bluuebunny/crossref_metadata_2025 huggingface dataset:
HEPATOPROTECTIVE ACTIVITY OF BAUHINIA RACEMOSA ROOTS EXTRACTS
Authors: Aravanan P , Jayakumari S
Published: January 2021

Of all types of plants, we come across everyday every plant is useful some more than other. Our predecessors left an ocean of knowledge regarding the usage of natural sources for medicinal purposes all that we need is, to work on the molecular level to better understand how to avoid negative effects. In the present study Chloroform and Ethanolic extracts of Bauhinia racemosa obtained by soxhlation were used in the determination of Hepatoprotective activity using Paracetamol induced hepatotoxicity method. Oral administration of Bauhinia racemosa Chloroform extract and Bauhinia racemosa Ethanolic Extract showed significant decrease in biochemical parameters such as the ALT, AST, ALP. Animals treated with Ethanolic extract at dose level of 200 mg/kg & 400 mg/kg b.w, p.o in Hepatotoxicity induced rats exhibited a significant reduction of ALP (178.2±1.65 & 169.1±1.88), AST (123.5±1.87 & 115.7±1.25), ALT (115.2±0.94 & 111.4±1.29) respectively. Extensive literature review showed that Bauhinia racemosa is capable of several pharmacological activities and the present study sheds light on the hepatoprotective nature of the selected plant.
FLOATING DRUG DELIVERY SYSTEM OF NSAIDS TO INCREASE GASTRIC RETENTION TIME IN UPPER PART OF GASTROINTESTINAL TRACT
Authors: Tripathi Ankita , Neupane Suraj , Bhardwaj Khushboo , Mishra Shiva , Gupta Meenakshi , Mishra Raj Kumar
Published: January 2021

The purpose of the present work is to prolong the gastric residence time of Lornoxicam by developing gastric floating drug delivery system. Lornoxicam is non-steroidal anti-inflammatory drugs. Its short half life 2 to 3 hrs and maximal absorption of upper part of gastrointestinal tract. The residence time of the dosage form in the stomach depends upon various factors like pH, size of the dosage form, food intake, and biological factors which include age, body weight gender, posture, and diseased states Floating tablet prepared by melt granulation techniques, using bees wax as a binder and the other polymers include HPMC 50cPs,15cPs,5cPs and Sodium Alginate. The Prepared granules were then evaluated for Precompression Properties. The best batches were then tabulated, and Evaluation was carried out for the following parameters with in vitro release, buoyancy, Floating Lag timed. Batch F12 and F13 Showed best Floating time of 12hrs and Floating Lag time of 60 second.
PLANTS WITH ANTIHYPERTENSIVE ACTIVITIES: A REVIEW
Authors: Suryani Lubis Indah Irma , Azizah Zikra , . Rusdi , Asra Ridho
Published: January 2021

Hypertension is one of the most common causes of morbidity and premature death worldwide. Hypertension or high blood pressure is a condition of an increase in systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg. Hypertension is very dangerous because in most cases there are no symptoms in the sufferer (silent killer). Conventional treatment for hypertension often causes various side effects, so that the choice of herbal treatment is being considered more. Medicinal plants such as Cratoxylum formosum, Adansonia digitata L., Vitex pubescens, Cinnamomum zeylanicum, Catharanthus roseus, Crotalaria burhia, Leersia hexandra, Moringa oleifera L., Allanblackia floribunda, Holarrhena floribunda, Berberis vulgaris, Morinda citrifolia L., Ficus carica, Bidens pilosa, Panax ginseng, Lantana camara, Allium sativum, Apium graveolens, Vitex cienkowskii, and Achillea wilhelmsii have antihypertensive activity which can be used as an alternative in the treatment and prevention of hypertension. This review article used the literature study method of national and international journals published in the last 10 years (2010-2020) that was done through several websites such as ScienceDirect, NCBI, ResearchGate and Google Scholar.
Copper‐Catalyzed Decarboxylative Alkylselenation of Propiolic Acids with Se Powder and Epoxides
Authors: Yao Yujing , Wang Caihong , Ma Yunfei , Zhang Jintao , Sun Dong , Chen Luya , Huang Lehao , Wu Ge
Published: February 2021

A copper‐catalyzed decarboxylative alkylselenation of propiolic acids with Se powder and epoxides leading to alkynyl selenides is developed. This protocol not only provides an approach to obtain alkynyl selenides with the formation of double C−Se bonds, but also expands the applicability of alkynyl carboxylic acid.

magnified image
Radiogenomics of gastroenterological cancer: The dawn of personalized medicine with artificial intelligence‐based image analysis
Authors: Hoshino Isamu , Yokota Hajime
Published: February 2021

Radiogenomics is a new field of medical science that integrates two omics, radiomics and genomics, and may bring a major paradigm shift in traditional personalized medicine strategies that require tumor tissue samples. In addition, the acquisition of the data does not require special imaging equipment or special imaging conditions, and it is possible to use image information from computed tomography, magnetic resonance imaging, positron emission tomography‐computed tomography in clinical practice, so the versatility and cost‐effectiveness of radiogenomics are expected. So far, the field of radiogenomics has developed, especially in the fields of brain tumors and breast cancer, but recently, reports of radiogenomic research on gastroenterological cancer are increasing. This review provides an overview of radiogenomic research methods and summarizes the current radiogenomic research in gastroenterological cancer. In addition, the application of artificial intelligence is considered to be indispensable for the integrated analysis of enormous omics information in the future, and the future direction of this research, including the latest technologies, will be discussed.
Biodegradation of heavy oil by fungal extracellular enzymes fromAspergillusspp. shows potential to enhance oil recovery
Authors: Zhang Junhui , Gao Hui , Lai Hangxian , Hu Shibin , Xue Quanhong
Published: February 2021

