bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curare: The Poisoned Arrow that Entered the Laboratory and Sparked a Moral Debate
Authors: Shmuely Shira 
Published: December 2018

Summary
Curare, a paralysing poison derived from South American plants, fascinated European explorers with its deadly powers. Generations of travellers were perplexed by how animals affected by curare showed no signs of suffering. British experimenters relabelled curare as an anaesthetic and used it to restrain animals during experiments. But during the 19th century, doubts started to appear: can a paralysed animal feel pain but be unable to express it? A scientific dispute emerged as not all British physiologists accepted Claude Bernard’s claim that curare affected only the motor nerves. The scientific controversy over curare reached the British parliament, and the Cruelty to Animals Act (1876) stated that curare would not be considered an anaesthetic. Nevertheless, antivivisection advocates continued to contest its use for decades. The article reveals new aspects of colonial import of bioactive plants in a case that reshaped the production of medical knowledge and presented epistemological and moral challenges.
Patient perspectives in gout: a review
Authors: Singh Jasvinder A. 
Published: December 2018

Purpose of review
Recent studies have produced evidence regarding the patient perspectives in gout including from disease experience to disease outcomes. Therefore, an overview on the topic can help improve our understanding of the patient experience.

Recent findings
This article explores several aspects of the patient perspective including the impact of gout on a patient's life, patient knowledge and beliefs regarding gout and its treatments, patient-perceived barriers to optimal medication adherence in gout and patient's perception of their gout. This article also summarizes any evidence of the association of patient perceptions to patient outcomes in gout.

Summary
A recognition of patient perspectives in gout has the potential to positively impact clinical care for gout. Discussion of disease impact, misperceptions about benefits/harms of urate-lowering therapy (ULT), and patient values/preferences regarding pharmacological and nonpharmacological treatments can lead to a better shared decision-making and improved outcomes in gout. These findings emphasize the importance of inclusion of patient perspective not only in clinical care and quality improvement and research initiatives but also in the design and implementation of the research agenda in gout. Inclusion of patient-reported outcomes in clinical research is likely to improve its relevance to patients with gout.
Concurrent Radiosurgery and Immune Checkpoint Inhibition
Authors: Murphy Blair , Walker Joshua , Bassale Solange , Monaco Debra , Jaboin Jerry , Ciporen Jeremy , Taylor Matthew , Dai Kubicky Charlotte 
Published: December 2018

Objectives:
The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control.

Methods:
We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined.

Results:
In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed.

Conclusions:
Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.
QUANTIFICATION OF RETINAL CAPILLARY NONPERFUSION IN DIABETICS USING WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Alibhai A. Yasin , De Pretto Lucas R. , Moult Eric M. , Or Chris , Arya Malvika , McGowan Mitchell , Carrasco-Zevallos Oscar , Lee ByungKun , Chen Siyu , Baumal Caroline R. , Witkin Andre J. , Reichel Elias , de Freitas Anderson Zanardi , Duker Jay S. , Fujimoto James G. , Waheed Nadia K. 
Published: December 2018

Purpose:
To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR).

Methods:
Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion.

Results:
The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0–0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2–3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0–14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR.

Conclusion:
Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.
MANAGEMENT OF GIANT RETINAL TEARS USING TRANSSCLERAL DIODE LASER RETINOPEXY AND SHORT-TERM POSTOPERATIVE TAMPONADE WITH PERFLUORO-N-OCTANE
Authors: Bhardwaj Gaurav , Connell Paul P. , Campbell William G. 
Published: December 2018

Purpose:
To determine the results of pars plana vitrectomy for giant retinal tear detachments using transscleral diode laser retinopexy and short-term postoperative tamponade with perfluoro-n-octane (PFnO).

Methods:
Twenty consecutive patients with fresh giant retinal tears were enrolled in a single-arm prospective study. One case was withdrawn for technical reasons. The remainder all underwent pars plana vitrectomy, PFnO injection, transscleral diode laser retinopexy to the edge of the giant retinal tear, and short-term postoperative heavy liquid tamponade. None of the cases had scleral buckling or lensectomy.

Results:
Nineteen cases (18 male and 1 female) with a mean age of 41 years (range 10–69 years) were followed up for a period of 6 months. Postoperative tamponade with PFnO was maintained for a mean of 7.6 days (range 4–21 days), after which it was exchanged for sulfur hexafluoride (SF6), perfluoropropane (C3F8) gas, or balanced salt solution. Final reattachment rate was 100%, with 3 (15.7%) patients requiring additional surgery. Best-corrected visual acuity at final follow-up was 20/40 or better in 11 eyes (58%), between 20/60 and 20/200 in 7 (37%), and 20/400 in 1 (5%).

