bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Benign CD8+ Proliferation: A Rare Affection that Can Mimic a Lymphoma Relapse
Authors: Osovská Marcela , Janíková Andrea , Křen Leoš , Marečková Andrea
Published: March 2019

Chronic benign CD8+ proliferation is a rare syndrome that can take the form of a variety of other diseases. Peripheral adenopathy, cytopenia, and infiltration of the liver, kidneys, bowels, or other organs are the most common clinical presentations of the syndrome. CD8+ expansion can be clonal and nonclonal. It generally occurs in patients with innate or acquired immunodeficiency (HIV+) or in patients receiving immunosuppressive therapy. It has been found repeatedly in patients who developed severe hypogammaglobulinemia after treatment with rituximab. Diagnosis of the disease can be difficult because it can mimic relapse of a lymphoma, and a common biopsy examination cannot identify the problem at first. The authors describe a case of a patient pretreated with rituximab who developed agammaglobulinemia and peripheral adenopathy. Biopsy of an enlarged lymph node showed “reactive lymphadenitis.” Additionally, a flow-cytometric examination revealed a pathological population of CD8+ lymphocytes. The treatment, which differed from treatments of lymphoma relapse, consisted of corticosteroids and IVIG substitutions and has led to a regression of clinical symptoms. With more frequent usage of rituximab, one can expect increased occurrence of a very rare CD8+ expansion that can reliably emulate the relapse of a lymphoma.
Relationship between Lower Urinary Tract Dysfunction and Clinical Features in Chinese Parkinson’s Disease Patients
Authors: Xu Duo , Han Shunchang , Wang Jue , Feng Juan
Published: March 2019

Background. Lower urinary tract (LUT) dysfunction is very common in Parkinson’s disease (PD) patients. However, the number of studies conducted on LUT dysfunction and its related factors in Chinese PD patients is very limited, and there is no international consensus concerning the results. Methods. This cross-sectional study enrolled 100 Chinese PD patients. The patients were classified based on their overactive bladder symptom score (OABSS) and then assigned to either a PD with overactive bladder (PD-OAB) group or a PD with no overactive bladder (PD-NOAB) group. A binary logistic regression analysis was performed to identify the accompanying factors for overactive bladder (OAB). Next, correlations between the OABSS and patient sex, age, age of onset, disease duration, MDS-UPDRS-III, H-Y stage, PD subtype, treatment, education, and nonmotor symptoms were analyzed to identify factors correlated with LUT dysfunction. Results. Eighty nine (89%) of the PD patients suffered from LUT dysfunction, and OAB was diagnosed in 45 (45%) of those PD patients. The most common lower urinary tract (LUT) symptom in the PD patients was nighttime frequency (86%), followed by urgency (50%), urge incontinence (34%), and daytime frequency (17%). Patients in the PD-OAB group had an older age and age of onset, were at a more advanced Hoehn–Yahr stage, and had more severe motor symptoms and nonmotor symptoms, including worse cognition, and a greater incidence of REM sleep behavior disorder (RBD). A binary logistic regression analysis showed that a lower Frontal Assessment Battery (FAB) score, higher H-Y stage, and RBD accompanied with a higher prevalence of OAB in PD patients. A multiple linear regression analysis showed that the OABSS was significantly influenced by the FAB score, H-Y stage, RBD, and age. Conclusions. The FAB score, H-Y stage, and RBD are accompanying factors for OAB. A higher OABSS in PD patients was related to a lower FAB score for frontal lobe executive dysfunction, a higher H-Y stage for severity of motor disorders, RBD, and an older age.
Minocycline Protects against Rotenone-Induced Neurotoxicity Correlating with Upregulation of Nurr1 in a Parkinson’s Disease Rat Model
Authors: Sun Congcong , Wang Yun , Mo Mingshu , Song Chengyuan , Wang Xingbang , Chen Si , Liu Yiming
Published: March 2019

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson’s disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.
On the vDVZ Discontinuity in Massive Conformal Gravity
Authors: Faria F. F.
Published: March 2019

By taking the massless limit of linearized massive conformal gravity coupled to a source, we show that the theory is free from the vDVZ discontinuity. This result is confirmed when we take the massless limit of the gravitational potential of the theory, which is shown to be finite at the origin.
Distributed Cooperative Backpressure-Based Traffic Light Control Method
Authors: Hao Shenxue , Yang Licai , Ding Li , Guo Yajuan
Published: March 2019

On the foundation of the original backpressure-based traffic light control algorithm, a distributed cooperative backpressure-based traffic light control method is proposed in this paper. The urban traffic network is modeled as a smart agent-controlled queuing network, in which the intersection agents exchange the queue length information and the selected activating light phase information of neighboring intersections through communications and determine the activating light phase at each time slot according to local traffic information. The improved phase pressure computation method considers the phase state of downstream intersections instead of only the queue length of the local intersections. Light phase switching coordination among adjacent intersections is achieved using the consensus-based bundle algorithm, in which the cooperative light phase switching problem is viewed as a task assignment issue among adjacent intersections. Simulation results illustrated that the proposed cooperative backpressure-based traffic light control method obtained better performance than the original backpressure-based and fixed-time traffic control methods.
The Attributable Direct Medical Cost of Healthcare Associated Infection Caused by Multidrug Resistance Organisms in 68 Hospitals of China
Authors: Jia Huixue , Li Weiguang , Hou Tieying , Ma Hongqiu , Yang Yun , Wu Anhua , Liu Yunxi , Wen Jianguo , Yang Huai , Luo Xiaoli , Xing Yawei , Zhang Weihong , Wu Yinghong , Ding Lili , Liu Weiping , Lin Ling , Li Ying , Chen Meilian , Li Liuyi
Published: March 2019