Microbial enhanced oil recovery makes a substantial contribution to the recovery of heavy oils; however, most methods use bacteria, with less attention paid to the potential of fungi. In this study, we investigated the efficiency of fungal extracellular enzymes in biotransformation of heavy oil fractions into light compounds. TwoAspergillusisolates (A. terreusandA. nidulans) with the ability to biodegrade heavy oil were isolated from bitumen. The extracellular enzymes from theseAspergillusisolates exhibited dehydrogenase and catechol 2,3‐dioxygenase activities. The biodegradation of heavy oil was coupled with abundant production of gases, mainly CO2and H2. Gas chromatography analysis revealed a redistribution ofn‐alkanes in heavy oil after treatment with crude enzyme extracts, which resulted in an increase in individualn‐alkanes. The viscosity of heavy oil was decreased considerably by enzymatic degradation. These results demonstrate the potential of fungal extracellular enzymes fromAspergillusspp. for applications in enhanced heavy oil recovery.
Mass transfer advantage of hierarchical structured cobalt‐based catalyst pellet for Fischer–Tropsch synthesis
Authors: Niu Congcong , Li Hansheng , Xia Ming , Wang Jungang , Chen Congbiao , Ma Zhongyi , Jia Litao , Hou Bo , Li Debao
Published: February 2021

The low effectiveness factor of catalyst pellet caused by high internal diffusion limitation is a common issue in fixed‐bed reactor. Nevertheless, hierarchical structured catalyst provides a promising solution for the contradiction between reaction activity and diffusion efficiency in large catalyst pellets. Herein, we studied the effect of pore structure parameters of the meso‐macroporous catalyst on Fischer–Tropsch synthesis performances through experiment and pellet scale reaction–diffusion simulation. The pellet simulation firstly elucidated the reason for the significant improvement on activity and product selectivity for the meso‐macroporous catalyst observed in our experiment. Further optimization via pellet simulation indicated the critical influences of wax filling degree and that the perfect matching between reaction and mass transfer rates by increasing macropore size and adjusting porosity within pellet enables the C5+ space–time yield to the maximum. This work could provide a theoretical guideline for the engineering design of the hierarchical structured catalyst pellet.
Benefits of biologic therapy administered for asthma on co‐existent chronic rhinosinusitis: A real‐world study
Authors: Bajpai Shilpika , Marino Michael J. , Rank Matthew A. , Donaldson Angela M. , O'Brien Erin K. , Lal Devyani
Published: February 2021

Background

Asthma and some chronic rhinosinusitis (CRS) subtypes are mediated by similar pathophysiologic mechanisms. The purpose of this study was to evaluate the effects of biologic therapy for asthma on co‐existent CRS in the “real‐world” setting.

Methods

A review of electronic health records (2016‐2019) at Mayo Clinic was conducted to identify asthma patients treated with biologics who had co‐existent CRS. Matched‐pair analyses compared pretherapy and posttherapy Lund‐Mackay computed tomography (CT) scores and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Performance of endoscopic sinus surgery (ESS) after initiating biologics was studied.

Results

We identified 247 patients who received anti‐asthma biologic therapy and had co‐existent CRS. Of these, 181 patients (73.3%) had CRS with nasal polyposis (CRSwNP) and 66 (26.7%) had CRS without nasal polyposis (CRSsNP). The biologics utilized were omalizumab (51.0%), mepolizumab (46.6%), benralizumab (10.5%), reslizumab (1.6%), and dupilumab (2.4%). Anti‐interleukin‐5 (anti‐IL‐5) intervention was associated with significant improvement in CT scores (CRS overall, CRSwNP subgroup, CRSsNP subgroup) and SNOT‐22 scores (CRS overall, CRSwNP subgroup). Patients on omalizumab had a decrease in CT scores, but not SNOT‐22 scores. ESS was performed in 206 patients (84.1%); 55 (22.3%) underwent surgery post–biologic intervention (anti‐IL‐5: 16.5%; omalizumab 27.8% of patients).

Conclusion

Anti‐IL‐5 agents were associated with improved CT and SNOT‐22 scores in the overall CRS group and in CRSwNP subgroup; CRSsNP patients showed improved CT scores only. Omalizumab improved CT but not SNOT‐22 scores. ESS was performed in 22% of patients after initiating biologics. These real‐world results may influence future trial designs and clinical applications of biologics for CRS. ©2021 ARSAAOA, LLC.
Generalizability of findings from a clinical sample to a community‐based sample: A comparison of ADNI and ARIC
Authors: Gianattasio Kan Z. , Bennett Erin E. , Wei Jingkai , Mehrotra Megha L. , Mosley Thomas , Gottesman Rebecca F. , Wong Dean F. , Stuart Elizabeth A. , Griswold Michael E. , Couper David , Glymour M. Maria , Power Melinda C. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: February 2021

Introduction

Clinic‐based study samples, including the Alzheimer's Disease Neuroimaging Initiative (ADNI), offer rich data, but findings may not generalize to community‐based settings. We compared associations in ADNI to those in the Atherosclerosis Risk in Communities (ARIC) study to assess generalizability across the two settings.

Methods

We estimated cohort‐specific associations among risk factors, cognitive test scores, and neuroimaging outcomes to identify and quantify the extent of significant and substantively meaningful differences in associations between cohorts. We explored whether using more homogenous samples improved comparability in effect estimates.

