bluuebunny/crossref_metadata_2025 huggingface dataset:
Work Engagement and Performance of Auditors in the Province of Apayao in the Implementation of Flexible Work Arrangements
Authors: Ucol Erwin John
Published: December 2024

This study examines the work engagement and performance of auditors in the Commission on Audit (COA) in Apayao, focusing on flexible work arrangements and the influence of demographic factors such as age, gender, education, and years of service. Using a quantitative approach, it evaluates engagement in three dimensions—vigor, dedication, and absorption—and measures performance for the first and second semesters of 2023. Descriptive, comparative, and correlational research designs are employed, with data gathered through a survey using the Utrecht Work Engagement Scale (UWES) and performance ratings. Findings reveal that auditors exhibit high engagement, particularly in dedication, reflecting a strong sense of pride and purpose in their roles. Performance ratings were consistently "Outstanding" across both semesters, indicating a high level of commitment. Statistical analysis shows that demographic factors significantly influence both engagement and performance, highlighting the need to tailor support strategies to individual backgrounds. However, the study found no significant relationship between engagement levels and performance, suggesting that other factors, such as resources and workload management, may play a larger role in shaping performance outcomes. This study concludes that while flexible work arrangements contribute positively to engagement and performance, engagement alone does not directly impact performance. It recommends that COA consider demographic characteristics in designing engagement programs, enhance support for flexible work arrangements, and address additional factors to optimize auditor effectiveness and well-being.
Assessment of occupational noise-related hearing impairment among dental health personnel
Authors: Al-Omoush Salah A , Abdul-Baqi Khader J , Zuriekat Margaret , Alsoleihat Firas , Elmanaseer Wijdan R , Jamani Kifah D
Published: November 2019

Objectives

The purpose of the study was to examine hearing thresholds among dental personnel. The secondary aim was to evaluate sound levels among dental equipment that dental personnel are exposed to.

Methods

Two hundred forty-four dentists, dental technicians, dental assistants, and dental students participated. Sixty-two participated as a control group. Audiological thresholds for the test groups were compared to the control group. All participants were from Jordan University Hospital. Participants completed a questionnaire in addition to their audiometric testing. Otoscopy, tympanometry, and pure tone audiometry were included in their assessment. Three-factor ANOVA and t tests were utilized to assess the statistical differences of hearing thresholds among the groups and between the two ears. Pearson correlation test was used to assess the effect of age, experience, and duration of exposure on the degree of hearing loss in the test groups for both ears.

Results

The authors reported statistically significant differences among hearing thresholds between the control group and others. Left hearing thresholds were noted to be significantly poorer in the left versus right ear at 1000, 2000, 4000, and 8000 Hz in dental assistants. The authors also reported a significant relationship between the degree of hearing impairment among dental assistants and the daily duration of exposure to dental occupational noise, followed by age.

Conclusion

Hearing impairment was higher among dental professionals than the control group and especially among dental assistants and technicians. The authors recommended screening guidelines and adapting hearing protection methods for dental professionals and particularly for dental assistants and technicians.
Factors Predictive of Radiographic Progression in Ankylosing Spondylitis
Authors: Sari Ismail , Lee Seunghun , Tomlinson George , Johnson Sindhu R. , Inman Robert D. , Haroon Nigil
Published: November 2019

Objective

Using a longitudinal observational cohort of ankylosing spondylitis (AS) patients, we sought to identify progression rates and factors predictive of spinal progression. As a secondary aim, we analyzed the effect of tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression.

Methods

AS patients who had baseline and follow‐up cervical and lumbar radiographs were included in the study. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A change of 2 mSASSS units in 2 years was defined as progression. The characteristics of the study group such as demographic, clinical, laboratory, and treatment history were collected.

Results

There were 350 patients in the study. The mean ± SD mSASSS increased from 9.3 ± 15.8 units at baseline to 17.7 ± 21.7 units by the sixth year. Mean ± SD changes in mSASSS between the years 0 to 2, 2 to 4, and 4 to 6 were 1.23 ± 2.68, 1.47 ± 2.86, and 1.52 ± 3.7 units, respectively. Overall, 24.3% of the group progressed over 2 years. Male sex (hazard ratio [HR] 2.46 [95% confidence interval (95% CI) 1.05, 5.76]), the presence of baseline damage (HR 7.98 [95% CI 3.98, 16]), increased inflammatory markers (log C‐reactive protein level HR 1.35 [95% CI 1.07, 1.70]), and TNFi use (HR 0.82 [95% CI 0.70, 0.96]) were predictive of radiographic progression. There was a 20% reduction in the rate of progression with TNFi.

Conclusion

Male sex, the presence of baseline damage, active disease state, and higher inflammatory markers confer a high risk for disease progression. Treatment with TNFi showed a disease‐modifying effect by slowing the rate of radiographic progression.
Worldcraft: Building Worlds One Project at a Time
Authors: Pahhota Daria
Published: November 2019

Over the last decade, Copenhagen‐ and New York‐based architecture and urbanism firm Bjarke Ingels Group (BIG) has enjoyed a meteoric rise on the world stage. Daria Pahhota has presided over this as its Chief Communications Officer, heading the team that decides where, when and how the practice disseminates its news, messages and personality. Here she gives us a glimpse behind the scenes.
Exhibiting Architecture: Between the Profession and the Public
Authors: Hopkins Owen
Published: November 2019

