bluuebunny/crossref_metadata_2025 huggingface dataset:
Judging homicide defendants by their brains: an empirical study on the use of neuroscience in homicide trials in Slovenia
Authors: Hafner Miha
Published: March 2019

This paper presents a study that analyses all available homicide trials in Slovenia between 1991 and 2015 for neuro-evidence. Almost every fifth case discusses neuroscience. The most prevalent type of neuro-evidence is neuro-psychological testing, less common are structural neuroimaging and electroencephalography, while we discovered no use of functional neuroimaging. The two largest categories of neurological conditions suffered by defendants are traumatic brain injury and brain damage due to long-term alcohol and drug abuse. When presented, neuro-evidence affected courts’ decisions in 85% of trials (15% of all tried homicide cases) and had an impact on the criminal sentence or another outcome of the trial in 79% of cases. By far most often neuro-evidence affects decisions regarding criminal capacity, ie insanity and (substantially) diminished capacity, which, in turn, strongly reflects in criminal sanctions. Neuroscience information is typically used to mitigate or even reduce the sentence, but never as an aggravating circumstance. It is also frequently utilized to support decisions about medical security measures (compulsory psychiatric treatment). This study further suggests that the double-edged sword of neuroscience is an elusive concept and that the mechanism by which neuroscience affects courts’ decisions in civil-law systems is different from the one in common-law jurisdictions.
Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing
Authors: Lu Yiyu , Fang Zhaoyuan , Li Meiyi , Chen Qian , Zeng Tao , Lu Lina , Chen Qilong , Zhang Hui , Zhou Qianmei , Sun Yan , Xue Xuefeng , Hu Yiyang , Chen Luonan , Su Shibing
Published: March 2019

Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths in Asia and Africa. Developing effective and non-invasive biomarkers of HCC for individual patients remains an urgent task for early diagnosis and convenient monitoring. Analyzing the transcriptomic profiles of peripheral blood mononuclear cells from both healthy donors and patients with chronic HBV infection in different states (i.e. HBV carrier, chronic hepatitis B, cirrhosis, and HCC), we identified a set of 19 candidate genes according to our algorithm of dynamic network biomarkers. These genes can both characterize different stages during HCC progression and identify cirrhosis as the critical transition stage before carcinogenesis. The interaction effects (i.e. co-expressions) of candidate genes were used to build an accurate prediction model: the so-called edge-based biomarker. Considering the convenience and robustness of biomarkers in clinical applications, we performed functional analysis, validated candidate genes in other independent samples of our collected cohort, and finally selected COL5A1, HLA-DQB1, MMP2, and CDK4 to build edge panel as prediction models. We demonstrated that the edge panel had great performance in both diagnosis and prognosis in terms of precision and specificity for HCC, especially for patients with alpha-fetoprotein-negative HCC. Our study not only provides a novel edge-based biomarker for non-invasive and effective diagnosis of HBV-associated HCC to each individual patient but also introduces a new way to integrate the interaction terms of individual molecules for clinical diagnosis and prognosis from the network and dynamics perspectives.
Conceptualization of the Morpheme and the Distinction Between Verbs and Nouns in Traditional Hebrew Grammars
Authors: Wormser Yehonatan
Published: March 2019

This paper deals with the traditional distinction between verbs and nouns, in which any verbal form is assigned to one of the seven constant verbal patterns (binyanim), while a nominal form might be assigned to various basic patterns which differ according to its root class (gizrah). It is suggested that this distinction, which is customarily applied in Hebrew grammars since the Middle Ages, is derived from an abstract implicit concept of the notion of the morpheme, which could be deduced from the stances expressed in the traditional discussion on the number of the Hebrew verbal patterns. Given that there is a fundamental semantic difference between the verbal system and the nominal system, this concept of the morpheme, based on the semantic profile of a given word, entailed the distinction between verbs and nouns.
Disentangling the physical parameters of gaseous nebulae and galaxies
Authors: Kashino Daichi , Inoue Akio K
Published: March 2019

We present an analysis to disentangle the connection between physical quantities that characterize the conditions of ionized H ii regions – metallicity (Z), ionization parameter (U), and electron density (ne) – and the global stellar mass (M*) and specific star formation rate (sSFR = SFR/M*) of the host galaxies. We construct composite spectra of galaxies at 0.027 ≤ z ≤ 0.25 from Sloan Digital Sky Survey, separating the sample into bins of M* and sSFR, and estimate the nebular conditions from the emission-line flux ratios. Specially, metallicity is estimated from the direct method based on the faint auroral lines [O iii]λ4363 and [O ii]λλ7320,7330. The derived metallicities cover a range of 12 + log O/H ∼ 7.6–8.9. It is found that the three nebular parameters, Z, U, and ne, are tightly correlated with the location in the M*–sSFR plane. With simple physically motivated ansätze, we derive scaling relations between these physical quantities by performing multiregression analysis. In particular, we find that U is primarily controlled by sSFR, as U∝sSFR0.43, but also depends significantly on both Z and ne. The derived partial dependence of U∝Z−0.36 is weaker than the apparent correlation (U∝Z−1.52). The partial dependence of U on ne is found to be $U \propto n_\mathrm{e}^{-0.29}$. The scaling relations we derived are in agreement with predictions from theoretical models and observations of each aspect of the link between these quantities. Our results provide a useful set of equations to predict the nebular conditions and emission-line fluxes of galaxies in semi-analytic models.
Cloud–cloud collision in the DR 21 cloud as a trigger of massive star formation
Authors: Dobashi Kazuhito , Shimoikura Tomomi , Katakura Shou , Nakamura Fumitaka , Shimajiri Yoshito
Published: March 2019

