bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding
Authors: La Mura Vincenzo , Garcia‐Guix Marta , Berzigotti Annalisa , Abraldes Juan G. , García‐Pagán Juan Carlos , Villanueva Candid , Bosch Jaime
Published: January 2020

Background and Aims

A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG.

Methods

A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1‐3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation‐free survival for 4 years. Another cohort (n = 231) served as the validation set.

Results

During follow‐up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the “gray zone” (i.e., high‐risk patients who had not died on follow‐up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results.

Conclusions

Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient’s baseline HVPG is over 16 mm Hg improves detection of high‐risk patients while markedly reducing the number of HVPG measurements required.
Thirty‐Day Readmission and Cost Analysis in Patients With Cirrhosis: A Nationwide Population‐Based Data
Authors: Chirapongsathorn Sakkarin , Poovorawan Kittiyod , Soonthornworasiri Ngamphol , Pan‐ngum Wirichada , Phaosawasdi Kamthorn , Treeprasertsuk Sombat
Published: January 2020

Accurate population‐based data are needed on the rate, economic impact, and the long‐term outcomes of readmission among patients with cirrhosis. To examine the rates, costs, and 1‐year outcomes of patients readmitted within 30 days following their index hospitalization for complications of cirrhosis, we conducted a nationwide, population‐based cohort study involving all patients with cirrhosis in Thailand from 2009 through 2013, using data from the National Health Security Office databases, which included those from nationwide hospitalizations. Readmission was captured from hospitals at all health care levels across the country within the Universal Coverage Scheme. For the 134,038 patients hospitalized with cirrhosis, the overall 30‐day readmission rate was 17%. Common causes of readmission consisted of complications of portal hypertension (47%) and infections (17%). After adjusting for multiple covariates, predictors of 30‐day readmission included hepatocellular carcinoma (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.84‐2.06), human immunodeficiency virus–related admission (OR 1.81, 95% CI 1.51‐2.17) and cholangiocarcinoma (OR 1.64, 95% CI 1.3‐2.05). In all, 2,936 deaths (13%) occurred during readmission, and an additional 14,425 deaths up to 1 year (63.5% total mortality among readmitted patients). Causes of death were mostly from liver‐related mortality. Average cost at index admission for those with a 30‐day readmission were significantly higher than those readmitted beyond 30 days or not readmitted. Conclusions: Patients hospitalized with cirrhosis complications had high rates of unscheduled 30‐day readmission. Average hospitalization costs were high, and only 36.5% of patients readmitted within 30 days survived at 1 year.
Fear driven compulsive behaviour is associated with worse long‐term outcome in obsessive–compulsive disorder
Authors: Ferreira Gabriela M. , Albertella Lucy , Moreira‐de‐Oliveira Maria Eduarda , Piquet‐Pessôa Marcelo , Yücel Murat , Lee Rico S.C. , Batista Karina B. , de Menezes Gabriela B. , Fontenelle Leonardo F.
Published: January 2020

Objectives

In this retrospective study of patients with obsessive–compulsive disorder (OCD), we assessed the relationship between different motivational drivers of compulsive behaviours and the response to naturalistic treatments (based mostly on high dose serotonin reuptake inhibitors [SRIs]).

Methods

Seventy‐six OCD patients were assessed with a structured diagnostic interview; the Habit, Reward and Fear Scale‐Revised (HRFS‐R); the Yale‐Brown Obsessive–Compulsive Scale (YBOCS); the Beck Depression Inventory (BDI); and the OCD Retrospective Assessment of Treatment Response (RATS), which includes information on SRIs administration (e.g., dose and duration of their use), augmentation strategies (such as antipsychotic use or exposure and response prevention intervention), and pre‐treatment YBOCS scores. Patients were naturalistically followed up for a mean of 7.28 (SD 5.51) years.

Results

Analysis revealed that the fear subscore of the HRFS was the only significant predictor (among a detailed battery of demographic, clinical and treatment factors) independently associated with greater delta (pre‐treatment minus post‐treatment) YBOCS scores.

Conclusions

In contrast to predictions (based on existing models), poorer treatment response was not associated with increased habit scores in the HRFS. Future longitudinal studies are needed to confirm whether increased fear as a driver for ritualistic behaviours is able to predict worse outcomes in OCD samples.
The necessity‐concern framework in the assessment of treatment adherence of psychiatric patients and the role of polypharmacy in a Spanish sample
Authors: De las Cuevas Carlos , Betancort Moisés , de Leon Jose
Published: January 2020

Objective

This study compares three measures (necessity and concern scores, the necessity‐concern differential, and a skeptical attitude vs. three other attitudes) for studying the relationship between the necessity‐concern framework and treatment adherence after considering the number of prescribed drugs.

Methods

The sample included 588 consecutive adult psychiatric outpatients in the Canary Islands, Spain. The necessity‐concern framework was assessed using a specific subscale of the Beliefs about Medicines Questionnaire. Adherence (yes/no) to 1,101 prescribed psychiatric drugs was assessed using the Sidorkiewicz adherence tool.

