bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic
Authors: Leon Kristoffer E. , Jacob Jesse T. , Franco-Paredes Carlos , Kozarsky Phyllis E. , Wu Henry M. , Fairley Jessica K. 
Published: April 2016

AbstractBackground.  Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage.Methods.  A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy.Results.  Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease “reactions”, severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1–96), but no single factor was associated with a delay in diagnosis.Conclusions.  The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage.
Why July Matters
Authors: Petrilli Christopher M. , Del Valle John , Chopra Vineet 
Published: April 2016

Each July, new graduates from premedical, medical, and residency programs, along with junior and midcareer faculty, acclimatize to their changing roles. During this month, overall efficiency, quality, and patient safety may suffer, a problem dubbed the “July effect.” The many transitions that occur in teaching hospitals during July are often implicated as the root cause of this problem. The question, then, of how best to improve the team-based clinical care provided in July remains important. In this Commentary, the authors outline a model that combines the team-based care paradigm with effective leadership, followership, and communication-based strategies and propose some actionable steps.
A key first step to enhancing patient safety in July is improving effective leadership through use of a select group of attendings whose teaching style empowers learners within a framework of close supervision. Second, programmatic efforts to pair these leaders with good followers are needed. Senior residents in July should be selected on their ability to mentor, guide, and support interns. Third, a system of free-flowing, bidirectional communication must be nurtured to ensure optimal outcomes. Adapting strategies from the airlines (e.g., interdisciplinary conferences to discuss optimal patient care approaches; checklists for daily activities such as sign-outs; directed feedback and debriefing techniques emphasizing actionable areas for improvement) is promising and worth studying.
Available data suggest that the “July effect” is real. Developing new and exploring existing approaches for allaying this phenomenon are important areas of further investigation.
A Hybrid Interview Model for Medical School Interviews: Combining Traditional and Multisampling Formats
Authors: Bibler Zaidi Nikki L. , Santen Sally A. , Purkiss Joel A. , Teener Carol A. , Gay Steven E. 
Published: April 2016

Problem
Most medical schools have either retained a traditional admissions interview or fully adopted an innovative, multisampling format (e.g., the multiple mini-interview) despite there being advantages and disadvantages associated with each format.

Approach
The University of Michigan Medical School (UMMS) sought to maximize the strengths associated with both interview formats after recognizing that combining the two approaches had the potential to capture additional, unique information about an applicant. In September 2014, the UMMS implemented a hybrid interview model with six, 6-minute short-form interviews—highly structured scenario-based encounters—and two, 30-minute semistructured long-form interviews. Five core skills were assessed across both interview formats.

Outcomes
Overall, applicants and admissions committee members reported favorable reactions to the hybrid model, supporting continued use of the model. The generalizability coefficients for the six-station short-form and the two-interview long-form formats were estimated to be 0.470 and 0.176, respectively. Different skills were more reliably assessed by different interview formats. Scores from each format seemed to be operating independently as evidenced through moderate to low correlations (r = 0.100–0.403) for the same skills measured across different interview formats; however, after correcting for attenuation, these correlations were much higher.

Next Steps
This hybrid model will be revised and optimized to capture the skills most reliably assessed by each format. Future analysis will examine validity by determining whether short-form and long-form interview scores accurately measure the skills intended to be assessed. Additionally, data collected from both formats will be used to establish baselines for entering students’ competencies.
Variability Over Time of Preoperative Sagittal Alignment Parameters
Authors: Menga Emmanuel N. , Spiegel Matthew A. , Vira Shaleen , Lafage Renaud , Henry Jensen K. , Liabaud Barthelemy , Oren Jonathan H. , Worley Nancy , Schwab Frank J. , Errico Thomas J. , Lafage Virginie , Protopsaltis Themistocles S. 
Published: April 2016

Study Design.
Retrospective review.

Objective.
To evaluate preoperative variability in radiographic sagittal parameters in adult spinal deformity (ASD).

Summary of Background Data.
In ASD surgical planning, deformity magnitude is determined from preoperative radiographs. There are no studies evaluating the clinical relevance and timing to repeat radiographs during interval clinic visits and timing to repeat radiograph for preoperative planning.

Methods.
A total of 139 patients with ASD with minimum two preoperative full-body spine x-rays were included. Cervical, thoracic, lumbar, pelvic, and hip/knee sagittal alignment parameters were analyzed using dedicated spine measurement software. Patients were grouped by time intervals between x-rays: A: 8 weeks or lesser, B: 10 to 20 weeks, and C: 21 weeks or more. Changes in sagittal parameters were correlated to age and deformity magnitude (T1 pelvic angle or pelvic tilt [PT] >20°).