Results

The proportion of associations that differed significantly between cohorts ranged from 27% to 34% across sample subsets. Many differences were substantively meaningful (e.g., odds ratios [OR] for apolipoprotein E ε4 on amyloid positivity in ARIC: OR = 2.8, in ADNI: OR = 8.6).

Discussion

A higher proportion of associations differed significantly and substantively than would be expected by chance. Findings in clinical samples should be confirmed in more representative samples.
Planar Hexacoordinate Carbons: Half Covalent, Half Ionic
Authors: Leyva‐Parra Luis , Diego Luz , Yañez Osvaldo , Inostroza Diego , Barroso Jorge , Vásquez‐Espinal Alejandro , Merino Gabriel , Tiznado William
Published: February 2021

Herein, the first global minima containing a planar hexacoordinate carbon (phC) atom are reported. The fifteen structures belong to the CE3M3+ (E=S–Te and M=Li–Cs) series and satisfy both geometric and electronic criteria to be considered as a true phC. The design strategy consisted of replacing oxygen in the D3h CO3Li3+ structure with heavy and less electronegative chalcogens, inducing a negative charge on the C atom and an attractive electrostatic interaction between C and the alkali‐metal cations. The chemical bonding analyses indicate that carbon is covalently bonded to three chalcogens and ionically connected to the three alkali metals.
Perovskite Oxide–Halide Solid Solutions: A Platform for Electrocatalysts
Authors: Wang Tao , Fan Juntian , Do‐Thanh Chi‐Linh , Suo Xian , Yang Zhenzhen , Chen Hao , Yuan Yating , Lyu Hailong , Yang Shize , Dai Sheng
Published: February 2021

The successful integration or hybridization of perovskite oxides with their halide cousins would enable the formation of both multi‐anionic and multi‐cationic solid solutions with unique metal‐ion sites and synergistic properties that could potentially surpass the performance of classic perovskites. However, such solid solutions had not been produced previously owing to their distinct formation energies and different synthesis conditions. Solid solutions combining perovskite oxides with fluorides were produced in this study by mechanochemical synthesis. The obtained perovskite oxide–halide solid solutions had highly mixed elements and valences, uniform element distributions, and single‐phase crystalline structures. The solid solution with an optimized combination of oxides and fluorides exhibited enhanced catalytic performance in the oxygen evolution reaction.
Controlling Energy Gaps of π‐Conjugated Polymers by Multi‐Fluorinated Boron‐Fused Azobenzene Acceptors for Highly Efficient Near‐Infrared Emission
Authors: Gon Masayuki , Wakabayashi Junko , Nakamura Masashi , Tanaka Kazuo , Chujo Yoshiki
Published: February 2021

We demonstrate that multi‐fluorinated boron‐fused azobenzene (BAz) complexes can work as a strong electron acceptor in electron donor‐acceptor (D‐A) type π‐conjugated polymers. Position‐dependent substitution effects were revealed, and the energy level of the lowest unoccupied molecular orbital (LUMO) was critically decreased by fluorination. As a result, the obtained polymers showed near‐infrared (NIR) emission (λPL=758–847 nm) with high absolute photoluminescence quantum yield (ΦPL=7–23%) originating from low‐lying LUMO energy levels of the BAz moieties (−3.94 to −4.25 eV). Owing to inherent solid‐state emissive properties of the BAz units, deeper NIR emission (λPL=852980 nm) was detected in film state. Clear solvent effects prove that the NIR emission is from a charge transfer state originating from a strong D‐A interaction. The effects of fluorination on the frontier orbitals are well understandable and predictable by theoretical calculation with density functional theory. This study demonstrates the effectiveness of fluorination to the BAz units for producing a strong electron‐accepting unit through fine‐tuning of energy gaps, which can be the promising strategy for designing NIR absorptive and emissive materials.
A review of collision detection for deformable objects
Authors: Wang Monan , Cao Jiaqi
Published: February 2021

In the process of simulating and modeling real objects, the phenomenon of objects penetrating each other may occur in the model, which is unrealistic and then the research of collision detection (CD) is generated. As a bottleneck of virtual environment simulation, researchers have conducted in‐depth research on CD, especially the CD of deformable objects. In this paper, we briefly review the related research on CD of deformable objects regarding relevant literature. First, we briefly introduce previous reviews of CD. Second, we review the popular research methods and limitations of CD between deformable objects. Third, we review the popular research methods and limitations of self‐collision detection in deformable objects. Finally, we discuss future directions of development. This review can be used as a reference for the application of CD in all directions.
The fucose‐specific lectin ANL from Aspergillus niger possesses anti‐cancer activity by inducing the intrinsic apoptosis pathway in hepatocellular and colon cancer cells
Authors: Jagadeesh Narasimhappagari , Belur Shivakumar , Campbell Barry J. , Inamdar Shashikala R.
Published: February 2021