Results

In the three logistic regression models including 1,101 drugs, with adherence as the dependent variable, the highly significant odds ratios (ORs) and their 95% confidence intervals (CIs) were (a) OR = 1.57 (CI = 1.37–1.79) for necessity and OR = 0.747 (CI = 0.660–0.847) for concern; (b) OR = 1.44 (CI = 1.32–1.58) for the necessity‐concern differential; and (c) OR = 0.452 (CI = 0.343–0.597) for a skeptical attitude (yes/no), defined as low necessity and high concern. In patients taking five or six drugs, adherence was associated with extremely high/low ORs for necessity, concern, and the differential.

Conclusion

If replicated, our results suggest clinicians need to pay careful attention to each drug in each patient taking five or six drugs, emphasize necessity, and listen carefully to patient concerns.
ECONOMIC ASSESSMENT OF WATER HARVESTING PLUS SUPPLEMENTAL IRRIGATION FOR IMPROVING WATER PRODUCTIVITY OF A PULSE–COTTON BASED INTEGRATED FARMING SYSTEM IN TELANGANA, INDIA†
Authors: Reddy Konda S. , Ricart Sandra , Maruthi Vegapareddy , Pankaj Prabhat K. , Krishna Tatipamula S. , Reddy A. Amarender
Published: January 2020

An integrated farming system (IFS) aims to sustain agricultural production, maintain farm incomes, safeguard the environment and respond to climate change impacts. Experiments in a tribal farmer's fields during 2016–2018 with two IFS models (pulse and cotton) were conducted in the Telangana region, India. An on‐farm reservoir (OFR) is designed for storing surface runoff based on the area and runoff coefficient determined through a modelling approach. The results demonstrated how supplemental irrigation and water harvesting are the most important and proven technologies for improving crop productivity and the efficient use of water in dryland areas of the semi‐arid tropics. The economic analysis indicated that after introduction of OFR technology, farmers' profits were increased under both scenarios of prolonged and short dry spells. According to the results, adoption of the OFR and IFS models not only ensured economic returns but provided regular employment even on less than 1 ha of land, which is usually non‐sustainable if monocropping is being practised. The approaches used in this work might be useful for guiding producers’ decisions in optimizing resources and selecting crops based on economic and water use efficiency. © 2020 John Wiley & Sons, Ltd.
The effects of combinations of limited ration and diazinon exposure on acetylcholinesterase activity, growth and reproduction in Oryzias latipes, the Japanese medaka
Authors: Flynn Kevin , Johnson Rodney , Lothenbach Doug , Swintek Joe , Whiteman Frank , Etterson Matthew
Published: January 2020

Environmental contamination can negatively impact fish populations. In addition to acute toxicity leading to death, toxicants can reduce fish growth and lower reproduction. The potential for adverse population level effects of environmental contaminants are estimated to conduct risk assessments from laboratory toxicity tests that most often measure apical endpoints related to growth, survival and reproduction. The relationships between these effect endpoints are being evaluated to predict shifts in fish population demography better after exposure to environmental toxicants. Environmental contaminants can also affect fish populations indirectly by reducing prey biomass. However, estimating the magnitude of the combined effects of prey reduction and direct toxicity is difficult and rarely attempted. Here we describe a toxicity test designed to estimate the effect on Japanese medaka of both reduced food and chronic exposure to diazinon, an acetylcholinesterase inhibiting organophosphate pesticide. Fish were reared with limited food ration and/or diazinon exposure through a full life cycle to assess possible interactions between the two stressors in their effects on growth and reproduction. Diazinon exposure (10 or 20 μg/L), reduced ration (50% and 25% of ad libitum), or combinations of both lowered growth rates and reproductive output of Japanese medaka. In addition, growth and reproduction alone were modeled, and then various relationships between the two stressors (diazinon and ration) and how they relate to growth and reproduction were modeled.
Transgenerational reproductive and developmental toxicity of tebuconazole in Caenorhabditis elegans
Authors: Lu Qian , Bu Yuanqing , Ma Lingyi , Liu Ran
Published: January 2020

The transgenerational reproductive and developmental toxicity of tebuconazole (TEB) in Caenorhabditis elegans was investigated over five generations (P0 − F4). Only parental C.elegans (P0) were exposed to TEB (0, 0.01, 0.1, 1, and 10 μg/L) for 24 h and the subsequent offspring (F1–F4) were grown under TEB‐free conditions. TEB exposure caused dose‐dependent reproductive defects and developmental impairments in C.elegans. In the P0 generation reproductive defects were observed such as: reduced brood size and embryo hatchability, prolonged generation time, retarded gonadal development, and slower germline proliferation, even at 0.01 μg/L, together with developmental toxicity with significant reduced body length and narrowed body width at 10 μg/L. Additionally, the brood size significantly reduced in F2, which began to recover from F3, but was still lower than the control in F4. The proportion of abnormalities increased significantly in F2 and reduced from F3, but was still higher than the control, suggesting that TEB could have cumulative potential and be passed to offspring through parental exposure. Furthermore, exposure to TEB (10 μg/L) in P0 significantly reduced the body length in F1, which began to recover from F2, and was the same level as the control in F4. There was a concentration‐dependent increase in body width in F1–F4, with a significant increase only observed in F1 at 10 μg/L. Thus, parental exposure to TEB induced transgenerational defects in both reproduction and development, emphasizing the significance of considering bio‐toxicity over multiple generations to conduct accurate assessment of environmental risks of toxicants.
An innovative occluder for cardiac defect: 3D printing and a biocompatibility research based on self‐developed bioabsorbable material—LA–GA–TMC
Authors: Sun Yiming , Xia Yinghui , Zhang Xingjian , Li Wenjing , Xing Quansheng
Published: January 2020