We report on a possible cloud–cloud collision in the DR 21 region, which we found through molecular observations with the Nobeyama 45 m telescope. We mapped an area of ∼8′ × 12′ around the region with 20 molecular lines including the 12CO(J = 1–0) and 13CO(J = 1–0) emission lines, and 16 of them were significantly detected. Based on the 12CO and 13CO data, we found five distinct velocity components in the observed region, and we call the molecular gas associated with these components “−42,”“−22,” “−3,” “9,” and “17” km s−1 clouds, after their typical radial velocities. The −3 km s−1 cloud is the main filamentary cloud ($\sim 31000\, M_{\odot }$) associated with young massive stars such as DR21 and DR21(OH), and the 9 km s−1 cloud is a smaller cloud ($\sim 3400\, M_{\odot }$) which may be an extension of the W75 region in the north. The other clouds are much smaller. We found a clear anticorrelation in the distributions of the −3 and 9 km s−1 clouds, and detected faint 12CO emission which had intermediate velocities bridging the two clouds at their intersection. These facts strongly indicate that the two clouds are colliding against each other. In addition, we found that DR21 and DR21(OH) are located in the periphery of the densest part of the 9 km s−1 cloud, which is consistent with results of recent numerical simulations of cloud–cloud collisions. We therefore suggest that the −3 and 9 km s−1 clouds are colliding, and that the collision induced the massive star formation in the DR21 cloud. The interaction of the −3 and 9 km s−1 clouds was previously suggested by Dickel, Dickel, and Wilson (1978, ApJ, 223, 840), and our results strongly support their hypothesis of the interaction.
VII Shakespeare
Authors: Young Jennifer , Smith Peter J , Parsons Elinor , Tarantino Elisabetta , Stelzer Emanuel , Bell Shirley , Haworth Ben , Lim Vanessa , O’Brien Sheilagh Ilona , Powell Louise
Published: March 2019

This chapter has four sections: 1. Editions and Textual Studies; 2. Shakespeare in the Theatre; 3. Shakespeare on Screen; 4. Criticism. Section 1 is by Jennifer Young; section 2 is by Peter J. Smith; section 3 is by Elinor Parsons; section 4(a) is by Elisabetta Tarantino; section 4(b) is by Emanuel Stelzer; section 4(c) is by Shirley Bell; section 4(d) is by Ben Haworth; section 4(e) is by Vanessa Lim; section 4(f) is by Sheilagh Ilona O’Brien; section 4(g) is by Louise Powell.
V The Early Sixteenth Century
Authors: Smith Edward
Published: March 2019

This chapter has six sections: 1. General: Drama and Prose; 2. General: Verse; 3. More; 4. Skelton; 5. Surrey; 6. Wyatt.
Furosemide Use and Time to Confirmation of Ureteral Patency During Intraoperative Cystoscopy
Authors: Patton Simon , Tanner Jean Paul , Prieto Isabel , Jackson Elisha , Greene Kristie , Bassaly Renee , Wyman Allison M.
Published: March 2019

OBJECTIVE:

To investigate the effect of intravenous administration of furosemide on the time to confirmation for ureteral patency during intraoperative cystoscopy.

METHODS:

In a double-blind randomized controlled trial, intravenous administration of furosemide 10 mg was compared with placebo (normal saline) to investigate the effect of furosemide on the time to confirmation for ureteral patency during intraoperative cystoscopy. The primary outcome was time to confirmation of ureteral patency. Secondary outcomes included adverse reaction to study medication and delayed diagnosis of ureteric injury. A sample size of 72 per group (N=144) was powered to detect a 3-minute difference in time to confirmation of ureteral patency between groups.

RESULTS:

From May 2017 to March 2018, 215 patients were eligible for inclusion and 150 were randomized, with 145 available for final evaluation. The two groups were similar in regard to baseline characteristics. The administration of intravenous furosemide 10 mg in a routine cystoscopy resulted in a shorter time to confirmation compared with the administration of the placebo (86.5 seconds, interquartile range 55.0–137.0 vs 165.0 seconds, interquartile range 77.0–280.0; P<.05). Furthermore, at any given time period, patients receiving intravenous administration of furosemide 10 mg were 2.3 times more likely to have ureteral patency confirmed compared with patients receiving normal saline (95% CI 1.59–3.23). There were no adverse events related to administration of intravenous furosemide and no delayed diagnoses of ureteric injury.

