bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical Shades of Gray: International Frequency of Scientific Misconduct and Questionable Research Practices in Health Professions Education
Authors: Artino Anthony R. , Driessen Erik W. , Maggio Lauren A. 
Published: August 2018

Purpose
To maintain scientific integrity and engender public confidence, research must be conducted responsibly. Whereas deliberate scientific misconduct such as data fabrication is clearly unethical, other behaviors—often referred to as questionable research practices (QRPs)—exploit the ethical shades of gray that color acceptable practice. This study aimed to measure the frequency of self-reported misconduct and QRPs in a diverse, international sample of health professions education (HPE) researchers.

Method
In 2017, the authors conducted an anonymous, cross-sectional survey study. The web-based survey contained 43 items that asked respondents to rate how often they had engaged in a variety of irresponsible research behaviors. The items were adapted from previously published surveys.

Results
In total, 590 HPE researchers took the survey. The mean age was 46 years (SD = 11.6), and the majority of participants were from the United States (26.4%), Europe (23.2%), and Canada (15.3%). The three most frequently reported irresponsible research behaviors were adding authors who did not qualify for authorship (60.6%), citing articles that were not read (49.5%), and selectively citing papers to please editors or reviewers (49.4%). Additionally, respondents reported misrepresenting a participant’s words (6.7%), plagiarizing (5.5%), inappropriately modifying results (5.3%), deleting data without disclosure (3.4%), and fabricating data (2.4%). Overall, 533 (90.3%) respondents reported at least one irresponsible behavior.

Conclusions
Notwithstanding the methodological limitations of survey research, these findings indicate that a substantial proportion of HPE researchers report a range of misconduct and QRPs. Consequently, reforms may be needed to improve the conduct of HPE research.
Extracellular Mitochondrial DNA and N-Formyl Peptides in Trauma and Critical Illness: A Systematic Review
Authors: Lubkin David T. , Bishawi Muath , Barbas Andrew S. , Brennan Todd V. , Kirk Allan D. 
Published: August 2018

Objectives:
Extracellular mitochondrial DNA and N-formyl peptides released following tissue damage may contribute to systemic inflammation through stimulation of the innate immune system. In this review, we evaluate existing in vivo human data regarding a role for mitochondrial DNA and N-formyl peptides in producing systemic inflammation in trauma and critical illness, investigate the utility of these molecules in risk prediction and clinical decision support, and provide suggestions for standardization of future research.

Data Sources:
PubMed, Embase (1971–2017).

Study Selection:
Studies measuring extracellular mitochondrial DNA and/or N-formyl peptides in acutely ill patients.

Data Extraction:
Fifty-four studies were analyzed. Data extracted included article characteristics, methods, results, and performance in clinical prediction.

Data Synthesis:
The most common patient types investigated were trauma (19 studies) and sepsis (eight). In studies comparing patient mitochondrial DNA or N-formyl peptide levels to healthy controls, 38 (90.5%) reported significantly elevated mitochondrial DNA levels in patients at first reported time point, as did the one study making this comparison for N-formyl peptides. Nine studies (81.8%) reported significantly elevated plasma/serum mitochondrial DNA levels in at least one time point in patients who developed inflammatory complications of their primary pathology compared with patients without inflammatory complications. For the ability of mitochondrial DNA to predict complications or outcomes, the area under the curve was 0.7 or greater in 84.6% of receiver operating characteristic curves, and 92.9% of odds, adjusted odds, risk, and hazard ratios were statistically significant.

Conclusions:
Extracellular mitochondrial DNA levels are elevated early in patients’ hospital courses in many acute illnesses and are higher in patients who develop inflammatory complications. Elevated mitochondrial DNA levels may be clinically useful in risk prediction and clinical decision support systems. Further research is needed to determine the role of extracellular N-formyl peptides in systemic inflammation and their possible clinical utility.
Radiologic Evaluation of Clinically Benign Rectal Neoplasms May Not Be Necessary Before Local Excision
Authors: Lee Lawrence , Arbel Leor , Albert Matthew R. , Atallah Sam B. , Hill James , Monson John R.T. 
Published: August 2018

BACKGROUND:
Local excision may be curative for benign and malignant rectal neoplasms. Because many early rectal cancers are discovered incidentally after local excision of clinically benign lesions, it is unclear whether preoperative imaging with transrectal ultrasound or MRI affects management.

