bluuebunny/crossref_metadata_2025 huggingface dataset:
The Accuracy of Conflict-of-Interest Disclosures Reported by Plastic Surgeons and Industry
Authors: Lopez Joseph , Samaha Georges , Purvis Taylor E. , Siegel Gabriel , Jabbari Javaneh , Ahmed Rizwan , Milton Jacqueline , Tufaro Anthony P. , May James W. , Dorafshar Amir H.
Published: May 2018

Background:

The purpose of this study was to analyze the frequency and nature of self-reported conflict-of-interest disclosures in the plastic surgery literature and to compare these findings to the Physician Payments Sunshine Act database.

Methods:

All articles published from August of 2013 through December of 2013 in four major plastic surgery journals were analyzed. For every publication, the conflict-of-interest disclosure statement for each investigator was reviewed. These statements were then compared to transactions of value for each investigator as reported by biomedical companies in the Sunshine Act database. An analysis was performed to identify and characterize specific factors associated with conflict-of-interest disclosures.

Results:

A total of 1002 independent investigators/authors were identified. Of these, 90 investigators (9 percent) self-reported a conflict of interest. In contrast, a total of 428 authors (42.7 percent) were found to have received transactions of value from a biomedical company according to the Sunshine Act database. Conversely, a total of 22 authors (2.2 percent) self-reported a conflict of interest but were not found to have received transactions of value in the Sunshine Act database. Our analysis found that (1) academic investigators, (2) transactions of value in excess of $500, and (3) publishing articles related to the sponsoring biomedical company were all statistically associated with reporting conflicts of interest (p < 0.0001).

Conclusions:

Discordance exists between investigator/authors self-reporting in scientific journals and the government-mandated reporting of conflicts of interest by industry. Factors associated with conflict-of-interest disclosure include academic status, transaction amount, and article content related to the sponsoring biomedical company.
Supportive Use of Adipose-Derived Stem Cells in Cell-Assisted Lipotransfer for Localized Scleroderma
Authors: Chen Bo , Wang Xiaojun , Long Xiao , Zhang Mingzi , Huang Jiuzuo , Yu Nanze , Xu Jing
Published: May 2018

Background:

The authors aimed to analyze factors related to lipotransfer for localized scleroderma, and to explore the feasibility of cell-assisted lipotransfer for localized scleroderma treatment.

Methods:

Abdominal fat samples were taken from six scleroderma patients without corticosteroid therapy, five scleroderma patients with corticosteroid therapy, and 10 normal liposuction patients. Their quantity, morphology, and proliferation ability were measured. Blood flow was measured by laser speckle contrast imaging in localized scleroderma lesions and normal contralateral regions for eight localized scleroderma patients. Bleomycin-induced skin fibrosis nude mice were also used to investigate differences between lipotransfer and cell-assisted lipotransfer. Fat weight was measured, and expression of transforming growth factor (TGF)-β1 and type III collagen in the injected skin was determined by immunohistochemistry.

Results:

The number of stem cells from scleroderma patients with corticosteroid treatment was significantly reduced. Mean blood perfusion in localized scleroderma lesions was not significantly different than in the contralateral normal regions. In normal nude mice, there were no significant changes in TGF-β1 and type III collagen between the control, lipotransfer, and cell-assisted lipotransfer groups, whereas in bleomycin-induced skin fibrosis nude mice, lipotransfer and cell-assisted lipotransfer reduced TGF-β1 and type III collagen expression.

Conclusions:

For scleroderma patients, fewer adipose-derived stem cells, because of a history of corticosteroid therapy and a local inflammatory microenvironment, are more important factors, whereas blood supply showed no significant change. Therefore, cell-assisted lipotransfer not only improves the survival rate of transplanted fat but also improves skin texture in bleomycin-induced skin fibrosis nude mice.
Innovative Surgical Approach Using a Mesh Sling for the Aging Neck
Authors: Gronovich Yoav
Published: May 2018

Background:

Rejuvenation of the neck is essential to achieve a young facade. Different approaches for aging neck rejuvenation have been developed throughout the years. Most of them focus on specific elements that contribute to the aging neck. The main drawbacks of these techniques are recurrence of the platysma bands, malposition, deformations, salivary problems, and defatting. These disadvantages and limitations have led the author to create a novel surgical approach to improve the aging neck that would be suitable for most patients. Instead of dealing with each of the elements of the aging neck, the author’s approach involves use of a sling to elevate all the descending elements as a whole to create a natural and longstanding result.

Methods:

Since March of 2014, 10 patients have been operated on for neck lifting with this new approach. Four different types of material have been used: absorbable synthetic braided (Vicryl) in five patients, semiabsorbable synthetic braided and monofilament (Vypro) in one patient, absorbable synthetic matrix (TIGR) in three patients, and biological mesh–allograft material (AlloDerm) in one patient. Follow-up visits were made after 10 days, 3 months, 6 months, and annually.