CONCLUSION:

Compared with placebo, intravenous administration of 10 mg furosemide at time of intraoperative cystoscopy resulted in a statistically significantly shorter time to confirmation of ureteral patency, though the clinical significance of this finding is small.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02960412.
What Is New in Cesarean Delivery?
Authors: Hansen Wendy F.
Published: March 2019

This month we focus on current research in cesarean delivery. Dr. Hansen discusses eight recent publications, which are concluded with a “bottom-line” that is the take-home message. A complete reference for each can be found on Box 1 on this page along with direct links to abstracts.
Nonunited Lower Extremity Fractures Initially Repaired Outside the Developed Western World Develop a High Rate of Postoperative Complications After Nonunion Repair
Authors: Carlock Kurtis D. , Hildebrandt Kyle R. , Konda Sanjit R. , Egol Kenneth A.
Published: March 2019

Objectives:

To evaluate the clinical and functional outcomes after operative repair of nonunited lower extremity fractures initially repaired outside the developed Western world.

Design:

Retrospective analysis of prospectively collected data.

Setting:

Academic medical center.

Patients/Participants:

From September 2004 through February 2017, 227 patients who underwent operative repair of a lower extremity fracture nonunion were prospectively enrolled in a research registry. All patients underwent previous fracture surgery and had at least 12 months of postoperative follow-up.

Intervention:

Repair of lower extremity fracture nonunion.

Main Outcome Measurements:

Postoperative complications, reoperation rate, time to union, and functional outcomes were assessed using the Short Musculoskeletal Function Assessment and Visual Analog Scale pain scores. Univariate and multivariate analyses were performed to evaluate the differences in patients who underwent initial fracture repair outside the developed Western world as opposed to within the United States.

Results:

Twenty-one patients (9.3%) underwent initial fracture repair outside the developed Western world. These patients had a greater incidence of infected nonunions (47.6% vs. 23.3%; P = 0.015) and failure of a previous implant at the time of presentation (52.4% vs. 22.8%; P = 0.003) than those initially managed within the United States. This cohort also experienced a greater rate of postoperative complications after nonunion repair (23.8% vs. 6.3%; P = 0.016). The geographic location of initial fracture repair was not associated with postoperative Short Musculoskeletal Function Assessment scores or Visual Analog Scale pain scores after controlling for possible confounding variables.

Conclusions:

Patients who present with a nonunited lower extremity fracture initially repaired outside the developed Western world experience a high rate of postoperative complications after fracture nonunion repair but can expect good short- and long-term functional outcomes.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Unilateral Osteotomy of Lumbar Facet Joint Induces a Mouse Model of Lumbar Facet Joint Osteoarthritis
Authors: Ni Shuangfei , Cao Yong , Liao Shenghui , Duan Chunyue , Jiang Liyuan , Hu Jianzhong , Lu Hongbin , Wu Tianding
Published: March 2019

Study Design.

The lumbar facet joint (LFJ) osteoarthritis (OA) model that highly mimics the clinical conditions was established and evaluated.

Objective.

Here, we innovatively constructed and evaluated the aberrant mechanical loading-related LFJ OA model.

Summary of Background Data.

LFJ is the only true synovial joint in a functional spinal unit in mammals. The LFJ osteoarthritis is considered to contribute 15% to 45% of low back pain. The establish of animal models highly mimicking the clinical conditions is a useful tool for the investigation of LFJ OA. However, the previously established animal models damaged the LFJ structure directly, which did not demonstrate the effect of aberrant mechanical loading on the development of LFJ osteoarthritis.

Methods.

In the present study, an animal model for LFJ degeneration was established by the unilateral osteotomy of LFJ (OLFJ) in L4/5 unit to induce the spine instability. Then, the change of contralateral LFJ was evaluated by morphological and molecular biological techniques.

Results.

We showed that the OLFJ induced instability accelerated the cartilage degeneration of the contralateral LFJ. Importantly, the SRμCT elucidated that the three-dimensional structure of the subchondral bone changed in contralateral LFJ, indicated as the abnormity of bone volume/total volume ratio (BV/TV), trabecular pattern factor (Tb. Pf), and the trabecular thickness (Tb. Th). Immunostaining further demonstrated the uncoupled osteoclastic bone resorption, and bone formation in the subchondral bone of contralateral LFJ, indicated as increased activity of osteoclast, osteoblast, and Type H vessels.

Conclusion.

We develop a novel LFJ OA model demonstrating the effect of abnormal mechanical instability on the degeneration of LFJ. This LFJ degeneration model that highly mimics the clinical conditions is a valuable tool to investigate the LFJ osteoarthritis.

Level of Evidence: N/A
Arterial Stiffness is Associated With Moderate to Vigorous Physical Activity Levels in Post-Myocardial Infarction Patients
Authors: Oliveira Nórton Luís , Alves Alberto Jorge , Ruescas-Nicolau Maria-Arantzazu , Silva Gustavo , Teixeira Madalena , Ribeiro Fernando , Oliveira José
Published: March 2019

Purpose:

Arterial stiffness has shown independent predictive value for all-cause and cardiovascular mortalities, as well as fatal and nonfatal coronary events. Physical activity (PA) is associated with reduced cardiovascular morbidity and mortality. The study aims to analyze the cross-sectional association of arterial stiffness with objectively measured PA in patients following acute myocardial infarction.

Methods:

One hundred patients were consecutively recruited after experiencing an acute myocardial infarction. Central arterial stiffness was measured through carotid-femoral pulse wave velocity (cf-PWV) and daily PA was assessed objectively during 7 consecutive days with accelerometers. To be valid, data required recordings of at least 8 hr/d on 5 d.