Healthcare associated infection (HAI) is known to increase the economic burden of patients while the medical cost due to MDRO HAI is even higher. Three hundred eighty-one multidrug resistance organisms (MDROs) healthcare associated infection (HAI) case-patients and three hundred eighty-one matched control-patients were identified between January and December in 2015. The average total hospitalization medical cost of the case group was $6127.65 and that of the control group was $2274.02. The difference between the case group and the control group was statistically significant (t = 21.07; P < 0.01). The attributable cost of MDRO HAI was $3853.63. The direct medical costs due to different MDRO infections were different. The increased medical costs of CR-AB, CR-KP, and CR-PA were significantly higher than that of MRSA, MRSE, ESBL E. coli, and ESBL Kp (P < 0. 05). Among the subitem expenses, the drug cost increased the most (the average cost was $1457.72), followed by the treatment fee and test fee; the differences were statistically significant (P < 0.01).
Highly Soluble Drugs Directly Granulated by Water Dispersions of Insoluble Eudragit® Polymers as a Part of Hypromellose K100M Matrix Systems
Authors: Mašková Eliška , Naiserová Martina , Kubová Kateřina , Mašek Josef , Pavloková Sylvie , Urbanová Martina , Brus Jiří , Vysloužil Jakub , Vetchý David
Published: March 2019

The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).
Rapidly Progressive Glomerulonephritis Secondary to IgA Nephropathy in a Patient with Systemic Lupus Erythematosus
Authors: Patel Amol M. , Karam Lily Anne Romero , Rojas Stephanie C. Fuentes , Redfearn Warren E. , Truong Luan D. , Gonzalez Juan M.
Published: March 2019

Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE). IgA nephropathy is a common type of primary glomerulonephritis. Renal manifestations in SLE patients are often due to lupus nephritis; however, renal diseases unrelated to lupus nephritis are rarely reported. While crescentic IgA nephropathy with rapid clinical progression is rare, its development in patients with SLE in the absence of lupus nephritis is even more unusual. A 74-year-old woman with a history of SLE without known renal involvement, chronic kidney disease stage IIIa, congestive heart failure, hypertension, and type 2 diabetes mellitus presented with acute kidney injury. Her creatinine continued to rise rapidly. Renal biopsy revealed mesangial proliferative glomerulonephritis with crescent formation. Immunofluorescent staining showed IgA and C3 mesangial deposition and absence of C4 and C1q, consistent with IgA nephropathy. She received a course of methylprednisolone and plasmapheresis. Unfortunately, her renal function continued to deteriorate, and she was started on hemodialysis which was continued after hospital discharge. This case illustrates crescentic IgA nephropathy without lupus nephritis as the cause of acute kidney injury in a patient with SLE. It highlights the observation that renal diseases other than lupus nephritis can develop in SLE patients.
Thermoelastic Coupling Vibration and Stability Analysis of Rotating Annular Sector Plates
Authors: Yang Yongqiang , Wang Zhongmin
Published: March 2019

This study investigates the thermoelastic coupling vibration and stability of rotating annular sector plates. Based on Hamilton’s principle and thermal conduction equation with deformation effect, the differential equation of transverse vibration for a rotating annular sector plate is established. The differential equation of vibration and corresponding boundary conditions are discretized by the differential quadrature method. Then, the thermoelastic coupling transverse vibrations under three different boundary conditions are calculated. The change curve of the first three order dimensionless complex frequencies of the rotating annular sector plate with the dimensionless angular speed are analyzed in the case of the thermoelastic coupling and uncoupling. The effects of the dimensionless angular speed, the ratio of inner to outer radius, the sector angle, and the dimensionless thermoelastic coupling coefficient on transverse vibration and stability of the annular sector plate are discussed. Finally, we obtained the type of instability and corresponding critical speed of the rotating annular sector plate in the case of the thermoelastic coupling and uncoupling.
Unusual Presentation of an Uncommon Disease: 24-Hour Cyclic Esotropia
Authors: Paciuc-Beja Miguel , Galicia-Alfaro Victor Hugo , Retchkiman-Bret Myriam
Published: March 2019

