bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
Authors: Ansari-Pour Naser , Zheng Yonglan , Yoshimatsu Toshio F. , Sanni Ayodele , Ajani Mustapha , Reynier Jean-Baptiste , Tapinos Avraam , Pitt Jason J. , Dentro Stefan , Woodard Anna , Rajagopal Padma Sheila , Fitzgerald Dominic , Gruber Andreas J. , Odetunde Abayomi , Popoola Abiodun , Falusi Adeyinka G. , Babalola Chinedum Peace , Ogundiran Temidayo , Ibrahim Nasiru , Barretina Jordi , Van Loo Peter , Chen Mengjie , White Kevin P. , Ojengbede Oladosu , Obafunwa John , Huo Dezheng , Wedge David C. , Olopade Olufunmilayo I.
Published: November 2021

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonalGATA3mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217andSYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.
Coalescence and directed anisotropic growth of starch granule initials in subdomains of Arabidopsis thaliana chloroplasts
Authors: Bürgy Léo , Eicke Simona , Kopp Christophe , Jenny Camilla , Lu Kuan Jen , Escrig Stephane , Meibom Anders , Zeeman Samuel C.
Published: November 2021

Living cells orchestrate enzyme activities to produce myriads of biopolymers but cell-biological understanding of such processes is scarce. Starch, a plant biopolymer forming discrete, semi-crystalline granules within plastids, plays a central role in glucose storage, which is fundamental to life. Combining complementary imaging techniques and Arabidopsis genetics we reveal that, in chloroplasts, multiple starch granules initiate in stromal pockets between thylakoid membranes. These initials coalesce, then grow anisotropically to form lenticular granules. The major starch polymer, amylopectin, is synthesized at the granule surface, while the minor amylose component is deposited internally. The non-enzymatic domain of STARCH SYNTHASE 4, which controls the protein’s localization, is required for anisotropic growth. These results present us with a conceptual framework for understanding the biosynthesis of this key nutrient.
BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma
Authors: Laubscher Dominik , Gryder Berkley E. , Sunkel Benjamin D. , Andresson Thorkell , Wachtel Marco , Das Sudipto , Roschitzki Bernd , Wolski Witold , Wu Xiaoli S. , Chou Hsien-Chao , Song Young K. , Wang Chaoyu , Wei Jun S. , Wang Meng , Wen Xinyu , Ngo Quy Ai , Marques Joana G. , Vakoc Christopher R. , Schäfer Beat W. , Stanton Benjamin Z. , Khan Javed
Published: November 2021

Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters the myogenic program and maintains the proliferative state while blocking terminal differentiation. Here, we investigated the contributions of chromatin regulatory complexes to FP-RMS tumor maintenance. We define the mSWI/SNF functional repertoire in FP-RMS. We find that SMARCA4 (encoding BRG1) is overexpressed in this malignancy compared to skeletal muscle and is essential for cell proliferation. Proteomic studies suggest proximity between PAX3-FOXO1 and BAF complexes, which is further supported by genome-wide binding profiles revealing enhancer colocalization of BAF with core regulatory transcription factors. Further, mSWI/SNF complexes localize to sites of de novo histone acetylation. Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes, which is recapitulated by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor.
A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division
Authors: Martini Silvia , Davis Khalil , Faraway Rupert , Elze Lisa , Lockwood Nicola , Jones Andrew , Xie Xiao , McDonald Neil Q. , Mann David J. , Armstrong Alan , Ule Jernej , Parker Peter J.
Published: November 2021

The PKCε-regulated genome protective pathway provides transformed cells a failsafe to successfully complete mitosis. Despite the necessary role for Aurora B in this programme, it is unclear whether its requirement is sufficient or if other PKCε cell cycle targets are involved. To address this, we developed a trapping strategy using UV-photocrosslinkable amino acids encoded in the PKCε kinase domain. The validation of the mRNA binding protein SERBP1 as a PKCε substrate revealed a series of mitotic events controlled by the catalytic form of PKCε. PKCε represses protein translation, altering SERBP1 binding to the 40 S ribosomal subunit and promoting the assembly of ribonucleoprotein granules containing SERBP1, termed M-bodies. Independent of Aurora B, SERBP1 is shown to be necessary for chromosome segregation and successful cell division, correlating with M-body formation. This requirement for SERBP1 demonstrates that Aurora B acts in concert with translational regulation in the PKCε-controlled pathway exerting genome protection.
Pattern transfer of large-scale thin membranes with controllable self-delamination interface for integrated functional systems
Authors: Park Jun Kyu , Zhang Yue , Xu Baoxing , Kim Seok
Published: November 2021

