bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profilin 1–mediated cytoskeletal rearrangements regulate integrin function in mouse platelets
Authors: Stritt Simon , Birkholz Inga , Beck Sarah , Sorrentino Simona , Sapra K. Tanuj , Viaud Julien , Heck Johannes , Gaits-Iacovoni Frédérique , Schulze Harald , Du Xiaoping , Hartwig John H. , Braun Attila , Bender Markus , Medalia Ohad , Nieswandt Bernhard 
Published: May 2018

Key Points
Profilin 1–mediated cytoskeletal dynamics regulate platelet β1- and β3-integrin function and turnover. Profilin 1 deficiency in platelets impairs hemostasis and results in a marked protection from arterial thrombosis.
Inverted Rearfoot posture in subjects with coexisting patellofemoral osteoarthritis in medial knee osteoarthritis: an exploratory study
Authors: Iijima Hirotaka , Ohi Hiroshi , Fukutani Naoto , Aoyama Tomoki , Kaneda Eishi , Abe Kaoru , Takahashi Masaki , Matsuda Shuichi 
Published: May 2018

AbstractBackgroundWhile abnormal rearfoot posture and its relationship to patellofemoral (PF) pain has been thoroughly discussed in the literature, its relationship to patellofemoral osteoarthritis (PFOA) has not been determined. This study aimed to examine whether rearfoot posture is associated with a higher prevalence of radiographic PFOA in a compartment‐specific manner in patients with medial tibiofemoral osteoarthritis (TFOA).MethodsParticipants from orthopedic clinics (n = 68, age 56–90 years, 75.0% female), diagnosed with radiographic medial TFOA (Kellgren/Lawrence [K/L] grade ≥ 2) were included in this study. The presence of PFOA and static rearfoot posture were evaluated using a radiographic skyline view and a footprint automatic measurement apparatus, respectively. The relationship between rearfoot posture and PFOA was examined using analysis of covariance and propensity score‐adjusted logistic regression analysis.ResultsOn average, patients with coexisting PFOA and medial TFOA (n = 39) had an inverted calcaneus 3.1° greater than those with isolated medial TFOA (n = 29). Increased calcaneus inverted angle was significantly associated with a higher probability of the presence of medial PFOA (odds ratio: 1.180, 95% confidence interval: [1.005, 1.439]; p = 0.043). Calcaneus inverted angle was not associated with higher odds of lateral PFOA presence based on the adjusted values.ConclusionsThe presence of an inverted rearfoot was associated with PFOA. Although these findings do not clearly indicate a biomechanical link between rearfoot posture and PFOA, this study shed light on the potential relationship between altered rearfoot posture and PFOA, as can be seen between rearfoot abnormality and PF pain.
An evaluation of in-office flexible fiber-optic biopsies for laryngopharyngeal lesions
Authors: Lee Francisco , Smith Kristine A. , Chandarana Shamir , Matthews T. Wayne , Bosch J. Douglas , Nakoneshny Steven C. , Dort Joseph C. 
Published: May 2018

Background Operative endoscopy and flexible fiber-optic in-office tissue biopsy are common techniques to assess suspicious laryngopharyngeal lesions. Methods The primary outcome was the delay to the initiation of treatment. Secondary outcomes were delay to biopsy, histopathological diagnosis, and assessment at a multidisciplinary oncology clinic. A retrospective analysis was performed to assess the relative delays between these approaches to biopsy of laryngopharyngeal lesions. Results There were 114 patients in the study cohort; 44 in-office and 70 operative endoscopic biopsies). The mean delay from consultation to biopsy was 17.4 days for the operative endoscopy group and 1.3 days for the in-office group. The mean delay from initial otolaryngology consultation to initiation of treatment was 51.7 days and 44.6 days for the operative endoscopy and in-office groups, respectively. Conclusion In-office biopsy reduced the time from initial consultation to biopsy. The temporal gains via in-office biopsy did not translate into faster access to treatment. This outcome highlights the opportunity to improve access to treatment for patients with early diagnosis.
Smartphone adapters for flexible Nasolaryngoscopy: A systematic review
Authors: Quimby A. E. , Kohlert S. , Caulley L. , Bromwich M. 
Published: May 2018