Results:

The cf-PWV showed a negative and significant association with total weekly time spent in moderate to vigorous PA (MVPA) (r = −0.416, P < .001). Patients classified as having higher risk according to arterial stiffness values (cf-PWV ≥10 m/sec) showed significantly lower time spent in MVPA than those below that threshold. The cf-PWV was significantly lower in patients performing >300 min of MVPA/wk than in those performing <150 min/wk (8.53 ± 2.08 vs 10.3 ± 2.44 m/sec, P = .021). Differences remained significant after adjustment for several confounders.

Conclusions:

Moderate to vigorous PA was inversely associated with arterial stiffness and time spent in MVPA was lower in patients after acute myocardial infarction, with cf-PWV above the risk threshold value (≥10 m/sec). These results seem to reinforce the importance of PA as a nonpharmacological tool for secondary cardiovascular prevention.
Somatoprosthetic Rehabilitation of Digitus Minimus Using Mini-Dental Implant: A Report of Negative Outcome
Authors: Aggarwal Himanshi , Anwar Mohd , Singh Saumyendra Vikram , Mishra Brijesh
Published: March 2019

Introduction

Although digitus minimus may possess the least range of motion in all fingers, its amputation due to any reason leads to severe emotional trauma along with compromise in aesthetics and function. Inadequate retention associated with conventional vacuum-retained finger prosthesis is one of the major areas of concern.

Case Report

A 23-year-old male patient reported with amputated little finger of left hand. Examination revealed minimal residual digit. A mini-dental implant with O-ring type of attachment was used to retain the customized silicone digit after early loading protocol. Excellent immediate results in terms of aesthetics, retention, and psychological satisfaction to the patient were obtained. However, implant failed at 3-months follow-up.

Conclusions

The use of mini-dental implants to retain finger prostheses in patients with short residual digits seems to be a viable clinical concept; however, this technique should be used cautiously.
Morphometric and Physiologic Modeling Study for Endovascular Occlusion in Pediatric Trauma Patients
Authors: Carrillo Louis , Skibber Max , Kumar Akshita , George Mitchell , Aziz Shahroz , T. Harting Matthew , Moore Laura J. , Cox Charles S.
Published: March 2019

The use of the resuscitative endovascular balloon occlusion of the aorta (REBOA) device is expanding in adult trauma. Reports of its use in pediatric patients have been published, but no guidelines currently exist nor has it been Food and Drug Administration approved in pediatrics. This project develops a model to determine appropriate balloon inflation volumes in pediatric patients to guide potential use. Artificial aortas were three-dimensional (3D) printed using synthetic polymers. Segments were created based on aortic diameters from 289 pediatric trauma patients’ computer tomography (CT) scans. These aortic segments were inserted into a circulatory system model featuring two branches to simulate abdominal and upper body perfusion (cerebral, cardiac, and upper extremities). Sonographic flow meters and pressure transducers were placed along the circuit, and measurements were recorded as a REBOA device was inflated in the aortic segment. A negative sigmoidal relationship was observed between device inflation and aortic flow occlusion, with the initial 50% of inflation causing a 10% reduction in flow, followed by a steep decline. With increasing inflation, distal aortic flow and pressure were found to have an inverse relationship with the upper body branch metrics. In conclusion, pediatric patients present with a range of vessel diameters that occlude at various REBOA balloon inflation volumes. This study provides a basis to establish initial inflation volumes for safe REBOA deployment in appropriate pediatric trauma patients.
Investigating the presence of qacA/B and mecA genes in Staphylococcus aureus strains isolated from metro stations in Tehran city of Iran
Authors: Arab YarMohammadi Mona , Eslami Majid , Amirmozafari Nour
Published: March 2019

Objective:

Staphylococcus aureus is responsible for a wide range of infections by invasion and toxin production in humans. The aim of this study was to investigate the presence of S. aureus at the surface environment of metro stations and the carriage of methicillin and quaternary ammonium compound (QAC) resistance genes.

Materials and methods:

Sampling was carried out in Tehran Metro from 2016 to 2017. One hundred samples were collected from metro wagons. The antibiotic susceptibility test was done with the disk diffusion test using cefoxitin, cefotaxime, cotrimoxazole, methicillin, and oxacillin antibiotics. Sensitivity to Deconex AF was measured by Broth dilution test. PCR technique was used to investigate the presence of mecA and qacA/B genes using specific primers.

Results:

Of the 40 samples isolated from the metro environment, resistance to cefoxitin was 2.5% (MRSA). The highest resistance rate was against amoxicillin (50%) and the lowest rate was against vancomycin and linezolid (0%). Also, 30% of the samples contained the qacA/B gene and 42.5% contained the mecA gene and 27.5% contained both genes. Forty percent of isolates had a minimum inhibitory concentration of 2.5 mg/ml and 40% had a MIC of 25 mg/ml.

Conclusion:

In this study, there was a close relationship between resistance to methicillin and resistance to QACs in S. aureus isolated from metro stations. It has also been shown that these isolates carry antibiotic resistance genes and are resistant to most common antibiotics used to eradicate these bacteria, such as third-generation cephalosporins, methicillin, and oxacillin, which are considered as serious warning to society.
Small Text on Product Labels Poses a Special Challenge for Emerging Presbyopes
Authors: Xu Renfeng , Chelales Erika , Rickert Martin , Muessel Rachel , Meyer Dawn , Thibos Larry N. , Bradley Arthur , Kollbaum Pete
Published: March 2019

SIGNIFICANCE

Approximately 10% of the lowercase text on nonprescription drug labels is smaller than the 1 mm required by the Food and Drug Administration. The small size, combined with the progressive decline in accommodative amplitude and gain, poses a reading challenge for middle-aged emerging presbyopes.