The L‐fucose‐specific lectin from Aspergillus niger (ANL), isolated from the corneal smears of a keratitis patient was reported earlier. Here, we examined the interaction of ANL with human hepatocellular and colon cancer cells, evaluated its anti‐cancer activity and diagnostic potential to detect aberrantly glycosylated tumour‐associated serum glycoproteins such as alpha‐fetoprotein (AFP). We observed that ANL strongly bound to both HepG2 and HT‐29 cell‐lines and this interaction was effectively blocked with L‐fucose and mucin in a dose and time‐dependent manner with an IC50 of 1.25 and 5 μg/mL for HepG2 and HT‐29 cells respectively at 48 hours. ANL treatment increased hypodiploidy and decreased the number of HepG2 cell in G0‐G1 phase at both 24 and 48 hours. Furthermore, ANL increased the level of apoptosis in both HepG2 and HT‐29 cells in a time‐dependent manner via enhanced production of reactive oxygen species and altered mitochondrial membrane potential, indicative of intrinsic apoptotis pathway activation. Immunoblot analysis confirmed the time‐dependent elevation of levels of cytochrome c, initiator caspase‐9 and activation of caspase‐3. ANL immunohistochemistry on colon cancer tissue and quantification of AFP in HCC patient serum samples by developing an ANL‐anti‐AFP antibody sandwich enzyme‐linked immunosorbent assay confirmed the diagnostic potential of ANL. Here, interaction of ANL with AFP could be effectively blocked in the presence of competing fucose‐bearing glycans. We found ANL to be more sensitive than Lens culinaris lectin, a well‐known fucose‐specific lectin and currently used diagnostic agent. ANL can be further explored as a diagnostic and anti‐cancer agent.
Expanding the Biocatalytic Toolbox with a New Type of ene/yne‐Reductase from Cyclocybe aegerita
Authors: Karrer Dominik , Gand Martin , Rühl Martin
Published: February 2021

This study introduces a new type of ene/yne‐reductase from Cyclocybe aegerita with a broad substrate scope including aliphatic and aromatic alkenes/alkynes from which aliphatic C8‐alkenones, C8‐alkenals and aromatic nitroalkenes were the preferred substrates. By comparing alkenes and alkynes, a ∼2‐fold lower conversion towards alkynes was observed. Furthermore, it could be shown that the alkyne reduction proceeds via a slow reduction of the alkyne to the alkene followed by a rapid reduction to the corresponding alkane. An accumulation of the alkene was not observed. Moreover, a regioselective reduction of the double bond in α,β‐position of α,β,γ,δ‐unsaturated alkenals took place. This as well as the first biocatalytic reduction of different aliphatic and aromatic alkynes to alkanes underlines the novelty of this biocatalyst. Thus with this study on the new ene‐reductase CaeEnR1, a promising substrate scope is disclosed that describes conceivably a broad occurrence of such reactions within the chemical landscape.
Probing the Local Reaction Environment During High Turnover Carbon Dioxide Reduction with Ag‐Based Gas Diffusion Electrodes
Authors: Dieckhöfer Stefan , Öhl Denis , Junqueira João R. C. , Quast Thomas , Turek Thomas , Schuhmann Wolfgang
Published: February 2021

Discerning the influence of electrochemical reactions on the electrode microenvironment is an unavoidable topic for electrochemical reactions that involve the production of OH− and the consumption of water. That is particularly true for the carbon dioxide reduction reaction (CO2RR), which together with the competing hydrogen evolution reaction (HER) exert changes in the local OH− and H2O activity that in turn can possibly affect activity, stability, and selectivity of the CO2RR. We determine the local OH− and H2O activity in close proximity to a CO2‐converting Ag‐based gas diffusion electrode (GDE) with product analysis using gas chromatography. A Pt nanosensor is positioned in the vicinity of the working GDE using shear‐force‐based scanning electrochemical microscopy (SECM) approach curves, which allows monitoring changes invoked by reactions proceeding within an otherwise inaccessible porous GDE by potentiodynamic measurements at the Pt‐tip nanosensor. We show that high turnover HER/CO2RR at a GDE lead to modulations of the alkalinity of the local electrolyte, that resemble a 16 m KOH solution, variations that are in turn linked to the reaction selectivity.
Precise Synthesis of Carbon Nanotubes and One‐Dimensional Hybrids from Templates†
Authors: Yang Xusheng , Zhao Xin , Liu Tianhui , Yang Feng
Published: February 2021

Carbon nanotubes (CNTs) present unique properties determined by their chiral structure. The main hurdle towards the wide applications is the difficulty to control the structure of CNTs and their hybrids that determines the properties. Precise synthesis with well‐defined templates is a promising approach to control the identical structure of carbon nanomaterials. In this review, we summarize main achievements on controlled synthesis of CNTs and hybrids on two aspects: chirality‐specific growth of CNTs from well‐defined catalysts and nanocarbon templates, atomically precise synthesis of one‐dimensional (1D) materials with the templates of CNTs. In the chirality‐controlled growth part, we focus on the design of structural templates and growth mechanisms. In the synthesis of CNT hybrids part, we organize the existing strategies based on types of 1D hybrids templated by CNTs, including confined nanotubes, linear carbon chains, nanowires, quasi‐1D van der‐Waals materials. The main advantages, challenges, and perspectives in further development are discussed.
Prevalence of potential interactions of medications, including herbs and supplements, before, during, and after chemotherapy in patients with breast and prostate cancer
Authors: Lee Richard T. , Kwon Nancy , Wu Jimin , To Connie , To Steven , Szmulewitz Russell , Tchekmedyian Raffi , Holmes Holly M. , Olopade Olufunmilayo I. , Stadler Walter M. , Von Roenn Jamie
Published: February 2021

Background

The use of herbs and supplements (HS) is common among patients with cancer, yet limited information exists about potential medication interactions (PMIs) with HS use around chemotherapy.

Methods

Patients with breast or prostate cancer who had recently finished chemotherapy at 2 academic medical centers were surveyed by telephone. Interviewers inquired about all medications, including HS, before, during, and after chemotherapy. Micromedex, Lexicomp, and Natural Medicines Comprehensive Database interaction software programs were used to determine PMIs.

