bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging new therapeutic antibody derivatives for cancer treatment
Authors: Jin Shijie , Sun Yanping , Liang Xiao , Gu Xinyu , Ning Jiangtao , Xu Yingchun , Chen Shuqing , Pan Liqiang
Published: February 2022

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells. The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies, such as antibody fragments, bispecific antibodies, and antibody derivatives (e.g., antibody–drug conjugates and immunocytokines). The miniaturization and multifunctionalization of antibodies are flexible and viable strategies for diagnosing or treating malignant tumors in a complex tumor environment. In this review, we summarize antibodies of various molecular types, antibody applications in cancer therapy, and details of clinical study advances. We also discuss the rationale and mechanism of action of various antibody formats, including antibody–drug conjugates, antibody–oligonucleotide conjugates, bispecific/multispecific antibodies, immunocytokines, antibody fragments, and scaffold proteins. With advances in modern biotechnology, well-designed novel antibodies are finally paving the way for successful treatments of various cancers, including precise tumor immunotherapy, in the clinic.
Desulfurivibrio spp. mediate sulfur-oxidation coupled to Sb(V) reduction, a novel biogeochemical process
Authors: Sun Xiaoxu , Kong Tianle , Li Fangbai , Häggblom Max M , Kolton Max , Lan Ling , Lau Vetter Maggie C Y , Dong Yiran , Gao Peng , Kostka Joel E , Li Baoqin , Sun Weimin
Published: February 2022

Antimony (Sb) contamination released from mine tailings represents a global threat to natural ecosystems and human health. The geochemical conditions of Sb tailings, which are oligotrophic and replete in sulfur (S) and Sb, may promote the coupled metabolism of Sb and S. In this study, multiple lines of evidence indicate that a novel biogeochemical process, S oxidation coupled to Sb(V) reduction, is enzymatically mediated by Desulfurivibrio spp. The distribution of Desulfurivibrio covaried with S and Sb concentrations, showing a high relative abundance in Sb mine tailings but not in samples from surrounding sites (i.e., soils, paddies, and river sediments). Further, the metabolic potential to couple S oxidation to Sb(V) reduction, encoded by a non-canonical, oxidative sulfite reductase (dsr) and arsenate reductase (arrA) or antimonate reductase (anrA), respectively, was found to be common in Desulfurivibrio genomes retrieved from metal-contaminated sites in southern China. Elucidation of enzymatically-catalyzed S oxidation coupled to Sb(V) reduction expands the fundamental understanding of Sb biogeochemical cycling, which may be harnessed to improve remediation strategies for Sb mine tailings.
Anaerobic carboxydotrophy in sulfur-respiring haloarchaea from hypersaline lakes
Authors: Sorokin Dimitry Y , Merkel Alexander Y , Messina Enzo , Tugui Claudia , Pabst Martin , Golyshin Peter N , Yakimov Michail M
Published: February 2022

Anaerobic carboxydotrophy is a widespread catabolic trait in bacteria, with two dominant pathways: hydrogenogenic and acetogenic. The marginal mode by direct oxidation to CO2 using an external e-acceptor has only a few examples. Use of sulfidic sediments from two types of hypersaline lakes in anaerobic enrichments with CO as an e-donor and elemental sulfur as an e-acceptor led to isolation of two pure cultures of anaerobic carboxydotrophs belonging to two genera of sulfur-reducing haloarchaea: Halanaeroarchaeum sp. HSR-CO from salt lakes and Halalkaliarchaeum sp. AArc-CO from soda lakes. Anaerobic growth of extremely halophilic archaea with CO was obligatory depended on the presence of elemental sulfur as the electron acceptor and yeast extract as the carbon source. CO served as a direct electron donor and H2 was not generated from CO when cells were incubated with or without sulfur. The genomes of the isolates encode a catalytic Ni,Fe-CODH subunit CooS (distantly related to bacterial homologs) and its Ni-incorporating chaperone CooC (related to methanogenic homologs) within a single genomic locus. Similar loci were also present in a genome of the type species of Halalkaliarchaeum closely related to AArc-CO, and the ability for anaerobic sulfur-dependent carboxydotrophy was confirmed for three different strains of this genus. Moreover, similar proteins are encoded in three of the four genomes of recently described carbohydrate-utilizing sulfur-reducing haloarchaea belonging to the genus Halapricum and in two yet undescribed haloarchaeal species. Overall, this work demonstrated for the first time the potential for anaerobic sulfur-dependent carboxydotrophy in extremely halophilic archaea.
Incidence trends for twelve cancers in younger adults—a rapid review
Authors: di Martino Erica , Smith Lesley , Bradley Stephen H. , Hemphill Scott , Wright Judy , Renzi Cristina , Bergin Rebecca , Emery Jon , Neal Richard D.
Published: February 2022

