bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical Dilation With a Nylon Monofilament for 0.1-mm Anastomoses
Authors: Yoshida Shuhei , Koshima Isao , Sasaki Ayano , Fujioka Yumio , Nagamatsu Shogo , Yokota Kazunori , Yamashita Shuji , Harima Mitsunobu 
Published: October 2018

AbstractDespite advances in supermicrosurgical techniques, the ability to anastomose vessels with a diameter of less than 0.2 mm remains limited. One of the reasons for this limitation is that the dilation methods currently available, such as inserting the tip of a microforceps into the lumen or topical application of a vasodilator such as papaverine hydrochloride or xylocaine spray, are not effective in very small vessels. To overcome this problem, we have developed a method whereby nylon monofilaments are placed inside the vessel lumen to act as a dilator. Using this method, a smaller nylon monofilament is inserted into the vessel as a guide before inserting a larger nylon monofilament as a dilator. After the smaller guide monofilament has been inserted, it is then much easier to insert another monofilament for dilation, even if it is a larger one. Using this method, even a vessel with a diameter of less than 0.1 mm could be dilated to greater than 0.2 mm. The dilator monofilament can also be used as an intravascular stent in the anastomosis. We have found that anastomosis of vessels with a diameter of less than 0.1 mm is possible using this method. In our experience, the immediate patency rate has been 100%. We believe mechanical dilation with a nylon monofilament is helpful for supermicrosurgery and even ultramicrosurgery.
Exploring the Protective Role and the Mechanism of Sphingosine 1 Phosphate in Endotoxic Cardiomyocytes
Authors: Kuai Feng , Wang Lei , Su Jianhua , Wang Yu , Han Yi , Zhou Suming 
Published: October 2018

ABSTRACT
FTY720 is a sphingosine 1 phosphate (S1P) receptor agonist approved for the treatment of multiple sclerosis, which is a chronic inflammatory autoimmune disorder. Sepsis is a complex syndrome associated with progressive endotoxemic developments, which finally leads to damage of multiple organs, including the heart. In critical patients, cardiovascular dysfunction due to sepsis is a major cause of death. Previous studies have shown an association between S1P and cardioprotection in the situation of ischemia reperfusion and myocardial infarction. Therefore, we will study the role of S1P towards endotoxic cardiomyocytes. Different doses of FTY720 were applied or not to endotoxic cardiomyocytes. The concentration of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 was measured by enzyme-linked immuno sorbent assay. Western blotting was used to analyze the downstream signaling pathways. We discovered that FTY720 reduced the levels of TNF-α and IL-6 through the NF-ΚB pathway, inhibited the expression of caspase-3, and activated both protein kinase B and extracellular signal-regulated kinase 1/2. Additionally, the activation of protein kinase B and extracellular signal-regulated kinase 1/2 could be inhibited by the S1P1 and S1P3 receptor antagonist vulcanized polyethylene23019. Therefore, we infer that S1P exerts a protective effect towards endotoxic cardiomyocytes by decreasing the levels of TNF-α and IL-6, regulating apoptotic and survival signaling pathway. The S1P1 and S1P3 receptors are involved in the prosurvival signal activation.
A Pediatric Nasogastroscope Facilitates Colorectal Endoscopic Stenting
Authors: Lamazza Antonietta , Fiori Enrico , Schillaci Alberto , Sterpetti Antonio V. 
Published: October 2018

Purpose:
Endoscopic placement of self-expandable metal stents (SEMSs) to relieve malignant colorectal obstruction has been widely accepted in clinical practice. Despite increasing experience, early and late complications occur with an incidence ranging from 4% to 20%.

Materials and Methods:
We have adopted a modification in the technique. A pediatric nasogastroscope (4.8 mm in diameter) has been used to pass the obstruction. It is possible to have a direct vision of the anatomy and pathology, and to pass the guidewire above the obstruction, through the nasogastroscope, under direct vision. Fluoroscopy was also used to follow the course of the guidewire and deployment of the stent.

Results:
Early and late complications have been reduced with the new technique.

