bluuebunny/crossref_metadata_2025 huggingface dataset:
Locomotion of an adult female and juvenile male aye‐aye (Daubentonia madagascariensis) in Torotorofotsy, Madagascar
Authors: Sefczek Timothy M. , McGraw W. Scott , Faralahy David M. , Manampisoa Gabriel M. , Louis Edward E.
Published: May 2021

Aye‐ayes (Daubentonia madagascariensis) locate and acquire invertebrates from within woody substrates at all levels of the rainforest; yet how their locomotion helps them accommodate this diet has not been explored in detail. We studied the locomotor behavior of an adult female (N = 1,085) and juvenile male (N = 708) aye‐aye in the undisturbed forest of Torotorofotsy, Madagascar from May to December 2017. We used bout sampling to record locomotion during foraging and travel of the two radio‐collared individuals. We used χ
2 tests to compare overall locomotion, travel, and foraging, as well as strata and support use. We performed a correspondence analysis to examine relationships between individual behaviors, strata, and support types. Leaping accounted for 47.9% and 50.1% of all locomotor activity in the adult female and juvenile male, respectively. Leaping was the most common behavior during travel in both individuals (59.2% and 53.9%, respectively), whereas head‐first descent was most frequent during foraging (35.0% and 48.0%, respectively). For all three locomotor categories, the main canopy (40.3%–79.6%) was used most frequently and trunks were the most frequently used support type (50.7%–60.0%). There is a strong association between strata and support use overall and during travel. Quadrupedal walking was significantly associated with the main canopy, as was head‐first descent with the low canopy. Our analysis demonstrates that aye‐ayes use a variety of locomotor behaviors to forage for invertebrates. Aye‐ayes’ ability to repurpose their positional repertoire to acquire other resources in degraded forests should not obscure the importance of invertebrates to this species.
HPV in the malignant transformation of sinonasal inverted papillomas: A meta‐analysis
Authors: Stepp Wesley H. , Farzal Zainab , Kimple Adam J. , Ebert Charles S. , Senior Brent A. , Zanation Adam M. , Thorp Brian D.
Published: May 2021

Objectives

: To date, there is still a significant debate on the role of human papilloma virus (HPV) infection in transformation of inverted papillomas (IPs) to squamous cell carcinoma (SCC). This study was designed to determine if the presence of HPV in a sinonasal IP increases the risk of malignant transformation to IPSCC.

Methods

: Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, 19 high‐quality case‐control and cohort studies with tissue‐diagnosed IP or IPSCC and HPV diagnosis were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method with correction for random effects. Subgroup, publication bias and a sensitivity analyses were also performed.

Results

: Nineteen studies with minimal bias met the inclusion criteria for quality and identified HPV infection in an IP. The pooled data revealed a strong association with progression to malignancy with an unweighted, pooled OR of 2.38 (CI95 1.47 to 3.83) and a weighted OR of 2.80 (CI95 1.42 to 5.51). Sensitivity analysis revealed that no single study contributed significantly to our pooled OR calculations (ORs 2.52 to 3.57). Subgroup analyses stratified by publication date, nucleic acid target, HPV detection method and type, sample size, and region all demonstrated a positive association of HPV with IPSCC.

Conclusions

: There appears to be a significant association between HPV infection and malignant transformation of IPs. While HPV testing is not currently the standard of care for IPs, these data suggest a link between the two and suggest further studies should be performed to identify a link between the virus and malignant transformation.
Botulinum toxin for chronic rhinitis: A systematic review and meta‐analysis
Authors: Rinzin Kencho , Hoang Minh P. , Seresirikachorn Kachorn , Snidvongs Kornkiat
Published: May 2021

Background

Botulinum toxin type A (BTX‐A) is a potential treatment for chronic rhinitis. This study aimed to assess the effectiveness and safety of BTX‐A in treating patients with chronic rhinitis.

Methods

Systematic searches of MEDLINE, Scopus, and EMBASE databases were performed. Randomized controlled trials (RCTs) that assessed the efficacy of BTX‐A in allergic rhinitis and/or nonallergic rhinitis patients, compared with either placebo or active treatment, were included. The outcomes were total nasal symptom (TNSS), disease‐specific quality of life (QOL), and adverse events.

Results

Nine RCTs (340 patients) met the eligibility criteria. Compared with placebo, the ≤ 12‐week effects favored BTX‐A injection on TNSS (standardized mean difference [SMD] ‐2.22, 95% confidence interval [CI] ‐3.27 to ‐1.17, p < 0.01, four RCTs). Beneficial effects > 12 weeks over placebo (MD ‐9.69, 95% CI ‐11.29 to ‐8.09, p < 0.01, one RCT) were demonstrated up to 24 weeks. However, the benefits were not shown on nasal congestion and individual nasal symptoms. Compared with active comparators (triamcinolone injection, ipratropium bromide, and cetirizine), there was no difference in the < 12‐week effect between groups on TNSS. There was no difference between BTX‐A and cetirizine on QOL (one RCT). The > 12‐week effects on TNSS and individual nasal symptoms favored BTX‐A over triamcinolone injection (one RCT). The risk ratio of adverse events favored BTX‐A over cetirizine (one RCT).

