bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat filtering drives the local distribution of congeneric species in a Brazilian white‐sand flooded tropical forest
Authors: Ribeiro Kelly F. O. , Martins Valéria F. , Wiegand Thorsten , Santos Flavio A. M.
Published: January 2021

The investigation of ecological processes that maintain species coexistence is revealing in naturally disturbed environments such as the white‐sand tropical forest, which is subject to periodic flooding that might pose strong habitat filtering to tree species. Congeneric species are a good model to investigate the relative importance of ecological processes that maintain high species diversity because they tend to exploit the same limiting resources and/or have similar tolerance limits to the same environmental conditions due to their close phylogenetic relationship. We aim to find evidence for the action and relative importance of different processes hypothesized to maintain species coexistence in a white‐sand flooded forest in Brazil, taking advantage of data on the detailed spatial structure of populations of congeneric species. Individuals of three Myrcia species were tagged, mapped, and measured for diameter at soil height in a 1‐ha plot. We also sampled seven environmental variables in the plot. We employed several spatial point process models to investigate the possible action of habitat filtering, interspecific competition, and dispersal limitation. Habitat filtering was the most important process driving the local distribution of the three Myrcia species, as they showed associations, albeit of different strength, to environmental variables related to flooding. We did not detect spatial patterns, such as spatial segregation and smaller size of nearby neighbors, that would be consistent with interspecific competition among the three congeneric species and other co‐occurring species. Even though congeners were spatially independent, they responded to differences in the environment. Last, dispersal limitation only led to spatial associations of different size classes for one of the species. Given that white‐sand flooded forests are highly threatened in Brazil, the preservation of their different habitats is of utmost importance to the maintenance of high species richness, as flooding drives the distribution of species in the community.
A critical comparison of integral projection and matrix projection models for demographic analysis
Authors: Doak Daniel F. , Waddle Ellen , Langendorf Ryan E. , Louthan Allison M. , Isabelle Chardon Nathalie , Dibner Reilly R. , Keinath Douglas A. , Lombardi Elizabeth , Steenbock Christopher , Shriver Robert K. , Linares Cristina , Begoña Garcia Maria , Funk W. Chris , Fitzpatrick Sarah W. , Morris William F. , DeMarche Megan L.
Published: January 2021

Structured demographic models are among the most common and useful tools in population biology. However, the introduction of integral projection models (IPMs) has caused a profound shift in the way many demographic models are conceptualized. Some researchers have argued that IPMs, by explicitly representing demographic processes as continuous functions of state variables such as size, are more statistically efficient, biologically realistic, and accurate than classic matrix projection models, calling into question the usefulness of the many studies based on matrix models. Here, we evaluate how IPMs and matrix models differ, as well as the extent to which these differences matter for estimation of key model outputs, including population growth rates, sensitivity patterns, and life spans. First, we detail the steps in constructing and using each type of model. Second, we present a review of published demographic models, concentrating on size‐based studies, which shows significant overlap in the way IPMs and matrix models are constructed and analyzed. Third, to assess the impact of various modeling decisions on demographic predictions, we ran a series of simulations based on size‐based demographic data sets for five biologically diverse species. We found little evidence that discrete vital rate estimation is less accurate than continuous functions across a wide range of sample sizes or size classes (equivalently bin numbers or mesh points). Most model outputs quickly converged with modest class numbers (≥10), regardless of most other modeling decisions. Another surprising result was that the most commonly used method to discretize growth rates for IPM analyses can introduce substantial error into model outputs. Finally, we show that empirical sample sizes generally matter more than modeling approach for the accuracy of demographic outputs. Based on these results, we provide specific recommendations to those constructing and evaluating structured population models. Both our literature review and simulations question the treatment of IPMs as a clearly distinct modeling approach or one that is inherently more accurate than classic matrix models. Importantly, this suggests that matrix models, representing the vast majority of past demographic analyses available for comparative and conservation work, continue to be useful and important sources of demographic information.
Biomedical Hydrogels Fabricated Using Diels–Alder Crosslinking
Authors: Cadamuro Francesca , Russo Laura , Nicotra Francesco
Published: January 2021

The Diels–Alder (DA) cycloaddition is one of the best methods for biomaterials conjugation to generate tools for biomedical applications. It is a biocompatible one‐step reaction, exploiting functional groups absent in natural biopolymers, doesn't require catalysts, and doesn't generate side products, an ideal “click reaction”. In this review we provide an overview on the recent examples in which the DA cycloaddition has been exploited in nanomedicine. Nanoparticles for drug delivery or diagnosis, and nanostructured biomaterials for regenerative medicine, have been efficiently generated exploiting the DA reaction to crosslink the polymeric components, in order to obtain nanoparticles or scaffolds with the required chemical and morphological properties, and to conjugate targeting agents or signalling molecules.
Syntheses and Applications of Spirocyclopropyl Oxindoles: A Decade Review
Authors: Sakla Akash P. , Kansal Pritish , Shankaraiah Nagula
Published: January 2021