Conclusions:
In the most recent experience of 64 patients, early and late complications have been reduced significantly. This new technique reduces radiation exposure by 70% for the patients and for the operators.
Compassion in palliative care: a review
Authors: Brito-Pons Gonzalo , Librada-Flores Silvia 
Published: October 2018

Purpose of review
Compassion has been recognized as a key aspect of high-quality healthcare, particularly in palliative care. This article provides a general review of the current understanding of compassion in palliative care and summarizes emergent compassionate initiatives in palliative care at three interdependent levels: compassion for patients, compassion in healthcare professionals, and compassionate communities at the end of life.

Recent findings
Compassion is a constructive response to suffering that enhances treatment outcomes, fosters the dignity of the recipient, and provides self-care for the giver. Patients and healthcare professionals value compassion and perceive a general lack of compassion in healthcare systems. Compassion for patients and for professionals’ self-care can be trained and implemented top-down (institutional policies) and bottom-up (compassion training). ‘Compassionate communities’ is an important emerging movement that complements regular healthcare and social services with a community-level approach to offer compassionate care for people at the end of life.

Summary
Compassion can be enhanced through diverse methodologies at the organizational, professional, and community levels. This enhancement of compassion has the potential to improve quality of palliative care treatments, enhance healthcare providers’ satisfaction, and reduce healthcare costs.
Targeting IL-1α in cancer cachexia: a narrative review
Authors: McDonald James J. , McMillan Donald C. , Laird Barry J.A. 
Published: October 2018

Purpose of review
Cachexia is defined as ongoing loss of skeletal muscle mass, with or without depletion of adipose tissue and is a common syndrome in cancer patients, affecting 50% of those diagnosed. Cachexia, which cannot be fully reversed and causes significant functional impairment is caused by various mechanisms such as an altered energy balance and disruption of homeostatic control by the central nervous system. This central nervous system deregulation involves hypothalamic pituitary adrenal (HPA) axis stimulation, which can be triggered by IL-1R1 engagement on neuronal processes and endothelium in the microvasculature of the hypothalamus. This review will explore current evidence regarding both the importance of IL-1α in the various components of cancer cachexia and its potential as a therapeutic target.

Recent findings
IL-1α, which signals through IL-1R1, has been identified as a key agonist in the IL-1 pathway. As such, IL-1α has been explored as a therapeutic target in cancer cachexia, leading to the development of bermekimab, a mAb which neutralizes IL-1α. With a limited array of medication currently available to treat cancer cachexia, bermekimab represents a possible therapy.

Summary
IL-1α is a key mediator in cachexia development and targeting this may be a viable therapeutic target.
Palliative care teaching shapes medical undergraduate students’ professional development: a scoping review
Authors: Noguera Antonio , Robledano Ramón , Garralda Eduardo 
Published: October 2018

Purpose of review
The aim of this review is to understand how palliative care teaching (PCT) as a patient-centered learning model, influences medical undergraduate students’ professional development.

Recent findings
To study PCT medical undergraduate students’ learning experiences, we have employed the medical teaching concept, ‘hidden curriculum,’ as a way of describing attitudes and behavior conveyed implicitly by palliative care educators. Fifteen studies were selected: ten of those studies used a qualitative approach; two are theoretical explanations of the topic explored, one guideline, one review and just one quantitative study, made up the review. Medical undergraduate students reported that after PCT, they felt they had acquired better attitudes for effective integration with the patient, such as empathy or holistic care; ethical principles, such as respect or humanization of their clinical practice; and commitment to an improvement in competences, such as self-awareness or self-esteem. They also reported improved behavior in effective integration with patients, such as communication, caring for patients’ families, and when addressing psychosocial, cultural and spiritual aspects; their commitment to improvement in competences, such as dealing with emotions and uncertainty; they learned team work as an effective way to interact within the health system; and to become more reliable, making themselves more available and dedicating enough time to each patient.