Many cancer referral guidelines use patient’s age as a key criterium to decide who should be referred urgently. A recent rise in the incidence of colorectal cancer in younger adults has been described in high-income countries worldwide. Information on other cancers is more limited. The aim of this rapid review was to determine whether other cancers are also increasing in younger age groups, as this may have important implications for prioritising patients for investigation and referral. We searched MEDLINE, Embase and Web of Science for studies describing age-related incidence trends for colorectal, bladder, lung, oesophagus, pancreas, stomach, breast, ovarian, uterine, kidney and laryngeal cancer and myeloma. ‘Younger’ patients were defined based on NICE guidelines for cancer referral. Ninety-eight studies met the inclusion criteria. Findings show that the incidence of colorectal, breast, kidney, pancreas, uterine cancer is increasing in younger age groups, whilst the incidence of lung, laryngeal and bladder cancer is decreasing. Data for oesophageal, stomach, ovarian cancer and myeloma were inconclusive. Overall, this review provides evidence that some cancers are increasingly being diagnosed in younger age groups, although the mechanisms remain unclear. Cancer investigation and referral guidelines may need updating in light of these trends.
Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)—a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma
Authors: Flach Susanne , Howarth Karen , Hackinger Sophie , Pipinikas Christodoulos , Ellis Pete , McLay Kirsten , Marsico Giovanni , Forshew Tim , Walz Christoph , Reichel Christoph A. , Gires Olivier , Canis Martin , Baumeister Philipp
Published: February 2022

Background

Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC.

Methods

We conducted a single-centre prospective cohort study to investigate ctDNA in patients with p16-negative HNSCC who received curative-intent primary surgical treatment. Whole-exome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tumour tissue. We utilised RaDaRTM, a highly sensitive personalised assay using deep sequencing for tumour-specific variants, to analyse serial pre- and post-operative plasma samples for evidence of minimal residual disease and recurrence.

Results

In 17 patients analysed, personalised panels were designed to detect 34 to 52 somatic variants. Data show ctDNA detection in baseline samples taken prior to surgery in 17 of 17 patients. In post-surgery samples, ctDNA could be detected at levels as low as 0.0006% variant allele frequency. In all cases with clinical recurrence to date, ctDNA was detected prior to progression, with lead times ranging from 108 to 253 days.

Conclusions

This study illustrates the potential of ctDNA as a biomarker for detecting minimal residual disease and recurrence in HNSCC and demonstrates the feasibility of personalised ctDNA assays for the detection of disease prior to clinical recurrence.
Primate anterior insular cortex represents economic decision variables proposed by prospect theory
Authors: Yang You-Ping , Li Xinjian , Stuphorn Veit
Published: February 2022

In humans, risk attitude is highly context-dependent, varying with wealth levels or for different potential outcomes, such as gains or losses. These behavioral effects have been modelled using prospect theory, with the key assumption that humans represent the value of each available option asymmetrically as a gain or loss relative to a reference point. It remains unknown how these computations are implemented at the neuronal level. Here we show that macaques, like humans, change their risk attitude across wealth levels and gain/loss contexts using a token gambling task. Neurons in the anterior insular cortex (AIC) encode the ‘reference point’ (i.e., the current wealth level of the monkey) and reflect ‘loss aversion’ (i.e., option value signals are more sensitive to change in the loss than in the gain context) as postulated by prospect theory. In addition, changes in the activity of a subgroup of AIC neurons correlate with the inter-trial fluctuations in choice and risk attitude. Taken together, we show that the primate AIC in risky decision-making may be involved in monitoring contextual information used to guide the animal’s willingness to accept risk.
Selective branch formation in ethylene polymerization to access precise ethylene-propylene copolymers
Authors: Zhang Yuxing , Kang Xiaohui , Jian Zhongbao
Published: February 2022

Polyolefins with branches produced by ethylene alone via chain walking are highly desired in industry. Selective branch formation from uncontrolled chain walking is a long-standing challenge to generate exclusively branched polyolefins, however. Here we report such desirable microstructures in ethylene polymerization by using sterically constrained α-diimine nickel(II)/palladium(II) catalysts at 30 °C–90 °C that fall into industrial conditions. Branched polyethylenes with exclusive branch pattern of methyl branches (99%) and notably selective branch distribution of 1,4-Me2 unit (86%) can be generated. The ultrahigh degree of branching (>200 Me/1000 C) enables the well-defined product to mimic ethylene-propylene copolymers. More interestingly, branch distribution is predictable and computable by using a simple statistical model of p(1-p)n (p: the probability of branch formation). Mechanistic insights into the branch formation including branch pattern and branch distribution by an in-depth density functional theory (DFT) calculation are elucidated.
Robust but weak winter atmospheric circulation response to future Arctic sea ice loss
Authors: Smith D. M. , Eade R. , Andrews M. B. , Ayres H. , Clark A. , Chripko S. , Deser C. , Dunstone N. J. , García-Serrano J. , Gastineau G. , Graff L. S. , Hardiman S. C. , He B. , Hermanson L. , Jung T. , Knight J. , Levine X. , Magnusdottir G. , Manzini E. , Matei D. , Mori M. , Msadek R. , Ortega P. , Peings Y. , Scaife A. A. , Screen J. A. , Seabrook M. , Semmler T. , Sigmond M. , Streffing J. , Sun L. , Walsh A.
Published: February 2022