OBJECTIVE:
The purpose of this study was to determine the diagnostic characteristics and effect of preoperative imaging on the incidence of malignancy in benign rectal lesions undergoing local excision.

DESIGN:
Prospective data from 2 institutions were included. Coarsened exact matching created a balanced cohort comparing imaging and no-imaging groups.

SETTING:
The study was conducted at high-volume specialist referral hospitals.

PATIENTS:
Adult patients undergoing local excision via transanal endoscopic surgery between 1997 and 2016 for clinically benign rectal neoplasms were included.

INTERVENTION:
The study intervention included preoperative imaging with transrectal ultrasound and/or MRI.

MAIN OUTCOME MEASURES:
We measured the incidence of malignancy and diagnostic accuracy of preoperative imaging.

RESULTS:
A total of 620 patients were included (272 with preoperative imaging and 348 without). There were 250 patients undergoing transrectal ultrasound, and 24 patients undergoing MRI (2 patients underwent both). Transrectal ultrasound and MRI correctly identified malignant polyps in 50% (11/22) and 44% (8/18). Overall agreement for benign versus malignant polyps between preoperative imaging and final pathology was κ = 0.30 (95% CI, 0.18–0.41) for transrectal ultrasound and 0.29 (95% CI, 0.01–0.57) for MRI. In both the overall and unmatched cohorts, the incidence of malignancy, margin involvement, and proportion of patients requiring salvage surgery was similar.

LIMITATIONS:
Data were obtained from 2 institutions with different equipment over a long time period.

CONCLUSIONS:
Preoperative imaging did not accurately identify malignancy in clinically benign rectal lesions and did not affect the incidence of malignancy, margin involvement, or proportion of patients requiring salvage surgery. Therefore, preoperative imaging may not be necessary for clinically benign lesions undergoing local excision. See Video Abstract at http://links.lww.com/DCR/A695.
A Rare Case of Malbranchea Species Pulmonary Infection in the Setting of Suspected Selective Immunoglobulin M Deficiency
Authors: Espinosa Ronald F. , Pyun John , Modena Brian D. , Crum-Cianflone Nancy 
Published: August 2018

Abstract
Humoral immunodeficiencies are traditionally associated with prolonged and recurrent respiratory tract infections, including unusual pathogens. We describe a case of a 63-year-old man with a history of chronic obstructive pulmonary disease and recurrent pneumonias (including Pseudomonas) who presented with cough, dyspnea, and respiratory failure with computed tomography imaging showing bilateral consolidations and cavitary lesions. The bronchoalveolar lavage fungal culture grew Malbranchea species, whereas viral, bacterial, and mycobacterial cultures were negative. Because of multiple hospitalizations for pneumonia and the presence of this unusual pathogen, quantitative immunoglobulin levels were obtained, revealing an undetectable total immunoglobulin M (IgM) level (<5 mg/dL) with normal levels of IgG (1270 mg/dL) and IgA (108 mg/dL). Complete blood count with differential and lymphocyte subsets (ie, CD4, CD8) showed no deficiency in immune cell counts, and human immunodeficiency virus antibody/antigen testing was negative. The patient improved clinically after antifungal therapy with posaconazole, and he additionally received prophylactic inhaled tobramycin given his history of recurrent pulmonary infections and suspected selective IgM deficiency.
Population Pharmacokinetic-Pharmacodynamic Modeling of a Novel Methylphenidate Extended-Release Orally Disintegrating Tablet in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder
Authors: Teuscher Nathan S. , Sikes Carolyn R. , McMahen Russ , Engelking Dorothy 
Published: August 2018

Abstract

Purpose/Background
A methylphenidate (MPH) extended-release orally disintegrating tablet (MPH XR-ODT) formulation was recently approved for attention-deficit/hyperactivity disorder treatment in children 6 to 17 years of age. This analysis sought to develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model to describe MPH XR-ODT PD-response data in a classroom study and use the model to simulate PD responses for a range of body weights and doses.

Methods/Procedures
The MPH XR-ODT PK/PD model was developed with pediatric and adult PK data from prior studies and efficacy data from a laboratory classroom study in children with attention-deficit/hyperactivity disorder. In these studies, the safety profile of MPH XR-ODT was consistent with other extended-release MPH formulations. The PK/PD model efficacy end point was the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score. Body weight effects on MPH clearance and volume of distribution were included in the resulting model. Simulations using the PK/PD model were performed for patients with body weights between 7 and 100 kg and MPH XR-ODT doses of 10 to 60 mg MPH hydrochloride equivalents.

