bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking specific biological signatures to different childhood adversities: findings from the HERO project
Authors: de Mendonça Filho Euclides José , Pokhvisneva Irina , Maalouf Christina Maria , Parent Carine , Mliner Shanna B. , Slopen Natalie , Williams David R. , Bush Nicole R. , Boyce William Thomas , Levitt Pat , Nelson Charles A. , Gunnar Megan R. , Meaney Michael J. , Shonkoff Jack P. , Silveira Patricia Pelufo ,   on behalf of the JPB Research Network on Toxic Stress
Published: January 2023

Background

Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited.

Methods

Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1β, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145).

Results

Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1β (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample.

Conclusions

Our results indicate that these biological response systems may react differently to different forms of early-life adversity.

Impact

Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking.

Children with higher socioeconomic disadvantage had higher TNF-α, IL-1β, and DHEA.

Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage.

Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.
Nucleic acid drug vectors for diagnosis and treatment of brain diseases
Authors: Lu Zhi-Guo , Shen Jie , Yang Jun , Wang Jing-Wen , Zhao Rui-Chen , Zhang Tian-Lu , Guo Jing , Zhang Xin
Published: January 2023

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.
Evolution of snow algae, from cosmopolitans to endemics, revealed by DNA analysis of ancient ice
Authors: Segawa Takahiro , Yonezawa Takahiro , Matsuzaki Ryo , Mori Hiroshi , Akiyoshi Ayumi , Navarro Francisco , Fujita Koji , Aizen Vladimir B , Li Zhongqin , Mano Shuhei , Takeuchi Nozomu
Published: January 2023

Recent studies of microbial biogeography have revealed the global distribution of cosmopolitans and dispersal of regional endemics, but little is known about how these processes are affected by microbial evolution. Here, we compared DNA sequences from snow/glacier algae found in an 8000-year-old ice from a glacier in central Asia with those from modern snow samples collected at 34 snow samples from globally distributed sites at the poles and mid-latitudes, to determine the evolutionary relationship between cosmopolitan and endemic phylotypes of snow algae. We further applied a coalescent theory–based demographic model to the DNA sequences. We found that the genus Raphidonema (Trebouxiophyceae) was distributed over both poles and mid-latitude regions and was detected in different ice core layers, corresponding to distinct time periods. Our results indicate that the modern cosmopolitan phylotypes belonging to Raphidonema were persistently present long before the last glacial period. Furthermore, endemic phylotypes originated from ancestral cosmopolitan phylotypes, suggesting that modern regional diversity of snow algae in the cryosphere is a product of microevolution. These findings suggest that the cosmopolitans dispersed across the world and then derived new localized endemics, which thus improves our understanding of microbial community formation by microevolution in natural environments.
Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis
Authors: Arimoto Kei-ichiro , Miyauchi Sayuri , Troutman Ty D. , Zhang Yue , Liu Mengdan , Stoner Samuel A. , Davis Amanda G. , Fan Jun-Bao , Huang Yi-Jou , Yan Ming , Glass Christopher K. , Zhang Dong-Er
Published: January 2023

While immunotherapy has emerged as a breakthrough cancer therapy, it is only effective in some patients, indicating the need of alternative therapeutic strategies. Induction of cancer immunogenic cell death (ICD) is one promising way to elicit potent adaptive immune responses against tumor-associated antigens. Type I interferon (IFN) is well known to play important roles in different aspects of immune responses, including modulating ICD in anti-tumor action. However, how to expand IFN effect in promoting ICD responses has not been addressed. Here we show that depletion of ubiquitin specific protease 18 (USP18), a negative regulator of IFN signaling, selectively induces cancer cell ICD. Lower USP18 expression correlates with better survival across human selected cancer types and delays cancer progression in mouse models. Mechanistically, nuclear USP18 controls the enhancer landscape of cancer cells and diminishes STAT2-mediated transcription complex binding to IFN-responsive elements. Consequently, USP18 suppression not only enhances expression of canonical IFN-stimulated genes (ISGs), but also activates the expression of a set of atypical ISGs and NF-κB target genes, including genes such as Polo like kinase 2 (PLK2), that induce cancer pyroptosis. These findings may support the use of targeting USP18 as a potential cancer immunotherapy.
Electric vehicle batteries alone could satisfy short-term grid storage demand by as early as 2030
Authors: Xu Chengjian , Behrens Paul , Gasper Paul , Smith Kandler , Hu Mingming , Tukker Arnold , Steubing Bernhard
Published: January 2023

The energy transition will require a rapid deployment of renewable energy (RE) and electric vehicles (EVs) where other transit modes are unavailable. EV batteries could complement RE generation by providing short-term grid services. However, estimating the market opportunity requires an understanding of many socio-technical parameters and constraints. We quantify the global EV battery capacity available for grid storage using an integrated model incorporating future EV battery deployment, battery degradation, and market participation. We include both in-use and end-of-vehicle-life use phases and find a technical capacity of 32–62 terawatt-hours by 2050. Low participation rates of 12%–43% are needed to provide short-term grid storage demand globally. Participation rates fall below 10% if half of EV batteries at end-of-vehicle-life are used as stationary storage. Short-term grid storage demand could be met as early as 2030 across most regions. Our estimates are generally conservative and offer a lower bound of future opportunities.
Inferring visual space from ultra-fine extra-retinal knowledge of gaze position
Authors: Zhao Zhetuo , Ahissar Ehud , Victor Jonathan D. , Rucci Michele
Published: January 2023

