bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Prenatal Smoking and Gestational Diabetes Mellitus
Authors: Bar-Zeev Yael , Haile Zelalem T. , Chertok Ilana Azulay
Published: December 2019

OBJECTIVE:

To evaluate whether there is an association between prenatal smoking and gestational diabetes mellitus (GDM).

METHODS:

We conducted a secondary data analysis using data from the Pregnancy Risk Assessment Monitoring System from 2009 to 2015. Outcome measures included self-reported GDM and change in smoking status during pregnancy (nonsmoker, quit smoking, reduced the amount smoked, smoked the same or more). Multivariable logistic regression analyses were performed to estimate the association between prenatal smoking and GDM status, adjusted for maternal age, race–ethnicity, prepregnancy body mass index (BMI) categories (underweight, normal [referent group], overweight, and obese), and gestational weight gain (inadequate, normal [referent group], and excessive), overall and stratified by prepregnancy BMI and gestational weight gain subgroups.

RESULTS:

A total of 222,408 women were included; 5.3% (n=12,897) had GDM. Most (48.1%) women had normal prepregnancy BMI, and 43.1% had excessive gestational weight gain. Mothers who continued to smoke the same or greater number of cigarettes or reduced the number of cigarettes smoked had higher odds of GDM (adjusted odds ratio [OR] 1.46, 95% CI 1.25–1.71 and OR 1.22, 95% CI 1.08–1.38, respectively). Smoking the same or more cigarettes was associated with higher odds of GDM in all subgroups of prepregnancy BMI or gestational weight gain.

CONCLUSION:

Prenatal smoking is associated with higher odds of GDM, after adjusting for known risk factors, and stratifying by prepregnancy BMI and gestational weight gain. Reducing smoking during pregnancy might reduce the risk of GDM and could be an additional reason for promoting smoking cessation among pregnant women.
Persistent Opioid Use After Hysterectomy in the United States, 2005–2015
Authors: Young Jessica C. , Wu Jennifer M. , Willis-Gray Marcella , Pate Virginia , Jonsson Funk Michele
Published: December 2019

OBJECTIVE:

To assess variables associated with opioid prescriptions filled perioperatively after hysterectomy and the risk of prolonged opioid use through 1 year after hysterectomy.

METHODS:

In this retrospective cohort study, we used the 2005–2015 IBM MarketScan databases to identify women aged at least 18 years who underwent hysterectomy. For opioid use, we identified filled prescriptions for opioid medications. We excluded women with prevalent opioid use, defined as an opioid prescription filled 180 to 30 days preoperatively or at least two prescriptions filled in the 30 days before surgery. We defined perioperative opioid use as any opioid prescription filled within 30 days before or 7 days after surgery. We used log-binomial regression to identify independent predictors of perioperative opioid prescription fill. To assess the risk of long-term opioid use, we estimated the proportion of women with ongoing monthly opioid prescriptions through 12 months after surgery and the proportion of women with any opioid prescription 3–6 months after surgery, mimicking published estimates.

RESULTS:

Among 569,634 women who underwent hysterectomy during the study period, 176,537 (30.9%) were excluded owing to prevalent opioid use. We found that 331,322 (84.3%) women filled a perioperative opioid prescription, with median quantity of 30 pills (interquartile range 25–40), and that younger (adjusted risk ratio [adjRR]18–24 0.91) and older (adjRR65–74 0.84; adjRR75+ 0.70) patients were less likely to receive a perioperative prescription compared with women aged 45–54. The proportion of women with continuous monthly fills of opioids through 2, 3, 6, and 12 months after surgery was 1.40%, 0.34%, 0.06%, and 0.02%, respectively.

CONCLUSION:

Most women who underwent hysterectomy in the United States from 2005 to 2015 filled a perioperative opioid prescription with a median quantity of 30 pills. The risk of prolonged opioid use through 6 months is quite low, at 0.06% or 1 in 1,547.
Risk of Stillbirth for Fetuses With Specific Birth Defects
Authors: Heinke Dominique , Nestoridi Eirini , Hernandez-Diaz Sonia , Williams Paige L. , Rich-Edwards Janet W. , Lin Angela E. , Van Bennekom Carla M. , Mitchell Allen A. , Nembhard Wendy N. , Fretts Ruth C. , Roberts Drucilla J. , Duke C. Wes , Carmichael Suzan L. , Yazdy Mahsa M. ,   for the National Birth Defects Prevention Study
Published: December 2019

OBJECTIVE:

To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects.

METHODS:

We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified.

RESULTS:

Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0–57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368–623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7–15), transverse limb deficiencies (26; 95% CI 16–39), longitudinal limb deficiencies (11; 95% CI 3–28), and limb defects due to amniotic bands (110; 95% CI 68–171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2–47), isolated spina bifida (24/1,000; 95% CI 17–34), and holoprosencephaly (30/1,000; 95% CI 10–68).