Results:

In all cases, the operations were uneventful. There were no major complications. Minor complication occurred in one patient with the Vypro mesh. The mesh caused stiffness and was replaced. Final aesthetic results were satisfactory in all cases.

Conclusions:

Current approaches for improvement of the aging neck do not fit all aging neck cases and are suitable for only a specific dominant element. The aging neck tends to reappear faster than expected because of recurrence or dominance of another element. The author’s novel approach is more predictable and is suitable for most cases regardless of the dominant part causing the aging. More experience and longer follow-up are needed to choose the most appropriate material for the mesh.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Predictors of Patient Satisfaction and Postoperative Complications in Penile Inversion Vaginoplasty
Authors: Massie Jonathan P. , Morrison Shane D. , Van Maasdam Judy , Satterwhite Thomas
Published: May 2018

Background:

Penile inversion vaginoplasty is the current gold standard procedure for male-to-female transgender patients seeking gender-confirming genital surgery. Although complication data have been reported extensively in the literature, studies on patient-reported outcomes are sparse. This study aimed to report both postoperative complications and patient-reported outcomes from the largest cohort in the United States to date to undergo penile inversion vaginoplasty. Ultimately, the authors hoped to identify the predictors of postoperative complications and patient satisfaction.

Methods:

A retrospective chart review of a single surgeon’s experience with penile inversion vaginoplasty was performed from July of 2014 to June of 2016. Patient demographic data, postoperative complications, and patient-reported outcome data were collected. Data were correlated by binary logistic regression to determine predictors of postoperative complications and patient satisfaction.

Results:

A total of 117 patients underwent penile inversion vaginoplasty. The most common complications were granulation tissue (26 percent), intravaginal scarring (20 percent), and prolonged pain (20 percent). Overwhelmingly, patients reported “feeling positively about their genitals” (94 percent) and “would do this operation again” (94 percent). Seventy-one percent of patients reported resolution of their gender dysphoria. The top predictors of patient dissatisfaction were intravaginal scarring, prolonged pain, excessive external scarring, loss of sensation, and hematoma/excessive bleeding.

Conclusions:

This is the largest study of penile inversion vaginoplasty in the United States to report on both postoperative complications and patient-reported outcomes. Despite moderate complication risk, patient satisfaction remains very high after penile inversion vaginoplasty, with the majority of patients reporting improvement of their gender dysphoria.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Self-Regulation and Executive Functioning as Related to Survival in Motor Neuron Disease: Preliminary Findings
Authors: Garcia-Willingham Natasha E. , Roach Abbey R. , Kasarskis Edward J. , Segerstrom Suzanne C.
Published: May 2018

Objective

Disease progression varies widely among patients with motor neuron disease (MND). Patients with MND and coexisting dementia have shorter survival. However, implications of mild cognitive and behavioral difficulties are unclear. The present study examined the relative contribution of executive functioning and self-regulation difficulties on survival over a 6-year period among patients with MND, who scored largely within normal limits on cognitive and behavioral indices.

Methods

Patients with MND (N = 37, age = 59.97 ± 11.57, 46% female) completed the Wisconsin Card Sorting Task as an executive functioning perseveration index. The Behavior Rating Inventory of Executive Functions (BRIEF-A) was used as a behavioral measure of self-regulation in two subdomains self-regulatory behavior (Behavioral Regulation) and self-regulatory problem-solving (Metacognition). Cox proportional hazard regression analyses were used.

Results

In total, 23 patients died during follow-up. In Cox proportional hazard regressions adjusted for a priori covariates, each 10-point t-score increment in patient-reported BRIEF-A self-regulatory behavior and problem-solving difficulties increased mortality risk by 94% and 103%, respectively (adjusted HR = 1.94, 95% CI = 1.07–3.52; adjusted HR = 2.03, 95% CI = 1.19–3.48). In sensitivity analyses, patient-reported self-regulatory problem-solving remained significant independent of disease severity and a priori covariates (adjusted HR = 1.68, 95% CI = 1.01–2.78), though the predictive value of self-regulatory behavior was attenuated in adjusted models (HR = 1.67, 95% CI = 0.85–3.27). Caregiver-reported BRIEF-A ratings of patients and Wisconsin Card Sorting Task perseverative errors did not significantly predict survival.

Conclusions

Preliminary evidence suggests patient-reported self-regulatory problem-solving difficulties indicate poorer prognosis in MND. Further research is needed to uncover mechanisms that negatively impact patient survival.
Mixed-Methods Evaluation of Real-Time Safety Reporting by Hospitalized Patients and Their Care Partners: The MySafeCare Application
Authors: Collins Sarah A. , Couture Brittany , Smith Ann DeBord , Gershanik Esteban , Lilley Elizabeth , Chang Frank , Yoon Cathy , Lipsitz Stuart , Sheikh Aziz , Benneyan James , Bates David W.
Published: May 2018

Objective

The aims of the study were to evaluate the amount and content of data patients and care partners reported using a real-time electronic safety tool compared with other reporting mechanisms and to understand their perspectives on safety concerns and reporting in the hospital.

