bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Genetic Contributors to New-Onset Atrial Fibrillation in Critically Ill Adults*
Authors: Kerchberger V. Eric , Huang Yi , Koyama Tatsuki , Shoemaker M. Benjamin , Darbar Dawood , Bastarache Julie A. , Ware Lorraine B. , Shaver Ciara M. 
Published: October 2019

Objectives:New-onset atrial fibrillation during critical illness is an independent risk factor for mortality. The ability to identify patients at high risk for new-onset atrial fibrillation is limited. We hypothesized that genetic susceptibility contributes to risk of new-onset atrial fibrillation in the ICU.Design:Retrospective sub-study of a prospective observational cohort study.Setting:Medical and general surgical ICUs in a tertiary academic medical center.Patients:One-thousand three-hundred sixty-nine critically ill patients admitted to the ICU for at least 2 days with no known history of atrial fibrillation who had DNA available for genotyping.Interventions:None.Measurements and Main Results:We genotyped 21 single-nucleotide polymorphisms associated with atrial fibrillation in ambulatory studies using a Sequenom platform (San Diego, CA). We collected demographics, medical history, and development of new-onset atrial fibrillation during the first four days of ICU admission. New-onset atrial fibrillation occurred in 98 patients (7.2%) and was associated with age, male sex, coronary artery disease, and vasopressor use. Single-nucleotide polymorphisms associated with new-onset atrial fibrillation were rs3853445 (nearPITX2,p= 0.0002), rs6838973 (nearPITX2,p= 0.01), and rs12415501 (inNEURL,p= 0.03) on univariate testing. When controlling for clinical factors, rs3853445 (odds ratio, 0.47; 95% CI, 0.30–0.73;p= 0.001) and rs12415501 (odds ratio, 1.72; 95% CI, 1.27–2.59;p= 0.01) remained significantly associated with new-onset atrial fibrillation. The addition of genetic variables to clinical factors improved new-onset atrial fibrillation discrimination in a multivariable logistic regression model (C-statistic 0.82 vs 0.78;p= 0.0009).Conclusions:We identified several single-nucleotide polymorphisms associated with new-onset atrial fibrillation in a large cohort of critically ill ICU patients, suggesting there is genetic susceptibility underlying this common clinical condition. This finding may provide new targets for future mechanistic studies and additional insight into the application of genomic information to identify patients at elevated risk for a common and important condition in the ICU.
Novel molecular targets for the treatment of lung cancer
Authors: Rosell Rafael , Karachaliou Niki , Arrieta Oscar 
Published: October 2019

Purpose of review
The mutational landscape in lung adenocarcinoma (LADC) is broadly recognized, particularly regarding the presence of the epidermal growth factor receptor (EGFR) mutation in non-smokers. However, even in the EGFR canonical-mutant LADC, other accompanying alterations surface which may have a major impact in prognosis and open possibilities to explore new therapeutic approaches.

Recent findings
Complex genomic rearrangements, including chromothripsis and chromoplexy, are the origin of most-known fusion oncogenes, including echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, Cluster of Differentiation 74-c-ros oncogene 1, and kinesin-1 heavy chain- rearranged during transfection. Quite often LADCs driven by fusion oncogenes are accompanied by SET domain containing 2 (SETD2) mutations. SETD2 mutations have been described in renal cancer and have been related to cisplatin resistance in LADCs. Suppression of the SETD2 function inhibits the signal transducer and transcription activator function and the interferon-signaling pathway, which could partially explain the lack of effectiveness of immunotherapy in LADCs driven by fusion oncogenes.

Summary
Targeted next-generation sequencing of DNA in the tumor tissue or in the circulating plasma of LADC is becoming indispensable for the accurate classification of LADCs that can receive appropriate targeted therapy. It is unquestionable that additional techniques, like RNA sequencing or the nCounter technology, can accomplish accurate assessment of an ample array of fusion oncogenes involved in LADCs.
Hard-wired Epimysial Recordings from Normal and Reinnervated Muscle Using a Bone-anchored Device
Authors: Lancashire Henry T. , Al Ajam Yazan , Dowling Robert P. , Pendegrass Catherine J. , Blunn Gordon W. 
Published: October 2019