London's Sir John Soane's Museum Senior Curator, Owen Hopkins, recounts the modern‐day encumbrances and successes of communicating architecture to the public. This mission to attract the public's understanding and appreciation of architecture is crucial to giving people the ‘tools’ with which to discuss and debate architecture thoughtfully in all arenas of civic life.
Figure Heads: Leadership and Succession in Architectural Practice
Authors: Cole Caroline
Published: November 2019

Colander Associates are experts in offering support and advice for architectural business development. The London firm's director Caroline Cole here explores various aspects of figurehead branding, with its ‘lone genius’ myth, as well as more collaborative modes of practice and their consequent corporate identity.
The Image of Architects: From the Explicit to the Inexplicit
Authors: Merrick Jay
Published: November 2019

Does size matter? Is it possible to retain the flavour and ambition of the work of an up‐and‐coming practice after it becomes successful, or large and international? Based in London, architectural journalist and critic Jay Merrick discusses and illustrates this conundrum, looking at a few practices and how their design prima materia is continually open to question.
Effective identification of sliding mode control parameters employing linear quadratic regulator and evolutionary computation techniques
Authors: Banazadeh Afshin , Khoshrooz Azad Reza , Emami Seyyed Ali
Published: November 2019

In this paper, a new technique to reduce the search space in evolutionary algorithms for operative identification of sliding mode control parameters is proposed, especially in the case of a rigid satellite. The reduced domain provides a solution closer to the actual optimum at a lower computational cost. The optimized sliding mode controller provides superior performance that eliminates the need for trial‐and‐error exploration. In this approach, a linear quadratic regulator is initially designed for the equivalent linear system. In order to reduce the convergence time and computational cost, the regulator history is then used as a reference to provide optimal space for the sliding mode control parameters. Consequently, boundaries of the optimal space are fed to the genetic algorithm to optimize the control parameters. On the other hand, the particle swarm optimization uses the midpoint of the optimal space as an initial guess. The validation process is performed by tuning the sliding mode control parameters for a rigid satellite, taking into account uncertainties associated with the inertia matrix. The simulation results suggest the convergence to the near‐optimal solution, and the stability and robustness of the controller are enhanced by this technique.
Role of the Hybrid Addition of Carbon Nanotubes and Graphene Nanoplatelets on the Corrosion Behavior of Plasma‐Sprayed Aluminum Oxide Nanocomposite Coating
Authors: Pandey Krishna Kant , Islam Aminul , Kumar Rakesh , Ghosh Rahul , Arjunan Venugopal , Keshri Anup Kumar
Published: November 2019

The effect of synergistic reinforcement of two types of carbon nanofillers, carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs), on the corrosion behavior of plasma‐sprayed alumina (Al2O3) nanocomposite coating in 3.5 wt% NaCl solution is studied. Incorporation of 1 wt% CNT and 0.5 wt% GNP into the Al2O3 matrix reduces the corrosion current density of the matrix from 2.78 to 0.21 μA cm−2, which drastically leads to a 13 times reduction in the corrosion rate of the Al2O3 matrix as compared with pure Al2O3 coating. The plausible reasons to this improvement are characterized by the filling of gaps, crevices, and microholes in the Al2O3 matrix by CNTs and GNPs and hydrophobic nature as well as chemical inertness of these reinforcements to the aggressive environment. Further, the corrosion products are analyzed by X‐ray diffraction and Raman spectroscopy for a much deeper insight into the mechanism of corrosion protection by these carbonaceous reinforcements. For the first time, the effect of CNT and GNP reinforcement on the corrosion behavior of plasma‐sprayed coatings is investigated.
A Brief Review on Thermal Metamaterials for Cloaking and Heat Flux Manipulation
Authors: Peralta Ignacio , Fachinotti Víctor D. , Álvarez Hostos Juan C.
Published: November 2019

Progress in material science has allowed the control of different physical fields in a manner that would be unachievable with ordinary materials. The development of engineered materials (the so‐called metamaterials) to control the conductive heat flux has revolutionized the manner of manipulating thermal energy and allowed the possibility of guiding the heat flux in ways difficult to accept for human intuition. Herein, a brief review regarding the recent progress and developments in thermal metamaterials conceived to perform several conductive heat flux manipulation tasks is provided. Deeply theoretical discussions concerning design methodologies are left a side, and the focus is made on the design and manufacturing feasibility of metamaterials for thermal cloaking and camouflage, heat flux concentration, and inversion, among other applications that lead to the next generation of thermal devices.
Prognostic factors associated with the survival of patients with gastric adenocarcinoma: A retrospective study
Authors: Chen Cheng‐Kuo , Feng Chun‐Lung , Yu Cheng‐Ju , Peng Cheng‐Yuan , Lai Hsueh‐Chou , Cheng Ken‐Sheng , Lin Yi‐Ching , Huang Wen‐Hsin , Kao Jung‐Ta
Published: November 2019