Direct transfer of pre-patterned device-grade nano-to-microscale materials highly benefits many existing and potential, high performance, heterogeneously integrated functional systems over conventional lithography-based microfabrication. We present, in combined theory and experiment, a self-delamination-driven pattern transfer of a single crystalline silicon thin membrane via well-controlled interfacial design in liquid media. This pattern transfer allows the usage of an intermediate or mediator substrate where both front and back sides of a thin membrane are capable of being integrated with standard lithographical processing, thereby achieving deterministic assembly of the thin membrane into a multi-functional system. Implementations of these capabilities are demonstrated in broad variety of applications ranging from electronics to microelectromechanical systems, wetting and filtration, and metamaterials.
Multi-decadal increase of forest burned area in Australia is linked to climate change
Authors: Canadell Josep G. , Meyer C. P. , Cook Garry D. , Dowdy Andrew , Briggs Peter R. , Knauer Jürgen , Pepler Acacia , Haverd Vanessa
Published: November 2021

Fire activity in Australia is strongly affected by high inter-annual climate variability and extremes. Through changes in the climate, anthropogenic climate change has the potential to alter fire dynamics. Here we compile satellite (19 and 32 years) and ground-based (90 years) burned area datasets, climate and weather observations, and simulated fuel loads for Australian forests. Burned area in Australia’s forests shows a linear positive annual trend but an exponential increase during autumn and winter. The mean number of years since the last fire has decreased consecutively in each of the past four decades, while the frequency of forest megafire years (>1 Mha burned) has markedly increased since 2000. The increase in forest burned area is consistent with increasingly more dangerous fire weather conditions, increased risk factors associated with pyroconvection, including fire-generated thunderstorms, and increased ignitions from dry lightning, all associated to varying degrees with anthropogenic climate change.
Stroke subtype-dependent synapse elimination by reactive gliosis in mice
Authors: Shi Xiaojing , Luo Longlong , Wang Jixian , Shen Hui , Li Yongfang , Mamtilahun Muyassar , Liu Chang , Shi Rubing , Lee Joon-Hyuk , Tian Hengli , Zhang Zhijun , Wang Yongting , Chung Won-Suk , Tang Yaohui , Yang Guo-Yuan
Published: November 2021

The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.
Towards non-blind optical tweezing by finding 3D refractive index changes through off-focus interferometric tracking
Authors: Landenberger Benjamin , Yatish  , Rohrbach Alexander
Published: November 2021

In modern 3D microscopy, holding and orienting arbitrary biological objects with optical forces instead of using coverslips and gel cylinders is still a vision. Although optical trapping forces are strong enough and related photodamage is acceptable, the precise (re-) orientation of large specimen with multiple optical traps is difficult, since they grab blindly at the object and often slip off. Here, we present an approach to localize and track regions with increased refractive index using several holographic optical traps with a single camera in an off-focus position. We estimate the 3D grabbing positions around several trapping foci in parallel through analysis of the beam deformations, which are continuously measured by defocused camera images of cellular structures inside cell clusters. Although non-blind optical trapping is still a vision, this is an important step towards fully computer-controlled orientation and feature-optimized laser scanning of sub-mm sized biological specimen for future 3D light microscopy.
Structural evolution of a DNA repair self-resistance mechanism targeting genotoxic secondary metabolites
Authors: Mullins Elwood A. , Dorival Jonathan , Tang Gong-Li , Boger Dale L. , Eichman Brandt F.
Published: November 2021