This study adopted the latest self‐developed bioabsorbable material lactide–glycolide–1,3‐trimethylene carbonate (LA–GA–TMC) and applied the three‐dimensional (3D) printing technique to manufacture the occluder for cardiac septal defects, so as to realize the individualized treatment of cardiac septal defects. At the same time, its biosafety was evaluated, with an aim to establish foundation for futural large‐scale animal experiment and clinical trial. The traditional “one‐pot synthesis” was modified, and the “two‐step synthesis method” was utilized to synthesize the LA–GA–TMC terpolymer at the lactide: glycolide: trimethylene carbonate ratio of 6:1:1.7. Afterward, the synthesized terpolymer was used as the raw material to fabricate the occluder model via using 3D printing technique. Then, its biocompatibility was comprehensively evaluated through cytocompatibility, blood compatibility, and histocompatibility. The occluder made from LA–GA–TMC 3D printing had favorable ductility and recoverability; besides, it possessed the temperature‐control feature, and the relative cell proliferation rates in extract liquids at various concentrations were all >70%, suggesting that it had favorable cytocompatibility. Moreover, hemolytic experiment revealed that its hemolytic rate was <5%, dynamic blood coagulation experiment demonstrated that the sample material moderately activated the blood coagulation, and the above findings suggested that it had good blood compatibility. In addition, implanting experiment in vivo revealed that its histocompatibility was superior to the traditional nitinol and the emerging poly‐l‐lactic acid. It is completely feasible to manufacture the cardiac septal defects occluder based on the novel absorbable material LA–GA–TMC, which has favorable biocompatibility, through 3D printing technique and it possesses broad prospects in large‐scale animal experiment and clinical trial.
Micro‐CT and histopathology methods to assess host response of aneurysms treated with shape memory polymer foam‐coated coils versus bare metal coil occlusion devices
Authors: Jessen Staci L. , Friedemann Molly C. , Mullen Annmarie E. , Ginn‐Hedman Anne‐Marie , Herting Scott M. , Maitland Duncan J. , Clubb Fred J.
Published: January 2020

Recent studies utilizing shape memory polymer foams to coat embolizing coils have shown potential benefits over current aneurysm treatments. In the current study utilizing a rabbit‐elastase aneurysm model, the performance of test article (foam‐coated coil [FCC]) and control (bare platinum coils [BPCs]) devices were compared at 30, 90, and 180 days using micro‐CT and histological assessments. The host response was measured by identifying the cells regionally present within the aneurysm, and assessing the degree of residual debris and connective tissue. The 3D reconstructions of aneurysms provided context for histologic findings, and aided in the overall aneurysm assessment. At all time points, >75% of the cells categorized in each aneurysm were associated with a bioactive yet biocompatible host response (vs. the remainder of cells that were associated with acute inflammation). The extracellular matrix exhibited a transition from residual fibrin at 30 days to a greater degree of connective tissue at 90 and 180 days. Although the control BPC‐treated aneurysms exhibited a greater degree of connective tissue at the earliest time point examined (30 days), by 180 days, the FCC‐treated aneurysms had more connective tissue and less debris overall than the control aneurysms. When considering cell types and extracellular matrix composition, the overall host response scores were significantly better in FCC‐treated aneurysms at the later time point. Based on the results of these metrics, the FCC device may lead to an advanced tissue remodeling response over BPC occlusion devices.
Complexes of helium with neutral molecules: Progress toward a quantitative scale of bonding character
Authors: Borocci Stefano , Grandinetti Felice , Sanna Nico , Antoniotti Paola , Nunzi Francesca
Published: January 2020

The complexes of helium with nearly 30 neutral molecules (M) were investigated by various techniques of bonding analysis and symmetry‐adapted perturbation theory (SAPT). The main investigated function was the local electron energy densityH(r), analyzed, in particular, so to estimate the degree of polarization (DoP) of He in the various He(M). As we showed recently (Borocci et al.,J. Comput. Chem., 2019, 40, 2318–2328), the DoP is a quantitative index that is generally informative about the role of polarization (induction plus charge transfer [CT]) and dispersion in noncovalent noble gas complexes. As further evidence in this regard, we presently ascertained quantitative correlations between the DoP(He) of the He(M) and indices based on the electron densityρ(r), including the molecular electrostatic potential at the HeM bond critical point, as well as the percentage contributions of induction and dispersion to the SAPT binding energies. Based also on the explicit evaluation of the CT, accomplished through the study of the charge‐displacement function, we derived a quantitative scale that ranks the He(M) according to their dispersive, inductive, and CT bonding character. Our taken approach could be conceivably extended to other types of noncovalent complexes.
Semiempirical methods do Fukui functions: Unlocking a modeling framework for biosystems
Authors: Grillo Igor Barden , Urquiza‐Carvalho Gabriel A. , Chaves Elton José Ferreira , Rocha Gerd Bruno
Published: January 2020