PURPOSE

The purpose of this study was to evaluate the impact of progressing presbyopia and near adds on the ability of middle-aged patients to read small text routinely encountered on product labels.

METHODS

Geometrical optics was used to determine the impact of changing viewing distance, accommodation, and pupil size on retinal blur size. We photographed 261 consumer product labels in grocery, personal care, and nonprescription (over-the-counter) drug categories and used character recognition software to identify and size 255,298 printed letters. We computed the impact of viewing distance on the ratio of blur to letter detail and used published blur ratios of ≤4 and ≤2 to identify the conditions that allowed for letter recognition and proficient reading, respectively.

RESULTS

Median/mode lowercase letter heights (in millimeters) were 1.39/1.16, 1.29/1.15, and 1.18/1.01, respectively, for groceries, personal care, and over-the-counter drug categories. Despite the increased angular subtense of approaching letters, blur ratios generally increased with reduced viewing distance because of increased defocus. Increased viewing distance decreased blur, but small (e.g., 1 mm) letters became too small to read proficiently (angular size <10 arcminutes) for distances beyond 37 cm. With larger pupils, blur ratios were too large to support proficient reading when accommodative amplitude dropped to ≤3 diopters. An add power sufficient to bring the far point closer than 37 cm was required to proficiently read small text.

CONCLUSIONS

Product labels, especially nonprescription drug packages, typically use fonts that are too small to be read proficiently by unaided emmetropes with emerging presbyopia. This problem can be ameliorated by correction of presbyopia at an earlier age and with higher add powers.
Learning Curves for Two Fiberscopes in Simulated Difficult Airway Scenario With Cumulative Sum Method
Authors: Altun Demet , Ozkan-Seyhan Tulay , Camci Emre , Sivrikoz Nukhet , Orhan-Sungur Mukadder
Published: March 2019

Introduction

The aims of this randomized prospective mannequin study were to determine the amount of attempts required for successful intubation using different fiberscopes (Bonfils and SensaScope) by inexperienced anesthesiologists in a difficult airway scenario and to build the associated learning curves.

Methods

Difficult airway simulation was achieved with tongue edema in mannequin. After approval of volunteers, we asked 15 anesthesiology residents without any experience with fiberscopes to intubate with each device in a random order. Intubation success (endotracheal intubation within 120 seconds), the degree of difficulty of intubation, and reality of simulation using a 10-point scale were recorded. Learning curves were generated with cumulative sum method.

Results

With Bonfils, 13 volunteers were able to pass lower decision boundary with a median number of 26 [95% confidence interval (CI) = 21.4–25.9] attempts, whereas in SensaScope, the same outcome was observed in 10 residents with a median number of attempts of 26 (95% CI = 23.5–32.5). Total success rate was found significantly higher with Bonfils compared with SensaScope (550/600 vs 512/600, respectively, P < 0.001). Intubation with Bonfils was considered as less difficult compared with SensaScope [median = 4 (95% CI = 3.32–4.42) and 6 (95% CI = 4.96–6.64), P = 0.01, respectively]. The reality of the simulation was rated as a median of 5 (95% CI = 4.37–5.8).

Conclusions

Although a similar number of attempts were required to reach predetermined competency for both fiberscopes, only 10 of residents were able to obtain the targeted success using SensaScope as compared with 13 with Bonfils. Inexperienced residents found intubation via Bonfils less difficult than SensaScope. High individual variability in obtaining competency observed in this study with cumulative sum analysis underlines the importance of defining success a priori to simulation, the need for follow-up of individual progress, and the need to offer adequate trials to achieve competency. Therefore, learning opportunities should be adapted accordingly.
Evaluation of antioxidant activity of alcohol-free Moru wine using on-line HPLC
Authors: Na Ha Gyoon , Cha Yun Ju , Shin Ji Woo , Kim Jun Hyung , Son Hyeon Uk , Shin Yong Woon , Jung Min Young , Choi Moon Suk , Jang Ki-Hyo
Published: March 2019

In this study, the chemical composition and antioxidant activities of Moru wine and alcohol-free Moru wine were evaluated. To prepare the alcohol-free analogue, Moru wine was subjected to either atmospheric distillation (NA-AD) or vacuum distillation (80 mbar, 55℃, NA-VD). Among the three different preparations of Moru wines, namely, Moru wine, NA-AD, and NA-VD, the total acidity was the highest in NA-VD, while the soluble solid content was the highest in Moru wine. The total phenolic content, total flavonoid content, and ABTS radical scavenging activity were the highest in NA-AD. The three different preparations of Moru wines were examined by an on-line high-performance liquid chromatography (HPLC)-2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)-based assay to identify the compounds responsible for the radical scavenging activity of wines. The results obtained for NA-AD and NA-VD in the on-line screening HPLC-ABTS assay were similar. At least 10 different compounds, namely, gallic acid, protocatechuic acid, chlorogenic acid, vanillic acid, caffeic acid, syringic acid, t-ferulic acid, rutin, naringin, and t-cinnamic acid, were identified from Moru wine, NA-AD, and NA-VD. Gallic acid (10.35-24.69 μg/mL) and syringic acid (9.29-43.98 μg /mL) were found to be the major polyphenols in Moru wine, NA-AD, and NA-VD.
Lifetime changes in CD4 count, viral load suppression and adherence among adolescents living with HIV in urban Peru
Authors: Rodriguez Carly A , Kolevic Lenka , Ramos Alicia , Wong Milagros , Munoz Maribel , Patel Kunjal , Franke Molly F
Published: March 2019