Microbes produce a broad spectrum of antibiotic natural products, including many DNA-damaging genotoxins. Among the most potent of these are DNA alkylating agents in the spirocyclopropylcyclohexadienone (SCPCHD) family, which includes the duocarmycins, CC-1065, gilvusmycin, and yatakemycin. The yatakemycin biosynthesis cluster inStreptomycessp. TP-A0356 contains an AlkD-related DNA glycosylase, YtkR2, that serves as a self-resistance mechanism against yatakemycin toxicity. We previously reported that AlkD, which is not present in an SCPCHD producer, provides only limited resistance against yatakemycin. We now show that YtkR2 and C10R5, a previously uncharacterized homolog found in the CC-1065 biosynthetic gene cluster ofStreptomyces zelensis, confer far greater resistance against their respective SCPCHD natural products. We identify a structural basis for substrate specificity across gene clusters and show a correlation between in vivo resistance and in vitro enzymatic activity indicating that reduced product affinity—not enhanced substrate recognition—is the evolutionary outcome of selective pressure to provide self-resistance against yatakemycin and CC-1065.
Optimal verification of the Bell state and Greenberger–Horne–Zeilinger states in untrusted quantum networks
Authors: Han Yun-Guang , Li Zihao , Wang Yukun , Zhu Huangjun
Published: November 2021

Bipartite and multipartite entangled states are basic ingredients for constructing quantum networks and their accurate verification is crucial to the functioning of the networks, especially for untrusted networks. Here we propose a simple approach for verifying the Bell state in an untrusted network in which one party is not honest. Only local projective measurements are required for the honest party. It turns out each verification protocol is tied to a probability distribution on the Bloch sphere and its performance has an intuitive geometric meaning. This geometric picture enables us to construct the optimal and simplest verification protocols, which are also very useful to detecting entanglement in the untrusted network. Moreover, we show that our verification protocols can achieve almost the same sample efficiencies as protocols tailored to standard quantum state verification. Furthermore, we establish an intimate connection between the verification of Greenberger–Horne–Zeilinger states and the verification of the Bell state. By virtue of this connection we construct the optimal protocol for verifying Greenberger–Horne–Zeilinger states and for detecting genuine multipartite entanglement.
A database of global coastal conditions
Authors: Castaneda-Guzman Mariana , Mantilla-Saltos Gabriel , Murray Kris A. , Settlage Robert , Escobar Luis E.
Published: November 2021

Remote sensing satellite imagery has the potential to monitor and understand dynamic environmental phenomena by retrieving information about Earth’s surface. Marine ecosystems, however, have been studied with less intensity than terrestrial ecosystems due, in part, to data limitations. Data on sea surface temperature (SST) and Chlorophyll-a(Chlo-a) can provide quantitative information of environmental conditions in coastal regions at a high spatial and temporal resolutions. Using the exclusive economic zone of coastal regions as the study area, we compiled monthly and annual statistics of SST and Chlo-aglobally for 2003 to 2020. This ready-to-use dataset aims to reduce the computational time and costs for local-, regional-, continental-, and global-level studies of coastal areas. Data may be of interest to researchers in the areas of ecology, oceanography, biogeography, fisheries, and global change. Target applications of the database include environmental monitoring of biodiversity and marine microorganisms, and environmental anomalies.
A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase
Authors: Douroudgari Hamed , Vahedpour Morteza
Published: November 2021