Spirocyclopropyl oxindole represents an emerging framework by unique amalgamation of versatile 2‐oxindole motif and highly strained cyclopropane unit. This scaffold is remarkable for its diverse medicinal and synthetic applications. The present review delivers a comprehensive overview of the strategies to afford spirocyclopropyl oxindoles and their potential synthetic transformations. The syntheses of spirocyclopropyl oxindoles have been described based on the type of precursors, including isatin, 3‐alkenyl oxindole, diazooxindole, oxindole, and 3‐chlorooxindole. Besides, the utility of different cyclopropanation reagents like sulfur ylide, MBH‐carbonate, carbenoid, vinyl selenone, etc. have also been emphasized. Furthermore, various ring‐expansion/opening reactions of spirocyclopropane oxindoles using dipolarophiles/nucleophiles have critically been illustrated.
Expedient Synthesis of 2‐Iminothiazolidines via Telescoping Reactions Including Iron‐Catalyzed Nitrene Transfer and Domino Ring‐Opening Cyclization (DROC)
Authors: Coin Guillaume , de Ferrier de Montal Oriane , Dubourdeaux Patrick , Latour Jean‐Marc
Published: January 2021

2‐iminothiazolidines are important scaffold for pharmaceutical drugs. Herein, we describe a fast and easy procedure for their synthesis by a telescoping reaction integrating an iron‐catalyzed nitrene transfer under mild conditions. The aziridination reaction of olefins is followed by the domino ring‐opening cyclization (DROC) of the aziridine intermediates with organic isothiocyanates catalyzed by a Lewis acid leading to the desired product. This new synthetic route allows time, step and purification economies, which is in agreement with the development of more efficient processes for the synthesis of small molecules.
A One‐Pot Two‐Step Enzymatic Pathway for the Synthesis of Enantiomerically Enriched Vicinal Diols
Authors: Giovannini Pier Paolo , Müller Michel , Presini Francesco , Baraldi Serena , Ragno Daniele , Di Carmine Graziano , Jacoby Christian , Bernacchia Giovanni , Bortolini Olga
Published: January 2021

Enantiomerically enriched 1,2‐diols are prominent compounds that find numerous applications in organic chemistry. They are privileged building blocks for the synthesis of APIs (Active Pharmaceutical Ingredients), broadly used as chiral ligands in asymmetric catalysis, and efficient auxiliaries employed to control the stereochemical outcome of total synthesis. Among the number of strategies developed for the preparation of these molecules, enzyme mediated reactions have gained a crucial role in the toolbox of organic chemists for their high efficiency and sustainability. Herein we describe a one‐pot two‐step protocol designed by combining a thiamine diphosphate (ThDP)‐dependent lyase and a NADH‐dependent reductase. The ThDP‐dependent acetoin:dichlorophenolindophenol oxidoreductase (Ao : DCPIP OR) is exploited to produce enantioenriched α‐hydroxyketones through the benzoin‐type condensation of methylacetoin with either aldehydes or activated ketones. The enantioenriched α‐hydroxyketones undergo the selective reduction into the corresponding 1,2‐diols in the same reaction mixture due to the addition of NAD+ and of the NADH‐dependent acetylacetoin reductase (AAR). Sodium formate was selected as the sacrificial reductive reactant to generate and recycle in situ the precious NADH by formate‐dehydrogenase. Unprecedented reported details on the cloning and expression of the AAR are reported as well.
Copper‐Catalyzed Three‐Component Reactions of 2‐Iodo‐2,2‐difluoroacetophenones, Alkynes, and Trimethylsilyl Cyanide
Authors: Wu Pingjie , Zheng Cheng , Wang Xia , Wu Jingjing , Wu Fanhong
Published: January 2021

A Cu(I)‐catalyzed three‐component reaction of 2‐iodo‐2,2‐difluoroacetophenones, alkynes, and TMSCN is described. The reaction provided a facile method for the synthesis of difluoroacyl‐substituted nitriles, which might be served as potentially useful fluoroorganic intermediates for further transformation in drug discovery. This method has broad substrate scope, good efficiency, and excellent stereoselectivity. Preliminary mechanistic investigation indicated that a radical‐mediated process was involved in this cyanodifluoroalkylation reaction.
Shedding light on CO2: Catalytic synthesis of solar methanol
Authors: Zhang Zeshu , Ding Xue , Yang Xiangguang , Tu Wenguang , Wang Lu , Zou Zhigang
Published: January 2021

The ever‐increasing carbon footprint has resulted in significant environmental impacts. The solar‐driven conversion of CO2 to methanol is an effective solution to the global energy shortage and the current greenhouse gas issue. This critical review presents a comprehensive overview of the recent research progress in the solar‐driven catalytic synthesis of methanol from CO2 and briefly outlines the relationships among the traditional photocatalysis, photoelectrocatalysis, and photothermal catalysis. The unique strategies for the design of catalysts are summarized and discussed. Finally, this review emphasizes the crucial issues that should be addressed in the field of photocatalysis.