Background:A combined approach for prosthetic attachment and control using a transcutaneous bone-anchored device and implanted muscle electrodes can improve function for upper-limb amputees. The bone-anchor provides a transcutaneous feed-through for muscle signal recording. This approach can be combined with targeted muscle reinnervation (TMR) to further improve myoelectric control.Methods:A bone-anchored device was implanted trans-tibially in n = 8 sheep with a bipolar recording electrode secured epimysially to the peroneus tertius muscle. TMR was carried out in a single animal: the peroneus tertius was deinnervated and the distal portion of the transected nerve to the peroneus muscle was coapted to a transected nerve branch previously supplying the tibialis anterior muscle. For 12 weeks (TMR) or 19 weeks (standard procedure), epimysial muscle signals were recorded while animals walked at 2 km·h−1.Results:After 19 weeks implantation following standard procedure, epimysial recording signal-to-noise ratio (SNR) was 18.7 dB (± 6.4 dB, 95% CI) with typical recordings falling in the range 10–25 dB. Recoveries in gait and muscle signals were coincident 6 weeks post-TMR; initial muscle activity was identifiable 3 weeks post-TMR though with low signal amplitude and signal-to-noise ratio compared with normal muscle recordings.Conclusions:Following recovery, muscle signals were recorded reliably over 19 weeks following implantation. In this study, targeted reinnervation was successful in parallel with bone-anchor implantation, with recovery identified 6 weeks after surgery.
Novel Surface Anatomic Landmarks of the Jowl to Guide Treatment with ATX-101
Authors: Shridharani Sachin M. 
Published: October 2019

Summary:
Facial appearance is critical to physical attractiveness, and maintaining a youthful face and neck is a major motivation for individuals seeking facial cosmetic procedures. A strong mandibular border without prominent jowls is one sign of a youthful face as jowling occurs with age, contributing to squaring of the face and loss of jawline definition. Excess jowl fat has traditionally been reduced with surgical liposuction when jowling is caused by fat flow across the mandible. The approval of ATX-101 (deoxycholic acid injection) for submental fat reduction provides a minimally invasive technique that may also be suitable for jowl fat reduction. The author has developed novel facial markings that consistently isolate the jowl fat area of concern at the mandible for treatment with ATX-101. The current work refreshes physicians on important jowl anatomical structures, defines the facial markings that consistently isolate the jowl, and describes an injection technique to safely treat excess jowl fat with ATX-101.
Measurement of Quality of Life in Keratoconus
Authors: Kandel Himal , Pesudovs Konrad , Watson Stephanie L. 
Published: October 2019

Purpose:
To identify and assess the quality of questionnaires used to measure quality of life in keratoconus and guide selection of the most appropriate questionnaire for evaluating the impact of keratoconus.

Methods:
A literature search was carried out in Scopus, Web of Science, PubMed, MEDLINE, Cochrane, and PsycINFO databases. Articles that described a questionnaire to measure quality of life in keratoconus were included. Information on psychometric properties and validity was extracted and analyzed based on a set of quality criteria. Finally, the impact of keratoconus and its management methods on quality of life was reviewed.

Results:
The search yielded 331 publications, of which 45 articles describing 18 (12 ophthalmic including 2 keratoconus-specific and 6 generic) questionnaires were reviewed. Most of the articles (40, 88.9%) described ophthalmic questionnaires not specific to keratoconus. The National Eye Institute Visual Function Questionnaire was the most frequently used questionnaire (n = 26). Only 4 articles provided information on psychometric properties. The Keratoconus Outcomes Research Questionnaire, the only validated keratoconus-specific questionnaire, had the most superior psychometric properties. However, it consists of items on only 2 domains of quality of life (activity limitation and symptoms). Overall, keratoconus management methods (spectacles, contact lenses, and cross-linking in early stages, corneal transplantation in late stages) improved quality of life. The quality of life scores were associated with clinical measures including visual acuity, corneal topography, pachymetry, and keratoconus severity.

Conclusions:
There is a need for a comprehensive and high-quality patient-reported outcome measure in keratoconus. A questionnaire should be chosen based on the purpose and the quality of the questionnaire. This review guides selection of an appropriate questionnaire.
The Price of Aesthetics After Nipple-Sparring Mastectomy
Authors: Akintayo Rachel M. , Weinstein Andrew L. , Olorunnipa Olushola B. , Otterburn David M. 
Published: October 2019

Background
Skin necrosis after nipple-sparing mastectomy (NSM) and deep inferior epigastric perforator (DIEP) breast reconstruction impacts cosmesis and patient satisfaction. Skin grafting might mitigate these sequelae, but oftentimes creates a color and texture mismatch with native breast skin. In contrast, abdominal skin on the DIEP flap is an excellent match and can be banked. The purposes of this study are to review our experience with skin banking of DIEP flaps and determine the cost-benefit of skin banking compared with other reconstructive options.

Methods
This was a retrospective review study conducted from 2011 to 2014 to examine patients undergoing staged DIEP reconstruction immediately after NSM. Medicare reimbursement costs using Current Procedural Terminology codes, and provider and facilities fees for conventional reconstructions options versus skin banking were obtained with subsequent cost-minimization and sensitivity analyses.