Summary
PCT seems to be an effective way of fostering medical undergraduate students’ patient-centered professional development.
Establishing a Core Outcome Measure for Life Participation: A Standardized Outcomes in Nephrology-kidney Transplantation Consensus Workshop Report
Authors: Ju Angela , Josephson Michelle A. , Butt Zeeshan , Jowsey-Gregoire Sheila , Tan Jane , Taylor Quinetta , Fowler Kevin , Dobbels Fabienne , Caskey Fergus , Jha Vivekanand , Locke Jayme , Knoll Greg , Ahn Curie , Hanson Camilla S. , Sautenet Benedicte , Manera Karine , Craig Jonathan C. , Howell Martin , Rutherford Claudia , Tong Allison 
Published: October 2018

Background.
Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis, but complications and side effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but is infrequently and inconsistently measured in trials. We convened a consensus workshop on establishing an outcome measure for life participation for use in all trials in kidney transplantation.

Methods.
Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from 8 countries participated in 6 facilitated breakout group discussions. Transcripts were analyzed thematically.

Results.
Four themes were identified. Returning to normality conveyed the patients’ goals to fulfill their roles (ie, in their family, work, and community) and reestablish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of “life” explicitly acknowledged life participation as a subjective concept that could refer to different activities (eg, employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations posttransplant (eg, due to complications and side-effects) distinguished between experiences in the first year posttransplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible, and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation.

Conclusions.
A feasible and validated core outcome measure for life participation is needed so that this critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision making and care of recipients.
Are molecular subgroups of medulloblastomas really prognostic?
Authors: Frappaz Didier , Faure-Conter Cécile , Meyronet David , Levard-Bonneville Alice , Beuriat Pierre-Aurélien , Sunyach Marie P. , Barritault Marc 
Published: October 2018

Purpose of review
Medulloblastoma is no more a unique disease. Clinical and biologic classification used so far are challenged by molecular classification(s). Following the consensus article that described four molecular groups of medulloblastoma in 2012, several articles in 2017 provided more relevant classifications that may impact on further clinical trial design.

Recent findings
Though wingless (WNT) and sonic hedgehog (SHH) are defined by the activation of their respective pathways, the age and type of activation define various subgroups with specific features and outcome. Groups 3 and 4 remain ill defined. The whole population of medulloblastoma may be divided in 12 subgroups: WNTαβ, SHHαβγδ, group 3αβγ and group 4αβγ. The paediatric population may be divided in seven subgroups: WNT, SHH of infants and children, and low-risk and high-risk groups 3 and 4. SHH of infants may be divided as iSHH-I vs. iSHH-II that have different prognosis. Moreover, specific drivers of groups 3 and 4 were reported.

Summary
These findings have and will have direct implications on the conception of clinical trials. Low-risk groups will benefit from less toxic therapies, and high-risk groups will benefit from targeted therapies.
Initiation of droxidopa during hospital admission for management of refractory neurogenic orthostatic hypotension in severely ill patients
Authors: McDonell Katherine E. , Preheim Brock A. , Diedrich Andre’ , Muldowney James A.S. , Peltier Amanda C. , Robertson David , Biaggioni Italo , Shibao Cyndya A. 
Published: October 2018

AbstractIntroductionOrthostatic hypotension (OH) is a common cause of hospitalization, particularly in the elderly. Hospitalized patients with OH are often severely ill, with complex medical comorbidities and high rates of disability. Droxidopa is a norepinephrine precursor approved for the treatment of neurogenic OH (nOH) associated with autonomic failure that is commonly used in the outpatient setting, but there is currently no data regarding the safety and efficacy of droxidopa initiation in medically complex patients.MethodsWe performed a retrospective review of patients started on droxidopa for refractory nOH while hospitalized at Vanderbilt University Medical Center between October 2014 and May 2017. Primary outcome measures were safety, change in physician global impression of illness severity from admission to discharge, and persistence on medication after 180-day follow-up.ResultsA total of 20 patients were identified through chart review. Patients were medically complex with high rates of cardiovascular comorbidities and a diverse array of underlying autonomic diagnoses. Rapid titration of droxidopa was safe and well-tolerated in this cohort, with no cardiovascular events or new onset arrhythmias. Supine hypertension requiring treatment occurred in four patients. One death occurred during hospital admission due to organ failure associated with end-stage amyloidosis. Treating physicians noted improvements in presyncopal symptoms in 80% of patients. After 6 months, 13 patients (65%) continued on droxidopa therapy.ConclusionIn a retrospective cohort of hospitalized, severely ill patients with refractory nOH, supervised rapid titration of droxidopa was safe and effective. Treatment persistence was high, suggesting that symptomatic benefit extended beyond acute intervention.
Revealing the nanoscale morphology of the primary cilium using super-resolution fluorescence microscopy
Authors: Yoon Joshua , Comerci Colin J. , Weiss Lucien E. , Milenkovic Ljiljana , Stearns Tim , Moerner W. E. 
Published: October 2018

