bluuebunny/crossref_metadata_2025 huggingface dataset:
Methanol soluble extractives of Pinus merkusii bark and its antioxidant activity
Authors: Masendra  , Purba B A V , Lukmandaru G
Published: September 2020

The major function of bark in trees is to protect the living tissues. This is due to the chemical extractives in the bark such as polyphenols and terpenoids. In Indonesia, the bark ofPinus merkusiiis of high economic value due to its use in the production of wood and oleoresins. Also, the presence of polyphenols in its bark has the potential of being used as antioxidant agents. Based on this, the aim of this study was to investigate antioxidant activity from the methanol extract ofP. merkusii bark.This methanol extract ofP. merkusiiwas subjected to gas chromatography mass spectrometric (GC-MS) method and antioxidant activity assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The GC-MS analysis showed that the extract sample contained phenolics and sugars as minor compounds with fatty acids and alcohols as major components. The antioxidant activity (IC50) of the sample was 1452.8 ± 208 μg/mL, which could be as a result of the presence of phenolic compounds, fatty acids and alcohols, as well as steroids and alkaloid in it.
Preparation and characterization of Gigantochloa robusta activated carbon to reduce COD levels of pharmaceutical waste
Authors: Saputra N A , Saputra I S , Yuniarti K , Andianto
Published: September 2020

Activated carbon prepared from Gigantochloa robusta was studied to reduce Chemical Oxygen Demand (COD) levels in pharmaceutical-liquid waste. Physical activator was used to produce Activated Carbon (AC) in temperature regulation of 750°C retort for 60 minutes. Dosage of AC powder were 0.25%, 0.5%, and 0.75% of 250 mL of pharmaceutical waste, respectively. Retention time variations of 30, 60, and 90 minutes were used in laboratory scale experiments. Proximate analysis including volatile substances, water content, ash content, fixed carbon and I2 adsorption were observed to characterize AC. This research shows that the produced AC successfully meets the SNI 06-3730-1995 standards. The study results show variations in COD removal between 9-23%. The best result was performed by the AC dosage of 0.75% over a 60 minutes retention time.
Microwave assisted dilute organic acid pre-treatment of oil palm empty fruit bunch to improve enzyme accessibility
Authors: Solihat N N , Hermiati E , Adi D T N
Published: September 2020

The depletion of fossil fuel is intriguing for researchers to find sustainable energy. Oil palm empty fruit bunch (OPEFB) is abundant biomass in Indonesia which is potential to be converted into bioethanol because of its high cellulose content. Suitable pre-treatment could increase the effectiveness of cellulose conversion into sugars. The aim of this study is to evaluate the effectiveness of Microwave-assisted Oxalic Acid pre-treatment (MOxA) and Enzymatic Hydrolysis (EH) to improve enzyme accessibility through variation of heating temperature, irradiation time, and EH incubation time. The higher the microwave heating temperature, longer irradiation time, and longer EH incubation time, the higher the glucose yield per pulp (GY) and reducing sugar yield (RSY) were observed. After MOxA at 200°C-15 min, as much as 43.22 % GY per initial biomass was obtained by EH for 10 days. SEM images showed more ruptures on the surface area of OPEFB fibre after MOxA that supported in increasing of enzyme digestibility. The XRD spectra demonstrated that the crystallinity index (CI) increased after MOxA because pre-treatment reduced amorphous components in the biomass. In addition, the FTIR spectra showed that peak intensity at 1714 cm−1 corresponded to hemicellulose was gradually reduced after MOxA while peaks corresponded to lignin was more discernible.
Biopellet properties of agathis wood fortified with its peeled-off bark
Authors: Wistara N J , Bahri S , Pari G
Published: September 2020

The agathis bark is expected to increase the energy content and durability of the resulting biopellet. The present research was aimed to analyze chemical components of agathis and to determine the quality of agathis wood biopellet fortified with it loosen bark. The klason lignin, extractives, holocellulose and α-cellulose content of wood and bark of the agathis were determined following the standard procedures of TAPPI T 222 0m-88, TAPPI T 204 0m-88, and Browning (1967), respectively. Biopellets of 15 mm diameter were prepared with pelletizing pressure of 1500 psi. The moisture content, ash content, density, durability, and calorific value of the resulting biopellet were compared to those required by DIN EN 14961-2 and 51731 standards. The α-cellulose and holocellulose content of the agathis bark were found lower than these of its wood. However, its klason lignin, extractive, and ash content were higher than these of its wood. The resulting biopellet retained the density of 0.61-0.71 g/cm3, moisture content of 0.42-4.52%, ash content of 0.79-2.73%, durability of 21.26-44.59%, and calorific value of 4,524-4,628 kcal/kg. Except for that of the biopellet density and durability, all parameters satisfied the requirements of DIN EN standards. Thermal analysis of biopellet showed that water loss occurred at 36-100°C and significant mass decomposition between 100 up to 475°C with the weight loss of 77.34-80.51%. No further decomposition was found at above 480°C.
Examination of fecal pellet physical characteristics of an invasive drywood termite, Cryptotermes dudleyi (Isoptera: Kalotermitidae): A potential approach for species marker and non-destructive monitoring method
Authors: Zega S L D , Fajar A , Himmi S K , Adi D S , Tarmadi D , Nandika D , Yusuf S
Published: September 2020