CONCLUSION:

Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis.
Intramedullary Cage Fixation for Proximal Humerus Fractures Has Low Reoperation Rates at 1 Year: Results of a Multicenter Study
Authors: Goodnough Lawrence Henry , Campbell Sean T. , Githens Thomas C. , DeBaun Malcolm R. , Bishop Julius A. , Gardner Michael J.
Published: December 2019

Objectives:

To determine reoperation rates after treatment of a proximal humerus fracture with cage fixation.

Design:

Retrospective case series.

Setting:

Eleven U.S. hospitals.

Patients:

Fifty-two patients undergoing surgical treatment of proximal humerus fractures.

Intervention:

Open reduction and internal fixation of a proximal humerus fracture with a proximal humerus cage.

Main Outcome Measurements:

Reoperation rate at 1 year.

Results:

At a minimum follow-up of 1 year, reoperations occurred in 4/52 patients (7.7%). Avascular necrosis (2/41) occurred in 4.9% of patients.

Conclusion:

Standard locked plating remains an imperfect solution for proximal humerus fractures. Proximal humerus cage fixation had low rates of revision surgery at 1 year. Proximal humerus cage fixation may offer reduced rates of complication and reoperation when compared with conventional locked plating for the management of proximal humerus fractures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Neurological Outcome and Complications in Patients With Surgically Treated Spinal Metastases
Authors: de Andrade Erion Junior , Martins Samilly Conceição Maia , Formentin Cleiton , Turolo Otávio , Vasconcelos Victor Leal de , Ghizoni Enrico , Tedeschi Helder , Joaquim Andrei Fernandes
Published: December 2019

Study Design.

Retrospective cohort.

Objective.

Evaluate the epidemiology of surgical patients with spinal metastases, identify the complications, and evaluate their neurological prognoses.

Summary of Background Data.

The development of new oncological treatments and screening tests have increased the survival of oncologic patients, and consequently, the incidence of metastatic lesions of the spine.

Methods.

Retrospective cohort of 40 patients surgically treated at the Hospital de Clínicas of UNICAMP for spinal metastases from January 2010 to September 2018, after diagnosis of symptomatic spinal cord compression and/or mechanical instability of the spine. Retrospectively analyzed patient charts applied the SINS score to evaluate the presence of mechanical instability. Neurological function was classified based on the Frankel index preoperative and postoperatively. To evaluate the association between variables, the Chi-square test, Fisher exact test, or Fisher–Freeman–Halton test was applied. For evaluating the improvement of neurological status between the Frankel scores before and after surgery, the McNemar test was applied for categorical and qualitative variables. In both the tests, variables with values of P > 0.05 were considered.

Results.

Pain as the reason for the first visit presented an odds ratio (OR) = 2.44 (95% [CI]: 1.14–5.2) for instrumentation need (P = 0.024). A higher SINS score corresponded to the indication for instrumentation surgery due to the instability of the spine (P = 0.004). Within 30 days postoperative, five patients (11.1%) had complications. There was a statistically significant neurological improvement in patients who underwent surgery (P = 0.002).

Conclusion.

Pain as the first symptom was related to mechanical instability of the spine and surgical instrumentation. Patients treated with surgery presented improvement of the neurological function in the postoperative period.

Level of Evidence: 3
Pedicle Screw Instrumentation in Scoliosis Surgery
Authors: Peiro-Garcia Alejandro , Teles Alisson R. , Ojaghi Reza , Ferri-de-Barros Fábio
Published: December 2019

Study Design.

Prospective experimental study with on-site simulation.

Objective.

To compare the accuracy and efficiency of different techniques for pedicle screw instrumentation (PSI).

Summary of Background Data.

Improving the safety and efficiency of PSI is a critical step to reduce the complication rates and the cost of scoliosis surgery. Innovative operative techniques for PSI have shown to safely improve efficiency, thereby reducing cost. Surgical simulation is a valuable tool to study different operative techniques.

Methods.

Five spine fellows instrumented 20 simulation models of a scoliotic spine with 10 pedicle screws per model. Four techniques were studied, including the conventional pedicle probe and the innovative sequential drilling technique, with or without computed tomography (CT)-based navigation. Our primary outcome measures were efficiency and accuracy of PSI. We analyzed the data with bivariate analyses using the Chi-square test for categorical variables and the Student t test or ANalysis Of VAriance with Bonferroni post-hoc tests for continuous variables.

Results.