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An immersed boundary method with y+‐adaptive wall function for smooth wall shear
Authors: Xu Yuncheng , Liu Xiaofeng
Published: January 2021

Immersed boundary (IB) method with a wall function for high Reynolds number flows is attractive when the boundary is complex and evolving. However, when combined with IB method, existing wall functions cannot produce smooth wall shear stress, which is important for many processes such as erosion. The root cause is the discontinuity between the log‐law and laminar layers in most wall functions. A wall function in IB methods is typically enforced through IB cells. However, for complex and evolving boundaries, IB cells can be located in either the log‐law layer or the laminar layer, which follow different laws. To remedy this, a new method is introduced with a y+‐adaptive strategy. The idea is that when an IB cell is too close to an IB, it is replaced by a neighboring fluid cell further away from the boundary. Consequently, all IB cells are in the log‐law layer. The resulting wall shear stress is much smoother. This adaptive strategy is a compromise between how accurate the location of an IB wall is represented and the smoothness of simulated wall shear. Example cases in 1D, 2D, and 3D show the y+‐adaptive wall function produces results compared well with theory and experiments.
Mono‐Gold(I)‐Catalyzed Enantioselective Intermolecular Reaction of Ynones with Styrenes: Tandem Diels–Alder and Ene Sequence
Authors: Nanko Masaki , Inaba Yuya , Sekine Keisuke , Mikami Koichi
Published: January 2021

Gold‐catalyzed intermolecular reaction leading to dihydronaphthalene derivatives in one pot from two equivalents of ynones with respect to styrene is uncovered. The [4+2] Diels–Alder cycloaddition of ynones and styrenes is catalyzed by a mono‐gold(I) complex and the conjugated acid to provide an unstable 3,8a‐dihydronaphthalene to subsequently undergo an intermolecular ene‐type reaction with the π‐activated ynone to afford multi‐component coupling dihydronaphthalene products. Linear relationships between chiral ligand‐gold complexes and chiral dihydronaphthalene products proves mono‐gold catalysis that triggers an asymmetric tandem Diels–Alder and ene reaction sequence.
Facile C−F Bond Activation Approach to FAMT‐Based Difluoromethyl‐BNCT Drug Candidates
Authors: Yokawa Akitaka , Hatanaka Miho , Mikami Koichi
Published: January 2021

Lithium 1,3‐bis(2,6‐diisopropylphenyl)‐1,3,2‐diazaborolidinyl‐2‐uide activates the C−F linkage of fluoroform (CF3H) to provide air‐stable difluoromethylborane compounds. Computational analysis of SN2‐type transition state for the C−F bond activation of fluoroform with boryllithium clarifies the mechanism involving the lithium dimeric species in the pre‐reaction complex. FAMT (=3‐fluoro‐l‐α‐methyl‐tyrosine)‐based difluoromethyl‐BNCT (boron neutron capture therapy) drug candidates is thus produced by the present C−F bond activation.
Estimating snow water equivalent using cosmic‐ray neutron sensors from the COSMOS‐UK network
Authors: Wallbank John R. , Cole Steven J. , Moore Robert J. , Anderson Seonaid R. , Mellor Edward J.
Published: January 2021

The intensity of cosmic ray neutrons is inversely correlated with the amount of water present in the surrounding environment. This effect is already employed by around 50 neutron sensors in the COSMOS‐UK network to provide daily estimates of soil moisture across the UK. Here, these same sensors are used to automatically provide estimates of snow water equivalent (SWE). Lying snow is typically ephemeral and of shallow depth for most parts of the UK. Moreover, soil moisture is usually high and variable, which acts to increase uncertainties in the SWE estimate. Nevertheless, even under such challenging conditions, both above ground and buried cosmic ray neutron sensors are still able to produce potentially useful SWE estimates. Triple collocation analysis suggests typical uncertainties of less than around 4 mm under UK snow conditions.
Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study
Authors: Byrd Doratha A. , Vogtmann Emily , Wu Zeni , Han Yongli , Wan Yunhu , Clegg‐Lamptey Joe‐Nat , Yarney Joel , Wiafe‐Addai Beatrice , Wiafe Seth , Awuah Baffour , Ansong Daniel , Nyarko Kofi , Hullings Autumn G. , Hua Xing , Ahearn Thomas , Goedert James J. , Shi Jianxin , Knight Rob , Figueroa Jonine D. , Brinton Louise A. , Garcia‐Closas Montserrat , Sinha Rashmi
Published: January 2021

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case‐control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population‐based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray‐Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13‐0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen‐conjugating and immune‐related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially‐mediated mechanisms of breast disease.
Reconciling the irreconcilable (talfeeq): The case of currency salam
Authors: Siddique Muhammad Zahid , Siddique Muhammad Abubakar
Published: January 2021

Currency salam is a financial product in the basket of Islamic finance that facilitates dealings in discounting of bills. Moreover, it allows provision for speculative future currency trading. This article shows that currency salam is prohibited in the light of Islamic rules of riba. Researchers have held three positions about modern currencies. The paper shows that the permissibility of currency salam is derived by combining together these three irreconcilable views about modern currencies. In other words, currency salam is the outcome of a fallacious methodology known as talfeeq which is merely a device of creating legal artifices (hiyal) for satisfying one's desires. It is argued that the permission of currency salam must be rejected because it is riba and it opens up the flood‐gate for financial speculations in the name of Islam. The paper also attempts to draw attention of the regulatory authorities to tackle this issue seriously as it will adversely affect the trust on Islamic banking regarding its Shariah compliance.
The relationship and optimal threshold of endometrial thickness with early clinical pregnancy in frozen embryo transfer cycles
Authors: Zhang Qian , Li Zhishu , Wang Yinghua , Lu Haiou , Yu Yuexin
Published: January 2021

Objective

To investigate the associations of endometrial thickness with pregnancy outcome in frozen embryo transfer (FET) cycles.