Background Flexible nasolaryngoscopy is an essential component of the otolaryngological physical exam. Historically, the ability to create and share video recordings of these endoscopic exams has been limited by poor mobility of fixed endoscopy towers. The advent of smartphone endoscope adapters has allowed physicians to create and share video recordings of endoscopy in a wide variety of locations that would not have previously been feasible. This paper sought to review the literature on the effect of smartphone endoscope adapters on patient care, patient satisfaction, and resident learning. Methods This systematic review was conducted according to PRISMA guidelines. A systematic literature search was performed for all relevant English language studies (1946–2017) using Ovid MEDLINE, PubMed, and EMBASE. The study protocol was registered with the PROSPERO database. Results A total of 91 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, three studies were selected and subjected to full-text extraction as well as quality assessment. These studies demonstrated high diagnostic accuracy and quality of smartphone adapter-recorded videos, and a benefit of these devices on resident education. Due to the heterogeneity of included studies’ methods and measures, a meta-analysis was not possible, so a qualitative synthesis of the literature results was performed. Conclusion Despite a paucity of data on the subject, the present study provided a comprehensive review of the literature, and suggested overall high diagnostic accuracy, quality, and enhancement of resident education with the use of smartphone endoscope adapters for flexible nasolaryngoscopy. Trial registration CRD42018086714.
Xenograft tumors derived from malignant pleural effusion of the patients with non‐small‐cell lung cancer as models to explore drug resistance
Authors: Xu Yunhua , Zhang Feifei , Pan Xiaoqing , Wang Guan , Zhu Lei , Zhang Jie , Wen Danyi , Lu Shun 
Published: May 2018

AbstractBackgroundNon‐small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10–12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient‐derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK‐ and EGFR‐targeted TKIs crizotinib and osimertinib, respectively.MethodsGenotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft‐bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically.ResultsThe histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule‐associated protein‐like 4‐ALK (EML4–ALK) gene fusion (patient/xenograft: CTC15035EML4–ALK) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063EGFR L858R, T790M)). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4–ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v‐RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol‐4‐phosphate 3‐kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R, T790M xenografts.ConclusionsWe successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology, which might be a useful tool to investigate the mechanisms of drug resistance in NSCLC.
Role of Kip2 during early mitosis – impact on spindle pole body separation and chromosome capture
Authors: Augustine Beryl , Chin Cheen Fei , Yeong Foong May 
Published: May 2018

ABSTRACT
Mitotic spindle dynamics are regulated during the cell cycle by microtubule motor proteins. In Saccharomyces cerevisiae, one such protein is Kip2p, a plus-end motor that regulates the polymerization and stability of cytoplasmic microtubules (cMTs). Kip2p levels are regulated during the cell cycle, and its overexpression leads to the formation of hyper-elongated cMTs. To investigate the significance of varying Kip2p levels during the cell cycle and the hyper-elongated cMTs, we overexpressed KIP2 in the G1 phase and examined the effects on the separation of spindle pole bodies (SPBs) and chromosome segregation. Our results show that failure to regulate the cMT lengths during G1-S phase prevents the separation of SPBs. This, in turn, affects chromosome capture and leads to the activation of spindle assembly checkpoint (SAC) and causes mitotic arrest. These defects could be rescued by either the inactivation of checkpoint components or by co-overexpression of CIN8, which encodes a motor protein that elongates inter-polar microtubules (ipMTs). Hence, we propose that the maintenance of Kip2p level and cMT lengths during early cell division is important to ensure coordination between SPB separation and chromosome capture by kinetochore microtubules (kMTs).
BMPR2 inhibits activin and BMP signaling via wild-type ALK2
Authors: Olsen Oddrun Elise , Sankar Meenu , Elsaadi Samah , Hella Hanne , Buene Glenn , Darvekar Sagar Ramesh , Misund Kristine , Katagiri Takenobu , Knaus Petra , Holien Toril 
Published: May 2018

ABSTRACT
TGF-β/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand-dependent downstream signaling. Activin A, a TGF-β superfamily member, inhibits growth of multiple myeloma cells, but the mechanism for this is unknown. We therefore aimed to clarify how activins affect myeloma cell survival. Activin A activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor, but may also activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2 (also known as ACVR1). We demonstrate that activin A and B activate SMAD1/5/8 in myeloma cells through endogenous wild-type ALK2. Knockdown of the type 2 receptor BMPR2 strongly potentiated activin A- and activin B-induced activation of SMAD1/5/8 and subsequent cell death. Furthermore, activity of BMP6, BMP7 or BMP9, which may also signal via ALK2, was potentiated by knockdown of BMPR2. Similar results were seen in HepG2 liver carcinoma cells. We propose that BMPR2 inhibits ALK2-mediated signaling by preventing ALK2 from oligomerizing with the type 2 receptors ACVR2A and ACVR2B, which are necessary for activation of ALK2 by activins and several BMPs. In conclusion, BMPR2 could be explored as a possible target for therapy in patients with multiple myeloma.
This article has an associated First Person interview with the first author of the paper.
Tricellular junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis
Authors: Wang Zhimin , Bosveld Floris , Bellaïche Yohanns 
Published: May 2018