The drilling techniques (free hand and navigated) were more efficient as compared with the pedicle probe techniques (P < 0.01). The navigated techniques resulted in better accuracy as compared with the free hand techniques (P = 0.036). Most pedicle breaches were medial (n = 32/52). The concave apical pedicle (T4 right side) had the highest incidence of breaches. There was no significant difference in efficiency comparing the free hand and the navigated pedicle probe techniques (P = 0.261) or comparing the free hand drilling and the navigated drilling techniques (P = 1.00).

Conclusion.

On site surgical simulation is a promising concept for teaching advanced procedural skills. Our findings suggest that navigation improves the accuracy of PSI while sequential drilling safely improves efficiency. Combining navigation with sequential drilling can significantly improve the accuracy and the efficiency of PSI in scoliosis surgery, as previously suggested with our published clinical data.

Level of Evidence: 4
Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury*
Authors: Cronin John N. , Crockett Douglas C. , Farmery Andrew D. , Hedenstierna Göran , Larsson Anders , Camporota Luigi , Formenti Federico
Published: December 2019

Objectives:

Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.

Design:

Preclinical study.

Setting:

Research laboratory.

Subjects:

Seven anesthetized pigs 28.7 kg (sd, 2.1 kg).

Interventions:

All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.

Measurements and Main Results:

Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20–40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729–908 µL/g]) than the dependent region (149 µL/g [120–178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12–46 µL/g]) and increased in the dependent region (39 µL/g [30–48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20–40% groups (r
2 = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r
2 = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with Pao
2/Fio
2 ratio (ρ = –0.77 and –0.93, respectively).

Conclusions:

In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening Pao
2/Fio
2.
Out of the Foxhole
Authors: Wynn Stephanie T.
Published: December 2019

As more veterans apply to nursing programs, nurse educators must acknowledge that many veterans are disadvantaged by moral injury and spiritual distress resulting from their military service. University faculty, in collaboration with Veterans Administration healthcare services, have found that referring students with unresolved spiritual distress to the Building Spiritual Strength intervention is a beneficial faith-based means for students to learn to manage their struggles and continue their education.
The 10 Cow Project
Authors: Johanson Linda
Published: December 2019

Using lessons from a modern parable about the 10-cow bride, a short-term medical missions team created a sustainable program for Ugandans, helping establish businesses for needy families by providing start-up farm animals. Christian nurses can partner with those in veterinary medicine to provide essential training related to health promotion and prevention of disease transmission in order to promote positive long-term outcomes of such projects.
A Community Respite Ministry/University Partnership Creates Meaningful Elder-Care Experiences
Authors: Yordy Morgan , Hare Julie
Published: December 2019

As the North American population of older adults increases, so does the need for nursing students to gain skills in geriatric care. Locating appropriate clinical sites for undergraduate students, including community and health promotion opportunities, prompted a public university's school of nursing to partner with a faith-based respite program. The collaboration between a public educational institution and a church-based program benefited the geriatric participants, the program leadership, and the nursing students and faculty.
Sequencing Ipilimumab Immunotherapy Before or After Chemotherapy (Nab-Paclitaxel and Bevacizumab) for the Treatment of BRAFwt (BRAF Wild-Type) Metastatic Malignant Melanoma
Authors: Markovic Svetomir N. , Suman Vera J. , Javed Asad , Reid Joel M. , Wall Darci J. , Erickson Lori A. , Ernstoff Marc , Anderson Daniel M.
Published: December 2019

Objectives:

With the introduction of novel immune therapeutics for the treatment of disseminated malignancies, we sought to evaluate whether deliberate sequencing of immunotherapy before/after conventional cytotoxic chemotherapy would have an impact on clinical outcomes in patients with previously treated metastatic melanoma. We sought to evaluate whether or not ipilimumab immunotherapy administered before or after cytotoxic chemotherapy (nab-paclitaxel+bevacizumab, AB) would impact clinical outcomes.

Methods:

We conducted a randomized phase 2 clinical trial of patients with BRAF wild-type metastatic melanoma (up to 2 prior therapies) who received either: (A) AB followed by ipilimumab therapy at progression; or (B) ipilimumab followed by AB treatment at progression. The primary goal of the study was a comparison of AB versus ipilimumab progression-free survival, with secondary clinical and laboratory endpoints.

Results:

This study did not reach full accrual due to concurrent Food and Drug Administration approval of anti-programmed cell death 1 agents. Nevertheless, the available data suggests a cumulative therapeutic advantage to the sequential use of ipilimumab followed by AB. Correlative laboratory data revealed a favorable effect on systemic immune homeostasis in patients receiving AB therapy, of potential interest in further investigations, especially in the context of chemotherapy/immunotherapy combinations.

