bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human-relevant preclinical in vitro models for studying hepatobiliary development and liver diseases using induced pluripotent stem cells
Authors: Chaudhari Pooja , Tian Lipeng , Ye Zhaohui , Jang Yoon-Young 
Published: February 2019

Pharmaceutical drug development and clinical testing is associated with billions of dollars, and often the time and money spent does not result in a viable drug formulation. The pharmaceutical industry has long relied on animal models for testing efficacy, toxicity and specificity of novel drugs. However, the studies cannot be fully relied upon, as animal models are not reflective of human pathophysiology and drug response, which results in drugs being pulled from development as late as at stage IV, after billions of dollars have already been invested in such an effort. With the advent of adult-induced pluripotent stem cell technology, came an era which offered the potential of pursing human relevant developmental and pathogenesis research and drug testing on patient-induced pluripotent stem cell-derived differentiated cells, consciously reflecting human responses with regard to drug safety, toxicity, efficacy, and side effects. Specifically, human-induced pluripotent stem cell-derived hepatobiliary cells and tissues may be a more human-relevant model system to address the biggest barrier to drug safety and approval: hepatotoxicity. In this review, we address the potential of human-induced pluripotent stem cell-based hepatobiliary differentiation technology as a means to study human liver development and hepatic cell fate determination, and to model liver diseases in an effort to develop a new human-relevant preclinical platform for drug development. Impact statement In this review, we address the potential of human-induced pluripotent stem cell-based hepatobiliary differentiation technology as a means to study human liver development and cell fate determination, and to model liver diseases in an effort to develop a new human-relevant preclinical platform for drug development.
Lyophilizing thrombin powder-based treatment for hemostasis during coil embolization of ruptured cerebral aneurysm: Two case reports
Authors: Jiang Changchun , Wang Wei , Wang Baojun , Li Yuechun , Liu Guorong , Zhang Tianyou , Fan Yu , Yang Junfeng , Li Xia , Hao Xiwa , Hao Fei , Zhao Junmei , Wang Shuguang , Jiang Chuhan 
Published: February 2019

Background Rupture of cerebral aneurysm is an inevitable complication during embolization, followed by subsequent acute subarachnoid hemorrhage or intracranial hematoma, and results in the aggravation of a patient’s condition. In particular, for patients who have had a ruptured aneurysm, urgent treatment strategies are required during operation. The most common hemostatic methods seen in clinical practices are as follows: after lowering the blood pressure, we continue to embolize the aneurysms with detachable coils as soon as possible or inject with Glubran/Onyx embolization liquids, as well as use a balloon catheter to temporarily block the blood supply. If the conditions are permissible, a balloon guiding catheter may even be used to restrict the proximal blood flow. At times, due to limitations of these methods, neurosurgeons are requested to perform craniotomy to treat the hemostasis. However, the delayed transition often leads to rapid deterioration of the patient’s condition and even death due to cerebral hernia. Case description We herein presented two cases of ruptured cerebral aneurysms to provide an alternative method for hemostasis and to save the lives of patients as much as possible. In an extremely urgent situation (conventional treatment is ineffective), we successfully saved the patient’s life by injecting lyophilizing thrombin powder (LTP) solution into the aneurysmal sac and the parent artery through a microcatheter. Conclusions To our knowledge, this is the first report of successful hemostasis during coil embolization of ruptured cerebral aneurysm with LTP. Further prospective studies are needed to confirm the safety and efficacy of LTP in cerebrovascular interventional therapy.
Posterior communicating and anterior communicating arteries on pre-thrombectomy computed tomography scans are associated with good outcomes irrespective of leptomeningeal collateral status
Authors: Yeo Leonard LL , Andersson Tommy , Holmberg Åke , Mpotsaris Anastasios , Söderman Michael , Holmin Staffan , Bhogal Pervinder , Cunli Yang , Gopinathan Anil , Tan Benjamin YQ , Gontu Vamsi , Kolloch Jens , KuntzeSöderqvist Åsa , Brouwer Patrick A , Cornelissen Sandra 
Published: February 2019

