bluuebunny/crossref_metadata_2025_split huggingface dataset:
DREAMM: a web-based server for drugging protein-membrane interfaces as a novel workflow for targeted drug design
Authors: Chatzigoulas Alexios , Cournia Zoe 
Published: November 2022

Abstract

Summary
The allosteric modulation of peripheral membrane proteins (PMPs) by targeting protein-membrane interactions with drug-like molecules represents a new promising therapeutic strategy for proteins currently considered undruggable. However, the accessibility of protein-membrane interfaces by small molecules has been so far unexplored, possibly due to the complexity of the interface, the limited protein-membrane structural information and the lack of computational workflows to study it. Herein, we present a pipeline for drugging protein-membrane interfaces using the DREAMM (Drugging pRotein mEmbrAne Machine learning Method) web server. DREAMM works in the back end with a fast and robust ensemble machine learning algorithm for identifying protein-membrane interfaces of PMPs. Additionally, DREAMM also identifies binding pockets in the vicinity of the predicted membrane-penetrating amino acids in protein conformational ensembles provided by the user or generated within DREAMM.

Availability and implementation
DREAMM web server is accessible via https://dreamm.ni4os.eu.

Supplementary information
Supplementary data are available at Bioinformatics online.
Analytical Quality-by-Design-Based Systematic Optimization of RP-HPLC Method Conditions to Analyze Simultaneously Chloroquine Phosphate and Flavopiridol in Stress-Induced Combined Drug Solution and Pharmaceutical Emulsions
Authors: Pawde Datta Maroti , Rahman Syed Nazrin Ruhina , Ponneganti Srikanth , Goswami Abhinab , Borkar Roshan Murlidhar , Shunmugaperumal Tamilvanan 
Published: November 2022

Abstract
A design of experiments (DoE)-driven RP-HPLC method conditions was employed to analyze simultaneously chloroquine (CQ) phosphate and flavopiridol (FLAP) in emulsions and solution. After subjecting the various critical method attributes to preliminary risk assessment and screening by Pareto-chart-based fractional factorial design, the 17 runs were produced in Box–Behnken design for optimization. Analysis of variance, lack of fit, prediction equations, 3D response surface plots and contour plots were used to evaluate the critical analytical attributes such as retention time, tailing factor and theoretical plate count. The optimized RP-HPLC method conditions include 262 nm as detection wavelength, 37°C temperature for column, 20-μl injection volume, 1-ml/min flow rate and mobile phase mixture [70:30 ratio of 0.4% triethylamine in methanol&sodium phosphate buffer (11 mM, pH 3.0)]. The studied validation parameters were found within the ICH–prescribed limits. Exposing the combined drug solution at oxidative stress condition resulted to diminish the FLAP recovery value (53.39 ± 0.86) and arrival of an extra chromatographic peak. However, the % drug entrapment efficiency values of 96.22 ± 2.47 and 85.86 ± 3.66, respectively, were noticed for CQ phosphate and FLAP in emulsions. Thus, DoE-driven approach could be helpful for systematically optimizing RP-HPLC method conditions.
Improved assembly and annotation of the sesame genome
Authors: Wang Mingcheng , Huang Jianwei , Liu Song , Liu Xiaofeng , Li Rui , Luo Junjia , Fu Zhixi 
Published: November 2022

Abstract
Sesame (Sesamum indicum L.) is an important oilseed crop that produces abundant seed oil and has a pleasant flavor and high nutritional value. To date, several Illumina-based genome assemblies corresponding to different sesame genotypes have been published and widely used in genetic and genomic studies of sesame. However, these assemblies consistently showed low continuity with numerous gaps. Here, we reported a high-quality, reference-level sesame genome assembly by integrating PacBio high-fidelity sequencing and Hi-C technology. Our updated sesame assembly was 309.35 Mb in size with a high chromosome anchoring rate (97.54%) and contig N50 size (13.48 Mb), which were better than previously published genomes. We identified 163.38 Mb repetitive elements and 24,345 high-confidence protein-coding genes in the updated sesame assembly. Comparative genomic analysis showed that sesame shared an ancient whole-genome duplication event with two Lamiales species. A total of 2,782 genes were tandemly duplicated. We also identified several genes that were likely involved in fatty acid and triacylglycerol biosynthesis. Our improved sesame assembly and annotation will facilitate future genetic studies and genomics-assisted breeding of sesame.
Soluble ST2 in plasma is associated with post-procedural no-or-slow reflow after primary percutaneous coronary intervention in ST-elevation myocardial infarction
Authors: Søndergaard Frederik T , Beske Rasmus P , Frydland Martin , Møller Jacob Eifer , Helgestad Ole K L , Jensen Lisette Okkels , Holmvang Lene , Goetze Jens P , Engstrøm Thomas , Hassager Christian 
Published: November 2022