Cryptotermes, one of the major drywood termite genera in Indonesia, is a cryptic species that isolates their presence inside a wood piece. Due to its cryptic lifecycle hidden away inside wood, monitoring its presence and also identifying the corresponding species has been a difficult process. One of the Cryptotermes species, native to Java island, Indonesia, is Cryptotermes dudleyi. In this preliminary study, we used C. dudleyi as a species model to find out whether fecal pellet physical characteristics can be used as a stable species marker to assist in non-destructive monitoring surveillance. The characteristics used were maximum diameter, diagonal width of maximum diameter, and 2D surface area and area perimeter. The study used fecal pellets from orphaned and mature colonies and three different dietaries (grass, hardwood, and softwood) to check whether the characteristic value of fecal pellets is narrow over various influences. The results showed that each characteristic tends to have unique mean and also its unique value range which depends on their collection site condition. Due to unique means and value range, the species marker become not so accurate and not robust enough as consequences in accommodating these unique means and value range. On the other hand, employing completely new clustering based on like-like axiom on individual fecal pellets may results in robust species marker as long as adequate data comparison from other species fecal pellets to validate the species marker is available.
Combination of citric acid and maltodextrin as bonding agent in sorghum bagasse particleboard
Authors: Syamani F A , Ramatia D , Sudarmanto  , Akbar F , Kusumah S S , Hermawan D
Published: September 2020

The interest of using natural binder in particleboard production is still the primary concern of many researchers. The use of citric acid as an adhesive has been investigated and show satisfying results, especially in particleboard physical properties. However, the particleboard had low bending strength due to high content of citric acid on the particleboard affected the brittleness of the particles. Therefore, the application of citric acid in particleboard production usually combined with other natural adhesives. In this study, a combination of citric acid (CA) and maltodextrin (MD) was used in the production of sorghum bagasse particleboard with a ratio of 1:1. The particleboard was produced with a target density of 0.8 g/cm3, using 15%, 20%, 25% and 30% CA-MD content, hot-pressed at 200°C and 5 MPa for 8 or 10 minutes. The mixture of citric acid and maltodextrin (1:1) was successfully acting as bonding agent in sorghum bagasse particleboard production, mainly when used at 30% adhesive content. The particleboard modulus of rupture and modulus of elasticity, fulfilled the standard of type 8 particleboard, according to JIS 5908. The particleboard physical properties were excellent, proved by the value of particleboard thickness swelling, which was under 12%. This is due to the superb bonding from the combination of citric acid and maltodextrin, as shown by the internal bond values, which exceeded 0.3 N/mm2, the minimum requirement for type 18 particleboards based on JIS A 5908.
A review of sustainable replanting eucalyptus: higher sustainable productivity
Authors: Sembiring N , Napitupulu H L , Sipahutar A I , Sembiring M T
Published: September 2020

Eucalyptus is a plant that has a very beneficial value to the environment such as can reduce the risk of forest fires, be efficient in water use, nature became more natural, restore land degradation or unproductive land, and the growth of these plants has a sustainable potential for biodiversity. Therefore, the need to replant eucalyptus in order to create a sustainable process for the environment to offers opportunities for wealth and prosperity, while also providing solutions for efficient ways to combat climate change. The purpose of this literature review is to provide information to the public about the benefits of plants that actually have extraordinary functions and characteristics but often get criticism from the community because of community disregard about the benefits It expects in the future eucalyptus can generate more wealth and benefits to the environment. Also, this review literature focuses on eucalyptus plants which provide significant benefits in various sectors, both for the environment and the industrial sector.
Limits of funneling efficiency in non-uniformly strained 2D semiconductors
Authors: Harats Moshe G , Bolotin Kirill I
Published: September 2020

Photoexcited electron-hole pairs (excitons) in transition metal dichalcogenides (TMDC) experience an effective force when these materials are non-uniformly strained. In the case of strain produced by a sharp tip pressing at the center of a suspended TMDC membrane, the excitons are transported to the point of the highest strain at the center of the membrane. This effect, exciton funneling, can be used to increase photoconversion efficiency in TMDC, to explore exciton transport and to study correlated states of excitons arising at their high densities. Here, we analyze the limits of funneling efficiency in realistic device geometries. The funneling efficiency in realistic monolayer TMDCs is found to be low,