Conclusions

BTX‐A improved TNSS and QOL in patients with chronic rhinitis. These effects were demonstrated up to 24 weeks post treatment. BTX‐A was safe, well tolerated, and may be considered in patients who are refractory to current standard‐of‐care therapies.
The Micromechanical Signature of Pituitary Adenomas: New Perspectives for the Diagnosis and Surgery
Authors: Meyer Mikaël , Bouchonville Nicolas , Gaude Christophe , Gay Emmanuel , Ratel David , Nicolas Alice
Published: May 2021

Pituitary adenomas are common tumors in the skull base that are associated with significant morbidity due to local compressive effects, hormonal hypersecretion, or treatment‐associated endocrine deficiency. Pituitary adenomas are often surgically resected to improve clinical symptoms, with the help of magnetic resonance imaging (MRI) to locate the tumor tissues. But still a large proportion of adenoma fail being located, being either too small or not dense enough. In addition, normal and tumor tissues do not always show optical contrast in endoscopic endonasal trans‐sphenoidal surgery. Finding new markers to delineate the tumor tissue has become mandatory to help the surgical procedure and limit relapses. Herein, an indentation‐type atomic force microscope is used to show that tumor tissues are two orders of magnitude softer than normal tissues, independent of the type of hormonal secretion. This softening correlates with the degradation of the reticulin, type IV collagen, and laminin scaffolds in all the tumors. This significant difference suggests that intraoperative lesion localization and margin assessment could be evaluated by an approach based on stiffness measurement.
Prediction of Chalcogen‐Doped VCl3 Monolayers as 2D Ferromagnetic Semiconductors with Enhanced Optical Absorption
Authors: Zhao Shan , Wan Wenhui , Ge Yanfeng , Liu Yong
Published: May 2021

In recent years, 2D ferromagnetic semiconductors have attracted much attention because of its potential application in spintronic devices. Using first‐principles calculations, the magnetic and optical properties of intrinsic and chalcogen‐doped VCl3 monolayers are investigated. In contrast to previous work, VCl3 monolayer is proved to be an antiferromagnetic semiconductor rather than a Dirac half‐metal after considering the electronic correlation effect. At a low S concentration x between and , S‐doped VCl3 monolayer forms a ferromagnetic semiconductor with a large bandgap and a strong exchange splitting in both valence and conduction bands. As the doping content x increases above , S‐doped VCl3 monolayer will change to be an anti‐ferromagnetic semiconductor and a non‐magnetic metal successively. Moreover, Se‐ and Te‐doped VCl3 monolayers can also form robust ferromagnetic semiconductors at low doping concentration. In particular, the Curie temperature of Se‐doped VCl3 monolayer can reach 170 K, higher than that of S‐ and Te‐doped VCl3 monolayers. At last, chalcogen‐doped VCl3 monolayers have enhanced optical absorption in the visible regions compared to intrinsic VCl3 monolayer. The results show that chalcogen‐doped VCl3 monolayers have promising potential applications in future spintronic and optoelectronic devices.
Motorized Macrocycle: A Photo‐responsive Host with Switchable and Stereoselective Guest Recognition
Authors: Liu Yue , Zhang Qi , Crespi Stefano , Chen Shaoyu , Zhang Xiu‐Kang , Xu Tian‐Yi , Ma Chang‐Shun , Zhou Shang‐Wu , Shi Zhao‐Tao , Tian He , Feringa Ben L. , Qu Da‐Hui
Published: May 2021

Designing photo‐responsive host–guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo‐responsive macrocyclic hosts, modulated by light‐driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first‐generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown‐ether‐like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host–guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi‐state light‐driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli‐responsive host–guest systems and dynamic materials.
A new Civilization and Its Discontents in times of COVID‐19?
Authors: Blass Heribert
Published: May 2021

The Covid‐19 pandemic brings into focus both the burdens on individuals, and the effects on the culture and society in general. In our encounters with our patients, we as psychoanalysts have experienced the broad spectrum of possible reactions to the viral threat, just as it is found throughout society: from real fear to panic or, on the contrary, to a denial of the impending danger. We are facing drastic changes which are connected with painful losses but sometimes also with new possibilities in our accustomed lives. Nevertheless, the loss of trust in the preservation of individual and general health and of economic existence as well goes beyond the individual and leads to tensions and even cracks in the supposed social consensus. Thus, in the relationship of the individual to society, the pandemic exacerbates the ambivalence between self‐interest and solidarity, not infrequently to the point of forming hostile attitudes. In this article, the author explores the question of to what extent it is possible to speak about a “new Civilization and Its Discontents” in light of the increasing social tensions under the conditions of the pandemic. It is the task of psychoanalysis to explicitly name the unconscious conflict between striving for pleasure and happiness or the search for security, in order to also contribute to dealing with the resulting aggression and fear of death in times of pandemic.
Sound discrimination of two sympatric, threatened fish species allows for their in situ mapping
Authors: Picciulin Marta , Bolgan Marta , Facca Chiara , Fiorin Riccardo , Riccato Federico , Malavasi Stefano
Published: May 2021

Human impacts on marine ecosystems are increasing and the number of fish species listed in the Red List is constantly growing. In the Mediterranean Sea, seven of the 10 bony fishes defined as Threatened by the IUCN are known to be vocal, including the target species of this study: the shi drum (Umbrina cirrosa Linnaeus, 1758) and the brown meagre (Sciaena umbra Linnaeus, 1758). As a result, non‐invasive passive acoustic monitoring (PAM) can be used to pinpoint their distribution at sea. However, for PAM to be effective, reliable acoustic discrimination is required because the sounds they emit during reproduction are remarkably similar (i.e. short broadband pulsed sounds).