The possibility that Arctic sea ice loss weakens mid-latitude westerlies, promoting more severe cold winters, has sparked more than a decade of scientific debate, with apparent support from observations but inconclusive modelling evidence. Here we show that sixteen models contributing to the Polar Amplification Model Intercomparison Project simulate a weakening of mid-latitude westerlies in response to projected Arctic sea ice loss. We develop an emergent constraint based on eddy feedback, which is 1.2 to 3 times too weak in the models, suggesting that the real-world weakening lies towards the higher end of the model simulations. Still, the modelled response to Arctic sea ice loss is weak: the North Atlantic Oscillation response is similar in magnitude and offsets the projected response to increased greenhouse gases, but would only account for around 10% of variations in individual years. We further find that relationships between Arctic sea ice and atmospheric circulation have weakened recently in observations and are no longer inconsistent with those in models.
Defect-driven antiferromagnetic domain walls in CuMnAs films
Authors: Reimers Sonka , Kriegner Dominik , Gomonay Olena , Carbone Dina , Krizek Filip , Novák Vit , Campion Richard P. , Maccherozzi Francesco , Björling Alexander , Amin Oliver J. , Barton Luke X. , Poole Stuart F. , Omari Khalid A. , Michalička Jan , Man Ondřej , Sinova Jairo , Jungwirth Tomáš , Wadley Peter , Dhesi Sarnjeet S. , Edmonds Kevin W.
Published: February 2022

Efficient manipulation of antiferromagnetic (AF) domains and domain walls has opened up new avenues of research towards ultrafast, high-density spintronic devices. AF domain structures are known to be sensitive to magnetoelastic effects, but the microscopic interplay of crystalline defects, strain and magnetic ordering remains largely unknown. Here, we reveal, using photoemission electron microscopy combined with scanning X-ray diffraction imaging and micromagnetic simulations, that the AF domain structure in CuMnAs thin films is dominated by nanoscale structural twin defects. We demonstrate that microtwin defects, which develop across the entire thickness of the film and terminate on the surface as characteristic lines, determine the location and orientation of 180∘ and 90∘ domain walls. The results emphasize the crucial role of nanoscale crystalline defects in determining the AF domains and domain walls, and provide a route to optimizing device performance.
Spatial-temporal dynamics of a microbial cooperative behavior resistant to cheating
Authors: Monaco Hilary , Liu Kevin S. , Sereno Tiago , Deforet Maxime , Taylor Bradford P. , Chen Yanyan , Reagor Caleb C. , Xavier Joao B.
Published: February 2022

Much of our understanding of bacterial behavior stems from studies in liquid culture. In nature, however, bacteria frequently live in densely packed spatially-structured communities. How does spatial structure affect bacterial cooperative behaviors? In this work, we examine rhamnolipid production—a cooperative and virulent behavior of Pseudomonas aeruginosa. Here we show that, in striking contrast to well-mixed liquid culture, rhamnolipid gene expression in spatially-structured colonies is strongly associated with colony specific growth rate, and is impacted by perturbation with diffusible quorum signals. To interpret these findings, we construct a data-driven statistical inference model which captures a length-scale of bacterial interaction that develops over time. Finally, we find that perturbation of P. aeruginosa swarms with quorum signals preserves the cooperating genotype in competition, rather than creating opportunities for cheaters. Overall, our data demonstrate that the complex response to spatial localization is key to preserving bacterial cooperative behaviors.
Enhanced germline stem cell longevity in Drosophila diapause
Authors: Easwaran Sreesankar , Van Ligten Matthew , Kui Mackenzie , Montell Denise J.
Published: February 2022

In many species including humans, aging reduces female fertility. Intriguingly, some animals preserve fertility longer under specific environmental conditions. For example, at low temperature and short day-length,Drosophila melanogasterenters a state called adult reproductive diapause. As in other stressful conditions, ovarian development arrests at the yolk uptake checkpoint; however, mechanisms underlying fertility preservation and post-diapause recovery are largely unknown. Here, we report that diapause causes more complete arrest than other stresses yet preserves greater recovery potential. During dormancy, germline stem cells (GSCs) incur DNA damage, activate p53 and Chk2, and divide less. Despite reduced niche signaling, germline precursor cells do not differentiate. GSCs adopt an atypical, suspended state connected to their daughters. Post-diapause recovery of niche signaling and resumption of division contribute to restoring GSCs. Mimicking one feature of quiescence, reduced juvenile hormone production, enhanced GSC longevity in non-diapausing flies. Thus, diapause mechanisms provide approaches to GSC longevity enhancement.
Unprecedentedly high activity and selectivity for hydrogenation of nitroarenes with single atomic Co1-N3P1 sites
Authors: Jin Hongqiang , Li Peipei , Cui Peixin , Shi Jinan , Zhou Wu , Yu Xiaohu , Song Weiguo , Cao Changyan
Published: February 2022

