bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual Dysfunction in Male Canadian Armed Forces Members and Veterans Seeking Mental Health Treatment
Authors: Richardson J Don , Ketcheson Felicia , King Lisa , Forchuk Callista A , Hunt Renée , St. Cyr Kate , Nazarov Anthony , Shnaider Philippe , McIntyre-Smith Alexandra , Elhai Jon D 
Published: July 2019

Abstract

Introduction
There is mixed evidence regarding how posttraumatic stress disorder (PTSD) symptom clusters are associated with sexual dysfunction (SD), and most studies to date have failed to account for potentially confounding variables. Our study sought to explore the unique contribution of PTSD symptom clusters on (a) lack of sexual desire or pleasure, and (b) pain or problems during sexual intercourse, after adjusting for comorbidities and medication usage.

Materials and Methods
Participants included 543 male treatment-seeking veterans and Canadian Armed Forces (CAF) personnel (aged <65 years), referred for treatment between September 2006 and September 2014. Each participant completed self-report measures of demographic variables, depressive symptom severity, chronic pain, alcohol misuse, and psychotropic medication usage as part of a standard clinical intake protocol. Hierarchical ordinal logistic regression analyses were used to determine the incremental contribution of PTSD symptom clusters on sexual dysfunction.

Results
Nearly three-quarters (71.5%) of participants reported a lack of sexual desire or pleasure and 40.0% reported pain or problems during intercourse. Regression analyses suggested that avoidant/numbing symptoms were the only symptoms to be independently associated with lacking sexual desire or pleasure (AOR = 1.10; 95% CI 1.05–1.15). None of the PTSD symptom clusters were independently associated with pain or problems during intercourse.

Conclusions
Sexual dysfunction is prevalent among male treatment-seeking CAF personnel and veterans. Results suggest that PTSD symptoms are differentially associated with sexual desire or pleasure concerns. Assessing sexual function among CAF personnel and veterans seeking treatment for PTSD is critical in order to treat both conditions and improve overall functioning.
Delivering Cas9/sgRNA ribonucleoprotein (RNP) by lentiviral capsid-based bionanoparticles for efficient ‘hit-and-run’ genome editing
Authors: Lyu Pin , Javidi-Parsijani Parisa , Atala Anthony , Lu Baisong 
Published: July 2019

AbstractTransient expression of the CRISPR/Cas9 machinery will not only reduce risks of mutagenesis from off-target activities, but also decrease possible immune response to Cas9 protein. Building on our recent developing of a system able to package up to 100 copies of Cas9 mRNA in each lentivirus-like particle (LVLP) via the specific interaction between aptamer and aptamer-binding proteins (ABP), here we develop a lentiviral capsid-based bionanoparticle system, which allows efficient packaging of Cas9/sgRNA ribonucleoprotein (RNP). We show that replacing the Tetraloop of sgRNA scaffold with a com aptamer preserves the functions of the guide RNA, and the com-modified sgRNA can package Cas9/sgRNA RNP into lentivirus-like particles via the specific interactions between ABP and aptamer, and sgRNA and Cas9 protein. These RNP bionanoparticles generated Indels on different targets in different cells with efficiencies similar to or better than our recently described Cas9 mRNA LVLPs. The new system showed fast action and reduced off-target rates, and makes it more convenient and efficient in delivering Cas9 RNPs for transient Cas9 expression and efficient genome editing.
Clinical evaluation of fitness to drive in patients with brain metastases
Authors: Valencia-Sanchez Cristina , Gorelkin Vanessa C , Mrugala Maciej M , Sharma Akanksha , Vora Sujay A , Ashman Jonathan B , Daniels Thomas B , Halyard Michele Y , Rule William G , Zhang Nan , Butterfield Richard J , Schild Steven E , Porter Alyx B 
Published: July 2019

Abstract

Background
Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA).

Methods
We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered.

Results
The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests.