Results.
The cohort had mean age 59 years, mean body mass index 27, 30% men, 95 patients with no prior spine surgery, and 44 patients at minimum 9 months since prior spine surgery. There were 25 patients in group A, 38 in B, and 71 in C. All radiographic measures showed good time-based consistency at intervals less than 21 weeks (groups A and B). Group C had significant increases in PT (1.5°) and hip extension (2.1°) (P < 0.05). These changes were greater in group C patients with previous surgery (PT 3.7°; P < 0.006, hip extension 3.2°; P < 0.025). Greater interval changes in parameters were also associated with higher magnitudes of deformity and younger patient ages.

Conclusion.
All sagittal radiographic parameters were statistically consistent at intervals of less than 21 weeks. In patients with more than 21 weeks between interval x-rays, change in PT was greater than the standard error of measurement for patients with prior surgery or severe deformity. Consideration should be made to obtain new x-rays for patients with ASD when the interval between clinical visits exceeds 5 months.

Level of Evidence: 4
Health-Related Quality of Life Improves Similarly in Patients With and Without Type 2 Diabetes After Cardiac Rehabilitation
Authors: Wald Caroline M. , Crecelius Anne R. 
Published: April 2016

PURPOSE:
Cardiovascular disease is the leading cause of death in the United States and results in substantial healthcare expenditures. Health-related quality of life (HRQoL) is an important aspect in long-term recovery for patients with cardiovascular disease. As such, improvement in HRQoL is a relevant outcome for determining cardiovascular rehabilitation (CR) program efficacy. Increasingly, diabetic patients are participating in CR and face additional challenges to HRQoL, yet there is a lack of research addressing program efficacy in this population. This study tested the hypothesis that CR would effect a favorable change in HRQoL for both diabetic (D; n = 37) and nondiabetic (N-D; n = 58) patients. Furthermore, we tested the hypothesis that the D group would demonstrate a greater overall change compared with the N-D group.

METHODS:
In this retrospective study, we reviewed the charts of 95 patients who completed a CR program and collected HRQoL measures using the COOP questionnaire, where lower scores indicate higher HRQoL.

RESULTS:
After CR, COOP scores for both the N-D improved (pre: 20.39 ± 0.79 vs post: 16.06 ± 0.75; P < .05) and D (pre: 20.92 ± 0.88 vs post: 15.84 ± 0.80; P < .05). HRQoL was not different between groups at the start of the program (P = .88) or at the end (P = .58), and thus, the improvement in HRQoL was not different between groups (P = .44).

CONCLUSIONS:
These results suggest that D and N-D patients do not differ in their HRQoL at the start or end of CR, and that the 2 groups show similar improvements from attending the program. Larger sample studies are needed to confirm these findings.
The Association Between Obesity and Hostility: The Mediating Role of Plasma Lipids
Authors: DIMITRIADIS DIMITRIOS G. , MAMPLEKOU EFTERPI , DIMITRIADIS PANAYIOTIS G. , KOMESSIDOU VASSO , PAPAKONSTANTINOU ALEXANDROS , DIMITRIADIS GEORGE D. , PAPAGEORGIOU CHARALAMBOS 
Published: April 2016

Objective:
Recent research indicates an association between obesity and psychopathology status, the nature of which remains unclear. We evaluated the mediating role of biochemical disturbances in this association among a treatment-seeking sample of obese individuals.

Method:
The study enrolled 143 consecutive overweight and obese individuals (mean age 35±9 y) and 143 normal-weight controls (mean age 34±9 y), matched by age and sex. We measured psychopathology features using the Symptom Checklist 90-Revised (SCL-90-R), a standardized self-evaluation rating scale, and biochemical parameters (plasma cholesterol, triglyceride, and fasting glucose levels) of all participants. Nonlinear regression models were used to estimate the associations among obesity, psychopathology, and biochemical factors.

Results:
Obesity was associated positively and significantly (P<0.05) with all of the SCL-90-R subscales, with the exception of anxiety and phobic anxiety, as well as with levels of plasma glucose, cholesterol (P<0.01), and triglycerides (P<0.001). Tests for mediation showed that obesity was significantly associated, for the mediators of plasma cholesterol [parameter estimate=−0.033, P<0.05] and triglycerides (parameter estimate=−0.059, P<0.05), only with hostility (parameter estimate=−0.024, P<0.05 and parameter estimate=−0.041, P<0.05, respectively).