ABSTRACT
In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored de novo formation of tricellular septate junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis.
Hypotheses, rationale, design, and methods for evaluation of a randomized controlled trial using Tocotrienol, an isomer of Vitamin E derived from palm oil, on the prevention of atrial fibrillation after coronary artery bypass grafting surgery
Authors: Musa Ahmad Farouk , Dillon Jeswant , Md Taib Mohamed Ezani , Mohamed Yunus Alwi , Nordin Rusli Bin , Kah Hay Yuen 
Published: May 2018

Background: One of the most common complications following coronary artery bypass grafting (CABG) surgery is atrial fibrillation (AF), which contributes towards increasing morbidity and mortality, length of hospital stay (LoHS) and reduced quality of life (QoL) of patients. Objectives: To determine whether the intake of Tocotrienol, a Vitamin E isomer derived from palm oil, before and immediately following CABG prevents AF, reduces LoHS, and improves the QoL of patients. Protocol: The study is registered with the National Medical Research Register with a trial number NMRR-17-1994-34963 and designed as a prospective, randomized controlled trial (RCT) with parallel groups. The experimental group will receive two 200mg Tocotrienol capsules each day, while the control group will receive two identical placebo (palm Super Olein) capsules per day. ECG readings will be used to detect AF post operatively, LoHS will be measured by checking the records from the National Heart Institute Hospital register, and the health-related Quality of Life (HRQoL) analysis (the Malay version of the Short Form 36 Questionnaire) will be used to analyse QoL. The sample size was calculated to be 140 in each arm of the RCT for a power of 0.8 and a significance level of 0.05. Funding: HOVID Berhad funds this research project. Expected outcomes: The primary endpoint is the development of postoperative AF, whilst the secondary endpoints are the LoHS and HRQoL of patients post CABG. Future implications: Prevention of AF and its complications such as cardiovascular or cerebrovascular events, especially stroke, is an important output. Malaysia is one of the biggest producers and exporters of palm oil and palm oil products. Thus, the possibility of marketing Tocotrienol, in reducing AF post CABG surgery, is a very important proposition indeed. Trial number: NMRR-17-1994-34963
Knowledge discovery for Deep Phenotyping serious mental illness from Electronic Mental Health records
Authors: Jackson Richard , Patel Rashmi , Velupillai Sumithra , Gkotsis George , Hoyle David , Stewart Robert 
Published: May 2018

Background: Deep Phenotyping is the precise and comprehensive analysis of phenotypic features in which the individual components of the phenotype are observed and described. In UK mental health clinical practice, most clinically relevant information is recorded as free text in the Electronic Health Record, and offers a granularity of information beyond what is expressed in most medical knowledge bases. The SNOMED CT nomenclature potentially offers the means to model such information at scale, yet given a sufficiently large body of clinical text collected over many years, it is difficult to identify the language that clinicians favour to express concepts. Methods: By utilising a large corpus of healthcare data, we sought to make use of semantic modelling and clustering techniques to represent the relationship between the clinical vocabulary of internationally recognised SMI symptoms and the preferred language used by clinicians within a care setting. We explore how such models can be used for discovering novel vocabulary relevant to the task of phenotyping Serious Mental Illness (SMI) with only a small amount of prior knowledge. Results: 20 403 terms were derived and curated via a two stage methodology. The list was reduced to 557 putative concepts based on eliminating redundant information content. These were then organised into 9 distinct categories pertaining to different aspects of psychiatric assessment. 235 concepts were found to be expressions of putative clinical significance. Of these, 53 were identified having novel synonymy with existing SNOMED CT concepts. 106 had no mapping to SNOMED CT. Conclusions: We demonstrate a scalable approach to discovering new concepts of SMI symptomatology based on real-world clinical observation. Such approaches may offer the opportunity to consider broader manifestations of SMI symptomatology than is typically assessed via current diagnostic frameworks, and create the potential for enhancing nomenclatures such as SNOMED CT based on real-world expressions.
In vitro evaluation of the antifungal activity of Marco (Ambrosia arborescens Mill.) and Matico (Aristeguietia glutinosa Lam.) on the pathogenic fungi that cause dermatomycosis (ringworm)
Authors: de los Ángeles Mosquera Tayupanta Tatiana , Ayala Valarezo Sandra Elizabeth , Vasquez Villareal Tatiana Alexandra , Montaluisa Álvarez María Belén 
Published: May 2018