Obtaining reactivity information from the molecular electronic structure of a chemical system is a computationally intensive process. As a way of probing reactivity information around that, there exist electron density response variables, such as the Fukui functions (FFs), which are well‐established descriptors that summarize the local susceptibility to react. These properties only require few single‐point quantum chemical calculations, but even then, the intrinsic high cost and unfavorable computational complexity with respect to the number of atoms in the system makes this approach available only to small fragments and systems. In this study, we explore the computation of FFs, showing that semiempirical quantum chemical methods can be used to obtain the reactivity information equivalent to that of a Density Functional Theory (DFT) functional, for the eight entire polypeptide chains. The combination of semiempirical methods with the frozen orbital approximation allows for the obtention of these reactivity descriptors for biological systems with reasonable accuracy and speed, unlocking the utilization of these methods for such systems. These results for the frozen orbital approximation can be additionally improved when other molecular orbitals from the frontier band are employed in the computation. We also show the potential of this computational protocol in the ligand–protein complexes of HIV‐1 protease, predicting which of those ligands are active inhibitors.
Exploring recent developments on 1,2,4‐triazole: Synthesis and biological applications
Authors: Sathyanarayana Reshma , Poojary Boja
Published: January 2020

Triazoles are nitrogen‐bearing heterocycles. In the last few decades, researchers have focused on fused heterocycles, as they have better pharmacological effect compared to triazoles alone. Among the two isomers of triazole, this article aims to explore the work carried out on 1,2,4‐triazole and N‐bridged heterocycles derived from 1,2,4‐triazole in last 18 years, highlight different synthetic pathways, and present a brief summary of the different biological activities possessed by 1,2,4‐triazole derivatives. The information collected in this article is expected to help researchers to discover novel therapeutic agents for better applications in the field of pharmaceutical science.
Advancements in synthesis of pharmacologically active imidazolidin‐4‐ones and stereochemistry of their Reactions with some Reagents
Authors: Saied Khaled F. , Abdelwahab Salwa S. , Hashem Heba E. , Kandeel Kamal A.
Published: January 2020

1‐Aryl, 1,3‐diaryl‐ and 5‐(2‐oxo‐2‐arylethyl)‐2‐thioxo‐imidazolidin‐4‐ones 2 were prepared as before, nevertheless, equivalent amounts of potassium hydroxide were added to the reaction conditions. This change, dramatically, reduced the reaction time and highly increased the yield of some derivatives. Treatment of 2 with sulfuric acid converted them into their analogous (E)/(E,Z)‐5‐(2‐oxo‐2‐arylethylidene) derivatives 3. Reactions of 2 and/or 3 with chromium trioxide affected their conversion into the corresponding 2,4‐diones 4 and 5, respectively. Treatment of 2 and/or 3 with ethyl bromoacetate affected conversion of the former into their respective 2,4‐diones 4, whereas it gave the respective 2‐alkylthio derivatives of the latter. Reactions of 2b with aromatic aldehydes gave mixtures of spiro‐1H‐ and 2H‐pyrrole diastereomers. Structures of the new products were evidenced by infrared, EI‐MS, 1H‐ and 13C‐NMR spectroscopic measurements. Many of the selected compounds showed good antimicrobial activity.
Synthesis of some novel N5‐sulfonylated and N1‐alkyated pyrazole derivatives and their antimicrobial activity in conjunction with molecular docking study
Authors: Metwally Nadia H. , Ragab Eman A. , Mohamed Mona S.
Published: January 2020

Some novel N5‐sulfonylated 4 were synthesized via sulfonylation of 5‐amino‐1H‐pyrazole derivative 1 with arylsulfonyl chlorides. On the other hand, N1‐alkylated pyrazoles 7 and 10 were synthesized through alkylation of compound 1 with each of chloroacetamides and ethylchloroacetate under different conditions. Condensation of compounds 4 and 7 with different aromatic aldehydes furnished the corresponding arylidene derivatives. In spite of, condensation of 10 with aromatic aldehydes afforded the 2‐(5‐amino‐2‐aryl‐1H‐pyrazol‐1‐yl)acetic acid. The structure of the newly synthesized compounds was elucidated by elemental analyses and spectral data. Also, the suggested mechanisms for their formation were studied. Additionally, some selected new compounds were screened against antimicrobial activity. Compound 7c exhibited a higher activity against Candida albicans (inhibition zone diameter [IZD] = 31.3 ± 0.6 mm) than the standard antibiotic Nystatin (IZD = 21 ± 0.5 mm). Also, compound 7c showed minimum inhibitory concentration = 125 and 250 μg/mL against Klebsiella pneumonia and Staphylococcus aureus, respectively. Molecular docking study also was carried out for compound 7c.
Ovariectomy and timing of impaired maxillary alveolar bone regeneration: An experimental study in rats
Authors: Kim Hyun Ju , Kim Kyoung‐Hwa , Lee Yong‐Moo , Ku Young , Heo Seong‐Joo , Rhyu In‐Chul , Seol Yang‐Jo
Published: January 2020

Background

The aim of this study was to seek the critical time for impairment of alveolar bone regeneration after ovariectomy (OVX) in rats.