Cyclic esotropia is an extremely uncommon form of strabismus. Classically, it follows a 48-hour cycle with 24 hours of orthotropia and 24 hours of manifest esotropia. We are reporting the first case of cyclic esotropia with a 24-hour cycle. A 7-year-old hyperopic female was seen with an esotropia of 6-month duration. Hyperopic glasses were prescribed by another ophthalmologist prior to our evaluation of the patient. While wearing her glasses, esotropia occurred during the morning and early afternoon. After 3.00pm, her eyes were “straight.” Many photographs were reviewed, confirming the esotropia pattern. Neurological evaluation was normal, including imaging and blood work to rule out thyroid pathology and myasthenia. After seeing the patient multiple times at different hours on different days, the diagnosis of cyclic esotropia was made. Bimedial recessions were performed with good results. The patient was still “straight” at distance and near 2 years after surgery.
Tubal Origin of “Ovarian” Low-Grade Serous Carcinoma: A Gene Expression Profile Study
Authors: Wang Yiying , Hong Shuhui , Mu Jingyi , Wang Yue , Lea Jayanthi , Kong Beihua , Zheng Wenxin
Published: March 2019

Objective. Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, serous cystadenomas, and serous borderline tumors. Our previous study with clinicopathological approach showed that the majority ovarian epithelial inclusions are derived from the fallopian tubal epithelia rather than from ovarian surface epithelia. This study was designed to gain further insight into the cellular origin of ovarian low-grade serous carcinomas by differential gene expression profiling studies. Methods. Gene expression profiles were studied in 43 samples including 11 ovarian low-grade serous carcinomas, 7 serous borderline tumors, 6 serous cystadenomas, 6 ovarian epithelial inclusions, 7 fallopian tubal epithelia, and 6 ovarian surface epithelia. Comprehensive analyses with hierarchical clustering, Rank-sum analysis and Pearson correlation tests were performed. Final validation was done on selected genes and corresponding proteins. Results. The gene expression profiles distinguished ovarian low-grade serous carcinomas from ovarian surface epithelia, but not from fallopian tubal epithelia cells. Hierarchical clustering analysis showed ovarian serous tumors and ovarian epithelial inclusions were clustered closely in a branch, but separated from ovarian surface epithelia. The results were further validated by selected proteins of OVGP1, WT-1, and FOM3, which were highly expressed in the samples of the fallopian tube, ovarian epithelial inclusions, and ovarian serous tumors, but not in ovarian surface epithelia. The reverse was true for the protein expression patterns of ARX and FNC1. Conclusions. This study provides evidence in a molecular level that ovarian low-grade serous carcinomas likely originate from the fallopian tube rather than from ovarian surface epithelia. Similar gene expression profiles among fallopian tube, ovarian epithelial inclusions, and serous tumors further support that ovarian low-grade serous carcinomas develop in a stepwise fashion. Such findings may have a significant implication for “ovarian” cancer-prevention strategies.
Seizures following Intoxication with a Common Antituberculosis Drug
Authors: Lahlou Adnane , Benlamkaddem Saïd , Berdai Mohamed Adnane , Harandou Mustapha
Published: March 2019

Isoniazid is an antimycobacterial agent commonly prescribed in most tuberculosis chemotherapy regimens. Its side effects are widely known including mainly liver toxicity and peripheral neuropathy. The toxic effects of isoniazid are dose-related. Toxic doses are estimated at 35–40 mg/kg and fatal doses at 150 mg/kg. Treatment consists primarily of basic life support, antiepileptic drugs, and pyridoxine. The case is of one of the children with intentional isoniazid poisoning, the drug belonging to an uncle currently under antituberculosis treatment, resulting in tonic-clonic seizures. During her hospitalization in the paediatric intensive care unit, her neurological status as well as her lab values was closely monitored, and despite initial deterioration, the patient was discharged from critical care a week after full recovery.
Modeling and Simulation of Nonmotorized Vehicles’ Dispersion at Mixed Flow Intersections
Authors: Liu Qiyuan , Sun Jian , Tian Ye , Ni Ying , Yu Shinan
Published: March 2019

Interactions between motorized and nonmotorized vehicles have drawn considerable attention from researchers. They are commonly seen at mixed flow intersections where nonmotorized vehicles, without the restriction of lane markers or physical barriers, may disperse into adjacent lanes and thus lead to complex interactions with motorized vehicles. Such a dispersion phenomenon between heterogeneous participants (e-bikes and bicycles as nonmotorized vehicles versus motorized vehicles) is difficult to model. In this paper, we were inspired by the dispersion of charged particles in an electric field and modeled the dispersion phenomenon of go-straight, nonmotorized vehicles at mixed flow intersections accordingly, as it was discovered in this research that these two dispersion phenomena share three underlying commonalities with each other. A novel particle dispersion model (PDM) based on a particle’s movement in an electric field is proposed. The model is calibrated and validated using 1,490 high-definition sets of trajectory data for go-straight, nonmotorized vehicles during 43 cycles at two typical mixed flow intersections. The PDM is compared with the social force model (SFM) on their dispersion characteristics that are used to describe the nonmotorized bicycles’ behavior. The results show that the PDM performs better than the SFM with regard to depicting the dispersion characteristic indices of the nonmotorized vehicles, such as the travel time, the dispersion intensity of heterogeneous nonmotorized vehicles, the sectional dispersion degree, and other dispersion characteristics.
Diagnosis and Treatment of a Symptomatic Posterior Cruciate Ganglion Cyst in a Child with Autism
Authors: Andreozzi Valerio , Monaco Edoardo , Conteduca Fabio , Iorio Raffaele , Mazza Daniele , Drogo Piergiorgio , Ferretti Andrea
Published: March 2019