Methods

This study used mixed methods including 20-month preimplementation and postimplementation trial evaluating MySafeCare, a web-based application, which allows hospitalized patients/care partners to report safety concerns in real time. The study compared MySafeCare submission rates for three hospital units (oncology acute care, vascular intermediate care, medical intensive care) with submissions rates of Patient Family Relations (PFR) Department, a hospital service to address patient/family concerns. The study used triangulation of quantitative data with thematic analysis of safety concern submissions and patient/care partner interviews to understand submission content and perspectives on safety reporting.

Results

Thirty-two MySafeCare submissions were received with an average rate of 1.7 submissions per 1000 patient-days and a range of 0.3 to 4.8 submissions per 1000 patient-days across all units, indicating notable variation between units. MySafeCare submission rates were significantly higher than PFR submission rates during the postintervention period on the vascular unit (4.3 [95% confidence interval = 2.8–6.5] versus 1.5 [95% confidence interval = 0.7–3.1], Poisson) (P = 0.01). Overall trends indicated a decrease in PFR submissions after MySafeCare implementation. Triangulated data indicated patients preferred to report anonymously and did not want concerns submitted directly to their care team.

Conclusions

MySafeCare evaluation confirmed the potential value of providing an electronic, anonymous reporting tool in the hospital to capture safety concerns in real time. Such applications should be tested further as part of patient safety programs.
Sustained Impact of a Pediatric Resident-Led Patient Safety Council
Authors: Parente Victoria , Feeney Colby , Page Laura , Johnson Shaina , Porada Kelsey , Cheifetz Ira , Stephany Alyssa
Published: May 2018

Objectives

The aim of the study was to evaluate the impact of a resident-led patient safety council. This study measured change in resident perceptions and knowledge of safety issues for 3 years, as well as behavioral choices to participate in patient safety activities during and after residency.

Methods

Pediatric residents formed a resident-led safety council to engage their peers in patient safety activities. Surveys were distributed annually from 2013 to 2015 to measure residents’ perception and knowledge surrounding patient safety. The number of patient safety reports submitted by residents was tracked for the same period. In addition, recent graduates were surveyed to assess the influence of the council on postresidency involvement in patient safety.

Results

Resident perception of the institutional culture of safety improved and knowledge of basic patient safety concepts increased. The number of resident-submitted safety reports increased from 6.2 to 15.2 reports per month in the 2013 and 2015 academic years, respectively. Surveys of recent graduates suggest that involvement with the safety council during residency fostered future engagement in patient safety.

Conclusions

This resident-led council models successful involvement of trainees in system-based patient safety. Such involvement can help shape the safety culture within a training program and encourages continued participation in patient safety after residency completion.
Brief Report: The Association of Chronic Pain and Long-Term Opioid Therapy With HIV Treatment Outcomes
Authors: Merlin Jessica S. , Long Dustin , Becker William C. , Cachay Edward R. , Christopoulos Katerina A. , Claborn Kasey , Crane Heidi M. , Edelman E. Jennifer , Harding Richard , Kertesz Stefan G. , Liebschutz Jane M. , Mathews W. Christopher , Mugavero Michael J. , Napravnik Sonia , C. O'Cleirigh Connall , Saag Michael S. , Starrels Joanna L. , Gross Robert
Published: May 2018

Background:

Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.

Methods:

This was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one “no-show” to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.

Results:

Among 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).

Conclusions:

Chronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.
The Effect of Transtemperal Approach and Placement of Intracranial Pressure Sensor Into Temporal Horn of Lateral Ventricle in Management of Spontaneous Supratentorial Intracerebral Hemorrhage Broken Into Ventricles
Authors: Wang Fei , Yang Tao , Niu Chaoshi
Published: May 2018

To investigate the effect of transtemperal approach and placement of intracranial pressure sensor into temporal horn of lateral ventricle in management of spontaneous supratentorial intracerebral hemorrhage broken into ventricles, a total of 37 patients with spontaneous supratentorial intracerebral hemorrhage broken into ventricles treated by operation from January 2016 to December 20l6 were analyzed retrospectively, of which 25 patients in simple transtemporal approach group and 12 patients in transtemperal approach and placement of intracranial pressure sensor into temporal horn of lateral ventricle group. All patients were followed up for 8 months to 1.5 years. Two groups were estimated by mortality, clearance rate of hematoma, removal rate of bone flap, good prognosis rate of ADL and incidence of hydrocephalus. The good prognosis rate of ADL and the incidence of hydrocephalus are only statistically significant between the two groups (P < 0.05). According to the result, the transtemperal approach and placement of intracranial pressure sensor into temporal horn of lateral ventricle in management of spontaneous supratentorial intracerebral hemorrhage broken into ventricles is a safe, effective, and less complication of treatment measure.
Growth Factors Release From Concentrated Growth Factors: Effect of β-Tricalcium Phosphate Addition
Authors: Bonazza Veronica , Hajistilly Christopher , Patel Dinker , Patel Jatan , Woo Rita , Cocchi Marco Angelo , Buffoli Barbara , Lancini Davide , Gheno Ezio , Rezzani Rita , Jahanzeb Sadia , Hunnisett Adrian , Almasri Maher , Lucchina Alberta Greco , Brucoli Matteo , Mortellaro Carmen , Rodella Luigi Fabrizio
Published: May 2018