<

5% both at room and low temperatures. This results from dominant diffusion at room temperature and short exciton lifetimes at low temperatures. On the other hand, in TMDC heterostructures with long exciton lifetimes the funneling efficiency reaches ∼50% at room temperature, as the exciton density reaches thermal equilibrium in the funnel. Finally, we show that Auger recombination limits funneling efficiency for intense illumination sources.
Brazilian regulatory authority contribution to the shielding dimensioning model of radiotherapy rooms proposed by the NCRP 151
Authors: L Braga Kelmo , G Gomes Renato , Terra André M B P T , Silva Ademir X , Medeiros Marcos P C , Stenders Ricardo M , Rebello Wilson F , Salata Camila , Santos Raphael F G , R Andrade Edson
Published: September 2020

The National Council on Radiation Protection and Measurements (NCRP) Report No. 151 is an essential document for bunker design commonly applied for radiotherapy treatment rooms. This document is used as a reference by several countries, including Brazil. The objective of this study is to evaluate the shielding dimensioning methodology recommended by NCRP 151, and compare it with the one adopted by the Brazilian regulatory authority. Radiotherapy rooms and respective doors were designed to use linear accelerators operating at 6, 10, 15, and 18 MeV under two different ways: (a) applying exclusively the methodology recommended by the NCRP 151, and (b) taking into consideration the complementary recommendations from the Brazilian authorities. The results suggest that designers in Brazil can count on at least 4 and 11% safety margin for dimensioning primary barriers in controlled and free areas respectively. Also 8% for secondary barriers in controlled areas, 9.7% for secondary barriers adjacent to the primary belt of free areas, and 6.6% for the lead of the doors.
SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation
Authors: Le Linh , Escobar Iliana E. , Ho Tina , Lefkovith Ariel J. , Latteri Emily , Haltaufderhyde Kirk D. , Dennis Megan K. , Plowright Lynn , Sviderskaya Elena V. , Bennett Dorothy C. , Oancea Elena , Marks Michael S.
Published: September 2020

SLC45A2 encodes a putative transporter in pigment cells and is mutated in oculocutaneous albinism (OCA) type 4. We show that SLC45A2 on mature melanosomes supports melanin synthesis by maintaining lumenal neutralization-initially orchestrated by transient OCA2 activity-and that a common variant imparts reduced activity due to protein instability.
Direct involvement of Hsp70 ATP hydrolysis in Ubr1-dependent quality control
Authors: Singh Amanjot , Vashistha Nidhi , Heck Jarrod , Tang Xin , Wipf Peter , Brodsky Jeffrey L. , Hampton Randolph Y.
Published: September 2020

Protein quality control (PQC) targets misfolded proteins for degradation. Ubr1 is a key E3 ligase in PQC; it requires HSP70 for this function. We show direct involvement of the HSP70 ATP cycle in Ubr1 PQC, suggesting a model for protein triage involving a kinetic "race" between HSP-mediated folding and Ubr1-dependent ubiquitination.
Choking as a cause of negative pressure pulmonary oedema (NPPE) in an older adult
Authors: Lonergan Bradley , Morgan Cerys , Al-Raweshidy Yasser , Singh Ravneeta
Published: September 2020

An 86-year-old female presented to the Emergency Department (ED) in respiratory distress after choking on a sandwich at home. Her family had noticed that she had had difficulty during and coughing after swallowing for several months. Her initial chest x-ray showed diffuse alveolar infiltrates in both lungs and blood tests showed normal white cells and C-Reactive Protein (CRP). She was started on intravenous antibiotics for presumed aspiration pneumonia and received 15 L of oxygen. However, the infiltration had dramatically improved, both radiologically and clinically, within 24 hours. She was diagnosed with negative pressure pulmonary oedema (NPPE) type 1 and made a rapid recovery. The Speech and Language Team diagnosed an impaired swallow and advised soft or bite-sized suitable foods. We discussed the ongoing risk of aspiration and long-term feeding options with the patient’s family. We agreed on a conservative plan for ‘risk feeding’, given her frailty and co-morbidities, and began discussions on ceilings of care. This case aims to raise awareness of NPPE so that it can be diagnosed, investigated and treated promptly. Although seen most commonly by intensivists and anaesthetists, it is relevant to those on the acute medical take and geriatricians managing patients with swallowing difficulties.
Iterative feature representation algorithm to improve the predictive performance of N7-methylguanosine sites
Authors: Dai Chichi , Feng Pengmian , Cui Lizhen , Su Ran , Chen Wei , Wei Leyi
Published: September 2020

Motivation

N7-methylguanosine (m7G) is an important epigenetic modification, playing an essential role in gene expression regulation. Therefore, accurate identification of m7G modifications will facilitate revealing and in-depth understanding their potential functional mechanisms. Although high-throughput experimental methods are capable of precisely locating m7G sites, they are still cost ineffective. Therefore, it’s necessary to develop new methods to identify m7G sites.