Transition metal single atom catalysts (SACs) with M1-Nx coordination configuration have shown outstanding activity and selectivity for hydrogenation of nitroarenes. Modulating the atomic coordination structure has emerged as a promising strategy to further improve the catalytic performance. Herein, we report an atomic Co1/NPC catalyst with unsymmetrical single Co1-N3P1 sites that displays unprecedentedly high activity and chemoselectivity for hydrogenation of functionalized nitroarenes. Compared to the most popular Co1-N4 coordination, the electron density of Co atom in Co1-N3P1 is increased, which is more favorable for H2 dissociation as verified by kinetic isotope effect and density functional theory calculation results. In nitrobenzene hydrogenation reaction, the as-synthesized Co1-N3P1 SAC exhibits a turnover frequency of 6560 h−1, which is 60-fold higher than that of Co1-N4 SAC and one order of magnitude higher than the state-of-the-art M1-Nx-C SACs in literatures. Furthermore, Co1-N3P1 SAC shows superior selectivity (>99%) toward many substituted nitroarenes with co-existence of other sensitive reducible groups. This work is an excellent example of relationship between catalytic performance and the coordination environment of SACs, and offers a potential practical catalyst for aromatic amine synthesis by hydrogenation of nitroarenes.
Enhanced corrosion resistance by engineering crystallography on metals
Authors: Wei X. X. , Zhang B. , Wu B. , Wang Y. J. , Tian X. H. , Yang L. X. , Oguzie E. E. , Ma X. L.
Published: February 2022

Nanometer-thick passive films, which impart superior corrosion resistance to metals, are degraded in long-term service; they are also susceptible to chloride-induced localized attack. Here we show, by engineering crystallographic configurations upon metal matrices adjacent to their passive films, we obtain great enhancement of corrosion resistance of FeCr15Ni15 single crystal in sulphuric acid, with activation time up to two orders of magnitude longer than that of the non-engineered counterparts. Meanwhile, engineering crystallography decreases the passive current density and shifts the pitting potential to noble values. Applying anodic polarizations under a transpassivation potential, we make the metal matrices underneath the transpassive films highly uneven with {111}-terminated configurations, which is responsible for the enhancement of corrosion resistance. The transpassivation strategy also works in the commercial stainless steels where both grain interior and grain boundaries are rebuilt into the low-energy configurations. Our results demonstrate a technological implication in the pretreatment process of anti-corrosion engineering.
Perovskite multifunctional logic gates via bipolar photoresponse of single photodetector
Authors: Kim Woochul , Kim Hyeonghun , Yoo Tae Jin , Lee Jun Young , Jo Ji Young , Lee Byoung Hun , Sasikala Assa Aravindh , Jung Gun Young , Pak Yusin
Published: February 2022

The explosive demand for a wide range of data processing has sparked interest towards a new logic gate platform as the existing electronic logic gates face limitations in accurate and fast computing. Accordingly, optoelectronic logic gates (OELGs) using photodiodes are of significant interest due to their broad bandwidth and fast data transmission, but complex configuration, power consumption, and low reliability issues are still inherent in these systems. Herein, we present a novel all-in-one OELG based on the bipolar spectral photoresponse characteristics of a self-powered perovskite photodetector (SPPD) having a back-to-back p+-i-n-p-p+ diode structure. Five representative logic gates (“AND”, “OR”, “NAND”, “NOR”, and “NOT”) are demonstrated with only a single SPPD via the photocurrent polarity control. For practical applications, we propose a universal OELG platform of integrated 8 × 8 SPPD pixels, demonstrating the 100% accuracy in five logic gate operations irrelevant to current variation between pixels.
Sleep health composites are associated with the risk of heart disease across sex and race
Authors: Lee Soomi , Mu Christina X. , Wallace Meredith L. , Andel Ross , Almeida David M. , Buxton Orfeu M. , Patel Sanjay R.
Published: February 2022

We examined whether subjectively and objectively measured sleep health composites have a relationship with heart disease. 6,820 adults (Mage = 53.4 years) from the Midlife in the United States study provided self-reported sleep characteristics and heart disease history. A smaller sample (n = 663) provided actigraphy sleep data. We tested two sleep health composites, based on self-report only and both self-report and actigraphy, across multiple sleep dimensions. We used a weighted sum approach, where higher scores indicated more sleep health problems. Modified Poisson regressions adjusted for sociodemographics and known risk factors. Having more sleep health problems was associated with a higher risk of heart disease using the self-report sleep health composite (aRR = 54%, P < .001) and the actigraphy/self-report composite (aRR = 141%, P < .001). Individual sleep dimensions of satisfaction, alertness, and efficiency (from the self-report composite) and regularity, satisfaction, and timing (from the actigraphy/self-report composite) were associated with the risk of heart disease. The effect size of each sleep health composite was larger than the individual sleep dimensions. Race moderated the association between the actigraphy/self-report sleep health composite and heart disease. There was no significant moderation by sex. Findings suggest poorer sleep health across multiple dimensions may contribute to heart disease risk among middle-aged adults.
Inequality and inequity in network-based ranking and recommendation algorithms
Authors: Espín-Noboa Lisette , Wagner Claudia , Strohmaier Markus , Karimi Fariba
Published: February 2022