Background:

Platelet concentrates represent a new approach to improve tissue regeneration and can be used alone or together with autogenous bone, recombinant human growth factors, and/or other biomaterials, to enhance tissue regeneration. Among platelet concentrates, concentrated growth factors (CGFs) exhibit an interesting clinical and biotechnological application potential.

Objective:

The aim of this study was to evaluate the in vitro release of 4 growth factors (bone morphogenetic proteins [BMP] -2, BMP-7, transforming growth factor [TGF] -β1, and insulin-like growth factor [IGF] -1) by the enzyme-linked immunosorbent assay (ELISA) technique, in CGFs mixed or not with β-tricalcium phosphate (β-TCP), using or not the Round-up device, at different times.

Methods:

CGFs were obtained from healthy volunteers, mixed or not with β-TCP, using or not the Round-up device. The release of 4 growth factors from these CGFs was then measured at 5 hours, 1, 3, 6, and 8 days, using the ELISA assay.

Results:

Comparison of the results obtained with those achieved for CGFs alone showed that BMP2 and BMP-7 release, significantly increased in CGFs mixed with Round-up and β-TCP, TGF-β1 release was similar to CGFs alone, whereas IG-1 release was lower compared with CGFs alone.

Conclusion:

The present data suggest that β-TCP addition to CGF could enhance and improve tissue regeneration, especially bone regeneration, increasing the release of some growth factors that play an important role in osteogenesis.
Palatal Wiring: Renewing an Old Technique (Circumpalatal Wiring)
Authors: Rahpeyma Amin , Khajehahmadi Saeedeh
Published: May 2018

Circumpalatal wiring has 2 negative points. The first is premature loosening of the wire and the second is tongue irritation caused by exposed wire in roof of the mouth. In this article, a modified technique (palatal wiring) is introduced in which these 2 problems are targeted. In this technique, a small bur hole is created into the hard palate, without the need for flap reflection and wire is passed through it, grasps in the nose, and returns to the oral cavity via sublabial puncture point then 2 ends are twisted in labial vestibule. Palatal wiring can be used alone or as an aid to firmly secure arch bar.
Integrating a Profile of Frontal Face With Its Mirror Image for Facial Reconstruction
Authors: Kaur Paramjit , Krishan Kewal , Sharma Suresh K. , Kanchan Tanuj
Published: May 2018

Introduction and Objectives:

Face recognition plays an important role in the field of biometrics, bioinformatics, and forensic identification. Human faces appear bilaterally symmetric. However, asymmetry is a norm in the human body and careful morphological and metric examination of the human face gives an exact idea of the asymmetry present in the face of an individual. Most of the studies on asymmetry of human face have been carried out with regard to evaluation of expressions in psychology, anthropology, and biometrics. In this preliminary study, an idea of the human face symmetry has been used for complete facial reconstruction. Sometimes, in the CCTV cameras and other surveillance systems, the complete face is not visible, but only a half of the frontal face is detectable. In all such cases, the mirror image of the face can be used to reconstruct the complete face of the person in question for representation-based face recognition. In previous studies related to forensic identification and in the discipline of computer science, mirror images have only been used to overcome and deal with the problem of nonsufficient training sample and have not been used for the reconstruction of the full facial profile.

Methodology:

In this article, we present a computerized methodology to generate the mirror image from one frontal half of the face (either left or right) and merging the both (input image and generated mirror image) halves to create the full face. The program was designed using METLAB computer program. This procedure is very simple, less time–consuming, and computationally efficient.

Results and Conclusion:

The results have been presented with regard to generate a complete face in those cases where only one frontal profile, that is, left or right sides of the face is available for examination. The scenario is commonly seen in those cases also where shadow almost hides one half of the face. The proposed methodology would also be useful for improving other facial reconstruction and recognition methods in forensic identification and in other medical fields such as plastic surgery, where creating full face still poses a technical challenge to a plastic surgeon. Some challenges, limitations, and future perspectives of the method have also been discussed in the article.
Alignment of Personality Is Associated With Increased Intraoperative Entrustment
Authors: Sutzko Danielle C. , Boniakowski Anna E. , Nikolian Vahagn C. , Georgoff Patrick E. , Matusko Niki , Thompson-Burdine Juliet A. , Stoll Hadley I. , Prabhu Kaustubh A. , Minter Rebecca M. , Sandhu Gurjit
Published: May 2018

Objective:

To determine the association between intraoperative entrustment and personality alignment.