Introduction. Intra-articular ganglion cysts of the knee joint are rare and mostly incidental findings in magnetic resonance imaging (MRI) or arthroscopy. Posterior cruciate ligament (PCL) ganglion cyst in a child is an extremely rare finding, and to the best of our knowledge, only one case has been described in the literature. We report a case of a large intra-articular ganglion cyst of the knee arising from the PCL in an autistic child. Case Presentation. An 8-year-old Caucasian boy affected by autism presented with nontraumatic knee pain. His parents, observing child’s gait, reported recurrent limp while walking, sometimes accompanied by knee locking. Clinical examination was hindered by the noncompliance of the patient and revealed painful limitation of terminal flexion and extension. MRI scans showed a large ganglion cyst located in the intercondylar notch. Arthroscopy confirmed an intrasubstance PCL ganglion cyst, extending both anteriorly and posteriorly. Complete excision of the cyst was performed, with full recovery of the child and no recurrence. Conclusion. In pediatric patients with pain or limited knee range of motion, physicians should consider the possibility of a ganglion cyst arising from the PCL, despite its rarity. Arthroscopic excision is a safe and effective procedure that guarantees a complete recovery of the patient with the lowest rate of recurrence.
A Case Report of Massive Acetaminophen Poisoning Treated with a Novel “Triple Therapy”: N-Acetylcysteine, 4-Methylpyrazole, and Hemodialysis
Authors: Kiernan Emily A. , Fritzges Julie A. , Henry Kathryn A. , Katz Kenneth D.
Published: March 2019

Massive acetaminophen (N-acetyl-p-aminophenol; APAP) ingestion is characterized by a rapid onset of mitochondrial dysfunction, including metabolic acidosis, lactemia, and altered mental status without hepatotoxicity which may not respond to the standard doses of N-acetylcysteine (NAC). A 64-year-old woman without medical history presented comatose after an ingestion of 208 tablets of Tylenol PM™ (APAP 500 mg and diphenhydramine 25 mg). The initial APAP concentration measured 1,017 µg/mL (therapeutic range 10-30 µg/mL), and elevated anion gap metabolic acidosis, lactemia, and 5-oxoprolinemia were detected. High-dose intravenous (IV) NAC, 4-methylpyrazole (4-MP), and hemodialysis (HD) were initiated. She was transferred to a liver transplant center and continued both NAC and HD therapies until complete resolution of metabolic acidosis and coma without developing hepatitis. She was discharged without sequelae. This is the fourth highest APAP concentration recorded in a surviving patient. Moreover, this is the first report of a novel “triple therapy” using NAC, 4-MP, and HD in the setting of massive APAP ingestion that presents with coma, elevated anion gap metabolic acidosis, and lactemia. Emergency physicians should recognize these critically ill patients and consider high-dose NAC, 4-MP, and HD to be initiated in the emergency department (ED).
A New Controlled-Release Material Containing Metronidazole and Doxycycline for the Treatment of Periodontal and Peri-Implant Diseases: Formulation and In Vitro Testing
Authors: Nastri Livia , De Rosa Alfredo , De Gregorio Vincenza , Grassia Vincenzo , Donnarumma Giovanna
Published: March 2019

Background. Several locally administered antimicrobials have been studied in the literature as adjunctive or primary treatments for periodontitis and peri-implantitis with conflicting results. Objective. The aim of this study was twofold: (1) the formulation of a controlled-release material containing metronidazole and doxycycline; (2) an in vitro evaluation of its antibacterial properties against planktonic and biofilm species involved in periodontal and peri-implant diseases. Methods. Doxycycline (10 mg/ml) and metronidazole (20 mg/ml) were incorporated into a hydroxyethylcellulose-polyvinylpyrrolidone-calcium polycarbophil gel. Three milliliters of gel were dialyzed against Dulbecco’s phosphate-buffered saline for 13 days. Antibiotics release at 3, 7, 10, and 13 days was determined spectroscopically. The inhibitory activity of the experimental gel was tested against A. actinomycetemcomitans, S. sanguinis, P. micra, and E. corrodens with an agar diffusion test, an inactivation biofilm test, and a confocal laser scanning microscope study (CLSMS) for S. sanguinis up to 20 days. Results. After 13 days, the released doxycycline was 9.7% (at 3 days = 1.2 mg; 7 days = 0.67 mg; 10 days = 0.76 mg; 13 days = 0.29 mg), while metronidazole was 67% (30 mg, 6.8 mg, 2.5 mg, and 0.9 mg at the same intervals). The agar diffusion test highlights that the formulated gel was active against tested microorganisms up to 312 h. Quantitative analysis of biofilm formation for all strains and CLSMS for S. sanguinis showed a high growth reduction up to 13 days. Conclusions. The in vitro efficacy of the newly formulated gel was confirmed both on planktonic species and on bacterial biofilm over a period of 13 days. The controlled-release gel containing metronidazole and doxycycline had an optimal final viscosity and mucoadhesive properties. It can be argued that its employment could be useful for the treatment of periodontal and peri-implant diseases, where conventional therapy seems not successful.
Tumor Landscapes: β-Catenin Drives Immune Desertification
Authors: Dangaj Denarda , Barras David , Coukos George
Published: March 2019

Immune checkpoint blockade therapy requires a preestablished activated immune landscape. Understanding tumor-intrinsic mechanisms that lead to T-cell desertification is key to resensitizing them to such therapies. The WNT/β-catenin tumor-intrinsic signaling is emerging as an immune exclusion pathway that holds high promise to counteract resistance to immunotherapy.

