bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Selection Shapes Seminal Vesicle Secretion Gene Expression in House Mice
Authors: Simmons Leigh W , Sloan Nadia S , Firman Renée C
Published: December 2019

Reproductive proteins typically have high rates of molecular evolution, and are assumed to be under positive selection from sperm competition and cryptic female choice. However, ascribing evolutionary divergence in the genome to these processes of sexual selection from patterns of association alone is problematic. Here, we use an experimental manipulation of postmating sexual selection acting on populations of house mice and explore its consequences for the expression of seminal vesicle secreted (SVS) proteins. Following 25 generations of selection, males from populations subjected to postmating sexual selection had evolved increased expression of at least two SVS genes that exhibit the signature of positive selection at the molecular level, SVS1 and SVS2. These proteins contribute to mating plug formation and sperm survival in the female reproductive tract. Our data thereby support the view that sexual selection is responsible for the evolution of these seminal fluid proteins.
Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans
Authors: Reed Kailee J , Svendsen Joshua M , Brown Kristen C , Montgomery Brooke E , Marks Taylor N , Vijayasarathy Tarah , Parker Dylan M , Nishimura Erin Osborne , Updike Dustin L , Montgomery Taiowa A
Published: December 2019

Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) are distinct classes of small RNAs required for proper germline development. To identify the roles of piRNAs and siRNAs in regulating gene expression in Caenorhabditis elegans, we subjected small RNAs and mRNAs from the gonads of piRNA and siRNA defective mutants to high-throughput sequencing. We show that piRNAs and an abundant class of siRNAs known as WAGO-class 22G-RNAs are required for proper expression of spermatogenic and oogenic genes. WAGO-class 22G-RNAs are also broadly required for transposon silencing, whereas piRNAs are largely dispensable. piRNAs, however, have a critical role in controlling histone gene expression. In the absence of piRNAs, histone mRNAs are misrouted into the nuclear RNAi pathway involving the Argonaute HRDE-1, concurrent with a reduction in the expression of many histone mRNAs. We also show that high-level gene expression in the germline is correlated with high level 22G-RNA production. However, most highly expressed genes produce 22G-RNAs through a distinct pathway that presumably involves the Argonaute CSR-1. In contrast, genes targeted by the WAGO branch of the 22G-RNA pathway are typically poorly expressed and respond unpredictably to loss of 22G-RNAs. Our results point to broad roles for piRNAs and siRNAs in controlling gene expression in the C. elegans germline.
Interventions to Increase Completion of Hepatitis B Vaccination in People who Inject Drugs: A Systematic Review and Meta-analysis
Authors: Tressler Stacy , Bhandari Ruchi
Published: December 2019

Increases in opioid misuse and injection drug use have resulted in a rise in acute cases of hepatitis B. We conducted a systematic review and meta-analysis of randomized studies to determine the effect (pooled odds ratio) of interventions to increase hepatitis B vaccination completion in people who inject drugs (PWID). Odds ratios from the included studies were combined to create a pooled odds ratio (OR) using the Inverse Heterogeneity Model. Eleven studies met the eligibility criterion of having a randomized intervention to increase hepatitis B virus vaccination completion among PWID. The odds of vaccine completion in the intervention group were greater than in the control/comparison group (pooled OR, 2.53; 95% confidence interval [CI], 1.07–5.99). Subgroup analysis indicated that financial incentives were most effective (OR, 7.01; 95% CI, 2.88–17.06), followed by accelerated vaccine schedules (OR, 1.90; 95% CI, 1.14–3.14). Interventions using financial incentives and accelerated vaccine schedules are moderately effective at increasing hepatitis B vaccination completion in PWID.
The influence of Megasphaera elsdenii on rumen morphometrics of cull cows immediately stepped up to a high-energy finishing diet
Authors: DeClerck Jonathan C , Reeves Nathan R , Miller Mark F , Johnson Bradley J , Ducharme Gary A , Rathmann Ryan J
Published: December 2019