Results

In this work, by using the iterative feature representation algorithm, we developed a machine learning based method, namely m7G-IFL, to identify m7G sites. To demonstrate its superiority, m7G-IFL was evaluated and compared with existing predictors. The results demonstrate that our predictor outperforms existing predictors in terms of accuracy for identifying m7G sites. By analyzing and comparing the features used in the predictors, we found that the positive and negative samples in our feature space were more separated than in existing feature space. This result demonstrates that our features extracted more discriminative information via the iterative feature learning process, and thus contributed to the predictive performance improvement.
Generation of chimeric mice with spermatozoa fully derived from embryonic stem cells using a triple-target CRISPR method forNanos3†
Authors: Miura Kento , Matoba Shogo , Hirose Michiko , Ogura Atsuo
Published: September 2020

Conditional knockout (cKO) mice have contributed greatly to understanding the tissue- or stage-specific functions of genes in vivo. However, the current cKO method requires considerable time and effort because of the need to generate two gene-modified mouse strains (Cre transgenic and loxP knockin) for crossing. Here, we examined whether we could analyze the germ cell-related functions of embryonic lethal genes in F0 chimeric mice by restricting the origin of germ cells to mutant embryonic stem cells (ESCs). We confirmed that the full ESC origin of spermatozoa in fertile chimeric mice was achieved by the CRISPR/Cas9 system using three guide RNAs targeting Nanos3, which induced germ cell depletion in the host blastocyst-derived tissues. Among these fertile chimeric mice, those from male ESCs with a Dnmt3b mutation, which normally causes embryo death, also produced F1 mice derived exclusively from the mutant ESCs. Thus, our new chimeric strategy readily revealed that Dnmt3b is dispensable for male germ cell development, in agreement with a previous cKO study. Our new approach enables us to analyze the germ cell functions of embryonic lethal genes in the F0 generation without using the current cKO method.
Difficulties with Speech-in-Noise Perception Related to Fundamental Grouping Processes in Auditory Cortex
Authors: Holmes Emma , Zeidman Peter , Friston Karl J , Griffiths Timothy D
Published: September 2020

In our everyday lives, we are often required to follow a conversation when background noise is present (“speech-in-noise” [SPIN] perception). SPIN perception varies widely—and people who are worse at SPIN perception are also worse at fundamental auditory grouping, as assessed by figure-ground tasks. Here, we examined the cortical processes that link difficulties with SPIN perception to difficulties with figure-ground perception using functional magnetic resonance imaging. We found strong evidence that the earliest stages of the auditory cortical hierarchy (left core and belt areas) are similarly disinhibited when SPIN and figure-ground tasks are more difficult (i.e., at target-to-masker ratios corresponding to 60% rather than 90% performance)—consistent with increased cortical gain at lower levels of the auditory hierarchy. Overall, our results reveal a common neural substrate for these basic (figure-ground) and naturally relevant (SPIN) tasks—which provides a common computational basis for the link between SPIN perception and fundamental auditory grouping.
Chylomicrons-Simulating Sustained Drug Release in Mesenteric Lymphatics for the Treatment of Crohn’s-Like Colitis
Authors: Yin Yi , Yang Jingjing , Pan Yongchun , Guo Zhen , Gao Yanfeng , Huang Liangyu , Zhou Dongtao , Ge Yuanyuan , Guo Feilong , Zhu Weiming , Song Yujun , Li Yi
Published: September 2020

Background and Aims

Alteration to both the structures and functions of mesenteric lymphatic vessels is a typical hallmark of Crohn’s disease [CD]. Dysfunctional lymphatics was observed in patients with both CD and experimental colitis, suggesting mesenteric lymphatics could be potential therapeutic targets. This study aimed to develop a nano-delivery system which can enhance drug delivery in mesenteric lymphatic tissue [MLT] and evaluate the therapeutic effects in Crohn’s colitis.

Methods

We designed a mesoporous silica nanoparticle [MSN] conjugated with long-chain fatty acid [LMSN] and covered with enteric coating [ELMSN] which can be specifically transported via the mesenteric lymphatic system. The therapeutic efficacy of laquinimod-loaded nanoparticles [LAQ@ELMSN] was evaluated in the well-established interleukin [IL]-10−/− spontaneous experimental colitis.