It has long been debated how humans resolve fine details and perceive a stable visual world despite the incessant fixational motion of their eyes. Current theories assume these processes to rely solely on the visual input to the retina, without contributions from motor and/or proprioceptive sources. Here we show that contrary to this widespread assumption, the visual system has access to high-resolution extra-retinal knowledge of fixational eye motion and uses it to deduce spatial relations. Building on recent advances in gaze-contingent display control, we created a spatial discrimination task in which the stimulus configuration was entirely determined by oculomotor activity. Our results show that humans correctly infer geometrical relations in the absence of spatial information on the retina and accurately combine high-resolution extraretinal monitoring of gaze displacement with retinal signals. These findings reveal a sensory-motor strategy for encoding space, in which fine oculomotor knowledge is used to interpret the fixational input to the retina.
DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer
Authors: Zhivagui Maria , Hoda Areebah , Valenzuela Noelia , Yeh Yi-Yu , Dai Jason , He Yudou , Nandi Shuvro P. , Otlu Burcak , Van Houten Bennett , Alexandrov Ludmil B.
Published: January 2023

Ultraviolet A light is commonly emitted by UV-nail polish dryers with recent reports suggesting that long-term use may increase the risk for developing skin cancer. However, the effect of radiation emitted by UV-nail polish dryers on the physiology and mutagenesis of mammalian cells remains unclear. Here, we show that irradiation by a UV-nail polish dryer causes high levels of reactive oxygen species, consistent with 8-oxo-7,8-dihydroguanine damage and mitochondrial dysfunction. Analysis of somatic mutations reveals a dose-dependent increase of C:G>A:T substitutions in irradiated samples with mutagenic patterns similar to mutational signatures previously attributed to reactive oxygen species. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and permanently engrave mutations on the genomes of primary mouse embryonic fibroblasts, human foreskin fibroblasts, and human epidermal keratinocytes.
Dynamics of CLIMP-63 S-acylation control ER morphology
Authors: Sandoz Patrick A. , Denhardt-Eriksson Robin A. , Abrami Laurence , Abriata Luciano A. , Spreemann Gard , Maclachlan Catherine , Ho Sylvia , Kunz Béatrice , Hess Kathryn , Knott Graham , S. Mesquita Francisco , Hatzimanikatis Vassily , van der Goot F. Gisou
Published: January 2023

The complex architecture of the endoplasmic reticulum (ER) comprises distinct dynamic features, many at the nanoscale, that enable the coexistence of the nuclear envelope, regions of dense sheets and a branched tubular network that spans the cytoplasm. A key player in the formation of ER sheets is cytoskeleton-linking membrane protein 63 (CLIMP-63). The mechanisms by which CLIMP-63 coordinates ER structure remain elusive. Here, we address the impact of S-acylation, a reversible post-translational lipid modification, on CLIMP-63 cellular distribution and function. Combining native mass-spectrometry, with kinetic analysis of acylation and deacylation, and data-driven mathematical modelling, we obtain in-depth understanding of the CLIMP-63 life cycle. In the ER, it assembles into trimeric units. These occasionally exit the ER to reach the plasma membrane. However, the majority undergoes S-acylation by ZDHHC6 in the ER where they further assemble into highly stable super-complexes. Using super-resolution microscopy and focused ion beam electron microscopy, we show that CLIMP-63 acylation-deacylation controls the abundance and fenestration of ER sheets. Overall, this study uncovers a dynamic lipid post-translational regulation of ER architecture.
Complementary peptides represent a credible alternative to agrochemicals by activating translation of targeted proteins
Authors: Ormancey Mélanie , Guillotin Bruno , Merret Rémy , Camborde Laurent , Duboé Carine , Fabre Bertrand , Pouzet Cécile , Impens Francis , Van Haver Delphi , Carpentier Marie-Christine , Clemente Hélène San , Aguilar Marielle , Lauressergues Dominique , Scharff Lars B. , Pichereaux Carole , Burlet-Schiltz Odile , Bousquet-Antonelli Cécile , Gevaert Kris , Thuleau Patrice , Plaza Serge , Combier Jean-Philippe
Published: January 2023