Though algorithms promise many benefits including efficiency, objectivity and accuracy, they may also introduce or amplify biases. Here we study two well-known algorithms, namely PageRank and Who-to-Follow (WTF), and show to what extent their ranks produceinequalityandinequitywhen applied to directed social networks. To this end, we propose adirected network model withpreferentialattachment andhomophily (DPAH) and demonstrate the influence of network structure on the rank distributions of these algorithms. Our main findings suggest that (i) inequality is positively correlated with inequity, (ii) inequality is driven by the interplay between preferential attachment, homophily, node activity and edge density, and (iii) inequity is driven by the interplay between homophily and minority size. In particular, these two algorithmsreduce,replicateandamplifythe representation of minorities in top ranks when majorities are homophilic, neutral and heterophilic, respectively. Moreover, when this representation is reduced, minorities may improve their visibility in the rank by connecting strategically in the network. For instance, by increasing their out-degree or homophily when majorities are also homophilic. These findings shed light on the social and algorithmic mechanisms that hinder equality and equity in network-based ranking and recommendation algorithms.
Modelling of the dynamic polarizability of macromolecules for single-molecule optical biosensing
Authors: Booth Larnii S. , Browne Eloise V. , Mauranyapin Nicolas P. , Madsen Lars S. , Barfoot Shelley , Mark Alan , Bowen Warwick P.
Published: February 2022

The structural dynamics of macromolecules is important for most microbiological processes, from protein folding to the origins of neurodegenerative disorders. Noninvasive measurements of these dynamics are highly challenging. Recently, optical sensors have been shown to allow noninvasive time-resolved measurements of the dynamic polarizability of single-molecules. Here we introduce a method to efficiently predict the dynamic polarizability from the atomic configuration of a given macromolecule. This provides a means to connect the measured dynamic polarizability to the underlying structure of the molecule, and therefore to connect temporal measurements to structural dynamics. To illustrate the methodology we calculate the change in polarizability as a function of time based on conformations extracted from molecular dynamics simulations and using different conformations of motor proteins solved crystalographically. This allows us to quantify the magnitude of the changes in polarizablity due to thermal and functional motions.
Numerical modeling and analysis of coaxial electrohydrodynamic jet printing
Authors: Wang Dazhi , Abbas Zeshan , Lu Liangkun , Zhao Xiangyu , Xu Pengfei , Zhao Kuipeng , Yin Penghe , Liang Junsheng
Published: February 2022

Coaxial electrohydrodynamic jet (CE-Jet) printing is an encouraging method for fabrication of high-resolution micro and nanostructures in MEMS systems. This paper presents a novel simulation work based on phase field method which is considered as a precise technique in fluid dynamics. The study explores influence of various parameters such as applied voltage, needle-substrate distance, dynamic viscosity, relative permittivity, needle size and flow rate on stability and resolution of CE-Jet morphologies. The morphology of CE-Jet exhibits that width of cone-jet profile and printed structures on substrate were directly proportional to relative permittivity and flow rate. In addition, it was inversely proportional to dynamic viscosity and applied voltage. The study examine that CE-Jet length of inner liquid is inversely proportional to needle-substrate distance in same time. It was later verified in experimental study by producing stable CE-Jet morphology with 300 μm diameter using optimized parameters (i.e., DC voltage 7.0 kV and inner liquid flow rate 400 nl/min) as compared to other validation studies such as 400 μm and 500 μm. The CE-Jet printing technique investigates significant changes in consistency and stability of CE-Jet morphologies and makes Jet unique and comparable when adjustment accuracy reaches 0.01 mm. PZT sol line structures with a diameter of 1 µm were printed directly on substrate using inner needle (diameter of 120 µm). Therefore, it is considered as a powerful tool for nano constructs production in M/NEMS devices.
Binding of cationic analogues of α-MSH to lipopolysaccharide and disruption of the cytoplasmic membranes caused bactericidal action against Escherichia coli
Authors: Tiwari Kanchan , Singh Madhuri , Kumar Prince , Mukhopadhyay Kasturi
Published: February 2022