Conclusions
There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.
Concept for an X-ray telescope system with an angular resolution booster
Authors: Maeda Yoshitomo , Iizuka Ryo , Hayashi Takayuki , Sato Toshiki , Nakaniwa Nozomi , Takeo Mai , Suzuki Hitomi , Ishida Manabu , Ikeda Shiro , Morii Mikio 
Published: July 2019

ABSTRACT
We present a concept for an X-ray imaging system with a high angular resolution and moderate sensitivity. In this concept, a two-dimensional detector, i.e., an imager, is put at a slightly out-of-focus position of the focusing mirror, rather than just at the mirror focus, as in the standard optics, to capture miniature images of objects. In addition, a set of multi-grid masks (or a modulation collimator) is installed in front of the telescope. We find that the masks work as a coded aperture camera and that they boost the angular resolution of the focusing optics. The major advantage of this concept is that a much better angular resolution, having an order of 2–3 or more than in the conventional optics, is achievable, while a high throughput (large effective area) is maintained, which is crucial in photon-limited high-energy astronomy, because any type of mirrors, including lightweight reflective mirrors, can be employed in our concept. If the signal-to-noise ratio is sufficiently high, we estimate that angular resolutions at the diffraction limit of 4″ and 0.″4 at ∼7 keV can be achieved with a pair of masks at distances of 1 m and 100 m, respectively.
Optimality of Debt under Flexible Information Acquisition
Authors: Yang Ming 
Published: July 2019

Abstract
This article studies a security design problem featuring flexible information acquisition. To raise liquidity, a seller issues a security backed by her asset in place at the price she proposes to a buyer. Before deciding whether to accept the offer, the buyer can acquire costly information about the underlying asset. This case differs from the existing literature on security design, in that the buyer has the full flexibility of choosing not only the amount of resources to spend in information acquisition, but also how to allocate them, depending on the shape of the security. Debt is shown to be the unique optimal security for the seller, as its payoff is the least sensitive to the value of its underlying asset. This minimizes the buyer’s incentive to acquire information and mitigates the resulting adverse selection. I do not assume monotonicity of the feasible securities nor impose various distributional assumptions on information structures. Instead, I identify conditions for general information costs that support the results.
Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients
Authors: Kabala Pawel A , Malvar-Fernández Beatriz , Lopes Ana P , Carvalheiro Tiago , Hartgring Sarita A Y , Tang Man Wai , Conde Carmen , Baeten Dominique L , Sleeman Matthew , Tak Paul P , Connor Jane , Radstake Timothy R , Reedquist Kris A , García Samuel 
Published: July 2019

Abstract

Objective
To examine the role of Tie2 signalling in macrophage activation within the context of the inflammatory synovial microenvironment present in patients with RA and PsA.

Methods
Clinical responses and macrophage function were examined in wild-type and Tie2-overexpressing (Tie2-TG) mice in the K/BxN serum transfer model of arthritis. Macrophages derived from peripheral blood monocytes from healthy donors, RA and PsA patients, and RA and PsA synovial tissue explants were stimulated with TNF (10 ng/ml), angiopoietin (Ang)-1 or Ang-2 (200 ng/ml), or incubated with an anti-Ang2 neutralizing antibody. mRNA and protein expression of inflammatory mediators was analysed by quantitative PCR, ELISA and Luminex.

Results
Tie2-TG mice displayed more clinically severe arthritis than wild-type mice, accompanied by enhanced joint expression of IL6, IL12B, NOS2, CCL2 and CXCL10, and activation of bone marrow-derived macrophages in response to Ang-2 stimulation. Ang-1 and Ang-2 significantly enhanced TNF-induced expression of pro-inflammatory cytokines and chemokines in macrophages from healthy donors differentiated with RA and PsA SF and peripheral blood-derived macrophages from RA and PsA patients. Both Ang-1 and Ang-2 induced the production of IL-6, IL-12p40, IL-8 and CCL-3 in synovial tissue explants of RA and PsA patients, and Ang-2 neutralization suppressed the production of IL-6 and IL-8 in the synovial tissue of RA patients.