Forty-five beef cull cows [body weight (BW) = 503 ± 58 kg; body condition score (BCS) = 2.1 ± 0.6] were randomized into two treatments to compare the effects of oral drenching of no probiotic vs. 100 mL of Megasphaera elsdenii NCIMB 41125 (M. elsdenii culture; Lactipro Advance; 2 × 108 cfu/mL; MS Biotec, Inc., Wamego, KS) on the realimentation of cull cows. The study featured a rapid 0-d step-up of concentrate-naïve cull cows to a 90% concentrate diet (1.43 Mcal/kg of NEg). The cows were finished for 35 d and were fitted with a wireless rumination tag (Allflex Flex Tag; SCR Engineers, Ltd, Netanya, Israel), which tracked head movement to record eating and chewing activity. Rumen morphometrics was recorded on the harvest floor, with each carcass assigned a rumenitis score, and a fragment of the cranial sac removed for further papillae analysis. An additional 23, thin, non-fed cull cows were harvested at the same abattoir to compare the effects of concentrate realimentation on ruminal morphometrics. Megasphaera elsdenii culture-drenched cattle registered a 13.3% increase in rumination time (39.27 min/d, P = 0.03) during the first week of the trial compared to controls. A numerical rumination advantage for M. elsdenii culture-administered cattle was observed during week 2 of trial (P = 0.17), with no differences between treatments from weeks 3 to 5 (P ≥ 0.40). Subjective rumenitis evaluations approached a tendency (P = 0.12), with non-M. elsdenii culture-drenched concentrate-fed cattle logging twice the score of their day 0 cohorts (2.52 vs. 1.17) suggesting considerable lactic insults occurred to the ruminal epithelium in the short 35-d trial. Despite the short feeding duration, concentrate realimentation prompted a significant improvement in mean papillae area (P < 0.01). Among concentrate-fed treatments, M. elsdenii culture-drenched cattle posted superior absorptive surface area (P = 0.01) and a greater ratio of papillae area of absorptive surface area (P = 0.05), suggesting that M. elsdenii culture is favorably altering the ecology of the rumen and promoting papillae growth perhaps by mitigating lactate-driven pH drops. In conclusion, M. elsdenii culture application in a 0-d step-up protocol to finishing diets can help mitigate the effects of ruminal acidosis.
Expectant Management of Hypertensive Disorders of Pregnancy and Future Cardiovascular Morbidity
Authors: Rosenbloom Joshua I. , Lewkowitz Adam K. , Lindley Kathryn J. , Nelson D. Michael , Macones George A. , Cahill Alison G. , Olsen Margaret A. , Stout Molly J.
Published: December 2019

OBJECTIVE:

To test the hypothesis that a longer length of time between diagnosis of hypertensive disorders of pregnancy and delivery is associated with increased risk of cardiovascular morbidity in the years after delivery.

METHODS:

This is a retrospective cohort study based in the New York State Inpatient Database. The first delivery for all patients from 2005 to 2014 who delivered preterm with an International Classification of Diseases, 9th Revision, Clinical Modification code for hypertensive disorders of pregnancy (excluding isolated chronic hypertension) was included. The duration between diagnosis and delivery was divided into 7 days or less or more than 7 days. The primary outcome was admission for a composite of cardiovascular disease, stroke, or death after the index delivery through December 31, 2014.

RESULTS:

There were 22,594 patients with a median follow-up period of 5.2 years: 19,750 (87.4%) were delivered within 7 days of diagnosis and 2,844 (12.6%) were delivered more than 7 days from diagnosis. The primary outcome occurred in 216 (1.1%) patients in the 0–7 days group (21 events/10,000 person-years) and 67 (2.4%) patients in the more than 7 days group (46 events/10,000 person-years), adjusted hazard ratio 1.45 (95% CI 1.09 to 1.93). The findings were robust in a number of sensitivity analyses.

CONCLUSIONS:

Prolonged expectant management of preterm hypertensive disorders of pregnancy is associated with an increased risk of maternal cardiac disease in the ensuing years.
Interpersonal Trauma as a Marker of Risk for Urinary Tract Dysfunction in Midlife and Older Women
Authors: Boyd Brittni A. J. , Gibson Carolyn J. , Van Den Eeden Stephen K. , McCaw Brigid , Subak Leslee L. , Thom David , Huang Alison J.
Published: December 2019

OBJECTIVE:

To examine relationships between interpersonal trauma exposures and urinary symptoms in community-dwelling midlife and older women.

METHODS:

We analyzed cross-sectional data from a multiethnic cohort of women aged 40–80 years enrolled in an integrated health care system in California. Lifetime history of intimate partner violence (IPV) and sexual assault, current posttraumatic stress disorder (PTSD) symptoms, and current urinary symptoms were assessed using structured-item questionnaires. Multivariable-adjusted logistic regression models examined associations between traumatic exposures and PTSD symptoms with any weekly urinary incontinence, stress-type incontinence, urgency-type incontinence, and nocturia two or more times per night.

RESULTS:

Of the 1,999 participants analyzed, 21.7% women reported lifetime emotional IPV, 16.2% physical IPV, 19.7% sexual assault, and 22.6% reported clinically significant PTSD symptoms. Overall, 45% reported any weekly incontinence, 23% stress-type incontinence, 23% urgency-type incontinence, and 35% nocturia. Exposure to emotional IPV was associated with any weekly incontinence (odds ratio [OR] 1.33, 95% CI 1.04–1.70), stress-type incontinence (OR 1.30, 95% CI 1.00–1.65), urgency-type incontinence (OR 1.30, 95% CI 1.00–1.70), and nocturia (OR 1.73, 95% CI 1.36–2.19). Physical IPV exposure was associated with nocturia (OR 1.35, 95% CI 1.04–1.77), but not incontinence. Sexual assault history was not associated with weekly incontinence of any type or nocturia. Symptoms of PTSD were associated with all urinary symptoms assessed, including any weekly incontinence (OR 1.46, 95% CI 1.15–1.85), stress-type incontinence (OR 1.70, 95% CI 1.32–2.20), urgency-type incontinence (OR 1.60, 95% CI 1.24–2.06), and nocturia (OR 1.95, 95% CI 1.55–2.45).