In earlier reports, we have shown the antimicrobial activity of a host neuropeptide, alpha-melanocyte stimulating hormone (α-MSH) and its cationic analogues against Staphylococcus aureus. These analogues of α-MSH showed enhanced staphylocidal activity without any significant mammalian cell toxicity. Therefore, here, we explored the antimicrobial activity of α-MSH and its cationic analogues against Escherichia coli. Though the presence of lipopolysaccharide (LPS) in Gram-negative bacteria enables them to resist most conventional antibiotics, encouragingly α-MSH and its four analogues showed killing of both logarithmic and stationary phase E. coli cells in a time, dose and cationicity-dependent manner. In fact, the most cationic analogue, KKK-MSH with a + 5 charge, demonstrated successful eradication of 105 CFU/mL of E. coli cells within 15 min at a concentration as low as 1 µM. BC displacement experiment revealed that cationicity of the peptides was directly related to the killing efficacy of these α-MSH analogues against E. coli cells via initial LPS-binding, leading to rapid disruption of the LPS-outer membrane complex followed by inner bacterial membrane damage and eventual cell death. Here, we propose α-MSH based cationic peptides as promising future agents with broad-spectrum antibacterial efficacy against both Gram-negative and Gram-positive pathogens.
Prioritization of putatively detrimental variants in euploid miscarriages
Authors: Buonaiuto Silvia , Biase Immacolata Di , Aleotti Valentina , Ravaei Amin , Marino Adriano De , Damaggio Gianluca , Chierici Marco , Pulijala Madhuri , D’Ambrosio Palmira , Esposito Gabriella , Ayub Qasim , Furlanello Cesare , Greco Pantaleo , Capalbo Antonio , Rubini Michele , Biase Sebastiano Di , Colonna Vincenza
Published: February 2022

Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed gp , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.
Climate and demography drive 7000 years of dietary change in the Central Andes
Authors: Wilson Kurt M. , McCool Weston C. , Brewer Simon C. , Zamora-Wilson Nicole , Schryver Percy J. , Lamson Roxanne Lois F. , Huggard Ashlyn M. , Brenner Coltrain Joan , Contreras Daniel A. , Codding Brian F.
Published: February 2022

Explaining the factors that influence past dietary variation is critically important for understanding changes in subsistence, health, and status in past societies; yet systematic studies comparing possible driving factors remain scarce. Here we compile the largest dataset of past diet derived from stable isotope δ13C‰ and δ15N‰ values in the Americas to quantitatively evaluate the impact of 7000 years of climatic and demographic change on dietary variation in the Central Andes. Specifically, we couple paleoclimatic data from a general circulation model with estimates of relative past population inferred from archaeologically derived radiocarbon dates to assess the influence of climate and population on spatiotemporal dietary variation using an ensemble machine learning model capable of accounting for interactions among predictors. Results reveal that climate and population strongly predict diet (80% of δ15N‰ and 66% of δ13C‰) and that Central Andean diets correlate much more strongly with local climatic conditions than regional population size, indicating that the past 7000 years of dietary change was influenced more by climatic than socio-demographic processes. Visually, the temporal pattern suggests decreasing dietary variation across elevation zones during the Late Horizon, raising the possibility that sociopolitical factors overrode the influence of local climatic conditions on diet during that time. The overall findings and approach establish a general framework for understanding the influence of local climate and demography on dietary change across human history.
Young children’s screen time during the first COVID-19 lockdown in 12 countries
Authors: Bergmann Christina , Dimitrova Nevena , Alaslani Khadeejah , Almohammadi Alaa , Alroqi Haifa , Aussems Suzanne , Barokova Mihaela , Davies Catherine , Gonzalez-Gomez Nayeli , Gibson Shannon P. , Havron Naomi , Horowitz-Kraus Tzipi , Kanero Junko , Kartushina Natalia , Keller Christina , Mayor Julien , Mundry Roger , Shinskey Jeanne , Mani Nivedita
Published: February 2022

Older children with online schooling requirements, unsurprisingly, were reported to have increased screen time during the first COVID-19 lockdown in many countries. Here, we ask whether younger children with no similar online schooling requirements also had increased screen time during lockdown. We examined children’s screen time during the first COVID-19 lockdown in a large cohort (n = 2209) of 8-to-36-month-olds sampled from 15 labs across 12 countries. Caregivers reported that toddlers with no online schooling requirements were exposed to more screen time during lockdown than before lockdown. While this was exacerbated for countries with longer lockdowns, there was no evidence that the increase in screen time during lockdown was associated with socio-demographic variables, such as child age and socio-economic status (SES). However, screen time during lockdown was negatively associated with SES and positively associated with child age, caregiver screen time, and attitudes towards children’s screen time. The results highlight the impact of the COVID-19 lockdown on young children’s screen time.
The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients
Authors: Mertens Ann , Gadeyne Stefanie , Lescrauwaet Emma , Carrette Evelien , Meurs Alfred , De Herdt Veerle , Dewaele Frank , Raedt Robrecht , Miatton Marijke , Boon Paul , Vonck Kristl
Published: February 2022

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.