Abstract

Aim
The no-or-slow-reflow phenomenon after primary percutaneous coronary intervention is associated with more extensive myocardial injury in patients with ST-elevation myocardial infarction (STEMI). Soluble suppression of tumourigenicity 2 (sST2) is released in acute myocardial response to injury, and an increase in plasma level in the initial phase of STEMI is associated with increased mortality and risk of heart failure. We have therefore explored the association of pre-intervention plasma sST2 with the post-procedural no-or-slow-reflow phenomenon in patients with STEMI.

Methods and results
We included consecutive patients with verified STEMI from two tertiary heart centres. Blood samples were collected at admission before angiography. Post-procedural coronary flow was assessed according to thrombolysis in myocardial infarction (TIMI) classification for STEMI. Patients were divided into two groups: post-procedural TIMI 0–2 as no-or-slow reflow and TIMI 3 as normal reflow. The association between sST2 and TIMI flow was explored using multiple logistic regression. A total of 1607 patients with available TIMI flow classification were included in the analysis. Normal reflow was seen in 1520 (94.6%), while 87 (5.4%) had no-or-slow reflow. No-or-slow-reflow patients had higher all-cause 30-day mortality [10 (11%) vs. 65 (4.3%), P = 0.006]. Pre-procedural sST2 was higher in the no-or-slow-flow group [47 ng/mL, interquartile range (IQR, 33–83) vs. 39 ng/mL (IQR 29–55), P &lt; 0.001] and was independently associated with post-procedural no-or-slow flow [two-fold sST2 increase: odds ratio 1.44 (1.15–1.78), P = 0.0012].

Conclusion
In patients with STEMI, the sST2 level at admission before coronary angiography is independently associated with the post-procedural no-or-slow-reflow phenomenon.
A giant and double-walled left atrial ball thrombus complicating a mitral stenosis: case report—a truck tire into the heart
Authors: Selimi Adelina , Ianni Umberto , Molisana Michela , Parato Vito Maurizio 
Published: November 2022

Abstract

Background
High thromboembolic risk associated with rheumatic mitral stenosis has been well established, especially in concomitant atrial fibrillation; however, the presence of left atrium ball thrombus is an uncommon finding.

Case Summary
A 75-year-old woman with a history of mild rheumatic mitral stenosis was admitted to Emergency Department with cardiogenic shock and high ventricular rate atrial fibrillation. Emergency electrical cardioversion was performed—before trans-oesophageal echocardiography (TOE)—due to haemodynamic deterioration which restored sinus rhythm.
Transthoracic echocardiography (TTE) revealed severe reduction of left ventricular ejection fraction (LVEF: 15%), severe rheumatic mitral stenosis and a large, perfectly rounded mass, situated at the ostium of left upper pulmonary vein. Due to the persistence of haemodynamic instability and acute pulmonary oedema the patient was intubated and mechanically ventilated and treated with intravenous administration of inotropes and high doses of diuretics. During the stay in Intensive Care Unit, a TOE confirmed a spherical and double-walled mass suggesting a working diagnosis of left atrial ball thrombus (LABT). The case was discussed in Heart Team and considering the poor haemodynamic status in the contest of refractory cardiogenic shock with evidence of multi-organ failure, emergency surgical thrombectomy and mitral valve replacement was deemed prohibitive. Patient developed cardiac arrest and emergency TTE showed left atrial mass engaged into the mitral valve totally obstructing the left ventricle inflow tract. The autopsy and histologic examination confirmed the thrombotic nature of the mass.