Conclusion:

Albeit limited in scope, our data suggest that cytotoxic therapy with nab-paclitaxel and bevacizumab appear to favorably alter systemic parameters of immune function of potential benefit in combination T-cell directed immune checkpoint inhibitor therapy.
Clinical Evaluation of the “Lifeline Suture” Technique for DSAEK in Cases Without Posterior Capsule Using a Novel Donor Insertion Device
Authors: Yokogawa Hideaki , Kobayashi Akira , Mori Natsuko , Nishino Tsubasa , Sugiyama Kazuhisa
Published: December 2019

Purpose:

This study investigated preliminary clinical outcomes of a suture pull-through technique for Descemet stripping automated endothelial keratoplasty (DSAEK) termed the “lifeline suture” technique using a newly developed donor inserter (NS Endo-Inserter: NSI; Hoya Co, Ltd, Tokyo, Japan) in cases of bullous keratopathy without posterior capsule.

Methods:

Six aphakic eyes without posterior capsule from 6 patients (mean age 73.8 ± 11.9 years) with bullous keratopathy were enrolled. DSAEK alone or as a vitreocorneal surgery was performed. Donor tissue was pulled into the anterior chamber using the NSI and a 9-0 polypropylene “lifeline suture” to prevent donor tissue from slipping into the vitreous cavity, which was removed at the end of surgery. Intraoperative and postoperative complications and 6-month postoperative central donor endothelial cell densities were measured and compared with preoperative values along with 6-month best-corrected visual acuity.

Results:

All donors were successfully loaded into the NSI and then pulled into the anterior chamber using the lifeline suture. No intraoperative complications, graft dislocation, or primary graft failures were noted. Six months postsurgery, mean endothelial cell density was 2027 ± 747 cells/mm2 (mean loss 27.2 ± 28.1%) and mean best-corrected visual acuity improved to 0.31 decimal (P = 0.018).

Conclusions:

In this preliminary case series of bullous keratopathy without posterior capsule, DSAEK outcomes using the novel NSI donor inserter with lifeline suture were comparable or better than the results expected with conventional strategies. Thus, this technique enabled apparently safe DSAEK, preventing donor migration into the vitreous cavity while maintaining a stable anterior chamber, and is suitable for complex eyes including aphakia, lacking posterior capsule, or avitreal.
Evaluation of Electronic Health Record Implementation in an Academic Oculoplastics Practice
Authors: Chen Allison J. , Baxter Sally L. , Gali Helena E. , Long Christopher P. , Ozzello Daniel J. , Liu Catherine Y. , Korn Bobby S. , Kikkawa Don O.
Published: December 2019

Purpose:

Despite increasing electronic health record (EHR) adoption, perceptions of EHRs are negative among ophthalmologists due to concerns about productivity, costs, and documentation. The authors evaluated the effects of EHR adoption in an oculoplastics practice, which had not been previously studied.

Methods:

Clinical volume, documentation time, time spent with patients, reimbursement, relative value units, and patient satisfaction were examined for 2 academic oculoplastics attendings between April 2018 and April 2019, with EHR implementation in September 2018.

Results:

The mean number of patients seen in a half-day clinic was 31.8 versus 27.7 (p = 0.018) pre- and post-EHR implementation, respectively. EHR implementation had no effect on total monthly reimbursement (p = 0.88) or total monthly relative value units (p = 0.54). Average reimbursement (p = 0.004) and relative value units (p = 0.001) per patient encounter were significantly greater with EHR use. Patient satisfaction scores improved (p = 0.018). Mean physician time per patient increased from 6.4 to 9.0 minutes (p < 0.001). Mean documentation time per patient increased from 1.7 to 3.6 minutes (p < 0.001). Average patient wait times decreased by 9 minutes (p = 0.03) with EHR use. No scribes were used.

Conclusions:

EHR implementation was associated with decreased patient volume without significant differences in total reimbursement. Although EHR adoption was associated with increased physician time devoted to patients and greater time expenditure on documentation, patients experienced decreased wait times. This suggests that EHR use streamlined the overall clinic flow without sacrificing physicians’ time with the patient. The author’s findings suggest that EHR implementation can be accomplished in an academic oculoplastics setting without negative impact on patient experience or reimbursement considerations.
Psychiatric and Other Medical Manifestations of Nitrous Oxide Abuse
Authors: Chien Wan-Hsi , Huang Ming-Chyi , Chen Lian-Yu
Published: December 2019

Background

Nitrous oxide (N2O), a commonly used anesthetic agent in dentistry, has emerged as a global public health threat in young population. Although N2O-related neurological sequelae such as spinal cord degeneration and sensorimotor peripheral neuropathy are well known, psychiatric manifestations of heavy N2O use remain unclear. Here, we presented 7 treatment-seeking patients with severe N2O use disorder to delineate the psychiatric profiles of N2O users in Asia.