Introduction

Viral load suppression and adherence to combined antiretroviral therapy (cART) have been shown to be lower in adolescents than in other age groups; however, this relationship has not been documented longitudinally from childhood to adolescence and has rarely been examined outside of high-resource settings and sub-Saharan Africa. To address this knowledge gap, we quantified longitudinal changes in CD4 cell count, viral load suppression, and cART adherence in adolescents living with HIV in urban, Peru.

Methods

We conducted a retrospective chart review among adolescents ages 10-18 years on cART and receiving care at a large, public sector pediatric hospital as of December 2015. We abstracted clinical notes indicating nonadherence and viral load and CD4 counts from childhood to adolescence. We modeled the association between age and each outcome with restricted cubic splines accounting for multiple observations per person, and graphed study outcomes by age.

Results

A median of 7.7 years (25th percentile=4.9, 75th percentile=10.2) of follow up were observed for 128 adolescents. Nearly 70% of patients had at least one nonadherence note and the proportion with nonadherence increased log-linearly with age (p<0.0001). The peak proportion with viral load suppression was 84% (95% CI: 79, 88) at age 13, which dropped to 67% (95% CI: 47, 83) by age 18. Mean CD4 count decreased at age 13, dropping from 723 cells/mm3 (95% CI: 666, 784) to 429 cells/mm3 (95% CI: 356, 517) by age 18.

Conclusion

This is the first report from Latin America to examine longitudinal changes in HIV outcomes from childhood into adolescence. Consistent with the limited evidence from other settings, decreases in viral load suppression and mean CD4 count occurred in early adolescence in tandem with increases in nonadherence. Adolescent-friendly cART adherence support interventions to target this critical period are urgently needed.
Patterns and predictors ofStaphylococcus aureuscarriage during the first year of life; a longitudinal study
Authors: Reiss-Mandel Aylana , Rubin Carmit , Maayan-Mezger Ayala , Novikov Ilya , Jaber Hanaa , Dolitzky Mordechay , Freedman Laurence , Rahav Galia , Regev-Yochay Gili
Published: March 2019

Objectives’

To determine the patterns ofS. aureuscarriage in the first year of life, its determinants and dynamics of transmission between mothers and infants.

Methods

Prospective longitudinal cohort study ofS. aureuscarriage among mothers and their infants. Monthly screenings from pregnancy/birth through the first year of the infant’s life. Medical and lifestyle data was collected. InfantS. aureuscarriage was detected by rectal and nasal swabs and maternal carriage by nasal swabs. Multivariate analysis and an NLMixed model were used to determine predictors of carriage andS. aureuspersistence.

Results

130S. aureuscarrier women and their 132 infants were included in the study. 93% of the infants acquiredS. aureussometime during the first year of life, 64% of them acquired the maternal strain, mostly (66%) during the first month of life. 70 women (52.50%) and 17 infants (14%) carriedS. aureuspersistently. Early acquisition ofS. aureuscarriage was associated with longer duration of initial carriage and was the most significant predictor ofS. aureuspersistence, while day-care center attendance was negatively associated with persistent carriage.

Conclusions

Early acquisition ofS. aureus, mostly from the mother, is an important determinant of carriage persistence in infancy.
Measures of states of consciousness during attentional and cognitive load
Authors: Nilsen André S. , Juel Bjørn E. , Storm Johan F.
Published: March 2019

Background

Developing and testing methods for reliably assessing states of consciousness in humans is important for both basic research and clinical purposes. Several potential measures, partly grounded in theoretical developments, have been proposed, and some of them seem to reliably distinguish between conscious and unconscious brain states. However, the degrees to which these measures may also be affected by changes in brain activity or conditions that can occur within conscious brain states have rarely been tested. In this study we test whether several of these measures are modulated by attentional load and related use of cognitive resources.

Methods

We recorded EEG from 12 participants while they passively received three types of stimuli: (1) transcranial magnetic stimulation (TMS) pulses (for measuring perturbational complexity), (2) auditory stimuli (for detection of auditory pattern deviants), or (3) audible clicks from a clock (spontaneous EEG, for measures of signal diversity and functional connectivity). We investigated whether the measures significantly differed between the passive condition and a attentional and cognitively demanding working memory task.

Results

Our results showed that in the attention-based auditory P3b ERP measure (global auditory pattern deviant) was significantly affected by increased attentional and cognitive load, while the various measures based on spontaneous and perturbed EEG were not affected.