Results

ELMSNs induced sustainable drug release that markedly increased drug concentration in MLT. In experimental colitis, the lymphatics-targeting drug delivery system suppressed lymphangitis and promoted lymphatic drainage. The downregulation of pro-inflammatory cytokines and the downstream NF-κB-related proteins efficiently inhibited lymphangiogenesis and restored tight junctions of mesenteric lymphatic vessels [MLVs]. LAQ@ELMSN showed a superior therapeutic effect in ameliorating intestinal inflammation compared with free drug administration. Alteration of gut microbiota and metabolites in experimental colitis was also reversed by LAQ@ELMSN.

Conclusion

Our study demonstrates a convenient, orally administered drug delivery system which enhances drug release in MLT. The results confirm the contribution of the mesenteric lymphatic system to the pathogenesis of gut inflammation and shed light on the application of lymphatics-targeting drug delivery therapy as a potential therapeutic strategy for CD treatment.
Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction
Authors: Bertrand Philippe B , Churchill Timothy W , Yucel Evin , Namasivayam Mayooran , Bernard Samuel , Nagata Yasufumi , He Wei , Andrews Carl T , Picard Michael H , Weyman Arthur E , Levine Robert A , Hung Judy
Published: September 2020

Aims 

The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR).

Methods and results 

The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3–5 mmHg, n = 3927), mid (5–10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049–1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively).

Conclusion 

In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3–5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.
Automatic processing of time domain induced polarization data using supervised artificial neural networks
Authors: Barfod Adrian S , Lévy Léa , Larsen Jakob Juul
Published: September 2020

Processing of geophysical data is a time consuming task involving many different steps. One approach for accelerating and automating processing of geophysical data is to look towards machine learning (ML). ML encompasses a wide range of tools, which can be used to automate complicated and/or tedious tasks. We present strategies for automating the processing of time-domain induced polarization (IP) data using ML. An IP data set from Grindsted in Denmark is used to investigate the applicability of neural networks for processing such data. The Grindsted data set consists of eight profiles, with approximately 2000 data curves per profile, on average. Each curve needs to be processed, which, using the manual approach, can take 1–2 hr per profile. Around 20 per cent of the curves were manually processed and used to train and validate an artificial neural network. Once trained, the network could process all curves, in 6–15 s for each profile. The accuracy of the neural network, when considering the manual processing as a reference, is 90.8 per cent. At first, the network could not detect outlier curves, that is where entire chargeability curves were significantly different from their spatial neighbours. Therefore, an outlier curve detection algorithm was developed and implemented to work in tandem with the network. The automatic processing approach developed here, involving the neural network and the outlier curve detection, leads to similar inversion results as the manual processing, with the two significant advantages of reduced processing times and enhanced processing consistency.
Adaptation of the iterative Marchenko scheme for imperfectly sampled data
Authors: van IJsseldijk Johno , Wapenaar Kees
Published: September 2020

The Marchenko method retrieves the responses to virtual sources in the Earth’s subsurface from reflection data at the surface, accounting for all orders of multiple reflections. The method is based on two integral representations for focusing- and Green’s functions. In discretized form, these integrals are represented by finite summations over the acquisition geometry. Consequently, the method requires ideal geometries of regularly sampled and colocated sources and receivers. Recently new representations were derived, which handle imperfectly sampled data. These new representations use point spread functions (PSFs) that reconstruct results as if they were acquired using a perfect geometry. Here, the iterative Marchenko scheme is adapted, using these new representations, to account for imperfect sampling. This new methodology is tested on a 2-D numerical data example. The results show clear improvement of the proposed scheme over the standard iterative scheme. By removing the requirement for perfect geometries, the Marchenko method can be more widely applied to field data.
Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated byN-glycans but by heparan sulfate proteoglycan interactions
Authors: Gludovacz Elisabeth , Schuetzenberger Kornelia , Resch Marlene , Tillmann Katharina , Petroczi Karin , Vondra Sigrid , Vakal Serhii , Schosserer Markus , Virgolini Nikolaus , Pollheimer Jürgen , Salminen Tiina A , Jilma Bernd , Borth Nicole , Boehm Thomas
Published: September 2020

Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination. No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis. After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min. Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures. The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively. Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo. The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants. High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs. Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively. A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575. These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
Endometrial thickness measurements among Asherman syndrome patients prior to embryo transfer
Authors: Movilla Peter , Wang Jennifer , Chen Tammy , Morales Blanca , Wang Joyce , Williams Alexandria , Reddy Himabindu , Tavcar Jovana , Loring Megan , Morris Stephanie , Isaacson Keith
Published: September 2020

STUDY QUESTION

Is there an association between endometrial thickness (EMT) measurement and clinical pregnancy rate among Asherman syndrome (AS) patients utilizing IVF and embryo transfer (ET)?

SUMMARY ANSWER

EMT measurements may not be associated with successful clinical pregnancy among AS patients undergoing IVF.