Discussion
A free-floating ball thrombus in the left atrium is an unusual occurrence in rheumatic mitral stenosis and it may cause fatal systemic embolization or acute left ventricular inflow obstruction, resulting in syncope, pulmonary congestion, and sudden cardiac death. When possible, emergency surgical thrombectomy and mitral valve replacement can be life-saving.
Prevalence and risk factors of cardiac thrombus prior to ventricular tachycardia catheter ablation in structural heart disease
Authors: Bonnin Thomas , Roumegou Pierre , Sridi Soumaya , Mahida Saagar , Bustin Aurélien , Duchateau Josselin , Tixier Romain , Derval Nicolas , Pambrun Thomas , Chniti Ghassen , Takagi Takamitsu , Kamakura Tsukasa , Krisai Philipp , Andre Clementine , Chauvel Rémi , Hocini Meleze , Haissaguerre Michel , Jais Pierre , Cochet Hubert , Sacher Frederic 
Published: November 2022

AbstractAimsAssess prevalence, risk factors, and management of patients with intra-cardiac thrombus referred for scar-related ventricular tachycardia (VT) ablation.Methods and resultsConsecutive VT ablation referrals between January 2015 and December 2019 were reviewed (n = 618). Patients referred for de novo, scar-related VT ablation who underwent pre-procedure cardiac computed tomography (cCT) were included. We included 401 patients [61 ± 14 years; 364 male; left ventricular ejection fraction (LVEF) 40 ± 13%]; 45 patients (11%) had cardiac thrombi on cCT at 49 sites [29 LV; eight left atrial appendage (LAA); eight right ventricle (RV); four right atrial appendage]. Nine patients had pulmonary emboli. Overall predictors of cardiac thrombus included LV aneurysm [odds ratio (OR): 6.6, 95%, confidence interval (CI): 3.1–14.3], LVEF &lt; 40% (OR: 3.3, CI: 1.5–7.3), altered RV ejection fraction (OR: 2.3, CI: 1.1–4.6), and electrical storm (OR: 2.9, CI: 1.4–6.1). Thrombus location-specific analysis identified LV aneurysm (OR: 10.9, CI: 4.3–27.7) and LVEF &lt; 40% (OR: 9.6, CI: 2.6–35.8) as predictors of LV thrombus and arrhythmogenic right ventricular cardiomyopathy (OR: 10.6, CI: 1.2–98.4) as a predictor for RV thrombus. Left atrial appendage thrombi exclusively occurred in patients with atrial fibrillation. Ventricular tachycardia ablation was finally performed in 363 including 7 (16%) patients with thrombus but refractory electrical storm. These seven patients had tailored ablation with no embolic complications. Only one (0.3%) ablation-related embolic event occurred in the entire cohort.ConclusionCardiac thrombus can be identified in 11% of patients referred for scar-related VT ablation. These findings underscore the importance of systematic thrombus screening to minimize embolic risk.
The Ruling Group Survival: Why Pakistan and Hungary Move Away from the US-led Order?
Authors: Balcı Ali , Yolcu Furkan Halit 
Published: November 2022

AbstractWhy do some smaller states signal to move away from the US-led liberal order? We look at the ruling group survival in smaller allies to answer this pressing puzzle. Despite accepting the merit of systemic explanations, we simply argue that the ruling groups in smaller states engage with revisionist powers in the international system to sustain and enhance their privileged positions in the domestic policy setting. Hungary, a NATO member, and Pakistan, a traditional ally of the United States, have long been showing signs of shifting toward the China/Russia axis. We explain the behavior of Hungary and Pakistan during the 2010s by focusing on the survival strategies of key ruling groups in those countries. We simply argue that relations of competing great powers with the ruling group in smaller states determine the fate of asymmetric alliance.
To Tell or Not: Chinese Older Adults’ Preferences for Disclosing or Concealing Serious Illness Diagnoses
Authors: Lou Yifan , Liu Jinyu , Carr Deborah 
Published: November 2022

Abstract

Background and Objectives
Knowledge of one’s medical diagnosis is critical for end-of-life decision making. However, a patient’s right to know their diagnosis is neither guaranteed nor protected by law in China. Doctors typically inform family members of the patient’s illness diagnosis and prognosis and let the family decide whether to disclose this information to the patient. This study examines midlife and older Chinese adults’ preferences for disclosure of their own and significant others’ diagnoses, and the sociodemographic, economic, and cultural factors associated with these preferences.

Research Design and Methods
We surveyed 571 adults ages 50+ in Shanghai from 2021 to 2022. Our outcome measures are preferences for diagnosis disclosures, including whether and to whom diagnoses should be disclosed. We characterize preference types using latent class analysis, and estimate multinomial logistic regression to identify the covariates associated with each preference type.