Summary Background Data:

For surgical residents, achieving operative autonomy has become increasingly difficult. The impact of faculty-resident operative interactions in accomplishing this goal is not well understood. We hypothesized that if operative dyads (faculty and resident) had personality alignment or congruency, then resident entrustment in the operating room would increase.

Methods:

We completed a retrospective analysis of 63 operations performed from September 2015 to August 2016. Operations were scored using OpTrust, a validated tool that assesses progressive entrustment of responsibility to surgical residents in the operating room. All dyads were classified as having congruent or incongruent personality alignment as measured by promotion or prevention orientation using the regulatory focus questionnaire. The association between personality congruence and OpTrust scores was identified using multivariable linear regression.

Results:

A total of 35 congruent dyads and 28 incongruent dyads were identified. Congruent dyads had a higher percentage of “very difficult” cases (33.3 vs. 7.4%, P = 0.017), female residents (37.1 vs. 14.3%, P = 0.042) and faculty with fewer years of experience (10.4 vs. 14.8%, P = 0.028) than incongruent dyads. In addition to post-graduate year level, dyad congruency was independently associated with a 0.88 increase (95% CI [0.27–1.49], P = 0.006) in OpTrust scores (overall range 2–8), after adjusting for case difficulty, faculty experience, and post-graduate year.

Conclusions:

Congruent operative dyads are associated with increased operative entrustment as demonstrated by increased OpTrust scores. Developing awareness and strategies for addressing incongruence in personality in the operative dyad is needed.
Data-driven Development of ROTEM and TEG Algorithms for the Management of Trauma Hemorrhage
Authors: Baksaas-Aasen Kjersti , Van Dieren Susan , Balvers Kirsten , Juffermans Nicole P. , Næss Pål A. , Rourke Claire , Eaglestone Simon , Ostrowski Sisse R. , Stensballe Jakob , Stanworth Simon , Maegele Marc , Goslings J. C. , Johansson Pär I. , Brohi Karim , Gaarder Christine
Published: May 2018

Objective:

Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs).

Background:

Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013.

Methods:

To identify significant VHA parameters capable of detecting TIC (defined as INR > 1.2), hypofibrinogenemia (< 2.0 g/L), and thrombocytopenia (< 100 x109/L), univariate regression models were constructed. Area under the curve (AUC) was calculated, and threshold values for TEG and ROTEM parameters with 70% sensitivity were included in the algorithms.

Results:

A total of, 2287 adult trauma patients (ROTEM: 2019 and TEG: 968) were enrolled. FIBTEM clot amplitude at 5 minutes (CA5) had the largest AUC and 10 mm detected hypofibrinogenemia with 70% sensitivity. The corresponding value for functional fibrinogen (FF) TEG maximum amplitude (MA) was 19 mm. Thrombocytopenia was similarly detected using the calculated threshold EXTEM-FIBTEM CA5 30 mm. The corresponding rTEG-FF TEG MA was 46 mm. TIC was identified by EXTEM CA5 41 mm, rTEG MA 64 mm (80% sensitivity). For hyperfibrinolysis, we examined the relationship between viscoelastic lysis parameters and clinical outcomes, with resulting threshold values of 85% for EXTEM Li30 and 10% for rTEG Ly30.

Based on these analyses, we constructed algorithms for ROTEM, TEG, and CCTs to be used in addition to ratio driven transfusion and tranexamic acid.

Conclusions:

We describe a systematic approach to define threshold parameters for ROTEM and TEG. These parameters were incorporated into algorithms to support data-driven adjustments of resuscitation with therapeutics, to optimize damage control resuscitation practice in trauma.
Methionine antagonizespara-aminosalicylic acid activity via affecting folate precursor biosynthesis pathway inMycobacterium tuberculosis
Authors: Howe Michael D. , Kordus Shannon L. , Cole Malcolm S. , Bauman Allison A. , Aldrich Courtney C. , Baughn Anthony D. , Minato Yusuke
Published: May 2018

para-Aminosalicylic acid (PAS) is a second-line anti-tubercular drug that is used for the treatment of drug-resistant tuberculosis (TB). PAS efficacy in the treatment of TB is limited by its lower potency againstMycobacterium tuberculosisrelative to many other drugs in the TB treatment arsenal. It is known that intrinsic metabolites, such aspara-aminobenzoic acid (PABA) and methionine, antagonize PAS and structurally related anti-folate drugs. While the basis for PABA-mediated antagonism of anti-folates is understood, the mechanism for methionine-based antagonism remains undefined. In the present study, we used both targeted and untargeted approaches to identify factors associated with methionine-mediated antagonism of PAS activity. We found that synthesis of folate precursors as well as a putative amino acid transporter play crucial roles in this process. We also discovered that intracellular biotin confers intrinsic PAS resistance in a methionine-independent manner. Collectively, our results demonstrate that methionine-mediated antagonism of anti-folate drugs occurs through sustained production of folate precursors.
Facial masculinity does not appear to be a condition-dependent male ornament in humans and does not reflect MHC heterozygosity
Authors: Zaidi Arslan A. , White Julie D. , Mattern Brooke C. , Liebowitz Corey R. , Puts David A. , Claes Peter , Shriver Mark D.
Published: May 2018

