bluuebunny/crossref_metadata_2025 huggingface dataset:
A narrative review of the pathophysiology of COVID‐19 infection among cancer patients: Current evidence and research perspectives
Authors: Ramani Vinod K. , Naik Radheshyam
Published: January 2021

Introduction

The mechanism by which a suppressed immune system of a cancer patient makes them susceptible to COVID‐19 is still unclear. Any delay or discontinuation of cancer care due to the pandemic is expected to have a detrimental impact on the outcome of cancer. A few studies have addressed the incidence of COVID‐19 among cancer patients, but the small sample size of such studies makes it difficult to draw inference to the general population.

Methods

For our review, ‘Pubmed’ database and Google search engines were used for searching the relevant articles. The criterion used for review includes their relevance to the defined review question, which is the pathophysiological mechanism of COVID‐19 among cancer patients and the relevant therapeutic interventions therewith. This review includes 20 studies and other relevant literature which address the determinants of COVID‐19 among Cancer patients.

Results

Delay in cancer diagnosis will increase the stage progression of cancer patients and increased mortality in the future. A short delay in administering cancer related treatment to aid the odds of patient surviving the acute SARS‐CoV‐2 infection, should be at the discretion of the treating Physician. Oncologists dilemma in the current situation includes titrating the density of drug doses and intensity of treatment regimen, for the optimal management of metastatic and adjuvant cancer patients. Patients are thus subjected to suboptimal treatment and undetected disease recurrence, To circumvent the immunosuppressive effects of chemotherapy, Providers need to consider staggered regimen or alternate therapies such as biological/immunotherapy, targeted therapy, anti‐angiogenic drugs, hormone therapy and/or antibody‐based therapeutics.

Conclusion

This review provides insights on the pathogenesis of SARS‐CoV‐2, which could enable Physicians in formulating therapeutic strategies for the management of severe patients, more so in Oncology settings, thus reducing the mortality. The key is to balance the continuation of urgent cancer care, but rationing the elective treatment according to the circumstances.
Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population‐based cohort studies
Authors: Iwase Madoka , Matsuo Keitaro , Koyanagi Yuriko N. Y. , Ito Hidemi , Tamakoshi Akiko , Wang Chaochen , Utada Mai , Ozasa Kotaro , Sugawara Yumi , Tsuji Ichiro , Sawada Norie , Tanaka Shiori , Nagata Chisato , Kitamura Yuri , Shimazu Taichi , Mizoue Tetsuya , Naito Mariko , Tanaka Keitaro , Inoue Manami
Published: January 2021

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large‐scale population‐based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random‐effects models. Among 158 164 subjects with 2 369 252 person‐years of follow‐up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04‐1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25‐2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04‐3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow‐up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.
Benzothiazole‐Phenothiazine Conjugate Based Molecular Probe for the Differential Detection of Glycated Albumin
Authors: Kumar Ashish , Datta Lakshmi Priya , Samanta Sourav , Arora Harshit , Govindaraju Thimmaiah
Published: January 2021

Glycation of albumin proteins is considered the pathophysiological hallmark of several chronic fatal disorders, including diabetes mellitus (DM) and Alzheimer's disease (AD). The optical detection of glycated albumin is a simple and cost‐effective tool with diagnostic implications for DM and AD. Herein, we developed a cyano derivative of the benzothiazole‐phenothiazine conjugate (TCNP) ‐based far‐red fluorescence probe for the differential detection of glycated bovine serum albumin (BSAG) over native BSA and oxidized BSA (BSAO). The selective fluorescence enhancement of TCNP in the presence of native BSA and BSAO and significant quenching in the presence of BSAG account for the distinct interaction between the probe and different structural variants of BSA. The high photostability and differential response towards native BSA and BSAG infer that TCNP is a potential molecular tool to assess the glycation induced structural changes of albumins.
The toxicity of ambient fine particulate matter (PM2.5) to vascular endothelial cells
Authors: Xie Wei , You Jia , Zhi Chenxi , Li Liang
Published: January 2021

Several epidemiologic and toxicological studies have widely regarded ambient fine particulate matter (PM2.5), the particles with an aerodynamic diameter less than 2.5 μm, as a strong potential threat to human health. PM2.5 exposure is mainly through the respiratory tract where it can permeate the lung alveoli and enter the blood circulation. After going into the circulation, PM2.5 directly confronts the vascular endothelial cells (VECs). The VECs, which are lined up in the innermost layer of the blood vessels, are essential in the homeostasis of physiological processes. Thus, the damage and dysfunction of VECs is a common cause of various diseases. In this review, we summarize the toxicity of PM2.5 to VECs including the pathophysiological mechanism and the effects of VEC‐mediated physiological functions. The review has discussed the association of impaired VEC function by PM2.5 with various diseases, indicating that the VECs may be an effective assessment of public health recommendations under PM2.5 exposure. Therefore, reducing the adverse effect of PM2.5 on VECs will prevent the potential occurrence and fatality of the relevant diseases in the future.
Evaluation of some new heterocycles bearing 2‐oxoquinolyl moiety as immunomodulator against highly pathogenic avian influenza virus (H5N8)
Authors: El‐Helw Eman A. E. , Morsy Alaa R. I. , Hashem Ahmed I.
Published: January 2021