Clinical trial registration number: NCT05031208.
Double-observer approach with camera traps can correct imperfect detection and improve the accuracy of density estimation of unmarked animal populations
Authors: Nakashima Yoshihiro , Hongo Shun , Mizuno Kaori , Yajima Gota , Dzefck Zeun’s C. B.
Published: February 2022

Camera traps are a powerful tool for wildlife surveys. However, camera traps may not always detect animals passing in front. This constraint may create a substantial bias in estimating critical parameters such as the density of unmarked populations. We proposed the 'double-observer approach' with camera traps to counter the constraint, which involves setting up a paired camera trap at a station and correcting imperfect detection with a reformulated hierarchical capture-recapture model for stratified populations. We performed simulations to evaluate this approach's reliability and determine how to obtain desirable data for this approach. We then applied it to 12 mammals in Japan and Cameroon. The results showed that the model assuming a beta-binomial distribution as detection processes could correct imperfect detection as long as paired camera traps detect animals nearly independently (Correlation coefficient ≤ 0.2). Camera traps should be installed to monitor a predefined small focal area from different directions to satisfy this requirement. The field surveys showed that camera trap could miss animals by 3–40%, suggesting that current density estimation models relying on perfect detection may underestimate animal density by the same order of magnitude. We hope that our approach will be incorporated into existing density estimation models to improve their accuracy.
Accessing the degree of Majorana nonlocality in a quantum dot-optical microcavity system
Authors: Ricco L. S. , Kozin V. K. , Seridonio A. C. , Shelykh I. A.
Published: February 2022

We explore the tunneling transport properties of a quantum dot embedded in an optical microcavity and coupled to a semiconductor-superconductor one-dimensional nanowire (Majorana nanowire) hosting Majorana zero modes (MZMs) at their edges. Conductance profiles reveal that strong light-matter coupling can be employed to distinguish between the cases of highly nonlocal MZMs, overlapped MZMs and MZMs with less degree of nonlocal feature. Moreover, we show that it is possible to access the degree of Majorana nonlocality (topological quality factor) by changing the dot spectrum through photon-induced transitions tuned by an external pump applied to the microcavity.
Internal friction angle model of particles
Authors: Zegzulka Jiri , Necas Jan , Rozbroj Jiri , Gelnar Daniel , Ramírez-Gómez Álvaro , Jezerska Lucie
Published: February 2022

Currently, pressure from industry to streamline processes by creating their simulation models, and thus to gradual digitization is increasing. The essence of representative simulation models of bulk materials is to understand the principles and laws of the real behavior of particles. The aim of this study is therefore to find and quantify the possibilities and principles of how particles can change their position relative to other particles. The possibilities of particle displacements were expressed using their specific trajectories and work ratios, or internal friction angle values. This created a new comprehensive model of the internal friction angle of particles independent of particle size. It enables the interpretation of the determined values of the angles of internal friction of particles and its application in the field of simulations of mass and process models. The model can be used to determine the basic composition of particles in volume and the dominant ways of their mutual displacements.
Ca2+-imaging and photo-manipulation of the simple gut of zebrafish larvae in vivo
Authors: Okamoto Shin-ichi , Hatta Kohei
Published: February 2022

Zebrafish larval gut could be considered as an excellent model to study functions of vertebrate digestive organs, by virtue of its simplicity and transparency as well as the availability of mutants. However, there has been scant investigation of the detailed behavior of muscular and enteric nervous systems to convey bolus, an aggregate of digested food. Here we visualized peristalsis using transgenic lines expressing a genetically encoded Ca2+sensor in the circular smooth muscles. An intermittent Ca2+signal cycle was observed at the oral side of the bolus, with Ca2+waves descending and ascending from there. We also identified a regular cycle of weaker movement that occurs regardless of the presence or absence of bolus, corresponding likely to slow waves. Direct photo-stimulation of circular smooth muscles expressing ChR2 could cause local constriction of the gut, while the stimulation of a single or a few neurons could cause the local induction or arrest of gut movements. These results indicate that the larval gut of zebrafish has basic features found in adult mammals despite the small number of enteric neurons, providing a foundation for the study, at the single-cell level in vivo,in controlling the gut behaviors in vertebrates.
Comparison of global definitions of metabolic syndrome in early pregnancy among the Rajarata Pregnancy Cohort participants in Sri Lanka
Authors: Jayasinghe Imasha Upulini , Agampodi Thilini Chanchala , Dissanayake Ajith Kumara , Srimantha Shalka Madushan , Agampodi Suneth Buddhika
Published: February 2022

Metabolic syndrome (MetS) in pregnancy shows epigenetic associations with intergenerational inheritance of metabolic diseases. The presence of different diagnostic criteria influences MetS prevalence estimates. We evaluated MetS and metabolic derangements to determine the utility of its assessment in early pregnancy. A cross-sectional analysis of metabolic derangements in pregnant women with period of gestation (POG) ≤ 12 weeks was done among Rajarata Pregnancy Cohort participants in Sri Lanka. 2682 women with mean age 27.9 year (SD-5.5) and median POG 8.0wk (IQR-3) were analyzed. Mean levels of triglycerides (TG), total cholesterol (TC), high-density-lipoprotein (HDL), low-density-lipoprotein (LDL), fasting plasma glucose, and 2 h oral glucose tolerance test were 87.71 (SD 38.7), 172.2 (SD 34.7), 49.6 (SD 11.5), 122.6 (SD 32.3), 82.2 (SD 12.8) and 120.3 (SD 11.5) respectively. All serum lipids except LDL increase significantly from 6 to 12 weeks, with TG by 23 and TC by 8 units. High MetS prevalence was observed with AHA/NHLBI (n = 150, 5.6%, 95% CI 4.8–6.5) followed by IDF (n = 144, 5.4%, 95% CI 4.6–6.3), NCEP-ATP III (n = 112, 4.2%, 95% CI 3.4–5.0) and WHO (n = 81, 3.0%, 95% CI 2.4–3.7) definitions respectively. Significant difference in prevalence was noted among different sociodemographic characteristics (p < 0.001). Regardless of the criterion used, the change of metabolic parameters in early pregnancy leads to significant differences in prevalence estimates of MetS. The best MetS definition concerning pregnancy outcomes needs to be determined with prospective studies.
Impacts of corn stover management and fertilizer application on soil nutrient availability and enzymatic activity
Authors: Galindo Fernando S. , Strock Jeffrey S. , Pagliari Paulo H.
Published: February 2022