CONCLUSION:

More than 20% of women in this multiethnic, community-based cohort reported a history of IPV, PTSD symptoms, or both, which were associated with symptomatic urinary tract dysfunction. Findings highlight the need to provide trauma-informed care of midlife and older women presenting with urinary symptoms.
Refining Angular Pregnancy Diagnosis in the First Trimester
Authors: Bollig Kassie J. , Schust Danny J.
Published: December 2019

OBJECTIVE:

To describe the natural history and outcomes of a large cohort of expectantly managed angular pregnancies diagnosed in the first trimester by specific ultrasound criteria.

METHODS:

We conducted a prospective case series of women with prenatally diagnosed angular pregnancy at a single academic tertiary care center from March 2017 to February 2019. Participants were identified at first-trimester ultrasound scan using specifically proposed diagnostic criteria for angular pregnancy and followed prospectively. Maternal and fetal data were gathered from the medical record.

RESULTS:

Forty-two cases of angular pregnancy were identified at first-trimester ultrasound scan. At presentation, 33 patients (79%) were asymptomatic, eight (19%) had vaginal bleeding, and two (5%) had pain. The mean gestational age at diagnosis was 7.4±1.0 weeks; the mean myometrial thickness was 5.1±1.6 mm (95% CI 4.6–5.6). At initial follow-up about 2 weeks later, 23 patients (55%) had ultrasound scans that normalized, 13 (31%) cases persisted as angular pregnancies, and six (14%) resulted in early pregnancy loss. After each gestation had been followed until completion, 33 (80%) pregnancies resulted in live birth and eight (20%) in early pregnancy loss. One patient was lost to follow-up. Of the 33 live births, 24 (73%) were vaginal deliveries, nine (27%) were cesarean deliveries, 27 (82%) were term deliveries, and six (18%) were preterm deliveries. There were no cases of uterine rupture, maternal death, abnormal placentation, or hysterectomy.

CONCLUSIONS:

In 42 cases of angular pregnancy diagnosed by first-trimester ultrasound examination, outcomes were largely positive, with an 80% live-birth rate and a 20% early pregnancy loss rate. Early diagnosis of angular pregnancy using the described criteria may represent an entity that more closely resembles a normal, noneccentric intrauterine pregnancy rather than an ectopic pregnancy. Therefore, most cases can be closely observed and efforts made to expectantly manage pregnancies while awaiting viability.
Information Women Choose to Receive About Prenatal Chromosomal Microarray Analysis
Authors: Hochner Hagit , Daum Hagit , Douiev Liza , Zvi Naama , Frumkin Ayala , Macarov Michal , Kimchi-Shaal Adva , Hacohen Nuphar , Eilat Avital , Faham Duha , Shkedi-Rafid Shiri
Published: December 2019

OBJECTIVE:

To examine the choices of women with both high-risk and low-risk pregnancies who are undergoing prenatal chromosomal microarray analysis in a clinical setting regarding three challenging types of findings: variants of uncertain clinical significance, susceptibility loci for neurodevelopmental disorders, and copy number variants associated with risks for adult-onset conditions. We assessed whether women's choices were associated with indications for testing or with one-on-one pretest genetic counseling.

METHODS:

In this cross-sectional study, medical records of women who underwent invasive prenatal chromosomal microarray analysis testing (N=1,070) at Hadassah Medical Center between June 2017 and February 2018 were examined for testing indications, choices regarding chromosomal microarray analysis findings, and type of pretest genetic counseling. Multivariable analyses to assess associations with testing indication and prior genetic counseling were carried out using logistic regression models.

RESULTS:

In total, 56% of women (n=593) chose to be informed of all three types of findings and 20% (n=218) chose not to be informed of any of the findings beyond high-penetrance childhood-onset pathogenic findings. Variants of uncertain clinical significance as a single choice was the least-selected finding (2.5%, n=27). Low-risk pregnancies (ie, those with normal biochemical screening and fetal ultrasound examinations) were associated with increased interest in receiving genetic information about adult-onset conditions (adjusted odds ratio [aOR] 1.7; 95% CI 1.18–2.33) and susceptibility loci (aOR 1.5; 95% CI 1.08–2.10).

CONCLUSION:

Women with both high-risk and low-risk pregnancies were generally more likely to choose to receive additional genetic information, albeit differences in preferences depend on testing indication and type of pretest counseling.
Severity of Preoperative Myelopathy Symptoms Affects Patient-reported Outcomes, Satisfaction, and Return to Work After Anterior Cervical Discectomy and Fusion for Degenerative Cervical Myelopathy
Authors: Goh Graham Seow-Hng , Liow Ming Han Lincoln , Ling Zhixing Marcus , Soh Reuben Chee Cheong , Guo Chang Ming , Yue Wai Mun , Tan Seang Beng , Chen John Li-Tat
Published: December 2019

Study Design.

Retrospective review of prospectively-collected registry data.

