bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Use of Trypan Blue During Canalicular Glaucoma Surgery to Identify Aqueous Outflow to Episcleral and Intrascleral Veins
Authors: Laroche Daniel , Nortey Andrea , Ng Chester 
Published: July 2018

Purpose:
We describe a novel technique comprising the use of trypan blue to confirm aqueous outflow to collector channels and aqueous veins after goniotomy with the Kahook Dual Blade (New World Medical, Rancho Cucamonga, CA). Intraocular dyes have been safely used during ophthalmic surgery to evaluate the patency of the trabecular meshwork and collector channels. Further, trypan blue has been safely used to stain the anterior capsule of the lens in cataract surgery, to enhance visualization for capsulorhexis; similarly, trypan blue has been safely used to stain the trabecular meshwork for enhanced visualization during glaucoma angle surgery. Channelography enables evaluation of the collector channels during canaloplasty with fluorescein dye; episcleral fluid wave enables evaluation of the intraoperative structural patency of the conventional outflow system, from the anterior chamber to the episcleral and conjunctival distal collectors after Trabectome goniotomy (NeoMedix Corporation, Tustin, CA).

Patients and Methods:
We evaluated 4 cases of glaucoma patients who underwent goniotomy with the Kahook Dual Blade to observe whether trypan blue could identify the patency of Schlemm’s canal and aqueous egress to episcleral and intrascleral veins.

Results:
We successfully confirmed the outflow pathway via Schlemm’s canal and collector channels with trypan blue in 3 of the 4 cases.

Conclusions:
We conclude that trypan blue can be used safely to confirm both aqueous outflow and the patency of Schlemm’s canal and aqueous veins during canalicular glaucoma surgery.
Molecular therapy for genetic and degenerative vestibular disorders
Authors: Sayyid Zahra N. , Kim Grace S. , Cheng Alan G. 
Published: July 2018

Purpose of review
The primary purpose of this review is to summarize current literature in the field of vestibular regeneration with a focus on recent developments in molecular and gene therapies.

Recent findings
Since the discovery of limited vestibular hair cell regeneration in mammals in the 1990s, many elegant studies have improved our knowledge of mechanisms of development and regeneration of the vestibular system. A better understanding of the developmental pathways of the vestibular organs has fueled various biological strategies to enhance regeneration, including novel techniques in deriving vestibular hair cells from embryonic and induced pluripotent stem cells. In addition, the identification of specific genetic mutations responsible for vestibular disorders has opened various opportunities for gene replacement therapy.

Summary
Vestibular dysfunction is a significant clinical problem with limited therapeutic options, warranting research on biological strategies to repair/regenerate the vestibular organs to restore function. The use of gene therapy appears promising in animal models of vestibular dysfunction.
Regulatory B cells and transplantation: almost prime time?
Authors: Mohib Kanishka , Cherukuri Aravind , Rothstein David M. 
Published: July 2018

Purpose of review
Regulatory B cells (Bregs) are potent inhibitors of the immune system with the capacity to suppress autoimmune and alloimmune responses. Murine transplant models showing that Bregs can promote allograft tolerance are now supported by clinical data showing that patients who develop operational tolerance have higher frequency of Bregs. Breg function has been widely studied resulting in improved understanding of their biology and effector mechanisms. However, our overall understanding of Bregs remains poor due the lack of specific marker, limited knowledge of how and where they act in vivo, and whether different Breg subpopulations exhibit different functions.

Recent findings
In this review we detail murine and human phenotypic markers used to identify Bregs, their induction, maintenance, and mechanisms of immune suppression. We highlight recent advances in the field including their use as biomarkers to predict allograft rejection, in-vitro expansion of Bregs, and the effects of commonly used immunosuppressive drugs on their induction and frequency.

Summary
Clinical data continue to emerge in support of Bregs playing an important role in preventing transplant rejection. Hence, it is necessary for the transplant field to better comprehend the mechanisms of Breg induction and approaches to preserve or even enhance their activity to improve long-term transplant outcomes.
Analysis of Prognostic Factors in Pancreatic Metastases
Authors: Ito Takashi , Takada Ryoji , Omoto Shunsuke , Tsuda Motoyuki , Masuda Daisuke , Kato Hironari , Matsumoto Toshihiko , Moriyama Ichiro , Okabe Yoshinobu , Shiomi Hideyuki , Ishida Etsuji , Hatamaru Keiichi , Hashimoto Shinichi , Tanaka Kiyohito , Kawamoto Hirofumi , Yanagisawa Akio , Katayama Toshiro , Yazumi Shujiro 
Published: July 2018

Objectives
Pancreatic metastases (PMs) account for 1% to 2% of pancreatic tumors, and their prognostic significance is poorly defined. We evaluated the incidence and clinical characteristics of primary tumors and defined prognostic factors.

