bluuebunny/crossref_metadata_2025 huggingface dataset:
The interplay between microRNA and alternative splicing of linear and circular RNAs in eleven plant species
Authors: Wang Huiyuan , Wang Huihui , Zhang Hangxiao , Liu Sheng , Wang Yongsheng , Gao Yubang , Xi Feihu , Zhao Liangzhen , Liu Bo , Reddy Anireddy S N , Lin Chentao , Gu Lianfeng
Published: January 2019

Motivation

MicroRNA (miRNA) and alternative splicing (AS)-mediated post-transcriptional regulation has been extensively studied in most eukaryotes. However, the interplay between AS and miRNAs has not been explored in plants. To our knowledge, the overall profile of miRNA target sites in circular RNAs (circRNA) generated by alternative back splicing has never been reported previously. To address the challenge, we identified miRNA target sites located in alternatively spliced regions of the linear and circular splice isoforms using the up-to-date single-molecule real-time (SMRT) isoform sequencing (Iso-Seq) and Illumina sequencing data in eleven plant species.

Results

In total, we identified 399 401 and 114 574 AS events from linear and circular RNAs, respectively. Among them, there were 64 781 and 41 146 miRNA target sites located in linear and circular AS region, respectively. In addition, we found 38 913 circRNAs to be overlapping with 45 648 AS events of its own parent isoforms, suggesting circRNA regulation of AS of linear RNAs by forming R-loop with the genomic locus. Here, we present a comprehensive database of miRNA targets in alternatively spliced linear and circRNAs (ASmiR) and a web server for deposition and identification of miRNA target sites located in the alternatively spliced region of linear and circular RNAs. This database is accompanied by an easy-to-use web query interface for meaningful downstream analysis. Plant research community can submit user-defined datasets to the web service to search AS regions harboring small RNA target sites. In conclusion, this study provides an unprecedented resource to understand regulatory relationships between miRNAs and AS in both gymnosperms and angiosperms.

Availability and implementation

The readily accessible database and web-based tools are available at http://forestry.fafu.edu.cn/bioinfor/db/ASmiR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome: a subgroup analysis from the RE-DUAL PCI trial
Authors: Oldgren Jonas , Steg Philippe Gabriel , Hohnloser Stefan H , Lip Gregory Y H , Kimura Takeshi , Nordaby Matias , Brueckmann Martina , Kleine Eva , ten Berg Jurrien M , Bhatt Deepak L , Cannon Christopher P
Published: January 2019

Aims

After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment.

Methods and results

In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35–0.63) for 110 mg and 0.67 (0.50–0.90) for 150 mg]; elective PCI [0.57 (0.43–0.76) for 110 mg and 0.76 (0.56–1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28–0.76) for 110 mg and 0.59 (0.34–1.04) for 150 mg]; or clopidogrel [0.51 (0.41–0.64) for 110 mg and 0.73 (0.58–0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10.

Conclusion

The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.
Unintended HIV-1 Transmission to a Sex Partner in a Study of a Therapeutic Vaccine Candidate
Authors: Lelièvre Jean-Daniel , Hocqueloux Laurent
Published: January 2019

We report a case of sexual transmission of human immunodeficiency virus (HIV) that occurred during treatment discontinuation in a therapeutic vaccine trial, following oral sex. Transmission occurred even though the index participant was an HIV/AIDS activist, particularly well informed about the risks and modalities of transmission. This case report highlights the risk of secondary transmission of HIV during cessation of treatment in HIV cure–related trials.
Simple Detection of Hepatitis B Virus in Using Loop-Mediated Isothermal Amplification Method
Authors: Chen Hua-Wei , Belinskaya Tatyana , Zhang Zhiwen , Ching Wei-Mei
Published: January 2019

Introduction

US Military and civilian personnel regularly deploy to regions that are endemic for the Hepatitis B virus (HBV), including the Western Pacific, Africa, Eastern Mediterranean, Southeast Asia, and Europe. When patients have life-threatening injuries that require any blood component that is not immediately available, they are typically transfused with locally collected fresh whole blood from a walking blood bank. Currently, there is no simple and easy method for sensitively screening fresh blood in deployed theaters of conflict.

Materials and methods

In order to fill the gap, we have developed a loop-mediated isothermal amplification (LAMP) assay to detect the presence of HBV in blood products. The primers were designed to target the gene of the pre-Surface/Surface antigen region of HBV. The amplification reaction mixture was incubated at 60°C for 60 min. The amplicon can be detected by a handheld fluorescence tube scanner or an immune-chromatography test strip.

Results

We were able to detect down to 10 copies of viral DNA by LAMP reaction for HBV DNA extracted from HBV-positive plasma. We also identified the optimal heat treatment condition (125°C for 10 min) for plasma specimens without requiring DNA extraction for the LAMP assay. The sensitivity of the assay was evaluated with polymerase chain reaction (PCR) confirmed HBV-positive samples. Using LAMP, we detected HBV in 107 out of 127 (84%) samples.