Results

A total of 67 subjects (age range, 39‐77 years) were evaluated in this study. Participants were primarily White patients (73%) with breast cancer (87%). The median number of medications was 11 (range, 2‐28) during the entire study and was highest during chemotherapy (7; range, 2‐22). Approximately four‐fifths (84%) used HS. A total of 1747 PMIs were identified, and they represented 635 unique PMIs across all 3 timeframes, with most occurring during chemotherapy. Prescription‐related PMIs (70%) were the most common type, and they were followed by HS‐related (56%) and anticancer treatment–related PMIs (22%). Approximately half of the PMIs (54%) were categorized as moderate interactions, and more than one‐third (38%) were categorized as major interactions. Patient use of HS increased from 51% during chemotherapy to 66% after chemotherapy, and this correlated with an increased prevalence of HS PMIs (46% to 60%). HS users were more likely to be at risk for a major PMI than non‐HS users (92% vs 70%; P = .038).

Conclusions

The use of HS remains prevalent among patients with cancer and may place them at risk for PMIs both during chemotherapy and after the completion of treatment.

Lay Summary

This study evaluates the risk of potential medication interactions for patients with breast or prostate cancer undergoing chemotherapy.

The results show that patients often use herbs and supplements during treatment. Prescription medications are most often associated with medication interactions, which are followed by herb and supplement–related interactions. More than one‐third of potential medication interactions are considered major.

Patients should be educated about the risk of herb and supplement–related medication interactions during treatment.
Determination of Binding Strengths of Host‐Guest Complexes in Deep Eutectic Solvents Using Spin Probe Methodology
Authors: Cantelli Andrea , Franchi Paola , Mezzina Elisabetta , Lucarini Marco
Published: February 2021

Electron paramagnetic resonance (EPR) and spin probe methodologies have been employed to study the complexation properties of cyclodextrins (CDs) and cucurbit[n]urils (CB[n]s) in the deep eutectic solvent (DES) choline chloride‐urea. In the presence of γ‐CD an affinity constant very similar to that measured in water was measured in DES with benzyl‐tert‐butyl nitroxide (BTBN). With β‐CD, complexation of BTBN is significantly depressed, although still maintained. Complexation of TEMPO radical probe by CB[7] or CB[8] was instead almost entirely cancelled in DES. In addition, this methodology enabled for the first time to measure the single rate constants for the association and dissociation processes with CDs in DES.
Calcium sensing receptor as a novel target for treatment of sepsis induced cardio‐renal syndrome: Need for exploring mechanisms
Authors: Yadav Shubham , Gupta Kirti , Deshmukh Khalid , Bhardwaj Loveinder , Dahiya Ashish , Krishan Pawan , Singh Gaaminepreet
Published: February 2021

Calcium sensing receptor (CaSR) is localized in various organs and plays diverse physiological and pathological roles. Several scientific contributions have suggested the involvement of this cell surface receptor in cardiac and renal diseases. Sepsis is considered to be one of the major causes of ICU admissions. Cardiac dysfunction and acute kidney injury are major manifestations of sepsis and associated with reduced survival. Presently, the treatment approaches for management of sepsis induced cardiac depression and kidney injury are not satisfactory. Activation of CaSR has been demonstrated to induce cardiomyocyte damage upon lipopolysaccaharde (LPS) exposure by enhancing calcium ion levels, ROS (reactive oxygen species) production, promotion of inflammation and apoptosis. In addition, CaSR seems to be a critical regulator of intracellular calcium ion levels, which is directly implicated in induction of mitochondrial dysfunction and release of various pro‐apoptotic pathways during sepsis. Certain evidences have also documented the expression of CaSR on neutrophils and T lymphocytes, where it is involved in activation of neutrophils and induces apoptosis of immune cells. Moreover, the expression of CaSR has been confirmed in podocytes, mesangial cells, proximal tubular cells and its activation is responsible for podocyte effacement, mesangial cell proliferation and proximal tubular cell apoptosis. We have analyzed the existing evidences, and critically discussed the possible mechanisms underlying CaSR activation mediated cardiac and renal dysfunction in sepsis condition.
Determination of vitamin E and its metabolites in equine urine using liquid chromatography–mass spectrometry
Authors: Favro Gianna , Habib Hadi , Gennity Ingrid , Puschner Birgit , Hales Erin N. , Finno Carrie J. , Moeller Benjamin C.
Published: February 2021

Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a hereditary, deteriorating central nervous disease in horses. Currently, the only way to confirm eNAD/EDM is through a postmortem histological evaluation of the central nervous system. Vitamin E, specifically the isoform alpha‐tocopherol (α‐TP), is known to protect eNAD/EDM susceptible horses from developing the clinical phenotype. While vitamin E is an essential nutrient in the diet of horses, there are no diagnostic tests able to quantitate vitamin E and its metabolites in urine. An ultra‐performance liquid chromatography‐atmospheric‐pressure chemical ionization mass spectrometry (UPLC‐APCI‐MS/MS) method was developed and validated following acidic hydrolysis and solid phase extraction to quantitate vitamin E and its metabolites in equine urine. A blank control horse urine matrix was used and spiked with different concentrations of analytes to form a standard curve using either alpha‐tocopherol‐d6 or chlorpropamide as the internal standard. Inter‐day and intra‐day statistics were performed to evaluate the method for accuracy (90% to 116%) and precision (0.75% to 14%). Matrix effects, percent recovery, and stability were also assessed. The method successfully analyzed alpha‐carboxyethyl hydroxychroman (α‐CEHC), alpha‐carboxymethylbutyl hydroxychromans (α‐CMBHC), gamma‐carboxyethyl hydroxychroman γ‐CEHC, and α‐TP concentrations in urine to determine a baseline levels of analytes in healthy horses, and can be used to determine concentrations of vitamin E metabolites in equine urine allowing for its evaluation as a diagnostic approach in the treatment of eNAD/EDM.
High‐resolution mass spectrometry‐based approach for the identification and profiling of the metabolites of taletrectinib formed in liver microsomes
Authors: Ye Yongbin , Guo Xiaojuan , He Xin , Zhang Mingwan , He Huiqing , Qiu Dafa , Guo Ziwen
Published: February 2021