The chemical resistance of drugs against any change in their composition and studying the rate of multiwell-multichannel reactions in the liquid phase, respectively, are the important challenges of pharmacology and chemistry. In this article, we investigate two challenges together through studying drug stability against its unimolecular reactions in the liquid phase. Accordingly, multiwell-multichannel reactions based on 1,4-H shifts are designed for simplified drugs such as 3-hydroxyl-1H-pyrrol-2(5H)-one, 3-hydroxyfuran-2(5H)-one, and 3-hydroxythiophen-2(5H)-one. After that, the reverse and forward rate constants are calculated by using the Rice Ramsperger Kassel Marcus theory (RRKM) and Eckart tunneling correction over the 298–360 K temperature range. Eventually, using the obtained rate constants, we can judge drug resistance versus structural changes. To attain the goals, the potential energy surfaces of all reactions are computed by the complete basis set-quadratic Becke3 composite method, CBS-QB3, and the high-performance meta hybrid density functional method, M06-2X, along with the universal Solvation Model based on solute electron Density, SMD, due to providing more precise and efficient results for the barrier heights and thermodynamic studies. To find the main reaction pathway of the intramolecular 1,4-H shifts in the target molecules, all possible reaction pathways are considered mechanistically in the liquid phase. Also, the direct dynamics calculations that carry out by RRKM theory on the modeled pathways are used to distinguish the main reaction pathway. As the main finding of this research, the results of quantum chemical calculations accompanied by the RRKM/Eckart rate constants are used to predict the stability of drugs. This study proposes a new way to examine drug stability by the computer-aided reaction design of target drugs. Our results show that 3-hydroxyfuran-2(5H)-one based drugs are the most stable and 3-hydroxythiophen-2(5H)-one based drugs are more stable than 3-hydroxy-1H-pyrrol-2 (5H)-one based drugs in water solution.
Dual electrochemical sensing of spiked virus and SARS-CoV-2 using natural bed-receptor (MV-gal1)
Authors: Ghazizadeh E. , Neshastehriz Ali , Firoozabadi Ali Dehghani , Yazdi Mohammad Kaji , Saievar-Iranizad Esmail , Einali Samira
Published: November 2021

It has been necessary to use methods that can detect the specificity of a virus during virus screening. In this study, we use a dual platform to identify any spiked virus and specific SARS-CoV-2 antigen, sequentially. We introduce a natural bed-receptor surface as Microparticle Vesicle-Galactins1 (MV-gal1) with the ability of glycan binding to screen every spiked virus. MV are the native vesicles which may have the gal-1 receptor. Gal-1 is the one of lectin receptor which can bind to glycan. After dropping the MV-gal1 on the SCPE/GNP, the sensor is turned on due to the increased electrochemical exchange with [Fe(CN)6]−3/−4 probe. Dropping the viral particles of SARS-CoV-2 cause to turn off the sensor with covering the sugar bond (early screening). Then, with the addition of Au/Antibody-SARS-CoV-2 on the MV-gal1@SARS-CoV-2 Antigen, the sensor is turned on again due to the electrochemical amplifier of AuNP (specific detection).For the first time, our sensor has the capacity of screening of any spike virus, and the specific detection of COVID-19 (LOD: 4.57 × 102 copies/mL) by using the natural bed-receptor and a specific antibody in the point of care test.
Effect of N-methyl-d-aspartate receptor enhancing agents on cognition in dementia: an exploratory systematic review and meta-analysis of randomized controlled trials
Authors: Chang Chun-Hung , Liu Chieh-Yu , Chen Shaw-Ji , Tsai Hsin-Chi
Published: November 2021

Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer’s Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076–0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145–0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.
New cine magnetic resonance imaging parameters for the differential diagnosis of chronic intestinal pseudo-obstruction
Authors: Sato Hiroki , Ogihara Hiroyuki , Takahashi Kazuya , Kawata Yuzo , Kojima Yuichi , Tominaga Kentaro , Yokoyama Junji , Hamamoto Yoshihiko , Terai Shuji
Published: November 2021

Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder whose diagnosis currently relies on subjective imaging assessments. Cine magnetic resonance imaging (MRI) may potentially improve the quantitative analysis of gastrointestinal motility; however, suitable CIPO detection parameters should be determined. Cine MRI was performed in seven patients with CIPO and 11 healthy controls. The logarithm of the Mahalanobis distance (x1) and distance variation per time (x2) were used as the original parameters to determine CIPO diagnostic thresholds. Furthermore, the correlation between cine MRI findings and CIPO severity was investigated. Threshold values of α = 1.10 and β = 0.15 for x1 and x2, respectively, produced a CIPO diagnosis sensitivity of 1.00 (7/7) and specificity of 0.82 (9/11). The resulting error was 0.11 (2/18). The two parameters were correlated (Pearson’s correlation coefficient: − 0.52). Any of the intestinal tracts of patients with severe CIPO requiring home parenteral nutrition belonged to the region defined by x1 ≥ 1.10 and x2 ≤ 0.15. Cine MRI is effective for the quantitative evaluation of small intestinal motility and CIPO diagnosis when using the abovementioned parameters and can be useful for treatment decision-making. However, these parameters have a wide distribution in healthy volunteers; this may complicate the detection of other disorders.
Magnonic key based on skyrmion clusters
Authors: Saavedra E. , Tejo F. , Vidal-Silva N. , Escrig J.
Published: November 2021