Conclusion

This LAMP assay has the potential to be used in resource-limited settings to improve the safety of locally collected blood in endemic regions.
Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy
Authors: Hu Yixin , Chen Aili , Zheng Xinchang , Lu Jun , He Hailong , Yang Jin , Zhang Ya , Sui Pinpin , Yang Jingyi , He Fuhong , Wang Yi , Xiao Peifang , Liu Xin , Zhou Yinmei , Pei Deqing , Cheng Cheng , Ribeiro Raul C , Hu Shaoyan , Wang Qian-fei
Published: January 2019

Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, P = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; P = 0.99) and overall (70.3 vs. 74.6%, P = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs (P < 0.001); 15.5 vs. 22.0 d for platelets (P < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF (n = 9) or SDC (n = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.
Choice of Empirical Antibiotic Therapy and Adverse Outcomes in Older Adults With Suspected Urinary Tract Infection: Cohort Study
Authors: Ahmed Haroon , Farewell Daniel , Francis Nick A , Paranjothy Shantini , Butler Christopher C
Published: January 2019

Background

Nitrofurantoin is widely recommended for empirical treatment of urinary tract infection (UTI), but primary care clinicians may prescribe alternative antibiotics to improve prognosis in older, sicker patients. We assessed whether prescribing alternative antibiotics was associated with reduced risk of adverse outcomes in older patients.

Methods

This retrospective cohort study included patients aged ≥65 years empirically treated for a UTI with nitrofurantoin, cefalexin, ciprofloxacin, or co-amoxiclav. We matched patients on their propensity to receive a nitrofurantoin prescription and used mixed-effects logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for reconsultation and represcription (proxy for treatment failure), hospitalization for UTI, sepsis, or acute kidney injury, and death.

Results

We identified 42 298 patients aged ≥65 years prescribed empirical nitrofurantoin, cefalexin, ciprofloxacin, or co-amoxiclav for a UTI. Compared with nitrofurantoin, patients prescribed cefalexin, ciprofloxacin, or co-amoxiclav had lower odds of reconsultation and represcription (OR for cefalexin = 0.85, 95% CI = 0.75–0.98; OR for ciprofloxacin = 0.48, 95% CI = 0.38–0.61, OR for co-amoxiclav = 0.77, 95% CI = 0.64–0.93). Patients prescribed cefalexin or ciprofloxacin had greater odds of hospitalization for sepsis (OR for cefalexin = 1.89, 95% CI = 1.03–3.47; OR for ciprofloxacin = 3.21, 95% CI = 1.59–6.50), and patients prescribed cefalexin had greater odds of death (OR = 1.44, 95% CI = 1.12–1.85).

Conclusions

Compared with nitrofurantoin, prescribing of alternative antibiotics for UTI in older people may be associated with lower rates of treatment failure but was not associated with reduced risk of UTI-related hospitalization or death.
Southern Sclerotium Root Rot Caused by Athelia rolfsii on Table Beet in New York
Authors: Pethybridge Sarah J. , Sharma Sandeep , Silva Alex , Bowden Carol , Murphy Sean , Knight Noel L. , Hay Frank S.
Published: January 2019

Southern Sclerotium root rot caused by Athelia rolfsii (syn. Sclerotium rolfsii) is a damaging soilborne disease of field and specialty crops. In 2015, 2016, and 2017, wilted plants, root rot, and decay in six table beet (Beta vulgaris spp. vulgaris) fields across New York were observed. In these outbreaks, losses ranged between 5 and 25%. White mycelial mats and golden brown sclerotia (1 to 2 mm diameter) were observed on diseased plants and decayed roots. The objective of this study was to identify the fungus associated with these symptoms and assess pathogenicity in table beet.
Variables Associated With the Use of Prophylactic Amitriptyline Treatment in Patients With Tension-type Headache
Authors: Palacios-Ceña Maria , Wang Kelun , Castaldo Matteo , Ordás-Bandera Carlos , Torelli Paola , Arendt-Nielsen Lars , Fernández-de-las-Peñas César
Published: January 2019

Objective:

The objective of this study was to investigate differences in clinical, psychological, and psychophysical outcomes according to use of prophylactic medication (amitriptyline) in tension-type headache (TTH).

Methods:

In total, 173 individuals with TTH participated. Headache features and symptomatic medication intake were collected with a 4-weeks headache diary at baseline and at 6-months. Burden of headache (Headache Disability Inventory-HDI), sleep quality (Pittsburgh Sleep Quality Index-PSQI), anxiety/depression (Hospital Anxiety and Depression Scale-HADS), and trait/state anxiety levels (State-Trait Anxiety Inventory-STAI) were also assessed at baseline. Pressure pain thresholds (PPT) were assessed over the temporalis, C5-C6 joint, second metacarpal, and tibialis anterior at baseline. Differences between participants taking or not taking prophylactic medication based on self-perceived effectiveness of the medication on headache characteristics were assessed.