Methods

A retrospective cohort study was performed looking at 1627 FET cycles from the Reproductive Medicine Center of the study hospital between January 2017 and July 2018. Endometrial ultrasonographic characteristics were recorded on the embryo transfer day in FET cycles.

Results

A total of 1627 FET cycles were included. The endometrial thickness was independently associated with clinical pregnancy outcomes after adjusting for potential confounders (odds ratio 1.06; 95% confidence interval [CI] 1.01–1.12). A non‐linear relationship was detected between endometrial thickness and pregnancy outcomes, whose point was 10.9 mm. The effect size of the left and right sides of the inflection point were 1.16 (95% CI 1.07–1.25) and 0.89 (95% CI 0.78–1.01), respectively. Subgroup analysis showed that the correlation between endometrial thickness and pregnancy outcome was consistent in all subgroups.

Conclusion

The relationship between endometrial thickness and pregnancy outcome was non‐linear and there is an inflection point. When endometrial thickness was less than 9.5 mm, it was positively related to clinical pregnancy rate. If it was beyond the inflection point, the pregnancy rate does not increase significantly.
Quazepam: Hypnotic Efficacy and Side Effects
Authors: Kales Anthony
Published: January 2021

Quazepam is a benzodiazepine hypnotic that can be useful in the adjunctive pharmacologic treatment of insomnia. It is slowly eliminated due to the long elimination half‐lives of the parent compound and its two active metabolites, 2‐oxoqua‐zepam and N‐desalkyl‐2‐oxoquazepam. This drug is recommended in doses of 15 mg for adults and 7.5 mg for geriatric patients. Sleep laboratory studies and clinical trials have shown that the 15 mg dose is quite efficacious for inducing and maintaining sleep not only with initial and short‐term use but also with continued use. The 7.5 mg dose which has been studied less extensively has also been shown to be effective for inducing and maintaining sleep. There is considerable evidence of carryover effectiveness both during drug administration and after withdrawal. Thus, rebound phenomena are not observed during administration (early morning insomnia and daytime anxiety) and after withdrawal (rebound insomnia). Furthermore, certain behavioral side effects that have occurred with certain benzodiazepines (triazolam) have not been reported with quazepam. The only notable side effect seen with quazepam is a variable degree of daytime sedation, which can be minimized by intermittent use of the 15 mg dose when necessary and use of the 7.5 mg dose in the elderly. In comparison to triazolam and temazepam, quazepam is more effective with short‐term use, and with continued use it maintains its efficacy in contrast to both of these drugs which show rapid development of tolerance. Most important, quazepam lacks the frequent and severe side effects increasingly reported with triazolam use or following its withdrawal.
The role of AMP‐activated protein kinase α1‐mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho
Authors: Chen Cheng , Wu Lin , Xie Caidie , Zhao Xiufen , Mao Huijuan , Xing Changying
Published: January 2021

Recently, the Klotho protein (Klotho) has received substantial attention as protective factor against cardiovascular complications of chronic kidney disease (CKD). However, the direct effect and mechanism of Klotho on endothelial cells injury are not well‐known. In this study, we incubated human vein umbilical endothelial cells (HUVECs) with uremic toxin indoxyl sulfate (IS) to mimic CKD internal environment and investigated the direct effect of Klotho on the HUVECs injury induced by IS and to explore the mechanism in this process. We found IS inhibited cell viability, increased endoplasmic reticulum stress, and mediated apoptosis of HUVECs. Treatment with Klotho significantly attenuated IS‐induced above effects. Furthermore, Klotho alleviated the IS toxic effect on HUVECs via promoting AMP‐activated protein kinase (AMPK) α1 phosphorylation instead of directly upregulating AMPKα1, which could be partly blocked by AMPK pathway inhibitor‐Compound C. In addition, Klotho also inhibited intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) expression induced by IS. Altogether, these results indicated that Klotho can protect HUVECs from IS‐induced injury by alleviating AMPKα1‐mediated endoplasmic reticulum stress.
Alternative human eIF5A protein isoform plays a critical role in mitochondria
Authors: Pereira Karina D. , Tamborlin Letícia , de Lima Tanes I. , Consonni Silvio R. , Silveira Leonardo R. , Luchessi Augusto D.
Published: January 2021

