bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two‐dimensional polynomial type canonical relaxation oscillator model for p53 dynamics
Authors: Demirkıran Gökhan , Kalaycı Demir Güleser , Güzeliş Cüneyt 
Published: February 2018

p53 network, which is responsible for DNA damage response of cells, exhibits three distinct qualitative behaviours; low state, oscillation and high state, which are associated with normal cell cycle progression, cell cycle arrest and apoptosis, respectively. The experimental studies demonstrate that these dynamics of p53 are due to the ATM and Wip1 interaction. This paper proposes a simple two‐dimensional canonical relaxation oscillator model based on the identified topological structure of ATM and Wip1 interaction underlying these qualitative behaviours of p53 network. The model includes only polynomial terms that have the interpretability of known ATM and Wip1 interaction. The introduced model is useful for understanding relaxation oscillations in gene regulatory networks. Through mathematical analysis, we investigate the roles of ATM and Wip1 in forming of these three essential behaviours, and show that ATM and Wip1 constitute the core mechanism of p53 dynamics. In agreement with biological findings, we show that Wip1 degradation term is a highly sensitive parameter, possibly related to mutations. By perturbing the corresponding parameters, our model characterizes some mutations such as ATM deficiency and Wip1 overexpression. Finally, we provide intervention strategies considering our observation that Wip1 seems to be an important target to conduct therapies for these mutations.
A Monoclonal Antibody-Based Enzyme-Linked Immunosorbent Assay for Determination of Homoharringtonine
Authors: Pongkitwitoon Benyakan , Sakamoto Seiichi , Nagamitsu Rika , Putalun Waraporn , Tanaka Hiroyuki , Morimoto Satoshi 
Published: February 2018

AbstractHomoharringtonine (HHT), also known as omacetaxine, is a natural compound found in the genus Cephalotaxus and is a promising pharmaceutical drug used for the treatment of chronic or accelerated phase chronic myeloid leukemia. As a tool for the quantitative determination of HHT, a specific monoclonal antibody against HHT (MAb 6A1) was generated by conjugates prepared via sodium periodate-mediated oxidation. The developed indirect competitive enzyme-linked immunosorbent assay (icELISA) using MAb 6A1 was found to be highly specific and sensitive with a limit of detection for HHT of 48.8 ng/mL. Validation assays to evaluate precision and accuracy of the method were conducted by the use of intra- and inter-assay analysis, recovery test, and comparison analysis between the amounts of HHT determined by ELISA and high-performance liquid chromatography. These results revealed that the established icELISA using MAb 6A1 is specific, sensitive, and reliable enough to be applied to the qualitative analysis for HHT. Furthermore, the results of this study support the usefulness of sodium periodate as a reagent for the conjugation between Cephalotaxus alkaloids and proteins for producing specific antibodies.
Erbliche Sehnerverkrankungen
Authors: Rüther Klaus 
Published: February 2018

ZusammenfassungTrotz der Seltenheit haben die erblichen Sehnerverkrankungen den Vorteil, dass sie oftmals durch die Anamnese erkannt werden können und die Diagnosesicherung heute sicher durch eine molekulargenetische Untersuchung geleistet werden kann. Als isolierte erbliche Sehnerverkrankungen sind im augenheilkundlichen Alltag die Leberʼsche hereditäre Optikusneuropathie (LHON) und die autosomal-dominante Optikusatrophie (ADOA) relevant.
Nicht organische Sehstörungen
Authors: Steffen Heimo 
Published: February 2018

ZusammenfassungNicht organische Sehstörungen sind in der augenärztlichen Praxis eine häufige Herausforderung. Im Kindesalter ist die häufigste Störung eine beidseits unklare Visusreduktion, im Erwachsenenalter eher eine einseitige Sehstörung. Dieser Beitrag soll den Augenarzt für Patienten mit nicht organischer Sehstörung sensibilisieren und einen Überblick über diagnostische Strategien bei Patienten mit dieser vermuteten Diagnose geben.
Endoscopic Endonasal Transplanum Transtuberculum Approach for the Resection of a Large Suprasellar Craniopharyngioma
Authors: Mangussi-Gomes João , Vellutini Eduardo , Truong Huy , Pahl Felix , Stamm Aldo 
Published: February 2018