The shi drum and the brown meagre are closely related, elusive, vocal sciaenids, partially overlapping in their ecological niche. During summer 2019, three PAM surveys were conducted along the tidal inlets of the Venice lagoon (Italy). Here, the calls of both species have been recognized according to their temporal features: shi drum sounds were made up of a lower number of longer pulses with a different envelope, repeated at a lower rate than those of the brown meagre. Further, shi drum and brown meagre sounds of different origins (aquaculture and semi‐natural conditions) were analysed and compared with those collected during the survey of the study area in order to validate the field collected data.

Call discrimination allowed for a fine‐scale species mapping, showing a partially overlapping distribution of the two species along the inlets. This is the first case in which two sciaenids have been documented to share their reproductive habitat in the Mediterranean Sea.

This study demonstrates that it is feasible to acoustically monitor the target species even in those parts of the Mediterranean Sea where they co‐exist. This, in its turn, could provide managers with the required data for effective conservation measures to be implemented.
Association between the discontinuation of substance use inpatient treatment and the risk of committing a crime leading to imprisonment: A Finnish registry‐based 5‐year follow‐up
Authors: Kaskela Teemu , Pitkänen Tuuli
Published: May 2021

Background

Discontinuation of substance use inpatient treatment is common, generally due to dropout and rule breaking. In turn, this is associated with worse long‐term substance use outcomes.

Aim

To investigate whether people who discontinued voluntary inpatient substance use treatment have a higher risk of imprisonment for a crime within 5 years of discontinuance than those who completed treatment.

Methods

This registry‐based follow‐up study focused on all inpatient treatment episodes between 2002 and 2009 (N = 2893) in a Finnish hospital for treating addictions. Data from national registers on criminality, hospitalisations and education were linked. Cox regression analysis was used.

Results

Discontinued treatment episodes were 1.4 times more likely to be followed by criminality leading to imprisonment during the 5‐year follow‐up period compared with completed treatment periods, after adjusting for age, gender, education, substance use diagnoses, earlier mental health disorders and prior imprisonments.

Conclusions

Our findings strengthen the argument for ensuring completion of substance use treatment episodes; better completion rates could decrease the harm caused by serious criminality. Indeed, we recommend that crime reduction should be included to the long‐term goals of substance use treatment.
Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report
Authors: Tagetti Angela , Marcon Denise , Moghetti Paolo , Spiazzi Giovanna , Fava Cristiano , Minuz Pietro
Published: May 2021

Key Clinical Message

Addison Disease is an uncommon, life‐threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.
Acute ischemic stroke after enjoying Top of Europe
Authors: Krasteva Marina P. , Pospieszny Katarzyna , Heldner Mirjam R.
Published: May 2021

Sudden onset of disturbed consciousness, neurocognitive deficits, and weakness of the proximal limbs are typical findings of a watershed stroke. Occurrence after an intense emotional experience and electrocardiogram changes are hints toward the rare cause of stroke of a takotsubo cardiomyopathy, even more if the stroke pattern is embolic.
A rare case of multiple minor salivary gland sialoliths in the masseteric region
Authors: Boamah Matthew Owusu , Brakohiapa Edmund Kwadwo Kwakye , Choi Shaun , Blankson Paa Kwesi , Parkins Grace E.
Published: May 2021

We report a case of a 59‐year‐old woman who presented with swelling of the right cheek. CT Scan showed three calculi located anteromedial to the masseter, and well isolated from other major salivary glands. Calculi were surgically removed with standard intraoral incision and exploration.
Lateral maxillary sinus floor elevation in the presence of a sinus osteoma: A case report
Authors: Mlouka Mootaz , Tlili Mohamed , Hamrouni Ali , Selmi Raki , Khanfir Faten , Khalfi Mohamed Salah , Ben Amor Faten
Published: May 2021

Eventhough the lateral sinus floor elevation is a well‐documented procedure, many factors can increase its difficulty. The presence an osteoma can be very challenging and must be managed with caution taking in consideration the lesions's size and extension.
Efficacy and safety of low‐dose imatinib in an elderly patient with mixed phenotype acute leukemia with t(9;22)(q34;q11.2);BCR‐ABL1
Authors: Okayama Yusuke , Takakuwa Teruhito , Otomaru Ippei , Horiuchi Mirei , Miura Akiko , Araki Taku , Fujitani Yotaro , Yamamura Ryosuke
Published: May 2021

Low‐dose imatinib with monitoring of drug concentrations in blood may successfully control Philadelphia chromosome‐positive mixed phenotype acute leukemia (Ph+MPAL), particularly in elderly patients with comorbidities.
Rehabilitation of squamous cell carcinoma defect with two‐piece hollow bulb obturator prosthesis – A case report
Authors: Kuttae Viswanathan Anitha , Ganapathy Dhanraj M.
Published: May 2021