The current agriculture main challenge is to maintain food production while facing multiple threats such as increasing world population, temperature increase, lack of agrochemicals due to health issues and uprising of weeds resistant to herbicides. Developing novel, alternative, and safe methods is hence of paramount importance. Here, we show that complementary peptides (cPEPs) from any gene can be designed to target specifically plant coding genes. External application of synthetic peptides increases the abundance of the targeted protein, leading to related phenotypes. Moreover, we provide evidence that cPEPs can be powerful tools in agronomy to improve plant traits, such as growth, resistance to pathogen or heat stress, without the needs of genetic approaches. Finally, by combining their activity they can also be used to reduce weed growth.
Timing and cell specificity of senescence drives postnatal lung development and injury
Authors: Yao Hongwei , Wallace Joselynn , Peterson Abigail L. , Scaffa Alejandro , Rizal Salu , Hegarty Katy , Maeda Hajime , Chang Jason L. , Oulhen Nathalie , Kreiling Jill A. , Huntington Kelsey E. , De Paepe Monique E. , Barbosa Guilherme , Dennery Phyllis A.
Published: January 2023

Senescence causes age-related diseases and stress-related injury. Paradoxically, it is also essential for organismal development. Whether senescence contributes to lung development or injury in early life remains unclear. Here, we show that lung senescence occurred at birth and decreased throughout the saccular stage in mice. Reducing senescent cells at this stage disrupted lung development. In mice (<12 h old) exposed to hyperoxia during the saccular stage followed by air recovery until adulthood, lung senescence increased particularly in type II cells and secondary crest myofibroblasts. This peaked during the alveolar stage and was mediated by the p53/p21 pathway. Decreasing senescent cells during the alveolar stage attenuated hyperoxia-induced alveolar and vascular simplification. Conclusively, early programmed senescence orchestrates postnatal lung development whereas later hyperoxia-induced senescence causes lung injury through different mechanisms. This defines the ontogeny of lung senescence and provides an optimal therapeutic window for mitigating neonatal hyperoxic lung injury by inhibiting senescence.
Deciphering the exact breakpoints of structural variations using long sequencing reads with DeBreak
Authors: Chen Yu , Wang Amy Y. , Barkley Courtney A. , Zhang Yixin , Zhao Xinyang , Gao Min , Edmonds Mick D. , Chong Zechen
Published: January 2023

Long-read sequencing has demonstrated great potential for characterizing all types of structural variations (SVs). However, existing algorithms have insufficient sensitivity and precision. To address these limitations, we present DeBreak, a computational method for comprehensive and accurate SV discovery. Based on alignment results, DeBreak employs a density-based approach for clustering SV candidates together with a local de novo assembly approach for reconstructing long insertions. A partial order alignment algorithm ensures precise SV breakpoints with single base-pair resolution, and a k-means clustering method can report multi-allele SV events. DeBreak outperforms existing tools on both simulated and real long-read sequencing data from both PacBio and Nanopore platforms. An important application of DeBreak is analyzing cancer genomes for potentially tumor-driving SVs. DeBreak can also be used for supplementing whole-genome assembly-based SV discovery.
Analytical solution of overlying pipe deformation caused by tunnel excavation based on Pasternak foundation model
Authors: Fu Daxi , Deng Bo , Yang Minghui , Zhen Binbin
Published: January 2023

The existing tunnel construction causes stratum deformation, which in turn leads to additional deformation and internal force of the overlying pipeline, thus increasing the risk of pipeline accidents. Then, how to correctly calculate the deformation and internal force of pipeline is the key to pipeline safety evaluation. To this end, this study firstly used the Pasternak foundation beam model to simulate the interaction of pipeline and soil, and divided the pipeline into the void area (i.e., pipeline-soil detachment) and the coordination area (i.e., pipeline-soil is always deformed together) between pipeline and soil. The differential equation of pipeline deflection for the void area and the coordination area were established respectively, and the solutions of pipeline deflection, the internal force of pipeline and the width of pipeline-soil void area were presented. Subsequently, the accuracy of the proposed method was verified by comparing with the available model and field test data, and it is found that the calculation results are too conservative without considering the pipeline-soil voiding phenomenon. Finally, the detailed parametric analysis was conducted. The results show that the pipeline deflection decreases with the increase of the pipeline-tunnel spacing between pipeline and tunnel, the pipeline bending stiffness and the soil elastic modulus, but increases with the increase of the formation loss rate, and the width of pipeline-soil void area increases with the increase of the pipeline-tunnel spacing, the pipeline bending stiffness and the soil elastic modulus.
Enhancement of the microwave photon-magnon coupling strength for a planar fabricated resonator
Authors: Girich Aleksey , Nedukh Sergiy , Polevoy Sergey , Sova Kateryna , Tarapov Sergey , Vakula Arthur
Published: January 2023

Planar resonators have a wide usage in modern microwave technologies and perspectives in novel quantum technologies development. As was demonstrated earlier, their utilization allows to achieve high values of microwave photon-magnon coupling strength—an important parameter in technologies of information coherent transfer from electromagnetic GHz range to the optical range. In the present work, the achievement of the high value of the microwave photon-magnon coupling strength by exploiting the increase of the spatial concentration of the magnetic component of the planar resonator electromagnetic field is reported. Starting from the conventional planar split-ring resonator design we increased the coupling strength up to 40% by modifying the resonator shape. The numerical simulation and experimental verification showed a predicted increase in the spatial concentration of the microwave magnetic component and showed the increased value of the microwave photon-magnon coupling strength as a sequence.
Chloroplasts evolved an additional layer of translational regulation based on non-AUG start codons for proteins with different turnover rates
Authors: Sadhu Leelavathi , Kumar Krishan , Kumar Saravanan , Dass Abhishek , Pathak Ranjana , Bhardwaj Amit , Pandey Pankaj , Van Cuu Nguyen , Rawat Bhupendra S. , Reddy Vanga Siva
Published: January 2023