Conclusion
Tie2 signalling enhances TNF-dependent activation of macrophages within the context of ongoing synovial inflammation in RA and PsA, and neutralization of Tie2 ligands might be a promising therapeutic target in the treatment of these diseases.
Disclosure against foreign clients and lawyers: lessons for trust lawyers from Kiobel v Cravath Swaine & Moore
Authors: Peacocke Teresa Rosen 
Published: July 2019

Abstract
The author highlights two cases in which the courts considered the impact of protective orders, also known as confidentiality clubs, in determining applications for disclosure of the protected material to parties, or for purposes, outside the terms of the orders. In both cases the applications failed. In the New York case of Kiobel v Cravath, Swaine & Moore LLP (2016), the litigation in which the protective order was imposed had closed, but the order was upheld. In HTC Corporation v Nokia Corporation (2013) in London, a party sought disclosure from its opponent that would circumvent the effect of the protective order made when the disclosure was made by a third party. The author considers the usefulness of such orders, notwithstanding certain weaknesses, for domestic and international contentious trust cases.
Comparison of clinical manifestations and outcomes of noncirrhotic and cirrhotic hepatocellular carcinoma patients with chronic hepatitis B
Authors: Hwan Yu Jung , Shin Jongbeom , Jin Young-Joo , Lee Jin-Woo 
Published: July 2019

Aim
The differences of the clinical features and survival outcomes between cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection remain to be determined. We evaluated clinical characteristics and survival outcomes of noncirrhotic HBV-associated HCC patients compared with cirrhotic patients.

Patients and methods
Between January 2005 and December 2015, 1345 patients were diagnosed to have HCC at our hospital. Of these, 860 HBV-associated HCC patients with (cirrhotic group, n = 519, 60.3%) or without cirrhosis (noncirrhotic group, n = 341, 39.7%) were retrospectively analyzed. Propensity score matching (PSM) was used to adjust for differences between the two groups.

Results
The noncirrhotic group had lower Child–Turcotte–Pugh (CTP) classes and greater tumor sizes and were less likely to have portal vein thrombosis than the cirrhotic group. Age and sex were not significantly different between the two groups. Cumulative overall survival (OS) rates at 2, 4, 6, and 8 years after treatment were significantly higher in the noncirrhotic group (67.2, 57.1, 43.2, and 38.3 vs. 58.3, 41.3, 33.2, and 27.8%, respectively, P < 0.001). However, no significant intergroup difference in OS rates was observed after PSM (P = 0.680). Significant predictive factors of OS were CTP class, tumor size, tumor number, and curative-intended treatment for the noncirrhotic group, and serum alanine aminotransferase, CTP class, tumor size, tumor number, and curative-intended treatment for the cirrhotic group.

Conclusion
After PSM, cumulative OS rates were similar between HBV-related HCC patients with and without cirrhosis, and they were clearly dependent on CTP class, regardless of the presence of cirrhosis itself both in cirrhotic and noncirrhotic patients.
Alternate Week Gemcitabine and Capecitabine
Authors: Johns Claire , Diaz Celso L. , Hwang Jimmy , Kerridge William D. , Ko Andrew H. , Tempero Margaret A. 
Published: July 2019

Objective
Determine whether a regimen of fixed dose rate gemcitabine plus capecitabine is effective and tolerable for advanced pancreatic adenocarcinoma.

Methods
We performed a retrospective analysis of 62 patients with locally advanced or metastatic pancreatic adenocarcinoma treated at the University of California San Francisco between 2008 and 2016. Treatment was an alternate week schedule of fixed dose rate 1000 mg/m2 gemcitabine and capecitabine 1000 mg/m3 (58 patients), 1200 mg/m3 (12 patients), or 650 mg/m3 (1 patient) for intended 12 cycles. We evaluated overall survival (OS), progression-free survival (PFS), radiologic response, and adverse events necessitating treatment modification.

Results
For metastatic patients, median OS was 10.3 months (95% confidence interval [CI], 6.7–12.1 months), and PFS was 5.6 months (95% CI, 2.6–7.7 months). In locally advanced patients, OS was 12.0 months (95% CI, 4.9–17.1 months), and PFS was 5.4 months (95% CI, 2.5–9.4 months). Radiologic response for metastatic disease (42 patients) was 19% objective response, 45% stable disease, and 36% progressive disease. Treatment required modification for 22 patients due to adverse events, most frequently hand-foot syndrome (18 patients).