Methods

Seven patients with severe N2O use disorder who sought treatment in Taipei City Psychiatric Center between 2017 and 2018 were enrolled. We used chart review method to retrospectively collect their clinical information including sociodemographics, psychiatric and substance history, urine toxicology findings, and treatment course.

Results

These N2O users all had diagnoses of severe N2O use disorder. They usually initiated N2O use in late adolescence and early adulthood. Six of them had histories of mood disorders; all of them reported other illicit substance use before using N2O. The main reasons for treatment seeking were irritability, psychotic symptoms, self-harm, or violent behaviors as four of them were given a diagnosis of substance-induced psychotic disorder. Urine drug screen showed negative for other illicit drug use except for 1 positive case for cannabis and 1 for amphetamine. Three of 7 cases were hospitalized because of the severity of their psychiatric symptoms and suicidal risk.

Conclusions

These cases with severe N2O use disorder showed high prevalence of psychotic symptoms and dangerous behaviors such as suicide or violence. This study highlights the addiction potential of N2O and its related adverse consequences in the psychiatric aspect.
TTF1-positive Papillary Epithelial Tumor of Pituitary: An Epithelial Variant of Pituicytoma?
Authors: Chatterjee Debajyoti , Lath Khushboo , Radotra Bishan D. , Gupta Ashok K. , Singh Paramjeet
Published: December 2019

Low-grade epithelial tumor of pituitary region with dominant papillary architecture is extremely rare. We describe a case of 20-year female who had a recurrent nonfunctioning pituitary tumor. Histologic examination revealed a low-grade epithelial tumor with predominant papillary architecture, lined by cuboidal to columnar epithelial cells. The tumor cells were immunpositive for cytokeratin (CK), CK7, epithelial membrane antigen, carcinoembryonic antigen and showed diffuse and strong nuclear positivity for thyroid transcription factor 1. They were negative for neuroendocrine markers and pituitary hormones. Ki-67 proliferation index was low (1%). Ultrastructural examination revealed presence of microvilli, intercellular tight junctions, and keratin filaments within the tumor cells and lack of neurosecretory granules. No lesion was identified in thyroid or lung on systemic evaluation. On the basis of the morphology, immunophenotype, ultrastructural findings, and diffuse thyroid transcription factor 1 positivity, this tumor may represent an epithelial variant of pituicytoma with dominant papillary architecture. This type of differentiation is extremely rare, and to the best of our knowledge, has not been described previously in the literature.
Validation of the QR1 Antibody for the Evaluation of PD-L1 Expression in Non–Small Cell Lung Adenocarcinomas
Authors: Brandone Nicolas , Mascaux Céline , Caselles Kevin , Rouquette Isabelle , Lantuejoul Sylvie , Garcia Stéphane
Published: December 2019

The evaluation of Programmed cell Death Ligand 1 (PD-L1) expression in the tumor cells with immunohistochemistry is a mandatory diagnostic step in the treatment of lung cancer. It is important to utilize validated antibodies that can reliably detect PD-L1 positive cells. Different antibodies have already been studied. In this present study, we compared a new clone (QR1, Quartett) with reference clones to determine if it can be used in place of previously identified reference clones. We built a tissue micro array (TMA) from 110 lung adenocarcinomas and compared it using immunohistodetection of four different clones: QR1, 22c3, Sp263, and E1L3N. We analyzed the correlation between the sample duplicates for each clone and then a correlation and the concordance between the clones were calculated. A total of 101 patients were exploitable; the duplicates for each clone had a strong correlation. The correlation was the strongest (r=0.82) between QR1 and 22c3 and less strong with the other clones. Totals of 78%, 79%, and 97% of the QR1 cases were concordant with 22c3 for the thresholds of <1%, 1% to 49%, and ≥50%, respectively. The sensitivities and specificities of QR1, compared with 22c3, were >75% and 81%, respectively. PD-L1 expression, analyzed in lung adenocarcinomas with QR1, is highly correlated and concordant with the main reference clone used in most laboratories (22c3). It can be used to replace the latter in clinical routine.
Brief Report: Randomized Controlled Trial of an Intervention to Match Young Black Men and Transwomen Who Have Sex With Men or Transwomen to HIV Testing Options in New York City (All About Me)
Authors: Frye Victoria , Nandi Vijay , Hirshfield Sabina , Chiasson Mary Ann , Wilton Leo , Usher DaShawn , Hoover Donald R. , Koblin Beryl A.
Published: December 2019

Background:

HIV testing is critical to HIV prevention and care. Infrequent HIV testing and late HIV diagnosis have been observed among young Black men who have sex with men and transwomen. Novel interventions to increase HIV testing rates among young Black men who have sex with men and transwomen are needed.

