bluuebunny/crossref_metadata_2025_split huggingface dataset:
How a High-Gradient Magnetic Field Could Affect Cell Life
Authors: Zablotskii Vitalii , Polyakova Tatyana , Lunov Oleg , Dejneka Alexandr 
Published: November 2016

AbstractThe biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins. By deriving a generalized form for the Nernst equation, we find that a relatively small magnetic field (approximately 1 T) with a large gradient (up to 1 GT/m) can significantly change the membrane potential of the cell and thus have a significant impact on not only the properties and biological functionality of cells but also cell fate.
Phosphorus K4 Crystal: A New Stable Allotrope
Authors: Liu Jie , Zhang Shunhong , Guo Yaguang , Wang Qian 
Published: November 2016

AbstractThe intriguing properties of phosphorene motivate scientists to further explore the structures and properties of phosphorus materials. Here, we report a new allotrope named K4 phosphorus composed of three-coordinated phosphorus atoms in non-layered structure which is not only dynamically and mechanically stable, but also possesses thermal stability comparable to that of the orthorhombic black phosphorus (A17). Due to its unique configuration, K4 phosphorus exhibits exceptional properties: it possesses a band gap of 1.54 eV which is much larger than that of black phosphorus (0.30 eV), and it is stiffer than black phosphorus. The band gap of the newly predicted phase can be effectively tuned by appling hydrostastic pressure. In addition, K4 phosphorus exibits a good light absorption in visible and near ultraviolet region. These findings add additional features to the phosphorus family with new potential applications in nanoelectronics and nanomechanics.
Rapid and efficient CRISPR/Cas9 gene inactivation in human neurons during human pluripotent stem cell differentiation and direct reprogramming
Authors: Rubio Alicia , Luoni Mirko , Giannelli Serena G. , Radice Isabella , Iannielli Angelo , Cancellieri Cinzia , Di Berardino Claudia , Regalia Giulia , Lazzari Giovanna , Menegon Andrea , Taverna Stefano , Broccoli Vania 
Published: November 2016

AbstractThe CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons. This system was employed to inactivate two genes associated with neurological disorder (TSC2 and KCNQ2) and achieved up to 85% efficiency of gene targeting in the differentiated cells. In particular, we devised a protocol that, combining the expression of the CRISPR components with neurogenic factors, generated functional human neurons highly enriched for the desired genome modification in only 5 weeks. This new approach is easy, fast and that does not require the generation of stable isogenic clones, practice that is time consuming and for some genes not feasible.
Predicting protein–ligand affinity with a random matrix framework
Authors: Lee Alpha A. , Brenner Michael P. , Colwell Lucy J. 
Published: November 2016

Significance
Developing computational methods to screen ligands against protein targets is a major challenge for drug discovery. We present a robust mathematical framework, inspired by random matrix theory, which predicts ligand binding to a target given the known ligand set of that target. Our method considers binding prediction as a denoising problem, recognizing that only some of the chemically important features associated with each ligand contribute to binding to a particular receptor. We use correlations among chemical features in the known ligand set, combined with random matrix theory, to eliminate statistically insignificant correlations. Our method outperforms existing algorithms in the literature. We show that our algorithm has the physical interpretation of estimating the ligand–target binding energy.
Role of nucleotide-binding oligomerization domain 1 (NOD1) and its variants in human cytomegalovirus control in vitro and in vivo
Authors: Fan Yi-Hsin , Roy Sujayita , Mukhopadhyay Rupkatha , Kapoor Arun , Duggal Priya , Wojcik Genevieve L. , Pass Robert F. , Arav-Boger Ravit 
Published: November 2016

Significance
Infection with human cytomegalovirus (HCMV) is a growing health problem, creating diagnostic and therapeutic challenges. Biomarkers for risk of infection are lacking, and the limited drugs that inhibit HCMV have major side effects. New strategies for virus control are needed. We report on the role of nucleotide-binding oligomerization domain 1 (NOD1), a cytoplasmic pattern recognition receptor, in HCMV suppression. NOD1 activation (through IKKα and IRF3) resulted in IFN response and HCMV inhibition. Specific mutations in NOD1 showed differential effects on HCMV replication in vitro. In a nested study of HCMV vaccine, specific polymorphisms in NOD1 were detected in HCMV-infected women compared with noninfected women. Our work provides direction for studies of innate immune response to HCMV and genetic susceptibility through NOD1.
Mouse model for acute Epstein–Barr virus infection
Authors: Wirtz Tristan , Weber Timm , Kracker Sven , Sommermann Thomas , Rajewsky Klaus , Yasuda Tomoharu 
Published: November 2016