The hydrazide obtained from furan‐2(3H)‐one integrated with a quinolin‐2(1H)‐one core reported previously by our research group was utilized as a building block synthon to obtain some pyrrolone, pyridazinone, oxadiazole, and triazole derivatives through treating with some carbon electrophilic reagents, for example, chloroacetyl chloride, benzoyl chloride, acetic anhydride, carbon disulfide, 3,4‐dimethoxybenzaldehyde, and 2‐oxoquinolin‐3‐carbaldehyde to achieve the target heterocycles. The newly synthesized compounds were evaluated as immunomodulator against highly pathogenic avian influenza virus (H5N8). The compounds 1, 11, and 17 displayed the highest potency (100% protection).
Newborn screening and disease variants predict neurological outcome in isovaleric aciduria
Authors: Mütze Ulrike , Henze Lucy , Gleich Florian , Lindner Martin , Grünert Sarah C. , Spiekerkoetter Ute , Santer René , Blessing Holger , Thimm Eva , Ensenauer Regina , Weigel Johannes , Beblo Skadi , Arélin Maria , Hennermann Julia B. , Marquardt Thorsten , Marquardt Iris , Freisinger Peter , Krämer Johannes , Dieckmann Andrea , Weinhold Natalie , Keller Mareike , Walter Magdalena , Schiergens Katharina A. , Maier Esther M. , Hoffmann Georg F. , Garbade Sven F. , Kölker Stefan
Published: January 2021

Isovaleric aciduria (IVA), a metabolic disease with severe (classic IVA) or attenuated phenotype (mild IVA), is included in newborn screening (NBS) programs worldwide. The long‐term clinical benefit of screened individuals, however, is still rarely investigated. A national, prospective, observational, multi‐center study of individuals with confirmed IVA identified by NBS between 1998 and 2018 was conducted. Long‐term clinical outcomes of 94 individuals with IVA were evaluated, representing 73.4% (for classic IVA: 92.3%) of the German NBS cohort. In classic IVA (N = 24), NBS prevented untimely death except in one individual with lethal neonatal sepsis (3.8%) but did not completely prevent single (N = 10) or recurrent (N = 7) metabolic decompensations, 13 of them occurring already neonatally. IQ (mean ± SD, 90.7 ± 10.1) was mostly normal but below the reference population (P = .0022) and was even lower in individuals with severe neonatal decompensations (IQ 78.8 ± 7.1) compared to those without crises (IQ 94.7 ± 7.5; P = .01). Similar results were obtained for school placement. In contrast, individuals with mild IVA had excellent neurocognitive outcomes (IQ 105.5 ± 15.8; normal school placement) and a benign disease course (no metabolic decompensation, normal hospitalization rate), which did not appear to be impacted by metabolic maintenance therapy. In conclusion, NBS reduces mortality in classic IVA, but does not reliably protect against severe neonatal metabolic decompensations, crucial for favorable neurocognitive outcome. In contrast, individuals with mild IVA had excellent clinical outcomes regardless of metabolic maintenance therapy, questioning their benefit from NBS. Harmonized stratified therapeutic concepts are urgently needed.
Performance evaluation of different probability distribution functions for computing Standardized Precipitation Index over diverse climates of Iran
Authors: Raziei Tayeb
Published: January 2021

Monthly precipitation time series of 46 synoptic stations distributed over diverse climates of Iran were investigated to identify the best‐fitted probability distribution function (PDF) to the monthly precipitation series aggregated at different timescales. The computed skewness and the probability of zero precipitation (PZP) values of the considered precipitation aggregations show that a large proportion of monthly precipitation data in the study period, especially in the warm months of the year, is zero. The skewness of all 12 individual monthly precipitation time series as well as their aggregation at 3‐ and 6‐months timescales were also found very high in many studied stations, particularly in those of the arid and semi‐arid climates of Iran. To identify the best candidate distribution function for computing Standardized Precipitation Index (SPI) in different climatic areas of Iran, the performances of a dozen statistical PDFs in fitting monthly precipitation aggregated at different timescales were statistically evaluated. The results showed that the two‐parameter gamma distribution best fits monthly precipitation time series over most parts of the country while the Pearson Type III (PE3) was identified as the best‐fitted model for 3‐ and 6‐months aggregation periods and general extreme value (GEV) distribution as the best candidate function in fitting precipitation aggregated at 9‐, 12‐, and 24‐month timescales. PE3 was also identified as the second best‐fitted model for both the shorter time scale (1‐month) and the longer timescales (9‐, 12‐, and 24 months). Considering that PE3 ranked either first or second in fitting precipitation time series aggregated at different timescales and in all climatic areas of Iran, it is chosen as the most appropriate distribution function in fitting precipitation aggregated at all considered timescales throughout Iran.
Stability of needle‐ and root‐derived biomarkers during litter decomposition
Authors: Altmann Jens G. , Jansen Boris , Palviainen Marjo , Kalbitz Karsten
Published: January 2021

Background and aims: Plant‐derived, ester‐bound substituted fatty acids have been used for decades as biomarkers to identify input of plant materials in sediments and soils. However, the long‐term decomposition patterns of these biomarker compounds under natural conditions are not well understood, although this is a basic prerequisite for quantitative biomarker applications.

Methods: For this study, we analyzed the decomposition patterns of root‐ and needle‐specific compounds of Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) in a litterbag study conducted over 3 years. Samples were analyzed by methanolic KOH extraction with previous removal of free extractable lipids.