Facial masculinity is thought to be a condition-dependent male ornament, reflecting immunocompetence in humans. To test this hypothesis, we calculated an objective measure of facial masculinity/femininity using three-dimensional images in a large sample (N = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. This suggests that variation in growth contributes, at least in part, to variation in facial masculinity, which is characteristic of condition-dependent traits. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not specifically a male ornament. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a well known genetic marker of immunity. We show that while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans as thought previously. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.
Intellectual contributions meriting authorship: Survey results from the top cited authors across all science categories
Authors: Patience Gregory S. , Galli Federico , Patience Paul A. , Boffito Daria C.
Published: May 2018

Authorship is the currency of an academic career for which the number of papers researchers publish demonstrates creativity, productivity, and impact. To discourage coercive authorship practices and inflated publication records, journals require authors to affirm and detail their intellectual contributions but this strategy has been unsuccessful as authorship lists continue to grow. Here, we surveyed close to 6000 of the top cited authors in all science categories with a list of 25 research activities that we adapted from the National Institutes of Health (NIH) authorship guidelines. Responses varied widely from individuals in the same discipline, same level of experience, and the same geographic region. Most researchers agreed with the NIH criteria and grant authorship to individuals that draft the manuscript, analyze and interpret data, and propose ideas. However, thousands of the researchers also value supervision and contributing comments to the manuscript whereas the NIH recommends discounting these activities when attributing authorship. People value the minutiae of research beyond writing and data reduction: researchers in the humanities value it less than those in pure and applied sciences; individuals from Far East Asia and Middle East and Northern Africa value these activities more than anglophones and northern Europeans. While developing national and international collaborations, researchers must recognize differences in peoples values while assigning authorship.
ThePseudomonas aeruginosaPilSR two-component system regulates both twitching and swimming motilities
Authors: Kilmury Sara L.N. , Burrows Lori L.
Published: May 2018

Motility is an important virulence trait for many bacterial pathogens, allowing them to position themselves in appropriate locations at appropriate times. Motility structures - pili and flagella - are also involved in sensing surface contact, which modulates pathogenicity. InPseudomonas aeruginosa, the PilS-PilR two-component system (TCS) regulates expression of the type IV pilus (T4P) major subunit PilA, while biosynthesis of the single polar flagellum is regulated by a hierarchical system that includes the FleSR TCS. Previous studies inGeobacter sulfurreducensandDichelobacter nodosusimplicated PilR in regulation of non-T4P-related genes, including some involved in flagellar biosynthesis. Here we used RNAseq analysis to identify genes in addition topilAwith changes in expression in the absence ofpilR. Among these were 10 genes inversely dysregulated by loss ofpilAversuspilR, even though bothpilAandpilRmutants lack T4P and pilus-related phenotypes. The products of those genes - many of which were hypothetical - may be important for virulence and surface-associated behaviours, as mutants had altered swarming motility, biofilm formation, type VI secretion, and pathogenicity in a nematode model. Further, the PilSR TCS positively regulated transcription offleSR, and thus many genes in the FleSR regulon. As a result,pilSRdeletion mutants had defects in swimming motility that were independent of the loss of PilA. Together these data suggest that in addition to controlling T4P expression, PilSR have a broader role in the regulation ofP. aeruginosamotility and surface sensing behaviours.
Diverse incubation rhythms in a facultatively uniparental shorebird – the Northern Lapwing
Authors: Sládeček Martin , Vozabulová Eva , Šálek Miroslav E. , Bulla Martin
Published: May 2018

Incubation by both parents is the most common form of care for eggs. Although the involvement of the two parents may vary dramatically between and within pairs, as well as over the day and breeding season, detailed description of this variation (especially in species with variable male contribution to incubation) is rare. Here, we continuously video-monitored 113 nests of Northern LapwingVanellus vanellusover the breeding season to reveal the diversity of incubation rhythms and parental involvement. We found great between-nest variation in the overall nest attendance (68 –94%; median = 87%) and in how much males incubated (0 – 37%; median = 13%). Notably, the less the males incubated, the lower was the overall nest attendance, even though females partially compensated for the males’ decrease. Overall, incubation rhythms changed little over the season and incubation period. However, as nights shorten with the progressing breeding season, the female longest night incubation bout shortened too. Essentially, nest attendance was highest, incubation bouts longest, exchange gaps shortest and male involvement lowest during the night. Also, males tended to incubate the most after sunrise and before sunset. To conclude, we revealed strong circadian rhythms and remarkable between nest differences in Northern Lapwing incubation (especially in male involvement), yet despite seasonal environmental trends (e.g. increasing temperature) Lapwing incubation rhythms remained relatively stable over the season and incubation period.
Human Als3p Antibodies are Surrogate Markers of NDV-3A Vaccine Efficacy Against Recurrent Vulvovaginal Candidiasis
Authors: Uppuluri Priya , Singh Shakti , Alqarihi Abdullah , Schmidt Clint S. , Hennessey John P. , Yeaman Michael R. , Filler Scott G. , Edwards John E. , Ibrahim Ashraf S.
Published: May 2018