Significance
Epstein–Barr Virus infects human B cells and drives them into proliferation and transformation. Although more than 90% of the human population is EBV-infected, EBV-driven pathologies including B-cell lymphomas are limited by a potent T-cell immune response. Here, we present a mouse model for acute EBV infection through conditional expression of two key EBV proteins, LMP1 and LMP2A. This model reproduces EBV-driven B-cell expansion, T-cell–mediated immune surveillance of EBV-infected B cells, and fatal lymphoproliferative disease when the T-cell response is compromised as in immunosuppressed or genetically impaired patients. It thus allows one to study EBV–host interaction functionally and from an angle that should help to develop new therapies for EBV-driven hematological diseases.
Article Commentary: Turning the Tide or Riptide? The Changing Opioid Epidemic
Authors: Kertesz Stefan G. 
Published: November 2016

The US opioid epidemic has changed profoundly in the last 3 years, in ways that require substantial recalibration of the US policy response. This report summarizes the changing nature of overdose deaths in Jefferson County (home to Birmingham, Alabama) using data updated through June 30, 2016. Heroin and fentanyl have come to dominate an escalating epidemic of lethal opioid overdose, whereas opioids commonly obtained by prescription play a minor role, accounting for no more than 15% of reported deaths in 2015. Such local data, along with similar reports from other localities, augment the insights available from the Centers for Disease Control and Prevention's current overdose summary, which lacks data from 2015–2016 and lacks information regarding fentanyl in particular. The observed changes in the opioid epidemic are particularly remarkable because they have emerged despite sustained reductions in opioid prescribing and sustained reductions in prescription opioid misuse. Among US adults, past-year prescription opioid misuse is at its lowest level since 2002. Among 12th graders it is at its lowest level in 20 years. A credible epidemiologic account of the opioid epidemic is as follows: although opioid prescribing by physicians appears to have unleashed the epidemic prior to 2012, physician prescribing no longer plays a major role in sustaining it. The accelerating pace of the opioid epidemic in 2015–2016 requires a serious reconsideration of governmental policy initiatives that continue to focus on reductions in opioid prescribing. The dominant priority should be the assurance of subsidized access to evidence-based medication-assisted treatment for opioid use disorder. Such treatment is lacking across much of the United States at this time. Further aggressive focus on prescription reduction is likely to obtain diminishing returns while creating significant risks for patients.
Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin
Authors: Thussagunpanit Jutiporn , Nagai Yuko , Nagae Miyu , Mashiguchi Kiyoshi , Mitsuda Nobutaka , Ohme-Takagi Masaru , Nakano Takeshi , Nakamura Hidemitsu , Asami Tadao 
Published: November 2016

Abstract
Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR1, a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.
Mumps Outbreak Among a Highly Vaccinated University Community—New York City, January–April 2014
Authors: Patel Leena N. , Arciuolo Robert J. , Fu Jie , Giancotti Francesca R. , Zucker Jane R. , Rakeman Jennifer L. , Rosen Jennifer B. 
Published: November 2016

Abstract

Background.
On 14 January 2014, a vaccinated student presented with parotitis. Mumps immunoglobulin M (IgM) testing was negative and reverse-transcription polymerase chain reaction (RT-PCR) testing was not performed, resulting in a missed diagnosis and the start of an outbreak at a New York City (NYC) university.

Methods.
Mumps case investigations included patient interviews, medical records review, and laboratory testing including mumps serology and RT-PCR. Case patients were considered linked to the outbreak if they attended or had epidemiologic linkage to the university. Epidemiologic, clinical, and laboratory data for outbreak cases residing in NYC were analyzed.

Results.
Fifty-six NYC residents with mumps were identified with onset between 12 January and 30 April 2014. Fifty-three cases (95%) were university students, 1 (2%) was a staff member, and 2 (4%) had epidemiologic links to the university. The median age was 20 years (range 18–37 years). All cases had parotitis. Three cases were hospitalized, including 1 of 2 cases with orchitis. Fifty-four (96%) cases had received ≥1 mumps-containing vaccine, 1 (2%) was unvaccinated due to religious exemption, and 1 (2%) had unknown vaccination status. Two of the 44 (5%) cases tested by serology were mumps IgM positive, and 27 of the 40 (68%) tested by RT-PCR were positive.

Conclusions.
Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status. RT-PCR is the preferred testing method; providers should not rely on IgM testing alone. High vaccination coverage and control measures likely limited the extent of the outbreak.
The Addiction Recovery Clinic: A Novel, Primary-Care-Based Approach to Teaching Addiction Medicine
Authors: Holt Stephen R. , Segar Nora , Cavallo Dana A. , Tetrault Jeanette M. 
Published: November 2016

Problem
Substance use is highly prevalent in the United States, but little time in the curriculum is devoted to training internal medicine residents in addiction medicine.