Objectives To demonstrate an endoscopic endonasal transplanum transtuberculum approach for the resection of a large suprasellar craniopharyngioma.
Design Single-case-based operative video.
Setting Tertiary center with dedicated skull base team.
Participants A 72-year-old male patient diagnosed with a suprasellar craniopharyngioma.
Main Outcomes Measured Surgical resection of the tumor and preservation of the normal surrounding neurovascular structures.
Results A 72-year-old male patient presented with a 1-year history of progressive bitemporal visual loss. He also referred symptoms suggestive of hypogonadism. Neurological examination was unremarkable and endocrine workup demonstrated mildly elevated prolactin levels. Magnetic resonance images demonstrated a large solid-cystic suprasellar lesion, consistent with the diagnosis of craniopharyngioma. The lesion was retrochiasmatic, compressed the optic chiasm, and extended into the interpeduncular cistern (Fig. 1). Because of that, the patient underwent an endoscopic endonasal transplanum transtuberculum approach.1
2
3 The nasal stage consisted of a transnasal transseptal approach, with complete preservation of the patient's left nasal cavity.4 The cystic component of the tumor was decompressed and its solid part was resected. It was possible to preserve the surrounding normal neurovascular structures (Fig. 2). Skull base reconstruction was performed with a dural substitute, a fascia lata graft, and a right nasoseptal flap (Video 1). The patient did well after surgery and referred complete visual improvement. However, he also presented pan-hypopituitarism on long-term follow-up.
Conclusions The endoscopic endonasal route is a good alternative for the resection of suprasellar lesions. It permits tumor resection and preservation of the surrounding neurovascular structures while avoiding external incisions and brain retraction.The link to the video can be found at: https://youtu.be/zmgxQe8w-JQ.
Der asymptomatische Patient mit schwerer Aortenstenose oder Mitralinsuffizienz: wann operieren?
Authors: Kaleschke Gerrit 
Published: February 2018

ZusammenfassungWährend symptomatische Herzklappenfehler nicht nur zur Symptomverbesserung, sondern meistens auch aus prognostischen Gründen eine Behandlungsindikation haben, ist die Situation bei noch asymptomatischen Klappenfehlern weniger eindeutig und zum Teil auch umstritten. Die Empfehlungen basieren vor allem auf Prädiktoren für ein schlechteres Outcome im Spontanverlauf oder nach Operation, wie beispielsweise eine progrediente, unter Umständen irreversible Schädigung von Ventrikelmyokard oder Pulmonalgefäßbett. Auch schwere Vitien können oft lange Zeit asymptomatisch bleiben. Ein Abwarten unter Beobachtung („watchful waiting“) kann dann eine sichere Vorgangsweise sein, wenn regelmäßige Kontrollen, die das rechtzeitige Erkennen von prognostisch ungünstigen Zeichen und in der Folge die zeitgerechte Intervention erlauben, gewährleistet sind. Für die Therapieentscheidung sind dabei das individuelle Eingriffsrisiko selbst, die Möglichkeit einer klappenerhaltenden Operation und die langfristigen potenziellen Komplikationen durch Klappenprothesen wie Endokarditis oder Thrombembolie bzw. Blutungsrisiken unter Antikoagulation zu berücksichtigen. Die aktuellen Leitlinien der ESC/EACTS geben praktische Hinweise und beziehen multimodale diagnostische Strategien in die Empfehlungen ein.
Strong control of Southern Ocean cloud reflectivity by ice-nucleating particles
Authors: Vergara-Temprado Jesús , Miltenberger Annette K. , Furtado Kalli , Grosvenor Daniel P. , Shipway Ben J. , Hill Adrian A. , Wilkinson Jonathan M. , Field Paul R. , Murray Benjamin J. , Carslaw Ken S. 
Published: February 2018

Significance
Simulated clouds over the Southern Ocean reflect too little solar radiation compared with observations, which results in errors in simulated surface temperatures and in many other important features of the climate system. Our results show that the radiative properties of the most biased types of clouds in cyclonic systems are highly sensitive to the concentration of ice-nucleating particles. The uniquely low concentrations of ice-nucleating particles in this remote marine environment strongly inhibit precipitation and allow much brighter clouds to be sustained.
Scalable, cGMP‐compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL‐15/lactadherin complexes
Authors: Watson Dionysios C. , Yung Bryant C. , Bergamaschi Cristina , Chowdhury Bhabadeb , Bear Jenifer , Stellas Dimitris , Morales‐Kastresana Aizea , Jones Jennifer C. , Felber Barbara K. , Chen Xiaoyuan , Pavlakis George N. 
Published: February 2018