Conclusion:
In this series of acute giant retinal tears, transscleral diode laser retinopexy together with the use of PFnO for short-term postoperative tamponade achieved excellent anatomical and visual results.
Deep Anterior Lamellar Keratoplasty in a Case of Hurler–Scheie Syndrome Undergoing Enzyme Replacement Therapy
Authors: Eah Kyu Sang , Lee Chang Mok , Kim Myoung Joon 
Published: December 2018

Purpose:
To report successful management of corneal clouding associated with Hurler–Scheie syndrome with deep anterior lamellar keratoplasty (DALK) undergoing concurrent enzyme replacement therapy (ERT).

Methods:
A 13-year-old boy with Hurler–Scheie syndrome (MPS I-HS) presented with corneal clouding in both eyes. He was on ERT with laronidase (Aldurazyme; Genzyme, Cambridge, MA) and had a visual acuity of 20/32 in both eyes. Seven years later, visual acuity in his left eye decreased to counting fingers and DALK was performed for vision recovery. Two years later, visual acuity in his right eye decreased to 20/100 and DALK was performed.

Results:
At his last visit, which was 3 years after right eye DALK and 5 years after left eye DALK, the grafts were clear and the corrected visual acuity in his right and left eyes was 20/30 and 20/25, respectively.

Conclusions:
The present case highlights the possible effectiveness of DALK in patients with mucopolysaccharidosis (MPS)-related corneal stromal opacification, treated with ERT.
Management of Functional Esophagogastric Junction Outflow Obstruction
Authors: Garbarino Stephanie , von Isenburg Megan , Fisher Deborah A. , Leiman David A. 
Published: December 2018

Goals:
Awareness of functional esophagogastric junction outflow obstruction (fEGJOO) has increased, but because there is no consensus on its management, we performed a systematic review of the literature to explore treatment strategies and outcomes.

Background:
EGJOO is a heterogenous disorder defined by high-resolution manometry parameters of elevated integrated relaxation pressure with preserved esophageal peristalsis. The etiology may be mechanical obstruction or idiopathic, the latter being fEGJOO.

Study:
The PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through June 2018 for all studies of adult patients describing a treatment strategy for fEGJOO or incomplete lower esophageal sphincter relaxation. The search strategy yielded 1792 studies and 8 (0.4%) met inclusion criteria.

Results:
All but one included studies were retrospective (n=184 patients). There were 5 interventions described, with botulinum toxin (Botox) injection (n=69) and expectant management (n=82) the most frequently reported, with success rates of 58% and 54%, respectively. There was substantial heterogeneity among patients and treatments were not directly compared, though reported symptom resolution was similar among all strategies with a mean follow-up time of 15 months.

Conclusions:
There are a variety of management strategies available for fEGJOO and some patients may not require any intervention. However, among 4 potential approaches aimed at disrupting lower esophageal sphincter hypertonicity, the largest existing evidence base supports either a therapeutic challenge of Botox injection or watchful waiting. Ultimately, these data indicate the need for further study with controlled trials to identify a definitive approach.
Second-line Treatments of Advanced Hepatocellular Carcinoma
Authors: Bakouny Ziad , Assi Tarek , El Rassy Elie , Nasr Fadi 
Published: December 2018

Background:
Advanced hepatocellular carcinoma (HCC) constitutes the second leading cause of cancer-related deaths. First-line therapy is either sorafenib or lenvatinib. Several treatment options have been recently added to the second-line treatment of advanced HCC. The aim of this network meta-analysis of randomized controlled trials was to compare the second-line treatments of advanced HCC.

Methods:
Network meta-analyses were computed for overall survival (OS), progression-free survival, rates of grade 3 to 5 adverse events, and for treatment discontinuation due to adverse events. OS was considered to be the primary outcome of this study, and everolimus was chosen to be the common comparator for efficacy analyses and placebo for safety analyses. Subgroup analyses were computed for OS in patients with hepatitis B, patients with hepatitis C, Asian patients, patients with macrovascular invasion, and patients with extrahepatic metastases.

Results:
Thirteen randomized controlled trials including 5076 patients and evaluating 11 agents were found to be eligible. Regorafenib [hazard ratio (HR)=0.60, 95% confidence interval (CI)=0.44-0.81] and cabozantinib (HR=0.72, 95% CI=0.55-0.95) were found to significantly prolong OS compared with everolimus. The effect of regorafenib on OS tended to be conserved across patient subgroups. Regorafenib was also found to significantly prolong progression-free survival (HR=0.46, 95% CI=0.35-0.62) and significantly increase the rates of grade 3 to 5 adverse events (odds ratios=3.18, 95% CI=2.22-4.54) and treatment discontinuation due to adverse events (odds ratios=2.67, 95% CI=1.21-5.87).