Findings/Results
In the PK/PD model, the maximal reduction in the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score was approximately 38 units, and the MPH concentration required to achieve 50% of the maximal reduction was 14.24 ng/mL, suggesting favorable efficacy for MPH XR-ODT. Simulations showed a direct correlation between the effective MPH XR-ODT dose and body weight, with heavier participants requiring higher doses for symptom control.

Implications/Conclusion
This model may help facilitate the dose-titration process by identifying an effective MPH XR-ODT target dose.
Quality-of-Life in Achilles Tendinopathy: An Exploratory Study
Authors: Ceravolo Michael L. , Gaida James E. , Keegan Richard J. 
Published: August 2018

Objective:This research aimed to explore the quality-of-life and experiences of people with Achilles tendinopathy.Design:This mixed-methods research used the 8-dimension Assessment of Quality-of-Life (AQoL-8D), focus groups and grounded theory analysis. AQoL-8D scores were compared with population normative scores. In focus groups, participants discussed their experiences with Achilles tendinopathy.Setting:An online survey was completed, followed by focus groups and interviews held at the University of Canberra.Participants:Adults with Achilles tendon pain were eligible to participate in the online survey, which was distributed through email and social media.Results:Complete survey responses were obtained from 92 individuals, and 11 individuals participated in focus groups and interviews. AQoL-8D scores were significantly lower in those with Achilles tendinopathy (79 ± 11 vs 81 ± 13). AQoL-8Ds of mental health, pain, senses, and the physical “super dimension” were also significantly lower. The difference exceeded the AQoL-8D minimum clinically important difference of 6% only for the pain dimension. Themes identified included adapting lifestyles, living with the condition, changes in mental and social well-being, conflict with identity, frustration, and individual experiences.Conclusions:Achilles tendinopathy is associated with a lower quality-of-life score, but on average, the difference does not exceed the minimum clinically important difference. In focus groups, some individuals described profound impacts on their life. This discrepancy likely reflects the variability of the impact across individuals. For some people, the effect is minimal, yet for those who tie their identity and social activities to fitness and physical activity, the effect can be profound.
Health care providers' perceptions regarding fundamental issues to consider prior to launching nurse practitioner training in Tanzania
Authors: Mboineki Joanes Faustine , Changying Chen , Zhang Weihong 
Published: August 2018

ABSTRACT

Background and purpose:
Although the demand for competent health care professionals and better services is high, studies concerning nursing education are not a priority in sub-Saharan African countries, as revealed in limited available records. Strengthening nursing education by establishing proper training models for newly developed advanced practice roles such as “nurse practitioner” (NP) will increase competency in nurses and reduce the shortage of skilled staff within the health care system, thereby enhancing the proper provision of health care services. The main purpose of this research was to investigate fundamental issues that should be considered in the launching of NP training.

Methods:
A descriptive qualitative design was used in this study. A nonprobability sampling approach and significantly purposeful sampling were also used to recruit 20 health care providers into the study. Individual face-to-face interviews were conducted on scheduled timings, which required an average of 30 minutes for each interview. Finally, a content analysis was used to identify the themes.

Conclusion:
The current working environment at the rural primary health care facilities is not convenient for the practices of NPs trained at the master's level. Therefore, before the training of NPs, the government and all stakeholders should strive to improve the environment of the facilities including adequate diagnostic equipment and on-time supply of drugs from the store. Institutions aiming to introduce programs for NPs must develop their curriculum based on currently available local and international guidelines.

Implications for practice:
Adequate preparation before launching an NP training program will be needed to help build a strong training and hence produce competent professionals.
The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing Impairment in Filipino Cochlear Implantees
Authors: Chiong Charlotte M. , Reyes-Quintos Ma. Rina T. , Yarza Talitha Karisse L. , Tobias-Grasso Celina Ann M. , Acharya Anushree , Leal Suzanne M. , Mohlke Karen L. , Mayol Nanette L. , Cutiongco-de la Paz Eva Maria , Santos-Cortez Regie Lyn P. 
Published: August 2018

Hypothesis:
Variants in SLC26A4 are an important cause of congenital hearing impairment in the Philippines.

