bluuebunny/crossref_metadata_2025_split huggingface dataset:
No association between cataract surgery and mitochondrial DNA damage with age-related macular degeneration in human donor eyes
Authors: Armbrust Karen R. , Karunadharma Pabalu P. , Terluk Marcia R. , Kapphahn Rebecca J. , Olsen Timothy W. , Ferrington Deborah A. , Montezuma Sandra R. 
Published: October 2021

PurposeTo determine whether age-related macular degeneration (AMD) severity or the frequency of retinal pigment epithelium mitochondrial DNA lesions differ in human donor eyes that have undergone cataract surgery compared to phakic eyes.MethodsEyes from human donors aged ≥ 55 years were obtained from the Minnesota Lions Eye Bank. Cataract surgery status was obtained from history provided to Eye Bank personnel by family members at the time of tissue procurement. Donor eyes were graded for AMD severity using the Minnesota Grading System. Quantitative PCR was performed on DNA isolated from macular punches of retinal pigment epithelium to quantitate the frequency of mitochondrial DNA lesions in the donor tissue. Univariable and multivariable analyses were performed to evaluate for associations between (1) cataract surgery and AMD severity and (2) cataract surgery and mitochondrial DNA lesion frequency.ResultsA total of 157 subjects qualified for study inclusion. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that only age was associated with AMD grade. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that none of these factors were associated with retinal pigment epithelium mitochondrial DNA lesion frequency.ConclusionsIn this study of human donor eyes, neither retinal pigment epithelium mitochondrial DNA damage nor the stage of AMD severity are independently associated with cataract surgery after adjusting for other AMD risk factors. These new pathologic and molecular findings provide evidence against a relationship between cataract surgery and AMD progression and support the idea that cataract surgery is safe in the setting of AMD.
Handgrip strength cutoff value predicting successful extubation in mechanically ventilated patients
Authors: Saiphoklang Narongkorn , Mokkongphai Nattawadee 
Published: October 2021

Background
Handgrip strength (HGS) is an alternative tool to evaluate respiratory muscle function. HGS cutoff value indicating extubation success or failure has not been investigated. This study aimed to determine HGS cutoff value to predict successful extubation.

Methods
A prospective study was conducted. Patients requiring intubated mechanical ventilation with intubation ≥ 48 hours in medical wards were recruited. HGS test was performed at 10 minutes before and 30 minutes after spontaneous breathing trial (SBT). Rapid shallow breathing index (RSBI) was measured at 10 minutes before SBT.

Results
Ninety-three patients (58% men) were included. Mean age was 71.6 ± 15.2 years. Weaning failure rate was 6.5%. The area under the ROC curve of 0.84 for the best HGS cutoff value at 10 minutes before SBT was 12.7 kg, with 75.9% sensitivity and 83.3% specificity (P = 0.005). The best HSG cutoff value at 30 minutes after SBT was 14.9 kg, with the area under the ROC curve of 0.82, with 58.6% sensitivity and 83.3% specificity (P = 0.009). The best RSBI cutoff value was 43.5 breaths/min/L, with the area under the ROC curve of 0.46, 33.3% sensitivity and 66.6% specificity (P = 0.737).

Conclusions
HGS may be a predictive tool to guide extubation with better sensitivity and specificity than RSBI. A prospective study is needed to verify HGS test as adjunctive to RSBI in ventilator weaning protocol.
Updatable learned index with precise positions
Authors: Wu Jiacheng , Zhang Yong , Chen Shimin , Wang Jin , Chen Yu , Xing Chunxiao 
Published: October 2021