Results:

In total, 49 (28%) reported taking prophylactic medication for the headaches (amitriptyline: 100%). From these, 11 (23%) reported no effect, 25 (51%) reported moderate effect, and 13 (26%) reported positive effect with medication. Patients taking prophylactic medication had longer headache history, higher frequency of headaches (61% CTTH), higher headache burden, worse quality of sleep, and higher depression than those not taking medication. Prophylactic medication was less effective in patients with generalized pressure pain hyperalgesia. No other significant differences were found.

Conclusions:

Prophylactic medication is used by TTH patients with higher headache frequency, higher headache burden, worse sleep quality, and higher depression. Lower effectiveness of prophylactic amitriptyline was associated with widespread pain hyperalgesia.
Oral Riboflavin to Assess Ureteral Patency During Cystoscopy
Authors: Stitely Michael L. , Harlow Keryn , MacKenzie Elliot
Published: January 2019

OBJECTIVE:

To evaluate whether oral riboflavin is more effective than placebo as a marker of ureteric patency at cystoscopy.

METHODS:

Patients scheduled for gynecologic surgery where cystoscopy was a planned component of the procedure were randomized to receive riboflavin 400 mg or placebo orally the night before surgery. During cystoscopy, the operating surgeon visualized ureteric jets and video recorded the cystoscopy portion of the procedure. The primary outcome was to determine whether orally administered riboflavin produced stronger yellow color of urine seen on cystoscopy than placebo on a 3-point scale. Secondary outcomes were to assess whether riboflavin administration improved ease of identifying ureteric jets (5-point scale) and whether a greater proportion of patients had both ureteric jets visualized with riboflavin compared with placebo. A sample size of 33 per group was planned.

RESULTS:

From June 28, 2017, to February 19, 2018, 72 women were screened and 66 were randomized, with 33 patients in each study group. The groups were similar in age, weight, body mass index, and ethnicity. The patients in the riboflavin group had significant increase of yellow-colored urine as rated by the operating surgeon, with a median of 2 compared with 1 on a 3-point scale (P<.001). The ureteral jets were more easily visualized in the riboflavin group as rated by the operating surgeon, with a median of 5 compared with 4 on a 5-point scale (P<.013). Bilateral ureteral patency was confirmed in 30 of 33 women (91%) in the riboflavin group and in 28 of 33 women (85%) in the placebo group (P=.71).

CONCLUSIONS:

The administration of riboflavin before gynecologic surgery improves the ease of visualizing the ureteric jets by inducing yellow coloration of the urine.

CLINICAL TRIALS REGISTRATION:

Australian New Zealand Clinical Trials Registry, 12616001367437.
Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate
Authors: Dianat Shokoufeh , Fox Edith , Ahrens Katherine A. , Upadhyay Ushma D. , Zlidar Vera M. , Gallo Maria F. , Stidd Reva L. , Moskosky Susan , Dehlendorf Christine
Published: January 2019

OBJECTIVE:

Counseling about potential side effects and health benefits of contraceptive methods could facilitate continued method use and method satisfaction, yet no evidence-based compilation of side effects and benefits exists to aid such counseling. Among contraceptive methods in the United States, depot medroxyprogesterone acetate (DMPA) injectables have the highest discontinuation rates, and most discontinuation is attributable to side effects. This review examines the side effects and health benefits of DMPA to inform counseling.

DATA SOURCES:

We searched PubMed, POPLINE, EMBASE, Web of Science, Campbell Collaboration Library of Systematic Reviews, the Cochrane Database of Systematic Reviews, the Cochrane Center Register of Controlled Trials, and ClinicalTrials.gov.

METHODS OF STUDY SELECTION:

We included English-language studies published from 1985 to 2016 that enrolled healthy, nonbreastfeeding females aged 13–49 years at risk of unintended pregnancy, compared intramuscular or subcutaneous progestin-only injectables to a contemporaneous comparison group, and addressed at least one key question: 1) What side effects are associated with progestin-only injectable contraceptive use? 2) What health benefits are associated with progestin-only injectable contraceptive use? Study quality was assessed using criteria from the U.S. Preventive Services Task Force.

TABULATION, INTEGRATION, AND RESULTS:

Twenty-four studies met inclusion criteria. None were randomized controlled trials. There were 13 prospective cohort, five retrospective cohort, four case–control, and two cross-sectional studies. Studies of moderate or high risk of bias suggest an association between DMPA use and weight gain, increased body fat mass, irregular bleeding, and amenorrhea. Inconsistent evidence exists for an association between DMPA use and mood or libido changes. Limited evidence exists for an association between DMPA use and decreased risk of cancers and tubal infertility.