Results: The concentrations of most detectable compounds had decreased after three years of incubation. The observed changes of concentrations followed a non‐linear path and cannot be explained by microbial uptake and metabolism alone. Other factors controlling the breakdown of ester‐bound lipids, like lipid oxidation must play a role. Between similar plant parts and different plant parts of the same species, the observed degradation patterns were heterogeneous. The estimated ratio of remaining root and needle biomass that may arise with the choice of a particular biomarker varies in this study between 0.6 and 40 times after three years.

Conclusion: This range of variation does not allow reliable conclusions about the contribution of roots and needles to decomposed organic matter based on biomarkers ratios.
Feature‐level fusion of laser‐induced breakdown spectroscopy and Raman spectroscopy for improving support vector machine in clinical bacteria identification
Authors: Teng Geer , Wang Qianqian , Cui Xutai , Wei Kai , Xiangli Wenting , Chen Guoyan
Published: January 2021

In clinical field, the diagnosis of many diseases and their development stages depend on the detection of the corresponding bacteria. Raman spectroscopy and laser‐induced breakdown spectroscopy (LIBS) are two novel spectral diagnostic technologies for clinical bacteria identification. Both of them have been used in clinical detection combined with optimized support vector machine (SVM). In this paper, two feature‐level fusion methods (before feature selection fusion [BFSF] and after feature selection fusion [AFSF]) were proposed to improve the performance of SVM classifier and reduce the analyzing time (including the parameter tuning, model training, and testing time) simultaneously by combining data of LIBS and Raman spectroscopy. Using the most important 10 feature lines as the inputs of the optimized classifier, the analyzing time could be reduced to 1 to 2 min and the correct classification rate (CCR) achieved 95.67%. Without optimizing SVM parameters, the two proposed methods could achieve rapid and accurate classification of pathogenic bacteria further. The AFSF method showed better results with less fusion features while the BFSF method achieved higher CCR at 100% with more features. Both two methods costed around 0.2 s for analysis. These indicate that the proposed feature‐level fusion methods can improve the performance of SVM for bacteria detection. Maintaining the highest diagnostic accuracy, they can achieve the minimum analyzing time.
Novel Technique for the Measurement of Fetal Right Modified Myocardial Performance Index Using Synchronized Images of Right Ventricular Inflow and Outflow and Clinical Application to Twin‐to‐Twin Transfusion Syndrome
Authors: Kang Ok‐Ju , Kim So Yeon , Lee Mi‐Young , Won Hye‐Sung , Choi Kwangyeon , Lee Jinyong , Kim Min‐ju
Published: January 2021

Objective

To evaluate the reproducibility of the fetal right modified myocardial performance index (Mod‐MPI) obtained by synchronizing the inflow and outflow images of the right ventricle (RV) and to evaluate its feasibility through clinical application to twin‐to‐twin transfusion syndrome (TTTS).

Methods

We prospectively evaluated 77 normal fetuses. Two experienced operators individually measured the right Mod‐MPI using two different methods: (1) separate recording of the RV inflow and outflow using pulsed‐wave Doppler (conventional method) and (2) synchronization of RV inflow and outflow images using the MPI + ™ function based on the closure click of the pulmonary valve (new method). To evaluate the clinical utility of the new method, we measured the right Mod‐MPI in 33 TTTS fetuses using the new method before and after the fetoscopic laser coagulation (FLC).

Results

There was no statistical difference in Mod‐MPI values between the two methods (p = .242). For both operators, the intra‐ and interoperator reproducibility of Mod‐MPI was high with both methods (ICCs >0.950). Among the components of Mod‐MPI measured using the new method, ejection time showed the highest reproducibility, whereas isovolumetric relaxation time demonstrated the lowest reproducibility. In TTTS fetuses, the Mod‐MPI significantly decreased after FLC in recipients, and there was no difference in MPI values before and after FLC in donors.

Conclusion

Right Mod‐MPI measurement after the synchronization of RV inflow and outflow images is a reliable technique for evaluating fetal right cardiac function. This novel method can also independently evaluate the systolic and diastolic functions of the right heart.
Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors
Authors: Ding Li , Zhuang Chunlin , Chen Fener
Published: January 2021

Drug discovery of human immunodeficiency virus (HIV) is a hot field in medicinal chemistry community for many years. The diarylpyrimidines (DAPYs) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) targeting reverse transcriptase, playing a great irreplaceable role in HIV transcriptional therapy. However, fast‐growing drug‐resistant mutations as nonnegligible challenge are still unpredictably appeared in the clinical practice, leading to deactivate or reduce the existing drugs. In the last 20 years, more and more novel DAPY derivatives have developed with the purpose to counter the mutants. Nevertheless, most of them have dissatisfactory pharmacokinetics (PK) or poor antiviral activity toward resistant mutant strains. In this article, we will analyze the NNRTI derivatives with promising druggability, and summarize a series of druggability modification strategies to improve the antiviral activity, reduce toxicity and improve the PK properties in recent years. The prospects of DAPYs and the directions for future efforts will be discussed.
Numerical methods for a problem of thermal diffusion in elastic body with moving boundary
Authors: Madureira Rodrigo L. R. , Rincon Mauro A. , Teixeira Marcello G.
Published: January 2021