Background:
Cochlear implantation is a standard rehabilitation option for congenital hearing impairment worldwide, but places a huge cost burden in lower-income countries. The study of risk factors such as genetic variants that may help determine genetic etiology of hearing loss and also predict cochlear implant outcomes is therefore beneficial.

Methods:
DNA samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced for the coding exons of SLC26A4. Exome sequencing was performed to confirm results.

Results:
Four cochlear implantees with bilaterally enlarged vestibular aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val) variant, which has a minor allele frequency of 0.0015 in Filipino controls. In patients with the SLC26A4 variant there was no association between cochlear implant outcome and age at implantation or duration of implant. There was also no association between the occurrence of the SLC26A4 variant and postsurgical audiometric thresholds and parents’ evaluation of aural/oral performance of children (PEACH) scores. On the other hand, the SLC26A4 variant increased presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000 Hz.

Conclusion:
The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of congenital hearing impairment in Filipinos and is associated with bilateral EVA and increased presurgical audiometric thresholds, but does not adversely affect post-implant outcomes.
Hearing Loss Asymmetry due to Chronic Occupational Noise Exposure
Authors: Sturman Cara Jane , Frampton Chris Miles , Ten Cate Wouter J. F. 
Published: August 2018

Objective:To determine whether occupational noise exposure causes symmetrical or asymmetrical hearing loss.Study Design:Retrospective Case Series.Setting:Otorhinolaryngology Specialist Centre.Patients:Seven hundred forty-four reports for occupational noise-induced hearing loss (NIHL) compensation were analyzed. Subjects with at least 40% of their total hearing loss due to occupational NIHL were included. Claimants with any confounding factor that could cause asymmetric hearing loss such as history of shooting, head, or ear trauma were excluded. With the strict inclusion criteria, 83 subjects were included in the study. Claimants with ≥40%, ≥60%, and ≥80% occupational NIHL of their total hearing loss were compared.Intervention(s):None.Main Outcome Measure(s):The left ear hearing threshold compared with the right ear hearing threshold (dB) at the frequencies 0.5 to 8 kHz.Results:In the total group, the left ear hearing threshold was statistically significantly higher compared with the right ear at 3 kHz (2.41 dB). In the subgroups ≥60% and ≥80% occupational NIHL of total hearing loss, the left ear hearing threshold was statistically significant higher compared with the right ear at 3 kHz, respectively, 3.81 dB and 5.53 dB and 4 kHz, respectively, 2.86 dB and 5.53 dB. An asymmetry of more than 10 dB at 3 and 4 kHz was observed in 39% and 30% of the subjects respectively. In these cases, the vast majority had more pronounced hearing loss in the left ear.Conclusion:Findings of this study further indicate that the left ear is more susceptible to noise exposure compared with the right ear.
Proposal of a Treatment Strategy for Eosinophilic Otitis Media Based on Middle Ear Condition
Authors: Esu Yoshihiko , Iino Yukiko , Masuda Maria , Kanazawa Hiromi , Yoshida Naohiro 
Published: August 2018

Objective:
We classified eosinophilic otitis media (EOM) into three grades (G1–G3) based on the middle ear mucosal thickness and aimed to establish a treatment strategy for EOM based on these pathological categories.

Study Design:
Retrospective cohort study.

Setting:
Tertiary referral center.

Patients:
We evaluated 136 ears of 68 patients (38 women, 30 men; average age, 56.1 yr; range, 32–80 yr) with bilateral EOM, including 14 surgically treated ears.

Interventions:
Diagnostics and treatment.

Main Outcome Measures:
Treatment responses to intratympanic instillation of triamcinolone acetonide (TA) and surgery.

Results:
G1 (mild) cases of EOM responded well to intratympanic TA. G2 (moderate) cases required both TA and systemic glucocorticoids. G3 (severe) cases with granulation were unresponsive to but tolerated the treatment. In 14 ears, granulation tissue was surgically removed and the area was covered with a gelatin sponge containing TA. After the surgery, the severity level of EOM decreased from G3 to G2 in 12 ears, and hearing improved in 4 ears. Three ears showed normalization of the tympanic membrane, and seven ears had less otorrhea. Risk factors for granulation (G3) were the presence of bacterial infection (p = 0.017) and diabetes mellitus (HbA1c of ≥6.5%) (P = 0.039) (odds ratios of 4.55 and 3.95, respectively).