ABSTRACTThe development of extracellular vesicles (EV) for therapeutic applications is contingent upon the establishment of reproducible, scalable, and high‐throughput methods for the production and purification of clinical grade EV. Methods including ultracentrifugation (U/C), ultrafiltration, immunoprecipitation, and size‐exclusion chromatography (SEC) have been employed to isolate EV, each facing limitations such as efficiency, particle purity, lengthy processing time, and/or sample volume. We developed a cGMP‐compatible method for the scalable production, concentration, and isolation of EV through a strategy involving bioreactor culture, tangential flow filtration (TFF), and preparative SEC. We applied this purification method for the isolation of engineered EV carrying multiple complexes of a novel human immunostimulatory cytokine‐fusion protein, heterodimeric IL‐15 (hetIL‐15)/lactadherin. HEK293 cells stably expressing the fusion cytokine were cultured in a hollow‐fibre bioreactor. Conditioned medium was collected and EV were isolated comparing three procedures: U/C, SEC, or TFF + SEC. SEC demonstrated comparable particle recovery, size distribution, and hetIL‐15 density as U/C purification. Relative to U/C, SEC preparations achieved a 100‐fold reduction in ferritin concentration, a major protein‐complex contaminant. Comparative proteomics suggested that SEC additionally decreased the abundance of cytoplasmic proteins not associated with EV. Combination of TFF and SEC allowed for bulk processing of large starting volumes, and resulted in bioactive EV, without significant loss in particle yield or changes in size, morphology, and hetIL‐15/lactadherin density. Taken together, the combination of bioreactor culture with TFF + SEC comprises a scalable, efficient method for the production of highly purified, bioactive EV carrying hetIL‐15/lactadherin, which may be useful in targeted cancer immunotherapy approaches.
Craniotomy and Survival for Primary Central Nervous System Lymphoma
Authors: Rae Ali I , Mehta Amol , Cloney Michael , Kinslow Connor J , Wang Tony J C , Bhagat Govind , Canoll Peter D , Zanazzi George J , Sisti Michael B , Sheth Sameer A , Connolly E Sander , McKhann Guy M , Bruce Jeffrey N , Iwamoto Fabio M , Sonabend Adam M 
Published: February 2018

Abstract

BACKGROUND
Cytoreductive surgery is considered controversial for primary central nervous system lymphoma (PCNSL).

OBJECTIVE
To investigate survival following craniotomy or biopsy for PCNSL

METHODS
The National Cancer Database-Participant User File (NCDB, n = 8936), Surveillance, Epidemiology, and End Results Program (SEER, n = 4636), and an institutional series (IS, n = 132) were used. We retrospectively investigated the relationship between craniotomy, prognostic factors, and survival for PCNSL using case–control design.

RESULTS
In NCDB, craniotomy was associated with increased median survival over biopsy (19.5 vs 11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR] 0.80, P < .001). We found a similar trend with survival for craniotomy vs biopsy in the IS (HR 0.68, P = .15). In SEER, gross total resection was associated with increased median survival over biopsy (29 vs 10 mo, HR 0.68, P < .001). The survival benefit associated with craniotomy was greater within recursive partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P < .001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P < .001). A surgical risk category (RC) considering lesion location and number, age, and frailty was developed. Craniotomy was associated with increased survival vs biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P = .01), but not high RC in the IS.

CONCLUSION
Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to benefit from cytoreductive surgery, ie, those with favorable RPA and RC.
FOREST Unbiased Galactic plane Imaging survey with the Nobeyama 45 m telescope (FUGIN). III. Possible evidence for formation of NGC 6618 cluster in M 17 by cloud–cloud collision
Authors: Nishimura Atsushi , Minamidani Tetsuhiro , Umemoto Tomofumi , Fujita Shinji , Matsuo Mitsuhiro , Hattori Yusuke , Kohno Mikito , Yamagishi Mitsuyoshi , Tsuda Yuya , Kuriki Mika , Kuno Nario , Torii Kazufumi , Tsutsumi Daichi , Okawa Kazuki , Sano Hidetoshi , Tachihara Kengo , Ohama Akio , Fukui Yasuo 
Published: February 2018