Conclusions:
Our data suggest that biological substrates that are critically related to obesity, such as dyslipidemia, may mediate, at least in part, the association between obesity and hostility.
Molecular Ultrasound Imaging of αvβ3-Integrin Expression in Carotid Arteries of Pigs After Vessel Injury
Authors: Rix Anne , Fokong Stanley , Heringer Sarah , Pjontek Rastislav , Kabelitz Lisa , Theek Benjamin , Brockmann Marc-Alexander , Wiesmann Martin , Kiessling Fabian 
Published: April 2016

Objectives
Interventions such as balloon angioplasty can cause vascular injury leading to platelet activation, thrombus formation, and inflammatory response. This induces vascular smooth muscle cell activation and subsequent re-endothelialization with expression of αvβ3-integrin by endothelial cells and vascular smooth muscle cell. Thus, poly-N-butylcyanoacrylate microbubbles (MBs) targeted to αvβ3-integrin were evaluated for monitoring vascular healing after vessel injury in pigs using molecular ultrasound imaging.

Materials and Methods
Approval for animal experiments was obtained. The binding specificity of αvβ3-integrin–targeted MB to human umbilical vein endothelial cells was tested with fluorescence microscopy. In vivo imaging was performed using a clinical ultrasound system and an 8-MHz probe. Six mini pigs were examined after vessel injury in the left carotid artery. The right carotid served as control. Uncoated MB, cDRG-coated MB, and αvβ3-integrin–specific cRGD-coated MB were injected sequentially. Bound MBs were assessed 8 minutes after injection using ultrasound replenishment analysis. Measurements were performed 2 hours, 1 and 5 weeks, and 3 and 6 months after injury. In vivo data were validated by immunohistochemistry.

Results
Significantly stronger binding of cRGD-MB than MB and cDRG-MB to human umbilical vein endothelial cells was found (P < 0.01). As vessel injury leads to upregulation of αvβ3-integrin, cRGD-MBs bound significantly stronger (P < 0.05) in injured carotid arteries than at the counter side 1 week after vessel injury and significant differences could also be observed after 5 weeks. After 3 months, αvβ3-integrin expression decreased to baseline and binding of cRGD-MB was comparable in both vessels. Values remained at baseline also after 6 months.

Conclusions
Ultrasound imaging with RGD-MB is promising for monitoring vascular healing after vessel injury. This may open new perspectives to assess vascular damage after radiological interventions.
Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection—Results of a Cross-Sectional Screening Study
Authors: Eskandary Farsad , Bond Gregor , Kozakowski Nicolas , Regele Heinz , Marinova Lena , Wahrmann Markus , Kikić Željko , Haslacher Helmuth , Rasoul-Rockenschaub Susanne , Kaltenecker Christopher C. , König Franz , Hidalgo Luis G. , Oberbauer Rainer , Halloran Philip F. , Böhmig Georg A. 
Published: April 2016

Background
Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR.

Methods
Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation. IgG MFI was analyzed after elimination of prozone effect, and complement-fixation was determined using C1q, C4d, or C3d assays.

Results
Among DSA+ study patients, 44 recipients (51%) had AMR, 24 of them showing C4d-positive rejection. Although DSA number or HLA class specificity were not different, patients with AMR or C4d + AMR showed significantly higher IgG, C1q, and C3d DSA MFI than nonrejecting or C4d-negative patients, respectively. Overall, the predictive value of DSA characteristics was moderate, whereby the highest accuracy was computed for peak IgG MFI (AMR, 0.73; C4d + AMR, 0.71). Combined analysis of antibody characteristics in multivariate models did not improve AMR prediction.

Conclusions
We estimate a 50% prevalence of silent AMR in DSA+ long-term recipients and conclude that assessment of IgG MFI may add predictive accuracy, without an independent diagnostic advantage of detecting complement-fixation.
Posttransplant Lymphoproliferative Disorders in Irish Renal Transplant Recipients: Insights From a National Observational Study
Authors: O'Regan John A. , Prendeville Susan , McCaughan Jennifer Anne , Traynor Carol , O'Brien Frank J. , Ward Francis L. , O'Donovan Denis , Kennedy Claire , Berzan Ecaterina , Kinsella Sinead , Williams Yvonne , O'Kelly Patrick , Deady Sandy , Comber Harry , Leader Mary , Conlon Peter J. 
Published: April 2016

Background
Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients.

Methods
Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population.

Results
We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified.