Conclusions:
This study showed that G3 EOM was unresponsive to conservative glucocorticoid treatment and required granulation tissue removal. Classification based on the middle ear pathology is useful for determining the most appropriate and successful treatment for EOM.
Preliminary Study on Antinuclear Antibodies in Patients With Chronic Dilatory Eustachian Tube Dysfunction
Authors: Fuchs Anna , Witte Torsten , Lenarz Thomas , Teschner Magnus 
Published: August 2018

Background and Hypothesis:There are some known reasons for chronic dilatory Eustachian tube dysfunction (chronic D-ETD, also known as chronic obstructive tube dysfunction), for example infections, hyperplastic adenoids, or tumors. In many cases though, none of these reasons apply. The question arises whether there might be an autoimmune pathogenesis in patients with idiopathic chronic D-ETD.Methods:The study includes 31 consecutive patients with chronic D-ETD and 92 consecutive blood donors (BD, comparative cohort). The production of antinuclear antibodies (ANA), as an indicator for autoimmune pathologies, was measured in the serum of patients and BD.Results:ANA titers were significantly higher in patients with chronic D-ETD, compared with BD (p = 0.0027). The results weighted clearly toward higher ANA titers in younger patients. A comparison of ANA titers in patients and BD aged less than 40 years showed a significant difference (p = 0.0062), whereas it was not significant between patients and BD aged ≥ 40 years (p = 0.19).Conclusion:The significant results of elevated ANA titers in chronic D-ETD make an autoimmune pathogenesis highly probable, at least in some of the patients concerned. Further research with higher numbers of patients is needed to confirm the hypothesis of an autoimmune chronic D-ETD. A better understanding of etiology and pathogenesis of chronic D-ETD might open up new and perhaps even causal therapeutic strategies.
Pancreatic Cancer–Induced Cachexia and Relevant Mouse Models
Authors: Henderson Sally E. , Makhijani Neil , Mace Thomas A. 
Published: August 2018

Abstract
Pancreatic cancer is the third leading cause of cancer death in the United States, with projections that it will become the second leading cause by the year 2030. It carries a dismal prognosis with a 5-year overall survival rate of less than 9% and is associated with numerous comorbidities, the most notable being cachexia. Defined as the loss of muscle mass not reversible by conventional nutritional support, cachexia is seen in over 85% of pancreatic cancer patients and contributes significantly to mortality, where nearly 30% of pancreatic cancer deaths are due to cachexia rather than tumor burden. Therefore, there is an urgent need to identify the mechanisms behind the development of muscle wasting in pancreatic cancer patients and design novel therapeutics targeting cachexia. This review highlights the current understanding surrounding the mechanisms underpinning the development of cachexia in pancreatic cancer, as well as the current mouse models of pancreatic cancer–induced muscle wasting described in the literature.
Contribution of Oral Hygiene and Cosmetics on Contamination of Gluten‐free Diet
Authors: Verma Anil K. , Lionetti Elena , Gatti Simona , Franceschini Elisa , Catassi Giulia Naspi , Catassi Carlo 
Published: August 2018

ABSTRACTObjectives:The only available treatment for celiac disease (CD) is the gluten‐free diet. It is unclear whether the presence of gluten in oral hygiene products and cosmetics that are applied on the mouth is a reason of concern for CD patients. The aim of this study was to test the level of gluten contamination in oral hygiene and cosmetic products available in the Italian market.Methods:A total of 66 products (toothpastes = 37; dental tablets = 2; mouthwashes = 5; lip‐balms = 10; lipsticks = 12) labelled gluten‐free or with unknown gluten content were randomly collected from different supermarkets and pharmacies. The gluten quantification was determined by the R5 ELISA method approved by EU regulations.Results:Out of 66 oral hygiene and cosmetics, 62 products (94%) were found to be gluten‐free (gluten level <20 ppm), while 4 (6%) (toothpastes = 3; lipsticks = 1) showed a gluten level >20 ppm (toothpastes: 20.7, 31.4, and 35 ppm; lipstick: 27.4 ppm). None of the selected products had ingredient derived from wheat, barley, or rye.Conclusions:Gluten contamination is currently not an issue in a wide array of cosmetic and oral hygiene products that are commonly in the market.