ABSTRACTSuper-resolution (SR) microscopy has been used to observe structural details beyond the diffraction limit of ~250 nm in a variety of biological and materials systems. By combining this imaging technique with both computer-vision algorithms and topological methods, we reveal and quantify the nanoscale morphology of the primary cilium, a tiny tubular cellular structure (~2-6 μm long and 200-300 nm diameter). The cilium in mammalian cells protrudes out of the plasma membrane and is important in many signaling processes related to cellular differentiation and disease. After tagging individual ciliary transmembrane proteins, specifically Smoothened (SMO), with single fluorescent labels in fixed cells, we use three-dimensional (3D) single-molecule SR microscopy to determine their positions with a precision of 10-25 nm. We gain a dense, pointillistic reconstruction of the surfaces of many cilia, revealing large heterogeneity in membrane shape. A Poisson surface reconstruction (PSR) algorithm generates a fine surface mesh, allowing us to characterize the presence of deformations by quantifying the surface curvature. Upon impairment of intracellular cargo transport machinery by genetic knockout or small-molecule treatment of cells, our quantitative curvature analysis shows significant morphological differences not visible by conventional fluorescence microscopy techniques. Furthermore, using a complementary SR technique, 2-color, 2D STimulated Emission Depletion (STED) microscopy, we find that the cytoskeleton in the cilium, the axoneme, also exhibits abnormal morphology in the mutant cells, similar to our 3D results on the SMO-measured ciliary surface. Our work combines 3D SR microscopy and computational tools to quantitatively characterize morphological changes of the primary cilium under different treatments and uses STED to discover correlated changes in the underlying structure. This approach can be useful for studying other biological or nanoscale structures of interest.
Flavor compounds in fermented Chinese alcoholic beverage alter gut microbiota and attenuate ethanol-induced liver damages
Authors: Fang Cheng , Du Hai , Xiaojiao Zheng , Zhao Aihua , Jia Wei , Xu Yan 
Published: October 2018

AbstractAlcoholic beverages which are consumed widely in most parts of the world have long been identified as a major risk factor for all liver diseases, particularly alcohol-induced liver disease (ALD). Recent compositional analyses suggest that Chinese Baijiu (CB), a clear alcoholic liquid distilled from fermented grains, contains large amounts of small molecule bioactive compounds in addition to a significant amount of ethanol. Here, in an experimental mouse model, we show that CB caused lower degrees of liver injury than pure ethanol by protecting against the decrease of the relative abundance of Akkermansia and increased relative abundance of Prevotella in the gut thereby preventing the destruction of the intestinal barrier. Furthermore, we demonstrated that ethanol-induced alteration of the gut microbiota profoundly affected the host metabolome. Compared with ethanol feeding, CB feeding resulted in higher concentrations of functional saturated LCFAs and SCFAs. Our results provide supporting evidence that ALD was profoundly influenced by host-gut microbiota metabolic interactions and that small molecule organic compounds in CB could attenuate ALD.
The Hox Transcription Factor Ubx stabilizes Lineage Commitment by Suppressing Cellular Plasticity
Authors: Domsch Katrin , Carnesecchi Julie , Disela Vanessa , Friedrich Jana , Trost Nils , Ermakova Olga , Polychronidou Maria , Lohmann Ingrid 
Published: October 2018

ABSTRACTDuring development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei ofDrosophilaembryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.
The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant
Authors: Bogdanow Boris , Eichelbaum Katrin , Sadewasser Anne , Wang Xi , Husic Immanuel , Paki Katharina , Hergeselle Martha , Vetter Barbara , Hou Jingyi , Chen Wei , Wiebusch Lüder , Meyer Irmtraud M. , Wolff Thorsten , Selbach Matthias 
Published: October 2018

SUMMARYA century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human-and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3’ splice site and functionally important for permissive infection. Independentin silicoevidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.