Background Collateral blood flow is known to be an important factor that sustains the penumbra during acute stroke. We looked at both the leptomeningeal collateral circulation and the presence of anterior and posterior communicating arteries to determine the factors associated with good outcomes and mortality. Methods We included all patients with acute ischaemic stroke in the anterior circulation, who underwent thrombectomy with the same thrombectomy device from 2013 to 2016. We assessed the leptomeningeal circulation by the Tan, Miteff and Maas validated scoring systems on pre-treatment computed tomographic angiography scans and looked at collateral flow through anterior and posterior communicating arteries. The results were good functional outcomes at 3 months (modified Rankin scale 0–2) and mortality. Results A total of 147 consecutive acute stroke patients treated with the Embotrap device were included with a median National Institutes of Health stroke scale of 15 (range 2–26). On multivariate analysis only younger age (odds ratio (OR) 0.96/year, 95% confidence interval (CI) 0.94–0.99, P = 0.026), lower National Institutes of Health stroke scale score (OR 0.87/point, 95% CI 0.80–0.93, P < 0.001), number of attempts (OR 0.80/attempt, 95% CI 0.65–0.99, P = 0.043) and the presence of a patent anterior communicating artery (OR 14.03, 95% CI 1.42–139.07, P = 0.024) were associated with good functional outcomes. The number of attempts (OR 1.66/attempt, 95% CI 1.21–2.29, P = 0.002) was significantly associated with mortality and the presence of a patent posterior communicating artery (OR 0.098, 95% CI 0.016–0.59, P = 0.011) was inversely associated with mortality. Conclusions Our study shows that the presence of anterior and posterior communicating arteries is significantly associated with good functional outcomes and reduced mortality, respectively, independent of the leptomeningeal circulation status.
Switching to riociguat: a potential treatment strategy for the management of CTEPH and PAH
Authors: Benza Raymond L. , Corris Paul A. , Ghofrani Hossein‐Ardeschir , Kanwar Manreet , McLaughlin Vallerie V. , Raina Amresh , Simonneau Gérald 
Published: February 2019

Currently, five classes of drug are approved for the treatment of pulmonary arterial hypertension (PAH): phosphodiesterase 5 inhibitors (PDE5i); endothelin receptor antagonists; prostacyclin analogs; the IP receptor agonist selexipag; and the soluble guanylate cyclase (sGC) stimulator riociguat. For patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), riociguat is currently the only approved pharmacotherapy. Despite the development of evidence‐based guidelines on appropriate use of specific drugs, in clinical practice patients are often prescribed PAH‐targeted therapies off label or at inadequate doses.PDE5i are the most often prescribed class of drugs as initial therapy, either alone or in combination with other drug classes. However, a proportion of patients receiving PAH therapies do not reach or maintain treatment goals. As PDE5i and riociguat target different molecules in the nitric oxide‐sGC‐cyclic guanosine monophosphate (NO‐sGC‐cGMP) signaling pathway, for patients with PAH without an initial or sustained response to PDE5i, there is a biological rationale for switching to riociguat. However, robust data from randomized controlled trials on the safety and efficacy of switching are lacking, as is formal guidance for clinicians. Here we review studies of sequential combination therapy, and trial data and case studies that have investigated switching between PAH‐approved therapies, particularly from PDE5i to riociguat in patients with PAH with an insufficient response to PDE5i, and in patients with CTEPH who were receiving off‐label treatment. These studies summarize the current evidence and practical real‐life experience on the concept of switching treatments.
Epidemiology of acute kidney injury and associated factors among patients with malignancy: Analysis of hospital inpatient database in Shanghai, China
Authors: Li Yang , Chen Xiaohong , Wang Yimei , Hu Jiachang , Xu Jiarui , Jiang Wuhua , Shen Bo , Teng Jie , Ding Xiaoqiang 
Published: February 2019