Two‐piece hollow bulb obturator maxillofacial prosthesis for hemi‐maxillectomy defect is given after surgical resection due to oral squamous cell carcinoma. Maxillofacial prosthodontists play a pivotal role in construction of prosthesis. Unique choices are made in prosthesis design depending on the clinical representation. Improvement in function, phonetics and esthetics was appreciated.
Facile Synthesis of Carbon‐Sulfur Scaffold with Transition‐Metal Sulfides and Oxides as Efficient Electrocatalysts for Oxygen Evolution Reaction
Authors: Tzadikov Jonathan , Geva Rotem , Azoulay Adi , Shalom Menny
Published: May 2021

Transition‐metal sulfides and oxides supported on carbon materials (MSOCs) are vastly explored as efficient electrocatalysts for water splitting, especially for the anodic oxygen evolution reaction (OER). In this work, we show the facile, scalable bottom‐up synthesis of MSOCs using available low‐cost metal salts, pyrene, and elemental sulfur as reactants. Upon condensation at high temperature, the monomers form a stable molten‐state intermediate, directing the synthesis of MSOCs due to strong coordination between the metallic cation‐sulfur‐pyrene. These materials exhibit excellent activity towards OER achieving low overpotentials of 284 and 325 mV at 10 and 100 mA cm−2. The effect of the carbon support is demonstrated through high mass activity of the materials (∼300 A g−1) compared to the materials with no support.
Optimization of Slag Mobility of Biomass Fuels in a Pilot‐scale Entrained‐Flow Gasifier
Authors: Mielke Konrad , Wu Guixuan , Eberhard Mark , Kolb Thomas , Müller Michael
Published: May 2021

The bioliq® process, developed at the Karlsruhe Institute for Technology, aims at the production of synthetic fuels and chemicals from biomass. The bioliq® technology is based on a two‐step process with decentral pyrolysis for the production of a transportable slurry from residual biomass and the central entrained‐flow gasification of the slurry by using biomass‐to‐liquid technology. This study is focused on the slag, which is formed by melting the inorganic ash components during gasification. To operate the gasifier smoothly, a range of desired viscosity has to be defined. A structure‐based viscosity model was used to predict the viscosity of the slags at the gasifier outlet. A good agreement between experimental and calculated viscosities is achieved for fully liquid slag systems.
Transmembrane Transport of Bicarbonate Unravelled
Authors: Martínez‐Crespo Luis , Hewitt Sarah H. , De Simone Nicola Alessandro , Šindelář Vladimír , Davis Anthony P. , Butler Stephen , Valkenier Hennie
Published: May 2021

Invited for the cover of this issue are Dr. Stephen Butler, Dr. Hennie Valkenier and co‐workers at Université Libre de Bruxelles, Loughborough University, Masaryk University, and the University of Bristol. The image depicts the transport of bicarbonate anions versus the spontaneous diffusion of CO2 across the lipid bilayer of a liposome. Read the full text of the article at 10.1002/chem.202100491.
Sheathless microflow cytometer utilizing two bulk standing acoustic waves
Authors: Wang Ce , Ma Yuting , Chen Zhongxiang , Wu Yunliang , Song Feifei , Qiu Jianping , Shi Mengdie , Wu Xiaodong
Published: May 2021

In recent years, microflow cytometry has become a popular research field because of its potential to provide low‐cost and disposable chips for complex cell analyses. Herein, we demonstrate a sheathless microflow cytometer which integrates a bulk standing acoustic wave based microchip capable of three dimensional cell focusing. Flow cytometry was successfully demonstrated using this system with a coefficient of variation (CV) of 2.16% with standard calibration beads. The sensitivities calibrated by rainbow beads are 518 MEFL in fluorescein Isothiocyanate (FITC) channel and 264 MEPE in P‐phycoerythrin (PE) channels, respectively. The linearities are more than 99% in both channels. The capability of the proposed microflow cytometer is further demonstrated by immunologically labeled leukocytes differentiation in blood. This acoustic‐based microflow cytometer did not require any sheath flows or complex structures and can be mass produced. Because of the simple fluid channel, the chip can be easily made pipeless, disposable for applications requiring no cross contamination. Moreover, with the gentle and bio‐compatible acoustic waves used, this technique is expected to maintain the viability of cells and other bioparticles.
Detection of retinal and blood Aβ oligomers with nanobodies
Authors: Habiba Umma , Descallar Joseph , Kreilaus Fabian , Adhikari Utpal K. , Kumar Sachin , Morley John W , Bui Bang V , Koronyo‐Hamaoui Maya , Tayebi Mourad
Published: May 2021

Introduction

Abnormal retinal changes are increasingly recognized as an early pathological change in Alzheimer's disease (AD). Although amyloid beta oligomers (Aβo) have been shown to accumulate in the blood and retina of AD patients and animals, it is not known whether the early Aβo deposition precedes their accumulation in brain.

Methods and results

Using nanobodies targeting Aβ1‐40and Aβ1‐42oligomers we were able to detect Aβ oligomers in the retina and blood but not in the brain of 3‐month‐old APP/PS1 mice. Furthermore, Aβ plaques were detected in the brain but not the retina of 3‐month‐old APP/PS1 mice.