WHAT IS KNOWN ALREADY

Clinical pregnancy rate after IVF is significantly lower in patients with a thin endometrium, defined as a maximum EMT of <7 mm. However, AS patients often have a thin EMT measurement due to intrauterine scarring, with a paucity of data and no guidance on what EMT cutoff is appropriate when planning an ET among these patients.

STUDY DESIGN, SIZE, DURATION

This is a retrospective cohort study of 45 AS patients treated at a specialized advanced hysteroscopic clinic from 1 January 2015, to 1 March 2019.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Review of EMT measurements prior to a total of 90 ETs, among 45 AS patients. The impact of the maximum EMT measurement prior to ET on clinical pregnancy rate was analyzed.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 25/45 (55.6%) AS patients ultimately went on to have ≥1 clinical pregnancy following a mean ± SD of 2.00 ± 1.26 ET attempts. There was a total of 90 ETs among the 45 AS patients, with 29/90 (32.2%) ETs resulting in a clinical pregnancy. Younger patient age (P = 0.05) and oocyte donation (P = 0.01) were the only variables identified to be significant predictors for a positive clinical pregnancy outcome on bivariate analysis. The mean EMT measurement prior to all ETs among AS patients was 7.5 ± 1.6 mm. EMT measurement prior to ET did not predict a positive clinical pregnancy on either bivariate (P = 0.84) or multivariable analysis (odds ratio 0.91, P = 0.60). 31.8% of EMT measurements measured <7.0 mm. In this small cohort, no difference in the clinical pregnancy rate was detected when comparing ETs with EMT measurements of <7.0 mm versus ≥7.0 mm (P = 0.83). The mean EMT measurement decreased with increasing AS disease severity; 8.0 ± 1.6 mm for mild disease, 7.0 ± 1.4 mm for moderate disease and 5.4 ± 0.1 mm for severe disease.

LIMITATIONS, REASONS FOR CAUTION

Our small sample size limits our ability to draw any definitive conclusions. In addition, patients utilized various infertility clinics. This limits our ability to evaluate the consistency of EMT measurements and the IVF care that was received.

WIDER IMPLICATIONS OF THE FINDINGS

EMT measurement cutoff values should be used with caution if canceling a scheduled ET in AS patients.

STUDY FUNDING/COMPETING INTEREST(S)

This study was not funded. K.I. reports personal fees from Karl Stroz and personal fees from Medtronics outside the submitted work. The other authors have no conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.
Epithelial Cell Biomarkers Are Predictive of Response to Biologic Agents in Crohn’s Disease
Authors: Osterman Mark T , VanDussen Kelli L , Gordon Ilyssa O , Davis Elisabeth M , Li Katherine , Simpson Kate , Ciorba Matthew , Glover Sarah C , Abraham Bincy , Guo Xueyan , Yee Eric U , Allard Felicia D , Perrigoue Jacqueline G , Claggett Brian , Shen Bo , Stappenbeck Thaddeus S , Liu Julia J
Published: September 2020

Background

Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ) and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis, with respect to response to VDZ.

Method

Ileal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of 2 biomarkers to VDZ was examined.

Results

Clinical response in UST was significantly higher than placebo (65% vs 39%; P = 0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs 20% (P = 0.02). For VDZ, clinical response with MVL of 1.35 to 1.55 µm was 82% vs 44% (<1.35 µm) and 40% (>1.55 µm; P = 0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis <14 positive cells/1000 IECs or MVL of 1.35 to 1.55 µm could identify 84% of responders and 67% of nonresponders (P = 0.001).

Conclusion

Ileal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, and combination of the 2 biomarkers enhanced the discriminate ability of responders from nonresponders to VDZ.
Epigenetics of Animal Personality: DNA Methylation Cannot Explain the Heritability of Exploratory Behavior in a Songbird
Authors: van Oers Kees , Sepers Bernice , Sies William , Gawehns Fleur , Verhoeven Koen J F , Laine Veronika N
Published: September 2020