Index plays an essential role in modern database engines to accelerate the query processing. The new paradigm of "learned index" has significantly changed the way of designing index structures in DBMS. The key insight is that indexes could be regarded as learned models that predict the position of a lookup key in the dataset. While such studies show promising results in both lookup time and index size, they cannot efficiently support update operations. Although recent studies have proposed some preliminary approaches to support update, they are at the cost of scarifying the lookup performance as they suffer from the overheads brought by imprecise predictions in the leaf nodes.
In this paper, we propose LIPP, a brand new framework of learned index to address such issues. Similar with state-of-the-art learned index structures, LIPP is able to support all kinds of index operations, namely lookup query, range query, insert, delete, update and bulkload. Meanwhile, we overcome the limitations of previous studies by properly extending the tree structure when dealing with update operations so as to eliminate the deviation of location predicted by the models in the leaf nodes. Moreover, we further propose a dynamic adjustment strategy to ensure that the height of the tree index is tightly bounded and provide comprehensive theoretical analysis to illustrate it. We conduct an extensive set of experiments on several real-life and synthetic datasets. The results demonstrate that our method consistently outperforms state-of-the-art solutions, achieving by up to 4X for a broader class of workloads with different index operations.
Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum
Authors: Habler Katharina , Kalla Anne-Sophie , Rychlik Michael , Bruegel Mathias , Teupser Daniel , Nährig Susanne , Vogeser Michael , Paal Michael 
Published: October 2021

Abstract

Objectives
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have revolutionized the therapeutic landscape in CF treatment. These vital drugs are extensively metabolized via CYP3A, so caution must be exercised in multimodal CF therapy because of the risk of adverse drug interactions. Our goal was to develop a highly sensitive assay for the purpose of therapeutic drug monitoring (TDM) in diagnostic laboratories.

Methods
After protein precipitation, the CFTR modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their metabolites ivacaftor-M1, ivacaftor-M6, and tezacaftor-M1 were separated with a two-dimensional chromatography setup within 5 min, and quantified with stable isotope-labeled internal standards. The method was validated according to the European Medicines Agency (EMA) guideline on bioanalytical method validation and applied to CF patient samples.

Results
Inaccuracy was ≤7.0% and the imprecision coefficient of variation (CV) was ≤8.3% for all quality controls (QCs). The method consistently compensated for matrix effects, recovery, and process efficiency were 105–115 and 96.5–103%, respectively. Analysis of CF serum samples provided concentrations comparable to the pharmacokinetic profile data reported in the EMA assessment report for the triple combination therapy Kaftrio.

Conclusions
We hereby present a robust and highly selective isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) assay for the simultaneous quantification of the so far approved CFTR modulators and their metabolites in human serum. The assay is suitable for state-of-the-art pharmacovigilance of CFTR modulator therapy in CF patients, in order to maximize safety and efficacy, and also to establish dose-response relationships in clinical trials.
Numerical study of time delay singularly perturbed parabolic differential equations involving both small positive and negative space shifts
Authors: Sahu Subal Ranjan , Mohapatra Jugal 
Published: October 2021

Abstract
A time dependent singularly perturbed differential-difference equation is considered.
The problem involves time delay and general small space shift terms.
Taylor series approximation is used to expand the space shift term.
A robust numerical scheme based on the backward Euler scheme
for the time and classical upwind scheme for space is proposed.
The convergence analysis is carried out. It is observed that
the proposed scheme converges
almost first order up to a logarithm term and optimal first order
in space on the Shishkin and Bakhvalov–Shishkin mesh, respectively.
Numerical results confirm the efficiency of the proposed scheme,
which are in agreement with the theoretical bounds.
Mini-medical school programs decrease perceived barriers of pursuing medical careers among underrepresented minority high school students
Authors: Abdulrazzak Abraham , Chandler Andrew , Lu Rosemary , Mobarakai Olivia , Lebron Bryan , Ingram Nicholas , Sheth Avni , Patel Neel , Parikh Shreel , Kumar Rita , Bedi Jessica , Diaw Ndeye Kane , Abonamah Adal , Lomiguen Christine , Fanning Stacey L. 
Published: October 2021

Abstract

Context
The percent of underrepresented minority (URM) students who apply to medical school has changed minimally in the past 40 years. Due to the lack of URM applicants, the consequent matriculation of URMs is grossly disproportionate from their percent representation of the US population. Increasing diversity among medical students and physicians has previously been identified as essential to decreasing healthcare disparities among US minorities.

Objectives
The objective of our study was to recognize the barriers of applying to medical school among URMs in high school.