Coupled parabolic‐hyperbolic system often appears in the studies of thermoelasticity, magnetoelasticity, biological problems and radiation hydrodynamics with high temperature. In this paper, we investigate a problem of thermal diffusion in elastic body with moving boundary. Three numerical methods, two uncoupled and one coupled, all with quadratic convergence order in time and space, are presented and compared in relation to the execution time. Tables and figures of the approximate solution are shown to verify the efficiency and feasibility of the proposed method. In addition, we show that the numerical results are consistent with the theoretical results. The approximate numerical solutions are calculated using the finite element method in spatial variable and finite difference method in time. To compare different numerical schemes, we show the convergence rates through numerical simulations with calculated error and the execution time.
Predictors of proper inhaler technique and asthma control in pediatric patients with asthma
Authors: Almomani Basima A. , Al‐Qawasmeh Batool S. , Al‐Shatnawi Samah F. , Awad Samah , Alzoubi Sirin A.
Published: January 2021

Background

Improper use of asthma inhalers is one of the potential factors of poor asthma control among children. This study aimed to assess the proper handling of asthma inhalers and asthma control in addition to factors influencing them among pediatric patients who self‐administer their inhalers.

Methods

A cross‐sectional study was conducted in Jordan from February 2019 to February 2020. All eligible pediatric patients with asthma attending outpatient settings were approached. The inhalation technique was assessed according to a standard checklist, and asthma control was assessed using the Asthma Control Test.

Results

A total of 150 patients were included in this study. A metered dose inhaler (MDI) was the most commonly used inhaler device (89.4%) which was used appropriately by only 13.4% of participants. Whereas, appropriate use of Turbohaler and Diskus was reported by 38.5% and 28.9%, respectively. The higher level of parental knowledge was associated with higher number of correct MDI steps (OR = 1.066; 95% CI = 1.010–1.125; p = .020) and less reported errors in critical steps (OR = 0.949; 95% CI = 0.900–0.999; p = .047). Higher level of both parental education and pediatric average stigma score (less stigmatized) were associated with better asthma control ([OR = 5.181; 95% CI = 1.238–21.677; p = .024], [OR = 2.825; 95% CI = 1.420–5.619; p = .003], respectively).

Conclusion

Continuous education on appropriate inhaler self‐administration for asthmatic children is highly recommended. Clinical pharmacists play a major role toward improving the administration of inhalers through patient training and counseling.
Improving the Stability of Trinitramide by Chemical Substitution: N(NF2)3 has Higher Stability and Excellent Propulsion Performance
Authors: Yaempongsa Dhebbajaj , Brinck Ann , Brinck Tore
Published: January 2021

The potential for improving the stability of trinitramide (N(NO2)3) by chemical substitution of the NO2 group has been investigated using Kohn‐Sham density functional theory [M06‐2X/6‐31+G(d,p)] and ab initio quantum chemistry [CBS‐QB3]. Monosubstituted analogs are generally found to have a decreased N‐NO2 bond dissociation enthalpy (BDE) because of increased stabilization of the N(NO2)X radical intermediate resulting from the bond cleavage. This is particularly apparent for N(NO2)2NH2, which has a BDE of only 54 kJ/mol. Instead it is shown that the stability of TNA can be significantly improved by substituting all three NO2 for the NF2 group. The resulting molecule, N(NF2)3, has a N−N BDE of 138 kJ/mol, which is 17 kJ/mol higher than the N−N BDE of N(NO2)3. In contrast to N(NO2)3, there are no indications that the stability of N(NF2)3 is significantly reduced in polar solvents. Condensed phase properties of N(NF2)3 have been estimated based on surface electrostatic potential calculations, and N(NF2)3 is estimated to be a liquid in the approximate temperature range of 170–290 K because of its nonpolar character. The performance of N(NF2)3 in propellant formulations with fuels rich in hydrogen and/or aluminum has been investigated. N(NF2)3 propellants are shown to outperform propellants based on standard oxidizers by up to 20 % in specific impulse and up to 100 % in density impulse. Compositions of N(NF2)3 and HMX have significantly higher detonation performance than CL‐20.
Interactions of two enantiomers of a designer antimicrobial peptide with structural components of the bacterial cell envelope
Authors: Ye Zhou , Aparicio Conrado
Published: January 2021

Antimicrobial peptides (AMPs) have great potential in treating multi‐drug resistant bacterial infections. The antimicrobial activity of d‐enantiomers is significantly higher than l‐enantiomers and sometimes selectively enhanced against Gram‐positive bacteria. Unlike phospholipids in the bacterial plasma membrane, the role of other bacterial cell envelop components is often overlooked in the mode of action of AMPs. In this work, we explored the structural interactions between the main different structural components in Gram‐negative/Gram‐positive bacteria and the two enantiomers of a designer AMP, GL13K. We observed that both l‐GL13K and d‐GL13K formed self‐assembled amyloid‐like nanofibrils when the peptides interacted with lipopolysaccharide and lipoteichoic acid, components of the outer membrane of Gram‐negative bacteria and cell wall of Gram‐positive bacteria, respectively. Another cell wall component, peptidoglycan, showed strong interactions exclusively with d‐GL13K and formed distinct laminar structures. This specific interaction between peptidoglycans and d‐GL13K might contribute to the enhanced activity of d‐GL13K against Gram‐positive bacteria as they have a much thicker peptidoglycan layer than Gram‐negative bacteria. A better understanding of the specific role of bacterial cell envelop components in the AMPs mechanism of action can guide the design of more effective Gram‐selective AMPs.
Advanced Series Resistance Imaging for Silicon Solar Cells via Electroluminescence
Authors: Dost Georg , Höffler Hannes , Greulich Johannes M.
Published: January 2021