Conclusions:
This network meta-analysis concludes that, based on current evidence, regorafenib could be the agent of choice in the second-line treatment of HCC, with cabozantinib as a possible alternative for sorafenib-intolerant patients.
Scientific Registry of Transplant Recipients program-specific reports: where we have been and where we are going
Authors: Kasiske Bertram L. , Salkowski Nicholas , Wey Andrew , Israni Ajay K. , Snyder Jon J. 
Published: December 2018

Purpose of review
Reporting provider data on quality to patients and the general public is increasingly common in healthcare. Reporting outcomes in solid organ transplantation has always been controversial and deserves careful consideration to ensure optimal results.

Recent findings
As mandated by Federal law, the Scientific Registry of Transplant Recipients publishes program-specific reports on transplant candidates, recipients, donors, and transplant outcomes every 6 months. Recent changes designed to make the results more easily understood by patients and the general public have been well received by patients and controversial among providers. In particular, outcomes are now reported using a five-tier system that distinguishes program results better than the old three-tier system, in which almost all programs were reported “as expected.” Metrics that reflect access to transplant are also reported, including transplant rate and survival on the waiting list. Possible measures of longer term outcomes and program rates of accepting organs for transplant are being explored.

Summary
Providing detailed information regarding transplant program practices and outcomes in ways that patients and the general public can understand remains a major focus of the Scientific Registry of Transplant Recipients. Efforts to improve data collection and metrics reported are ongoing.
“I’m a Survivor”
Authors: Meiklejohn Judith A. , Bailie Ross , Adams Jon , Garvey Gail , Bernardes Christina M. , Williamson Daniel , Marcusson Beverly , Arley Brian , Martin Jennifer H. , Walpole Euan T. , Valery Patricia C. 
Published: December 2018

Background
Disparity in outcomes between Indigenous and non-Indigenous people after cancer diagnosis is multifactorial, including lower cancer screening participation, later diagnosis, reduced access and uptake of cancer treatment, higher rate of comorbidities, and barriers accessing the health system. Little is known about cancer survivorship experiences.

Objective
The aim of this study was to explore Indigenous Australian cancer survivor's perspectives of cancer survivorship.

Methods
Indigenous people who completed cancer treatment 6 months to 5 years before fieldwork were recruited from a tertiary hospital and remote primary health service for this qualitative study. Data collection was guided by yarning methods, a culturally appropriate method emphasizing storytelling. Data were interpreted using a social constructionist framework.

Results
Thirteen women and 6 men were interviewed. Participants' past experiences contributed to their specific identity as survivors. Participants described factors affecting a positive transition from cancer patient to cancer survivor and the importance of ongoing family support in helping to manage survivorship. Finally, participants described a range of community support they received and provided to others and how this improved their cancer survivorship.

Conclusion
Although a range of experiences are presented, this study provides evidence that the survivorship perspectives of Indigenous cancer survivors may be, in part, shared by non-Indigenous cancer survivors.

Implications for Practice
Acknowledging Indigenous cancer survivors' past experiences and how these influence their overall well-being is important for providing patient-centered and culturally appropriate care. Nurses and other healthcare professionals may use this knowledge to foster a range of coping strategies to assist Indigenous cancer survivors to live well.
The Role of Interpersonal Problems and Family Environment in the Association Between Impulsivity and Suicidal Ideation
Authors: Wang Chenxu , Mo Juanchan , Niu Xiaoxiao , Jia Xuji , Lin Lin 
Published: December 2018

Abstract
Impulsivity, interpersonal problems, and family environment are important factors in the development of suicidal ideation, but the pathway of these factors on suicidal ideation is not clear. This study constructed a moderated mediation model to examine whether interpersonal problems mediated the relationship between impulsivity and suicidal ideation and whether this mediating process was moderated by family environment. For this purpose, 902 college students from Tianjin Normal University located in the north of China were recruited to participate in this study with Barratt Impulsiveness Scale, Adolescent Self-Rating Life Events Check List, Family Environment Scale, and Beck Scale for Suicidal Ideation. Impulsivity could significantly predict suicidal ideation, and the relationship between impulsivity and suicidal ideation was significantly mediated by interpersonal problems; furthermore, the mediating effect and the directing effect were significantly moderated by family environment. These findings contribute to our understanding of a comprehensive interpretation of both environmental and individual factors' impacts on suicidal ideation.
The Risk of Suicide and Self-Harm in Adolescents Is Influenced by the “Type” of Mood Disorder
Authors: Parker Gordon , Ricciardi Tahlia 
Published: December 2018