Methods
This retrospective study of 39 Japanese tertiary referral hospitals (January 2005 to August 2015) analyzed patient and tumor characteristics and survival time. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival and prognostic factors, respectively.

Results
We enrolled 159 patients with a pathologic diagnosis of PM. The most common primary tumor was renal cell carcinoma (38.4%), followed by lung cancer (24.5%), colorectal cancer (11.3%), and sarcoma (6.3%). Eight patients were lost during follow-up, and 151 patients were included for statistical analysis. Median overall survival was 43.0 months, and the 5-year survival rate was 42.6%. Multivariate analysis identified 3 independent prognostic factors: extrapancreatic metastasis (hazard ratio, 2.13; 95% confidence interval, 1.11–4.07; P = 0.02), tumor-related symptoms at diagnosis (hazard ratio, 5.39; 95% confidence interval, 2.92–9.91; P < 0.001), and pathologic diagnosis of primary tumors (P < 0.001).

Conclusions
Treatment strategies and prognoses for PMs completely differ according to the primary tumor type. A definitive pathologic diagnosis of PMs is essential for selecting the appropriate treatment.
Early Predictors of Abdominal Hemorrhage Among Critically Ill Patients With Pancreatitis
Authors: Labarca Eduardo , Zubia Felix , Maraví-Poma Enrique , Martinez Felipe 
Published: July 2018

Objective
To establish incidence, risk factors, and prognostic implications of abdominal hemorrhage (AH) among critically ill patients with acute pancreatitis (AP).

Methods
Prospective cohort study in 46 intensive care units aimed at describing the characteristics of critically ill patients with AP (Epidemiología de la Pancreatitis Aguda en Medicina Intensiva Study). Adult patients with AP and at least 1 organ failure were included. The presence of AH was established either by using computed tomography, magnetic resonance imaging, or by direct visualization during surgery. Statistical analyses were carried out using multivariate logistic regression.

Results
Three hundred seventy-four patients were studied. Most were men (62.6%), with a mean (standard deviation) age of 60.4 (15.6) years. Most episodes (56.4%) of AP were severe, and 28.9% died during their hospital stay. Thirty-eight patients (10.2%; 95% confidence interval, 7.3%-13.7%) developed AH. The odds of presenting AH was influenced by age, the underlying cause of pancreatitis, and the presence of shock or respiratory failure on admission.

Conclusions
Abdominal hemorrhages were common among critically ill patients with pancreatitis. These early predictors may be of use in detecting patients at risk of developing them.
A Cognitive-Behavioral Intervention for the Symptom Clusters of Chinese Patients With Gastrointestinal Tract Cancer Undergoing Chemotherapy
Authors: Zhang Xinqiong , Wang Qin , Zhang Xiaomin , Wu Xiaoting , Wang Qiuping , Hong Jingfang 
Published: July 2018

Background
Patients with gastrointestinal tract (GIT) cancer undergoing chemotherapy often experience several symptoms that constitute symptom clusters and can cause patients to suffer. Effective interventions are lacking for this kind of patients.

Objective
The aims of this study were to test the feasibility and acceptability of a cognitive-behavioral (CB) intervention developed for Chinese patients with GIT cancer undergoing chemotherapy and to estimate the efficacy of the intervention for symptom clusters.

Methods
In this pilot, quasi-randomized controlled trial, 40 patients were assigned to the CB intervention or control group. The CB intervention, considering characteristics of patients and Chinese culture, contained 4 sections including cognitive reframing, cancer-diet education, relaxation, and exercise techniques. Symptom clusters, illness perception, anxiety, and depression were measured.

Results
Thirty-nine patients (97.5%) completed the study program and expressed willingness to follow the intervention. Compared with the control group, all outcomes were improved (all P < .05) in the CB group after the intervention, except for the gastrointestinal symptom cluster (t = 0.25, P = .802). In the CB group, the scores of all outcomes (all P < .05) decreased except for depression (t = 1.76, P = .095).