Herein, a method for advanced series resistance imaging via electroluminescence (EL) for silicon solar cells is presented. The well‐known method by Haunschild et al. is revisited. The Fuyuki assumption of a linear relation between diffusion length and EL signal is shown to be not applicable to silicon devices nowadays due to larger minority charge carrier diffusion lengths and thinner solar cells. A new relation derived by Breitenstein is used here instead. The updated method for series resistance and saturation current imaging based on two EL images, which show a far superior separation of contrast and almost 60% shorter data acquisition times in comparison with the original method by Haunschild, is presented. The Weber contrast of the unwanted signal caused by recombination in resistance image is reduced from 0.89 to 0.44, using the advanced method for a prominent feature on the sample cell. The contrast due to resistance stays at the same level. The dark saturation current density images show 20% higher peaks at recombination active areas and also a 5% low.
Postirradiation Annealing and Reirradiation Study of High‐Dose Proton‐Irradiated Fe–Cu Model Alloys by Positron Annihilation and Nanoindentation
Authors: Zhao Wenzeng , Shi Jianjian , Yang Zhihui , Liu Xiangbing , Cao Xingzhong , Wang Baoyi , Wu Yichu
Published: January 2021

The microstructural evolution of postirradiation annealing (PIA) and reirradiation in high‐dose proton‐irradiated Fe–Cu model alloys (Cu: 0.05 and 0.1 wt%) at high temperature (about ≈290 °C) is investigated using positron annihilation and nanoindentation. The positron results show that vacancy defects and Cu precipitates are produced in high‐dose proton‐irradiated Fe–Cu alloys. Under PIA at 500 °C, vacancy defects are recovered substantially, whereas Cu precipitates still remain in Fe–Cu alloys. After reirradiation, theSparameter in the damaged region evidently increases when compared with the postirradiation annealed samples. It is suggested that Cu precipitates remain in the postirradiation annealed samples that strongly affect the formation and growth of vacancy defects. More defects are produced in reirradiated samples, resulting in higherSparameters. The nanoindentation results show obvious hardening in the reirradiated samples. Both vacancy defects and Cu precipitates lead to the hardening of high‐dose proton‐irradiated Fe–Cu model alloys.
A body‐mounted device for MRI‐guided spinal therapy
Authors: Squires Alexander , Hovet Sierra , Li Rui , Oshinski John , Ho Tse Zion Tsz
Published: January 2021

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no cure and limited treatment options. Recent studies have shown that delivering cellular therapeutics to the ventral horn of the spinal cord can effectively halt neurodegeneration associated with ALS in small animal models.

Methods

We developed a robotic system that assists with MRI‐guided percutaneous injections to the spinal cord. The needle positioning robot consists of two linear axes with motorised translational sleds for two‐degree‐of‐freedom (2‐DOF) needle translation and a radial template for 2‐DOF discrete rotation.

Results

The robot's targeting capability, evaluated using phantom models and swine cadavers, showed mean targeting errors of 0.48 and 2.84 mm, respectively. The duration of the targeting procedure is approximately 60 min, with an extra 10 min for each additional injection.

Conclusions

The presented robot does not affect imaging quality during MRI‐guided procedures, and it enables a simplified workflow for MRI‐guided spinal therapy.
Design, Synthesis and Molecular Docking of Chalcone Derivatives as Potential Anticancer Agents
Authors: Abosalim Heba M. , Nael Manal A. , El‐Moselhy Tarek F.
Published: January 2021

Twenty derivatives of chalcones were synthesized and their anticancer activities were estimated against both breast and liver cancer besides two human normal cell lines. Out of our candidates, there were five compounds 3 b, 3 d, 3 h, 7 and 10 b that revealed a broad superlative antitumor activity against both HepG2 and MCF7 cell lines. Surprisingly, 3 h showed the most powerful anticancer activity (GI50=5.43±0.170 μM for MCF7 and GI50=1.80±0.50 μM for HepG2) and displayed the most effective inhibition activity on tubulin with IC50=4.51±0.13 μM. 3 h exerted low toxicity toward both normal human, Hs371.T and AML12, cell lines. 3 h revealed arrest of cell cycle at G2/M and induced apoptosis compared to control cells. Docking study of all newly derivatives was achieved to decide the preeminent binding mode. Generally, the outcome of the docking study showed that 3 h had better binding mode.
Copper(I) Complex of Dihydro Bis(2‐Mercapto Benzimidazolyl) Borate as an Efficient Homogeneous Catalyst for the Synthesis of 2H‐Indazoles and 5‐Substituted 1H‐Tetrazoles
Authors: Khalili Dariush , Evazi Roya , Neshat Abdollah , Aboonajmi Jasem
Published: January 2021