Methods

A total of 32 female rats were used. Test group rats were divided into a 2M group (n = 8), a 3M group (n = 8) and a 4M group (n = 8) according to the duration from OVX to defect creation. Bilateral OVX was performed in all test groups, and a sham operation was performed in the control group (n = 8). Drill‐hole defects (1.5 mm diameter, 2 mm length) were created on both sides of the maxilla. All rats were euthanized 2 and 4 weeks after the surgery. Microcomputed tomographic (micro‐CT), histological, and histomorphometric analyses and in vitro experiments were performed.

Results

The 4M group showed significantly less new bone formation and a lower bone mineral density than the other groups in the micro‐CT analysis. The histomorphometric analysis also revealed that the 4M group showed significantly less new bone formation than the control and 2M groups. The rats in the 4M group showed significantly higher alkaline phosphatase expression levels and a larger number of calcified nodules than rats in the other groups, whereas osteoclastic activity was significantly lower in the 4M group than in the other groups.

Conclusions

The critical time for impairment of alveolar bone regeneration was 4 months after OVX in rats.
Oil‐in‐water emulsions containing tamarind seed gum during in vitro gastrointestinal digestion: rheological properties, stability, and lipid digestibility
Authors: Udomrati Sunsanee , Pantoa Thidarat , Gohtani Shoichi , Nakajima Mitsutoshi , Uemura Kunihiko , Kobayashi Isao
Published: January 2020

BACKGROUND

Polysaccharides may enhance/inhibit lipid digestibility of oil‐in‐water (O/W) emulsions because of their emulsifying and/or stabilizing ability and can also affect the formation, stability, and viscosity of emulsions. Tamarind seed gum (TSG) was used as the sole emulsifier/stabilizer to stabilize an O/W emulsion prepared using high‐speed homogenization. We investigated the effects of various TSG concentrations (50–150 g kg−1) on the lipid digestibility, rheological properties, and stability of O/W emulsions during in vitro gastrointestinal digestion.

RESULTS

A low concentration (50 g kg−1) and a high concentration (150 g kg−1) of TSG reduced lipid digestibility by about 33% and 45%, respectively, compared to the control sample (without TSG). However, the emulsion containing the intermediate TSG concentration at 100 g kg−1 was the most efficient in the inhibition of lipid digestion, reducing lipid digestibility by about 70% compared to that of the control sample. The stability of emulsion tended to enhance as the concentration of TSG increased. The size of oil droplets before passing through the intestinal phase and the viscosity of the intestinal digested system may be important factors for enhancing/inhibiting lipid digestibility of emulsions. The destabilization of the emulsion during digestion was not clearly detected by rheological analysis because rheological characteristics (e.g. flow behavior index) were mainly driven by TSG.

CONCLUSIONS

The addition of TSG in O/W emulsions inhibited lipid digestibility. TSG at a concentration of 100 g kg−1 was the most efficient in the inhibition of lipid digestibility, suggesting that TSG is an attractive alternative ingredient for control of lipid digestibility of emulsion foods. © 2020 Society of Chemical Industry
Aberrant distribution and function of plasmacytoid dendritic cells in patients with ankylosing spondylitis are associated with unfolded protein response
Authors: Liu Chin‐Hsiu , Chou Chung‐Tei , Chen Chen‐Hung , Chen Chun‐Hsiung , Yang Shii‐Yi , Ko Yi‐An , Wu Yi‐Ting , Wang Chih‐Chien , Liu Feng‐Cheng , Yue Chung‐Tai , Hung Shih‐Chieh , Tzeng I‐Shiang , Tsai Wen‐Chan , Lin Kuo‐I
Published: January 2020

Although human leucocyte antigen (HLA)‐B27 is strongly associated with ankylosing spondylitis (AS), the association of unfolded protein response (UPR) induced by HLA‐B27 misfolding in AS remains controversial. Since dendritic cells (DCs) are crucial in induction of AS in HLA‐B27‐transgenic rats, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of pDCs and UPR in AS. Peripheral pDCs were isolated from 27 HLA‐B27(+) AS patients and 37 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. We found a significantly higher frequency of pDCs in the peripheral blood, BM, or inflamed synovium of hips, which is associated with the enhanced expression of pDC trafficking molecules, CCR6 and CCL20 in the synovium of AS patients. Functional analysis further revealed that several inflammatory cytokines, including TNFα, IL‐6, and IL‐23, secreted by pDCs were significantly increased in AS patients as compared with those in controls. Remarkably, protein kinase RNA‐like endoplasmic reticulum kinase (PERK) pathway in UPR was up‐regulated in pDCs of AS patients. Notably, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs of AS patients. Further, the extent of PERK activation was significantly associated with the increased disease severity of AS patients. Our data uncover the aberrant distribution and function of pDCs in AS patients. The up‐regulated PERK pathway in UPR of pDCs not only contributes to enhanced cytokine production of pDCs, but also is associated with increased disease activity of AS patients.
Identification and functional characterization of a novel heterozygous missense variant in the LPL associated with recurrent hypertriglyceridemia‐induced acute pancreatitis in pregnancy
Authors: Shi Xiao‐Lei , Yang Qi , Pu Na , Li Xiao‐Yao , Chen Wei‐Wei , Zhou Jing , Li Gang , Tong Zhi‐Hui , Férec Claude , Cooper David N. , Chen Jian‐Min , Li Wei‐Qin
Published: January 2020

Background

Acute pancreatitis in pregnancy (APIP) is a life‐threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia‐induced APIP (HTG‐APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency.