Gastric cancer is one of the most common gastrointestinal malignancies and is a lethal cancer. This study aimed to assess the factors affecting the survival and benefit of various therapeutic modalities in gastric adenocarcinoma (GAC) patients. Between March 2006 and October 2015, 121 GAC cases were identified by pathology and divided into groups I (surgery group; n = 41), II (IIa: 19 cases without treatment; IIb: 27 cases with palliative treatment), and III (combined surgery and postoperative chemotherapy; n = 34). Furthermore, the factors affecting early (12‐month) mortality and therapeutic outcomes between these groups were assessed over the study period. Patients who underwent treatment had longer survival than those who did not (groups I+IIb+III vs IIa, P < .001); group I provided the longest survival benefit among groups over the study period (Figure 2). Analyzing 12‐month mortality, significant differences were found in groups I vs IIa (P < .001), groups I vs IIb (P < .001), groups III vs IIa (P < .001), and groups III vs IIb (P < .001) in overall patients and in groups I vs IIa (P < .001), groups I vs IIb (P = .017), groups III vs IIa (P < .001), and groups III vs IIb (P < .001) in advanced‐stage patients (Table 2). Overall, the independent factors included advanced tumor stage (hazard ratio = 8.038, P = .007), absent treatment (hazard ratio = 14.009, P = .009), higher bilirubin (hazard ratio = 8.198, P = .047), and higher CEA (hazard ratio = 3.999, P = .030). Surgery provides better survival benefit, but palliative chemotherapy could also prolong unresectable GAC patients' survival. Factors of better liver preservation, lower carcinoembryonic antigen (CEA), and less aggressive tumor condition play crucial roles in predicting patients' survival.
Coagulation mixing studies: Utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests
Authors: Favaloro Emmanuel J.
Published: November 2019

Coagulation testing underpins the investigation of hemostasis and/or monitoring of anticoagulation therapy for prevention and/or treatment of thrombosis related pathology. Assessment of coagulation results requires comparison against a normal reference range or interval (NRR/NRI). Results flagged as “abnormal” (ie, above the NRR/NRI for patients not on anticoagulant therapy), typically require further evaluation. eg, follow up or reflexive testing is used to identify the reason for prolongation, especially when supported by clinical context (eg, bleeding). Mixing tests may have utility to help identify the pathway of follow‐up testing (ie, towards investigation of factor deficiencies, or else inhibitors), and are also useful for investigation of lupus anticoagulants (LA). In general, mixing tests that “correct” tend to suggest the presence of factor deficiencies, where as those that do not correct suggest the presence of “inhibitors”. Various approaches can be used to identify correction/non‐correction, and all have strengths and limitations. Furthermore, eventual identification of causal factor deficiencies or even “inhibitors” may (eg, factor VIII or IX deficiencies or inhibitors) or may not (eg, factor XII deficiency) be clinically important. Ultimately, mixing studies performed in view of appropriate clinical scenarios (eg, bleeding patient) and for LA investigations in symptomatic patients will have best utility.
A review of sonographic thyroid volume and iodine sufficiency in children: An Australian perspective
Authors: Johnson Ayaka , Edwards Christopher , Reddan Tristan
Published: November 2019

Sonographic measurement of the thyroid gland volume is a safe and reliable method for epidemiologic studies in iodine deficiency disorders. Several factors such as age, sex and anthropometric characteristics are known to be the determinants of thyroid gland size but the most widely studied is the effect of insufficient iodine intake. Low iodine intake induces enlargement of the thyroid gland known as goitre. The assessment of urinary iodine concentration alone is not reliable as it can vary daily within individuals. Urinary iodine concentration in conjunction with sonographic thyroid gland measurements is a widely used method of thyroid gland assessment. Establishment of normative thyroid volume is essential for the assessment of iodine deficiency disorders, and studies have been conducted in several countries. These studies have shown that thyroid gland volumes are likely population‐specific even in iodine‐sufficient countries limiting the effectiveness of international reference ranges. Based on currently available data of sonographic thyroid gland volume measurements and how they vary across populations of school children, this review argues for the establishment of population‐specific reference ranges in regions such as Australia, which are now considered iodine‐sufficient.
Simulation vs. Understanding: A Tension, in Quantum Chemistry and Beyond. Part A. Stage Setting
Authors: Hoffmann Roald , Malrieu Jean‐Paul
Published: November 2019

We begin our tripartite Essay with a triangle of understanding, theory and simulation. Sketching the intimate tie between explanation and teaching, we also point to the emotional impact of understanding. As we trace the development of theory in chemistry, Dirac's characterization of what is known and what is needed for theoretical chemistry comes up, as does the role of prediction, and Thom's phrase “To predict is not to explain.” We give a typology of models, and then describe, no doubt inadequately, machine learning and neural networks. In the second part, we leave philosophy, beginning by describing Roald's being beaten by simulation. This leads us to artificial intelligence (AI), Searle's Chinese room, and Strevens’ account of what a go‐playing program knows. Back to our terrain—we ask “Quantum Chemistry, † ca. 2020?” Then move to examples of AI affecting social matters, ranging from trivial to scary. We argue that moral decisions are hardly to be left to a computer. At this point, we try to pull the reader up, giving the opposing view of an optimistic, limitless future a voice. But we don't do justice to that view—how could we? We return to questioning the ascetic dimension of scientists, their romance with black boxes. Onward: In the 3rd part of this Essay, we work our way up from pessimism. We trace (another triangle!) the special interests of experimentalists, who want the theory we love, and reliable numbers as well. We detail in our own science instances where theory gave us real joy. Two more examples‐on magnetic coupling in inorganic diradicals, and the way to think about alkali metal halides, show us the way to integrate simulation with theory. Back and forth is how it should be—between painfully‐obtained, intriguing numbers, begging for interpretation, in turn requiring new concepts, new models, new theoretically grounded tools of computation. Through such iterations understanding is formed. As our tripartite Essay ends, we outline a future of consilience, with a role both for fact‐seekers, and searchers for understanding. Chemistry's streak of creation provides in that conjoined future a passage to art and to perceiving, as we argue we must, the sacred in science.
Identification of Catalytic Sites for Oxygen Reduction in Metal/Nitrogen‐Doped Carbons with Encapsulated Metal Nanoparticles
Authors: Chen Ming‐Xi , Zhu Mengzhao , Zuo Ming , Chu Sheng‐Qi , Zhang Jing , Wu Yuen , Liang Hai‐Wei , Feng Xinliang
Published: November 2019