Chloroplasts have evolved from photosynthetic cyanobacteria-like progenitors through endosymbiosis. The chloroplasts of present-day land plants have their own transcription and translation systems that show several similarities with prokaryotic organisms. A remarkable feature of the chloroplast translation system is the use of non-AUG start codons in the protein synthesis of certain genes that are evolutionarily conserved from Algae to angiosperms. However, the biological significance of such use of non-AUG codons is not fully understood. The present study was undertaken to unravel the significance of non-AUG start codons in vivo using the chloroplast genetic engineering approach. For this purpose, stable transplastomic tobacco plants expressing a reporter gene i.e. uidA (GUS) under four different start codons (AUG/UUG/GUG/CUG) were generated and β-glucuronidase (GUS) expression was compared. To investigate further the role of promoter sequences proximal to the start codon, uidA was expressed under two different chloroplast gene promoters psbA and psbC that use AUG and a non-AUG (GUG) start codons, respectively, and also showed significant differences in the DNA sequence surrounding the start codon. Further, to delineate the role of RNA editing that creates AUG start codon by editing non-AUG codons, if any, which is another important feature of the chloroplast transcription and translation system, transcripts were sequenced. In addition, a proteomic approach was used to identify the translation initiation site(s) of GUS and the N-terminal amino acid encoded when expressed under different non-AUG start codons. The results showed that chloroplasts use non-AUG start codons in combination with the translation initiation site as an additional layer of gene regulation to over-express proteins that are required at high levels due to their high rates of turnover.
Plant nitrogen retention in alpine grasslands of the Tibetan Plateau under multi-level nitrogen addition
Authors: Yu Jiaoneng , Xu-Ri  , Qu Songbo , Li Fengzi , Wei Da , Borjigidai Almaz
Published: January 2023

Nitrogen (N) deposition might alleviate degradation of alpine grassland caused by N limitation on the Tibetan Plateau (TP). To determine such limitation and quantify the N-induced N retention in plant, a six-year fertilization experiment with six levels of N addition rates (0, 1, 2, 4, 8 and 16 g N m−2 yr−1) was conducted in the Namco alpine steppe and additional 89 experiments with multi-level N addition were also synthesized worldwide among which 27 sites were on the TP. In general, N addition promoted N retention in plants, and this increasing trend diminished at the critical N rate (Ncr). The maximum N retention capacity (MNRC) of plants at Ncr was strongly correlated with initial aboveground net primary productivity with a slope of 0.02, and the MNRC of grasslands globally ranged from 0.35 to 42.59 g N m−2 yr−1, approximately account for 39% of Ncr. Tibetan alpine grassland had a low average MNRC (2.24 g N m−2 yr−1) with distinct regional characteristic, which was much lower in the western TP (0.80 g N m−2 yr−1) than the eastern TP (4.10 g N m−2 yr−1). Our results inferred 0.33–1.21 Tg N yr−1 (0.22–0.79 g N m−2 yr−1) can be retained and 5.65–20.11 Tg C yr−1 (3.67–13.06 g C m−2 yr−1) can be gained by Tibetan alpine grasslands under current N deposition level. With the aggravation of N deposition, the alpine steppe ecosystem might continuously absorb N and C until N deposition reaches Ncr.
Eco-evolutionary modelling of microbial syntrophy indicates the robustness of cross-feeding over cross-facilitation
Authors: Boza G. , Barabás G. , Scheuring I. , Zachar I.
Published: January 2023

Syntrophic cooperation among prokaryotes is ubiquitous and diverse. It relies on unilateral or mutual aid that may be both catalytic and metabolic in nature. Hypotheses of eukaryotic origins claim that mitochondrial endosymbiosis emerged from mutually beneficial syntrophy of archaeal and bacterial partners. However, there are no other examples of prokaryotic syntrophy leading to endosymbiosis. One potential reason is that when externalized products become public goods, they incite social conflict due to selfish mutants that may undermine any mutualistic interactions. To rigorously evaluate these arguments, here we construct a general mathematical framework of the ecology and evolution of different types of syntrophic partnerships. We do so both in a general microbial and in a eukaryogenetic context. Studying the case where partners cross-feed on each other’s self-inhibiting waste, we show that cooperative partnerships will eventually dominate over selfish mutants. By contrast, systems where producers actively secrete enzymes that cross-facilitate their partners’ resource consumption are not robust against cheaters over evolutionary time. We conclude that cross-facilitation is unlikely to provide an adequate syntrophic origin for endosymbiosis, but that cross-feeding mutualisms may indeed have played that role.
Characterization of diffractive bifocal intraocular lenses
Authors: Mendroch Damian , Altmeyer Stefan , Oberheide Uwe
Published: January 2023