CONCLUSION:

Higher-quality research is needed to clarify DMPA's side effects and benefits. In absence of such evidence, patient-centered counseling should incorporate the available evidence while acknowledging its limitations and recognizing the value of women's lived experiences.
Application of next-generation sequencing for the diagnosis of fetuses with congenital heart defects
Authors: Qiao Fengchang , Hu Ping , Xu Zhengfeng
Published: January 2019

Purpose of review

Congenital heart defects (CHDs) are the most common type of birth defects, and are thought to result from genetic–environmental interactions. Currently, karyotype and chromosomal microarray analyses are the primary methods used to detect chromosomal abnormalities and copy number variations in fetuses with CHD. Recently, with the introduction of next-generation sequencing (NGS) in prenatal diagnosis, gene mutations have been identified in cases of CHD. The purpose of this review is to summarize current studies about the genetic cause of fetal CHD, paying particular attention to the application of NGS for fetuses with CHD.

Recent findings

In addition to chromosomal abnormalities, gene mutations are an important genetic cause of fetal CHD. Furthermore, incidences of pathogenic mutations in fetuses with CHD are associated with the presence of other structural anomalies, but are irrelevant to the categories of CHD.

Gene mutations are important causes of fetal CHD and NGS should be applied to all fetuses with normal karyotype and copy number variations, regardless of whether the CHD is isolated or syndromic.
Benzodiazepines in Pregnancy
Authors: SHYKEN JAYE M. , BABBAR SHILPA , BABBAR SHAWETA , FORINASH ALICIA
Published: January 2019

Benzodiazepine use and dependence are on the rise as well as the number of deaths attributable to the combination of opioids and benzodiazepines. Anxiety, the most frequent condition for which benzodiazepines are prescribed, occurs commonly, and is increasingly noted to coincide with pregnancy. Use of both benzodiazepine anxiolytics and anxiety in pregnancy is associated with preterm delivery and low birth weight. Short-term neonatal effects of hypotonia, depression, and withdrawal are described but long-term sequelae, if any, are poorly understood. Benzodiazepines are associated with physical dependence and withdrawal symptoms which can be serious. To avoid withdrawal, tapering off these medications is recommended. What is known about the pharmacology and pharmacokinetics, pregnancy implications, tapering schedules, and alternative strategies for anxiety are discussed.
Substance Abuse in Pregnancy
Authors: RYAN SHAWN A.
Published: January 2019

Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Like many other chronic diseases, addiction often involves cycles of relapse and remission. It is key that clinicians understand it as such and treat it appropriately with evidence-based interventions including medication-assisted treatment.
Systematic Review of the Effectiveness of the Neonatal Early-Onset Sepsis Calculator
Authors: Helmbrecht Ashley R. , Marfurt Stephanie , Chaaban Hala
Published: January 2019

Neonatal early-onset sepsis is a serious health concern for term and late preterm infants. Screening for early-onset sepsis is often challenging due to variation in practice, nonspecific laboratory markers, and clinical findings that mimic immaturity. This systematic review evaluates the evidence for the effectiveness of the Neonatal Early-Onset Sepsis Calculator (EOScalc) as a screening tool to appropriately identify neonatal early-onset sepsis and the ability to decrease unnecessary antibiotic use in late preterm and term infants. A comprehensive search of retrospective cohort and retrospective case-control studies was conducted using 5 databases. Studies were included if they evaluated the EOScalc within the defined parameters of use and excluded if they were not published. Six studies were identified and included from 2014 to 2017. Study comparisons varied on the basis of differing clinical practice and use of the EOScalc. Findings included in this review suggest that utilization of the EOScalc can reduce empiric antibiotic therapy, unnecessary laboratory testing, and separation of infants and mothers without increasing infant mortality.
Effects of Paternal Skin-to-Skin Contact in Newborns and Fathers After Cesarean Delivery
Authors: Huang Xiaoli , Chen Liling , Zhang Li
Published: January 2019

The objective of this study was to investigate the effects of paternal skin-to-skin contact (SSC) on newborns and fathers after cesarean delivery. In total, 108 neonates born via elective cesarean delivery and their fathers were recruited into this study. The neonates were randomly divided into 2 groups (n = 54 each). Newborns in the treatment group received SSC from their fathers shortly after cesarean delivery, whereas those from the control group received only routine care. The neonates' physical condition, breastfeeding rate, and the paternal psychological outcomes were compared between the 2 groups. The newborns in the treatment group had a more stable heart rate and forehead temperature, less duration of crying, and started feeding behavior earlier. The duration of breastfeeding after SSC in the treatment group was longer as well, with statistical significance, than the control group (P < .05). In addition, fathers in the treatment group had lower scores of anxiety and depression and better role attainment than those in the control group, with statistical significance (P < .05). The paternal SSC after cesarean delivery was beneficial for newborns by stabilizing newborns' physical conditions and increasing the breastfeeding rate. Meanwhile, it could significantly reduce anxiety and depression of fathers and facilitate their role attainment.
Acupuncture for pain caused by prostate cancer
Authors: Wang Jisheng , Lei Yi , Bao Binghao , Yu Xudong , Dai Hengheng , Chen Fei , Li Haisong , Wang Bin
Published: January 2019

Background:

Prostate cancer is a male malignant tumor disease with high prevalence in recent years. Patients with advanced prostate cancer are more likely to have bone metastasis and strong bone pain, and even lead to pathological fracture, which has a serious impact on the quality of life of patients. Acupuncture has good clinical efficacy in treating pain caused by prostate cancer. This review hopes to adopt meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of pain caused by prostate cancer and provides evidence for its application in clinical practice.

