative 12 c/d decreased at 1 month and 3 months (P<0.01) and 18 c/d decreased at 1 month (P=0.002); whereas in the OK group, all the postoperative photopic CS values decreased at 1 month (all P<0.01) and 3 months (P<0.05) and increased to the normal level at 6 months (P>0.05). While as to the mesopic CS, in the fLASIK group, the 3 c/d, 6 c/d, and 18 c/d decreased at 1 month (P<0.05) and in the OK group, the 3 c/d decreased at 1 month and 3 months (P<0.05) and the 6 c/d decreased at 3 months (P=0.041), and the 12 c/d and 18 c/d decreased at 1 month (P<0.01).

Conclusions:
These results show that fLASIK provides better visual quality than OK for patients with low-to-moderate myopia.
Photopic, Mesopic, and Scotopic Visual Acuity After 18 mW/cm2 Accelerated Corneal Cross-Linking
Authors: Asgari Soheila , Hashemi Hassan , Miraftab Mohammad , Shahhoseini Saied , Jafarzadhpur Ebrahim , Mehravaran Shiva , Fotouhi Akbar 
Published: February 2017

Objectives:
One-year changes in uncorrected (UDVA) and corrected (CDVA) distance visual acuity under different lighting conditions after accelerated cross-linking (CXL) in patients with progressive keratoconus in comparison with nontreated cases.

Methods:
In this nonrandomized clinical trial, the sample included 50 eyes in the CXL group and 40 eyes in the control group. Visual acuity was tested under photopic (100 lux), mesopic (20 lux), and scotopic (0.5 lux) lighting conditions at 6 months and 1 year.

Results:
Changes in all studied variables were similar in the two groups (all P>0.05) after adjusting for age, but the 0.02±0.17 logMAR reduction in scotopic UDVA in the CXL group showed a difference of marginal significance compared with the control group (P=0.061). In cases with baseline UDVA≤20/40, 1-year adjusted results in the CXL and control groups were, respectively, 0.61±0.34 and 0.83±0.35 logMAR for photopic UDVA (P=0.021), 0.48±0.22 and 0.68±0.27 logMAR for mesopic UDVA (P=0.033), and 0.21±0.14 and 0.26±0.07 logMAR for mesopic CDVA (P=0.056). In those with baseline UDVA greater than 20/40, 1-year adjusted results in the CXL and control groups were, respectively, 0.12±0.20 and 0.06±0.10 logMAR for mesopic UDVA (P=0.034) and 0.15±0.18 and 0.07±0.06 logMAR for scotopic UDVA (P=0.024). Other vision indices showed no significant intergroup differences (all P>0.05).

Conclusion:
Poor vision (UDVA≤20/40) keratoconus cases are more likely to achieve improved vision or a halt in its deterioration after CXL. In cases with good vision (UDVA>20/40), however, although further photopic vision impairment is halted, they may experience worse vision under mesopic and scotopic conditions.
How to Predict Oral Rehydration Failure in Children With Gastroenteritis
Authors: Geurts Dorien , Steyerberg Ewout W. , Moll Henriëtte , Oostenbrink Rianne 
Published: February 2017

ABSTRACTObjectives:Oral rehydration is the standard in most current guidelines for young children with acute gastroenteritis (AGE). Failure of oral rehydration can complicate the disease course, leading to morbidity due to severe dehydration. We aimed to identify prognostic factors of oral rehydration failure in children with AGE.Methods:A prospective, observational study was performed at the Emergency department, Erasmus Medical Centre, Rotterdam, The Netherlands, 2010–2012, including 802 previously healthy children, ages 1 month to 5 years with AGE. Failure of oral rehydration was defined by secondary rehydration by a nasogastric tube, or hospitalization or revisit for dehydration within 72 hours after initial emergency department visit.Results:We observed 167 (21%) failures of oral rehydration in a population of 802 children with AGE (median 1.03 years old, interquartile range 0.4–2.1; 60% boys). In multivariate logistic regression analysis, independent predictors for failure of oral rehydration were a higher Manchester Triage System urgency level, abnormal capillary refill time, and a higher clinical dehydration scale score.Conclusions:Early recognition of young children with AGE at risk of failure of oral rehydration therapy is important, as emphasized by the 21% therapy failure in our population. Associated with oral rehydration failure are higher Manchester Triage System urgency level, abnormal capillary refill time, and a higher clinical dehydration scale score.
Intestinal Metaplasia of the Esophagus in Children With Esophageal Atresia
Authors: Hsieh Helen , Frenette Adam , Michaud Laurent , Krishnan Usha , Dal‐Soglio Dorothée B. , Gottrand Frederic , Faure Christophe 
Published: February 2017

Objectives:Patients with esophageal atresia/tracheoesophageal fistula (EA‐TEF) can develop Barrett esophagus as a long‐term consequence of their condition. Intestinal metaplasia (IM), a risk factor for developing adenocarcinoma of the esophagus, has not been well characterized in the pediatric population.Methods:Retrospective review of patients with EA‐TEF followed at 3 academic pediatric centers between the years 1997 and 2014.Results:Among 542 children and adolescents, 1.3% (7 patients, 5 girls) were diagnosed with IM based on endoscopy and pathology. Six of the patients had EA‐TEF type C, whereas the last patient had a “long gap” type A atresia. Patients were diagnosed with gastric metaplasia either before the IM diagnosis in 4 patients or concomitantly in 3. The median (range) age of diagnosis for gastric metaplasia was 7.9 (range 2–17.2) and for IM 10.9 (2–17.2) years. Gastroesophageal reflux (GER) symptoms were nonspecific. Five patients were on proton pump inhibitor therapy for symptomatic GER at the time of diagnosis of IM. 2 of the 7 patients had previously undergone Nissen fundoplication. One patient, who had undergone a Nissen fundoplication, was restarted on proton pump inhibitor once the diagnosis of IM was made. All patients had repeated endoscopy and dysplasia was not observed with a median follow‐up of 1.7 (range 1–4.9) years.Conclusions:IM occurs in patients with EA‐TEF, some as young as 2 years. Therefore, early endoscopic surveillance should be considered in this GER‐prone population.