Results
The proportion of patients who developed mastectomy skin necrosis was 12.1%, and that of those who had a positive retroareolar biopsy corresponding to an average surface area of 58.3 cm2 was 3.0%. Average per patient cost of skin banking was $1224, $844 more than split-thickness skin graft (STSG) without Integra, $420 more than STSG with Integra, and $839.01 more than full-thickness skin graft. Sensitivity analysis demonstrates that skin banking was less than managing mastectomy skin loss with STSG and Integra when the incidence of necrosis >10 cm2 exceeded 25.3%.

Conclusions
Skin banking maximizes aesthetic outcomes after skin loss from either positive margins or skin flap necrosis. Use of this technique should occur especially in select patients at increased risk of mastectomy skin flap/nipple-areola complex (NAC) necrosis and/or suspicion for occult NAC carcinoma. Furthermore, among reconstructive plastic surgeons whose rate of mastectomy flap/NAC necrosis >10 cm2 exceeds 25.3%, sensitive analysis favors undergoing a staged reconstruction after NSM.
Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors
Authors: Uemura Jun , Okano Keiichi , Oshima Minoru , Suto Hironobu , Ando Yasuhisa , Kumamoto Kensuke , Kadota Kyuichi , Ichihara Shuji , Kokudo Yasutaka , Maeba Takashi , Nanno Yoshihide , Toyama Hirochika , Takada Yasutsugu , Shimada Mitsuo , Hanazaki Kazuhiro , Masaki Tsutomu , Suzuki Yasuyuki 
Published: October 2019

Objective:
The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs).

Background:
The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear.

Methods:
We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings.

Results:
Kaplan–Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1–66.9, P = 0.003) in G2 PNETs.

Conclusions:
Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.
Knockdown of circular RNA CEP128 suppresses proliferation and improves cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p
Authors: Hua Lin , Huang Lifa , Zhang Xin , Feng Haoke , Shen Bin 
Published: October 2019

Background
Circular RNAs serve as key players in the development of tumorigenesis and chemoresistance. Circular RNA CEP128 has been reported to be involved in the development of chemoresistance. However, the role of circular RNA CEP128 in the resistance of glioma cells to temozolomide has not yet been characterized.

Methods
The expression of circular RNA CEP128, miR-145-5p, and ATP-binding cassette super-family G member 2 was evaluated using quantitative real-time PCR and western blot. The effects of circular RNA CEP128 on glioma cell proliferation and chemoresistance were evaluated by cell count kit-8 assay and colony formation assay. Luciferase reporter assay was performed for target validation.

Results
Circular RNA CEP128 was upregulated in glioma tissues and cell lines. Moreover, circular RNA CEP128 expression was higher in temozolomide-resistant glioma cells compared with that in their parental cells. Knockdown of circular RNA CEP128 inhibited cell proliferation, reduced the expression of ATP-binding cassette super-family G member 2, as well as reduced resistance to temozolomide in glioma cells. Additionally, miR-145-5p was underexpressed in glioma cells as well as temozolomide-resistant glioma cells. Also, miR-145-5p was identified as a target of circular RNA CEP128. Overexpression of miR-145-5p inhibited the proliferation of U251/temozolomide cells and reduced the expression of ATP-binding cassette super-family G member 2, however, these changes induced by miR-145-5p overexpression were blocked by circular RNA CEP128 overexpression.

Conclusion
Knockdown of circular RNA CEP128 suppresses cell proliferation and improves the cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p, suggesting that circular RNA CEP128 might be a promising target for overcoming the resistance of glioma cells to temozolomide.
t-SNE transformation: a normalization method for local features of single-cell RNA-seq data
Authors: Chengrui An , Bacardit Jaume , Nijia Zhang , Bingbing Wu 
Published: October 2019

AbstractSingle-cell RNA sequencing has been widely used by biology researchers. There are many analysis tools developed accordingly. However, almost all of them use log transformation in the process of normalization, which may result in system bias on global features of datasets. It is considered that they may not be suitable for researchers who expect local and detailed features of datasets, such as rare cell population and independent expressed genes. In this study, we developed a method called t-SNE transformation to replace log transformation. We found that it can well respond to some specific bio-markers in real datasets. When the cluster number was changed, t-SNE transformation was steadier than log transformation. Further study showed that clustering after t-SNE transformation detected the residual cells more accurately after majority cells of one type were removed manually. It was also sensitive to a highly-variated independent gene added artificially. In conclusion, t-SNE transformation is an alternative normalization for detecting local features, especially interests arouse in cell types with rare populations or highly-variated but independently expressed genes.
The secretome of a parasite alters its host’s behaviour but does not recapitulate the behavioural response to infection
Authors: Berger Chloé Suzanne , Aubin-Horth Nadia 
Published: October 2019