See related article by Luke et al., p. 3074
A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression
Authors: Auciello Francesca R. , Bulusu Vinay , Oon Chet , Tait-Mulder Jacqueline , Berry Mark , Bhattacharyya Sohinee , Tumanov Sergey , Allen-Petersen Brittany L. , Link Jason , Kendsersky Nicholas D. , Vringer Esmee , Schug Michelle , Novo David , Hwang Rosa F. , Evans Ronald M. , Nixon Colin , Dorrell Craig , Morton Jennifer P. , Norman Jim C. , Sears Rosalie C. , Kamphorst Jurre J. , Sherman Mara H.
Published: March 2019

Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features transdifferentiation of tissue-resident pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, a process induced by PDAC cells but of unclear significance for PDAC progression. Here, we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state. Specifically, stroma-derived lysophosphatidylcholines support PDAC cell synthesis of phosphatidylcholines, key components of cell membranes, and also facilitate production of the potent wound-healing mediator lysophosphatidic acid (LPA) by the extracellular enzyme autotaxin, which is overexpressed in PDAC. The autotaxin–LPA axis promotes PDAC cell proliferation, migration, and AKT activation, and genetic or pharmacologic autotaxin inhibition suppresses PDAC growth in vivo. Our work demonstrates how PDAC cells exploit the local production of wound-healing mediators to stimulate their own growth and migration.

Significance:

Our work highlights an unanticipated role for PSCs in producing the oncogenic LPA signaling lipid and demonstrates how PDAC tumor cells co-opt the release of wound-healing mediators by neighboring PSCs to promote their own proliferation and migration.

See related commentary by Biffi and Tuveson, p. 578.

This article is highlighted in the In This Issue feature, p. 565
Nonpharmacological Relaxation Technology for Office-Based Rhinologic Procedures
Authors: Marino Michael J. , Luong Amber , Yao William C. , Citardi Martin J.
Published: March 2019

Background: Office-based rhinologic procedures are increasingly performed to control costs and enhance patient convenience. Adequate management of pain and anxiety is essential for the technical performance of these procedures, in addition to ensuring patient comfort. Pharmacologic agents are often used to manage anxiety and pain. Nonpharmacological adjuncts may be useful for achieving these effects without oral opioids and benzodiazepines. Methods: Charts of patients who underwent office-based rhinologic procedures with the NuCalm system (Solace Lifesciences, Inc., Wilmonton, DE, USA) in combination with local anesthesia were reviewed. NuCalm is a proprietary system that combines cranial electrotherapy stimulation, neuroacoustic software, light-blocking lenses, and topical γ-­aminobutyric acid. Patients rated their pain and anxiety before, during, and after the procedure. Results: Twenty-five patients underwent office procedures using the NuCalm system. Preoperative anxiety (2.00) was significantly higher than postoperative anxiety (1.25) according to patient reporting on a 5-point scale (p = 0.005). Preoperative pain (1.83) was not significantly different from intraoperative (2.54) and postoperative pain (2.04, p = 0.054). Conclusions: A variety of office-based rhinologic procedures are technically feasible and can be performed with adequate patient comfort without the use of oral drugs. Adjuncts to pharmacologic agents may enhance pain control and anxiety management and improve patient tolerance of these procedures.
Long-Term Neurodevelopmental and Functional Outcomes of Infants Born Very Preterm and/or with a Very Low Birth Weight
Authors: Hollanders Jonneke J. , Schaëfer Nina , van der Pal Sylvia M. , Oosterlaan Jaap , Rotteveel Joost , Finken Martijn J.J. ,   on behalf of the Dutch POPS-19 Collaborative Study Group
Published: March 2019