Taletrectinib is a potent, orally active, and selective ROS1/NTRK kinase inhibitor. The aim of this study was to study the metabolism of taletrectinib in rat, dog, and human liver microsomes. The biotransformation of taletrectinib was carried out using rat, dog, and human liver microsomes supplemented with nicotinamide adenine dinucleotide phosphate tetrasodium salt (NADPH) and uridine diphosphate glucuronic acid (UDPGA). The microsomal incubations were conducted at 37°C for 60 min. The formed metabolites were identified by ultrahigh performance liquid chromatography coupled to high‐resolution tandem mass spectrometry (UHPLC‐HRMS) using electrospray ionization in the positive ion mode. They were identified by accurate masses and MS/MS spectra and based on their fragmentation pathways. With UHPLC‐HRMS, a total of 10 metabolites including one glucuronide conjugate (M7) were structurally identified. M9 and M10 were unambiguously identified as taletrectinib alcohol and taletrectinib ketone, respectively, using reference standards. The phase I metabolic pathways of taletrectinib involved N‐dealkylation, O‐dealkylation, oxidative deamination, and oxygenation; the phase II metabolic pathways referred to glucuronidation. The current study investigated the in vitro metabolic fate of taletrectinib in animals and human species, which would bring us considerable benefits for the subsequent studies focusing on the pharmacological effect and toxicity of this drug.
Genome‐wide SNP discovery and QTL mapping for economic traits in a recombinant inbred line of Oryza sativa
Authors: Li Gengmi , Yang Qianhua , Li Deqiang , Zhang Tao , Yang Li , Qin Jian , Tang Bin , Guo Xiaojiao , Cao Yingjiang , You Shumei , Li Zhaoxiang , Luo Jing , Wan Xianqi , Liu Ying , Huang Fu , Guo Longbiao , Jiang Kaifeng , Zheng Jiakui
Published: February 2021

The objective of the study was to understand the genetic basis of eight traits conferring grain appearance and yield in a recombinant inbred line (RIL8) derived from a cross between cultivated Indica rice varieties Dexiang074B and Pujiang6. We conducted whole genome re‐sequencing for the two parental lines and genotyping by sequencing (GBS) for the RIL8 population. Next, we aligned the clean reads to the rice genome Nipponbare IRGSP 1.0, constructed the genetic linkage map (GLM), and performed the quantitative trait loci (QTL) analysis. In total, 2631 high‐quality markers were generated for 315 RIL8 samples. We identified a rice GLM containing 12 linkage groups (total map distance: 1946.71 cM; average map distance: 0.74 cM) and 98 QTLs related to the rice yield, including 31 high credible QTLs. In addition, 39 QTLs were identified to be associated with the G*E interaction. While most of the QTLs were co‐localized with previously reported rice QTLs, some novel QTLs were identified for the first time in this study. These findings provide a genetic basis for developing cultivated rice with good economic characteristics based on molecular breeding technologies.
Arbitrage trading and price discovery of the regular and mini Taiwan stock index futures
Authors: Chen Yu‐Lun , Lee Yen‐Hsien , Chou Robin K. , Chang Ya‐Kai
Published: February 2021

We investigate the contributions of the Taiwan regular and mini index futures to price discovery. We find that the regular futures provide more price discovery, which is inconsistent with the findings for the US futures markets. This dominance of regular futures became relatively weaker after the introduction of the standard portfolio analysis of the risk margin system because of more arbitrage trades mainly executed by institutional investors. We show the effect of the introduction of an integrated margin system on the price‐discovery processes and efficiencies for futures with the same underlying asset but different contract sizes.
Assisted estimation of gene expression graphical models
Authors: Yi Huangdi , Zhang Qingzhao , Sun Yifan , Ma Shuangge
Published: February 2021

In the study of gene expression data, network analysis has played a uniquely important role. To accommodate the high dimensionality and low sample size and generate interpretable results, regularized estimation is usually conducted in the construction of gene expression Gaussian Graphical Models (GGM). Here we use GeO‐GGM to represent gene‐expression‐only GGM. Gene expressions are regulated by regulators. gene‐expression‐regulator GGMs (GeR‐GGMs), which accommodate gene expressions as well as their regulators, have been constructed accordingly. In practical data analysis, with a “lack of information” caused by the large number of model parameters, limited sample size, and weak signals, the construction of both GeO‐GGMs and GeR‐GGMs is often unsatisfactory. In this article, we recognize that with the regulation between gene expressions and regulators, the sparsity structures of a GeO‐GGM and its GeR‐GGM counterpart can satisfy a hierarchy. Accordingly, we propose a joint estimation which reinforces the hierarchical structure and use the construction of a GeO‐GGM to assist that of its GeR‐GGM counterpart and vice versa. Consistency properties are rigorously established, and an effective computational algorithm is developed. In simulation, the assisted construction outperforms the separation construction of GeO‐GGM and GeR‐GGM. Two The Cancer Genome Atlas data sets are analyzed, leading to findings different from the direct competitors.
Can economic links explain lead–lag relations across firms?
Authors: Zeng Kailin , Atta Mills Ebenezer Fiifi Emire
Published: February 2021