Conclusions
Alternate week schedule of fixed dose rate gemcitabine and capecitabine was active and tolerable for advanced pancreatic adenocarcinoma. Overall survival and PFS were comparable to first-line treatments. Importantly, adverse effects appear less severe than first-line treatments.
Severity and Mortality Predictors of Pediatric Acute Respiratory Distress Syndrome According to the Pediatric Acute Lung Injury Consensus Conference Definition
Authors: Prasertsan Pharsai , Anuntaseree Wanaporn , Ruangnapa Kanokpan , Saelim Kantara , Geater Alan 
Published: July 2019

Objectives:
The objective of this study was to assess the prevalence, severity, and outcomes of pediatric acute respiratory distress syndrome in a resource-limited country. In addition, we sought to explore the predisposing factors that predicted the initial severity, a change from mild to moderate-severe severity, and mortality.

Design:
Retrospective study.

Setting:
PICU in Songklanagarind Hospital, Songkhla, Thailand.

Patients:
Children 1 month to 15 years old with acute respiratory failure admitted to the PICU from January 2013 to December 2016.

Interventions:
None.

Measurements and Main Results:
From a total of 1,738 patients admitted to PICU, 129 patients (prevalence 7.4%) were diagnosed as pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition. The patients were categorized by severity. Fifty-seven patients (44.2%) were mild, 35 (27.1%) were moderate, and 37 (28.1%) were severe. After multivariable analysis was performed, factors significantly associated with moderate to severe disease at the initial diagnosis were Pediatric Risk of Mortality III score (odds ratio, 1.08; 95% CI, 1.03–1.15; p = 0.004), underlying oncologic/hematologic disorder (odds ratio, 0.32; 95% CI, 0.12–0.77; p = 0.012), and serum albumin level (odds ratio, 0.46; 95% CI, 0.27–0.80; p = 0.006), whereas underlying oncologic/hematologic disorder (odds ratio, 5.33; 95% CI, 1.33–21.4) and hemoglobin (odds ratio, 0.63; 95% CI, 0.44–0.89) predicted the progression of this syndrome within 7 days. The 30-day all-cause mortality rate was 51.2% (66/129). The predictors of mortality were the Pediatric Risk of Mortality III score (odds ratio, 1.12; 95% CI, 1.02–1.24; p = 0.017), underlying oncologic/hematologic disorder (odds ratio, 7.81; 95% CI, 2.18–27.94; p = 0.002), receiving systemic steroids (odds ratio, 4.04; 95% CI, 1.25–13.03; p = 0.019), having air leak syndrome (odds ratio, 5.45; 95% CI, 1.57–18.96; p = 0.008), and presenting with multiple organ dysfunction (odds ratio, 7.41; 95% CI, 2.00–27.36; p = 0.003).

Conclusions:
The prevalence and mortality rate of pediatric acute respiratory distress syndrome in a developing country are high. The oncologic/hematologic comorbidity had a significant impact on the severity of progression and mortality.
Matched Retrospective Cohort Study of Thiamine to Treat Persistent Hyperlactatemia in Pediatric Septic Shock*
Authors: Weiss Scott L. , Blowey Bridget , Keele Luke , Ganetzky Rebecca , Murali Chaya N. , Fitzgerald Julie C. , Sutton Robert M. , Berg Robert A. 
Published: July 2019

Objectives:
Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia.

Design:
Retrospective matched cohort study.

Setting:
Single academic PICU.

Patients:
Six thiamine-treated cases and nine matched controls.

Interventions:
None.

Measurements and Main Results:
The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1–64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0–22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (–9.0, –17.0 to -5.0 vs –7.2, –9.0 to –5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups.