The eukaryotic translation initiation factor 5A (eIF5A) is the only known protein containing the amino acid residue hypusine, essential for its activity. Hypusine residue is produced by a posttranslational modification involving deoxyhypusine synthetase and deoxyhypusine hydroxylase. Herein, we aimed to describe the role of the alternative human isoform A on mitochondrial processes. Isoform A depletion modulates oxidative metabolism in association with the downregulation of mitochondrial biogenesis‐related genes. Through positive feedback, it increases cell respiration leading to highly reactive oxygen species production, which impacts mitochondrial bioenergetics. These metabolic changes compromise mitochondrial morphology, increasing its electron density and fission, observed by transmission electron microscopy. This set of changes leads the cells to apoptosis, evidenced by increased DNA fragmentation and proapoptotic BAK protein content increase. Thus, we show that the alternative eIF5A isoform A is crucial for energy metabolism controlled by mitochondria and cellular survival.
Estimations of FH···X hydrogen bond energies from IR intensities: Iogansen's rule revisited
Authors: Tupikina Elena Yu. , M. Tolstoy Peter , A. Titova Anna , A. Kostin Mikhail , S. Denisov Gleb
Published: January 2021

In this work the possibility of using the IR intensity of the stretching vibration νs of proton donor group for estimation of hydrogen bond strength was investigated. For a set of complexes with FH···X (X = F, N, O) hydrogen bonds in the wide range of energies (0.1–49.2 kcal/mol) vibrational frequencies νs and their intensities A were calculated (CCSD at complete basis set limit). The validity of the previously proposed linear proportionality between the intensification of the stretching vibration νs in IR spectra and hydrogen bond enthalpy –ΔH = 12.2 (A. V. Iogansen, Spectrochimica Acta A 1999) was examined. It is shown that for a range of similar hydrogen bond types with complexation energies ∆E <15 kcal/mol the ∆E() function remains similar to that proposed in the Iogansen's work, while upon strengthening this dependency becomes significantly nonlinear. We examined two other parameters ( and ) related to IR intensity as descriptors of hydrogen bond strength which are proportional to transition dipole moment matrix element and mass‐independent dipole moment derivative. It was found that the dependency ∆E() stays linear in the whole studied range of complexation energies and it can be used for evaluation of ∆E from infrared spectral data with the accuracy about 2 kcal/mol. The mass‐independent product is an appropriate descriptor for sets of complexes with various hydrogen bond types. Simple equations proposed in this work can be used for estimations of hydrogen bond strength in various systems, where experimental thermodynamic methods or direct calculations are difficult or even impossible.
GC–MS of some lycorine‐type Amaryllidaceae alkaloids
Authors: Berkov Strahil , Torras‐Claveria Laura , Viladomat Francesc , Suárez Sergio , Bastida Jaume
Published: January 2021

The search for novel bioactive compounds and the identification of known ones in the plant kingdom are a challenge for the scientists working in different fields of plant science. In the recent years, mass spectrometry is the most frequently applied method for analysis of complex mixtures of plant metabolites. Twenty‐two alkaloids of different lycorine skeleton subtypes (with a Δ3,4 double bond, with a Δ4,11 double bond, with saturated rings C and D, and with aromatic ring C) were subjected to separation with gas chromatography and studied with electron impact mass spectrometry including single quadropole (GC‐EIMS), tandem mass (GC‐EIMS/MS) and high resolution mass (EI‐HRMS) detectors in order to determine their fragmentation pattern. The compounds showed excellent separation and specific MS fragmentation allowing structural determination. The GC–MS can be successfully applied for searching new and identification of known bioactive molecules, chemotaxonomical and chemoecological studies, among others, within the Amaryllidoideae subfamily.
Molecular characterization of non‐polio enteroviruses isolated from acute flaccid paralysis patients in Uganda
Authors: Tushabe Phionah , Howard Wayne , Bwogi Josephine , Birungi Molly , Eliku James P. , Kakooza Proscovia , Bukenya Henry , Namuwulya Prossy , Gaizi Joseph , Tibanagwa Mayi , Kabaliisa Theopista , Mulindwa Julius , Muhanguzi Dennis , Suchard Melinda , Gumede Nicksy , Bakamutumaho Barnabas
Published: January 2021

Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non‐polio enteroviruses (NPEVs). Specific NPEVs have been described in polio‐like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% wereEnterovirus Band 9% wereEnterovirus Aspecies. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children less than 5 years (77/89; 86.5%) and male patients were more common (54/89; 60.7%). Echovirus 11 (11/89; 12.4%) was frequently observed and phylogenetic analysis of these sequences revealed high diversity. Coxsackievirus B5 (CV‐B5), CV‐B6, E21, and EV‐B69 were only seen in patients with residual paralysis. Analyses of the EV‐A71 sequence indicated a unique genogroup.
Prevention of posttraumatic osteoarthritis at the time of injury: Where are we now, and where are we going?
Authors: Mason Deborah , Englund Martin , Watt Fiona E.
Published: January 2021

This overview of progress made in preventing post‐traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra‐articular or topical interventions, and 5 short‐term intra‐articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%–50%, 20%–70%, and 0%–40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a “whole joint” approach to assessing efficacy, would improve the translation of promising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA. An international workshop addressing this in 2016 considered inclusion criteria and study design, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design and high‐quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field.
Survival Impact of Surgical Resection in Locally Advanced T4b Oral Squamous Cell Carcinoma
Authors: Gangopadhyay Abhishek , Bhatt Supreet , Nandy Kunal , Rai Shreya , Rathod Priyank , Puj Ketul Sureshbhai
Published: January 2021

Objective/Hypothesis

With non‐surgical treatment, T4b oral squamous cell carcinoma (OSCC) have an unacceptably poor prognosis. A subset of patients if selected wisely for surgery, can have significantly improved survival. The present study aims to explore the feasibility of radical resection and neoadjuvant chemotherapy (NACT) in the T4b OSCC and their impact on survival, along with the factors affecting it.