This article studies the driving sources of cross‐firm lead–lag relations in returns which are generated by the Granger‐causality test with a long estimation window. The authors observed that economic links such as customer–supplier relationships and peer effects only account for a small share of the frequently observed cross‐firm lead–lag relations. Instead, most of the cross‐firm lead–lag relations are driven by several classical factors. On average, 95% of the cross‐firm lead–lag relations disappear after controlling for the three classical Fama–French factors, “betting against beta” and a few industry factors such as utility, oil, construction, and finance. This article represents novel evidence that classical factors designed for explaining the contemporaneous stock returns also contains important information for future returns. Investors trading on the signals generated by the relevant classical factors can obtain significant and positive returns.
Financial crises, firm‐level shocks and large downturns: Evidence from Greece
Authors: Giannoulakis Stelios , Sakellaris Plutarchos
Published: February 2021

How do firm‐specific shocks contribute to large economic downturns associated with financial crises? Using a large and representative dataset on Greek firms covering all sectors of the economy over the period 2000–2014, we find that the contribution of firm‐specific shocks to the volatility of aggregate sales growth increased substantially (about 30%) during the Greek financial crisis and dominated the contribution of macro‐economic and sectoral shocks. We also find that, throughout the sample period, inter‐firm linkages are two and a half times as important as the direct effect of firm shocks in driving aggregate fluctuations. However, during the financial crisis, the Greek economy became more granular, and the direct effect of firm‐specific shocks had increased importance in driving aggregate volatility.
Tetrahydrobiopterin deficiencies: Lesson from clinical experience
Authors: Bozaci Ayse Ergul , Er Esra , Yazici Havva , Canda Ebru , Kalkan Uçar Sema , Güvenc Saka Merve , Eraslan Cenk , Onay Hüseyin , Habif Sara , Thöny Beat , Coker Mahmut
Published: February 2021

Objectives

The present study describes clinical, biochemical, molecular genetic data, current treatment strategies and follow‐up in nine patients with tetrahydrobiopterin (BH4) deficiency due to various inherited genetic defects.

Methods

We analyzed clinical, biochemical, and molecular data of nine patients with suspected BH4 deficiency. All patients were diagnosed at Ege University Faculty of Medicine in Izmir, Turkey and comprised data collected from 2006 to 2019. The diagnostic laboratory examinations included blood phenylalanine and urinary or plasma pterins, dihydropteridine reductase (DHPR) enzyme activity measurement in dried blood spots, folic acid and monoamine neurotransmitter metabolites in cerebrospinal fluid, as well as DNA sequencing.

Results

Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency, two with 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency, three with sepiapterin reductase (SR) deficiency, and three with DHPR deficiency. Similar to previous observations, the most common clinical symptoms are developmental delay, intellectual disability, and movement disorders. All patients received treatment with l‐dopa and 5‐hydroxytryptophan, while only the ar GTPCH, the PTPS, and one DHPR deficient patients were supplemented in addition with BH4. The recommended dose range varies among patients and depends on the type of disease. The consequences of BH4 deficiencies are quite variable; however, early diagnosis and treatment will improve outcomes.

Conclusions

As BH4 deficiencies are rare group of treatable neurometabolic disorders, it is essential to diagnose the underlying (genetic) defect in newborns with hyperphenylalaninemia. Irreversible brain damage and progressive neurological deterioration may occur in untreated or late diagnosed patients. Prognosis could be satisfying in the cases with early diagnose and treatment.
Performance of a rapid antigen test in the diagnosis of SARS‐CoV‐2 infection
Authors: Ciotti Marco , Maurici Massimo , Pieri Massimo , Andreoni Massimo , Bernardini Sergio
Published: February 2021

Diagnostics is crucial for a prompt identification of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infected patients, their isolation and treatment. Real‐time PCR is the reference method for the diagnosis of SARS‐CoV‐2 infection; however, the unprecedented increase in the number of infections worldwide calls for faster and easy methods that do not require skilled personnel and special equipment. Rapid antigen tests have been developed and used as first line screening. Here, we assessed the performance of a rapid antigen test in comparison to a real‐time qualitative PCR as gold standard. Fifty nasopharyngeal swabs from suspected cases of SARS‐CoV‐2 infection have been tested by Coris coronavirus disease 2019 Ag Respi‐Strip test and Allplex 2019n‐CoV assay. Of the 50 nasopharyngeal swabs tested, 11 were negative by both tests, 27 were negative by Ag test but positive by real‐time PCR, and 12 were positive by both methods. PCR detected the 39 positive samples at a median cycle threshold (Ct) value of 22.78 (mean: 24.51; range: 13.59–39.6). In the 12 concordant samples, the median Ct value was 17.37. The sensitivity of the Ag test was 30.77% (95% confidence interval [CI]: 17.02%–47.57%), specificity 100% (95% CI: 71.51%–100.00%), positive predictive value 100%, negative predictive value 85.25% (95% CI: 82.42%–87.69%), and accuracy 86.15% (95% CI: 73.45%–94.28%). The level of agreement between the two tests was poor, k = 0.164. The Ag test performs well in the presence of high viral loads, whereas lower levels are missed. Considering the poor sensitivity of the method, real‐time PCR remains the gold standard as front line screening for SARS‐CoV‐2 infection.
Soil phosphorus cycling is modified by carbon and nitrogen fertilization in a long‐term field experiment
Authors: Wang Ye , Bauke Sara L. , von Sperber Christian , Tamburini Federica , Guigue Julien , Winkler Pauline , Kaiser Klaus , Honermeier Bernd , Amelung Wulf
Published: February 2021

Background and aims: Phosphorus (P) is an essential element for crop growth. However, while links of P turnover in soils to carbon (C) and nitrogen (N) availability have been described, it remains to be clarified how combinations of fertilizer C and N additions affect stocks and cycling of distinct P fractions at different soil depths. The objectives of our study were (1) to assess how soil total P stocks are affected by organic amendments and N fertilization, (2) to evaluate how different soil P fractions respond to N fertilization, and (3) to verify whether N fertilization increases soil biological P cycling.