The development of metal‐N‐C materials as efficient non‐precious metal (NPM) catalysts for catalysing the oxygen reduction reaction (ORR) as alternatives to platinum is important for the practical use of proton exchange membrane fuel cells (PEMFCs). However, metal‐N‐C materials have high structural heterogeneity. As a result of their high‐temperature synthesis they often consist of metal‐Nx sites and graphene‐encapsulated metal nanoparticles. Thus it is hard to identify the active structure of metal‐N‐C catalysts. Herein, we report a low‐temperature NH4Cl‐treatment to etch out graphene‐encapsulated nanoparticles from metal‐N‐C catalysts without destruction of co‐existing atomically dispersed metal‐Nx sites. Catalytic activity is much enhanced by this selective removal of metallic nanoparticles. Accordingly, we can confirm the spectator role of graphene‐encapsulated nanoparticles and the pivotal role of metal‐Nx sites in the metal‐N‐C materials for ORR in the acidic medium.
Controlled Synthesis of a Vacancy‐Defect Single‐Atom Catalyst for Boosting CO2 Electroreduction
Authors: Rong Xin , Wang Hong‐Juan , Lu Xiu‐Li , Si Rui , Lu Tong‐Bu
Published: November 2019

The reaction of precursors containing both nitrogen and oxygen atoms with NiII under 500 °C can generate a N/O mixing coordinated Ni‐N3O single‐atom catalyst (SAC) in which the oxygen atom can be gradually removed under high temperature due to the weaker Ni−O interaction, resulting in a vacancy‐defect Ni‐N3‐V SAC at Ni site under 800 °C. For the reaction of NiII with the precursor simply containing nitrogen atoms, only a no‐vacancy‐defect Ni‐N4 SAC was obtained. Experimental and DFT calculations reveal that the presence of a vacancy‐defect in Ni‐N3‐V SAC can dramatically boost the electrocatalytic activity for CO2 reduction, with extremely high CO2 reduction current density of 65 mA cm−2 and high Faradaic efficiency over 90 % at −0.9 V vs. RHE, as well as a record high turnover frequency of 1.35×105 h−1, much higher than those of Ni‐N4 SAC, and being one of the best reported electrocatalysts for CO2‐to‐CO conversion to date.
3D Electron Diffraction Unravels the New Zeolite ECNU‐23 from the “Pure” Powder Sample of ECNU‐21
Authors: Liu Xue , Luo Yi , Mao Wenting , Jiang Jingang , Xu Hao , Han Lu , Sun Junliang , Wu Peng
Published: November 2019

A novel crystalline high‐silica zeolite with 12×8‐membered ring (R) channel system is prepared with the aid of the 3D electron diffraction (3D ED) technique. A crystal with the same topology as one of the predicted daughter structures of CIT‐13 germanosilicate, named ECNU‐23 (East China Normal University 23) was coincidentally detected by the 3D ED investigation during the structure characterization of the “pure” powder sample of existing one‐dimension (1D) 10‐R ECNU‐21. By controlling the alkaline‐assisted hydrolysis under moderate conditions, we purified the phase of ECNU‐23 by selectively breaking and removing the chemically weak Ge(Si)‐O‐Ge and metastable Si‐O‐Si bonds. Its structure was determined based on the 3D ED data, and confirmed by high‐resolution TEM images and powder X‐ray diffraction (PXRD) data. The aluminosilicate Al‐ECNU‐23 shows unique catalytic properties in the isomerization/ disproportionation of m‐xylene as solid‐acid catalyst.
Simulation vs. Understanding: A Tension, in Quantum Chemistry and Beyond. Part B. The March of Simulation, for Better or Worse
Authors: Hoffmann Roald , Malrieu Jean‐Paul
Published: November 2019

In the second part of this Essay, we leave philosophy, and begin by describing Roald's being trashed by simulation. This leads us to a general sketch of artificial intelligence (AI), Searle's Chinese room, and Strevens’ account of what a go‐playing program knows. Back to our terrain—we ask “Quantum Chemistry, † ca. 2020?” Then we move to examples of Big Data, machine learning and neural networks in action, first in chemistry and then affecting social matters, trivial to scary. We argue that moral decisions are hardly to be left to a computer. And that posited causes, even if recognized as provisional, represent a much deeper level of understanding than correlations. At this point, we try to pull the reader up, giving voice to the opposing view of an optimistic, limitless future. But we don't do justice to that view—how could we, older mammals on the way to extinction that we are? We try. But then we return to fuss, questioning the ascetic dimension of scientists, their romance with black boxes. And argue for a science of many tongues.
Atypical Hybrid Metal–Organic Frameworks (MOFs): A Combinative Process for MOF‐on‐MOF Growth, Etching, and Structure Transformation
Authors: Lee Sujeong , Oh Sojin , Oh Moonhyun
Published: November 2019