Conclusions:
Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production.
Rates and Predictors of Using Opioids in the Emergency Department to Treat Migraine in Adolescents and Young Adults
Authors: Connelly Mark , Glynn Earl F. , Hoffman Mark A. , Bickel Jennifer 
Published: July 2019

Objectives
This study aimed to determine the rate and context in which opioids are used to treat migraine in adolescents and young adults seen in emergency care settings.

Methods
Data from 2010 to 2016 in the Cerner Health Facts electronic health record data warehouse were analyzed using multilevel logistic regression to estimate the population likelihood of an opioid being used in the emergency department (ED) to treat a primary diagnosis of migraine in adolescents and young adults and to evaluate the extent to which this likelihood varies as a function of characteristics of the patient (age, sex, race, and insurance), encounter (referral source, provider specialty, and encounter duration and year), and ED (region, setting, size, payer mix, and academic status).

Results
The study identified 14,494 eligible ED encounters with unique patients, of which 23% involved an opioid. Likelihood of being treated with opioids was significantly higher for patients who were older, female, white, and seen by a surgeon and who had longer encounters and encounters earlier in the time period sampled. Sites varied widely in percentage of encounters involving opioids (mean, 26.4% ± 20.1%; range, 0–100%), with higher rates associated with smaller sites with relatively higher proportions of commercially insured patients.

Conclusions
Use of opioids in the ED to treat migraine in youth is fairly common, with rate variation reflecting broader trends in for whom opioids tend to be more likely to be prescribed. These findings may be helpful for benchmarking and informing quality improvement efforts aimed at reducing unwarranted opioid exposure in youth.
Blood Oxygen Level–Dependent Response Changes in the Ipsilateral Primary Somatosensory Cortex and Thalamus of Patients With Moyamoya Disease During Median Nerve Electrical Stimulation
Authors: Qiao Peng-Gang , Cheng Xu , Zuo Zhi-Wei , Han Cong , Yang Zheng-Han , Li Gong-Jie 
Published: July 2019

Objective
The objective of this study was to investigate the changes in the blood oxygen level–dependent (BOLD) response in the ipsilateral primary somatosensory cortex (SI) and thalamus of patients with moyamoya disease (MMD) during sensory stimulation.

Methods
Sixty-four MMD patients, and 15 healthy volunteers were enrolled. Thirty-three MMD patients exhibited paroxysmal numbness or hypoesthesia in the unilateral limbs. Fifteen patients with acroparesthesia underwent unilateral encephaloduroarteriosynangiosis (EDAS). All volunteers underwent BOLD functional magnetic resonance imaging (BOLD-fMRI) under median nerve electrical stimulation (MNES). Blood oxygen level–dependent fMRI data were processed to obtain time-signal intensity curves in the activation areas of the bilateral SI and thalamus. Processed dynamic susceptibility contrast-enhanced magnetic resonance imaging data were used to measure the time to peak of the BOLD response in the regions of interest, including the bilateral SI, thalamus, and cerebellum. Changes in the time-signal intensity curve–related hemodynamic parameters in the ipsilateral SI and thalamus were examined between healthy controls, nonacroparesthesia patients, and asymptomatic and symptomatic sides of unilateral acroparesthesia patients during MNES. Changes in these parameters in MMD patients before and after EDAS were examined.

Results
Compared with healthy volunteers, 3 groups of MMD patients exhibited an increased peak of the positive BOLD response in the ipsilateral thalamus during MNES (0.65 ± 0.24 vs 0.79 ± 0.35, 0.94 ± 0.57, and 0.89 ± 0.50; P = 0.0335). The positive response peak in the ipsilateral SI markedly increased in MMD patients with acroparesthesia during MNES on the asymptomatic side (0.56 ± 0.37 vs 0.38 ± 0.27, P = 0.0243). The time to peak negative response in the ipsilateral SI was prolonged during MNES on the symptomatic side after EDAS (12.14 ± 8.90 seconds vs 18.86 ± 9.20 seconds, P = 0.0201).

Conclusions
During sensory stimulation treatment, BOLD response changes occurred in the ipsilateral SI and thalamus of MMD patients. These changes enabled the contralateral hemisphere of the brain to better deal with sensory stimuli.