Conclusion

These results suggest that retinal accumulation of Aβo originates from peripheral blood and precedes cognitive decline and Aβo deposition in the brain. This provides a very strong basis to develop and implement an “eye test” for early detection of AD using nanobodies targeting retinal Aβ.
Fractal geometry applied to the analysis of cervix biopsy
Authors: Rodríguez‐Velásquez Javier Oswaldo , Barrios‐Arroyave Freddy Andrés , Correa‐Herrera Sandra Catalina , Grisales‐Gutiérrez Carlos Evelio , Prieto‐Bohórquez Signed Esperanza , Jattin‐Balcázar Jairo Javier , Ruiz‐Morales Jhon Jairo
Published: May 2021

Background

the measurement of the spaces of occupation of irregular objects in the context of fractal geometry has had some applications at a cellular morphometric level, where characterizations of normality and disease have been established. The objective of the present study is to apply a fractal methodology to characterize images from cervical colposcopy.

Materials and methods

a mathematical and geometrical characterization of 67 cell samples was performed by measuring cellular fractal characteristics through the Box‐Counting method, being nine normal, eight low‐intraepithelial lesions, 16 high‐intraepithelial lesions, eight carcinomas in situ, 20 squamous cell carcinomas and six endocervical carcinomas.

Results

the values of fractal dimension of the nuclear and cytoplasmic borders with respect to the totality varied between 0.719 to 1128 and 0.81 to 1024 while the occupation spaces in the 2 pixels grid were between 293 to 1606 and 64 to 693 respectively and in the 4 pixels grid oscillated between 153 to 894 and 36 to 361, respectively. Exocervical cells values had sensitivities between 78.3% to 100% in order to differentiate them from different types of cervical lesions.

Conclusions

according to the results obtained, the mathematical values found are suggestive of being able to differentiate between normality and some colposcopy‐guided cervical biopsy lesions.
Molecular approaches reveal weak sibship aggregation and a high dispersal propensity in a non‐native fish parasite
Authors: Prunier Jérôme G. , Saint‐Pé Keoni , Blanchet Simon , Loot Géraldine , Rey Olivier
Published: May 2021

Inferring parameters related to the aggregation pattern of parasites and to their dispersal propensity are important for predicting their ecological consequences and evolutionary potential. Nonetheless, it is notoriously difficult to infer these parameters from wildlife parasites given the difficulty in tracking these organisms. Molecular‐based inferences constitute a promising approach that has yet rarely been applied in the wild. Here, we combined several population genetic analyses including sibship reconstruction to document the genetic structure, patterns of sibship aggregation, and the dispersal dynamics of a non‐native parasite of fish, the freshwater copepod ectoparasite Tracheliastes polycolpus. We collected parasites according to a hierarchical sampling design, with the sampling of all parasites from all host individuals captured in eight sites spread along an upstream–downstream river gradient. Individual multilocus genotypes were obtained from 14 microsatellite markers, and used to assign parasites to full‐sib families and to investigate the genetic structure of T. polycolpus among both hosts and sampling sites. The distribution of full‐sibs obtained among the sampling sites was used to estimate individual dispersal distances within families. Our results showed that T. polycolpus sibs tend to be aggregated within sites but not within host individuals. We detected important upstream‐to‐downstream dispersal events of T. polycolpus between sites (modal distance: 25.4 km; 95% CI [22.9, 27.7]), becoming scarcer as the geographic distance from their family core location increases. Such a dispersal pattern likely contributes to the strong isolation‐by‐distance observed at the river scale. We also detected some downstream‐to‐upstream dispersal events (modal distance: 2.6 km; 95% CI [2.2–23.3]) that likely result from movements of infected hosts. Within each site, the dispersal of free‐living infective larvae among hosts likely contributes to increasing genetic diversity on hosts, possibly fostering the evolutionary potential of T. polycolpus.
Lewis Base‐Catalyzed Cycloaddition of Heterocyclic Alkenes with 2,2,2‐Trifluorodiazoethane (CF3CHN2): Access to Trifluoromethylated Pyrazolines and Pyrazoles
Authors: Cao Tingting , Yang Zhen , Sun Yunfang , Zhao Nannan , Lu Shan , Zhang Jing , Wang Lei
Published: May 2021

An efficient Lewis base catalytic protocol to biologically important trifluoromethylated pyrazolines and pyrazoles is developed through triazene‐heterocyclic alkene cycloaddition reactions of an array of oxa‐/aza‐benzonorbornadienes and coumarins with CF3CHN2. This triazene‐ heterobicyclic alkene cycloaddition procedure features good functional group tolerance, scaffold diversity, and feasible late‐stage functionalization of some representative natural products.
A comparative study of CE‐SDS, SDS‐PAGE, and Simple Western—Precision, repeatability, and apparent molecular mass shifts by glycosylation
Authors: Scheller Christin , Krebs Finja , Wiesner Rebecca , Wätzig Hermann , Oltmann‐Norden Imke
Published: May 2021