Objective.

To compare the patient-reported outcomes, satisfaction, and return to work among a large cohort of patients stratified by preoperative myelopathy severity undergoing Anterior Cervical Discectomy and Fusion (ACDF) for Degenerative Cervical Myelopathy.

Summary of Background Data.

Recent clinical practice guidelines noted a lack of studies stratifying their sample based on preoperative disease severity. The benefits of early surgical intervention for patients with mild myelopathy remain uncertain.

Methods.

A prospectively-maintained registry was retrospectively reviewed for all patients who underwent primary ACDF for Degenerative Cervical Myelopathy. Patients were stratified based on severity of preoperative myelopathy symptoms according to the Japanese Orthopaedic Association (JOA) scale: mild (>13), moderate (9–13), or severe (<9). Patients were prospectively followed for at least 2 years.

Results.

In total, 219 patients were included: 74 mild, 94 moderate, and 51 severe cases. The mild group had significantly better Neurogenic Symptoms (NS), Neck Disability Index (NDI), SF-36 Physical (PCS), and Mental Component Summary at baseline (P < 0.05). Neck and arm pain scores were similar at all time points. At 2 years, the severe group still had significantly worse patient-reported outcomes and lower rates of satisfaction, expectation fulfilment and return to work. However, they had significantly greater improvement in JOA, Neurogenic Symptoms, NDI, PCS, and Mental Component Summary, and a larger proportion attained minimal clinically important difference (MCID) for NDI and PCS. All three groups had similar proportions attaining MCID for JOA.

Conclusion.

Patients with severe myelopathy experienced a greater improvement after ACDF. Although fewer patients attained MCID, early surgical intervention for patients with mild myelopathy should also be considered, as this may allow patients to maintain their higher functional status. They also had high rates of postoperative satisfaction and return to work. The clinical trajectory outlined in this study may provide valuable prognostic information for patients.

Level of Evidence: 3
Association of leukocyte telomere length with non-alcoholic fatty liver disease in patients with type 2 diabetes
Authors: Zhang Min , Hu Man-Li , Huang Jiao-Jiao , Xia San-Shan , Yang Yan , Dong Kun
Published: December 2019

Background:

Leukocyte telomere has been shown to be related to insulin resistance-related diseases, such as type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study investigated the association of leukocyte telomere length (LTL) with NAFLD in T2DM patients.

Methods:

Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length analysis in 120 T2DM patients without NAFLD and 120 age-matched T2DM patients with NAFLD. NAFLD was clinically defined by manifestations of ultrasonography. The correlation between LTL and clinical and biochemical parameters were analyzed by Pearson correlation or Spearman correlation analysis. Factors for NAFLD in T2DM patients were identified using multiple logistic regressions.

Results:

LTL in T2DM patients with NAFLD were significantly longer than those without NAFLD (6400.2 ± 71.8 base pairs [bp] vs. 6023.7 ± 49.5 bp, P < 0.001), especially when diabetes duration was less than 2 years. Meanwhile, the trend of shorter LTL was associated with the increased diabetes duration in T2DM patient with NAFLD, but not in T2DM patients without NAFLD. Finally, LTL (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.002, P = 0.001), as well as body mass index (OR: 1.314, 95% CI: 1.169–1.477, P < 0.001) and triglycerides (OR: 1.984, 95% CI: 1.432–2.747, P < 0.001), had a significant association with NAFLD status in T2DM patients.

Conclusions:

T2DM patients with NAFLD had a significantly longer LTL than those without NAFLD. The longer LTL was especially evident in the early stage of T2DM, indicating that longer LTL may be used as a biomarker for NAFLD in T2DM patients.
New therapeutic approaches for endometriosis besides hormonal therapy
Authors: Chen Fang-Ying , Wang Xi , Tang Rui-Yi , Guo Zai-Xin , Deng Yu-Zhou-Jia , Yu Qi
Published: December 2019

Objective:

Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis

Data sources:

Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms “endometriosis” and “non-hormonal therapy.”

Study selection:

Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English.

Results:

Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies.

Conclusions:

Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.
Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Recurrence
Authors: Viani Gustavo A. , Arruda Caio V. , Hamamura Ana C. , Faustino Alexandre C. , Freitas Bendo Danelichen Anielle , Guimarães Flavio S.
Published: December 2019

Purpose:

The purpose of this study was to evaluate the treatment efficacy of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer recurrence and to assess whether there is any relationship between biologically effective dose (BED) and local control (LC).

Materials and Methods:

Eligible studies were identified on Medline, Embase, and the Cochrane Library, and the proceedings of annual meetings through May 2019 were also identified. A meta-regression analysis was performed to assess whether there is a relationship between BED and LC. In the univariate analysis, studies were separated by the study design, the number of metastatic sites, the site of metastases, radiotherapy machine, and prostate-specific antigen level at the time of SBRT. A P-value <0.05 was considered significant.