Abstract
We present 12CO (J = 1–0), 13CO (J = 1–0), and C18O (J = 1–0) images of the M 17 giant molecular clouds obtained as part of the FUGIN (FOREST Ultra-wide Galactic Plane Survey In Nobeyama) project. The observations cover the entire area of the M 17 SW and M 17 N clouds at the highest angular resolution (∼19″) to date, which corresponds to ∼0.18 pc at the distance of 2.0 kpc. We find that the region consists of four different velocity components: a very low velocity (VLV) clump, a low velocity component (LVC), a main velocity component (MVC), and a high velocity component (HVC). The LVC and the HVC have cavities. Ultraviolet photons radiated from NGC 6618 cluster penetrate into the N cloud up to ∼5 pc through the cavities and interact with molecular gas. This interaction is correlated with the distribution of young stellar objects in the N cloud. The LVC and the HVC are distributed complementarily after the HVC is displaced by 0.8 pc toward the east-southeast direction, suggesting that collision of the LVC and the HVC created the cavities in both clouds. The collision velocity and timescale are estimated to be 9.9 km s−1 and 1.1 × 105 yr, respectively. The high collision velocity can provide a mass accretion rate of up to 10$^{-3}{\,\,}M_{\odot }\:$yr−1, and the high column density (4 × 1023 cm−2) might result in massive cluster formation. The scenario of cloud–cloud collision likely explains well the stellar population and the formation history of the NGC 6618 cluster proposed by Hoffmeister et al. (2008, ApJ, 686, 310).
Paradigm Shift in Geriatric Low Back Pain Management: Integrating Influences, Experiences, and Consequences
Authors: Simon Corey B , Hicks Gregory E 
Published: February 2018

Abstract
Geriatric low back pain (LBP) can have a profound impact on physical activity and can cause a decline in physical function, which is a major health risk for older adults. Within the last decade, physical therapist management of LBP has shifted from an emphasis on pathoanatomical mechanisms, such as spine degeneration, to addressing psychological distress factors. Although this approach is promising, the complexity of LBP in older adults (including biological, psychological, cognitive, and social influences), which may differ from that in younger adults, must be considered. Further, outcome assessment should represent not only the LBP experience (eg, pain intensity, pain with movement) but also LBP consequences, such as physical activity decline and physical function decline. This perspective discusses influences on geriatric LBP, experiences, and consequences with the goal of facilitating standardized and comprehensive physical therapist management.
Effectiveness and Downstream Healthcare Utilization for Patients That Received Early Physical Therapy Versus Usual Care for Low Back Pain
Authors: Rhon Daniel I. , Miller Robert B. , Fritz Julie M. 
Published: February 2018

Study Design.
Randomized controlled trial.

Objective.
The aim of this study was to compare early physical therapy versus usual care in patients with low back pain.

Summary of Background Data.
Early physical therapy (PT) has been associated with reduced downstream healthcare utilization in retrospective studies, but not investigated prospectively in the military health system.

Methods.
Military service members seeking care from a general practitioner were recruited. Patients attended a 20-minute self-management class with focus on psychosocial resilience and then randomized to usual care only (UC) versus immediately starting a 3-week physical therapy program (PT). Primary outcome was the Oswestry Disability Index at 1 year. Secondary outcomes included Oswestry scores at 4- and 12-week follow-up, numeric pain rating scale, global rating of change, and healthcare utilization at 1 year. Analysis of covariance was used to compare differences between groups, significance set at 0.05. Trial Registration: clinicaltrials.gov: NCT01556581

Results.
A total of 119 patients (mean age 27.2 years; mean BMI 27.8 kg/m2; 15.1% female) enrolled (61 randomized to UC; 58 to PT). No between-group differences found on the Oswestry after 1 year. A between-group difference in Oswestry was present at 4 weeks (mean difference = 4.4; 95% CI: 0.41–10.1; P = 0.042) favoring PT. Total 1-year mean healthcare costs did not differ significantly between groups (UC $5037; 95 CI $4171–$6082 and PT $5299; 95 CI $4367–$6431). The portion of total mean healthcare costs related to low back pain was lower for UC ($1096; 95% CI $855–$1405) compared to PT ($2016, 95% CI $1570–$2590).

Conclusion.
There was no difference between usual care and early PT after 1 year. PT provided greater improvement in disability after 4 weeks. As both groups improved, the impact of the education may have been underestimated. Patients in the PT group utilized greater back-pain-related healthcare resources, but overall healthcare costs did not differ compared to UC.

Level of Evidence: 2
Analysis of Two Orthokeratology Lens Designs and Comparison of Their Optical Effects on the Cornea
Authors: Marcotte-Collard Rémy , Simard Patrick , Michaud Langis 
Published: February 2018

Purpose:
This study aims to analyze two commercial orthokeratology lens designs and compare their optical effects at the corneal level.