Corn stover is a global resource used in many industrial sectors including bioenergy, fuel, and livestock operations. However, stover removal can negatively impact soil nutrient availability, especially nitrogen (N) and phosphorus (P), biological activity, and soil health. We evaluated the effects of corn stover management combined with N and P fertilization on soil quality, using soil chemical (nitrate, ammonium and Bray-1 P) and biological parameters (β-glucosidase, alkaline phosphatase, arylsulfatase activities and fluorescein diacetate hydrolysis—FDA). The experiment was performed on a Mollisol (Typic Endoaquoll) in a continuous corn system from 2013 to 2015 in Minnesota, USA. The treatments tested included six N rates (0 to 200 kg N ha−1), five P rates (0 to 100 kg P2O5 ha−1), and two residue management strategies (residue removed or incorporated) totalling 60 treatments. Corn stover management significantly impacted soil mineral-N forms and enzyme activity. In general, plots where residue was incorporated were found to have high NH4+ and enzyme activity compared to plots where residue was removed. In contrast, fields where residue was removed showed higher NO3− than plots where residue was incorporated. Residue management had little effect on soil available P. Soil enzyme activity was affected by both nutrient and residue management. In most cases, activity of the enzymes measured in plots where residue was removed frequently showed a positive response to added N and P. In contrast, soil enzyme responses to applied N and P in plots where residue was incorporated were less evident. Soil available nutrients tended to decrease in plots where residue was removed compared with plots where residue was incorporated. In conclusion, stover removal was found to have significant potential to change soil chemical and biological properties and caution should be taken when significant amounts of stover are removed from continuous corn fields. The residue removal could decrease different enzymes related to C-cycle (β-glucosidase) and soil microbial activity (FDA) over continuous cropping seasons, impairing soil health.
The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli
Authors: Lindblad Anna , Johansson Charlotte , Persson Katarina , Demirel Isak
Published: February 2022

The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1β release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response of bladder epithelial cells during infection with uropathogenic Escherichia coli (UPEC). Human bladder epithelial cells (5637) and CRISPR/Cas9 generated caspase-1, caspase-4 and NLRP3 knockdown cells were stimulated with the UPEC strain CFT073. Using Olink proteomics and real time RT-PCR, we showed that caspase-1, caspase-4 and NLRP3 are vital for the expression of many inflammatory genes and proteins from bladder epithelial cells. When investigating the effect of inflammasome-associated proteins on neutrophils, we found that conditioned medium from UPEC-infected caspase-4 knockdown cells significantly increased phagocytosis of CFT073 and significantly decreased ROS production from neutrophils. In contrast, conditioned medium from UPEC-infected NLRP3 knockdown cells significantly decreased the phagocytosis of CFT073 and significantly increased the ROS production from neutrophils. In conclusion, we showed that the inflammasome-associated proteins contribute to the host cell response during UPEC infection.
Trends in quality of primary care in the United States, 2007–2016
Authors: Saxena Anshul , Ramamoorthy Venkataraghavan , Rubens Muni , McGranaghan Peter , Veledar Emir , Nasir Khurram
Published: February 2022

During the past decade, many reforms were proposed and implemented for improving primary care in the US. This study assessed improvements in quality of primary care, using a nationally representative database. We conducted a retrospective trend analysis of National Inpatient Sample data (2007–2016). The quality of primary care was assessed using Prevention Quality Indicators (PQIs), which consist of 13 sets of preventable hospitalization conditions. PQI hospitalization decreased from 154,565 to 151,168 per million hospitalizations during the study period (relative decrease, 2.2%; P = 0.041). Age-adjusted hospitalization rate increased for diabetes short-term complications (relative increase, 46.9%; P < 0.001) and lower-extremity amputations (relative increase, 15.1%; P = 0.035). Age stratified trends showed that hospitalization rates decreased significantly in all age-groups for diabetes short-term complications. For lower-extremity amputations, hospitalization rates increased significantly in younger age groups and decreased significantly in the older age groups. All other PQIs showed either decreasing or no change in trends. Adults aged 18–64 years should be the focus for future prevention attempts for diabetes complications. Identifying and acting on the factors responsible for these changes could help in reversing the concerning trends observed in this study. Existing strategies should focus on improving access to diabetes care and self-management.