The structural, compositional, and morphological features of metal–organic frameworks (MOFs) govern their properties and applications. Construction of hybrid MOFs with complicated structures, components, or morphologies is significant for the development of well‐organized MOFs. An advanced route is reported for construction of atypical hybrid MOFs with unique morphologies and complicated components: 1) MOF‐on‐MOF growth of a 3D zeolitic imidazolate framework (ZIF) on a ZIF‐L template, 2) etching of a part of the 2D ZIF‐L template, and 3) structural transformation of 2D ZIF‐L into 3D ZIF. The formation of core–shell‐type MOF rings and plates is controlled by regulating the three processes. The formation route for the core–shell‐type MOF rings and plates was monitored by tracking changes in morphology, structure, and composition. Carbon materials prepared from the pyrolysis of the core–shell‐type hybrid MOFs displayed enhanced oxygen reduction reaction activities compared to their monomeric counterparts.
Novel anion exchange membrane with low ionic resistance based on chloromethylated/quaternized‐grafted polystyrene for energy efficient electromembrane processes
Authors: Golubenko Daniel V. , Van der Bruggen Bart , Yaroslavtsev Andrey B.
Published: November 2019

A novel anion‐exchange membrane has been manufactured by chloromethylation and subsequent quaternization of polystyrene within a graft copolymer films based on UV‐oxidized polymethylpentene. Particular attention is given to the kinetics of chloromethylation and the influence of the reaction conditions on the properties of the anion‐exchange membranes. By means of variation of the polystyrene content and its crosslinking degree we have obtained membranes that have an ion‐exchange capacity from 1.1 to 2.9 mmole g−1, anion transport numbers between 91.0 and 95.5% and specific ionic conductivities ( ranging from 2 to 25 mS cm−1. The developed membranes due to their low thickness and high conductivities have a remarkably low surface ionic resistance of around 0.6 Ω cm2. It was calculated that the use of the developed materials will increase the efficiency of reverse electrodialysis energy production by 8–10% compared to the state of the art membranes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48656.
Low expression of long noncoding RNA CTC‐297N7.9 predicts poor prognosis in patients with hepatocellular carcinoma
Authors: Zhu Sicong , Huang Xuelian , Zhang Kelin , Tan Wenliang , Lin Zhirong , He Qing , Chen Yajin , Shang Changzhen
Published: November 2019

Background

Long noncoding RNAs (lncRNAs) are reported to play important roles in tumorigenesis of various malignant tumors. However, the clinical significance of aberrant lncRNA expression in hepatocellular carcinoma (HCC) is still elusive.

Methods

Firstly, a differentially expressed lncRNA CTC‐297N7.9 in HCC was detected by analyzing the data from The Cancer Genome Atlas (TCGA). Secondly, the expression level of CTC‐297N7.9 was examined in four HCC cell lines and 60 pairs of HCC tissues by polymerase chain reaction (PCR) assay at our center. Thirdly, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of CTC‐297N7.9 for HCC. Correlation and survival analysis of HCC patients from the TCGA and our center were also carried out to assess the predictive value of CTC‐297N7.9. Finally, survival prognostic models were established combining lncRNA expression and other clinical parameters.

Results

The expression of CTC‐297N7.9 was downregulated in HCC cell lines and HCC tissues. ROC curve revealed its significant diagnostic value in HCC. CTC‐297N7.9 expression correlated with serum alpha‐fetal protein (AFP), tumor stage, and tumor differentiation. Survival analysis indicated that overall survival (OS) and disease‐free survival (DFS) are all positively associated with CTC‐297N7.9 expression, especially in patients without viral hepatitis or cirrhosis. Cox regression analysis showed that CTC‐297N7.9 expression level is an independent prognostic factor for both OS and DFS in HCC patients. Based on the model, CTC‐297N7.9 was observed to be negatively correlated to risk score, indicating its role as a protective factor for HCC.

Conclusion

Our study demonstrated that the low expression of CTC‐297N7.9 is associated with poor prognosis in HCC patients, suggesting its possible role as a potential prognostic marker for HCC.
Photoimmunotherapy targeting biliary‐pancreatic cancer with humanized anti‐TROP2 antibody
Authors: Nishimura Takashi , Mitsunaga Makoto , Sawada Ryoichi , Saruta Masayuki , Kobayashi Hisataka , Matsumoto Noriko , Kanke Toru , Yanai Hiroyuki , Nakamura Koji
Published: November 2019

Photoimmunotherapy (PIT) is a new type of tumor‐specific treatment utilizing monoclonal antibody (mAb)‐photosensitizer conjugates and near‐infrared (NIR) light irradiation. One potential PIT target, the type I transmembrane protein TROP2, is expressed at high levels in many cancers, including pancreatic carcinoma (PC) and cholangiocarcinoma (CC), in which its expression is correlated with poor prognosis and tumor aggressiveness. In this study, we assessed the efficacy of PIT utilizing newly developed humanized anti‐TROP2 mAb conjugated to the photosensitizer IR700 (TROP2‐IR700) for PC and CC. Immunohistochemistry on PC and CC tissue microarrays confirmed that TROP2 is overexpressed in about half of PC and CC specimens. Using cultured PC and CC cells, TROP2‐IR700 localized TROP2‐specific and target‐specific cell killing was observed after NIR light irradiation. In addition, TROP2‐IR700 was localized to mouse xenograft tumors expressing TROP2 after intravenous injection. PC and CC xenograft tumor growth was significantly inhibited by TROP2‐targeted PIT relative to controls. The efficacy of TROP2‐targeted PIT in vitro and against xenografted tumors in vivo suggests promise as a therapy for human PC and CC, both of which currently have dismal prognoses and limited therapeutic options.
Using a PCR‐Based Method To Analyze and Model Large, Heterogeneous Populations of DNA
Authors: Andrade Helena , Thomas Alvin K. , Lin Weilin , Reddavide Francesco V. , Zhang Yixin
Published: November 2019