SDS gel electrophoresis is a commonly used approach for monitoring purity and apparent molecular mass (Mr) of proteins, especially in the field of quality control of biopharmaceutical proteins. The technological installation of CE‐SDS as the replacement of the slab gel technique (SDS‐PAGE) is still in progress, leading to a continuous improvement of CE‐SDS instruments. Various CE‐SDS instruments, namely Maurice (CE‐SDS/CE‐SDS PLUS) and Wes by ProteinSimple as well as the microchip gel electrophoresis system LabChip® GXII Touch™ HT by PerkinElmer were tested for precision and repeatability compared to SDS‐PAGE (Bio‐Rad). For assessing these quality control parameters, standard model proteins with minor post‐translational modifications were used. Overall, it can be concluded that the CE‐SDS‐based methods are similar to SDS‐PAGE with respect to these parameters. Quality characteristics of test systems gain more significance by testing proteins that do not behave like model proteins. Therefore, glycosylated proteins were analyzed to comparatively investigate the influence of glycosylation on Mr determination in the different instruments. In some cases, high deviations were found both among the methods and with regard to reference values. This article provides possible explanations for these findings.
Concentration‐ and time‐dependent induction of Cyp1a and DNA damage response by benzo(a)pyrene in LMH three‐dimensional spheroids
Authors: Sharin Tasnia , Gyasi Helina , Jones Stephanie P. , Crump Doug , O'Brien Jason M.
Published: May 2021

In vitro liver toxicity tests performed using cell lines cultured as two‐dimensional (2D) monolayer have limited CYP450 activity and may be inadequate for screening chemicals that require activation to exert toxicity. Metabolic competence is greatly improved using three‐dimensional (3D) cell culture. In this study, Cyp1a induction, and subsequent DNA damage response induced by benzo(a)pyrene (BaP) were compared in 2D monolayer cells and 3D spheroids of the chicken hepatic cell line, LMH. Cells were exposed to BaP (0.1–100 μM) for different durations: 8, 24, 35, or 48 hr. Cyp1a activity, mRNA expression of Cyp1a and DNA damage response (DDR) genes, and phosphorylation of H2AX (γH2AX) were determined using the EROD assay, a customized PCR array, and flow cytometry, respectively. EROD activity was induced at 8 hr and achieved maximal induction at 24 hr in spheroids; earlier time points than for monolayer cells. In spheroids, BaP exposure resulted in a concentration‐dependent increase in Cyp1a4 mRNA expression at 8 hr followed by upregulation of DDR genes at 24 hr, whereas Cyp1a4 mRNA induction was only observed at 48 hr in monolayer cells. Cyp1a5 mRNA was induced at 8 hr in monolayer cells but maximum induction was greater in spheroids. An increase in γH2AX was observed at 24 hr in spheroids; this endpoint was not evaluated in monolayer cells. These results suggest that BaP metabolism precedes the DNA damage response and occurs earlier in 3D spheroids. This study demonstrates that LMH 3D spheroids could be a suitable metabolically‐competent in vitro model to measure genotoxicity of chemicals that require metabolic activation by Cyp1a.
Lactoferrin could alleviate liver injury caused by Maillard reaction products with furan ring through regulating necroptosis pathway
Authors: Fan Linlin , Wang Fengen , Yao Qianqian , Wu Haoming , Wen Fang , Wang Jiaqi , Li Huiying , Zheng Nan
Published: May 2021

As classical MRPs, the toxic effects of furosine, pyralline, and 5‐hydroxymethylfurfural (5‐HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5‐HMF in several foods using ultrahigh‐performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL‐7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis‐related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p‐MLKL necroptosis pathway and downstream inflammatory reaction.
Effect of garlic powder supplementation on blood pressure and hs‐C‐reactive protein among nonalcoholic fatty liver disease patients: A randomized, double‐blind, placebo‐controlled trial
Authors: Soleimani Davood , Parisa Moosavian Seyedeh , Zolfaghari Hamid , Paknahad Zamzam
Published: May 2021

Based on the anti‐inflammatory and antihypertensive properties of garlic, the current study was designed to evaluate the garlic powder effects on blood pressure and high‐sensitivity C‐reactive protein (hs‐CRP) among Nonalcoholic Fatty Liver Disease patients (NAFLD). This randomized, double‐blind, placebo‐controlled trial study was conducted on 110 patients with NAFLD. The patients were randomly divided into 2 groups, receiving two tablets of either 400 mg garlic or placebo daily for 15 weeks. At baseline and the end of the study, blood pressure and hs‐CRP were determined. Of 110 patients enrolled in the trial, 98 subjects were included in the final analysis. After the intervention, systolic blood pressures (SBP) (mean: −7.89; 95%CI:‒11.39 to −4.39 mm Hg), diastolic blood pressure (DBP) (mean: −5.38; 95%CI: −7.77 to −3 mm Hg), and Mean Arterial Pressure (MAP) (mean: −6:95%CI: −8.4 to −3.6 mm Hg) decreased significantly in the garlic group as compared to the placebo group. Also, the percentage of reduced hs‐CRP was significantly higher in the intervention group compared with the control group (mean: −16.1; 95%CI: −32.7 to −0.53; p = .035). Moreover, a positive correlation was observed between the percentage change in hs‐CRP and percentage changes in SBP (r = 0.221; p = .029), DBP (r = 0.166; p = .012), and MAP (r = 0.210; p = .038). Garlic supplementation can be a safe and potentially adjunct treatment to reduce blood pressure and the risk of cardiovascular disorders in patients with NAFLD.
Distinct effects of prematurity on MRI metrics of brain functional connectivity, activity, and structure: Univariate and multivariate analyses
Authors: Chiarelli Antonio M. , Sestieri Carlo , Navarra Riccardo , Wise Richard G. , Caulo Massimo
Published: May 2021