Objective: This study aimed to understand the incidence of acute kidney injury in cancer patients, to figure out which clinical factors could increase the risks of acute kidney injury, and then to assess the effect of acute kidney injury on in-hospital mortality, length of stay, and hospital cost. Methods: This study was designed as a retrospective cohort study based on the hospital inpatient database in Zhongshan Hospital, Shanghai, China. Patients with malignancy and admitted to the hospital between 1 October 2014 and 30 September 2015 were recruited. Data on demographics, comorbidities, and clinical records were exported for analysis. Acute kidney injury was diagnosed using KDIGO (Kidney Disease: Improving Global Outcomes) criteria and stratified into community-acquired and hospital-acquired acute kidney injury. Multivariate model and survival analysis were applied to discover the influencing factors of acute kidney injury among cancer patients. Results: Of the 26,914 eligible cancer admissions, 3326 acute kidney injury cases were identified with an incidence of 12.4%. Of them, 2961 patients located in acute kidney injury stage 1 and another 365 cases developed to stage 2–3. The highest rates were localized to renal cancer (27.3%), multiple myeloma (24.1%), and leukemia (23.9%). Patients with older age and hematologic cancer shared a higher acute kidney injury incidence. Pre-existing chronic kidney disease (adjusted odds ratio = 7.14), heart failure (adjusted odds ratio = 4.20), surgery/chemotherapy (adjusted odds ratio = 0.99/2.28), hyponatremia (adjusted odds ratio = 2.84), hypokalemia (adjusted odds ratio = 2.42), and hyperuricemia (adjusted odds ratio = 2.62) were the major factors associated with acute kidney injury. In-hospital mortality for acute kidney injury patients was 5.1% as compared with those without acute kidney injury (0.8%). Survival analysis reveals that the risk of death was higher among patients with hospital-acquired acute kidney injury (adjusted hazard ratio = 4.50) and severe acute kidney injury stage (adjusted hazard ratio = 2.68/3.91). Furthermore, the length of stay (13.5 days) and hospital cost (45,066 CNY) were significantly greater in patients with community-acquired acute kidney injury. Conclusion: Acute kidney injury was common in cancer patients and associated with an ominous outcome. Pre-existing comorbidities, electrolyte disturbances, and abnormal biochemical were the predicting factors for acute kidney injury incidence. Better monitoring of electrolytes, identification of high-risk patients, and early acute kidney injury diagnosis should be considered as a priority during anti-cancer treatment.
Outcomes of 25-Gauge Vitrectomy With Relaxing Retinectomy for Retinal Detachment Secondary to Proliferative Vitreoretinopathy
Authors: Jiang Yi , Oh Daniel J. , Messenger Wyatt , Lim Jennifer I. 
Published: February 2019

Purpose: The aim of this study is to evaluate visual and anatomic outcomes of 25-gauge vitrectomy with relaxing retinectomies for complex retinal detachment (RD) secondary to proliferative vitreoretinopathy (PVR). Methods: A single-center, retrospective case series of 44 patients who had undergone a 25-gauge vitrectomy with a relaxing retinectomy for the treatment of combined RD and PVR was performed. Preoperative characteristics, intraoperative techniques, and outcomes were analyzed. The rates of attachment, complications, and visual acuity were analyzed. Institutional review board/ethics committee approval was obtained, and the described research adhered to the tenets of the Declaration of Helsinki. Results: At the final follow-up, 27 eyes (61%) had attachment after 1 surgery, 41 eyes (93%) ultimately had attached retinas, 3 eyes (7%) had hypotony, 3 eyes had become phthisical (7%), and 24 eyes (56%) had improved visual acuity. After stratifying by visual outcomes, 20/400 or better best-corrected visual acuity was not associated with age ( P = .66), RD etiology ( P = .61), preoperative hypotony ( P = .60), nor size of retinectomy ( P = .48). Patients achieving 20/400 vision or better were statistically more likely to be pseudophakic ( P = .024) and have silicone oil removal ( P < .0001). Conclusion: The use of 25-gauge vitrectomy and relaxing retinectomy provides a high rate of reattachment and improved visual acuity.
FGF23 and its role in X-linked hypophosphatemia-related morbidity
Authors: Beck-Nielsen Signe Sparre , Mughal Zulf , Haffner Dieter , Nilsson Ola , Levtchenko Elena , Ariceta Gema , de Lucas Collantes Carmen , Schnabel Dirk , Jandhyala Ravi , Mäkitie Outi 
Published: February 2019