Methods
To identify and assess the prevalence of barriers, surveys were distributed to participants of Med-Achieve, a mini-medical school program of diverse high school students in New York City during the 2019–2020 academic year.

Results
Among students who will be first in their immediate family to attend college, 80.0% perceived a barrier to pursuing medical school. Specified barriers indicated include the cost of medical school (77%), a lack of guidance/role models (53.9%), and the predicted inability to do well in medical school classes (53.9%). At the end of the program, a statistically significant reduction in the barrier of lack of guidance/role models was seen.

Conclusions
This study highlights the benefit of mini-medical school programs, especially programs with a mentoring component, to decrease the perceived barriers of applying to medical school among URMs. It also suggests the potential role of similar programs to increase diversity in medicine and to decrease healthcare disparities among minorities in the United States.
Superenhancer–transcription factor regulatory network in malignant tumors
Authors: Liang Yuan , Li Linlin , Xin Tian , Li Binru , Zhang Dalin 
Published: October 2021

Abstract

Objective
This study aims to identify superenhancer (SE)–transcriptional factor (TF) regulatory network related to eight common malignant tumors based on ChIP-seq data modified by histone H3K27ac in the enhancer region of the SRA database.

Methods
H3K27ac ChIP-seq data of eight common malignant tumor samples were downloaded from the SRA database and subjected to comparison with the human reference genome hg19. TFs regulated by SEs were screened with HOMER software. Core regulatory circuitry (CRC) in malignant tumor samples was defined through CRCmapper software and validated by RNA-seq data in TCGA. The findings were substantiated in bladder cancer cell experiments.

Results
Different malignant tumors could be distinguished through the H3K27ac signal. After SE identification in eight common malignant tumor samples, 35 SE-regulated genes were defined as malignant tumor-specific. SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. In vitro experimental data verified the presence of a SE–TF regulatory network in bladder cancer, and SE–TF regulatory network enhanced the malignant phenotype of bladder cancer cells.

Conclusion
The SE–TF regulatory network with SMAD3 as the core TF may participate in the carcinogenesis of malignant tumors.
Generation of hexagonal close-packed ring-shaped structures using an optical vortex
Authors: Kawaguchi Haruki , Umesato Kei , Takahashi Kanta , Yamane Keisaku , Morita Ryuji , Yuyama Ken-ichi , Kawano Satoyuki , Miyamoto Katsuhiko , Kohri Michinari , Omatsu Takashige 
Published: October 2021

Abstract
An optical vortex possesses a ring-shaped spatial profile and orbital angular momentum (OAM) owing to its helical wavefront. This form of structured light has garnered significant attention in recent years, and it has enabled new investigations in fundamental physics and applications. One such exciting application is laser-based material transfer for nano-/micro-fabrication. In this work, we demonstrate the application of a single-pulse optical vortex laser beam for direct printing of ring-shaped structures composed of hexagonal close-packed, mono-/multi-layered nanoparticles which exhibit ‘structural color’. We compare and contrast the interaction of the vortex beam with both dielectric and metallic nanoparticles and offer physical insight into how the OAM of vortex beams interacts with matter. The demonstrated technique holds promise for not only photonic-based nano-/micro-fabrication, but also as a means of sorting particles on the nanoscale, a technology which we term ‘optical vortex nanoparticle sorting’.
Comprehensive multidimensional study of the self-assembly properties of a three residue substituted β3 oligoamide
Authors: Buchanan Claire , Hinds Mark G. , Puskar Ljiljana , Garvey Christopher J. , Mechler Adam 
Published: October 2021