Conclusions
We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.
Pan-cancer analysis of the metabolic reaction network
Authors: Gatto F. , Nielsen J. 
Published: April 2016

ABSTRACTMetabolic reprogramming is considered a hallmark of malignant transformation. However, it is not clear whether the network of metabolic reactions expressed by cancers of different origin differ from each other nor from normal human tissues. In this study, we reconstructed functional and connected genome-scale metabolic models for 917 primary tumors based on the probability of expression for 3,765 reference metabolic genes in the sample. This network-centric approach revealed that tumor metabolic networks are largely similar in terms of accounted reactions, despite diversity in the expression of the associated genes. On average, each network contained 4,721 reactions, of which 74% were core reactions (present in >95% of all models). Whilst 99.3% of the core reactions were classified as housekeeping also in normal tissues, we identified reactions catalyzed byARG2, RHAG, SLC6andSLC16family gene members, andPTGS1andPTGS2as core exclusively in cancer. The remaining 26% of the reactions were contextual reactions. Their inclusion was dependent in one case (GLS2) on the absence ofTP53mutations and in 94.6% of cases on differences in cancer types. This dependency largely resembled differences in expression patterns in the corresponding normal tissues, with some exceptions like the presence of theNANP-encoded reaction in tumors not from the female reproductive system or of theSLC5A9-encoded reaction in kidney-pancreatic-colorectal tumors. In conclusion, tumors expressed a metabolic network virtually overlapping the matched normal tissues, raising the possibility that metabolic reprogramming simply reflects cancer cell plasticity to adapt to varying conditions thanks to redundancy and complexity of the underlying metabolic networks. At the same time, the here uncovered exceptions represent a resource to identify selective liabilities of tumor metabolism.
Convergent evolution of sperm gigantism and the developmental origins of sperm size variability inCaenorhabditisnematodes
Authors: Vielle Anne , Callemeyn-Torre Nicolas , Gimond Clotilde , Poullet Nausicaa , Gray Jeremy C. , Cutter Asher D. , Braendle Christian 
Published: April 2016

AbstractSperm cells provide crucial, if usually diminutive, ingredients to successful sexual reproduction as the source of centrioles and half the diploid genome. Despite this essential conserved function, sperm competition and coevolution with female traits can drive spectacular change in size and shape of these motile cells. Here we characterize four repeated instances of convergent evolution of sperm gigantism inCaenorhabditisnematodes using phylogenetic comparative methods on 26 species. Species at the extreme end of the 50-fold range of sperm-cell volumes across the genus have sperm capable of comprising up to 5% of egg-cell volume, representing severe attenuation of the magnitude of anisogamy. Exploring potential genetic and developmental determinants ofCaenorhabditissperm size variation, we uncover significant differences in mean and variance of sperm size among genotypes, between sexes of androdioecious species, as well as within and between individuals of identical genotypes. We demonstrate that the developmental basis of sperm size variation, both within and between species, becomes established during an early stage of sperm development, i.e. at the formation of primary spermatocytes while subsequent meiotic divisions contribute little further sperm size variability. These findings provide first insights into the developmental determinants of inter-and intraspecific sperm size differences inCaenorhabditis. Together, our results provide a novel integrative view on the developmental and evolutionary origins ofCaenorhabditissperm size variation. We hypothesize that life history and/or ecological differences among species favoured the evolution of alternative sperm competition strategies toward either many smaller sperm or fewer larger sperm, with gigantic sperm potentially providing a means of paternal care via gametic provisioning or as a potent vehicle for sexual conflict over offspring development.
Comparative analysis of protein evolution and RNA structural changes in the genome of pre-epidemic and epidemic Zika virus
Authors: Ramaiah Arunachalam , Dai Lei , Contreras Deisy , Sinha Sanjeev , Sun Ren , Arumugaswami Vaithilingaraja 
Published: April 2016

ABSTRACTZika virus (ZIKV) infection is associated with microcephaly, neurological disorders and poor pregnancy outcome1-3and no vaccine is available. Although ZIKV was first discovered in 1947, the exact mechanism of virus replication and pathogenesis still remains unknown. Recent outbreaks of Zika virus in the Americas clearly suggest a better adaptation of viral strains to human host. Understanding the conserved and adaptive features in the evolution of ZIKV genome will reveal the molecular mechanism of virus replication and host adaptation. Here, we show comprehensive analysis of protein evolution and changes in RNA secondary structures of ZIKV strains including the current 2015-16 outbreak. To identify the constraints on ZIKV evolution, selection pressure at individual codons, immune epitopes, co-evolving sites, and RNA structures were analyzed. The proteome of current 2015/16 epidemic ZIKV strains of Asian genotype is found to be genetically conserved due to genome-wide negative selection on codons, with limited positive selection. Predicted RNA structures at the 5’ and 3’ ends of ZIKV strains reveal substantial changes such as an additional stem loop which makes it similar to that of Yellow Fever Virus. Concisely, the targeted changes at both the amino acid and the RNA levels contribute to the better adaptation of ZIKV strains to human host with an enhanced neurotropism.