Premature birth affects the developmental trajectory of the brain during a period of intense maturation with possible lifelong consequences. To better understand the effect of prematurity on brain structure and function, we performed blood‐oxygen‐level dependent (BOLD) and anatomical magnetic resonance imaging (MRI) at 40 weeks of postmenstrual age on 88 newborns with variable gestational age (GA) at birth and no evident radiological alterations. We extracted measures of resting‐state functional connectivity and activity in a set of 90 cortical and subcortical brain regions through the evaluation of BOLD correlations between regions and of fractional amplitude of low‐frequency fluctuation (fALFF) within regions, respectively. Anatomical information was acquired through the assessment of regional volumes. We performed univariate analyses on each metric to examine the association with GA at birth, the spatial distribution of the effects, and the consistency across metrics. Moreover, a data‐driven multivariate analysis (i.e., Machine Learning) framework exploited the high dimensionality of the data to assess the sensitivity of each metric to the effect of premature birth. Prematurity was associated with bidirectional alterations of functional connectivity and regional volume and, to a lesser extent, of fALFF. Notably, the effects of prematurity on functional connectivity were spatially diffuse, mainly within cortical regions, whereas effects on regional volume and fALFF were more focal, involving subcortical structures. While the two analytical approaches delivered consistent results, the multivariate analysis was more sensitive in capturing the complex pattern of prematurity effects. Future studies might apply multivariate frameworks to identify premature infants at risk of a negative neurodevelopmental outcome.
The GEOMON network of Czech catchments provides long‐term insights into altered forest biogeochemistry: From acid atmospheric deposition to climate change
Authors: Oulehle Filip , Fischer Milan , Hruška Jakub , Chuman Tomáš , Krám Pavel , Navrátil Tomáš , Tesař Miroslav , Trnka Miroslav
Published: May 2021

In 1994, a network of small catchments (GEOMON) was established in the Czech Republic to determine input–output element fluxes in semi‐natural forest ecosystems recovering from anthropogenic acidification. The network consists from 16 catchments and the primary observations of elements fluxes were complemented by monitoring of biomass stock, element pools in soil and vegetation, and the main water balance components. Over last three decades, reductions of SO2, NOx and NH3 emissions were followed by sulphur (S) and nitrogen (N) deposition reductions of 75% and 30%, respectively. Steeper declines of strong acid anion concentrations compared to cations (Ca, Mg, Na, K, NH4) in precipitation resulted in precipitation pH increase from 4.5 to 5.2 in bulk precipitation and from 4.0 to 5.1 in spruce throughfall. Stream chemistry responded to changes in deposition: S leaching declined. However at majority of catchments soils acted as a net source of S to runoff, delaying recovery. Stream pH increased at acidic streams (pH < 6) and aluminium concentration decreased. Stream nitrate (NO3) concentration declined by 60%, considerably more than N deposition. Stream NO3 concentration was tightly positively related to stream total dissolved nitrogen to total phosphorus (P) ratio, suggesting the role of P availability on N retention. Trends in dissolved organic carbon fluxes responded to both acidification recovery and to runoff temporal variation. An exceptional drought occurred between 2014 and 2019. Over this recent period, streamflow decreased by ≈ 40% on average compared to 1990s, due to the increases of soil evaporation and vegetation transpiration by ≈ 30% and declines in precipitation by ≈ 15% on average across the elevational gradient. Sharp decreases of stream runoff at catchments <650 m a.s.l. corresponded to areas of recent forest decline caused by bark beetle infestation on drought stressed spruce forests. Understanding of the interactions among legacies of acidification and eutrophication, drought effects on the water cycle and forest disturbance dynamics is requisite for effective management of forested ecosystems under anthropogenic influence.
The prognostic value of weight and body composition changes in patients with non‐small‐cell lung cancer treated with nivolumab
Authors: Degens Juliette H.R.J. , Dingemans Anne‐Marie C. , Willemsen Anna C.H. , Gietema Hester A. , Hurkmans Daan P. , Aerts Joachim G. , Hendriks Lizza E.L. , Schols Annemie M.W.J.
Published: May 2021

Background

It is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non‐small‐cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second‐line nivolumab.

Methods

All patients with stage IV NSCLC, who were treated with second‐line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated. Skeletal muscle mass (SMM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at the first lumbar level on computed tomography images obtained before initiation of nivolumab and at week 6 of treatment. The contribution of changes in body weight (defined as >2% loss), SMM, VAT, and SAT to OS was analysed by Kaplan–Meier method and adjusted for clinical confounders in a Cox regression analysis. The results from the study cohort were validated in another Dutch cohort from Erasmus Medical Center, Rotterdam.

Results

One hundred and six patients were included in the study cohort. Loss of body weight of >2% at week 6 was an independent predictor for poor OS (hazard ratio 2.39, 95% confidence interval 1.51–3.79, P < 0.001) when adjusted for gender, >1 organ with metastasis, pretreatment hypoalbumenaemia, and pretreatment elevated C‐reactive protein. The result was confirmed in the validation cohort (N = 62). Loss of SMM as a feature of cancer cachexia did not significantly predict OS in both cohorts. Significant (>2%) weight loss during treatment was reflected by a significant loss of VAT and SAT, while loss of SMM was comparable between weight‐stable and weight‐losing patients.