Synopsis

The search for the hereditary mechanisms underlying quantitative traits traditionally focused on the identification of underlying genomic polymorphisms such as single-nucleotide polymorphisms. It has now become clear that epigenetic mechanisms, such as DNA methylation, can consistently alter gene expression over multiple generations. It is unclear, however, if and how DNA methylation can stably be transferred from one generation to the next and can thereby be a component of the heritable variation of a trait. In this study, we explore whether DNA methylation responds to phenotypic selection using whole-genome and genome-wide bisulfite approaches. We assessed differential erythrocyte DNA methylation patterns between extreme personality types in the Great Tit (Parus major). For this, we used individuals from a four-generation artificial bi-directional selection experiment and siblings from eight F2 inter-cross families. We find no differentially methylated sites when comparing the selected personality lines, providing no evidence for the so-called epialleles associated with exploratory behavior. Using a pair-wise sibling design in the F2 intercrosses, we show that the genome-wide DNA methylation profiles of individuals are mainly explained by family structure, indicating that the majority of variation in DNA methylation in CpG sites between individuals can be explained by genetic differences. Although we found some candidates explaining behavioral differences between F2 siblings, we could not confirm this with a whole-genome approach, thereby confirming the absence of epialleles in these F2 intercrosses. We conclude that while epigenetic variation may underlie phenotypic variation in behavioral traits, we were not able to find evidence that DNA methylation can explain heritable variation in personality traits in Great Tits.
Clinical decision support system, using expert consensus-derived logic and natural language processing, decreased sedation-type order errors for patients undergoing endoscopy
Authors: Shen Lin , Wright Adam , Lee Linda S , Jajoo Kunal , Nayor Jennifer , Landman Adam
Published: September 2020

Objective

Determination of appropriate endoscopy sedation strategy is an important preprocedural consideration. To address manual workflow gaps that lead to sedation-type order errors at our institution, we designed and implemented a clinical decision support system (CDSS) to review orders for patients undergoing outpatient endoscopy.

Materials and Methods

The CDSS was developed and implemented by an expert panel using an agile approach. The CDSS queried patient-specific historical endoscopy records and applied expert consensus-derived logic and natural language processing to identify possible sedation order errors for human review. A retrospective analysis was conducted to evaluate impact, comparing 4-month pre-pilot and 12-month pilot periods.

Results

22 755 endoscopy cases were included (pre-pilot 6434 cases, pilot 16 321 cases). The CDSS decreased the sedation-type order error rate on day of endoscopy (pre-pilot 0.39%, pilot 0.037%, Odds Ratio = 0.094, P-value < 1e-8). There was no difference in background prevalence of erroneous orders (pre-pilot 0.39%, pilot 0.34%, P = .54).

Discussion

At our institution, low prevalence and high volume of cases prevented routine manual review to verify sedation order appropriateness. Using a cohort-enrichment strategy, a CDSS was able to reduce number of chart reviews needed per sedation-order error from 296.7 to 3.5, allowing for integration into the existing workflow to intercept rare but important ordering errors.

Conclusion

A workflow-integrated CDSS with expert consensus-derived logic rules and natural language processing significantly reduced endoscopy sedation-type order errors on day of endoscopy at our institution.
Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes
Authors: Wang Liang , He Xiaosheng , Ugai Tomotaka , Haruki Koichiro , Lo Chun-Han , Hang Dong , Akimoto Naohiko , Fujiyoshi Kenji , Wang Molin , Fuchs Charles S , Meyerhardt Jeffrey A , Zhang Xuehong , Wu Kana , Chan Andrew T , Giovannucci Edward L , Ogino Shuji , Song Mingyang
Published: September 2020

Background

Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes.

Methods

We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes.

Results

We documented 1175 CRC patients with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (all Pheterogeneity < .005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α  level of .005.

Conclusions

Risk factor profiles may differ for CRC arising from different molecular pathways.
RoadRunner: a fast and flexible exoplanet transit model
Authors: Parviainen H
Published: September 2020

I present RoadRunner, a fast exoplanet transit model that can use any radially symmetric function to model stellar limb darkening (LD) while still being faster to evaluate than the analytical transit model for quadratic LD by Mandel & Agol. CPU and GPU implementations of the model are available in the pytransit transit modelling package, and come with platform-independent parallelization, supersampling, and support for modelling complex heterogeneous time series. The code is written in numba-accelerated python (and the GPU model in opencl) without c or fortran dependencies, which allows for the LD model to be given as any python-callable function. Finally, as an example of the flexibility of the approach, the latest version of pytransit comes with a numerical limb darkening model that uses LDTk-generated limb darkening profiles directly without approximating them by analytical models.
linestacker: a spectral line stacking tool for interferometric data
Authors: Jolly Jean-Baptiste , Knudsen Kirsten K , Stanley Flora
Published: September 2020