Conclusion
The CB intervention is partially feasible and acceptable. It may also help to improve part of the symptom clusters of Chinese patients with GIT cancer undergoing chemotherapy. However, some modifications are needed in future studies to better test effectiveness.

Implications for Practice
Symptom management remains a major problem in clinical nursing. Such a CB intervention can be beneficial to the clinical management of symptom clusters.
Efficacy of Pelvic Floor Muscle Training in Women With Overactive Bladder Syndrome: A Systematic Review
Authors: Monteiro Silvia , Riccetto Cassio , Araújo Angélica , Galo Laryssa , Brito Nathália , Botelho Simone 
Published: July 2018

(Abstracted from Int Urogynecol J 2018; doi: 10.1007/s00192-018-3602-x)
In the adult population, the prevalence of symptoms in an overactive bladder (OAB) is approximately 17%. In women, it can reach 50%.
Toddler With Intermittent Abnormal Behavior
Authors: Sharawat Indar Kumar , Dawman Lesa 
Published: July 2018

Abstract
Psychosis is a state of altered behavior and mentation, and it is rarely reported in preschool children. Isoniazid is a commonly used drug in the treatment and prophylaxis of tuberculosis. It may cause psychosis in overdose but rarely with usual recommended doses. We report a case of drug-induced psychosis secondary to isoniazid intake in a 3-year-old child. She developed intermittent abnormal behavior for 2 weeks after intake of isoniazid. Drug-induced psychosis was a possibility, and the responsible drug was stopped. She improved following the withdrawal of isoniazid.
Analgesic Efficacy of Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe Pain in Children
Authors: Quinn Kellie , Kriss Sabina , Drapkin Jefferson , Likourezos Antonios , Pushkar Illya , Brady Jason , Yasavolian Matthew , Chitnis Salil S. , Motov Sergey , Fromm Christian 
Published: July 2018

PurposeThis study aimed to compare analgesic efficacy of intranasal (IN) ketamine to IN fentanyl for moderate to severe pain in children in a pediatric emergency department.MethodsA prospective, randomized, double-blinded, noninferiority study evaluating children aged 3 to 17 years in a pediatric emergency department with acute moderate to severe pain was conducted. Patients received either 1 mg/kg of IN ketamine or 1.5 μg/kg of IN fentanyl and were evaluated after 10, 20, 30, and 60 minutes. The primary outcome was the degree of pain reduction after 20 minutes.ResultsTwenty-two patients were enrolled (11 in each group). Underlying pain conditions represented were musculoskeletal injury (73%) and abdominal pain (27%). At 20 minutes after analgesia, there was no significant difference in pain scores between the fentanyl (median, 2; range, 0–8) and ketamine groups (median, 4; range, 0–7;P= 0.20). The ketamine group showed a significantly greater rate of adverse effects, 73% versus 9% (P= 0.002), and throughout the course of the study period, 7 patients in the ketamine group (64%) group showed some degree of sedation versus no one in the fentanyl group (P= 0.004).ConclusionsThere was insufficient power to support the analgesic noninferiority of IN ketamine at a dose of 1 mg/kg compared with IN fentanyl at a dose of 1.5 μg/kg in children experiencing painful conditions at 20 minutes after administration. Intranasal ketamine was found to be inferior to IN fentanyl in relieving pain at 10 minutes and was found to have significantly greater rates of sedation and dizziness.
Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial
Authors: Jespersen Sanne , Hønge Bo Langhoff , Krarup Henrik , Medstrand Patrik , Sørensen Allan , Medina Candida , Té David da Silva , Correira Faustino Gomes , Erikstrup Christian , Østergaard Lars , Wejse Christian , Laursen Alex Lund ,   for the Bissau HIV Cohort study group
Published: July 2018

Background:
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1–infected patients in Guinea-Bissau.

Methods:
This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1–infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment.

Results:
Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52].

Conclusions:
In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.
Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
Authors: Córdoba-Moreno Marlina O. , Todero María Florencia , Fontanals Adriana , Pineda Gonzalo , Daniela Montagna , Yokobori Noemí , Ramos María Victoria , Barrientos Gabriela , Toblli Jorge E. , Isturiz Martín A. , Rearte Bárbara 
Published: July 2018

ABSTRACTSepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxicshock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.
Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1)
Authors: Hidaka Masaaki , Eguchi Susumu , Okuda Koji , Beppu Toru , Shirabe Ken , Kondo Kazuhiro , Takami Yuko , Ohta Masayuki , Shiraishi Masayuki , Ueno Shinichi , Nanashima Atsushi , Noritomi Tomoaki , Kitahara Kenji , Fujioka Hikaru 
Published: July 2018

Objective:
The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010.