Methods: We collected soil samples from a long‐term field experiment established in 1984 in Rauischholzhausen, Germany. The soil is a Haplic Luvisol and received either no organic fertilizer (NOF), farmyard manure (FYM) or a combination of organic and mineral N fertilizer (OMF). Each treatment additionally received three levels of mineral N: 0 kg ha−1 y−1 (N0), 100 kg ha−1 y−1 (N100), and 200 kg ha−1 y−1 (N200). The organic fertilizers were applied by a manure spreader and the N fertilizer (calcium ammonium nitrate) was applied in spring as top dressing by a plot fertilizer machine. We estimated stocks of P in fractions isolated by sequential P fractionation, and assessed the oxygen isotopic composition of 1 M HCl‐extractable phosphate (δ18OP).

Results: We found that increased organic matter (OM) addition and mineral N inputs caused significant decreases in the stocks of resin‐ and NaHCO3‐extractable P in the topsoil (0–30 cm). Mineral N fertilization alone resulted in significant increases in stocks of resin‐, NaHCO3‐, and NaOH‐extractable P in the upper subsoil (30–50 cm). These changes occurred for both inorganic and organic P. The subsoil δ18OP values were closer to expected equilibrium values in soil fertilized with mineral N, indicative of more intensive biological P cycling than in the treatments without mineral N inputs.

Conclusions: These findings suggest that long‐term OM and mineral N fertilization promotes topsoil P losses from labile fractions by crop uptake with an enrichment of these P forms in the subsoil, and an overall increase in biological P cycling in both top‐ and subsoil horizons upon N fertilization.
Cancer surgery during the COVID‐19 pandemic: The experience of a comprehensive cancer center performing preoperative screening by RT‐PCR and chest CT scan
Authors: Guerlain Joanne , Haroun Fabienne , Voicu Alexandra , Honoré Charles , Griscelli Franck , Temam Stéphane , Benmoussa Nadia , Gorphe Philippe , de Baere Thierry , Ammari Samy , Garcia Gabriel , Balleyguier Corinne , Rimareix Françoise , Gouy Sébastien , Sitbon Philippe , Gachot Bertrand , Breuskin Ingrid , Suria Stéphanie , Moya‐Plana Antoine
Published: February 2021

Background and Objectives

During the worldwide pandemic of coronavirus disease 2019 (COVID‐19), oncological procedures considered to be urgent could not be delayed, and a specific procedure was required to continue surgical activity. The objective was to assess the efficacy of our preoperative screening algorithm.

Methods

This observational retrospective study was performed between the 25th of March and the 12th of May 2020 in a comprehensive cancer center in France. Patients undergoing elective oncologic surgery were tested by preoperative nasopharyngeal reverse‐transcription polymerase chain reaction (RT‐PCR) that could be associated with a chest computerized tomography (CT) scan.

Results

Of the 510 screening tests (in 477 patients), only 5% (15/477) were positive for COVID‐19 in 24 patients (18 RT‐PCR+ and 7 CT scan+/RT‐PCR−). Four patients were ultimately false positives based on the CT scan. In total, only 4.2% (20/477) of the patients were COVID‐19+. The positivity rate decreased with time after the containment measures were implemented (from 7.4% to 0.8%). In the COVID‐19+ group, 20% of the patients had postoperative pulmonary complications, whereas this was the case for 5% of the patients in the COVID‐19 group.

Conclusions

Maintaining secure surgical activity is achievable and paramount in oncology care, even during the COVID‐19 pandemic, with appropriate screening based on preoperative RT‐PCR.
A comparison of depth of necrosis among adjuvant therapies used for the treatment of benign bone tumors
Authors: Bombardier Brenden , Haase Douglas , Sweeney Kyle , Friedman Elizabeth , Poppe Tanner , Hughes Nicole
Published: February 2021

Background and Objectives

Benign bone tumors are often treated with extended curettage utilizing an adjuvant therapy to eliminate any remaining tumor cells. The purpose of this study was to explore and compare the histologic depth of necrosis created by various adjuvant therapies used in the treatment of benign bone tumors.

Methods

A high‐speed burr was utilized to create cortical defects within porcine humeri and femora. Phenol, polymethyl methacrylate (PMMA), argon beam coagulation (ABC), liquid nitrogen, and the Bipolar Hemostatic Sealer (BHS) were each applied to five defects, with an additional five defects left untreated as a control. The maximal depth of necrosis was determined under microscopic examination.

Results

The phenol, PMMA, ABC, liquid nitrogen, and BHS demonstrated an average histologic depth of necrosis of 0.30, 0.78, 2.54, 2.54, and 0.92 mm, respectively, each of which was significantly increased compared to the control group (p = .001, .003, .003, .01, and  <.001). Their respective variances, a measure of reproducibility, were 0.01, 0.09, 0.96, 1.93, and 0.03 mm2.

Conclusion

This study confirms, through histologic analysis, adjuvant therapies create a rim of cellular necrosis beyond that of burring during extended curettage, supporting their use in the treatment of benign bone tumors. Furthermore, it provides a head‐to‐head comparison.