Background: Birth weight (BW) is often used as a proxy for gestational age (GA) in studies on preterm birth. Recent findings indicate that, in addition to perinatal outcomes, subjects born very preterm (VP; GA < 32 weeks) differ from those with a very low birth weight (VLBW; BW < 1,500 g) in postnatal growth up to their final height. Objective: To study whether neurodevelopmental and functional outcomes at the age of 19 years differ in VP and/or VLBW subjects. Methods: 705 19-year-old subjects from the Project on Preterm and Small-for-Gestational-Age Infants (POPS) cohort were classified as (1) VP+/VLBW+ (n = 354), (2) VP+/VLBW– (n = 144), or (3) VP–/VLBW+ (n = 207), and compared with regard to IQ as assessed with the Multicultural Capacity Test-intermediate level; neuromotor function using Touwen’s examination of mild neurologic dysfunction; hearing loss; self- and parent-reported behavioral and emotional functioning; educational achievement and occupation; and self-assessed health using the Health Utilities Index and the London Handicap Scale. Results: VP+/VLBW– infants, on average, had 3.8-point higher IQ scores (95% confidence interval [CI] 0.5–7.1), a trend towards higher educational achievement, 3.3-dB better hearing (95% CI 1.2–5.4), and less anxious behavior, attention problems, and internalizing behavior than to VP+/VLBW+ subjects. VP–/VLBW+ infants reported 1.8 increased odds (95% CI 1.2–2.6) of poor health compared to VP+/VLBW+ subjects. Conclusions: At the age of 19 years, subjects born VP+/VLBW+, VP+/VLBW–, and VP-/VLBW+ have different neurodevelopmental and functional outcomes, although effect sizes are small. Hence, the terms VP and VLBW are not interchangeable. We recommend, at least for industrialized countries, to base inclusion in future studies on preterm populations on GA instead of on BW.
Mediterranean Diet Index (KIDMED) Adherence, Socioeconomic Determinants, and Nutritional Status of Portuguese Children: The Eat Mediterranean Program
Authors: Rito Ana Isabel , Dinis Ana , Rascôa Carla , Maia António , Mendes Sofia , Stein-Novais Camila , Lima João
Published: March 2019

Background: Despite its health benefits, adherence to the Mediterranean diet (MD) has been decreasing, particularly in young generations and in Mediterranean regions, including Portugal. Socioeconomic and lifestyle factors have been shown to influence children and adolescents’ eating habits. This study aimed to assess the association between socioeconomic factors and children’s nutritional status with the MD adherence using the Eat Mediterranean (EM) program. Methods: Participant’s BMI and adherence to the MD diet was assessed at baseline and after the intervention. Data regarding socioeconomic status and KIDMED Index were collected using a family record form. The intervention consisted of various educational sessions addressing the principles and promoting a Mediterranean dietary pattern in schools belonging to two municipalities in the central area of Portugal. A total of 1,772 participants (from preschool to secondary school) met the inclusion criteria for the study. Results: At the end of the program, the adherence to the MD diet improved significantly with participants increasing their adherence to an optimal diet by 17.6%. Daily intake of foods belonging to the MD diet also increased significantly, and the intake of high energy density foods decreased. Mother’s educational level and household income were significantly (p < 0.0001) associated with optimal MD adherence by participants, in both stages. Nutritional status was not associated with the KIDMED Index. Discussion: The EM program showed to be effective in increasing MD adherence in this study population since optimal MD adherence was reported in most participants at the end of the EM program. Household income and mother’s educational level were positively associated with the diet quality of the children and adolescents.
HIF1α Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia
Authors: Liang Xiao , Liu Xuemei , Lu Fuxin , Zhang Yunling , Jiang Xiangning , Ferriero Donna M.
Published: March 2019

Hypoxia-inducible factor 1α (HIF1α) is a key regulator of oxygen homeostasis, and its target genes mediate adaptive, protective, and pathological processes. The role of HIF1α in neuronal survival is controversial and the brain maturation stage is important in determining its function in brain ischemia or hypoxia-ischemia (HI). In this study, we used neuron-specific HIF1α knockout mice at postnatal day 9 (P9), and immature cortical neurons (days 7–8 in vitro) treated with the HIF1α inhibitor 2-methoxyestradiol (2ME2) or stabilizer dimethyloxalylglycine (DMOG), to examine the function of neuronal HIF1α in neonatal HI in vivo (Vannucci model) and in vitro (oxygen glucose deprivation, OGD). Inhibition of HIF1α with 2ME2 in primary neurons or deletion of neuronal HIF1α in P9 mice increased both necrotic and apoptotic cell death following HI, as evaluated by the protein levels of 145/150-kDa and 120-kDa spectrin breakdown products 24 h after HI. DMOG attenuated neuronal death right after OGD. Acute pharmacological manipulation of HIF1α synchronously regulated the expression of its targets, vascular endothelial growth factor (VEGF) and erythropoietin (Epo), in the same manner. The in vivo findings agree with our previous data using the same HIF1α-deficient mice at an earlier age. This study confirms the role of neuronal HIF1α signaling in the endogenous protective responses following HI in the developing brain.
Endoscopic Lung Volume Reduction: An Expert Panel Recommendation – Update 2019
Authors: Herth Felix J.F. , Slebos Dirk-Jan , Criner Gerard J. , Valipour Arschang , Sciurba Frank , Shah Pallav L.
Published: March 2019