Background:
Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported.

Methods:
A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified.

Results:
A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis.

Conclusions:
Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.
Management of chronic inflammatory demyelinating polyradiculopathy
Authors: Doneddu Pietro E. , Nobile-Orazio Eduardo 
Published: July 2018

Purpose of review
To review the recent advances in the management and treatment of chronic inflammatory demyelinating polyradiculopathy (CIDP).

Recent findings
Recent studies confirm the efficacy/safety of long-term intravenous immunoglobulin (IVIg) and short-term subcutaneous immunoglobulin (SCIg) therapy in CIDP. New outcome measures have been recently proposed and further studies evaluated the properties of those already in use. The presence of antibodies against proteins at the node of Ranvier was associated with specific clinical features and treatment response. Fingolimod adds to the list of immunosuppressive agents that failed to be effective in a controlled trial.

Summary
Several studies evaluating the best strategy to provide maintenance IVIg treatment in CIDP are in progress. SCIg were shown to be an alternative to IVIg for maintenance treatment while their efficacy as initial therapy should be further addressed. New outcome measures have been shown to be effective in detecting treatment response in clinical trials, but their use in clinical practice remains uncertain. Similarly unsettled is the role of nerve imaging techniques as biomarker in CIDP. The discovery of antibodies against proteins at the node of Ranvier has rekindled a keen interest in the pathogenesis of CIDP and the potential therapeutic role of new agents.
Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells
Authors: Brown Amanda M. , Arancillo Marife , Lin Tao , Catt Daniel R. , Zhou Joy , Lackey Elizabeth P. , Stay Trace L. , Zuo Zhongyuan , White Joshua J. , Sillitoe Roy V. 
Published: July 2018

One-sentence summaryCerebellar stellate cells and basket cells shape distinct Purkinje cell firing propertiesAbstractPurkinje cells receive synaptic input from several classes of interneurons. Here, we address the roles of inhibitory molecular layer interneurons in establishing Purkinje cell functionin vivo.Using conditional genetics approaches in mice, we compare how the lack of stellate cell versus basket cell GABAergic neurotransmission sculpts the firing properties of Purkinje cells. We take advantage of an inducibleAscl1CreERallele to spatially and temporally target the deletion of the vesicular GABA transporter,Vgat, in developing neurons. Selective depletion of basket cell GABAergic neurotransmission increases the frequency of Purkinje cell simple spike firing and decreases the frequency of complex spike firing in adult behaving mice. In contrast, lack of stellate cell communication increases the regularity of Purkinje cell simple spike firing while increasing the frequency of complex spike firing. Our data uncover complementary roles for molecular layer interneurons in shaping the rate and pattern of Purkinje cell activityin vivo.
Mendelian Randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
Authors: Porcu Eleonora , Rüeger Sina , Lepik Kaido ,   eQTLGen Consortium, Santoni Federico A. , Reymond Alexandre , Kutalik Zoltán 
Published: July 2018

AbstractGenome-wide association studies (GWAS) identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs (eQTLs), indicating their potential involvement in the regulation of gene expression.Here, we propose an advanced transcriptome-wide summary statistics-based Mendelian Randomization approach (called TWMR) that uses multiple SNPs jointly as instruments and multiple gene expression traits as exposures, simultaneously.When applied to 43 human phenotypes it uncovered 2,369 genes whose blood expression is putatively associated with at least one phenotype resulting in 3,913 gene-trait associations; of note, 36% of them had no genome-wide significant SNP nearby in previous GWAS analysis. Using independent association summary statistics (UKBiobank), we confirmed that the majority of these loci were missed by conventional GWAS due to power issues. Noteworthy among these novel links is educational attainment-associated BSCL2, known to carry mutations leading to a mendelian form of encephalopathy. We similarly unraveled novel pleiotropic causal effects suggestive of mechanistic connections, e.g. the shared genetic effects of GSDMB in rheumatoid arthritis, ulcerative colitis and Crohn’s disease.Our advanced Mendelian Randomization unlocks hidden value from published GWAS through higher power in detecting associations. It better accounts for pleiotropy and unravels new biological mechanisms underlying complex and clinical traits.