linestacker is a new open access and open source tool for stacking of spectral lines in interferometric data. linestacker is an ensemble of casa tasks, and can stack both 3D cubes or already extracted spectra. The algorithm is tested on increasingly complex simulated data sets, mimicking Atacama Large Millimeter/submillimeter Array, and Karl G. Jansky Very Large Array observations of [C ii] and CO(3–2) emission lines, from z ∼ 7 and z ∼ 4 galaxies, respectively. We find that the algorithm is very robust, successfully retrieving the input parameters of the stacked lines in all cases with an accuracy ≳90 per cent. However, we distinguish some specific situations showcasing the intrinsic limitations of the method. Mainly that high uncertainties on the redshifts (Δz > 0.01) can lead to poor signal-to-noise ratio improvement, due to lines being stacked on shifted central frequencies. Additionally, we give an extensive description of the embedded statistical tools included in linestacker: mainly bootstrapping, rebinning, and subsampling. Velocity rebinning is applied on the data before stacking and proves necessary when studying line profiles, in order to avoid artificial spectral features in the stack. Subsampling is useful to sort the stacked sources, allowing to find a subsample maximizing the searched parameters, while bootstrapping allows to detect inhomogeneities in the stacked sample. linestacker is a useful tool for extracting the most from spectral observations of various types.
The anatomy of a star-forming galaxy II: FUV heating via dust
Authors: Benincasa S M , Wadsley J W , Couchman H M P , Pettitt A R , Keller B W , Woods R M , Grond J J
Published: September 2020

Far-ultraviolet (FUV) radiation greatly exceeds UV, supernovae (SNe), and winds in the energy budget of young star clusters but is poorly modelled in galaxy simulations. We present results of the first isolated galaxy disc simulations to include photoelectric heating of gas via dust grains from FUV radiation self-consistently, using a ray-tracing approach that calculates optical depths along the source–receiver sightline. This is the first science application of the TREVR radiative transfer algorithm. We find that FUV radiation alone cannot regulate star formation. However, FUV radiation produces warm neutral gas and is able to produce regulated galaxies with realistic scale heights. FUV is also a long-range feedback and is more important in the outer discs of galaxies. We also use the superbubble feedback model, which depends only on the SN energy per stellar mass, is more physically realistic than common, parameter-driven alternatives and thus better constrains SN feedback impacts. FUV and SNe together can regulate star formation without producing too much hot ionized medium and with less disruption to the interstellar medium compared to SNe alone.
Spirals, shadows, and precession in HD 100453 – I. The orbit of the binary
Authors: Gonzalez Jean-François , van der Plas Gerrit , Pinte Christophe , Cuello Nicolás , Nealon Rebecca , Ménard François , Revol Alexandre , Rodet Laetitia , Langlois Maud , Maire Anne-Lise
Published: September 2020

In recent years, several protoplanetary discs have been observed to exhibit spirals, both in scattered light and (sub)millimetre continuum data. The HD 100453 binary star system hosts such a disc around its primary. Previous work has argued that the spirals were caused by the gravitational interaction of the secondary, which was assumed to be on a circular orbit, coplanar with the disc (meaning here the large outer disc, as opposed to the very small inner disc). However, recent observations of the CO gas emission were found incompatible with this assumption. In this paper, we run SPH simulations of the gas and dust disc for seven orbital configurations taken from astrometric fits and compute synthetic observations from their results. Comparing to high-resolution ALMA 12CO data, we find that the best agreement is obtained for an orbit with eccentricity e = 0.32 and semimajor axis a = 207 au, inclined by 61° relative to the disc plane. The large misalignment between the disc and orbit planes is compatible with the tidal evolution of a circumprimary disc in an eccentric, unequal-mass binary star.
Coronal vertical structure variations in normal branch of GX 17+2: AstroSat’s SXT and LAXPC perspective
Authors: Malu S , Sriram K , Agrawal V K
Published: September 2020

We performed spectro-temporal analysis in the 0.8–50 keV energy band of the neutron star Z source GX 17+2 using AstroSat Soft X-ray Telescope (SXT) and Large Area X-ray Proportional Counter (LAXPC) data. The source was found to vary in the normal branch (NB) of the hardness–intensity diagram. Cross-correlation studies of LAXPC light curves in soft and hard X-ray band unveiled anticorrelated lags of the order of few hundred seconds. For the first time, cross-correlation studies were performed using SXT soft and LAXPC hard light curves and they exhibited correlated and anticorrelated lags of the order of a hundred seconds. Power density spectrum displayed normal branch oscillations (NBOs) of 6.7–7.8 Hz (quality factor 1.5–4.0). Spectral modelling resulted in inner disc radius of ∼12–16 km with Γ ∼ 2.31–2.44 indicating that disc is close to the innermost stable circular orbit and a similar value of disc radius was noticed based on the reflection model. Different methods were used to constrain the corona size in GX 17+2. Using the detected lags, corona size was found to be 27–46 km (β = 0.1, β = vcorona/vdisc) and 138–231 km (β = 0.5). Assuming the X-ray emission to be arising from the boundary layer (BL), its size was determined to be 57–71 km. Assuming that BL is ionizing the disc’s inner region, its size was constrained to ∼19–86 km. Using NBO frequency, the transition shell radius was found to be around 32 km. Observed lags and no movement of the inner disc front strongly indicate that the varying corona structure is causing the X-ray variation in the NB of Z source GX 17+2.