Methods and analysis:

We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata 13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis.

Ethics and dissemination:

This systematic review will evaluate the efficacy and safety of acupuncture for pain caused by prostate cancer. Owing to the fact that all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be anonymously analyzed during the review process trial.

Trial registration number:

PROSPERO CRD42018111550
A cut-off value of shear wave speed to distinguish nonalcoholic steatohepatitis candidates
Authors: Suda Takeshi , Kanefuji Tsutomu , Abe Atsushi , Nagayama Itsuo , Hoshi Takahiro , Morita Shinichi , Yagi Kazuyoshi , Hatakeyama Shigeaki , Hayatsu Masafumi , Hasegawa Noboru , Terai Shuji
Published: January 2019

To distinguish and characterize nonalcoholic steatohepatitis (NASH) candidates from among medical checkup visitor diagnosed with nonalcoholic fatty liver diseases (mcNAFLDs).

A cut-off value has not been established to differentiate NASH at the earliest stage in NAFLD.

Shear wave speed (SWS) was measured in the livers of 480 mcNAFLDs. NASH candidates were screened out by adopting a statistically defined cut-off value of SWS and were characterized in terms of food preference.

SWS ranged between 1.11 and 2.18 m/s and fit a Gaussian distribution (r2 = 0.98) with an average and SD of 1.324 and 0.0847 m/s, respectively, in 320/160 males/females 64.4 (interquartile range 57.3–69.4) years old. The average plus SD (1.41 m/s) screened out 82 (17.1%) NASH candidates, who were significantly older (66.8 vs. 64.1 years old, P = 0.001) and had higher fibrosis 4 index values (1.58 vs. 1.33, P < 0.0001) than the remaining mcNAFLDs. The number of patients with a BMI greater than 25 kg/m2 was 118 (29.6%) mcNAFLDs and 34 (41.5%) NASH candidates, with a significantly higher frequency in NASH candidates (P = 0.05). Obese patients preferentially ate fatty acids in general, while NASH candidates preferred to consume several long-chain unsaturated fatty acids irrespective of their BMI.

These results suggest that NASH candidates who have a longer disease duration and pathological progression can be distinguished from mcNAFLDs by a statistically defined cut-off value of SWS. The defined value indicates that there are different food habitats associated with obesity and NAFLD progression.
Subjective rating scale for discourse: Evidence from the efficacy of subjective rating scale in amnestic mild cognitive impairments
Authors: Kim JungWan , Shim Jihye , Yoon Ji Hye
Published: January 2019

In clinical settings, the language ability of patients with neurologic communication disorders have been measured by quantitative parameters such as the total number of words in dialogue and picture description tasks. However, this quantitative analysis requires a long period of time in order to analyze the quantitative parameters, and results can differ according to discourse tasks. The purposes of this study are to explore whether SR-D may predict the quantitative measures of discourse tasks. Forty patients with amnestic MCI and 40 normal elderly participated in the study. We gathered responses to 10 items regarding SR-D and analyzed the quantitative measures of narrative discourse through 3 discourse tasks (i.e, picture description, dialogue, procedural discourse). We found significant differences in MLTW, CIU, and SR-D scores between the 2 groups. In particular, 4 items were significantly correlated with the performance of MLTW and CIU. Sensitivity and specificity of these 4 items were 100% and 75%, respectively. In terms of economic opportunity costs, objective measures cannot be evaluated to be practical, since it is used in research rather than clinical diagnosis in general. Therefore, evaluation of discourse using a few items proven in its sensitivity and specificity could allow a wide use of such measure in not only research but also in clinical diagnosis. These findings suggest that subjective measures of narrative discourse may be valid with objective language tests to predict individual discourse performance.
Resolution of left ventricular thrombus by edoxaban after failed treatment with warfarin overdose
Authors: Kao Pei-Heng , Chou Ping-Yin , Hsu Po-Chao , Huang Tien-Chi
Published: January 2019

Rationale:

Although novel oral-anticoagulants are widely used in patients with atrial fibrillation (AF) for stroke prevention, there was only limited evidence for their use in left ventricular (LV) thrombus.

Patient concerns:

A 41-year-old man who presented with acute onset of right-hand clumsiness and aphasia even under high international normalized ratio (INR: 7.64) from warfarin use. He was previously treated with warfarin for the LV thrombus and non-valvular AF. Brain magnetic resonance imaging (MRI) showed multiple acute infarction in the cortex of the bilateral frontal lobes, left parietal lobe, and bilateral central semiovale, which highly suggested embolic stroke.

Diagnosis:

The repeated transthoracic echocardiogram still revealed LV thrombus (1.27 × 0.90 cm), which failed to respond to warfarin therapy.