In this work, catalytic activity of a series of copper(I) complexes containing dihydrobis(2‐mercapto‐benzimidazolyl) borate (Bb), and phosphine co‐ligands was investigated in the synthesis of N‐heterocycle compounds including 2H‐indazoles and 5‐substituted 1H‐tetrazoles. The copper(I) complex containing tricyclohexylphosphine co‐ligand, [Cu(Bb)(PCy3)], displayed the highest catalytic activities for the formation of 2H‐indazoles and 1H‐tetrazoles. Apart from the nontoxicity and strong σ‐donating ability of the introduced ligands, the introduced catalyst required easy handling processes. The catalytic reactions were successfully performed at low catalyst loadings in either PEG‐200 or DMF and in relatively short reaction times. The diversity of these reactions was also explored with 20 and 12 examples. Finally, the current catalytic system is amenable to large‐scale production of these N‐heterocycle compounds.
Elaeocarpus Ganitrus Structured Mesoporous Hybrid Mn3+/4+ loaded Zirconia Self Assembly as a Versatile Amperometric Probe for the Electrochemical Detection of Nitrite
Authors: Gangadharappa Manjushree Somashettihalli , Raghu Madihalli Srinivas , Kumar Sandeep , Parashuram Lakshminarayana , Kumar Velu Udaya
Published: January 2021

Selective and highly sensitive detection of nitrite is always a challenge for electrochemist for the administration of nitrite in water and food samples. In this regard nanostructured materials are crown choice. In the present investigation, we have prepared uniformly ordered hybrid Mn3+/4+ : ZrO2 nanoganitrus via hydrothermal method, characterized by XRD, BET, SEM, TEM and XPS to understand the structural and morphological features of the material and used for the electrocatalytic determination of nitrite. The preparation process resulted in the formation of nanoganitrus heterostructures with honeycomb arrangement. High surface area, ganitrus structure and hybrid Mn3+/4+ in the material was correlated to its robust electrochemical performance. Thus, prepared sensor showed highly selective and sensitive determination of nitrite with a good linear range of 250 μM to 10,000 μM with correlation coefficient of 0.998 and a sensitivity of 38.8 μAmM−1 cm−2. The limit of Detection of nitrite sensing system was 93 μM at a signal to noise ratio of 3. Also, the sensor showed prominent reproducibility, good stability, anti‐interference performance and also the prepared sensor was successfully used for the detection of nitrite in real samples.
The Same Oxidation‐State Introduction of Hypervalent Sulfur via Transition‐Metal Catalysis
Authors: Wang Ming , Jiang Xuefeng
Published: January 2021

Sulfonyl compounds have attracted considerable interest due to their extensive applications in drug discovery, agricultural, and material science. The access to the assembly of SO2‐containing compounds via the same oxidative‐state introduction of hypervalent sulfur has come to the fore in the recent years. Especially, the transition‐metal‐involved synthesis of hypervalent sulfur compounds is the most effective strategy since SO2 is easy to insert into the metal‐carbon bonds. This review discusses the application of the same oxidation‐state introduction of hypervalent sulfur strategy under the transition‐metal‐catalyzed conditions, and presents according to different metal catalysts and the synthesized diversity hypervalent sulfur‐containing compounds skeletons, including sulfonamides, sulfones, sulfinamides, sulfonyl acids and sulfonyl fluorides.
Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis
Authors: Schulz Emmanuelle
Published: January 2021

Since the discovery of their extraordinary reactivity in the hydrolytic kinetic resolution of terminal epoxides about twenty years ago, chiral cobalt‐salen complexes have been shown to be essential for many other asymmetric catalytic reactions. This account summarizes the inspiring works dedicated to the discovery of their new reactivity and their mode of action, as well as the new processes towards the optimization of their cooperativity for bimetallic activation and the implementation of their effective immobilization, including also our contribution on these topics.
A Laplacian SVM Based Semi‐Supervised Classification Using Multi‐Local Linear Model
Authors: Ren Yanni , Zhu Huilin , Tian Yanling , Hu Jinglu
Published: January 2021

Semi‐supervised learning considers a classification problem of learning from both labeled and unlabeled data. This paper proposes a semi‐supervised classification method, in which the potential separation boundary is detected and its information is ingeniously incorporated into a Laplacian support vector machine (LapSVM) in both kernel level and graph level. By applying a pseudo‐labeling approach, the input space is first divided into several linear separable partitions along the potential separation boundary. A multi‐local linear model is then built for the separation boundary, by interpolating multiple local linear models assigned to the local linear separable partitions. The multi‐local linear model is further formulated into a linear regression form with a new input vector in the spanned feature space, which contains the information of potential separation boundary. Then the linear parameters are estimated globally by a LapSVM algorithm. Furthermore, the input in the spanned feature space and pseudo labels are used to construct a label guided graph. Numerical experiments on various real‐world datasets and visual representation on toy example exhibit the effectiveness of the proposed method. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Enhanced anticancer potency of hydroxytyrosol and curcumin by PLGA‐PAA nano‐encapsulation on PANC‐1 pancreatic cancer cell line
Authors: Jadid Mahdieh Farhoudi Sefidan , Shademan Behrouz , Chavoshi Reza , Seyyedsani Nasrin , Aghaei Elnaz , Taheri Elham , Goleij Pouya , Hajazimian Saba , Karamad Vahidreza , Behroozi Javad , Sabet Mehrdad Nasrollahzadeh , Isazadeh Alireza , Baradaran Behzad
Published: January 2021