Endoscopic lung volume reduction (ELVR) therapies are gaining prominence as a treatment option with guideline recommendations by COPD GOLD and NICE and the recent FDA approval for endobronchial valves. The transition from an experiment-based therapy only to clinical care comes with new challenges. A significant volume of evidence-based data has been published; all data demonstrate consistent improvements in several aspects of patient outcomes. Patients suffering from severe air trapping and thoracic hyperinflation seem to benefit the most from ELVR. In addition to lung function, baseline assessment should ideally include cardiopulmonary exercise testing, high-resolution computer tomography scan, perfusion scintigraphy, and echocardiography. This expert ELVR statement updates best practice recommendations from 2017 regarding patient selection and utilization of these various techniques for treating patients with advanced emphysema.
Idiopathic Papular Dermatitis in the Spectrum of Chronic Papular Eruptions (Subacute Prurigo): Reappraisal and Diagnostic Algorithm
Authors: Ollech Ayelet , Hodak Emmilia , David Michael , Trattner Akiva , Didkovsky Elena , Pavlovsky Lev
Published: March 2019

Background: The clinical diagnosis of papular eruptions is common but poorly characterized in the literature and the etiology is often unknown. Objective: To characterize the entity of idiopathic papular dermatitis in the spectrum of chronic papular eruptions. Methods: The cohort consisted of patients who presented at a tertiary medical center in 2005–2014 with a papular eruption of at least 4 months’ duration. Findings on histological analysis and thorough clinical investigation, performed in all cases, were collected. The patients completed a questionnaire on disease course and outcome. Results: Sixty-five patients were included. Sixteen patients showed morphological changes over time and were excluded. Investigations in the remaining 49 patients with a consistent papular morphology yielded a well-defined diagnosis in 23 (46%). Twenty-six patients (54%; 14 male) were diagnosed with idiopathic papular dermatitis. Their mean age at onset was 61.6 ± 14.4 years and the mean duration of disease 3.11 ± 2.726 years. In 60%, the rash resolved with conservative treatment during follow-up (mean 4.35 ± 2.53 years). Conclusions: Chronic papular eruptions encompass a wide range of skin diseases. In more than half of the cases, the etiopathogenesis remains unclear. On the basis of our results, we propose a diagnostic algorithm for idiopathic papular dermatitis.
Neurofibromatosis Type 1 – Association with Breast Cancer, Basal Cell Carcinoma of the Skin, and Low-Grade Peripheral Nerve Sheath Sarcoma: Case Report and Literature Review
Authors: Zapata Laguado Martin Ignacio , Lizarazo Hurtado Diego Vicente , Bonilla Gomez Carlos Eduardo
Published: March 2019

Neurofibromatosis type 1 is a rare medical condition that raises the probability of having distinct types of malignant and benign neoplasms. Nevertheless, the association with breast cancer is rare, and metachronic neoplasia with a distinct histologic subtype is an association that has never been reported before. Here we describe a case of a primary breast tumor, with posterior development of basal cell carcinoma of the skin, and a low-grade peripheral nerve sheath sarcoma.
Dental Cone Beam Computed Tomography in Children: Clinical Effectiveness and Cancer Risk due to Radiation Exposure
Authors: De Felice Francesca , Di Carlo Gabriele , Saccucci Matteo , Tombolini Vincenzo , Polimeni Antonella
Published: March 2019

Firstly used in the early 90s to generate 3-dimensional projections of X-ray images, cone beam computed tomography (CBCT) has resulted in a large application in dentomaxillofacial imaging, even in children. CBCT uses ionizing radiation that may cause damage to the DNA, and children are at the greatest carcinogenesis risk due to their higher tissue radiosensitivity and their longer life expectancy compared to adults. The questions of whether the cancer risk is really increased after repeated dental CBCT in childhood and of what the underlying biological basis is have become hot topics in the field of dentistry and radiobiology. We performed an overview of the current literature to assess an acceptable role of CBCT in pediatric dentistry.
Appropriate Management of Attenuated Familial Adenomatous Polyposis: Report of a Case and Review of the Literature
Authors: Sokic-Milutinovic Aleksandra
Published: March 2019

Hereditary polyposis syndromes in which APC gene germline mutations can lead to colorectal carcinogenesis are familial adenomatous polyposis (FAP), attenuated FAP (AFAP) and MUTYH-associated polyposis. All 3 syndromes increase the potential for the development of colorectal cancer. AFAP is diagnosed if less than 100 adenomas are detected in the colon at presentation. AFAP is inherited in an autosomal dominant manner. We present a case of a 22-year-old female with AFAP who was treated with endoscopic polypectomy and surveilled by annual colonoscopy. Guidelines for AFAP surveillance suggest annual colonoscopy with endoscopic polypectomy in asymptomatic individuals. Indications for immediate surgery include documented or suspected cancer or significant symptoms. Preferred surgical option in AFAP is colectomy and ileo-rectal anastomosis. Surveillance of the AFAP patients should include upper GI endoscopy and duodenoscopy with random biopsies of fundic gland polyps and endoscopic resection of detected adenomas. Annual thyroid ultrasound is indicated due to increased risk for thyroid cancer. In pediatric patients tested positive for germline mutation of APC gene screening for hepatoblastoma using alpha-fetoprotein and liver ultrasound should be performed.
Isolation and Characterization of Interspersed Repeated Sequences in the Common Lizard, Zootoca vivipara, and Their Conservation in Squamata
Authors: Petraccioli Agnese , Guarino Fabio M. , Kupriyanova Larissa , Mezzasalma Marcello , Odierna Gaetano , Picariello Orfeo , Capriglione Teresa
Published: March 2019