Interventions:

Due to acute infarctions occurred under supratherapeutic range of INR, we switched warfarin to edoxaban (dose: 60 mg/day) after INR decreased to less than 2.

Outcomes:

The thrombus disappeared after receiving edoxaban for 23 days, and no more recurrent stroke was noted for more than 6 months.

Lessons:

This is the first case demonstrates that while facing ineffective treatment of warfarin for LV thrombus, edoxaban could be safely and effectively used under this situation.
Musculoskeletal ultrasound: a useful tool for diagnosis of hip developmental dysplasia
Authors: Mureşan Simona , Mărginean Maria Oana , Voidăzan Septimiu , Vlasa Ionuţ , Sîntean Ioana
Published: January 2019

Developmental dysplasia of the hip (DDH) is one of the most common congenital abnormalities of the musculoskeletal apparatus in newborns. The aim of this study was to analyze the contribution of ultrasonography in the detection of DDH in newborns and infants, identifying the regional incidence of this pathology in the central area of Romania, emphasizing the risk factors that underlie DDH etiopathogenicity.

This article represents a retrospective study of 847 newborns and infants examined in the Imagistic Department of a medical center from the central area of Romania, between January 1 and December 31, 2016. The ultrasound examinations were performed for the bilateral coxofemoral joints, using the method and technique described by Graf. For subjects born in the same medical center, data regarding mother's age, birth weights, and type of delivery (natural vs. caesarian section) were statistically analyzed.

In our study group, the frequency of ultrasound diagnosis obtained from the examinations of right and left hips showed that the most frequent stage was type IA, and the rarest stage was III. The IA stage of right coxofemoral joints (87.3%) was higher than in the left coxofemoral joints (87.2%). The incidence of hip dysplasia (type III) diagnosed with ultrasound examinations in subjects from the central area of Romania was 0.2% (0.1% in both hips and 0.1% for the left coxofemoral joint).

The musculoskeletal ultrasound examination is effective in early detection of hip dysplasia. The implementation of national and regional programs that promote indications, risk factors, and the screening age for DDH in both rural and urban areas could be a step forward in the early diagnosis of hip dysplasia for newborns and infants. The low incidence of DDH from our study group is not able to identify the role of advanced age of the mother, high birth weight of the newborn, or caesarean section as risk factors involved in the etiology of hip dysplasia. The implementation of national and regional programs that promote the musculoskeletal ultrasound as a screening imagistic investigation for DDH, in both rural and urban areas, could be a step forward in the early diagnosis of hip dysplasia for newborns and infants.
Cranial aspergillosis in immunocompetent patient: a case report
Authors: Mousavi Seyed Alireza , Mohebali Navideh , Miratashiyazdi Seyed Masoud , Shahcheraghi Seyed Hossein
Published: January 2019

Aspergillosis of the central nervous system is an uncommon sickness, particularly if the patient is immunocompetent. In the immunocompetent individuals, the regular way for the fungus to access the CNS is diffusion by the blood from extracranial sites, commonly the lungs. In this report, a 44-year-old man with no history of recent surgery or immunodeficiency had an episode of falling. A cranial mass close to the cerebrum revealed to be as aspergillosis abscess throughout the operation. This case is showing the significance of assuming a cranial mass as aspergilloma in the differential diagnosis.
Gardner-Diamond Syndrome in an Adolescent With Suicidal Ideation: A Case Report
Authors: KARA TAYFUN , TOPKARCI ZEYNEP , GÖRDÜ ZÜLFIKAR , AKALTUN İSMAIL
Published: January 2019

Gardner-Diamond syndrome (GDS) is a rare disease often seen in young women involving painful localized inflammation and ecchymosis. Ecchymosis usually develops spontaneously after emotional stress. The pathophysiology of the disease is not fully understood, and little is known about management modalities for this syndrome. The primary approach of health professionals in the evaluation of this rare condition should involve identification of cases and investigation of potential accompanying psychiatric pathologies. The case presented here highlights the importance of assessing for GDS and reviews descriptions of GDS in the context of the existing literature.
The Association of Lifetime Suicide Attempts With Anxiety Disorders in Patients With Bipolar Disorder
Authors: KOCABAS OKTAY , SEVINCOK LEVENT , MEMIS CAGDAS O. , DOGAN BILGE
Published: January 2019

The association of lifetime suicidal behaviors with anxiety disorders (ADs) in patients with bipolar disorder (BD) has been controversial. In this study, we hypothesized that certain types of ADs were related to the occurrence of past suicide attempts (SAs) independent of the severity of the BD, including the presence of past affective episodes. Lifetime diagnoses of BD and ADs were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders (SCID-I). Of the total sample of 200 patients with BD, 32.0% had at least 1 past SA. The mean number of previous hospitalizations, a history of social AD, and a history of posttraumatic stress disorder were strongly associated with past SAs in patients with bipolar I disorder. The presence of lifetime social AD was associated with lifetime SAs independent of previous depressive episodes. Therefore, we suggest that social AD itself is associated with a greater risk for SAs in patients with BD independent of the presence of depression.
Drug-Drug Interactions (DDIs) in Psychiatric Practice, Part 3: Pharmacokinetic Considerations
Authors: PRESKORN SHELDON H.
Published: January 2019