Many chemotherapeutic regimens have been investigated for advanced unresectable and metastatic pancreatic cancer (PC), but with only minimal improvement in survival and prognosis. Here, we investigated anti‐cancer function of free and nano‐encapsulated hydroxytyrosol (Hyd) and curcumin (Cur), and its combinations (Hyd‐Cur) on PANC‐1 cell line. The poly lactide‐co‐glycolide‐co‐polyacrylic acid (PLGA‐co‐PAA) nano‐encapsulated Hyd and Cur were synthesized, and MTT assay was performed to evaluate cytotoxic effects of free and nano‐encapsulated Hyd, Cur, and Hyd‐Cur. Effects of free and nano‐encapsulated Hyd, Cur, and Hyd‐Cur were evaluated on viability, migration, morphological alterations, colony formation, and apoptosis on PANC‐1 cells. We observed that free and nano‐encapsulated Hyd, Cur, and Hyd‐Cur significantly increased apoptosis rates as well as significantly decreased viability, migration, and colony formation in PANC‐1 cells. According to our results, Hyd‐Cur combination and nano‐encapsulation therapy exerts more profound apoptotic and anti‐proliferative effects on PANC‐1 cells than free Hyd or Hyd monotherapy.
David John Calvert
Authors: Campbell Edward G.
Published: January 2021

Throughout his professional career, he did his utmost to ensure that his patients and their owners received the very best care.
Quantitative analysis of zirconium alloys using borate fusion and wavelength dispersive X‐ray fluorescence spectrometry
Authors: Sieber John , Marlow Anthony , Paul Rick , Barber Charles , Wood Laura , Yu Lee , Rieke Alaina , Carl Raymond , Kutnerian Amy , McCandless Jessica , Wallace Candace
Published: January 2021

The National Institute of Standards and Technology uses borate fusion, wavelength dispersive X‐ray fluorescence (WDXRF) spectrometry and synthetic calibration standards for high performance, quantitative analyses of alloys reacted and partially dissolved for fusion into borate beads. Conversion from metal matrix to low Z glass preserves measurement sensitivity. Synthetic calibration standards closely match fused samples, yielding very low uncertainties in results. This approach was applied to zirconium alloys of ≥90% Zr and 17 elements: Al, Co, Cr, Cu, Fe, Hf, Mn, Mo, Nb, Ni, P, Pb, Sn, Ta, Ti, V, and W. To demonstrate capabilities, it was applied to Standard Reference Material (SRM) 360b Zirconium (Sn‐Fe‐Cr) Alloy, renewal SRM 360c, plus discontinued Zr alloy SRMs: 360, 360a, 1210 through 1215, and 1234 through 1239. Eleven elements exhibit biases ≤5% for these SRMs. Additional validation used comparative test methods of inductively coupled plasma (ICP) mass spectrometry, ICP optical emission spectrometry and prompt gamma‐ray activation analysis. This WDXRF method gives results of high enough quality to certify the valid elements in conjunction with results from one or more independent methods. Several phenomena complicate the approach. Normal Zr dissolution using HNO3 + HF, forms Zr(NO3)4 in solution and concentrates it on drying. Zr(NO3)4 sublimes at low temperatures, causing uncontrolled loss of Zr as the temperature exceeds 100°C. Rapidly heated Zr(NO3)4 may explode. Digestion with HF alone works well. High‐purity ZrO2 and LiF were used for matrix matching of calibration standards, requiring determinations of trace elements in the high‐purity ZrO2.
Succession Planning Governance Case
Authors: Hilb Martin
Published: January 2021

Michael Miller is the founder of a successful international high-tech company in the medical field. The total staff includes 3500 employees, 90% of which are outside Switzerland.

Miller’s company was successful in acquiring Phamtex International, another family-owned company. Miller offered the CEO position for the new merged company to John Kennedy who was the successful former CEO of Phamtex International.

Suddenly Michael Miller realized that he had no successor for John Kennedy in case of his leave.
Governance of Gender Diversity Case
Authors: Dart Beatrix
Published: January 2021

Gender diversity on boards has become accepted as an important step to increase governance, risk assessment, and innovative thinking for companies. However, the arguments of finding merit-based candidates, a narrow definition of the board skills matrix, and the desire to add “who you know” have proven to be lasting obstacles for many female board candidates. This short case highlights the importance of making a conscious effort to expanding board searches past the usual networks to lead to boards with better decision-making abilities by adding female board directors.
University Governance Case
Authors: Maxwell Tudor , Bianchini Stefano
Published: January 2021

This case addresses the challenge of leadership succession in a highly respected master’s program at a university in Australia. The director, who was also the program’s lead professor, was due to retire, and the distinctive nature of the program made it particularly difficult to find a suitable replacement. To complicate the challenge, the university’s central administration was not supportive of that master’s degree, whereas it achieved the highest satisfaction ratings in the university from students and enjoyed good support from industry; the director’s insistence on quality of educational experience resulted in tight control of student admission, fewer students, and lower revenue than competing programs.

A highly engaged group of students and alumni took on this challenge, working with the outgoing director to sustain impressive results over a 5-year period.
NPO Governance Case
Authors: Felício J. Augusto , Rodrigues Ricardo
Published: January 2021

Social organizations play a very important role in ensuring social cohesion and well-being, but constraints on public expenditure mean fiercer competition for financial resources and greater difficulties in accessing these resources.