Results:

Twenty-three observational studies with a total of 1441 lesions treated were included in the meta-analysis. The proportional rate of LC, progression-free survival, and androgen deprivation–free survival was 0.976 (95% confidence interval [CI]: 0.96-0.98), 0.413 (95% CI: 0.378-0.477), and 20.1 months (95% CI: 14.5-25.6), respectively. In the meta-regression, a linear relationship between BED and LC was detected (P=0.017). Stratifying the BED into 3 levels (BED<100 Gy3, BED 100 to 130 Gy3, and BED>130 Gy3), a significant difference was observed between BED<100 Gy3 (LC=88%) versus BED>100 Gy3 (LC=96%). The rate of any acute and late grade ≥2 toxicity was 1.3% and 1.2%, respectively.

Conclusions:

The LC rate with SBRT was excellent with minimal severe acute/late toxicity. Our data suggest a dose relationship between BED and LC, with BED >100 Gy3 resulting in better rates of LC.
Methods to Account for Uncertainty in Latent Class Assignments When Using Latent Classes as Predictors in Regression Models, with Application to Acculturation Strategy Measures
Authors: Elliott Michael R. , Zhao Zhangchen , Mukherjee Bhramar , Kanaya Alka , Needham Belinda L.
Published: December 2019

Latent class models have become a popular means of summarizing survey questionnaires and other large sets of categorical variables. Often these classes are of primary interest to better understand complex patterns in data. Increasingly, these latent classes are reified into predictors of other outcomes of interests, treating the most likely class as the true class to which an individual belongs even though there is uncertainty in class membership. This uncertainty can be viewed as a form of measurement error in predictors, leading to bias in the estimates of the regression parameters associated with the latent classes. Despite this fact, there is very limited literature treating latent class predictors as measurement error models. Most applications ignore this issue and fit a two-stage model that treats the modal class prediction as truth. Here, we develop two approaches—one likelihood-based, the other Bayesian—to implement a joint model for latent class analysis and outcome prediction. We apply these methods to an analysis of how acculturation behaviors predict depression in South Asian immigrants to the United States. A simulation study gives guidance for when a two-stage model can be safely implemented and when the joint model may be required.
Patients With Isolated Craniofacial Dysplasia Report Better Quality of Life Compared With Those With Craniofacial Dysplasia and Extracranial Involvement
Authors: Hagelstein-Rotman Marlous , Genders Stijn W. , Andela Cornelie D. , Dijkstra Sander , Majoor Bas C.J. , Notting Irene C. , Hamdy Neveen A.T. , Appelman-Dijkstra Natasha M.
Published: December 2019

Purpose:

Craniofacial fibrous dysplasia (CFD) is a subtype of fibrous dysplasia/McCune-Albright syndrome (FD/MAS) characterized by FD lesions in one or more of the skull bones. The orbit is often involved, with facial pain, facial deformity, and increased risk of compressive optic neuropathy as associated clinical manifestations possibly leading to altered illness perceptions and impairments in quality of life(QoL). The aim of this study was to evaluate illness perceptions and QoL in patients with CFD among our FD/MAS cohort.

Methods:

One hundred ninety-one patients were included. Illness perceptions and QoL were assessed by using validated questionnaires, that is, the Illness Perceptions Questionnaire–Revised and the Short-Form 36. Patients were first grouped as CFD versus non-CFD, a second selection was based on the presence of “Isolated CFD” versus “CFD+PFD/MAS.” Non-CFD patients were grouped as monostotic fibrous dysplasia “MFD” versus polyostotic “PFD/MAS.”

Results:

Patients with isolated CFD attributed less symptoms to their disease compared with patients with CFD+PFD/MAS (p < 0.05). Furthermore, patients with isolated CFD reported better QoL on all domains (except role emotional and mental health) compared with patients with CFD+PFD/MAS (p < 0.05). Patients with isolated CFD also reported better QoL compared with non-CFD groups (on 3 out of 8 subscales) (p < 0.05).

Conclusions:

Patients with isolated CFD attribute less symptoms to their disease and report better QoL compared with patients with CFD with extracranial involvement or FD without cranial involvement. These findings indicate that craniofacial involvement alone is not sufficient to cause negative illness perceptions and impairments in QoL. Therefore, it can be postulated that isolated CFD should be considered a unique patient subtype within the spectrum of FD/MAS patients.
Reconstruction of Large Upper Eyelid Defects With Bilobed Flap and Tarsoconjunctival Graft
Authors: Yazici Bulent , Ozturker Can , Cetin Efe Ayse
Published: December 2019

Purpose:

To describe the reconstruction of large upper eyelid defects with bilobed flap and tarsoconjunctival graft.

Methods:

The medical records of 5 patients who underwent upper eyelid tumor excision and eyelid reconstruction with a bilobed flap were reviewed. Various parameters, including demographic and clinical data, defect diameter, primary defect closure, complications, and follow-up time, were recorded. After tumor excision, the posterior lamella was reconstructed with an autologous tarsoconjunctival graft and anterior lamella with a superiorly based lateral bilobed flap.