This column is the third in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first column in this series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs and how to recognize such DDIs, and strategies for avoiding them. The second column in the series further discussed strategies for avoiding and/or minimizing adverse outcomes from DDIs. This third column deals with pharmacokinetic considerations concerning DDIs in psychiatric practice. Specifically, this column discusses the 2 major types of pharmacokinetically mediated DDIs: those mediated by cytochrome P450 (CYP) enzymes and those mediated by transport proteins. The role of each of these regulatory proteins in the pharmacokinetics of drugs is reviewed as well as how genetically determined variation in the functional activity of these regulatory proteins can alter the accumulation of a drug in the body (ie, via CYP enzymes) and in specific compartments of the body (ie, via transport proteins), either increasing or decreasing their accumulation leading to either reduced efficacy or increased toxicity. This column further explains how coprescribed drugs can also affect the functional integrity of these regulatory proteins and lead to differences from usual in the accumulation of drugs dependent on the activity of these CYP enzymes and drug transporters. This phenomenon is known as phenoconversion in which a patient can functionally change from his or her genetic status, for example, having extensive or normal metabolism, to having poor or slow metabolism and hence greater accumulation than would be expected based on the patient’s genotype.
A Comparison of Endoscopic Reduction for Medial Blowout Fractures Using a Bioresorbable Panel and Silastic Sheet
Authors: Kim Joo Yeon , Jung Tae Young , Kwon Jae Hwan
Published: January 2019

Background:

The aim of the study was to compare the effectiveness of endoscopic endonasal reduction using a bioresorbable panel and silastic sheet packed with Merocel for blowout fractures of the medial orbital wall.

Design:

Retrospective study.

Methods:

The study group consisted of 147 patients who underwent endoscopic endonasal reduction of a blowout fracture of the medial orbital wall between January 2005 and December 2016. Fifty-seven fractures were repaired using a splint formed by a silastic sheet and Merocel (splint group), whereas 90 fractures were repaired using a bioresorbable panel for interposition (interposition group). Postoperative complications and surgical outcomes of the 2 groups were compared.

Results:

Preoperative diplopia in both groups (n = 30) was resolved except 1 in interposition group after the reduction. Enophthalmos was resolved in 10 cases in the splint group and in 6 cases in the interposition group. In postoperative CT scans, 20 of the 57 cases in the splint group exhibited under- or overcorrection, compared with 9 of the 90 cases in the interposition group (P < 0.05). There were no sinus infections or implant-related side effects in the interposition group except for implant extrusion in 4 cases, whereas 7 cases developed sinusitis in the splint group (P < 0.05).

Conclusions:

Endonasal endoscopic reduction using a bioresorbable panel may be considered as a surgical alternative for the treatment of medial orbital blowout fractures.
Right-Sided Complete Third Branchial Cleft Fistula
Authors: Yildirim Ugur , Atmaca Sinan , Koyuncu Mehmet
Published: January 2019

Branchial cleft anomalies occur due to insufficient closure of cavities during embryogenesis. These anomalies consist of cysts, sinuses, and fistulas, with the rarest type being fistulas. A 29-year-old male presented at the authors’ clinic with a right-sided complete third branchial cleft fistula. Fistula track excision surgery was successfully performed and no recurrence was observed in the 12-month follow-up after the surgery. While second branchial cleft fistula is the most common, third and fourth brancial cleft fistulas are extremely rare. In addition, they are usually incomplete and almost always on the left side.
From mathematical axioms to mathematical rules of proof: recent developments in proof analysis
Authors: Negri Sara , von Plato Jan
Published: January 2019

A short text in the hand of David Hilbert, discovered in Göttingen a century after it was written, shows that Hilbert had considered adding a 24th problem to his famous list of mathematical problems of the year 1900. The problem he had in mind was to find criteria for the simplicity of proofs and to develop a general theory of methods of proof in mathematics. In this paper, it is discussed to what extent proof theory has achieved the second of these aims.

This article is part of the theme issue ‘The notion of ‘simple proof’ - Hilbert's 24th problem’.
Identification of proofs via syzygies
Authors: Malheiro António , Reis José Francisco
Published: January 2019

In 1900, Hilbert gave a lecture at the International Congress of Mathematicians in Paris, for which he prepared 23 problems that mathematicians should solve during the twentieth century. It was found that there was a note on a 24th problem focusing on the problem of simplicity of proofs. One of the lines of research that was generated from this problem was the identification of proofs. In this article, we present a possible method for exploring the identification of proofs based on the membership problem original from the theory of polynomial rings. To show this, we start by giving a complete worked-out example of a membership problem, that is the problem of checking if a given polynomial belongs to an ideal generated by finitely many polynomials. This problem can be solved by considering Gröbner bases and the corresponding reductions. Each reduction is a simplification of the polynomial and it corresponds to a rewriting step. In proving that a polynomial is a member of an ideal, a rewriting process is used, and many different such processes can be considered. To better illustrate this, we consider a graph where each rewriting step corresponds to an edge, and thus a path corresponds to a rewriting process. In this paper, we consider the identification of paths, within the context of the membership problem, to propose a criterion of identification of proofs.