Conclusions

Weight loss, characterized by loss of subcutaneous and visceral adipose tissues, at week 6 of treatment with nivolumab, is a significant poor prognostic factor for survival in patients with Stage IV NSCLC.
Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia
Authors: Lu Shanshan , Li Yiwei , Shen Qiang , Zhang Wanli , Gu Xiaofan , Ma Mingliang , Li Yiming , Zhang Liuqiang , Liu Xuan , Zhang Xiongwen
Published: May 2021

Background

Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti‐inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.

Methods

The in vitro cell models of C2C12 myotube atrophy and 3T3‐L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour‐bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.

Results

Carnosol and its analogues [dimethyl‐carnosol (DCS) and dimethyl‐carnosol‐D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3‐L1 adipocytes in vitro. Interestingly, CS and its analogues exhibited stronger inhibitive effects on muscle atrophy induced by tumour necrosis factor‐α (TNF‐α) (CS, P < 0.001; DCS, P < 0.001; DCSD, P < 0.001) in C2C12 myoblasts than on muscle atrophy induced by IL‐6 (CS, P < 0.05; DCS, P = 0.08; DCSD, P < 0.05). In a C26 tumour‐bearing mice model, administration of CS or its analogue DCSD significantly prevented body weight loss without affecting tumour size. At the end of the experiment, the body weight of mice treated with CS and DCSD was significantly increased by 11.09% (P < 0.01) and 11.38% (P < 0.01) compared with that of the C26 model group. CS and DCSD also improved the weight loss of epididymal adipose tissue in C26 model mice by 176.6% (P < 0.01) and 48.2% (P < 0.05) increase, respectively. CS and DCSD treatment partly preserved gastrocnemius myofibres cross‐sectional area. CS treatment decreased the serum level of TNF‐α (−95.02%, P < 0.01) but not IL‐6 in C26 tumour‐bearing mice. Inhibition on NF‐κB and activation of Akt signalling pathway were involved in the ameliorating effects of CS and its analogues on muscle wasting both in vitro and in vivo. CS and its analogues also alleviated adipose tissue loss by inhibiting NF‐κB and AMPK signalling pathways both in vitro and in vivo.

Conclusions

CS and its analogues exhibited anticachexia effects mainly by inhibiting TNF‐α/NF‐κB pathway and decreasing muscle and adipose tissue loss. CS and its analogues might be promising drug candidates for the treatment of cancer cachexia.
Mild anemia as a single independent predictor of mortality in patients with COVID‐19
Authors: Tremblay Douglas , Rapp Joseph L. , Alpert Naomi , Lieberman‐Cribbin Wil , Mascarenhas John , Taioli Emanuela , Ghaffari Saghi
Published: May 2021

The coronavirus disease 2019 (COVID‐19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented international health crisis. COVID‐19 clinical presentations cover a wide range from asymptomatic to severe illness and death. Given the limited therapeutic resources and unexpected clinical features of the disease, readily accessible predictive biomarkers are urgently needed to improve patient care and management. We asked the degree to which anemia may influence the outcome of patients with COVID‐19. To this end, we identified 3777 patients who were positively diagnosed with COVID‐19 between March 1 and April 1 2020 in New York City. We evaluated 2,562 patients with available red blood cell, hemoglobin, and related laboratory values. Multivariable cox proportional hazards regression showed that anemia was a significant independent predictor of mortality (hazard ratio (HR): 1.26, 95% Confidence Interval [CI]: 1.06‐1.51), independent of age, sex, and comorbidities. There was a direct correlation between the degree of anemia and the risk of mortality when hemoglobin was treated as a continuous variable (HRadj 1.05; [CI]: 1.01‐1.09). The hemoglobin level that was maximally predictive of mortality, was 11.5 g/dL in males and 11.8 g/dL in females. These findings identify a routinely measured biomarker that is predictive of disease outcomes and will aid in refining clinical care algorithms and optimize resource allocation. Mechanisms of impacts of anemia on COVID‐19 outcome are likely to be multiple in nature and require further investigation.
Effects of mesenchymal stromal cell-derived extracellular vesicles in acute respiratory distress syndrome (ARDS): Current understanding and future perspectives
Authors: Su Yue , Guo Haiyan , Liu Qinghua
Published: May 2021

Acute respiratory distress syndrome (ARDS) is a devastating and life-threatening syndrome that results in high morbidity and mortality. Current pharmacologic treatments and mechanical ventilation have limited value in targeting the underlying pathophysiology of ARDS. Mesenchymal stromal cells (MSCs) have shown potent therapeutic advantages in experimental and clinical trials through direct cell-to-cell interaction and paracrine signaling. However, safety concerns and the indeterminate effects of MSCs have resulted in the investigation of MSC-derived extracellular vesicles (MSC-EVs) due to their low immunogenicity and tumorigenicity. Over the past decades, soluble proteins, microRNAs, and organelles packaged in EVs have been identified as efficacious molecules to orchestrate nearby immune responses, which attenuate acute lung injury by facilitating pulmonary epithelium repair, reducing acute inflammation, and restoring pulmonary vascular leakage. Even though MSC-EVs possess similar bio-functional effects to their parental cells, there remains existing barriers to employing this alternative from bench to bedside. Here, we summarize the current established research in respect of molecular mechanisms of MSC-EV effects in ARDS and highlight the future challenges of MSC-EVs for clinical application.