Study Design

This is a retrospective analysis of 302 consecutive patients with T4b OSCC presented at our institute between July 2015 and January 2016.

Methods

Three different treatment protocols were decided depending on the extent of the disease—upfront resection, NACT (followed by surgery or chemo/radiation depending on the response), or upfront non‐surgical treatment (chemotherapy and/or radiotherapy).

Results

Upfront surgery was done in 67 (22.19%) patients and 155 (51.32%) patients received NACT. The rest of the patients received upfront non‐surgical treatment. The overall response rate of NACT was 23.23% and the resectability rate was 36.13%. The median OS for the whole population was 12 months (30 months for the surgical group and 9 months for the non‐surgical group). There was no survival difference between supra versus infra‐notch tumors (P value = .552) or post‐NACT versus upfront surgery (P value = .932). Nodal involvement was the most important poor prognostic factor affecting both DFS (P = .006) and OS (P = .002).

Conclusions

With proper patient selection after thorough clinico‐radiological assessment, a subset of T4b OSCC can be operated with curative intention; either upfront or after downstaging with NACT, which ultimately translates into improved survival.

Level of Evidence

3 Laryngoscope, 131:E2266–E2274, 2021
Investigation of eATRP for a Carboxylic‐Acid‐Functionalized Ionic Liquid Monomer
Authors: Hu Weiling , Xu Lan
Published: January 2021

Electrochemically mediated atom transfer radical polymerization (eATRP) is a promising technique for precise control over polymer molecular weights (MWs), molecular weight distribution (Đ), and complex architectures under low concentrations of copper‐based ATRP catalysts. Herein, eATRP of ionic liquid monomer (ILM), 1‐vinyl‐3‐propionate imidazolium tetrafluoroborate (VPI+BF4−), containing carboxylic acid groups is inquired in aqueous media. In the polymerization process of water‐soluble VPI+BF4−, the protonation and dissociation of catalysts have great influence on the polymerization reaction. Various polymerization parameters, including applied potential (Eapp), pH, degree of polymerization (DP) (from 100 to 300), and the catalyst concentration (from 5 × 10−4 to 1.5 × 10−3 m) are examined. Under certain polymerization conditions, poly(ionic liquids) (PILs) with a well‐controlled MWs and narrow Đ are obtained. The controlled/living property of the polymerization process is reflected by the linear first‐order kinetics, linear increase of MWs with monomer conversion, and the probability of complete reactivation of the polymerization by repetitively altering the Eapp values. This work provides a new perspective for the precise synthesis of PIL‐based block copolymers with adjustable properties; meanwhile, the eATRP of monomer containing carboxylic acid groups is expected to develop functional materials with pH responsiveness and biocompatibility.
TEMPO‐Substituted Poly(ethylene sulfide) for Solid‐State Electro‐Chemical Charge Storage
Authors: Hatakeyama‐Sato Kan , Wakamatsu Hisato , Matsumoto Satoshi , Sadakuni Karin , Matsuoka Koji , Nagatsuka Tomomi , Oyaizu Kenichi
Published: January 2021

A poly(ethylene sulfide) backbone is introduced as the main chain of a radical polymer. Anionic ring‐opening polymerization of an episulfide monomer substituted with 2,2,6,6tetramethylpiperidin1oxyl (TEMPO), a robust nitroxide radical, yields the corresponding polythioether. Compared to the traditional poly(ethylene oxide) backbone, the new polymer shows a lower glass transition temperature (−10 °C), and about threefold higher solid‐state ionic conductivity. The polythioether is also shown to improve the charge/discharge properties of a cathode in solid‐state lithium‐ion batteries.
Exploring Interrater Disagreement on Essential Tremor Using a Standardized Tremor Elements Assessment
Authors: Becktepe Jos , Gövert Felix , Balint Bettina , Schlenstedt Christian , Bhatia Kailash , Elble Rodger , Deuschl Günther
Published: January 2021

Background

Patients with upper limb action tremor frequently exhibit additional neurological signs of uncertain significance. Clinicians vary in their interpretation, and interrater agreement on the final diagnosis is poor.

Objectives

A new clinical tool for assessing the presence or absence of clinical signs that are important in axis‐1 classification of tremor patients is introduced: the Standardized Tremor Elements Assessment (STEA). Interrater agreement is determined, and signs leading to disagreement in the final diagnosis are identified.