The study of populations of large size and high diversity is limited by the capability of collecting data. Moreover, for a pool of individuals, each associated with a unique characteristic feature, as the pool size grows, the possible interactions increase exponentially and quickly go beyond the limit of computation and experimental studies. Herein, the design of DNA libraries with various diversity is reported. By using a facile analytical method based on real‐time PCR, the diversity of a pool of DNA can be evaluated to allow extraordinarily high heterogenicity (e.g., >1 trillion). It is demonstrated that these DNA libraries can be used to model heterogeneous populations; these libraries exhibit functions such as self‐protection, suitability for biased expansion, and the possibility to evolve into amorphous structures. The method has shown the remarkable power of parallel computing with DNA, since it can resemble an analogue computer and be applied in selection‐based biotechnology methods, such as DNA‐encoded chemical libraries. As a chemical approach to solve problems traditionally for genetic and statistical analysis, the method provides a quick and cost‐efficient evaluation of library diversity for intermediate steps through a selection process.
Natural Deep Eutectic Solvents as Performance Additives for Peroxygenase Catalysis
Authors: Ma Yunjian , Li Yongru , Ali Shahid , Li Peilin , Zhang Wuyuan , Rauch Marine C. R. , Willot Sébastien J.‐P. , Ribitsch Doris , Choi Young Hae , Alcalde Miguel , Hollmann Frank , Wang Yonghua
Published: November 2019

Natural deep eutectic solvents (NADES) are proposed as alternative solvents for peroxygenase‐catalysed oxyfunctionalization reactions. Choline chloride‐based NADES are of particular interest as they can serve as solvent, enzyme‐stabiliser and sacrificial electron donor for the in situ H2O2 generation. This report provides the first proof‐of‐concept and basic characterisation of this new reaction system. Highly promising turnover numbers for the biocatalysts of up to 200,000 have been achieved.
Design and Analysis of the 4‐Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure‐Activity Relationships
Authors: Asquith Christopher R. M. , Laitinen Tuomo , Bennett James M. , Wells Carrow I. , Elkins Jonathan M. , Zuercher William J. , Tizzard Graham J. , Poso Antti
Published: November 2019

The 4‐anilinoquinoline and 4‐anilinoquinazoline ring systems have been the focus of significant efforts in prior kinase drug discovery programs, which have led to approved medicines. Broad kinome profiles of these compounds have now been assessed with the advent of advanced screening technologies. These ring systems, while originally designed for specific targets including epidermal growth factor receptor (EGFR), but actually display a number of potent collateral kinase targets, some of which have been associated with negative clinical outcomes. We have designed and synthesized a series of 4‐anilinoquin(az)olines in order to better understand the structure‐activity relationships of three main collateral kinase targets of quin(az)oline‐based kinase inhibitors: cyclin G associated kinase (GAK), STE20‐like serine/threonine‐protein kinase (SLK) and serine/threonine‐protein kinase 10 (STK10). This was achieved through a series of quantitative structure‐activity relationship (QSAR) analysis, water mapping of the kinase ATP binding sites and extensive small‐molecule X‐ray structural analysis.
Synthesis of Combretastatin‐A4 Carboxamidest that Mimic Sulfonyl Piperazines by a Molecular Hybridization Approach: in vitro Cytotoxicity Evaluation and Inhibition of Tubulin Polymerization
Authors: Jadala Chetna , Sathish Manda , Anchi Pratibha , Tokala Ramya , Lakshmi Uppu Jaya , Reddy Velma Ganga , Shankaraiah Nagula , Godugu Chandraiah , Kamal Ahmed
Published: November 2019

Molecular hybridization approach is a promising structural modification tool to design new chemical entities (NCEs) by mimicking two different pharmacophoric units into one scaffold to enhance the biological properties. With this aim, combretastatin‐A4 acids were integrated with sulfonyl piperazine scaffolds as a one molecular platform and evaluated for their in vitro antiproliferative activity against a panel of human cancer lines cell lines namely, lung (A549), mouse melanoma (B16F10), breast (MDA MB‐231and MCF‐7) and colon (HCT‐15) by MTT assay. Amongst which the compound (E)‐3‐(4‐Chlorophenyl)‐1‐(4‐((4‐chlorophenyl)sulfonyl)piperazin‐1‐yl)‐2‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one (5 ab) displayed significant IC50 values in the range of 0.36 to 7.08 μm against the selected cancer cell lines. Moreover, 5 ab was found to be the most potent member of this series with IC50 0.36±0.02 μm. Further investigations revealed that the compound 5 ab displayed significant inhibition of tubulin assembly with IC50 5.24±0.06 μm and molecular docking studies also disclosed the binding of 5 ab effectively in CA4 binding space at the colchicine binding site. The flow cytometric analysis demonstrated that the compound 5 ab caused cell cycle arrest at G2/M phase in A549 cells. Compound 5 ab induced apoptosis in A549 cells which was further evaluated by different staining assays such as DAPI and AO which undoubtedly speculated, the induction of apoptosis. To study the anti‐migration with 5 ab, cell migration/scratch wound assay was performed and the extent of apoptosis was studied by Annexin‐V, including mitochondrial potential by JC‐1 staining.
Physiological assessment of high glucose neurotoxicity in mouse and rat retinal explants
Authors: Calbiague Víctor M. , Vielma Alex H. , Cadiz Bárbara , Paquet‐Durand Francois , Schmachtenberg Oliver
Published: November 2019