Results:

All 5 patients (3 women, 2 men; age: 42–87 years) had malignant epidermal (n = 2) or adnexal (n = 3) tumors. Mean excisional defect diameter was between 18.5 and 25 mm. In all patients, the anterior lamellar defect was closed primarily with a bilobed flap. After surgery, a total of 4 complications occurred in 3 patients. One patient required orbital exenteration because of tumor recurrence. In the other patients, the functional and esthetic results were satisfactory. Follow-up time ranged from 4 to 102 months.

Conclusion:

Lateral periorbital bilobed flap can be a good alternative for the single-stage reconstruction of large upper eyelid defects.
Nonketotic Hyperglycemia-related Seizures of Left Parieto-occipital Origin: A Case Report
Authors: Chen Yu-Shiue , Chen Tsang-Shan , Huang Chin-Wei
Published: December 2019

INTRODUCTION

Nonketotic hyperglycemia–related seizures are not uncommonly encountered in clinical practice. Their presentation varies, and they may cause serious consequences if they remain unnoticed.

CASE

We report a case of nonketotic hyperglycemia-related seizures of unique left parieto-occipital origin and semiology, presenting as focal aware (simple partial) and impaired awareness (complex partial) seizures, including contralateral limb convulsion and apraxialike behavior.

DISCUSSION

Nonketotic hyperglycemia–related seizures can present with a relatively unique semiology. Careful education to the patients and family regarding attention to the paroxysmal symptoms and an effort to maintain good glycemic control are mandatory in clinical practice.
Development and testing of a module to promote generic oral contraceptive prescribing among nurse practitioners
Authors: Chee Mark , Lenti Gena , Farnan Jeanne , Cook Michelle , Weissman Arlene , Wallingford September , Moriates Christopher , Shah Neel , Lynch Shalini , Stebbins Marilyn , Ngooi Samantha , Norenberg Allison , Millard Steven , Samarth Anita , Zhang James X. , Meltzer David O. , Tracy Chris , Arora Vineet M.
Published: December 2019

Although generic oral contraceptives (OCPs) can improve adherence and reduce health care expenditures, use of generic OCPs remains low, and the factors that affect generic prescribing are not well understood. We aimed to understand the barriers and facilitators of generic OCP prescribing and potential solutions to increase generic OCP prescribing, as well as pilot an educational module to address clinician misconceptions about generic OCPs. We developed focus group scripts using the 4D model of appreciative inquiry. A total of four focus groups occurred, two at the American Association of Nurse Practitioners (AANP) national conference and two at the American College of Physicians (ACP) Internal Medicine meeting. Focus group transcripts were analyzed using a constant comparative method with no a priori hypothesis to generate emerging and reoccurring themes. Findings from these focus groups were used to develop an educational module promoting generic OCP prescribing. Participants were recruited from the AANP Network for Research and the ACP Research Panel. This study demonstrates that health system factors, workflow factors, clinician factors, and patient factors were the main barriers to and facilitators of generic OCP prescribing. Nurse practitioners were responsive to an educational module and reported increased willingness to discuss and prescribe generic OCPs after completing the module. Interventions to increase generic OCP prescribing must address clinician and patient factors within the context of workflow and larger health system factors.
Safety and efficacy of bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes with positive biomarkers undergoing percutaneous coronary intervention: a report from the Acute Catheterization and Urgent Intervention Triage Strategy trial
Authors: Huang Xin , Chen Shmuel , Redfors Björn , Zhang Yiran , Souza Cristiano F. , Mehran Roxana , Bansilal Sameer , Kirtane Ajay J. , Brener Sorin J. , Feite Frederick , Dangas George D. , Ben-Yehuda Ori , Stone Gregg W.
Published: December 2019

Objectives

There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.

Patients and methods

We compared the net adverse clinical events [composite ischemia – (death, myocardial infarction, or unplanned ischemic revascularization) – or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy.

Results

Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis.

Conclusion

Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.
Peer Feedback
Authors: Lal M. Maureen
Published: December 2019

Feedback is a necessary and important part of career growth, and feedback from peers is shown to improve everything from job performance to quality outcomes. So why is feedback so hard to give and receive? This month's Magnet® Perspectives examines the role of feedback in the workplace; why peer feedback programs are gaining traction, especially in nursing; and how your organization can benefit from a formal, systematic peer feedback process. The column also explores how the Magnet environment promotes peer feedback and offers tips to help you create a successful program that fosters openness and communication.
Growing Acceptability of Undetectable = Untransmittable but Widespread Misunderstanding of Transmission Risk: Findings From a Very Large Sample of Sexual Minority Men in the United States
Authors: Rendina H. Jonathon , Cienfuegos-Szalay Jorge , Talan Ali , Jones Stephen Scott , Jimenez Ruben H.
Published: December 2019

Background:

Several studies have demonstrated no linked HIV transmissions in serodifferent sexual encounters where the partner with HIV has an undetectable viral load. As a result, awareness and dissemination of treatment as prevention, and movements such as “Undetectable = Untransmittable” (U = U), has grown.

Setting:

We conducted an online cross-sectional survey from November 2017 through September 2018 to gather data from a total of 111,747 sexual minority men (SMM) in the United States.