Methods:

A randomized controlled trial among 236 young Black men and transwomen who have sex with men or transwomen evaluated the efficacy of an intervention that included completion of a brief survey and receipt of a personalized recommendation of an optimal HIV testing approach. Participants completed a computerized baseline assessment and were randomized to electronically receive either a personalized recommendation or standard HIV testing information. Follow-up surveys were conducted online at 3 and 6 months.

Results:

Retention was 92% and 93% at 3-month and 6-month follow-up, respectively. At baseline, 41% of participants reported that they tested for HIV in the past 3 months and another 25% between 4 and 6 months ago. Intent-to-treat analyses found that participants randomized to the experimental arm (personalized recommendation) were not significantly more likely to test for HIV compared with participants in the standard HIV testing information control arm at 3 months (76% vs. 71%; P = 0.40) and 6 months (73% vs. 72%; P = 0.81), respectively.

Conclusions:

This study evaluated an innovative intervention to increase HIV testing by matching individuals to optimal HIV testing approaches. Participants in both arms increased past 3-month HIV testing, suggesting that providing information on options and/or raising risk awareness is sufficient to significantly increase HIV testing.

Trial registration:

ClinicalTrial.gov NCT02834572 https://clinicaltrials.gov/ct2/show/NCT02834572.
High- and Low-Contrast Letter Acuity Perception Matures With Age in Normally Sighted Children
Authors: Waldman Amy T. , Lavery Amy M. , Liu Geraldine W. , Avery Robert A. , Liu Grant T. , Maguire Maureen G. , Ying Gui-shuang , Banwell Brenda L.
Published: December 2019

Background:

High-contrast visual acuity (HCVA) changes with age, yet little is known about pediatric-specific age- and sex-normative values for low-contrast letter acuity (LCLA). We define maturational changes in monocular and binocular HCVA and LCLA in childhood and adolescence.

Methods:

Normally sighted youth (ages 5–20 years, without neurologic or ophthalmologic disease and best-corrected HCVA of 20/25 or better in each eye) were recruited. Mean monocular and binocular scores using Early Treatment Diabetic Retinopathy Study (for HCVA) and 2.5% and 1.25% Sloan (for LCLA) charts and the magnitude of binocular summation were calculated using 2-year bins. Relationships between scores and age were explored using scatterplots with Locally Weighted Scatterplot Smoothing (LOWESS) and analysis of variance that accounts for intereye correlation, followed by test of linear trend for age effect.

Results:

Among 101 (202 eyes) healthy participants (mean age 13 years, 42% males), monocular and binocular scores varied by age, with highest mean scores achieved in the 13 to 14–year age group for both HCVA and LCLA. Between the ages of 5 and 14.9 years, monocular scores increased linearly with age (0.76 letter/year for HCVA, 1.11 letters/year for 2.5% LCLA, and 0.97 letter/year for 1.25% LCLA; allP< 0.0001). Binocular HCVA scores also increased with age between 5 and 14.9 years (0.71 letters/year,P< 0.0001). The magnitude of binocular summation for HCVA or LCLA did not change with age.

Conclusions:

HCVA and LCLA abilities mature into adolescence, peak between 13 and 14.9 years of age, and then plateau into adulthood. Evaluation of patients with visual deficits should consider age-expected normal visual acuity.
Knowledge Driven Phenotyping
Authors: Wu Honghan , Wang Minhong , Zeng Qianyi , Chen Wenjun , Pan Jeff Z. , Sudlow Cathie , Robertson Dave
Published: December 2019

Extracting patient phenotypes from routinely collected health data (such as Electronic Health Records) requires translating clinically-sound phenotype definitions into queries/computations executable on the underlying data sources by clinical researchers. This requires significant knowledge and skills to deal with heterogeneous and often imperfect data. Translations are time-consuming, error-prone and, most importantly, hard to share and reproduce across different settings. This paper proposes a knowledge driven framework that (1) decouples the specification of phenotype semantics from underlying data sources; (2) can automatically populate and conduct phenotype computations on heterogeneous data spaces. We report preliminary results of deploying this framework on five Scottish health datasets.
Local authority variation in uptake of the HPV vaccine in Greater Manchester and school-level factors: a cross-sectional ecological study
Authors: Senior Steven L. , Fletcher Rebecca , Cleary Paul , Farmer Siobhan
Published: December 2019

Background

Human papillomavirus (HPV) is the main cause of cervical cancer and contributes to a number of other cancers that affect both men and women. Vaccines exist that offer protection against the most common cancer-causing HPV types. In England, a school-based vaccination programme for girls has been in place since 2008 but vaccine coverage rates have declined since its introduction. Understanding variation between schools and between local authorities may help to inform quality improvement and guide policy development and commissioning.