Methods:
This is a retrospective study on subjects seeking an orthokeratology fitting for myopia management at the Université de Montréal clinic between January 2013 and August 2015. Group A included the first 64 subjects fitted with a 4-curve lens design (Paragon CRT; Paragon) who met the inclusion criteria, whereas group B included the same number of subjects fitted with a 5-curve lens design (Dreamlens; Polymer Technology, Rochester, NY). Topographic tangential maps were collected at baseline and 3 months after fitting. The differential map was generated for each patient and analyzed, which involved determining the radius of the central distance zone (CDZ) and the power and width of the high convex zone (HCZ). Results were compared between the two groups, taking baseline refraction into account. Finally, a correlation was estimated between topographic data and corneal parameters (flat and steep K, the corneal eccentricity of each principal meridian).

Results:
The CDZ for group A is significantly larger than the one generated for group B both horizontally (t(126)=12.12, P<0.01) and vertically (t(126)=15.690, P<0.01). However, there was no significant difference regarding the HCZ power generated. The only correlations found were a strong positive association between CDZ radius and HCZ power generated by lens A nasally (r=0.450; P=0.000) and temporally (r=0.558; P=0.000), and a weaker association between the baseline refractive error, along with the nasal (r=0.237; P=0.033) and temporal (r=0.288; P=0.028) HCZ power for lens B.

Conclusion:
The four- and five-curve orthokeratology lens designs generate significantly different optical modifications on the cornea. This can affect reports on orthokeratology efficacy for myopia management as well as the lens selection when used for myopia correction.
Terrien Marginal Degeneration Complicated by a Corneoscleral Cyst
Authors: Lee Tian Loon , Lee Hwei Yee , Tan Johnson Choon Hwai 
Published: February 2018

Purpose:
To describe a case of inflammatory Terrien's marginal degeneration (TMD) in a young Chinese girl complicated by a corneoscleral cyst who ultimately underwent surgical treatment with cyst excision, corneal patch graft and amniotic membrane graft.

Methods:
Case report.

Results:
A 12-year-old Chinese female presented initially with redness and discharge from her right eye with bilateral superior corneal thinning. The patient was diagnosed with TMD. She subsequently developed a corneoscleral cyst 2 years later which doubled in size within 1 year. The patient underwent a cyst excision with lamellar corneal patch graft and amniotic membrane grafting. Histopathological examination of the cyst wall showed a lining of squamous epithelium, consistent with a corneoscleral cyst.

Conclusions:
This is an interesting case highlighting the rare complication of corneoscleral cyst in a young patient with inflammatory TMD. Excision of the cyst with a corneal patch graft and amniotic membrane grafting without any chemical cautery is effective in preventing recurrence.
Changes in Siblings Over Time After the Death of a Brother or Sister From Cancer
Authors: Akard Terrah Foster , Skeens Micah A. , Fortney Christine A. , Dietrich Mary S. , Gilmer Mary Jo , Vannatta Kathryn , Barrera Maru , Davies Betty , Wray Sarah , Gerhardt Cynthia A. 
Published: February 2018

Background
Limited research has examined the impact of a child’s death from cancer on siblings. Even less is known about how these siblings change over time.

Objective
This study compared changes in siblings 1 (T1) and 2 (T2) years after the death of a brother or sister from cancer based on bereaved parent and sibling interviews.

Methods
Participants across 3 institutions represented 27 families and included bereaved mothers (n = 21), fathers (n = 15), and siblings (n = 26) ranging from 8 to 17 years old. Participants completed semistructured interviews. Content analysis identified emerging themes and included frequency counts of participant responses. McNemar tests examined differences in the frequency of responses between T1 and T2 data.

Results
Participants reported similar types of changes in bereaved siblings at both time points, including changes in sibling relationships, life perspectives, their personal lives, and school performance. A new theme of “openness” emerged at T2. Frequencies of responses differed according to mother, father, or sibling informant. Overall, participants less frequently reported changes at T2 versus T1. Compared with findings in the first year, participants reported greater sibling maturity at follow-up.

Conclusion
Overall changes in bereaved siblings continued over 2 years with less frequency over time, with the exception of increases in maturity and openness.

Implications for Practice
Providers can educate parents regarding the impact of death of a brother or sister over time. Nurses can foster open communication in surviving grieving siblings and parents as potential protective factors in families going through their grief.