Approach
In 2014, the authors developed and launched the Addiction Recovery Clinic (ARC) to address this educational gap while also providing outpatient clinical services to patients with substance use disorders. The ARC is embedded within the residency primary care practice and is staffed by three to four internal medicine residents, two board-certified addiction medicine specialists, one chief resident, and one psychologist. Residents spend one half-day per week for four consecutive weeks at the ARC seeing new and returning patients. Services provided include pharmacological and behavioral treatments for opioid, alcohol, and other substance use disorders, with direct referral to local addiction treatment facilities as needed. Visit numbers, a patient satisfaction survey, and an end-of-rotation resident evaluation were used to assess the ARC.

Outcomes
From 2014 to 2015, 611 patient encounters occurred, representing 97 new patients. Sixty-one (63%) patients were seen for opioid use disorder. According to patient satisfaction surveys, 29 (of 31; 94%) patients reported that the ARC probably or definitely helped them to cope with their substance use. Twenty-eight residents completed the end-of-rotation evaluation; all rated the rotation highly.

Next Steps
The ARC offers a unique primary-care-based approach to exposing internal medicine residents to the knowledge and skills necessary to diagnose, treat, and prevent unhealthy substance use. Future research will examine other clinical and educational outcomes.
Fast Click Rate Electrocochleography and Auditory Brainstem Response in Normal-Hearing Adults Using Continuous Loop Averaging Deconvolution
Authors: Kaf Wafaa A. , Lewis Kelly M. , Yavuz Erdem , Dixon Samantha M. , Van Ess Mark , Jamos Abdullah M. , Delgado Rafael E. 
Published: November 2016

Objectives:
Using the continuous loop averaging deconvolution (CLAD) technique for conventional electrocochleography (ECochG) and auditory brainstem response (ABR) recordings, the effects of testing at high stimulus rates may have the potential to diagnose disorders of the inner ear and auditory nerve. First, a body of normative data using the CLAD technique must be established.

Design:
Extratympanic click ECochG and ABR to seven stimulus rates using CLAD were measured simultaneously from a tympanic membrane electrode and surface electrodes on the forehead and mastoid of 42 healthy individuals.

Results:
Results showed that the compound action potential (AP) of the ECochG and waves I, III, and V of the ABR decreased in amplitude and increased in latency as stimulus rate was increased from standard 7.1 clicks/s up to 507.81 clicks/s, with sharp reduction in AP amplitude at 97.66 clicks/s and reaching asymptote at 292.97 clicks/s. The summating potential (SP) of the ECochG, however, stayed relatively stable, resulting in increased SP/AP ratios with increasing rate. The SP/AP amplitude ratio showed more stability than AP amplitude findings, thus it is recommended for use in evaluation of cochlear and neural response.

Conclusions:
Results of both amplitude and latency data from this normative neural adaptation function of the auditory pathway serves as guide for improving diagnostic utility of both ECochG and ABR using CLAD as a reliable technique in distinguishing inner ear and auditory nerve disorders.
What’s New in Pediatric Medial Epicondyle Fractures?
Authors: Beck Jennifer J. , Bowen Richard E. , Silva Mauricio 
Published: November 2016

Background:
Medial epicondyle fractures are predominantly seen in adolescent, male patients. Historically, nonoperative intervention was the mainstay of treatment. With increasing upper extremity demands of young athletes and reports of valgus instability after nonoperative treatment, there has been an increased interest in operative indications. Controversy regarding proper imaging and measurement of displacement complicates decision-making algorithms. Review of recent literature is required for improved decision making.

Methods:
We searched the PubMed database for all papers related to the treatment of medial epicondyle fractures in patients under 18 years of age published between January 1, 2005 and March 15, 2016. This resulted in 39 papers written in English for review. Papers were included based upon subject matter and contribution of new findings to literature. Review articles were excluded.

Results:
In total, 39 papers were reviewed and 30 were included in this review. Five classic manuscripts on medial epicondyle fractures in children provide appropriate historical and background information as needed.

Conclusions:
Medial epicondyle fractures represent a variety of low and high-energy mechanisms, displacement, treatment options, and complications. This paper reviews recent literature on these topics. Controversy regarding imaging modality, displacement measurement accuracy, and surgical indications still exist. Long term, patient based, functional outcome studies of operative versus nonoperative treatment are needed to improve our treatment algorithms of this injury. Treatment algorithms should be individualized to each specific patient and fracture.