This case study is focused on CAJIL, a nonprofit social organization that, in this demanding context, is implementing a large-scale investment project. For this reason, CAJIL needs to reinforce the governance structure to assure investors and the implicated public institutions that CAJIL is capable of completing the project and responding to the management challenges associated with the increase in activity and complexity linked to this investment.
M&A Governance Case
Authors: Hilb Martin
Published: January 2021

M-Tec is a high-tech computer company based in Geneva, Switzerland. Its shares have traded at values consistently higher than the listing price.

The recent acquisition of a rival business of equal size resulted in an additional, positive movement in the share price.

Despite the positive performance, however, a major challenge has arised at the board level.

Three directors opposed the acquisition based on their conviction that the purchase price was too high.
Board of Directors as a Strategic Sparring Partner
Authors: Lombriser Roman
Published: January 2021

What role can board of directors play in the strategy process of an SME? The case of “Light-Tech” (a luxury lamp producer) shows how. The chairman and several of the other directors had bad feelings about the issue of technology replacement. Contrary to the top management team, they were not convinced that the breakthrough of the new LED technology in the market was still far away. To address this issue, the board of directors—together with the executive team—performed a scenario analysis for about 3 hours. Then, the board requested the top management team to formulate a precautionary strategy which much better prepares the SME for the pessimistic scenario. Result: 2 years later, the pessimistic scenario reveals itself as reality. By performing a scenario analysis together with the top management team, the board of directors were able to play an important role as constructive sparring partners.
Arthroscopic lateral retinacular release improves patello-femoral and femoro-tibial kinematics in patients with isolated lateral retinacular tightness
Authors: Pohlig Florian , Lenze Ulrich , Lenze Florian Walter , Lazic Igor , Haug Alexander , Hinterwimmer Stefan , Graichen Heiko , von Eisenhart-Rothe Ruediger
Published: January 2021

Purpose

Arthroscopic lateral retinacular release (LRR) has long been considered the gold standard for the treatment for anterior knee pain caused by lateral retinacular tightness (LRT). However, one-third of patients experience continuous pain postoperatively, which is thought to be related to persistent maltracking of the patella and altered femoro-tibial kinematics. Therefore, the aim of the present study was to simultaneously assess femoro-tibial and patello-femoral kinematics and identify the influence of arthroscopic LRR.

Methods

Sixteen healthy volunteers and 12 patients with unilateral, isolated LRT were prospectively included. Open MRI scans with and without isometric quadriceps contraction were performed in 0°, 30° and 90° of knee flexion preoperatively and at 12 months after surgery. Patellar shift, tilt angle, patello-femoral contact area and magnitude of femoro-tibial rotation were calculated by digital image processing.

Results

Postoperatively, patellar shift was significantly reduced at 90° of knee flexion compared to preoperative values. The postoperative patellar tilt angle was found to be significantly smaller at 30° of knee flexion compared to that preoperatively. Isometric muscle contractions did not considerably influence patellar shift or tilt in either group. The patello-femoral contact area increased after LRR over the full range of motion (ROM), with significant changes at 0° and 90°. Regarding femoro-tibial kinematics, significantly increased femoral internal rotation at 0° was observed in the patient group preoperatively, whereas the magnitude of rotation at 90° of knee flexion was comparable to that of healthy individuals. The pathologically increased femoral internal rotation at 30° without muscular activity could be significantly decreased by LRR. With isometric quadriceps contraction no considerable improvement of femoral internal rotation could be achieved by LRR at 30° of knee flexion.

Conclusions

Patello-femoral and femoro-tibial joint kinematics could be improved, making LRR a viable surgical option in carefully selected patients with isolated LRT. However, pathologically increased femoral internal rotation during early knee flexion remained unaffected by LRR and thus potentially accounts for persistent pain.

Level of evidence

II.
Low-frequency variability of the Pacific Subtropical Cells as reproduced by coupled models and ocean reanalyses
Authors: Graffino Giorgio , Farneti Riccardo , Kucharski Fred
Published: January 2021

Low-frequency variability of the Pacific Subtropical Cells (STCs) is investigated using outputs from several models included in the two latest phases of Coupled Model Intercomparison Project (CMIP), CMIP5 and CMIP6, as well as ocean reanalysis products. Our analysis focuses on historical simulations and an idealised future scenario integration. Mass and heat transport diagnostics are employed to assess how coupled models and ocean reanalyses reproduce Pacific STCs total and interior transport convergence at the equator and their relationship with equatorial Pacific sea surface temperature (SST). Trends of mass and heat transport are also evaluated, in order to study how the STCs are expected to change in a warming climate. A large spread is obtained across models in simulated mass transports, confirming that coupled models do not agree on reproducing observed Pacific STCs dynamics, with very limited improvement by CMIP6 models. Compared to ocean reanalysis products, coupled models tend to underestimate the STCs interior transport convergence, and are less efficient on propagating the signal generated by the subtropical wind stress towards the equator. Also, mass transport obtained from ocean reanalyses exhibit larger variability, and these products also better reproduce the STCs-SST relationship. Future scenario simulations suggest a weakening (strengthening) of the heat transport by the North (South) Pacific cell under warmer conditions, with a general agreement across models. Equatorward mass transport trends do not confirm this for total and interior components, but they do for the western boundary component.