Methods

Three tremor‐focussed and one dystonia‐focussed movement disorder specialists rated 59 videos of patients with upper limb action tremor syndromes using STEA. Interrater agreements for final diagnosis and STEA items were calculated.

Results

Interrater agreement regarding the final diagnosis was higher within the group of tremor specialists and poor between dystonia and tremor specialists. Greater agreement was found for items characterizing tremor than for signs of dystonia.

Conclusions

Clinical signs leading to diagnostic disagreement were identified with STEA, and STEA should therefore be useful in future studies of diagnostic disagreement. The thresholds for considering neurological signs as soft versus significant for ataxia, parkinsonism, dystonia, etc. are critically important in tremor classification and must be studied across movement disorder subspecialties, not simply within a pool of tremor specialists.
Modeling and simulation of fractional order COVID‐19 model with quarantined‐isolated people
Authors: Aslam Muhammad , Farman Muhammad , Akgül Ali , Sun Meng
Published: January 2021

The dynamics of diseases and effectiveness of control policies play important role in the prevention of epidemic diseases. To this end, this paper is concerned with the design of fractional order coronavirus disease (COVID‐19) model with Caputo Fabrizio fractional derivative operator of order Ω ∈ (0, 1] for the COVID‐19. Verify the nonnegative special solution and convergence of the scheme with in the domain. Caputo‐Fabrizio technique apply with Sumudu transformation method is used to solve the fractional order COVID‐19 model. Fixed point theory and Picard Lindelof approach are used to provide the stability and uniqueness of the results. Numerical simulations conspicuously demonstrate that by applying the proposed fractional order model, governments could find useful and practical ways for control of the disease.
Photonic crystal based photoelectrochemical cell for solar fuels
Authors: Zhang Xiwen , John Sajeev
Published: January 2021

The solar fuel production efficiency of photoelectrochemical cells based on TiO2 is primarily limited by the low optical absorption coefficient and concomitant long penetration depth of visible light compared with the minority charge carrier diffusion length. A TiO2 photoelectrode consisting of a slanted conical‐pore photonic crystal immersed in water and integrated on a reflective back‐contact is proposed to reduce the light penetration depth by more than 10 times and branch the electron and hole transports into dimensions matching their diffusion lengths. This brings the photoelectrolytic process into the high‐efficiency operating regime. The maximum achievable photocurrent density for a lightly doped TiO2 with the imaginary part of the dielectric constant 0.01 in the visible range reaches 7.65 mA cm‐2.
Convergence analysis of reproducing kernel particle method to elliptic eigenvalue problem
Authors: Hu Hsin‐Yun , Chen Jiun‐Shyan
Published: January 2021

In this work we aim to provide a fundamental theory of the reproducing kernel particle method for solving elliptic eigenvalue problems. We concentrate on the convergence analysis of eigenvalues and eigenfunctions, as well as the optimal estimations which are shown to be related to the reproducing degree, support size, and overlapping number in the reproducing kernel approximation. The theoretical analysis has also demonstrated that the order of convergence for eigenvalues is in the square of the order of convergence for eigenfunctions. Numerical results are also presented to validate the theoretical analysis.
First-in-Class Selective HDAC6 Inhibitor (ACY-1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma
Authors: Amengual Jennifer E. , Lue Jennifer K. , Ma Helen , Lichtenstein Renee , Shah Bijal , Cremers Serge , Jones Simon , Sawas Ahmed
Published: January 2021

Trial Information

ClinicalTrials.gov  Identifier: NCT02091063 Sponsor: Acetylon Pharmaceuticals Principal Investigator: Jennifer E. Amengual IRB Approved: Yes

Lessons Learned

Oral selective HDAC6 inhibitors could allow for decreased toxicity compared to pan-class inhibitors, and increased ease of use. ACY-1215 is well tolerated and led to disease stabilization in 50% of patients treated on a twice-daily dosing schedule. Rational drug combinations with ACY-1215 improve efficacy in patients with lymphoma. Biomarkers such as XBP-1 level or HDAC6-score may improve patient selection.

Background

ACY-1215, ricolinostat, is an oral, first-in-class isoform-selective HDAC6 inhibitor. HDAC6 is a class IIb deacetylase and plays a critical role in protein homeostasis via the unfolded protein response (UPR). Lymphocytes generate a large repertoire of antibodies and depend on an activated UPR to maintain proteostasis. Lymphomas utilize this biology to evade programmed cell death. In preclinical models of lymphoma, ACY-1215 disrupted proteostasis, triggering apoptosis.

Methods

We translated these findings into a multi-institution, open-label, dose-escalation phase Ib/II study aimed to determine the safety and efficacy in patients with relapsed and refractory lymphoma.

Results

Twenty-one patients with heavily pretreated lymphoma were accrued. Patients in the phase Ib portion were enrolled on one of two dose cohorts [Arm A: 160 mg daily (n = 3) or Arm B: 160 mg twice daily (n = 10)]. ACY-1215 was well tolerated. There were no dose limiting toxicities. Most adverse events were grade 1–2, including diarrhea (57%), nausea (57%), and fatigue (43%). Grade 3–4 toxicities were rare and included anemia (9.5%) and hypercalcemia (9.5%). An additional 8 patients were enrolled on the phase II portion, at 160 mg twice daily. Sixteen patients were evaluable for response. ACY-1215 did not result in any complete or partial responses in patients treated. Eight patients had stable disease (50%) lasting a median duration of 4.5 months, all of whom were treated twice daily. Disease progressed in eight patients (50%) at cycle 2. Five patients were not evaluable due to disease progression prior to cycle 2. The median PFS was 56 days.