Multifocal intraocular lenses incorporate a variety of design considerations, including dimensioning of the base monofocal shape and the diffraction grating. While studying three different lens models, we present a practical approach for mathematical modelling and evaluation of these geometries. Contrary to typical lens measurement methods, non-contact measurements were performed on the Alcon SN6AD1, HumanOptics MS 612 DAY and the AMO ZMA00 lenses using a confocal microscope. Subsequent data processing includes centering, tilting correction, filtering and an algorithmic decomposition into a conic and polynomial part and the diffraction grating. Lastly, evaluation of fitting parameters and grating shape is done to allow for inferences about further optical properties. Results and analysis show the confocal microscope to be a suitable imaging method for lens measurements. The processing of this data enables the reconstruction of the annular diffraction grating over the complete lens diameter. Apodization, near addition and diffraction efficiency characteristics are found utilizing the grating shape. Additionally, near-optical axis curvature, asphericity and higher order polynomials are identified qualitatively from the reconstruction of the monofocal base form. Derived properties also include the lens optical base and addition power. By making use of the surface geometries, as well as the lens’ material and thickness, a full lens model can be created for further studies. In summary, our analytical approach enables the insight to various intraocular lens design decisions. Furthermore, this procedure is suitable for lens model creation for research and simulation.
Protective effects of chitosan based salicylic acid nanocomposite (CS-SA NCs) in grape (Vitis vinifera cv. ‘Sultana’) under salinity stress
Authors: Aazami Mohammad Ali , Maleki Maryam , Rasouli Farzad , Gohari Gholamreza
Published: January 2023

Salinity is one of the most important abiotic stresses that reduce plant growth and performance by changing physiological and biochemical processes. In addition to improving the crop, using nanomaterials in agriculture can reduce the harmful effects of environmental stresses, particularly salinity. A factorial experiment was conducted in the form of a completely randomized design with two factors including salt stress at three levels (0, 50, and 100 mM NaCl) and chitosan-salicylic acid nanocomposite at three levels (0, 0.1, and 0.5 mM). The results showed reductions in chlorophylls (a, b, and total), carotenoids, and nutrient elements (excluding sodium) while proline, hydrogen peroxide, malondialdehyde, total soluble protein, soluble carbohydrate, total antioxidant, and antioxidant enzymes activity increased with treatment chitosan-salicylic acid nanocomposite (CS-SA NCs) under different level NaCl. Salinity stress reduced Fm', Fm, and Fv/Fm by damage to photosynthetic systems, but treatment with CS-SA NCs improved these indices during salinity stress. In stress-free conditions, applying the CS-SA NCs improved the grapes' physiological, biochemical, and nutrient elemental balance traits. CS-SA NCs at 0.5 mM had a better effect on the studied traits of grapes under salinity stress. The CS-SA nanoparticle is a biostimulant that can be effectively used to improve the grape plant yield under salinity stress.
Left atrial appendage thrombus formation, potential of resolution and association with prognosis in a large real-world cohort
Authors: Hautmann Martina , Zacher Michael , Fuchs Sophia , Pérez Christian Muñoz , Ahmidou Akram , Kerber Sebastian , Barth Sebastian
Published: January 2023

Comprehensive data on factors influencing left atrial appendage (LAA) thrombus formation, resolution and impact on survival are limited. In this single-center, retrospective study 7759 (2010–2015) patients with symptomatic ongoing atrial fibrillation (AF) on admission were screened for LAA thrombi. 450 patients had LAA thrombi. 481 patients without LAA thrombi were randomly selected as controls. We assessed clinical, echocardiographic, laboratory parameters and long-term survival of both groups. Patients with LAA thrombi compared to controls were older, had more strokes, higher CHA2DS2 -VASc scores, worse renal function, less controlled diabetes, advanced heart failure, lower LAA emptying velocities, higher levels of cardiac and inflammatory markers (all p < 0.001). 56.3% of followed-up patients (304) dissolved their LAA thrombi. Chances of thrombus resolution increased with rising LAA flow velocities (OR 1.061, p = 0.022), whereas advanced age (OR 0.950, p < 0.001) and presence of permanent AF (OR 0.354, p < 0.001) decreased chances of thrombus resolution. Presence of LAA thrombi was associated with a markedly reduced 10-year survival probability (31% versus 69%). LAA thrombus formation is promoted by advanced structural heart disease, inflammation, diabetes and impaired renal function. Younger age, non-permanent AF and higher LAA flow velocities were predictors of thrombus resolution. Thrombus formation was associated with poor prognosis.
A preclinical study comparing single- and double-root 3D-printed Ti–6Al–4V implants
Authors: Chung Inna , Lee Jungwon , Li Ling , Seol Yang-Jo , Lee Yong-Moo , Koo Ki-Tae
Published: January 2023