Conclusion

Measures of conscious state based on complexity, diversity, and effective connectivity, are not affected by attentional and cognitive load, suggesting that these measures can be used to test both for the presence and absence of consciousness.
Structure-guided enhancement of selectivity of chemical probe inhibitors targeting bacterial seryl-tRNA synthetase
Authors: Cain Ricky , Salimraj Ramya , Punekar Avinash S. , Bellini Dom , Fishwick Colin W. G. , Czaplewski Lloyd , Scott David J. , Harris Gemma , Dowson Christopher G. , Lloyd Adrian J. , Roper David I.
Published: March 2019

Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high resolution X-ray crystal structures of the Escherichia coli and Staphylococcus aureus seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than two orders of magnitude compared to their human homologue, demonstrating a route to selective chemical inhibition of these bacterial targets.
Effective Clustering for Single Cell Sequencing Cancer Data
Authors: Ciccolella Simone , Patterson Murray , Bonizzoni Paola , Vedova Gianluca Della
Published: March 2019

Single cell sequencing (SCS) technologies provide a level of resolution that makes it indispensable for inferring from a sequenced tumor, evolutionary trees or phylogenies representing an accumulation of cancerous mutations. A drawback of SCS is elevated false negative and missing value rates, resulting in a large space of possible solutions, which in turn makes it difficult, sometimes infeasible using current approaches and tools. One possible solution is to reduce the size of an SCS instance — usually represented as a matrix of presence, absence, and uncertainty of the mutations found in the different sequenced cells — and to infer the tree from this reduced-size instance. In this work, we present a new clustering procedure aimed at clustering suchcategoricalvector, or matrix data — here representing SCS instances, calledcelluloid. We show that celluloid clusters mutations with high precision: never pairing too many mutations that are unrelated in the ground truth, but also obtains accurate results in terms of the phylogeny inferred downstream from the reduced instance produced by this method. We demonstrate the usefulness of a clustering step by applying the entire pipeline (clustering + inference method) to a real dataset, showing a significant reduction in the runtime, raising considerably the upper bound on the size of SCS instances which can be solved in practice. Our approach, celluloid:clustering single cell sequencing data around centroidsis available athttps://github.com/AlgoLab/celluloid/under an MIT license, as well as on thePython Package Index(PyPI) athttps://pypi.org/project/celluloid-clust/
Honey bee (Apis mellifera) larval pheromones regulate gene expression related to foraging task specialization
Authors: Ma R , Rangel J , Grozinger CM
Published: March 2019

Background

Foraging behavior in honey bees (Apis mellifera) is a complex phenotype which is regulated by physiological state and social signals. How these factors are integrated at the molecular level to modulate foraging behavior has not been well-characterized. The transition of worker bees from nursing to foraging behavior is mediated by large-scale changes in brain gene expression, which are influenced by pheromones produced by the queen and larvae. Larval pheromones can also stimulate foragers to leave the colony to collect pollen, but the mechanisms underpinning this rapid behavioral plasticity are unknown. Furthermore, the mechanisms through which foragers specialize on collecting nectar or pollen, and how larval pheromones impact these different behavioral states, remains to be determined. Here, we investigated the patterns of gene expression related to rapid behavioral plasticity and task allocation among honey bee foragers exposed to two larval pheromones, brood pheromone (BP) and (E)-beta-ocimene (EBO).

Results

We hypothesized that both pheromones would alter expression of genes in the brain related to foraging and would differentially impact expression of genes in the brains of pollen compared to nectar foragers. Combining data reduction, clustering, and network analysis methods, we found that foraging preference (nectar vs. pollen) and pheromone exposure are each associated with specific brain gene expression profiles. Furthermore, pheromone exposure has a strong transcriptional effect on genes that are preferentially expressed in nectar foragers. Representation factor analysis between our study and previous landmark honey bee transcriptome studies revealed significant overlaps for both pheromone communication and foraging task specialization.

Conclusions

Social signals (i.e. pheromones) may invoke foraging-related genes to upregulate pollen foraging at both long and short time scales. These results provide new insights into how social signals integrate with task specialization at the molecular level and highlights the important role that brain gene expression plays in behavioral plasticity across time scales.
CDC6 regulates both G2/M transition and metaphase-to-anaphase transition during the first meiosis of mouse oocytes
Authors: Yi Zi-Yun , Meng Tie-Gang , Ma Xue-Shan , Li Jian , Zhang Chun-Hui , Ouyang Ying-Chun , Schatten Heide , Qiao Jie , Sun Qing-Yuan , Qian Wei-Ping
Published: March 2019

Cell division cycle protein CDC6 is essential for the initiation of DNA replication. CDC6 was recently shown to inhibit the microtubule-organizing activity of the centrosome. Here, we show that CDC6 is localized to the spindle from Pro-MI to MII stages of oocytes, and it plays important roles at two critical steps of oocyte meiotic maturation. CDC6 depletion facilitated the G2/M transition (GV breakdown, GVBD) through regulation of Cdh1 and cyclin B1 expression and CDK1 phosphorylation in a GVBD-inhibiting culture system containing milrinone. Furthermore, GVBD was significantly decreased after knockdown of cyclin B1 in CDC6-depleted oocytes, indicating that the effect of CDC6 loss on GVBD stimulation was mediated, at least in part, by raising cyclin B1. Knockdown of CDC6 also caused abnormal localization of γ-tubulin, resulting in defective spindles, misaligned chromosomes, cyclin B1 accumulation and spindle assembly checkpoint (SAC) activation, leading to significant Pro-MI/MI arrest and PB1 extrusion failure. These phenotypes were also confirmed by time-lapse live cell imaging analysis. The results indicate that CDC6 is indispensable for maintaining G2 arrest of meiosis and functions in G2/M checkpoint regulation in mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.