Level of Evidence:
Level 5.
Novel Homozygous Missense Mutation in CAPN3 Gene Detected in a Saudi Arabian Family With Limb–Girdle Muscular Dystrophy Type 2A
Authors: Al-Harbi Talal M. , Abdulmana' Sameeh O. , Dridi Walid 
Published: November 2016

Abstract
More than 300 mutations were identified in Calpainopathy (CAPN3) gene in limb–girdle muscular dystrophy type 2A (LGMD2A) patients. LGMD2A type is also known as Calpainopathy, which is characterized by selective atrophy and weakness of proximal limb muscles. We report a Saudi Arabian family with weakness in limb–girdle distribution: waddling gait, positive Gowers' sign, and marked muscle atrophy in the shoulder and pelvic girdle muscles. We sequenced all exonic and intronic regions of the CAPN3 gene and identified c.1699 G>A variant as a novel variant not previously described in other patients. In silico predictions indicate that this is probably a disease-causing mutation. Here, for the first time, we report this c.1699 G>A new variant in the CAPN3 gene that can be considered as a robust genetics factor causing LGMD2A disease.
Gastrointestinal and Urologic Sphincter Dysfunction in Stiff Person Syndrome
Authors: Dumitrascu Oana M. , Tsimerinov Evgeny I. , Lewis Richard A. 
Published: November 2016

Abstract

Objectives:
Stiff person syndrome is a neurologic disorder characterized by axial rigidity leading to progressive disability, with broad clinical spectrum.

Methods:
We report 2 cases with unique clinical presentation.

Results:
Two young men suffered progressive urinary retention requiring bladder catheterization, anorectal spasms and constipation, complicated subsequently with lower extremity trigger-induced spasms, and gait instability. Associated symptoms revealed brainstem involvement (vertigo, diplopia, and cranial neuropathies) and dysautonomia (abnormal sweating and orthostatic hypotension). Anal manometry demonstrated incomplete relaxation of the anal sphincter. The first case was associated with diabetes mellitus type I, did not respond to classical therapies, but was responsive to rituximab. The second case responded to intravenous immunoglobulin infusions. Paraneoplastic profiles were negative, and anti-GAD65 antibody titers remained elevated despite successful therapeutic responses.

Conclusions:
We want to raise awareness that stiff person syndrome can present with esophageal, anorectal, and urethral sphincter disturbance. Rituximab is a good therapeutic option in intractable cases.
A Simple High-Performance Liquid Chromatography for Determining Lapatinib and Erlotinib in Human Plasma
Authors: Ohgami Masahiro , Homma Masato , Suzuki Yoshiharu , Naito Kanako , Yamada Motoko , Mitsuhashi Shoichi , Fujisawa Fumie , Kojima Hiroshi , Kaburagi Takayuki , Uchiumi Keiko , Yamada Yutaka , Bando Hiroko , Hara Hisato , Takei Keiji 
Published: November 2016

Background:
Lapatinib and erlotinib are used for cancer treatment, showing large interindividual variability. Therapeutic drug monitoring may be useful for assessing the clinical outcomes and adverse events. A simple high-performance liquid chromatography UV method was developed for the determination of lapatinib and erlotinib in human plasma.

Methods:
An aliquot of plasma sample spiked with internal standard was treated with acetonitrile to precipitate the proteins. Lapatinib and erlotinib were separated on an octadecylsilyl silica gel column using a mobile phase consisting of acetonitrile, methanol, water, and trifluoroacetic acid (26:26:48:0.1) pumped at a flow rate of 1.0 mL/min. The detection wavelength was set at 316 nm.

Results:
The calibration curves for lapatinib and erlotinib were linear (r = 0.9999) in the range of 0.125–8.00 mcg/mL. The extraction recoveries for both lapatinib and erlotinib at the plasma concentration of 0.125–8.00 mcg/mL were higher than 89.9% with coefficients of variation less than 3.5%. The coefficients of variation for intraday and interday assays of lapatinib and erlotinib were less than 5.1% and 6.1%, respectively.

Conclusions:
The present method can be used for blood concentration monitoring for lapatinib or erlotinib in exactly the same conditions.
Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?
Authors: Kaya Serdar , Paparella Michael M. , Cureoglu Sebahattin 
Published: November 2016

Hypothesis:The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis.Background:Previous reports have shown that otosclerosis can lead to vestibular symptoms.Methods:We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group–with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)–versus 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs.Results:In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (−) subgroup (p < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (−) group in the LSC and in the PSC (p < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (p > 0.05).Conclusion:We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms.