bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding of anti-dsDNA antibodies to proximal tubular epithelial cells contributes to renal tubulointerstitial inflammation
Authors: Yung Susan , Ng Claudia Y.C. , Au Kin Yi , Cheung Kwok Fan , Zhang Qing , Zhang Chenzhu , Yap Desmond Y.H. , Chau Mel K.M. , Chan Tak Mao 
Published: October 2016

Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody (Ab) deposition on tubulointerstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA Abs on inflammatory processes in cultured proximal renal tubular epithelial cells (PTEC, HK-2 cells) and their association with serum levels of interleukin (IL)-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in patients. Binding of anti-dsDNA Abs to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry. IL-6, IL-8 and MCP-1 secretion, mitogen-activated protein kinase (MAPK) activation and the effect of mycophenolic acid (MPA) were investigated by ELISAs and Western blot analysis. NZBWF1/J mice with active nephritis were randomized to receive either mycophenolate mofetil (MMF) (100 mg/kg per day) or vehicle for up to 12 weeks to study renal histopathology focusing on tubulointerstitial changes. Our results demonstrated that anti-dsDNA Abs bound to HK-2 cell surface and induced IL-6, IL-8 and MCP-1 secretion through distinct MAPK pathways. MPA inhibited anti-dsDNA Ab binding to HK-2 cells and suppressed apical and basolateral IL-6 and IL-8, but not MCP-1, secretion. Anti-dsDNA Ab level correlated with serum and tubulointerstitial expression of IL-6, IL-8 and MCP-1. MMF treatment in NZBWF1/J mice reduced anti-dsDNA Ab production and MAPK activation in the renal tubulointerstitium, together with decreased IL-6 and MCP-1 expression. Our data demonstrate that anti-dsDNA Abs contribute to inflammatory processes in the tubulointerstitium in lupus nephritis through their binding to proximal renal tubular epithelial cells and induction of pro-inflammatory mediators, and MPA ameliorates anti-dsDNA Ab induced IL-6 and IL-8 secretion in these cells.
Fibrotic Tissue and Middle Turbinate Exhibit Similar Mechanical Properties. Is Fibrosis a Solution in Nasal Polyposis?
Authors: Gregório Luciano , Pezato Rogério , Felici Rafael , Kosugi Eduardo 
Published: October 2016

Introduction Nasal polyposis (NP) is a chronic inflammatory condition of the upper airway characterized by overgrowth of nasal mucosa. Recent studies have shown a mechanical dysfunction in the nasal polyp tissue.
Objective This study aims to evaluate the mechanical properties of nasal fibrotic tissue.
Method This study was an institutional review board approved translational study in 20 participants (8 patients with NP, 7 patients with nasal synechiae, and 5 subjects without sinus disease (control group). We used Controlled Disc Stimulation equipment to compare the curve Pressure/Volume created during the saline solution infusion.
Results The increase of pressure in response to solution injection was lower in the nasal polyp group when compared with control middle turbinate group and fibrotic group. No significant difference was found in the pressure response during solution injection between fibrotic group and control middle turbinate group.Inferior turbinate group showed significant difference when compared with control middle turbinate group.
Conclusion The mechanical dysfunction found in the nasal mucosa of patients with NP provides new insight into this condition. These data allow the belief that the fibrosis has a potential role in increasing interstitial hydrostatic pressure and, consequently, mitigating edema formation in NP.
F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase
Authors: Oliver Jason D. , Sibley Graham E. M. , Beckmann Nicola , Dobb Katharine S. , Slater Martin J. , McEntee Laura , du Pré Saskia , Livermore Joanne , Bromley Michael J. , Wiederhold Nathan P. , Hope William W. , Kennedy Anthony J. , Law Derek , Birch Mike 
Published: October 2016

Significance
New antifungal drugs that act via novel mechanisms are urgently needed to combat the high mortality of invasive fungal disease and the emergence of resistance to existing therapies. We describe the discovery, structure, activity, and mechanism of action of F901318, a new antifungal agent. A member of a novel class of antifungals, the orotomides, F901318 acts via inhibition of dihydroorotate dehydrogenase, an enzyme of de novo pyrimidine biosynthesis. F901318 is currently in clinical development for the treatment of invasive aspergillosis.
Uneven Reductions in High School Students’ Alcohol use from 2007 to 2012 by Age, Sex, and Socioeconomic Strata
Authors: Jackson Nicki , Denny Simon , Sheridan Janie , Fleming Terry , Clark Terryann , Peiris-John Roshini , Ameratunga Shanthi 
Published: October 2016

Background: Many Western countries have reported declines in adolescent alcohol use. This study examined changes in adolescent alcohol use in New Zealand between 2007 and 2012 and explored variations across sociodemographic strata. Methods: Data from 2 nationally representative, cross-sectional high school surveys conducted in 2007 ( n = 7709) and 2012 ( n = 7266) were examined. Changes in the prevalence of drinking in the past 4 weeks were examined among the total sample, as well as the frequency of drinking in the past 4 weeks and typical drinking-occasion quantity among drinkers. Only students residing in urban areas were included. Variation in changes was investigated across 4 demographic groups characterized by age (<16 years, ≥16 years) and sex. Interactions with household- and neighborhood-level socioeconomic position (SEP) identified any differential changes between socioeconomic strata. Results: From 2007 to 2012, significantly fewer students consumed alcohol in the past 4 weeks. Interaction analyses demonstrated that, among young females (<16 years), declines were significantly greater among those of high household SEP when compared with those of low household SEP. Among drinkers, reductions in the frequency of drinking were found among all demographic groups and SEP strata. Interaction analyses revealed that only young males (<16 years) showed significantly reduced typical drinking-occasion quantities. Among young females, significant interactions revealed a shift towards increasing typical drinking-occasion quantities among those of low household and neighborhood SEP, whereas their more advantaged counterparts showed no significant change over time. Conclusions: Fewer drinking occasions characterized the major declines in adolescent drinking between 2007 and 2012. Whereas young males showed reductions in the typical quantity consumed, young females of low household and neighborhood SEP progressed towards higher typical quantities. To address the uneven distribution of alcohol-related harm and improve the targeting of harm reduction initiatives, it remains imperative to examine changes in both the overall shift and shape of the distribution curve.
Scholarly Concentration Program Development: A Generalizable, Data-Driven Approach
Authors: Burk-Rafel Jesse , Mullan Patricia B. , Wagenschutz Heather , Pulst-Korenberg Alexandra , Skye Eric , Davis Matthew M. 
Published: October 2016

Purpose
Scholarly concentration programs—also known as scholarly projects, pathways, tracks, or pursuits—are increasingly common in U.S. medical schools. However, systematic, data-driven program development methods have not been described.

Method
The authors examined scholarly concentration programs at U.S. medical schools that U.S. News & World Report ranked as top 25 for research or primary care (n = 43 institutions), coding concentrations and mission statements. Subsequently, the authors conducted a targeted needs assessment via a student-led, institution-wide survey, eliciting learners’ preferences for 10 “Pathways” (i.e., concentrations) and 30 “Topics” (i.e., potential content) augmenting core curricula at their institution. Exploratory factor analysis (EFA) and a capacity optimization algorithm characterized best institutional options for learner-focused Pathway development.

Results
The authors identified scholarly concentration programs at 32 of 43 medical schools (74%), comprising 199 distinct concentrations (mean concentrations per program: 6.2, mode: 5, range: 1–16). Thematic analysis identified 10 content domains; most common were “Global/Public Health” (30 institutions; 94%) and “Clinical/Translational Research” (26 institutions; 81%). The institutional needs assessment (n = 468 medical students; response rate 60% overall, 97% among first-year students) demonstrated myriad student preferences for Pathways and Topics. EFA of Topic preferences identified eight factors, systematically related to Pathway preferences, informing content development. Capacity modeling indicated that offering six Pathways could guarantee 95% of first-year students (162/171) their first- or second-choice Pathway.

Conclusions
This study demonstrates a generalizable, data-driven approach to scholarly concentration program development that reflects student preferences and institutional strengths, while optimizing program diversity within capacity constraints.
The Causes of Errors in Clinical Reasoning: Cognitive Biases, Knowledge Deficits, and Dual Process Thinking
Authors: Norman Geoffrey R. , Monteiro Sandra D. , Sherbino Jonathan , Ilgen Jonathan S. , Schmidt Henk G. , Mamede Silvia 
Published: October 2016

Contemporary theories of clinical reasoning espouse a dual processing model, which consists of a rapid, intuitive component (Type 1) and a slower, logical and analytical component (Type 2). Although the general consensus is that this dual processing model is a valid representation of clinical reasoning, the causes of diagnostic errors remain unclear. Cognitive theories about human memory propose that such errors may arise from both Type 1 and Type 2 reasoning. Errors in Type 1 reasoning may be a consequence of the associative nature of memory, which can lead to cognitive biases. However, the literature indicates that, with increasing expertise (and knowledge), the likelihood of errors decreases. Errors in Type 2 reasoning may result from the limited capacity of working memory, which constrains computational processes. In this article, the authors review the medical literature to answer two substantial questions that arise from this work: (1) To what extent do diagnostic errors originate in Type 1 (intuitive) processes versus in Type 2 (analytical) processes? (2) To what extent are errors a consequence of cognitive biases versus a consequence of knowledge deficits?
The literature suggests that both Type 1 and Type 2 processes contribute to errors. Although it is possible to experimentally induce cognitive biases, particularly availability bias, the extent to which these biases actually contribute to diagnostic errors is not well established. Educational strategies directed at the recognition of biases are ineffective in reducing errors; conversely, strategies focused on the reorganization of knowledge to reduce errors have small but consistent benefits.
Intermittent Cervical Traction for Treating Neck Pain
Authors: Yang Jheng-Dao , Tam Ka-Wai , Huang Tsai-Wei , Huang Shih-Wei , Liou Tsan-Hon , Chen Hung-Chou 
Published: October 2016

Study Design.
A meta-analysis.

Objective.
The aim of this study was to perform a comprehensive search of current literature and conduct a meta-analysis of randomized controlled trials (RCTs) to assess the neck pain relieving effect of intermittent cervical traction (ICT).

Summary of Background Data.
Neck pain is a common and disabling problem with a high prevalence in general population. It causes a considerable burden on the health care system with a substantial expenditure. ICT is a common component of physical therapy for neck pain in the outpatient clinic. However, the evidence regarding the effectiveness of ICT for neck pain is insufficient.

Methods.
Data were obtained from the PubMed, Cochrane Library, Embase, and Scopus databases from the database inception date to July 02, 2016. RCTs reporting the effects of ICT on neck pain, including those comparing the effects of ICT with those of a placebo treatment, were included. Two reviewers independently reviewed the studies, conducted a risk of bias assessment, and extracted data. The data were pooled in a meta-analysis by using a random-effects model.

Results.
The meta-analysis included seven RCTs. The results indicated that patients who received ICT for neck pain had significantly lower pain scores than those receiving placebos did immediately after treatment (standardized mean difference = −0.26, 95% confidence interval = −0.46 to −0.07). The pain scores during the follow-up period and the neck disability index scores immediately after treatment and during the follow-up period did not differ significantly.

Conclusion.
ICT may have a short-term neck pain-relieving effect. Some risks of bias were noted in the included studies, reducing the evidence level of this meta-analysis. Additional high-quality RCTs are required to clarify the long-term effects of ICT on neck pain.

Level of Evidence: 1
The Power of Low Back Pain Trials
Authors: Froud Robert , Rajendran Dévan , Patel Shilpa , Bright Philip , Bjørkli Tom , Eldridge Sandra , Buchbinder Rachelle , Underwood Martin 
Published: October 2016

Study Design.
A systematic review of nonspecific low back pain trials published between 1980 and 2012.

Objective.
To explore what proportion of trials have been powered to detect different bands of effect size; whether there is evidence that sample size in low back pain trials has been increasing; what proportion of trial reports include a sample size calculation; and whether likelihood of reporting sample size calculations has increased.

Summary of Background Data.
Clinical trials should have a sample size sufficient to detect a minimally important difference for a given power and type I error rate. An underpowered trial is one within which probability of type II error is too high. Meta-analyses do not mitigate underpowered trials.

Methods.
Reviewers independently abstracted data on sample size at point of analysis, whether a sample size calculation was reported, and year of publication. Descriptive analyses were used to explore ability to detect effect sizes, and regression analyses to explore the relationship between sample size, or reporting sample size calculations, and time.

Results.
We included 383 trials. One-third were powered to detect a standardized mean difference of less than 0.5, and 5% were powered to detect less than 0.3. The average sample size was 153 people, which increased only slightly (∼4 people/yr) from 1980 to 2000, and declined slightly (∼4.5 people/yr) from 2005 to 2011 (P < 0.00005). Sample size calculations were reported in 41% of trials. The odds of reporting a sample size calculation (compared to not reporting one) increased until 2005 and then declined

JOURNAL/spne/04.03/00007632-201706010-00018/display-formula1/v/2024-02-04T231331Z/r/image-tiff

.

Conclusion.
Sample sizes in back pain trials and the reporting of sample size calculations may need to be increased. It may be justifiable to power a trial to detect only large effects in the case of novel interventions.

Level of Evidence: 3
Vermilion Only Cross-lip Flap for Treating Whistle Deformity in Secondary Bilateral Cleft Lip Repair
Authors: Sheckter Clifford C. , Menard Robert M. 
Published: October 2016

Summary:
Bilateral cleft lip repairs can result in various secondary deformities. One more commonly seen deformity, the whistle deformity, is characterized by a reduced or absent tubercle, orbicularis muscle diastasis, and abnormalities of the philtrum with notched appearance of cupid’s bow. Various techniques have been described to address these problems. One common procedure is the lip-switch flap originally described by Abbe in 1898, which has been modified by various surgeons. In these procedures, lower lip vermilion, mucosa, orbicularis, and lip skin are transposed to the upper lip on a pedicle that is later divided. In all these variations of the lip-switch procedure, the transposed tissue involves the entire lower lip skin—leaving large, unsightly, and unnecessary scars. It also brings abnormal tissue into the philtrum further distorting the upper lip. A modified cross-lip flap that is limited to the taking only mucosa, vermilion, and orbicularis is feasible and provides an optimal reconstruction without compromising additional tissue.
CALCIFICATION OF A HYDROPHILIC ACRYLIC INTRAOCULAR LENS AFTER PARS PLANA VITRECTOMY
Authors: Khurana Rahul N. , Werner Liliana 
Published: October 2016

Purpose:
Anterior surface calcification of a hydrophilic acrylic intraocular lens (IOL) associated with iatrogenic exposure of air after an uncomplicated pars plana vitrectomy is described.

Methods:
The clinical and histochemical findings of a patient who developed postoperative opacification of a hydrophilic acrylic intraocular lens are retrospectively reviewed.

Results:
A 63-year-old woman developed fine granular opacifications on the anterior surface of the intraocular lens 8 months after a pars plana vitrectomy with iatrogenic exposure of air. The intraocular lens was explanted and histochemical analysis confirmed the presence of calcium.

Conclusion:
Physicians should be aware of this complication and be cautious about the use of intraocular gas in either the front or the back of the eye in patients with hydrophilic acrylic intraocular lenses.
Recovery-Oriented Mental Health Practice in a Community Care Unit: An Exploratory Study
Authors: McKenna Brian , Oakes Jane , Fourniotis Niki , Toomey Nigel , Furness Trentham 
Published: October 2016

ABSTRACT
A recovery-oriented model of care has become the major focus of mental health service delivery in the state of Victoria, Australia. However, there is a total absence of knowledge of recovery-oriented mental health practice in community care units (CCUs). Therefore, the aims of this exploratory study were to: (a) describe what aspects of the current model of care fit within the domains of recovery; and (b) describe the pragmatic processes that staff use to mold their care within the domains of recovery. Twenty-one key stakeholders provided informed voluntary consent to participate in one-to-one interviews. Six content domains evolved to include: (a) a common vision: “a continuous journey”; (b) promoting hope; (c) promoting autonomy and self-determination; (d) meaningful engagement; (e) holistic and personalized care; and (f) community participation and citizenship. The CCU appeared to be on a journey of transformation toward personal recovery. However, clinicians were grappling with an identified tension among personal recovery and clinical recovery. The tension among personal recovery and clinical recovery may be attributed to the psychosocial rehabilitation model of care, which was previously systemic in Victorian CCUs.
Strangulation by Feeding Tube in a 23-Month-Old With Down Syndrome
Authors: Woodham Paige C. , Fulcher James W. , Ward Michael E. 
Published: October 2016

Abstract
Ligature strangulation, although typically homicidal in nature, has been reported as accidental in both the pediatric and adult populations. The unique mode of accidental strangulation with a gastric feeding tube in a 23-month-old with Down syndrome is currently unreported in the literature and has prompted us to report this case and look into safety modifications that can be made to these common medical devices. Given the number of children with gastric feeding tubes and concern over this exact scenario brought up by parents, it is unusual that a similar case has not been reported.
Determination of Phenotypic Resistance Cutoffs From Routine Clinical Data
Authors: Pironti Alejandro , Walter Hauke , Pfeifer Nico , Knops Elena , Lübke Nadine , Büch Joachim , Di Giambenedetto Simona , Kaiser Rolf , Lengauer Thomas ,   The EuResist Network Study Group
Published: October 2016

Background:HIV-1 drug resistance can be measured with phenotypic drug-resistance tests. However, the output of these tests, the resistance factor (RF), requires interpretation with respect to the in vivo activity of the tested variant. Specifically, the dynamic range of the RF for each drug has to be divided into a suitable number of clinically meaningful intervals.Methods:We calculated a susceptible-to-intermediate and an intermediate-to-resistant cutoff per drug for RFs predicted by geno2pheno[resistance]. Probability densities for therapeutic success and failure were estimated from 10,444 treatment episodes. The density estimation procedure corrects for the activity of the backbone drug compounds and for therapy failure without drug resistance. For estimating the probability of therapeutic success given an RF, we fit a sigmoid function. The cutoffs are given by the roots of the third derivative of the sigmoid function.Results:For performance assessment, we used geno2pheno[resistance]RF predictions and the cutoffs for predicting therapeutic success in 2 independent sets of therapy episodes. HIVdb was used for performance comparison. On one test set (n = 807), our cutoffs and HIVdb performed equally well receiver operating characteristic curve [(ROC)–area under the curve (AUC): 0.68]. On the other test set (n = 917), our cutoffs (ROC–AUC: 0.63) and HIVdb (ROC–AUC: 0.65) performed comparatively well.Conclusions:Our method can be used for calculating clinically relevant cutoffs for (predicted) RFs. The method corrects for the activity of the backbone drug compounds and for therapy failure without drug resistance. Our method's performance is comparable with that of HIVdb. RF cutoffs for the latest version of geno2pheno[resistance]have been estimated with this method.