Results
Three latent classes were identified. The transparent group (34%) believed patients, whether self or a significant other, should be informed of their own diagnoses. The contradictory group (50%) held conflicting attitudes; they preferred to know their own diagnosis but preferred that significant others not be informed of their diagnoses. The avoidant group (16%) preferred not to know their own diagnosis and similarly preferred not to disclose significant others’ diagnoses to them. Familism attitudes were positively associated with holding contradictory views. Experiences with hospitalization and medical decision making for family members were associated with holding transparent views.

Discussion and Implications
We discuss the importance of illness disclosure for honoring patients’ autonomous decision making.
Parametric spectral inversion of seismic source, path and site parameters: application to northeast Italy
Authors: Cataldi Laura , Poggi Valerio , Costa Giovanni , Parolai Stefano , Edwards Benjamin 
Published: November 2022

SUMMARY
Strong ground motion prediction is a fundamental topic in the field of engineering seismology, as it provides the input for seismic hazard studies as well as for vulnerability and risk assessment. The spectral modelling approach can provide a realistic representation of ground motion behaviour, possibly including its frequency variability, as the full ground motion spectrum is modelled analytically. In its parametric form, this approach requires a careful calibration of the model, starting from empirical observations and fitting the source, path and the site-specific response assuming a predefined physically constrained functional form. This study explores the use of spectral modelling for a study area in northeast Italy, at the border with Slovenia and Austria. It is based on the parametrization of seismic source and attenuation effects, and it also allows to estimate site effects, as a by-product. The main innovation with respect to standard spectral modelling is the inclusion of dedicated uncertainty estimators in the functional form. Parametric inversion of source and path attenuation is performed on a data set corresponding to 23 events recorded by 24 stations located within the target area. The modular inversion setup allows to properly include a priori constraints in the mathematical solution to reduce trade-off between variables. Spectral amplification at each site is defined with respect to the network average rock condition, and its frequency-dependent component is estimated from residual analysis after the inversion. Inverted source parameters are comparable with reference values for the region available from literature (with seismic moments between ${10}^{13}$ and ${10}^{15}$ N·m, and related stress drop values in the range $1.5 - 15.5\ {\rm{MPa}}$); the same is also true for average attenuation properties (e.g. apparent frequency-independent attenuation quality factor ${Q}_0$ of $1145$). For a selection of stations with available characterization based on different methods, a preliminary comparison of site-specific response functions shows that both the frequency value and amplitude of the main amplification peaks are well recovered. These encouraging results open to the possibility of subsequently using the calibrated model for forward modelling purposes.
A splice site mutation in theFvePHPgene is associated with leaf development and flowering time in woodland strawberry
Authors: Wang Baotian , Li Weijia , Xu Kexin , Lei Yingying , Zhao Di , Li Xue , Zhang Junxiang , Zhang Zhihong 
Published: November 2022

AbstractLeaves and flowers are crucial for the growth and development of higher plants. In this study we identified a mutant with narrow leaflets and early flowering (nlef) in an ethyl methanesulfonate-mutagenized population of woodland strawberry (Fragaria vesca) and aimed to identify the candidate gene. Genetic analysis revealed that a single recessive gene, nlef, controlled the mutant phenotype. We found that FvH4_1g25470, which encodes a putative DNA polymerase α with a polymerase and histidinol phosphatase domain (PHP), might be the candidate gene, using bulked segregant analysis with whole-genome sequencing, molecular markers, and cloning analyses. A splice donor site mutation (C to T) at the 5′ end of the second intron led to an erroneous splice event that reduced the expression level of the full-length transcript of FvePHP in mutant plants. FvePHP was localized in the nucleus and was highly expressed in leaves. Silencing of FvePHP using the virus-induced gene silencing method resulted in partial developmental defects in strawberry leaves. Overexpression of the FvePHP gene can largely restore the mutant phenotype. The expression levels of FveSEP1, FveSEP3, FveAP1, FveFUL, and FveFT were higher in the mutants than those in ‘Yellow Wonder’ plants, probably contributing to the early flowering phenotype in mutant plants. Our results indicate that mutation in FvePHP is associated with multiple developmental pathways. These results aid in understanding the role of DNA polymerase in strawberry development.
Molecular and Functional Characterization of Human Intestinal Organoids and Monolayers for Modeling Epithelial Barrier
Authors: Jelinsky Scott A , Derksen Merel , Bauman Eric , Verissimo Carla S , van Dooremalen Wies T M , Roos Jamie Lee , Higuera Barón Celia , Caballero-Franco Celia , Johnson Bryce G , Rooks Michelle G , Pott Johanna , Oldenburg Bas , Vries Robert G J , Boj Sylvia F , Kasaian Marion T , Pourfarzad Farzin , Rosadini Charles V 
Published: November 2022

Abstract

Background
Patient-derived organoid (PDO) models offer potential to transform drug discovery for inflammatory bowel disease (IBD) but are limited by inconsistencies with differentiation and functional characterization. We profiled molecular and cellular features across a range of intestinal organoid models and examined differentiation and establishment of a functional epithelial barrier.