The common lizard (Zootoca vivipara) displays characteristic cytogenetic, reproductive, molecular, and biogeographic variability. This species comprises oviparous and viviparous populations with disjunct distribution and sex chromosome polymorphisms, from simple ZZ/ZW to complex Z1Z1Z2Z2/Z1Z2W systems with different morphologies of the W chromosome. In this study, we used the primers SINE A and SINE B and a newly designed primer pair to (1) obtain information on the presence and distribution of transposable elements (TEs) in 8 squamate families and (2) assess the chromosomal location of SINE Squam elements in Z. vivipara. PCR amplification with SINE A and SINE B produced single or multiple products in different Z. vivipara populations, subsequently used to design the SINE-Zv primers. Using the newly designed SINE-Zv primers, we identified 2 sequences of about 700 and 300 bp (SINE-Zv 700 and SINE-Zv 300) in all the investigated populations of Z. vivipara. Fluorescence in situ hybridizations showed a preferential localization of SINE-Zv sequences in the peritelomeric regions of almost all chromosomes, with the exception of the W. Both sequences contained a distinct segment of SINE Squam2. SINE-Zv 700 appeared to be restricted to Z. vivipara, while SINE-Zv 300 contained a partial Gypsy sequence that is highly conserved among Squamata and showed high identity values (72-93%) with several transcripts from different species. Using the same primers, we also highlighted the presence of another highly conserved Gypsy-like fragment in snakes which displayed significant similarity with the stomatin-like protein 2 of colubrids. Our results suggest that SINEs and the Gypsy-like elements are widely distributed among squamates and may have played an active role in their genomic evolution and differentiation.
Further Delineation of the Microcephaly-Micromelia Syndrome Associated with Loss-of-Function Variants in DONSON
Authors: Abdelrahman Hanadi A. , John Anne , Ali Bassam R. , Al-Gazali Lihadh
Published: March 2019

The DONSON gene encodes the downstream neighbor of SON, a replisome component that stabilizes the replication fork during replication. A severe form of microcephalic dwarfism, microcephaly-micromelia syndrome (MIMIS), has been recently associated with DONSON biallelic loss of function. Affected fetuses suffer severe growth restriction, microcephaly, and variable limb malformations which result in intrauterine or perinatal death. All described fetuses carried a homozygous founder mutation (c.1047-9A>G), a splice-altering variant that leads to transcript degradation. We evaluated 2 newborns from a consanguineous Emirati family with severe microcephaly, micromelia, craniofacial dysmorphism, and skeletal abnormalities; both died shortly after birth. Here, we report the second homozygous loss-of-function variant (c.763C>T) in DONSON causing MIMIS, and we provide detailed clinical description of this very rare disorder. In addition, we review all MIMIS cases in the literature and summarize the striking features of this phenotype. This manuscript is aimed to increase the clinical understanding of this rare, extremely severe disorder and encourage clinical and molecular geneticists to consider screening for DONSON loss-of-function variants in families with recurrent pregnancy loss and/or perinatal deaths.
Bowel Preparation for Colonoscopy in Children: 1 Day PEG-3350 with Bisacodyl versus 3 Day Sennosides
Authors: Tutar Engin , Bayrak Nevzat Aykut , Volkan Burcu , Ertem Deniz
Published: March 2019

Background and Objectives: Bowel preparation (BP) for colonoscopy is a challenging procedure in children and different regimens have been used for this purpose. Polyethylene glycol (PEG) is the most preferred agent in recent years. The primary aim of this study was to evaluate the efficacy of 1-day PEG-3350 with bisacodyl (PEG-B) and comparing it with 3-day sennosides A+B. Method: In this prospective, randomized, and single-blinded study, children aged 2–18 years were included in the PEG-B group for 1 day or in Senna group for 3 days. The effectiveness of BP was assessed according to the Ottawa and Boston BP scales, compliance and adverse effects were also recorded. Pre- and post-preparation biochemistry were obtained for investigation of safety of both regimens. Results: Successful BP was observed in 88.3% (n = 53/60) of PEG-B and 86% (n = 55/64) of Senna groups according to Boston scale, and it was 85% (n = 51/60) and 84.4% (n = 54/64), respectively, according to Ottawa scale. The cecal intubation rate was 96.7% (n = 58/60) in the PEG-B group and 93.8% (n = 60/64) in the Senna group. Ease of administration and disturbance in regular daily activities was better in the PEG-B group (p < 0.05). There was no major adverse event and biochemical abnormality in both groups. The correlation between Ottawa and Boston scales was found to be excellent (r2 = –0.954, p < 0.01). Conclusions: The efficacy, safety, and adverse effect profile of 1-day BP with PEG-B regimen was found to be similar to 3-day sennosides regimen, however, the PEG-B regimen had advantages such as short duration, ease of administration, and better patient comfort. Also, high correlation rate between the Boston and Ottawa scales in pediatric patients was remarkable.