Background: Currently, there is a trend towards using natural and ethnopharmacological species with therapeutic potential. This investigation evaluated the antifungal activity of two species in the Ecuadorian Andes, which are used in treating dermatomycosis: Ambrosia arborescens Mill. (Marco) and Aristeguietia glutinosa Lam. (Matico). Methods: We worked with seven concentrations (100 to 700ppm) of Ambrosia arborescens Mill. extract and ten concentrations (0.5 to 5%) of essential oil (EO) of Aristeguietia glutinosa Lam. on Trichophyton mentagrophytes ATCC 9533, Trichophyton rubrum ATCC 28188, Microsporum canis ATCC 36299 and Candida albicans ATCC 10231. The methodology used was a modified version of the Kirby-Bauer method, using diffusion in agar wells. Results: The Tukey test, after the one-way Anova, determined effective concentrations of EO: 5% for Trichophyton mentagrophytes, 4.5% for Trichophyton rubrum, 5% for Microsporum canis and 2% for Candida albicans. In the extracts, the concentration of 700ppm was used for Trichophyton mentagrophytes, Trichophyton rubrum, and 600ppm for Microsporum canis and Candida albicans. Conclusions: The evaluation of the antifungal activity of the Ambrosia arborescens extract showed inhibition in the studied dermatophytes in each one of the planted concentrations (100 to 700ppm). The evaluation of the antifungal activity of Aristeguietia glutinosa EO showed inhibition in the studied dermatophytes in each of the planted concentrations (0.5 to 5%).
Service Systems with Heterogeneous Customers: Investigating the Effect of Telemedicine on Chronic Care
Authors: Rajan Balaraman , Tezcan Tolga , Seidmann Abraham 
Published: May 2018

Medical specialists treating chronic conditions typically face a heterogeneous set of patients. Such heterogeneity arises because of differences in medical conditions as well as the travel burden each patient faces to visit the clinic periodically. Given this heterogeneity, we compare the strategic behavior of revenue-maximizing and welfare-maximizing specialists and prove that the former will serve a smaller patient population, spend more time with the patients, and have shorter waiting times. We also analyze the impact of telemedicine technology on patient utility and the specialists’ operating decisions. We consider both the case when specialists can freely set their own fee for service and the case when fees are set exogenously by a third-party payer. We prove that with the introduction of telemedicine, the specialists become more productive and the overall social welfare increases, although some patients, unexpectedly, will be worse off. Our analytical results lead to some important policy implications for facilitating the further deployment of telemedicine in the care of chronically ill patients. This paper was accepted by Serguei Netessine, operations management.
Clinical application of a 3D-printed scaffold in chronic wound treatment: a case series
Authors: Sun Haining , Lv Huayao , Qiu Fanghui , Sun Duolun , Gao Yue , Chen Ning , Zheng YongKe , Deng Kunxue , Yang Yaya , Zhang Haitao , Xu Tao , Ren Dongni 
Published: May 2018

Objective: This case series evaluates the safety and effectiveness of 3D-printed scaffold in chronic wounds. The scaffold is a composite of natural and synthetic materials, and can be prepared in the form of powder or membrane. Method: We recruited patients with pressure ulcera (PU) and/or a diabetic foot ulcers (DFU). We used two methods: 3D-printed scaffolds alone, or 3D-printing powder mixed with platelet-rich fibrinogen (PRF). Clinicians and patients were asked to rate the scaffold's ease of application and comfort during use. Results: A total of five patients were recruited; four with a PU and one with a DFU. For the patient treated with the 3D-printed scaffold membrane (n=1), their PU healed in 28 days, and for patients treated with the 3D-printed scaffold powder (n=2), their PUs healed in 54 days. For the patients treated with the 3D-printing powder mixed with PRF (n=2), the patient with a PU healed in 11 days, and the patient with the DFU healed in 14 days. All clinicians rated the 3D-printed scaffold as ‘easy’ or ‘very easy’ to use, and patients rated their comfort during wear and at dressing change as ‘good’ or ‘very good’. Conclusion: This study demonstrated that 3D-printed scaffold was convenient to use, have the potential to improve wound healing rates, and provided a safe and effective way for treating chronic wounds.