One of the tissues of the central nervous system most affected by diabetes is the retina. Despite a growing understanding of the biochemical processes involved in glucose toxicity, little is known about the physiological consequences of chronic high glucose (HG) on individual neurons and neuronal circuits. Electroretinogram recordings suggest that retinal bipolar cells (BCs), which filter and transmit photoreceptor output to the inner retina, are among the first cells affected by diabetic conditions, and may therefore serve as sensitive early biomarkers for incipient neuronal damage caused in diabetes. Here, we comparatively assessed retinal integrity, calcium responses, and the electrophysiological profiles of specific BC types of mouse and rat organotypic retinal explants after 1 to 3 weeks in tissue culture, under moderate glucose (MG) and HG conditions. While the retinal layers of both rodent species displayed a progressively reduced thickness in culture, BCs retained their electrophysiological profiles and remained morphologically identifiable for up to 2 weeks. Responses to glutamate and endogenous inhibitory responses were routinely observed, indicating that the retinal circuitry remained intact during this period. Significant physiological differences between MG and HG conditions were evident in calcium signals and in the time course of responses to glutamate, but the voltage‐gated current profiles of BCs displayed only minor variations. Overall, rat retina appeared slightly more sensitive to HG levels compared with mouse. In conclusion, electrophysiological analysis of neuronal function in rodent retinal explants is useful for the study of early damage due to HG neurotoxicity.
Unsaturation‐Dependent Nanostructures Self‐Assembled from Oligopeptide Amphiphiles Capable of Generating Singlet Oxygen
Authors: Feng Jia‐Ru , Qin Si‐Yong , Rong Lei , Cheng Yin‐Jia , Ma Yi‐Han , Zhang Ai‐Qing
Published: November 2019

We report here on three oligopeptide amphiphiles (OPA1‐3) with different unsaturated double bonds, which self‐assemble into shape‐specific nanostructures. It was found that OPA1 with saturated hydrophobic tail self‐assembled into conventional cylindrical nanofibers, while the unsaturated OPA2‐3 molecules self‐organized into helical nanoarchitectures. Due to the different double bond numbers in hydrophobic tails of OPA2‐3, the helical pitch and width of their self‐assemblies varied. Specially, linoleic acid‐bearing OPA3 could be oxidized by lipoxidase to create hydroperoxide‐containing OPA4, which further generated singlet oxygen (1O2) in the presence of catalytic iron (II) ion. The established system may provide a self‐deliverable nanoplatform for 1O2‐mediated cancer treatment.
Alkali and Alkaline‐Earth Cations in Complexes with Small Bioorganic Ligands: Ab Initio Benchmark Calculations and Bond Energy Decomposition
Authors: López Roberto , Díaz Natalia , Suárez Dimas
Published: November 2019

Herein, we report a computational database for the complexes of alkali [Li(I), Na(I), K(I)] and alkaline‐earth [Be(II), Mg(II) and Ca(II)] cations with 25 small ligands with varying charge and donor atoms (“O”, “N”, and “S”) that provides geometries and accurate bond energies useful to analyze metal‐ligand interactions in proteins and nucleic acids. The role of the ligand→metal charge transfer, the equilibrium bond distance, the electronegativity of the donor atom, the ligand polarizability, and the relative stability of the complexes are discussed in detail. The interacting quantum atoms (IQA) method is used to decompose the binding energy into electrostatic and quantum mechanical contributions. In addition, bond energies are also estimated by means of multipolar electrostatic calculations. No simple correlation exists between bond energies and structural/electronic descriptors unless the data are segregated by the type of ligand or metal. The electrostatic attraction of some molecules (H2O, NH3, CH3OH) towards the metal cations is well reproduced using their (unrelaxed) atomic multipoles, but the same comparison is much less satisfactory for other ligands (e. g. benzene, thiol/thiolate groups, etc.). Besides providing reference structures and bond energies, the database can contribute to validate molecular mechanics potentials capable of yielding a balanced description of alkali and alkaline‐earth metals binding to biomolecules.
Incomplete Electrocyclization of a Sterically Hindered 1,4‐Diphosphabutadiene
Authors: Shinozaki Tomokazu , Rosas‐Sánchez Alfredo , Hashizume Daisuke , Ito Shigekazu
Published: November 2019

Butadiene is the simplest neutral acyclic closed‐shell π‐conjugated system and is typically sufficiently stable enough to avoid electrocyclization to cyclobutene. In contrast, most congeners of butadiene containing heavier elements are easily converted into the corresponding 4‐membered cyclobutene system. Herein, we demonstrate that the gauche 1,4‐diphosphabutadiene (P=C−C=P) skeleton in a sterically encumbered 2,3‐bis(phosphanylidene)‐1,4‐disilinane can be remarkably perturbed due to “incomplete electrocyclization” where P=C−C=P partially form the corresponding 1,2‐dihydrodiphosphete (3,4‐diphosphacyclobutene) by [2+2] electrocyclization. 31P NMR data obtained in solution indicated that the coexistence of a closed ring substantially reduces the open‐ring characteristics of the P=C−C=P moiety. However, the 31P CP‐MAS spectrum of 2,3‐bis(phosphanylidene)‐1,4‐disilinane showed that the P=C−C=P structure is predominant in the solid‐state. Single‐crystal X‐ray analysis revealed that decreasing the temperature promoted the generation of small amounts of incomplete 1,2‐dihydrodiphosphete system in the crystalline state. Furthermore, the 1,2‐dihydrodiphosphete units disappeared upon warming the single crystal, and this unique solid‐state electrocyclization reaction was reversible.
Incremental utility of expanded mutation panel when used in combination with microRNA classification in indeterminate thyroid nodules
Authors: Jackson Sara , Kumar Gyanendra , Banizs Anna B. , Toney Nicole , Silverman Jan F. , Narick Christina M. , Finkelstein Sydney D.
Published: November 2019

INTRODUCTION

Focused and expanded mutation panels were assessed for the incremental utility of using an expanded panel in combination with microRNA risk classification.