Recently, double-root implants have been investigated using 3D-printed technology. Here, we investigated damping capacity, microcomputed tomographic (micro-CT) and histological analyses of double-root 3D-printed implants compared with single-root 3D printed implants. Single- and double-root 3D-printed implants were fabricated and placed at both sides of mandibular third and fourth premolars in four beagle dogs. The damping capacity was measured, and periapical X-rays were taken every 2 weeks for 12 weeks. The bone volume/tissue volume (BV/TV) and bone mineral density (BMD) around the implants were measured with micro-CT. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were measured in histological samples. The implant stability values between the groups were not significantly different, except at 4 and 12 weeks. The marginal bone changes were similar at the mesial and distal areas between the groups. The BV/TV and BMD values of the double-root 3D-printed implants showed no statistical difference through micro-CT analysis, but the double-root 3D-printed implants showed lower BIC and BAFO values through histomorphometric analysis compared to the single-root 3D-printed implants. Compared to single-root implants, 3D-printed double-root implants demonstrated comparable stability and bone remodeling around the fixtures, but the statistically significant bone loss in the furcation area remains problematic.
Geographical variation of common childhood illness and its associated factors among under-five children in Ethiopia: spatial and multilevel analysis
Authors: Chilot Dagmawi , Diress Mengistie , Yismaw Gela Yibeltal , Sinamaw Deresse , Simegn Wudneh , Andualem Amare Agmas , Seid Abdulwase Mohammed , Bitew Desalegn Anmut , Seid Mohammed Abdu , Eshetu Habitu Birhan , Kibret Anteneh Ayelign , Belay Daniel Gashaneh
Published: January 2023

Although substantial progress has been made in reducing child mortality over the last three decades, the magnitude of the problem remains immense. Ethiopia is one of the countries with a high under-five mortality rate due to childhood illnesses including acute respiratory infections, diarrhea, and fever that varies from place to place. It is vital to have evidence of the factors associated with childhood illnesses and the spatial distribution across the country to prioritize and design targeted interventions. Thus, this study aimed to investigate the spatial cluster distribution and associated factors with common childhood illnesses. Secondary data analysis based on the 2016 Ethiopian Demographic and Health Survey data was carried out. A total weighted sample of 10,417 children was included. The study used ArcGIS and SaTScan software to explore spatial distribution. For associated factors, a multilevel binary logistic regression model was fitted using STATA V.14 software. Adjusted Odds Ratios (AOR) with a 95% Confidence Interval (CI) andp-value ≤ 0.05 in the multivariable model were used to declare significant factors associated with the problem. ICC, MOR, PCV, and deviance (−2LLR) were used to check model fitness and model comparison. In this study, the prevalence of common childhood illnesses among under-five children was 22.5% (95% CI: 21.6–23.3%). The spatial analysis depicted that common childhood illnesses have significant spatial variation across Ethiopia. The SaTScan analysis identified significant primary clusters in Tigray and Northern Amhara regions (log-likelihood ratio (LLR) = 60.19,p < 0.001). In the multilevel analysis, being rural residence [AOR = 1.39, 95% CI (1.01–1.98)], small child size at birth [AOR = 1.36, 95% CI (1.21–1.55)], high community poverty [AOR = 1.26, 95% CI (1.06–1.52)], mothers aged 35–49 [AOR = 0.81, 95% CI (0.69–0.94)], the household had electricity [AOR = 0.77, 95% CI (0.61–0.98)], the household had a refrigerator [AOR = 0.60, 95% CI (0.42–0.87)], improved drinking water [AOR = 0.82, 95% CI (0.70–0.95)], improved toilet [AOR = 0.72, 95% CI (0.54–0.94)], average child size at birth [AOR = 0.83, 95% CI (0.75–0.94)] were significantly associated with common childhood illnesses. Common childhood illnesses had spatial variations across Ethiopia. Hotspot areas of the problem were found in the Tigray, Northern Amhara, and Northeast SNNPR. Both individual and community-level factors affected common childhood illnesses distribution and prevalence in Ethiopia. Therefore, public health intervention should target the hotspot areas of common childhood illnesses to reduce their incidence in the country.
Using survey data to estimate the impact of the omicron variant on vaccine efficacy against COVID-19 infection
Authors: Rufino Jesús , Baquero Carlos , Frey Davide , Glorioso Christin A. , Ortega Antonio , Reščič Nina , Roberts Julian Charles , Lillo Rosa E. , Menezes Raquel , Champati Jaya Prakash , Fernández Anta Antonio
Published: January 2023