Conclusion

ACY-1215 is an oral selective HDAC6 inhibitor that was safe in patients with relapsed and refractory lymphoid malignancies and led to disease stabilization in half of the evaluable patients.
Facile way of dynamically tailoring microporous structures in polyvinylidene fluoride films prepared by thermally induced phase separation
Authors: Yang Bin , Chen Qinting , Ding Mengya , Pan Yang , Zhang Peng , Wang Shuqing , Qian Jiasheng , Miao Jibin , Xia Ru , Chen Peng , Shi You , Tu Youlei
Published: January 2021

Polyvinylidene fluoride (PVDF) films were prepared via thermally induced phase separation (TIPS) using diphenyl carbonate as the diluter in an attempt to disclose the competitive relationship between crystal growth and droplet growth during phase separation process. By varying the quenching temperature different temperature gradient fields were established, which were theoretically evaluated via enthalpy transformation method. The effects of polymer concentration and quenching temperature on evolution of hierarchical morphologies in TIPS films were systematically investigated. According to the morphological characteristics, the cross‐sectional morphology of the films with lower polymer concentration (ΦP = 25%) could be divided into three layers; while that of higher polymer concentration counterpart (ΦP = 55%) only presented a bi‐layered structure. The reason for this could be ascribed to the effect of cooling rate on both crystal growth and droplet growth during TIPS process, which further determined the formation of the hierarchical structure in microporous films. With an increasing quenching temperature, both pore size and porosity of PVDF films increased, accompanied by an improvement on both thermal stability and dynamic mechanical thermal property. The present study could insightfully supply a facile route to fabricate structure‐controllable microporous films of crystalline polymers via an appropriate regulation of the TIPS quenching parameters.
Robust principal component analysis‐based prediction of protein‐protein interaction hot spots
Authors: Sitani Divya , Giorgetti Alejandro , Alfonso‐Prieto Mercedes , Carloni Paolo
Published: January 2021

Proteins often exert their function by binding to other cellular partners. The hot spots are key residues for protein‐protein binding. Their identification may shed light on the impact of disease associated mutations on protein complexes and help design protein‐protein interaction inhibitors for therapy. Unfortunately, current machine learning methods to predict hot spots, suffer from limitations caused by gross errors in the data matrices. Here, we present a novel data pre‐processing pipeline that overcomes this problem by recovering a low rank matrix with reduced noise using Robust Principal Component Analysis. Application to existing databases shows the predictive power of the method.
Where are the new herbicides?
Authors: Qu Ren‐Yu , He Bo , Yang Jing‐Fang , Lin Hong‐Yan , Yang Wen‐Chao , Wu Qiong‐You , Li Qing X , Yang Guang‐Fu
Published: January 2021

Herbicide resistance has become one of the foremost problems in crop production worldwide. New herbicides are required to manage weeds that have evolved resistance to the existing herbicides. However, relatively few herbicides with new modes of action (MOAs) have been discovered in the past two decades. Therefore, the discovery of new herbicides (i.e., new chemical classes or MOAs) remains a primary but ongoing strategy to overcome herbicide resistance and ensure crop production. In this mini‐review, starting with the inherent characteristics of the target proteins and the inhibitor structures, we propose two strategies for the rational design of new herbicides and one computational method for the risk evaluation of target mutation‐conferred herbicide resistance. The information presented here may improve the utilization of known targets and inspire the discovery of herbicides with new targets. We believe that these strategies may trigger the sustainable development of herbicides in the future. © 2021 Society of Chemical Industry
Renewable energy public–private partnerships in developing countries: Determinants of private investment
Authors: Fleta‐Asín Jorge , Muñoz Fernando
Published: January 2021

In this research, we study, for the first time, the determinants of private investment participation in public–private partnership (PPPs) projects in renewable energies. We analyse a broad sample formed by 1,371 PPPs from 63 developing countries in the period 1997–2016. Using a Tobit estimation technique, our findings reveal that PPPs that are smaller, younger, where the private partner takes more responsibilities, and the prime revenue source comes from the electricity consumers' payments, show a greater degree of private investors' participation. In addition, better institutional and economic environments impact positively on the attractiveness of private investment. Other interesting findings are that the support of multilateral development banks (MDBs) positively affects the participation of private investors in renewable energy PPPs, and this becomes more important when the institutional and economic frameworks are weaker. The article sheds light for practitioners and policymakers on promoting actions that reinforce the determinants that positively affect private participation. In this way, government actions that promote the institutional financing of third parties, as well as improvements to their institutions and economic environment, enable efforts to be prioritised due to the positive impact it has on private participation. Similarly, good indicators of these factors allow private investors to select projects that will be more successful.