METHODS

Molecular results were reviewed for patients who underwent either a focused mutation panel (ThyGenX®) or an expanded mutation panel (ThyGeNEXT®) for strong and weak oncogenic driver mutations and fusions. microRNA results (ThyraMIR®) predictive of malignancy, including strong positive results highly specific for malignancy, were examined.

RESULTS

Results of 12 993 consecutive patients were reviewed (focused panel = 8619, expanded panel = 4374). The expanded panel increased detection of strong drivers by 8% (P < .001), with BRAFV600E and TERT promoters being the most common. Strong drivers were highly correlated with positive microRNA results of which 90% were strongly positive. The expanded panel increased detection of coexisting drivers by 4% (P < .001), with TERT being the most common partner often paired with RAS. It increased the detection of weak drivers, with RAS and GNAS being the most common. 49% of nodules with weak drivers had positive microRNA results of which 33% were strongly positive. The expanded panel also decreased the number of nodules lacking mutations and fusions by 15% (P < .001), with 8% of nodules having positive microRNA results of which 22% were strongly positive.

CONCLUSIONS

Using expanded mutation panels that include less common mutations and fusions can offer increased utility when used in combination with microRNA classification, which helps to identify high risk of malignancy in the cases where risk is otherwise uncertain due to the presence of only weak drivers or the absence of all drivers.
Development of LB film taste sensor for beer degradation evaluation and its physical properties
Authors: Yazawa Masayoshi , Takahashi Kazunari , Uchida Hidekazu , Hasegawa Yuki
Published: November 2019

In general, beer degradation is evaluated by sensory test; however, it depends on the subjectivity of an inspector. Therefore, it is highly required that an objective evaluation method is developed. It has been clarified that the degradation degree of beer proceeds mainly by oxidation of components derived from malt and formation of nonelectrolyte trans‐2‐nonenal. In this study, we developed LB film taste sensor using metal complex for evaluating the degradation degree of beer with trans‐2‐nonenal concentrations. In addition, the physical properties of three metal electrodes and sensing film surface were evaluated with AFM and FT‐IR, and these results and the sensor response characteristics were compared and discussed for improving the sensitivity as a sensor for beer degradation evaluation.
Effects of latitudinal, seasonal, and daily temperature variations on chytrid fungal infections in a North American frog
Authors: Sonn Julia M. , Utz Ryan M. , Richards‐Zawacki Corinne L.
Published: November 2019

As human activities alter environmental conditions, the emergence and spread of disease represents an increasing threat to wildlife. Studies that examine how host–pathogen relationships play out across seasons and latitudes can serve as proxies for understanding how natural and anthropogenic changes in climate may influence infection and disease dynamics. Amphibians are ideal host organisms for studying the impacts of climate on disease because they are ectothermic and threatened by chytridiomycosis, a recently emerged and globally important disease caused by fungal pathogens in the genus Batrachochytrium. Previous studies suggest that temperature affects the interaction between amphibians and Batrachochytrium pathogens. However, a clearer understanding of this host–pathogen–environment interaction is needed to predict how the risk of chytridiomycosis will vary in space and time. Here, we investigate how daily, seasonal, and latitudinal variations in temperature affect the incidence and impact of Batrachochytrium dendrobatidis (Bd) infection in a broadly distributed host, the northern cricket frog (Acris crepitans), using a combination of field and laboratory studies. In a four‐year field study conducted at three latitudes, we found that daily maximum air temperature over a 15‐d period prior to sampling best predicted patterns of Bd infection and that the lightest infection loads followed periods when these temperatures exceeded 25°C. In a laboratory exposure experiment, we found pathogen load and mortality to be greater at temperatures that mimic winter temperatures at the southern extent of this host's range than for scenarios that mimic temperature conditions experienced in other areas and seasons. Taken together, our findings suggest that changes in temperature across timescales and latitudes interact to influence the dynamics of infection and disease in temperate amphibians.
Multigenerational migration of fall armyworm, a pest insect
Authors: Westbrook J. , Fleischer S. , Jairam S. , Meagher R. , Nagoshi R.
Published: November 2019

Multigenerational insect migration commonly expands poleward, but meteorological influences are not clearly understood. We coupled biological and physical processes for the agricultural and invasive pest Spodoptera frugiperda (fall armyworm), by modeling its seasonal migration, and comparing simulated migrations to observed captures, and population genetic markers, at a continental scale. Simulations corroborated the spatial distribution and mixing of Texas and Florida source populations defined by genetic haplotypes. Positive relationships were found between first weeks of simulated and observed immigration, and between genetic and simulated metrics. The capacity to project biotic‐, migratory‐, and meteorology‐induced shifts in insect distributions will aid strategic implementation of crop protection measures and economic analyses of host‐resistant germplasm deployment in response to a warming climate.