This article is part of the theme issue ‘The notion of ‘simple proof’ - Hilbert's 24th problem’.
Paracoccus suum sp. nov., isolated from a pig farm dust collector
Authors: Heo Jun , Cho Ha-Young , Kim Jeong-Seon , Hong Seung-Beom , Kwon Soon-Wo , Kim Soo-Jin
Published: January 2019

A Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, coccoid- or short rod-shaped bacterial strain, designated SC2-6T, was isolated from a dust collector of a pig farm located in Wanju-gun, Jeollabuk-do, Republic of Korea. Strain SC2-6T grew within the ranges of 10–37 °C (28–30 °C, optimally), pH 6.0–10.0 (pH 7.0–8.0, optimally) and 0–3% NaCl (w/v). The 16S rRNA gene sequence similarity of strain SC2-6T showed the highest values to

Paracoccus kondratievae

GBT (96.3%),

Paracoccus denitrificans

DSM 413T (96.3%) and

Paracoccus sanguinis

5503T (96.1%). The phylogenetic tree based on the 16S rRNA gene sequences revealed that strain SC2-6T belonged to the genus

Paracoccus

and clustered with

Paracoccus pacificus

F14T. The phylogenetic tree based on the rpoD gene sequences also demonstrated that strain SC2-6T fell into the clade of the genus

Paracoccus

. The DNA G+C content was 66.9 mol%. The major respiratory quinone was ubiquinone-10 and the major fatty acids (> 10% of the total fatty acids) were summed feature 8 (comprising C18 : 1 ω6c and/or C18 : 1 ω7c). The polar lipids were composed of diphosphatidylglycerol, phosphatidylcholine, an unidentified glycolipid, two unidentified aminolipids and two unidentified lipids. On the basis of phenotypic, phylogenetic and genomic data, strain SC2-6T was classified in the genus

Paracoccus

as a member of a novel species, for which the name Paracoccus suum sp. nov. is proposed. The type strain is SC2-6T (=KACC 19328T=NBRC 113110T).
A genome-wide association study identifies that the GDF5 and COL27A1 genes are associated with knee pain in UK Biobank (N = 171, 516)
Authors: Meng Weihua , Adams Mark J , Palmer Colin NA ,   The 23andMe Research Team, Shi Jingchunzi , Auton Adam , Ryan Kathleen A. , Jordan Joanne M. , Mitchell Braxton D. , Jackson Rebecca D. , Yau Michelle S. , McIntosh Andrew M , Smith Blair H
Published: January 2019

Objective

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and replicate them using cohorts from 23andMe, the Osteoarthritis Initiative (OAI), and the Johnston County Osteoarthritis Study (JoCo).

Methods

We performed a genome-wide association study of knee pain in the UK Biobank, where knee pain was ascertained through self-report and defined as “knee pain in the last month interfering with usual activities”. A total of 22,204 cases and 149,312 controls were included in the discovery analysis. We tested our top and independent SNPs (P < 5 × 10−8) for replication in 23andMe, OAI, and JoCo, then performed a joint meta-analysis between discovery and replication cohorts using GWAMA. We calculated the narrow-sense heritability of knee pain using Genome-wide Complex Trait Analysis (GCTA).

Results

We identified 2 loci that reached genome-wide significance, rs143384 located in the GDF5 (P = 1.32 × 10−12), a gene previously implicated in osteoarthritis, and rs2808772, located near COL27A1 (P = 1.49 × 10−8). These findings were subsequently replicated in independent cohorts and increased in significance in the joint meta-analysis (rs143384: P = 4.64 × 10−18; rs2808772: P −11 = 2.56 × 10−1’). The narrow sense heritability of knee pain was 0.08.

Conclusion

In this first reported genome-wide association meta-analysis of knee pain, we identified and replicated two loci in or near GDF5 and COL27A1 that are associated with knee pain.
ya||a: GPU-powered Spheroid Models for Mesenchyme and Epithelium
Authors: Germann Philipp , Marin-Riera Miquel , Sharpe James
Published: January 2019

ya||a is yet another parallel agent-based model for morphogenesis. It is several orders of magnitude faster than onventional models, because it runs on GPUs and because it has been designed for performance: Previously only complex and therefore computationally expensive models could simulate both mesenchyme and epithelium. We chose o extend the simple spheroid model by the addition of spin-like polarities to simulate epithelial sheets and tissue polarity. We also incorporate recently developed models for protrusions and migration. ya||a is written in concise, plain UDA/C++ and available at github.com/germannp/yalla under the MIT license.