Methods

The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG‐APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells.

Results

A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein.

Conclusion

This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG‐APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG‐APIP.
Role of NPR2 mutation in idiopathic short stature: Identification of two novel mutations
Authors: Hwang Il Tae , Mizuno Yusuke , Amano Naoko , Lee Hye Jin , Shim Young Suk , Nam Hyo‐Kyoung , Rhie Young‐Jun , Yang Seung , Lee Kee‐Hyoung , Hasegawa Tomonobu , Kang Min Jae
Published: January 2020

Background

C‐type natriuretic peptide (CNP, NPPC) and its receptor, natriuretic peptide receptor‐B (NPR‐B, NPR2), are critical for endochondral ossification. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. This study was performed to identify the NPR2 mutations in Korean patients with idiopathic short stature (ISS).

Methods

One hundred and sixteen subjects with nonsyndromic ISS were enrolled in this study, and the NPPC and NPR2 were sequenced. In silico prediction and in vitro functional analysis, using a cell‐based assay, were performed to confirm their protein derangement.

Results

Mean age at diagnosis of ISS was 8.0 years, and the height z‐score was −2.65. Three pathogenic variants (R921Q, R495C, and Y598N) and one benign variant (R787W) of the NPR2 were identified, while no novel sequence variant of the NPPC was found in all subjects. Two novel pathogenic mutants (R495C and Y598N) were predicted as highly pathogenic by several computational methods. In vitro study involving stimulation with CNP, R495C‐, and Y598N‐transfected cells showed decreased cGMP production compared to wild type‐transfected cells.

Conclusion

Heterozygous NPR2 mutations were found in 2.6% of ISS Korean subjects. This prevalence and the dominant‐negative effect of mutant NPR‐B on growth signals imply that it is one of genetic causes of ISS.
On a q‐Laplace–type integral operator and certain class of series expansion
Authors: Al‐Omari S. K. Q.
Published: January 2020

In this paper, we develop a q‐theory of the q‐Laplace–type integral operators qL2 and ql2 introduced by Uçar and Albayrak in 2011. We derive several identities and establish various results related to the q‐Laplace–type integral operators of various classes of q‐special functions and q‐series expansions. By using a q‐series representation of the q‐analogues, we obtain results enfolding power series of even orders. Further, by utilizing the new results, we obtain formulas and conclusions associated with q‐hypergeometric functions of first and second types. In a brief reading, we finally establish new formulas involving q‐trigonometric and q‐Bessel functions as well.
New insight into the organization of myelin water using deuterium NMR
Authors: Eliav Uzi , Wehrli Felix W. , Navon Gil
Published: January 2020

Purpose

Myelin water is commonly characterized by its short proton T2 relaxation time, suggesting strong association with the polar head groups of the bilayer constituents. Deuterium NMR of water in ordered structures exhibits splittings as a result of quadrupolar interactions that are observable using the double‐quantum filter. The purpose of the current study was to identify and characterize the water populations.

Methods

The 2H double‐quantum‐filtered spectroscopic experiments were conducted at 62 MHz (9.4 T) on a sample of reconstituted myelin from ovine spinal cord after exchange of native water with D2O.

Results

Signals passing the double‐quantum filter were attributed to 2 water pools: 1 consisting of a doublet of 650‐Hz splitting, and a second unsplit signal. Similar signals were observed in the sciatic and optic nerves and in the spinal cord. Further, data suggest that diffusion of water molecules in these 2 pools (Dapp ≤ 5 × 10−7 cm2/s) is either hindered or restricted. An estimate of exchange lifetime of 10‐15 ms between water pertaining to the single peak and that of the split peaks suggests exchange occurs in a slow‐intermediate rate regime. Further distinction between the 2 pools was obtained from T1 measurements. Deuterons belonging to the doublet resonance were found to have short T1, estimated to be on the order of 10‐20 ms, whereas those corresponding to the single peak were close to that of bulk D2O.

Conclusion

The results suggest that myelin extract water consists of 2 hindered populations with distinct degrees of anisotropic motion that can be studied by 2H double‐quantum‐filtered NMR.
Characterization complex collagen fiber architecture in knee joint using high‐resolution diffusion imaging
Authors: Wang Nian , Mirando Anthony J. , Cofer Gary , Qi Yi , Hilton Matthew J. , Johnson G. Allan
Published: January 2020

Purpose

To evaluate the complex fiber orientations and 3D collagen fiber network of knee joint connective tissues, including ligaments, muscle, articular cartilage, and meniscus using high spatial and angular resolution diffusion imaging.