Summary statement

We show that CDC6 is indispensable for maintaining G2 arrest of mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.
MethylCal: Bayesian calibration of methylation levels
Authors: Ochoa Eguzkine , Zuber Verena , Fernandez-Jimenez Nora , Bilbao Jose Ramon , Clark Graeme R. , Maher Eamonn R. , Bottolo Leonardo
Published: March 2019

Bisulfite amplicon sequencing has become the primary choice for single-base methylation quantification of multiple targets in parallel. The main limitation of this technology is a preferential amplification of an allele and strand in the PCR due to methylation state. This effect, known as “PCR bias”, causes inaccurate estimation of the methylation levels and calibration methods based on standard controls have been proposed to correct for it. Here, we present a Bayesian calibration tool, MethylCal, which can analyse jointly all CpGs within a DMR or CpG island, avoiding “one-at-a-time” CpG calibration. This enables more precise modeling of the methylation levels observed in the standard controls. It also provides accurate predictions of the methylation levels not considered in the controlled experiment, a feature that is paramount in the derivation of the corrected methylation degree. We tested the proposed method on eight independent assays (two CpG islands and six imprinting DMRs) and demonstrated its benefits, including the ability to detect outliers. We also evaluated MethylCal’s calibration in two practical cases, a clinical diagnostic test on 18 patients potentially affected by Beckwith-Wiedemann syndrome, and 17 individuals with celiac disease. The calibration of the methylation levels obtained by MethylCal allows a clearer identification of patients undergoing loss or gain of methylation in borderline cases and could influence further clinical or treatment decisions. MethylCal is availability as an R package onhttps://github.com/lb664/MethylCal.
Random birth order and bursty Notch ligand expression drive the stochastic AC/VU cell fate decision inC. elegans
Authors: Kienle Simone , Gritti Nicola , Kroll Jason R. , Kriselj Ana , Goos Yvonne , van Zon Jeroen S.
Published: March 2019

Cells in developing organisms must robustly assume the correct fate in order to fulfill their specific function. At the same time, cells are strongly affected by molecular fluctuations, i.e. ‘noise’, leading to inherent variability in individual cells. During development, some cells are thought to exploit such molecular noise to drive stochastic cell fate decisions, with cells randomly picking one cell fate out of several possible ones. Yet, how molecular noise drives such decisions is an open question. We address this question using a novel quantitative approach to study one of the best-understood stochastic cell fate decisions: the AC/VU decision inC. elegansgonad development. Here, two initially equivalent cells, Z1.ppp and Z4.aaa, interact, so that one cell becomes the anchor cell (AC) and the other a ventral uterine precursor cell (VU). It is thought that the symmetry is broken when small molecular fluctuations are amplified into cell fate by positive feedback loops in the Notch signaling pathway. To identify the noise sources that drive the AC/VU decision, we used a novel time-lapse microscopy approach to follow expression dynamics in live animals and single molecule FISH to quantify gene expression with single mRNA resolution. We found not only that random Z1.ppp/Z4.aaa birth order biased the decision outcome, with the first-born cell typically assuming VU fate, but that the strength of this bias and the speed of the decision decreased as the two cells were born closer together in time. Moreover, we find that the Notch ligandlag-2/Deltaexhibited strongly stochastic expression already in the two mother cells, Z1.pp/Z4.aa. Combining experiments with mathematical models, we showed that the resulting asymmetry inlag-2/Deltalevels inherited by the daughter cells, Z1.ppp/Z4.aaa, stochastic symmetry breaking when both cells are born at similar times. Together, our results suggest that two independent noise sources, birth order and stochasticlag-2/Deltaexpression, are exploited to amplify noise into cell fate in a manner that ensures a robust decision.
Polyphosphate initiates tau aggregation through intra- and intermolecular scaffolding
Authors: Wickramasinghe S. P. , Lempart J. , Merens H. E. , Murphy J. , Jakob U. , Rhoades E.
Published: March 2019

The aggregation and deposition of tau is a hallmark of a class of neurodegenerative diseases called tauopathies. Despite intensive study, cellular and molecular factors that trigger tau aggregation are not well understood. Here we provide evidence for two mechanisms relevant to the initiation of tau aggregation in the presence of cytoplasmic polyphosphates (polyP): changes in the conformational ensemble of monomer tau and noncovalent cross-linking of multiple tau monomers. We identified conformational changes throughout full-length tau, most notably diminishment of long-range interactions between the termini coupled with compaction of the microtubule binding and proline rich regions. We found that while the proline rich and microtubule binding regions both contain polyP binding sites, the proline rich region is a requisite for compaction of the microtubule binding region upon binding. Additionally, both the magnitude of the conformational change and the aggregation of tau are dependent on the chain length of the polyP polymer. Longer polyP chains are more effective at intermolecular, noncovalent cross-linking of tau. These observations provide an understanding of the initial steps of tau aggregation through interaction with a physiologically relevant aggregation inducer.