Methods

Cross-sectional, ecological analysis of vaccine uptake among 164 schools representing 13,127 children in eight out of ten local authorities in Greater Manchester. Logistic mixed effects regression models were used to test for associations between school level factors and vaccine uptake, while allowing for variation between local authorities.

Results

In multivariable mixed effects models, lower vaccination rates were associated with: increasing numbers of children eligible for vaccination; increasing proportions of children eligible for free school meals; increasing proportions of children with English as an additional language; Ofsted ‘inadequate’ ratings; Christian and Muslim faith schools; independent schools and special schools.

Conclusions

Consistent with previous studies on vaccine uptake, this study identifies a number of factors that are associated with uptake of the school-based HPV vaccine programme. We also show that local authority variation remains after adjustment for the mix of schools in each area. This evidence may be used to guide vaccine providers, commissioners, and policymakers who want to increase uptake of the school-based HPV vaccine.
Comparison of intradermal injection and epicutaneous laser microporation for antitumor vaccine delivery in a human skin explant model
Authors: Duinkerken Sanne , Lübbers Joyce , Stolk Dorian , Vree Jana , Ambrosini Martino , Kalay Hakan , van Kooyk Yvette
Published: December 2019

Human skin is a prime vaccination site containing multiple antigen presenting cells (APC), including Langerhans cells (LC) and dendritic cells (DC). APC deliver antigens to lymph nodes for induction of adaptive immunity through stimulating antigen specific T- and B-cells. Since intradermal (ID) injections require specific training, easy applicable delivery systems like laser microporation are emerging. In mice, combination of laser treatment and allergen injection showed enhanced T-cell responses and skewing of B-cell responses without adjuvants. However, it remains to be elucidated whether laser microporation can alter human skin DC phenotype and function without adjuvants. In an ex-vivo human skin explant model, we compared ID injection and laser microporation as anti-tumor vaccination strategy. A melanoma specific synthetic long peptide and multivalent dendrimer with gp100 antigen were used as vaccine formulation to measure APC phenotype, emigration and ability to stimulate gp100 specific CD8+ T-cells. We show that skin APC phenotype and emigration capacity was similar after laser microporation and ID injection. However, laser microporation reduced vaccine uptake by APC, resulting in decreased induction of gp100 specific CD8+ T-cell activation. To conclude, in our human skin model ID injection remains the most potent strategy to deliver antigens to skin APC for T-cell induction.

Graphical Abstract
ReferenceSeeker: rapid determination of appropriate reference genomes
Authors: Schwengers O. , Hain T. , Chakraborty T. , Goesmann A.
Published: December 2019

The large and growing number of microbial genomes available in public databases makes the optimal selection of reference genomes necessary for many in-silico analyses, e.g. single nucleotide polymorphism detection, scaffolding and comparative genomics, increasingly difficult. Here, we present ReferenceSeeker, a novel command line tool combining a fast kmer profile-based database lookup of candidate reference genomes with subsequent calculation of highly specific average nucleotide identity (ANI) values for the rapid determination of appropriate reference genomes. Pre-built databases for bacteria, archaea, fungi, protozoa and viruses based on the RefSeq database are provided for download.

Availability and Implementation

ReferenceSeeker is open source software implemented in Python. Source code and binaries are freely available for download at https://github.com/oschwengers/referenceseeker under the GNU GPL3 license.

Contact

referenceseeker@computational.bio
Bipartite functional fractionation within the default network supports disparate forms of internally oriented cognition
Authors: Chiou Rocco , Humphreys Gina F. , Lambon Ralph Matthew A.
Published: December 2019

The ‘default network’ (DN) becomes active when the mind is steered internally towards self-generated thoughts but turns dormant when the mind is directed externally towards the outside world. While hypotheses have been proposed to characterise the association and dissociation between different component areas of the DN, it remains unclear how they coalesce into a unitary network and fractionate into different sub-networks. Here we identified two distinct subsystems within the DN – while both subsystems show common disinterest in externally-oriented visuospatial tasks, their functional profiles differ strikingly according to the preferred contents of thoughts, preferred modes of task requirement, and causative neural dynamics among network nodes. Specifically, one subsystem comprises key nodes of the frontotemporal semantic regions. This network shows moderate dislike to visuospatial tasks, shows proclivity for task-contexts with restraints on thoughts and responses, and prefers thoughts that are focused on other people. By contrast, the other subsystem comprises the cortical midline structure and angular gyri. This network shows strong aversion to visuospatial tasks, favours task-contexts allowing free self-generated thoughts without constraints, and prefers thoughts that are focused on self. Furthermore, causative connectivity reveals that task-contexts systematically alter the dynamics within and between subsystems, suggesting flexible adaption to situational demands. This ‘self/inward vs. others/outward’ separation within the broad DN resembles recent discoveries regarding a dyadic structure within the frontoparietal network that comprises regions controlling memories/thoughts vs. regions controlling sensory-motoric processes, and echoes burgeoning views that the brain is organised with a spectrum-like architecture along gradational changes of ‘inward vs. outward’ preferences.