Methods:

Participants provided sociodemographic data and answered questions regarding biomedical status, HIV and STI prevention behaviors, drug use, condomless anal sex, and perceived accuracy of the U = U message. We conducted analyses to understand factors associated with perceived accuracy of U = U stratified by HIV status.

Results:

Overall, 53.2% of the sample perceived U = U as accurate, with the highest rates among HIV-positive SMM (83.9%), followed by HIV-negative (53.8%) and status-unknown (39.0%) SMM. Multivariable models showed accuracy beliefs were, on average, 1–2% higher for each consecutive month of recruitment. Consistent with previous work, there was greater heterogeneity among HIV-negative and unknown men, with several factors differentiating perceived accuracy, compared with SMM with HIV. Perceived transmission risk levels with undetectable partners were skewed well above accurate levels, and greater perceived transmission risk was associated with lower perceived accuracy of U = U.

Conclusions:

Public confidence in treatment as prevention and U = U is growing, but clear, unequivocal messaging about the effectiveness of U = U is critical. Owing to misunderstandings of risk, language that focuses on protective benefits rather than transmission risks may reach more people and allow for better comparisons with PrEP and condoms.
Self-selected step length asymmetry is not explained by energy cost minimization in individuals with chronic stroke
Authors: Nguyen Thu M. , Jackson Rachel W. , Aucie Yashar , de Kam Digna , Collins Steven H. , Torres-Oviedo Gelsy
Published: December 2019

Background

Asymmetric gait post-stroke is associated with decreased mobility, yet individuals with chronic stroke often self-select an asymmetric gait despite being capable of walking more symmetrically. The purpose of this study was to test whether self-selected asymmetry could be explained by energy cost minimization. We hypothesized that short-term deviations from self-selected asymmetry would result in increased metabolic energy consumption, despite being associated with long-term rehabilitation benefits. Other studies have found no difference in metabolic rate across different levels of enforced asymmetry among individuals with chronic stroke, but used methods that left some uncertainty to be resolved.

Methods

In this study, ten individuals with chronic stroke walked on a treadmill at participant-specific speeds while voluntarily modulating step length asymmetry. We included only participants with significant self-selected asymmetry who were able to significantly alter asymmetry using visual biofeedback. Conditions included targeting zero asymmetry, self-selected asymmetry, and double the self-selected asymmetry. Participants were trained with the biofeedback system in one session, and data were collected in three subsequent sessions with repeated measures. Self-selected asymmetry was consistent across sessions. A similar protocol was conducted among unimpaired participants.

Results

Participants with chronic stroke substantially altered step length asymmetry using biofeedback, but this did not affect metabolic rate (ANOVA, p = 0.8). In unimpaired participants, self-selected step length asymmetry was close to zero and corresponded to the lowest energy cost (ANOVA, p = 6e-4). While the symmetry of unimpaired gait may be the result of energy cost minimization, self-selected step length asymmetry in individuals with chronic stroke cannot be explained by a similar least-effort drive.

Conclusions

Interventions that encourage changes in step length asymmetry by manipulating metabolic energy consumption may be effective because these therapies would not have to overcome a metabolic penalty for altering asymmetry.
Targeting dual signaling pathways in concert with immune checkpoints for the treatment of pancreatic cancer
Authors: Knudsen Erik S , Kumarasamy Vishnu , Chung Sejin , Vail Paris , Tzetzo Stephanie , Ruiz Amanda , Seshadri Mukund , Abrams Scott I , Wang Jianmin , Witkiewicz Agnieszka K
Published: December 2019

Pancreatic cancer harbors a poor prognosis due to the lack of effective systemic therapies. Here we interrogated means to target key effector pathways down-stream from KRAS. We found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumor progression. These effects were associated with stable cell cycle arrest, as well as the induction of multiple genes associated with interferon response and antigen presentation in an RB-dependent fashion. Using single cell sequencing and complementary approaches, we found that the combination of CDK4/6 and MEK inhibition had a significant impact on increasing T-cell infiltration and altering myeloid populations, while potently cooperating with immune checkpoint inhibitors. Together, these data indicate that there are canonical and non-canonical features of CDK4/6 and MEK inhibition that impact on the tumor and host that can contribute to durable control for tumors in combination with immune checkpoint inhibitor therapy.
Co-transcriptional folding of a bio-orthogonal fluorescent scaffolded RNA origami
Authors: Torelli Emanuela , Kozyra Jerzy W. , Shirt-Ediss Ben , Piantanida Luca , Voïtchovsky Kislon , Krasnogor Natalio
Published: December 2019

The scaffolded origami technique has provided an attractive tool for engineering nucleic acid nanostructures. This paper demonstrates scaffolded RNA origami folding in vitro in which all components are transcribed simultaneously in a single-pot reaction. Double-stranded DNA sequences are transcribed by T7 RNA polymerase into scaffold and staple strands able to correctly fold in high yield into the nanoribbon. Synthesis is successfully confirmed by atomic force microscopy and the unpurified transcription reaction mixture is analyzed by an in gel-imaging assay where the transcribed RNA nanoribbons are able to capture the specific dye through the reconstituted split Broccoli aptamer showing a clear green fluorescent band. Finally, we simulate the RNA origami in silico using the nucleotide-level coarse-grained model oxRNA to investigate the thermodynamic stability of the assembled nanostructure in isothermal conditions over a period of time.