Abstract
Substituted β3 oligoamides form a unique self-assembling system where each monomer folds into a helix containing approximately three β3 amino acids per turn, yielding a geometrically well-defined cylindrical building block that, when N-acylated, is able to self-assemble head-to-tail into nanorods that can reach several 100 μm length. It was shown in previous works that self-assembly can be achieved with a three residue long oligoamide as well that lacks any intramolecular H-bonds, yet it crystallizes in a helix-like conformation. The self-assembly properties of these small oligoamides are however elusive, suggesting a more complex system than the self-assembly of the H-bond stabilized helical monomers. Here we focus on the self-assembly behaviour of a three residue oligoamide, Ac-β3[LIA] where the letters denote the side chain of the analogous α amino acid. Ac-β3[LIA] can yield highly inhomogeneous suspensions in water with a broad range of large fibrous structures that seem to be very stable, yet occasionally fibre growth is only observed upon heating. The small size of the monomer suggests a highly dynamic equilibrium yet all previous attempts failed to clearly identify low molecular weight species. Therefore a special methodology was employed in this study to characterize the suspensions at different size ranges: SANS that is optimal to measure the small oligomers and cross sectional diameter of the assemblies, DLS that is sensitive to the large populations and therefore the length of the superstructures, and NMR that is sensitive to monomeric and small oligomeric form, in conjunction with IR spectroscopy to probe the folding and AFM to image the morphology of the assemblies. Temperature ramping was used to perturb the system to probe the dynamicity of the self-assembly. It was found that the anomalous self-assembly behaviour of Ac-β3[LIA] is caused by its two stable conformations, a helix-building “horseshoe” fold and a linear conformer. The latter is exclusively found in monomeric form in solution whereas the horseshoe fold is stable in solid phase and in fibrous assemblies. Small oligomers were absent. Thus the self-assembly of Ac-β3[LIA] is arrested by the activation energy need of the conformation change; fibre growth might be triggered by conditions that allow increased conformational freedom of the monomers. This observation may be used to develop strategies for controlled switchable self-assembly.
Aggregation-induced emission (AIE): emerging technology based on aggregate science
Authors: Hu Rong , Zhang Guiquan , Qin Anjun , Tang Ben Zhong 
Published: October 2021

Abstract
Functional materials serve as the basic elements for the evolution of technology. Aggregation-induced emission (AIE), as one of the top 10 emerging technologies in chemistry, is a scientific concept coined by Tang, et al. in 2001 and refers to a photophysical phenomenon with enhanced emission at the aggregate level compared to molecular states. AIE-active materials generally present new properties and performance that are absent in the molecular state, providing endless possibilities for the development of technological applications. Tremendous achievements based on AIE research have been made in theoretical exploration, material development and practical applications. In this review, AIE-active materials with triggered luminescence of circularly polarized luminescence, aggregation-induced delayed fluorescence, room-temperature phosphorescence, and clusterization-triggered emission at the aggregate level are introduced. Moreover, high-tech applications in optoelectronic devices, responsive systems, sensing and monitoring, and imaging and therapy are briefly summarized and discussed. It is expected that this review will serve as a source of inspiration for innovation in AIE research and aggregate science.
Rechtswissenschaft als transdisziplinäres Netzwerk. Zur Verortung von Rechtssoziologie und Rechtsvergleichung
Authors: Eller Klaas Hendrik 
Published: October 2021

ZusammenfassungIn einem weitsichtigen Beitrag für die Erstausgabe der „Zeitschrift für Rechtssoziologie“ hat Dieter Martiny 1980 für eine Annäherung von Rechtssoziologie und Rechtsvergleichung plädiert. Der folgende Beitrag unternimmt anlässlich des Jubiläums dieser Zeitschrift eine Relektüre von Martinys Text und zeichnet in einer verschränkten Disziplinengeschichte von Rechtssoziologie und Rechtsvergleichung deren Berührungspunkte in den letzten Jahrzehnten nach. Darunter fallen Projekte der Harmonisierung und Quantifizierung von Recht, die beiden Disziplinen hohes praktisches Renommee eingebracht haben, aber wichtige Methodenfragen unbeantwortet ließen. In jüngerer Zeit führt die globalisierungsgetriebene Pluralisierung von Recht zur bislang engsten Verschränkung beider Disziplinen. Damit ist zugleich verbunden, dass die einzelne Disziplinengrenze an Bestimmungskraft verliert und an ihre Stelle ein multidimensionales, bewegliches System wechselnder disziplinärer Versatzstücke tritt. Dies wird hier beschrieben als Übergang von eineminterdisziplinären zu einemtransdisziplinären Paradigma der Rechtswissenschaft. Letzterem liegt das Bild eines Netzwerks der am Recht interessieren Disziplinen, darunter der Rechtssoziologie und Rechtsvergleichung, zugrunde. Das transdisziplinäre Paradigma dürfte die disziplinären Beziehungen künftiger Rechtsforschung zunehmend anleiten.
Thermal anomalies and phase transitions in Pb2Sc2Si2O9 and Pb2In2Si2O9
Authors: Gogolin Mathias , Murshed M. Mangir , Bayarjargal Lkhamsuren , Klimm Detlef , Gesing Thorsten M. 
Published: October 2021