Symptoms-based detection of SARS-CoV-2 infection is not a substitute for precise diagnostic tests but can provide insight into the likely level of infection in a given population. This study uses symptoms data collected in the Global COVID-19 Trends and Impact Surveys (UMD Global CTIS), and data on variants sequencing from GISAID. This work, conducted in January of 2022 during the emergence of the Omicron variant (subvariant BA.1), aims to improve the quality of infection detection from the available symptoms and to use the resulting estimates of infection levels to assess the changes in vaccine efficacy during a change of dominant variant; from the Delta dominant to the Omicron dominant period. Our approach produced a new symptoms-based classifier, Random Forest, that was compared to a ground-truth subset of cases with known diagnostic test status. This classifier was compared with other competing classifiers and shown to exhibit an increased performance with respect to the ground-truth data. Using the Random Forest classifier, and knowing the vaccination status of the subjects, we then proceeded to analyse the evolution of vaccine efficacy towards infection during different periods, geographies and dominant variants. In South Africa, where the first significant wave of Omicron occurred, a significant reduction of vaccine efficacy is observed from August-September 2021 to December 2021. For instance, the efficacy drops from 0.81 to 0.30 for those vaccinated with 2 doses (of Pfizer/BioNTech), and from 0.51 to 0.09 for those vaccinated with one dose (of Pfizer/BioNTech or Johnson & Johnson). We also extended the study to other countries in which Omicron has been detected, comparing the situation in October 2021 (before Omicron) with that of December 2021. While the reduction measured is smaller than in South Africa, we still found, for instance, an average drop in vaccine efficacy from 0.53 to 0.45 among those vaccinated with two doses. Moreover, we found a significant negative (Pearson) correlation of around − 0.6 between the measured prevalence of Omicron in several countries and the vaccine efficacy in those same countries. This prediction, in January of 2022, of the decreased vaccine efficacy towards Omicron is in line with the subsequent increase of Omicron infections in the first half of 2022.
Validation of a motion model for soccer players’ sprint by means of tracking data
Authors: Narizuka Takuma , Takizawa Kenta , Yamazaki Yoshihiro
Published: January 2023

In soccer game analysis, the widespread availability of play-by-play and tracking data has made it possible to test mathematical models that have been discussed mainly theoretically. One of the essential models in soccer game analysis is a motion model that predicts the arrival point of a player ints. Although many space evaluation and pass prediction methods rely on motion models, the validity of each has not been fully clarified. This study focuses on the motion model proposed by Fujimura and Sugihara (Fujimura–Sugihara model) under sprint conditions based on the equation of motion. A previous study indicated that the Fujimura–Sugihara model is ineffective for soccer games because it generates a circular arrival region. This study aims to examine the validity of the Fujimura–Sugihara model using soccer tracking data. Specifically, we quantitatively compare the arrival regions of players between the model and real data. We show that the boundary of the player’s arrival region is circular rather than elliptical, which is consistent with the model. We also show that the initial speed dependence of the arrival region satisfies the solution of the model. Furthermore, we propose a method for estimating valid kinetic parameters in the model directly from tracking data and discuss the limitations of the model for soccer games based on the estimated parameters.
On the importance of structural equivalence in temporal networks for epidemic forecasting
Authors: Kister Pauline , Tonetto Leonardo
Published: January 2023

Understanding how a disease spreads in a population is a first step to preparing for future epidemics, and machine learning models are a useful tool to analyze the spreading process of infectious diseases. For effective predictions of these spreading processes, node embeddings are used to encode networks based on the similarity between nodes into feature vectors, i.e., higher dimensional representations of human contacts. In this work, we evaluated the impact ofhomophilyandstructural equivalenceon embedding for disease spread prediction by testing them on real world temporal human contact networks. Our results show that structural equivalence is a useful indicator for the infection status of a person. Embeddings that are balanced towards the preservation of structural equivalence performed better than those that focus on the preservation of homophily, with an average improvement of 0.1042 in the f1-score (95% CI 0.051 to 0.157). This indicates that structurally equivalent nodes behave similarly during an epidemic (e.g., expected time of a disease onset). This observation could greatly improve predictions of future epidemics where only partial information about contacts is known, thereby helping determine the risk of infection for different groups in the population.
Epidemiological, clinical and hematological profiles of visceral leishmaniasis among patients visiting Tefera Hailu Memorial Hospital, Northeast Ethiopia: a 4 year retrospective study
Authors: Debash Habtu , Bisetegn Habtye , Nigatie Marye , Abeje Getu , Feleke Daniel Getacher
Published: January 2023

Visceral leishmaniasis is a major, life-threatening parasitic disease that still remains a serious public health problem in Ethiopia. Understanding the epidemiological, clinical, and hematological profiles of visceral leishmaniasis patients is important for implementing evidence-based control strategies. It is also important for early treatment and to decrease the mortality rate from the disease. Therefore, this study was aimed at assessing the epidemiological, clinical, and hematological profiles of visceral leishmaniasis among patients visiting Tefera Hailu Memorial Hospital, Northeast Ethiopia. A retrospective study was conducted at Tefera Hailu Memorial Hospital from September 2017 to August 2021. Data were collected from the medical records of suspected patients who were tested by the rK39 rapid diagnostic by strictly following standard operating procedures. The data was summarized using Microsoft Excel and analyzed using SPSS 26 version software. Descriptive statistics were used to describe the epidemiological, clinical, and hematological profiles of visceral leishmaniasis patients. A p-value < 0.05 was considered statistically significant. The overall positivity rate for visceral leishmaniasis was 23.4% (132/564). The result of this study indicated a fluctuating yet declining trend in VL over the past 4 years. From a total of 132 VL confirmed cases, the numbers of cases were highest among males (78.0%), those 15–29 years of age (37.1%), and urban residents (89.4%). Furthermore, Abergele (11.0%), Sehala (6.0%), and Ziquala (5.0%) districts had the highest number of VL cases. The major clinical presentations of patients were fever (96.2%), splenomegaly (94.7%), and general weakness (80.3%). With regard to hematological profiles, the most common findings were anemia (86.4%), thrombocytopenia (81.8%), leucopenia (78.8%), neutropenia (74.2%), and pancytopenia (71.2%). In the study area, the VL positivity rate was high. Our findings also concluded that VL causes significant alterations in clinical and hematological parameters. Therefore, the zone health office and other concerned stakeholders should strengthen evidence-based control programs for VL.
Association between weekend catch-up sleep and dyslipidemia among Korean workers
Authors: Jang Ye Seul , Park Yu Shin , Hurh Kyungduk , Park Eun-Cheol , Jang Sung-In
Published: January 2023