AbstractBackgroundX-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of thePhosphate Regulating Endopeptidase Homolog, X-Linked(PHEX) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood.MethodsThe role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH.ResultsThe pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations.ConclusionsBy describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.
RETRACTED ARTICLE: miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization
Authors: Lin Xiaobin , Wang Shuyi , Sun Min , Zhang Chunxiao , Wei Chen , Yang Chaogang , Dou Rongzhang , Liu Qing , Xiong Bin 
Published: February 2019

Abstract
Background
Tumor microenvironment (TME) is a complex environment containing tumor cells, tumor-associated macrophages (TAMs), interstitial cells, and non-cellular components. Epithelial–mesenchymal transition (EMT), as a major actor in cancer tumorigenicity and metastasis, was involved in the interaction between TAMs and tumor cells. However, the potential mechanisms of EMT and how EMT-programmed tumor cells affect M2-like TAMs still need further exploration.

Methods
An integrated analysis of nine CRC miRNA expression datasets was performed. Functional assays, including the EdU, clone formation, wound healing, and transwell assays, were used to determine the anticancer role of miR-195-5p in human CRC progression. Furthermore, RNA immunoprecipitation, RNA decay, and dual-luciferase reporter assays were used to determine the mechanism of miR-195-p CRC progression. Then co-culture, migration, and ELISA assays were applied to determine the role of miR-195-5p in macrophage recruitment and alternative polarization. Xenograft mouse models were used to determine the role of miR-195-5p in CRC tumorigenicity and TAM polarization in vivo.

Results
An integrated analysis confirmed that miR-195-5p was significantly downregulated in CRC tissues, and patients with a low level of miR-195-5p had significantly shortened overall survival as revealed by the TCGA-COAD dataset. Altered miR-195-5p in colon cancer cells led to distinct changes of proliferation, migration, invasion, and EMT. Mechanistically, miR-195-5p regulated NOTCH2 expression in a post-transcriptional manner by directly binding to 3′-UTR of the Notch2 mRNA. Subsequently, miR-195-5p/NOTCH2 suppressed GATA3-mediated IL-4 secretion in CRC cells and ultimately inhibited M2-like TAM polarization.

Conclusions
miR-195-5p may play a vital role in regulating NOTCH2-mediated tumor cell EMT, thereby affecting IL-4-related M2-like TAM polarization in CRC.
Metachronous or synchronous male breast and prostate cancers a duality to lookout for.
Authors: Mukendi Alain Mwamba , Van Den Berg Eunice , Pather Sugeshnee , Padayachee Rushen Siva 
Published: February 2019

Introduction: Breast cancer is well known as the stereotypical women's cancer, and prostate cancer represents the well-known stereotypical male counterpart. While prostate cancer carries the potential to metastasize to the breast, the synchronous or metachronous co-occurrence of primary breast and primary prostate cancers is quite unusual. Prostate cancer in men of African descent may have its own behaviour with regards to its relationship with male breast cancer. Case presentation: Case 1: A 64 year old male presented to Chris Hani Baragwanath Hospital (CHBAH) with a 2 years history of a painless left breast lump. A core biopsy was done and confirmed breast carcinoma. Tamoxifen was started but, due to disease progression, he underwent left modified radical mastectomy followed by chemotherapy. Prostate biopsy was done for raised Prostate Specific Antigen (PSA) and suspicious prostate on digital rectal examination. A prostatic adenocarcinoma was subsequently diagnosed with bone metastases on bone scan. He was started on Androgen deprivation therapy and followed up every 3 months. Case 2: A 68 year old male presented to CHBAH with a 1 year history of a painless right breast lump. A core biopsy confirmed breast cancer. Tamoxifen was started, followed by right modified radical mastectomy and chemotherapy for disease progression. A raised PSA and suspicious prostate on digital rectal examination prompted a prostate biopsy revealing a prostatic adenocarcinoma. Bone scan was negative for metastasis. He is currently on 3 monthly Androgen deprivation therapy and awaiting radiation. Conclusion: This clinical practice article not only presents this exceptionally rare duality but highlights that both cancers can coexist either as sporadic conditions, or as a result of genetic mutations. Thus, we suggest that men with prostate cancer be screened clinically, biochemically and genetically for breast cancer and vice versa.
Mobile Messaging for Offline Group Formation in Prosocial Activities: A Large Field Experiment
Authors: Sun Tianshu , Gao Guodong (Gordon) , Jin Ginger Zhe 
Published: February 2019