Abstract
Pb2Sc2Si2O9 and Pb2In2Si2O9, respectively, the scandium and indium containing structural analogues of the mineral kentrolite are grown by spontaneous crystallization from a PbO flux. The corresponding polycrystalline powder samples are synthesized by conventional solid-state approach. The compounds are thoroughly characterized using temperature-dependent single crystal and powder X-ray diffraction, heat capacity measurements, second harmonic generation experiments and Raman spectroscopy. At ambient conditions, both compounds crystallize in the non-centrosymmetric Pna21 space group and undergo phase transitions to the centrosymmetric Pbcn space group at elevated temperatures. The Pbcn into Pna21 phase transitions are complemented by the signals of the temperature-dependent second harmonic generation. The specific heat capacity exhibits distinct cusp, supporting the λ-type second-order phase transition. The temperature dependency of some selective Raman modes further complements the findings, showing softening and hardening of the phonons across the phase transitions.
Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation
Authors: Chadani Yuhei , Sugata Nobuyuki , Niwa Tatsuya , Ito Yosuke , Iwasaki Shintaro , Taguchi Hideki 
Published: October 2021

AbstractContinuous translation elongation, irrespective of amino acid sequences, is a prerequisite for living organisms to produce their proteomes. However, nascent polypeptide products bear an inherent risk of elongation abortion. For example, negatively charged sequences with occasional intermittent prolines, termed intrinsic ribosome destabilization (IRD) sequences, weaken the translating ribosomal complex, causing certain nascent chain sequences to prematurely terminate translation. Here, we show that most potential IRD sequences in the middle of open reading frames remain cryptic and do not interrupt translation, due to two features of the nascent polypeptide. Firstly, the nascent polypeptide itself spans the exit tunnel, and secondly, its bulky amino acid residues occupy the tunnel entrance region, thereby serving as a bridge and protecting the large and small ribosomal subunits from dissociation. Thus, nascent polypeptide products have an inbuilt ability to ensure elongation continuity.
Operation Algorithm of the Adaptive Mechanism for Managing the Strategy Implementation in Digital Business Environment
Authors: Nikolaiev Mykola , Cherniavska Tetiana 
Published: October 2021

Purpose: To substantiate the elements of a complex mechanism for adaptive business strategies implementation and to develop an algorithm for its operation in a digital environment.
Findings: A hypothesis about the positive impact of global digitalization of business on the formation of an adaptive mechanism for managing the business strategy implementation. It is proved that in the digital environment the indicative tools and flexible methods of making managerial decisions are activated, the efficiency of functioning of the corresponding mechanisms increases. The author offers adaptive mechanism for managing the business strategy implementation in the conditions of digital environment, substantiates its components, determines the tools for environmental diagnostics, selection and implementation of adaptive strategies, and highlights the principles of operation and interconnection of the subsystems of the mechanism. The article reveals functions and tasks of the adaptive mechanism and offers the algorithm of its introduction in the conditions of the digital environment.
Practical Implications: The results of the study can be used in the practice of management of modern economic entities in order to ensure management decisions and strategic development in the context of global digitalization of business.
Originality/Value: For the first time, the author proposes the adaptive mechanism for managing the business strategy implementation in a digital environment and substantiates its components, functions, methods and tools.
Future Research: Risk management of adaptive strategies, indicative technologies of diagnostics of digital environment, systematization of world experience of strategic adaptive management.

Paper type: Theoretical