A Phase 1b/2a clinical trial of NDV-3A vaccine containing a Candida albicans recombinant Als3 protein protected women <40 years old from recurrent vulvovaginal candidiasis (RVVC). We investigated the potential use of anti-Als3p sera as surrogate marker of NDV-3A efficacy. Pre- and post-vaccination sera from subjects who experienced recurrence of VVC (R) versus those who were recurrence-free (non-recurrent, NR) were evaluated. Anti-Als3p antisera obtained were evaluated for; 1) titer and subclass profile; 2) their ability to influence C. albicans virulence traits including hyphal elongation, adherence to plastic, invasion of vaginal epithelial cells, biofilm formation on plastic and catheter material, and susceptibility to neutrophil killing in vitro. Serum IgG titers in NR patients were consistently higher than in R patients, particularly for anti-Als3 subclass IgG2. Sera from vaccinated NR patients reduced hyphal elongation, adhesion to plastic, invasion of vaginal epithelial cells and biofilm formation significantly more than pre-immune sera, or sera from R- or placebo-group subjects. Pre-adsorption of sera with C. albicans germ tubes eliminated these effects, while heat inactivation did not. Finally, sera from NR subjects enhanced neutrophil-mediated killing of C. albicans relative to pre-immune sera or sera from R patients. Our results suggest that higher Als3p antibody titers are associated with protection from RVVC, attenuate C. albicans virulence and augment immune clearance of the fungus in vitro. Thus, Als3p serum IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated with NDV-3A.

Abbreviations

Als3p

Agglutinin-like sequence 53 3 protein

AUC

area under the curve

CFU

colony forming unit

ConA

Concanavalin A

ELISA

enzyme-linked immunosorbent assay

Hyr1p

hyphal regulating protein 1

IRB

institutional review board

OPK

opsonophagocytic killing

NR

non-recurrent

NDV-3

recombinant His-tagged N-terminus of Als3p R formulated with alum

NDV-3A

recombinant N-terminus of Als3p R formulated with alum recurrent

RVVC

recurrent vulvovaginal candidiasis

ROC

Receiver-operating characteristic

Sap2

secreted aspartyl proteinase 2

SE

silicone elastomer

VVC

vulvovaginal candidiasis

YNB

yeast nitrogen base

YPD

yeast peptone dextrose
Development of algorithms for automated detection of cervical pre-cancers with a low-cost, point-of-care, Pocket colposcope
Authors: Asiedu Mercy Nyamewaa , Simhal Anish , Chaudhary Usamah , Mueller Jenna L. , Lam Christopher T. , Schmitt John W. , Venegas Gino , Sapiro Guillermo
Published: May 2018

Goal

In this work, we propose methods for (1) automatic feature extraction and classification for acetic acid and Lugol’s iodine cervigrams and (2) methods for combining features/diagnosis of different contrasts in cervigrams for improved performance.

Methods

We developed algorithms to pre-process pathology-labeled cervigrams and to extract simple but powerful color and textural-based features. The features were used to train a support vector machine model to classify cervigrams based on corresponding pathology for visual inspection with acetic acid, visual inspection with Lugol’s iodine, and a combination of the two contrasts.

Results

The proposed framework achieved a sensitivity, specificity, and accuracy of 81.3%, 78.6%, and 80.0%, respectively when used to distinguish cervical intraepithelial neoplasia (CIN+) relative to normal and benign tissues. This is superior to the average values achieved by three expert physicians on the same data set for discriminating normal/benign cases from CIN+ (77% sensitivity, 51% specificity, 63% accuracy).

Conclusion

The results suggest that utilizing simple color- and textural-based features from visual inspection with acetic acid and visual inspection with Lugol’s iodine images may provide unbiased automation of cervigrams.

Significance

This would enable automated, expert-level diagnosis of cervical pre-cancer at the point-of-care.
Phenotype-specific enrichment of Mendelian disorder genes near GWAS regions across 62 complex traits
Authors: Freund Malika Kumar , Burch Kathryn , Shi Huwenbo , Mancuso Nicholas , Kichaev Gleb , Garske Kristina M. , Pan David Z. , Pajukanta Päivi , Pasaniuc Gleb , Arboleda Valerie A.
Published: May 2018

Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we quantify the overlap of genes identified through large-scale genome-wide association studies (GWAS) for 62 complex traits and diseases with genes known to cause 20 broad categories of Mendelian disorders. We identify a significant enrichment of phenotypically-matched Mendelian disorder genes in GWAS gene sets. Further, we observe elevated GWAS effect sizes near phenotypically-matched Mendelian disorder genes. Finally, we report examples of GWAS variants localized at the transcription start site or physically interacting with the promoters of phenotypically-matched Mendelian disorder genes. Our results are consistent with the hypothesis that genes that are disrupted in Mendelian disorders are dysregulated by noncoding variants in complex traits, and demonstrate how leveraging findings from related Mendelian disorders and functional genomic datasets can prioritize genes that are putatively dysregulated by local and distal non-coding GWAS variants.
The RHIM within the M45 protein from murine cytomegalovirus forms heteromeric amyloid fibrils with RIPK1 and RIPK3
Authors: Pham Chi L. L. , Strange Merryn , O’ Carroll Ailis , Shanmugam Nirukshan , Sierecki Emma , Gambin Yann , Steain Megan , Sunde Margaret
Published: May 2018

The M45 protein from murine cytomegalovirus protects infected murine cells from death by necroptosis and can protect human cells from necroptosis induced by TNFR activation, when heterologously expressed. We show that the N-terminal 90 residues of the M45 protein, which contain a RIP Homotypic Interaction Motif (RHIM), are sufficient to confer protection against TNFR-induced necroptosis. This N-terminal region of M45 drives rapid self-assembly into homo-oligomeric amyloid fibrils and interacts with the RHIMs of human RIPK1 and RIPK3 kinases to form heteromeric amyloid fibrils in vitro. An intact RHIM core tetrad is required for the inhibition of cell death by M45 and we show that mutation of those key tetrad residues abolishes homo- and hetero-amyloid assembly by M45 in vitro, suggesting that the amyloidogenic nature of the M45 RHIM underlies its biological activity. Our results indicate that M45 mimics the interactions made by RIPK1 with RIPK3 in forming heteromeric amyloid structures.
Generation of the squamous epithelial roof of the 4thventricle
Authors: Campo-Paysaa Florent , Clarke Jonathan DW , Wingate Richard JT
Published: May 2018

We use the transparency of zebrafish embryos to reveal thede novogeneration of a simple squamous epithelium and identify the cellular architecture in the epithelial transition zone that ties this squamous epithelium to the columnar neuroepithelium within the embryo’s brain. The simple squamous epithelium of the rhombencephalic roof plate is pioneered by distinct mesenchymal cells at the dorsal midline of the neural tube. Subsequently a progenitor zone is established at the interface between columnar epithelium of the rhombic lip and the expanding squamous epithelium of the roof plate. Surprisingly this interface consists of a single progenitor cell type that we have named the veil cell. Veil cells expressgdf6aand constitute a lineage restricted stem zone that generates the squamous roof plate by direct transformation and asymmetrically fated divisions. Experimental restriction of roof plate expansion leads to extrusion of veil cell daughters and squamous cells, suggesting veil cell fate is regulated by the space available for roof plate growth.
Sera from individuals with narrowly focused influenza virus antibodies rapidly select viral escape mutationsin ovo
Authors: Davis Amy K.F. , McCormick Kevin , Gumina Megan E. , Petrie Joshua G. , Martin Emily T. , Xue Katherine S. , Bloom Jesse D. , Monto Arnold S. , Bushman Frederic D. , Hensley Scott E.
Published: May 2018

Influenza viruses use distinct antibody escape mechanisms depending on the overall complexity of the antibody response that is encountered. When grown in the presence of a hemagglutinin (HA) monoclonal antibody, influenza viruses typically acquire a single HA mutation that reduces the binding of that specific monoclonal antibody. In contrast, when confronted with mixtures of HA monoclonal antibodies or polyclonal sera that have antibodies that bind several HA epitopes, influenza viruses acquire mutations that increase HA binding to host cells. Recent data from our laboratory and others suggest that some humans possess antibodies that are narrowly focused on HA epitopes that were present in influenza virus strains that they were likely exposed to in childhood. Here, we completed a series of experiments to determine if humans with narrowly focused HA antibody responses are able to select for influenza virus antigenic escape variantsin ovo.We identified three human donors that possessed HA antibody responses that were heavily focused on a single HA antigenic site. Remarkably, sera from all three of these donors selected single HA escape mutations duringin ovopassage experiments, similar to what has been previously reported for single monoclonal antibodies. These single HA mutations directly reduced binding of serum antibodies used for selection. We propose that new antigenic variants of influenza viruses might originate in individuals that produce antibodies that are narrowly focused on HA epitopes that were present in viral strains that they encountered in childhood.

Importance

Influenza vaccine strains must be updated frequently since circulating viral strains continuously change in antigenically important epitopes. Our previous studies have demonstrated that some individuals possess antibody responses that are narrowly focused on epitopes that were present in viral strains that they encountered during childhood. Here, we show that influenza viruses rapidly escape this type of polyclonal antibody response when grownin ovoby acquiring single mutations that directly prevent antibody binding. These studies improve our understanding of how influenza viruses evolve when confronted with narrowly focused polyclonal human antibodies.