Methods

Two rat knee joints were scanned using a modified 3D diffusion‐weighted spin echo pulse sequence with the isotropic spatial resolution of 45 μm at 9.4T. The b values varied from 250 to 1250 s/mm2 with 31 diffusion encoding directions for 1 rat knee. The b value was fixed to 1000 s/mm2 with 147 diffusion encoding directions for the second knee. Both the diffusion tensor imaging (DTI) model and generalized Q‐sampling imaging (GQI) method were used to investigate the fiber orientation distributions and tractography with the validation of polarized light microscopy.

Results

To better resolve the crossing fibers, the b value should be great than or equal to 1000 s/mm2. The tractography results were comparable between the DTI model and GQI method in ligament and muscle. However, the tractography exhibited apparent difference between DTI and GQI in connective tissues with more complex collagen fibers network, such as cartilage and meniscus. In articular cartilage, there were numerous crossing fibers found in superficial zone and transitional zone. Tractography generated with GQI also resulted in more intact tracts in articular cartilage than DTI.

Conclusion

High‐resolution diffusion imaging with GQI method can trace the complex collagen fiber orientations and architectures of the knee joint at microscopic resolution.
Types of love as a function of satisfaction and age
Authors: Clemente Miguel , Gandoy‐Crego Manuel , Bugallo‐Carrera Cesar , Reig‐Botella Adela , Gomez‐Cantorna Cristina
Published: January 2020

Research studies on love have focused on the study of typologies, among which Sternberg's triangular theory of love and the typology of Hendrick and Hendrick deriving from that of Sternberg have been the most common and empirically verified. Love types have been linked to all types of sociodemographic and psychological variables. However, these studies possess shortcomings: When the data are analyzed according to age, only a few ranges are studied; with respect to other variables such as satisfaction, typically only two levels are studied, and no continuous study is conducted. This study attempts to overcome these limitations. It analyzes types of love according to the two systems noted earlier and based on two variables: age and satisfaction. For satisfaction, the Satisfaction With Life Scale (SWLS) by Diener et al. was used, and 439 subjects aged 15 to 89 years participated in the study. The results show that both of the variables—age and satisfaction—explain that love types occur in varying degrees; however, satisfaction is more predictive than is age. Possibilities for future research are discussed.
The Impact of Proximal Roux‐en‐Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism
Authors: Chen Kuan‐Fu , Chan Lingtak‐Neander , Senn Taurence D. , Oelschlager Brant K. , Flum David R. , Shen Danny D. , Horn John R. , Lin Yvonne S.
Published: January 2020

Background

Roux‐en‐Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity.

Aim

The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen.

Materials and Methods

Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre‐RYGBS baseline and 3 and 12 months post‐RYGBS). Plasma was collected at pre‐specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography–mass spectrometry for APAP, APAPglucuronide (APAP‐gluc), APAP‐sulfate (APAP‐sulf), APAP‐cysteine (APAP‐cys), and APAP‐Nacetylcysteine (APAP‐nac).

Result

Following RYGBS, peak APAP concentrations at the 3‐month and 12‐month visits increased by 2.0‐fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP‐gluc, APAP‐sulf, APAP‐cys, and APAP‐nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)‐to‐APAP AUC for all four metabolites decreased at 3 and 12 months post‐RYGBS compared to the presurgical baseline. In a simulation of expected steady‐state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post‐RYGBS patients had higher steady‐state peak APAP concentrations compared to healthy individuals and obese pre‐RYGBS patients, though APAP exposure was unchanged compared to healthy individuals.

Conclusion

Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.
Parameters of reported childhood sexual abuse and assault in adolescents and adults with borderline personality disorder
Authors: Temes Christina M. , Magni Laura R. , Aguirre Blaise A. , Goodman Marianne , Ridolfi Maria Elena , Zanarini Mary C.
Published: January 2020

Objective

Prior research has demonstrated a link between childhood sexual abuse and borderline personality disorder (BPD) in adolescents and adults and has indicated that more severe abuse is related to poorer psychosocial functioning. The present study describes the overall severity of sexual abuse/assault in adolescents and adults with BPD and compares both groups on specific parameters of abusive and assaultive experiences.

Methods

Participants included 104 adolescent (aged 13–17 years) inpatients with BPD and 290 adult inpatients with BPD. All participants completed two interviews that assessed the presence and severity of sexual abuse/assault.

Results

Of the studied patients with BPD, 26.0% of adolescents and 62.4% of adults reported a childhood history of sexual abuse/assault before the age of 18. Adults had higher scores on an index of sexual abuse severity than adolescents, and a higher proportion of adults reported scores in the severe range. Adults with BPD were also more likely than adolescents to report having experienced sexual abuse/assault that occurred at multiple developmental stages, was frequent (i.e. weekly basis or more), was longer in duration (i.e. a year or more) and was perpetrated by a parent. The groups did not differ on other parameters.