Our work suggests that the scaffolded origami technique is a valid, and potentially more powerful, assembly alternative to the single-stranded origami technique for future in vivo applications.

Abstract Figure
Heme uptake inLactobacillus sakeievidenced by a new ECF-like transport system
Authors: Verplaetse Emilie , André-Leroux Gwenaëlle , Duhutrel Philippe , Coeuret Gwendoline , Chaillou Stéphane , Nielsen-Leroux Christina , Champomier-Vergès Marie-Christine
Published: December 2019

Lactobacillus sakeiis a non-pathogenic lactic acid bacterium and a natural inhabitant of meat ecosystems. Although red meat is a heme-rich environment,L. sakeidoes not need iron or heme for growth, while possessing a heme-dependent catalase. Iron incorporation intoL. sakeifrom myoglobin and hemoglobin was formerly shown by microscopy and theL. sakeigenome reveals a complete equipment for iron and heme transport. Here, we report the characterization of a five-gene cluster (lsa1836-1840) encoding a putative metal iron ABC transporter. Interestingly, this cluster, together with a heme dependent catalase gene, is also conserved in other species from the meat ecosystem. Our bioinformatic analyses revealed that the locus might refer to a complete machinery of an Energy Coupling Factor (ECF) transport system. We quantifiedin vitrothe intracellular heme in wild-type (WT) and in our Δlsa1836-1840deletion mutant using an intracellular heme sensor and ICP-Mass spectrometry for quantifying incorporated57Fe heme. We showed that in the WTL. sakei, heme accumulation occurs fast and massively in the presence of hemin, while the deletion mutant was impaired in heme uptake; this ability was restored byin transcomplementation. Our results establish the main role of theL. sakeiLsa1836-1840 ECF-like system in heme uptake. This research outcome shed new light on other possible functions of ECF-like systems.

Importance

Lactobacillus sakeiis a non-pathogenic bacterial species exhibiting high fitness in heme rich environments such as meat products, although it does not need iron nor heme for growth. Heme capture and utilization capacities are often associated with pathogenic species and are considered as virulence-associated factors in the infected hosts. For these reasons, iron acquisition systems have been deeply studied in such species, while for non-pathogenic bacteria the information is scarce. Genomic data revealed that several putative iron transporters are present in the genome of the lactic acid bacteriumL. sakei.In this study, we demonstrate that one of them, is an ECF-like ABC transporter with a functional role in heme transport. Such evidence has not yet been brought for an ECF, therefore our study reveals a new class of heme transport system.
Growth and mortality of the oak processionary moth,Thaumetopoea processioneaL., on two oak species: direct and trait-mediated effects of host and neighbour species identity
Authors: Damestoy Thomas , Moreira Xoaquín , Jactel Hervé , Valdes-Correcher Elena , Plomion Christophe , Castagneyrol Bastien
Published: December 2019

The presence of heterospecific neighbours can affect damage caused by pest insects on focal plants. However, how plant neighbours influence herbivore performance is poorly understood. We tested the independent and interactive effects of tree species identity and tree neighbour type (conspecific vs. heterospecific) on the performance of a major oak pest, the oak processionary moth larvae (OPM,Thaumetopoea processionea) fed onQuercus roburandQ. petraea. We performed a factorial greenhouse experiment in which we grew two oak saplings per pot, either from the same species or from both species. We quantified growth and mortality of OPM larvae, leaf phenolic compounds, C:N ratio and bud phenology. OPM larvae performed significantly better onQ. petraeathan onQ. robur, regardless of plant neighbour type. Phenolic compounds and C:N, but not phenology, differed between oak species and neighbour species identity. Only bud phenology had a significant effect on OPM performance, which was better when young larvae had access to recently unfolded leaves, regardless of oak species and neighbour identity. Although oak neighbour identity altered the expression of leaf traits, this effect had no measurable consequences on OPM performance. However, further studies should consider the effect of oak species neighbour on OPM preferences for eitherQ. roburorQ. petraea, in pure and mixed stands, before translating current results into recommendations for forest management.

Author Contribution

TD and BC conceived the study and acquired the data. TD performed experiment and analysed the data. EV, TD and XM performed the chemical analyses. TD and BC drafted the first version of the manuscript and all authors wrote the final version of the manuscript.

TD, BC conceived and designed research. TD performed experiment and analysed data. EV, TD, XM performed the chemical analyses. TD, BC wrote the manuscript. All authors read and approved the manuscript.

AM and DB conceived and designed research. AM and BB conducted experiments. GR contributed new reagents or analytical tools. AM, BB and GR analysed data. AM wrote the manuscript. All authors read and approved the manuscript.