In this paper, we use mobile messaging to leverage recipients’ social ties and encourage offline prosocial activities in groups. In particular, we conduct a randomized field experiment with 80,000 blood donors and study how behavioral interventions and economic rewards motivate offline group formation. We find that two commonly used interventions—reminder messages and individual reward—are ineffective in motivating group formation because they do not compensate donors for the cost of bringing friends. In contrast, we find that group reward—a new reward that is contingent on a donor bringing a friend—is effective in motivating group formation. Furthermore, group reward tends to attract different types of donors, especially those who are traditionally less active in online social settings but have more local social ties. Structural estimation further reveals the underlying mechanisms, suggesting that group reward is four times more cost-effective than individual reward in driving total donation. Our study suggests that motivating offline group formation is a promising approach to boost prosocial activities.The online appendix is available at https://doi.org/10.1287/mnsc.2018.3069 .This paper was accepted by Chris Forman, information systems.
Confocal fluorescence microscopy for geometry parameter measurements of submerged micro-structures
Authors: Mikulewitsch Merlin , von Freyberg Axel , Fischer Andreas 
Published: February 2019

Due to the challenging environment of micro-manufacturing techniques
where the workpiece is submerged in a fluid, a contactless in
situ capable measurement is required for quality control.
However, the in situ conditions and the small
specimen dimensions hinder the use of conventional metrology. Confocal
fluorescence microscopy is shown to enable step height measurements of
a specimen submerged in a 2.6 mm thick fluid layer with an uncertainty
of 8.8 μm by fitting a model of the fluorescence intensity to the
measured signal. To ascertain the potential of the proposed
measurement approach, the minimal achievable uncertainty of 0.07 μm
for a shot-noise-limited signal is derived.
Parameters for Validating a Hospital Pneumatic Tube System
Authors: Farnsworth Christopher W , Webber Daniel M , Krekeler James A , Budelier Melissa M , Bartlett Nancy L , Gronowski Ann M 
Published: February 2019

AbstractBACKGROUNDPneumatic tube systems (PTSs) provide rapid transport of patient blood samples, but physical stress of PTS transport can damage blood cells and alter test results. Despite this knowledge, there is limited information on how to validate a hospital PTS.METHODSWe compared 2 accelerometers and evaluated multiple PTS routes. Variabilities in PTS forces over the same routes were assessed. Response curves that demonstrate the relationship between the number and magnitude of accelerations on plasma lactate dehydrogenase (LD), hemolysis index, and potassium in PTS-transported blood from volunteers were generated. Extrapolations from these relationships were used to predict PTS routes that may be prone to false laboratory results. Historical data and prospective patient studies were compared with predicted effects.RESULTSThe maximum recorded g-force was 10g for the smartphone and 22g for the data logger. There was considerable day-to-day variation in the magnitude of accelerations (CV, 4%–39%) within a single route. The linear relationship between LD and accelerations within the PTS revealed 2 PTS routes predicted to increase LD by ≥20%. The predicted increase in LD was similar to that observed in patient results when using that PTS route.CONCLUSIONSHospital PTSs can be validated by documenting the relationship between the concentrations of analytes in plasma, such as LD, with PTS forces recorded by 3-axis accelerometers. Implementation of this method for PTS validation is relatively inexpensive, simple, and robust.