Conclusions

Taken together, these results suggest that adults with BPD are more likely to report childhood sexual abuse/assault than adolescents with BPD. Additionally, adults report histories of sexual abuse/assault that are more severe than adolescents with BPD, with specific differences observed in timing, frequency, duration and perpetrator. © 2020 John Wiley & Sons, Ltd.
Liquid Biopsy Based Single‐Cell Transcriptome Profiling Characterizes Heterogeneity of Disseminated Tumor Cells from Lung Adenocarcinoma
Authors: Dong Yu , Wang Zhuo , Shi Qihui
Published: January 2020

The advent of rapid and inexpensive sequencing technology allows scientists to decipher intra‐tumor heterogeneity spatially and temporally for resolving the evolutionary history of tumor and the underlying mechanism. However, studies on characterizing heterogeneity of disseminated tumor cells (DTCs) in liquid biopsies are rare because of the rarity and low viability of DTCs as well as a large number of non‐tumor cells. Here, high‐throughput single‐cell transcriptome sequencing technology and rare DTC enrichment method are employed to decipher the heterogeneity and distinct molecular signatures of DTCs in malignant pleural effusion (MPE) from lung adenocarcinoma. Single‐cell transcriptomes of 8213 MPE‐derived cells are acquired for bioinformatics analysis. In these cells from MPE, five main cell populations including tumor, mesothelial, monocyte, T and B cells are identified with specific markers for each group. Tumor cells present in MPE are further divided into four distinct subgroups that are found to be associated with immune response, cell proliferation, apoptosis, and cell adhesion, respectively. Based on the single‐cell dataset of MPE‐derived DTCs, 19 tumor‐specific markers are identified that are also highly expressed at RNA and protein levels in tumor tissues as candidate markers for detection of extraordinarily rare circulating tumor cells in the blood.
Assessing the lifetime performance index for Kumaraswamy distribution under first‐failure progressive censoring scheme for ball bearing revolutions
Authors: Abd El‐Monsef Mohamed Mohamed Ezzat , Hassanein Wafaa Anwar Abd El‐Latif
Published: January 2020

First‐failure progressive censoring schemes have potential usefulness in practice where budget constraints in place or there is a necessary for speedy test. To test the process capability, the lifetime performance index CL is widely recommended for evaluating the performance of the products lifetime. This paper is devoted to construct the maximum likelihood estimator of the lifetime performance index CL and the hypothesis testing technique for implementing CL under first‐failure progressive censoring sample from Kumaraswamy population. Finally, to illustrate the potentiality of the proposed procedure, two real engineering applications and a simulated example are given.
On monitoring the process mean of autocorrelated observations with measurement errors using the w‐of‐w runs‐rules scheme
Authors: Shongwe Sandile C. , Malela‐Majika Jean‐Claude , Castagliola Philippe
Published: January 2020

Runs‐rules have been widely used since the 1950s in industrial and nonindustrial process monitoring applications to improve the performance of basic and other traditional monitoring schemes. However, none of the studies on runs‐rules have accounted for a process with a combined effect of measurement errors and autocorrelation. Hence, in this paper, the use of the w‐of‐w runs‐rules to improve the performance of the Shewhart
scheme using an additive model with a constant variance and a first‐order autoregressive model is proposed. To reduce the combined negative effect of measurement errors and autocorrelation, we implement a sampling strategy based on rational subgroups in which (a) multiple measurements per item are taken (instead of a standard single measurement) and (b) non‐neighboring observations are gathered. Moreover, the latter sampling strategy is incorporated into the values of probability elements of a Markov chain matrix which is used to derive some closed‐form expressions for the zero‐ and steady‐state run‐length distribution. The main finding of this study is that, with respect to some overall performance measures, the proposed scheme outperforms the existing Shewhart
scheme by a significant margin. A real‐life example is used to illustrate the practical implementation of the proposed scheme.
Templateless Synthesis of Ultra‐Microporous 3D Graphitic Carbon from Cyclodextrins and Their Use as Selective Catalyst for Oxygen Activation
Authors: Rendón‐Patiño Alejandra , Santiago‐Portillo Andrea , Vallés‐Garcia Cristina , Palomino Miguel , Navalón Sergio , Franconetti Antonio , Primo Ana , Garcia Hermenegildo
Published: January 2020

Pyrolysis of α‐, β‐, and γ‐cyclodextrins at 900 °C gives rise to the formation of crystalline graphitic porous nanoparticles (GCD), where the dimensions of the pores are uniform in the range from 0.63 to 0.97 nm, from Gα‐CD to Gγ‐CD, as determined by transmission electron microscopy. It is found that, while for Gβ‐CD and Gγ‐CD, the surface area measured by N2 adsorption is about 330–550 m2 g−1, respectively, no area can be measured for Gα‐CD with N2 or Ar due to its small pore dimensions. However, CO2 adsorption reveals for Gα‐CD the presence of ultra‐microporosity and a surface area of 727 m2 g−1. GCD exhibits activity as metal‐free catalysts for the aerobic oxidation of alcohols and the activity increases as the pore dimension decreases. Density functional theory calculations indicate that this high catalytic activity for O2 activation derives from confinement effects that favor charge transfer from the graphitic walls to O2. Studies on the formation mechanism shows that the key step leading to the formation of the channels is the melting of cyclodextrin precursors that makes possible the assembly of these capsules before their transformation into microporous graphitic particles.