ABSTRACTParasites with complex life cycles have been proposed to manipulate the behaviour of their intermediate hosts to increase the probability of reaching their final host. The cause of these drastic behavioural changes could be manipulation factors released by the parasite in its environment (the secretome), but this has rarely been assessed. We studied a non-cerebral parasite, the cestodeSchistocephalus solidus, and its intermediate host, the threespine stickleback (Gasterosteus aculeatus), whose response to danger becomes significantly diminished when infected. These altered behaviours appear only during late infection, when the worm is ready to reproduce in its final avian host. Sympatric host-parasite pairs show higher infection success for parasites, suggesting that the secretome effects could differ for allopatric host-parasite pairs with independent evolutionary histories. We tested the effects of secretome exposure on behaviour by using secretions from the early and late infection ofS. solidusand by injecting them in healthy sticklebacks from a sympatric and allopatric population. Contrary to our prediction, secretome from late infection worms did not result in more risky behaviours, but secretome from early infection resulted in more cautious hosts, only in fish from the allopatric population. Our results suggest that the secretome ofSchistocephalus soliduscontains molecules that can affect host behaviour, that the causes underlying the behavioural changes in infected sticklebacks are multifactorial, and that local adaptation between host-parasite pairs may extend to the response to the parasite’s secretome content.
Modeling the Hemodynamic Response Function for Prediction Errors in the Ventral Striatum
Authors: Bravo-Hermsdorff Gecia , Niv Yael 
Published: October 2019

AbstractTo make sensible inferences about neural activation from fMRI data it is important to accurately model the hemodynamic response function (HRF), i.e., the hemodynamic response evoked by a punctuate neural event. HRF models have been derived for sensory areas, where it is relatively clear what events cause a neural impulse response. However, this is obviously harder to do for higher order cortices such as prefrontal areas. Therefore, one HRF model is commonly used for analyzing activity throughout the brain, despite the fact that hemodynamics are known to vary across regions. For instance, several fMRI studies use a canonical HRF to analyze ventral striatum (VS) activity where converging evidence indicates that reward prediction error signals drive neural activity. However, the VS is a target of prominent dopaminergic projections, known to modulate vasculature and affect BOLD activity, suggesting that the HRF in the VS may be especially different from those in other brain areas. To address this, we use data from an experiment focused on learning from prediction-error signals to derive a VS-specific HRF model (VS-HRF). We show that this new VS-HRF increases statistical power in model comparison. Our result is of particular relevance to studies comparing computational models of learning and/or decision making in the VS, and for connectivity analyses, where the use of an (even slightly) inaccurate HRF model can lead to erroneous conclusions. More broadly, our study highlights the importance of the choice of HRF model in determining the significance of the results obtained in classical univariate fMRI analysis.
Multidimensional value creation through different reverse supply chain relationships in used clothing sector
Authors: Pal Rudrajeet , Sandberg Erik , Paras Manoj Kumar 
Published: October 2019

PurposeThis paper aims to purport deeper understanding of, and instigate theoretical elaboration to, multidimensional value created through different reverse supply chain (RSC) relationships.Design/methodology/approachBy capturing the relationships (and their differences) constituted and embedded in three “extreme” case studies from global used clothing supply chain, the sources of multidimensional values are explored in line with Dyer and Singh’s (1998) relational theory.FindingsIn the RSC, when downstream relationships are typically more opportunistic, value is created using inter-personal ways of knowledge sharing and through use of informal safeguards. In contrast, the upstream RSC relationships are more symbiotic, and value is created through more seamless (and routinized) knowledge sharing practices, and additional use of more formal transaction-specific controls or financial incentives as safeguarding instruments.Research limitations/implicationsThe use of consolidated case studies may affect the consistency in the findings presented. Another limitation relates to deriving propositions per each source presented in relational theory.Practical implicationsPractitioners particularly from industries whose global RSCs include different natures of relationships and multiple value incentives can be benefited through this study.Originality/valueThe paper extends the original sources of value creation prescribed in relational theory by contextualizing them in RSCs. It depicts how multidimensional values are created relationally by dyadic partners as the nature of relationship differs between upstream and downstream.
Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod
Authors: Kanekura Takuro , Arimura Akiko , Kirishima Mari , Tanimoto Akihide 
Published: October 2019

AbstractPembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll‐like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7–9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75‐year‐old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well‐differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.