Significance

Rather than construing the default network (DN) as ‘task-negative’ regions that passively react to off-task mind-wandering, researchers have begun to acknowledge the active role of the DN in supporting internally-directed cognition. Here we found a striking dichotomy within the DN in terms of the subsystems’ task-driven functional and connectivity profiles, extending beyond previous inferences using meta-analysis and resting-state fMRI. This dichotomy reflects a local manifestation of a macro-scale gradient representation spanning across the broad cerebral cortex. This cortical gradient increases its representational complexity, from primitive sensory and motoric processing, through lexical-semantic codes for language tasks, to abstract self-generated thoughts in task-free contexts. These findings enable a framework where the separate yet related literatures of semantic cognition and default-mode processes converge.
Ecophysiological traits of a clonal grass in its climate change response
Authors: Kosová Veronika , Hájek Tomáš , Hadincová Věroslava , Munzbergova Zuzana
Published: December 2019

Background

Understanding the ability of species to respond to climate change is essential for prediction of their future distribution. When migration is not adequate, reaction via phenotypic plasticity or genetic adaptation is necessary. While many studies investigated the importance of plasticity and genetic differentiation (plant origin) in growth related traits, we know less about differentiation in ecophysiological traits. In addition, the existing studies looking at plant physiology usually do not estimate the consequences of these physiological changes for species performance.

Methods

We used a clonal grass Festuca rubra originating from localities representing factorially crossed gradients of temperatures and precipitations. We cultivated the plants in growth chambers set to simulate temperature and moisture regime in the four most extreme localities. We measured net photosynthetic rate, chlorophyll fluorescence, SLA, osmotic potential, stomatal density and stomatal length as range of ecophysiological traits and tested their relationship to plant fitness measured as ramet number and biomass.

Key results

We found strong phenotypic plasticity in photosynthetic traits and genetic differentiation in stomatal traits. In most traits, the effects of temperature interacted with the effects of moisture. The relationship between the ecophysiological and fitness-related traits was significant but weak.

Conclusions

Ecophysiological response of Festuca rubra to climate change is driven by phenotypic plasticity as well as by genetic differentiation indicating potential ability of the populations to adapt to new climatic conditions. The changes in ecophysiological traits translate into plant fitness even though other unmeasured factors also play an important role in fitness determination. Inclusion of species ecophysiology into studies of species adaptation to climate can still increase our ability to understand how species may respond to novel conditions.
On deleterious mutations in perennials: inbreeding depression, mutation load and life-history evolution
Authors: Lesaffre Thomas , Billiard Sylvain
Published: December 2019

In Angiosperms, perennials typically present much higher levels of inbreeding depression than annuals. One hypothesis to explain this pattern stems from the observation that inbreeding depression is expressed across multiple life stages in Angiosperms. It posits that increased inbreeding depression in more long-lived species could be explained by differences in the way mutations affect fitness in these species, through the life stages at which they are expressed. In this study, we investigate this hypothesis. We combine a physiological growth model and multilocus population genetics approaches to describe a full genotype-to-phenotype-to-fitness map. We study the behaviour of mutations affecting growth or survival, and explore their consequences in terms of inbreeding depression and mutation load. Although our results only agree with empirical data within a narrow range of conditions, we argue that they may point us towards the type of traits susceptible to underlie inbreeding depression in long-lived species, that is traits under sufficiently strong selection, on which selection decreases sharply as life expectancy increases. Then, we study the role deleterious mutations maintained at mutation-selection balance may play in the coevolution between growth and survival strategies.

Description of the manuscript

The main text of the manuscript, excluding captions and headers, is 5712 words long. There are 4 figures in the main text, numbered from 1 to 4. In the present file, pages 1 to 33 correspond to the main text (including title page, abstract and litterature cited), while the remaining pages (33 to 72) correspond to appendices. There are 5 sections in Appendices, which are all available at the end of the manuscript file. There are 12 figures in Appendices, numbered from S1 to S12.
Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye
Authors: Miller Adam C. , Urban Elizabeth , Lyons Eric L. , Herman Tory G. , Johnston Robert J.
Published: December 2019

Diversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes inDrosophilais controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In SsONR7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in SsOFFR7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, activates expression of Spineless in a random subset of R7s. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.
Widespread use of the “ascidian” mitochondrial genetic code in tunicates
Authors: Pichon Julien , Luscombe Nicholas M. , Plessy Charles
Published: December 2019

Background

Ascidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI’s GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences.

Methods

We collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such asOikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes.

Results

All tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons.

Conclusions

We recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.