Within competitive sociocultural environments, most Korean workers are likely to shorten their sleep duration during the weekday. Short sleep duration is associated with dyslipidemia; however, studies on the correlation between various sleep patterns and dyslipidemia are still lacking. In hence this study aimed to investigate the association between weekend catch-up sleep (CUS) and dyslipidemia among South Korean workers. Our study used data from the 8th Korea National Health and Nutrition Examination Survey (KNHANES). The analysis covered 4,085 participants, excluding those who were diagnosed with dyslipidemia and not currently participating in economic activities. Weekend CUS was calculated as the absolute difference between self-reported weekday and weekend sleep duration. Dyslipidemia was diagnosed based on the levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in blood samples collected after 9–12 h of fasting. After adjusting for sociodemographic, economic, health-related, and sleep-related factors, a negative association of weekend CUS with dyslipidemia was observed in male workers (odds ratio: 0.76, 95% confidence interval: 0.61–0.95). Further, workers with total sleep duration of 7–8 h, night workers, and white-collar workers with CUS were at relatively low risk of dyslipidemia compared to the non-CUS group. Less than 2 h of weekend CUS was negatively related to dyslipidemia in Korean workers, especially males. This suggests that sleeping more on weekends for workers who had a lack of sleep during the week can help prevent dyslipidemia.
One-class machine learning classification of skin tissue based on manually scanned optical coherence tomography imaging
Authors: Liu Xuan , Ouellette Samantha , Jamgochian Marielle , Liu Yuwei , Rao Babar
Published: January 2023

We investigated a method for automatic skin tissue characterization based on optical coherence tomography (OCT) imaging. We developed a manually scanned single fiber OCT instrument to perform in vivo skin imaging and tumor boundary assessment. The goal is to achieve more accurate tissue excision in Mohs micrographic surgery (MMS) and reduce the time required for MMS. The focus of this study was to develop a novel machine learning classification method to automatically identify abnormal skin tissues through one-class classification. We trained a deep convolutional neural network (CNN) with a U-Net architecture for automatic skin segmentation, used the pre-trained U-Net as a feature extractor, and trained one-class support vector machine (SVM) classifiers to detect abnormal tissues. The novelty of this study is the use of a neural network as a feature extractor and the use of a one-class SVM for abnormal tissue detection. Our approach eliminated the need to engineer the features for classification and eliminated the need to train the classifier with data obtained from abnormal tissues. To validate the effectiveness of the one-class classification method, we assessed the performance of our algorithm using computer synthesized data, and experimental data. We also performed a pilot study on a patient with skin cancer.
ATM inhibitor KU60019 synergistically sensitizes lung cancer cells to topoisomerase II poisons by multiple mechanisms
Authors: Shu Jianfeng , Wang Xiaofang , Yang Xuejie , Zhao Guofang
Published: January 2023

Type II topoisomerases (TOP2) poisons represent one class of the most successful and widely prescribed chemotherapeutics, which is frontline therapy for a myriad of systemic cancers and solid tumors, including lymphomas, leukemias, and lung cancer. Despite this, treatment with this class of drugs induces unwanted side effects (including cardiovascular morbidity and secondary malignancies). Additionally, the emergence of drug resistance also greatly compromises the clinical use of these drugs. To enhance therapeutic efficiency while lowering unwanted side effects, new insights into effective combination therapy are required. In this study we found that KU60019, a novel, and highly specific ATM kinase inhibitor interferes with the association of ATM with TOP2β and stabilizes TOP2β-DNA cleavage complex, thereby impairing the repair of TOP2 poison-induced DSBs and contributes to genome stability, leading to accelerated cell death. In H1299 as well as in A549 lung cancer cell lines, biologically, KU60019 combined with VP-16 (one of the TOP2 poisons) synergistically suppressed the growth of cells and survival and triggered a much higher apoptosis rate. In summary, we provide a proof-of-concept strategy that ATM inhibitors combined with TOP2 poison would synergistically suppresses lung cancer cell survival as well as reduce DNA damage responses, thus may lowering the possibility of cardiotoxicity and secondary malignancy linked to therapy.