Abstract
We sought to examine the extent to which suicidal ideation and self-harm are associated with a set of psychiatric conditions in senior high school students. A total of 1577 students completed an anonymous survey assessing lifetime rates of mood, anxiety, and eating disorders; the extent to which the presence of any depressive condition attracted bullying; help-seeking strategies; as well as rates of self-harm and suicidal ideation and plans over differing periods. Suicidal ideation and plans together with self-harm rates were distinctly higher in those with a melancholic depressive or a bipolar disorder (compared with those with nonmelancholic depression or an anxiety or eating disorder) and generally higher in females, whereas numbers of those with such conditions attending a mental health professional were low. Thus, for those with a mood disorder, the type of the condition appears to have a distinct impact on the likelihood of suicide and self-harm.
Simultaneous Versus Sequential Heart-liver Transplantation: Ideal Strategies for Organ Allocation
Authors: Rucker A. Justin , Anderson Kevin L. , Mulvihill Michael S. , Yerokun Babatunde A. , Barbas Andrew S. , Hartwig Matthew G. 
Published: December 2018

Background
Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL.

Methods
The Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research file was queried for adult recipients waitlisted for both heart and liver transplantation. The United Network for Organ Sharing thoracic and liver databases were linked to facilitate examination of waitlist and transplant characteristics for simultaneously listed patients. Univariate survival analysis was used to determine overall survival.

Results
Of the 236 patients meeting inclusion criteria, 200 underwent SHL, 7 sequentially underwent LAH, and 29 received heart transplantation only (isolated orthotopic heart transplantation [iOHT]). Recipients of SHL were less likely to have an episode of acute rejection before discharge (LAH, 14.2%; SHL, 2.4%; iOHT, 3.6%; P = .019) or be treated for acute rejection within 1 year after transplantation (LAH, 14.3%; SHL, 2.5%; iOHT, 13.8%; P = .007). Otherwise, postoperative hospital length of stay, stroke, need for dialysis, and need for pacemaker placement were comparable across groups. Ten-year survival similarly favored both LAH and SHL over iOHT (LAH: 100%, 71.4%, 53.6%; SHL: 87.1%, 80.4%, 52.1%, iOHT: 70.1%, 51.6%, 27.5% for 1-, 5-, and 10-year survivals, respectively, P = .003). However, median time between heart and liver transplant was 302 days in patients undergoing sequential transplantation.

Conclusions
Although transplantation in a simultaneous or sequential fashion yields equivalent outcomes, a high fraction of patients undergoing initial heart transplant alone fail to proceed to subsequent liver transplantation. Therefore, in patients with combined heart and liver failure with a projected need for 2 allografts, simultaneous transplantation is associated with maximum benefit.
Detailed analysis of paternal knockoutGrb10mice suggests effects on stability of social behavior, rather than social dominance
Authors: Rienecker Kira D. A. , Chavasse Alexander T. , Moorwood Kim , Ward Andrew , Isles Anthony R. 
Published: December 2018

ABSTRACTImprinted genes are highly expressed in monoaminergic regions of the midbrain and their functions in this area are thought to have an impact on mammalian social behaviors. One such imprinted gene isGrb10, of which the paternal allele is currently recognized as mediating social dominance behavior. However, there has been no detailed study of social dominance inGrb10+/pmice. Moreover, the original study examined tube-test behavior in isolated mice 10 months of age. Isolation testing favors more territorial and aggressive behaviors, and does not address social dominance strategies employed in group housing contexts. Furthermore, isolation stress impacts midbrain function and dominance related behavior, often through alterations in monoaminergic signaling. Thus, we undertook a systematic study ofGrb10+/psocial rank and dominance behavior within the cage group, using a number of convergent behavioral tests. We examined both male and female mice to account for sex differences, and tested cohorts aged 2, 6, and 10 months to examine any developments related to age. We found group-housedGrb10+/pmice do not show evidence of enhanced social dominance, but cages containingGrb10+/pand wildtype mice lacked the normal correlation between three different measures of social rank. Moreover, a separate study indicated isolation stress induced inconsistent changes in tube test behavior. Taken together, these data suggest future research onGrb10+/pmice should focus on on the stability of social behaviors, rather than dominanceper se.