Methods
Patient-derived organoids or monolayers were generated from control or IBD patient–derived colon or ileum and were molecularly or functionally profiled. Biological or technical replicates were examined for transcriptional responses under conditions of expansion or differentiation. Cell-type composition was determined by deconvolution of cell-associated gene signatures and histological features. Differentiated control or IBD-derived monolayers were examined for establishment of transepithelial electrical resistance (TEER), loss of barrier integrity in response to a cocktail of interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and prevention of cytokine-induced barrier disruption by the JAK inhibitor, tofacitinib.

Results
In response to differentiation media, intestinal organoids and monolayers displayed gene expression patterns consistent with maturation of epithelial cell types found in the human gut. Upon differentiation, both colon- and ileum-derived monolayers formed functional barriers, with sustained TEER. Barrier integrity was compromised by inflammatory cytokines IFN-γ and TNF-α, and damage was inhibited in a dose-dependent manner by tofacitinib.

Conclusions
We describe the generation and characterization of human colonic or ileal organoid models capable of functional differentiation to mature epithelial cell types. In monolayer culture, these cells formed a robust epithelial barrier with sustained TEER and responses to pharmacological modulation. Our findings demonstrate that control and IBD patient-derived organoids possess consistent transcriptional and functional profiles that can enable development of epithelial-targeted therapies.
Optimising database searching in pharmacy education
Authors: Hope Denise L , Grant Gary D , Rogers Gary D , King Michelle A 
Published: November 2022

Abstract

Objectives
To determine the effectiveness of databases in a pharmacy education literature search.

Methods
Six databases (CINAHL, ERIC, Google Scholar, Ovid MEDLINE, Science Direct and Scopus) were compared for effectiveness in identifying pharmacy education literature. Articles were coded for database of retrieval and results cross-referenced. Sensitivity, precision and number of unique retrievals were calculated.

Key findings
Scopus yielded the highest sensitivity (65%) and precision (47%). The combination of three databases (Scopus, Science Direct and Google Scholar) identified 97% (n = 64) of 66 relevant articles.

Conclusions
Pharmacy education literature searches require more than one database, ideally Scopus, Science Direct and Google Scholar.
Subspecific Synonym ofMonochamus alternatus(Coleoptera: Cerambycidae): Population Genetics and Morphological Reassessment
Authors: Lee Seunghyun , Oh Dae-Ju , Lee Seunghwan , Chung Sang bae , Dong-soon Kim 
Published: November 2022

AbstractMonochamus alternatus Hope, 1842, is a major forest pest that hosts the pathogenic pinewood nematode (PWN), Bursaphelenchus xylophilus (Steiner and Buhrer, 1934) Nickle 1970. Taxonomically, M. alternatus is currently divided into two subspecies, based on morphology and geography: Monochamus alternatus alternatus Hope, 1842 in China, Taiwan, Tibet, Vietnam, and Laos and Monochamus alternatus endai Makihara, 2004 in South Korea and Japan. Despite their economic importance, the subspecies taxonomy of M. alternatus has never been tested after the first description. In this study, we aimed to reassess the subspecies taxonomy of M. alternatus using molecular and morphological data. For morphological analysis, we examined three major morphological characters (pronotal longitudinal band, granulation on humeri, and elytral proximomedial spine) from 191 individuals from China, Korea, and Taiwan. Population genetic structures were examined using 85 de novo sequences and 82 public COI sequences from China, Korea, Japan, Malaysia, Taiwan, and a few intercepted specimens from the United States. All the genetic data were aligned as three different multiple sequence alignments. Individuals from each subspecies were morphologically and genetically scattered, not clustered according to subspecies in any of the analyses. Therefore, a new synonymy is proposed: Monochamus alternatus Hope, 1842 = Monochamus alternatus endai, syn. n. This study suggests a more robust classification of M. alternatus for the first time and ultimately will pose a substantial impact on implementing quarantine or forestry policies.