In this work, we report the excitation of spin-waves modes in skyrmion clusters hosted in Co/Pt nanodots by applying an in-plane magnetic field pulse. The direction at which the magnetic field is applied enables the excitation of five main spin-waves modes that are understood in terms of only azimuthal-like modes, which are shown to be strongly dependent on the number of skyrmions stabilized in the system. This feature converts the present system in a mechanism to activate and suppress a set of given modes, which in turn we propose to be utilized as a magnonic key based skyrmion cluster. Our results could be useful in manufacturing potential magnonic logic devices based in skyrmionic textures.
Reduced and stable feature sets selection with random forest for neurons segmentation in histological images of macaque brain
Authors: Bouvier C. , Souedet N. , Levy J. , Jan C. , You Z. , Herard A.-S. , Mergoil G. , Rodriguez B. H. , Clouchoux C. , Delzescaux T.
Published: November 2021

In preclinical research, histology images are produced using powerful optical microscopes to digitize entire sections at cell scale. Quantification of stained tissue relies on machine learning driven segmentation. However, such methods require multiple additional information, or features, which are increasing the quantity of data to process. As a result, the quantity of features to deal with represents a drawback to process large series or massive histological images rapidly in a robust manner. Existing feature selection methods can reduce the amount of required information but the selected subsets lack reproducibility. We propose a novel methodology operating on high performance computing (HPC) infrastructures and aiming at finding small and stable sets of features for fast and robust segmentation of high-resolution histological images. This selection has two steps: (1) selection at features families scale (an intermediate pool of features, between spaces and individual features) and (2) feature selection performed on pre-selected features families. We show that the selected sets of features are stables for two different neuron staining. In order to test different configurations, one of these dataset is a mono-subject dataset and the other is a multi-subjects dataset to test different configurations. Furthermore, the feature selection results in a significant reduction of computation time and memory cost. This methodology will allow exhaustive histological studies at a high-resolution scale on HPC infrastructures for both preclinical and clinical research.
Structural, energetic and lipophilic analysis of SARS-CoV-2 non-structural protein 9 (NSP9)
Authors: de O. Araújo Jéssica , Pinheiro Silvana , Zamora William J. , Alves Cláudio Nahum , Lameira Jerônimo , Lima Anderson H.
Published: November 2021

In SARS-CoV-2 replication complex, the Non-structural protein 9 (Nsp9) is an important RNA binding subunit in the RNA-synthesizing machinery. The dimeric forms of coronavirus Nsp9 increase their nucleic acid binding affinity and the N-finger motif appears to play a critical role in dimerization. Here, we present a structural, lipophilic and energetic study about the Nsp9 dimer of SARS-CoV-2 through computational methods that complement hydrophobicity scales of amino acids with molecular dynamics simulations. Additionally, we presented a virtual N-finger mutation to investigate whether this motif contributes to dimer stability. The results reveal for the native dimer that the N-finger contributes favorably through hydrogen bond interactions and two amino acids bellowing to the hydrophobic region, Leu45 and Leu106, are crucial in the formation of the cavity for potential drug binding. On the other hand, Gly100 and Gly104, are responsible for stabilizing the α-helices and making the dimer interface remain stable in both, native and mutant (without N-finger motif) systems. Besides, clustering results for the native dimer showed accessible cavities to drugs. In addition, the energetic and lipophilic analysis reveal that the higher binding energy in the native dimer can be deduced since it is more lipophilic than the mutant one, increasing non-polar interactions, which is in line with the result of MM-GBSA and SIE approaches where the van der Waals energy term has the greatest weight in the stability of the native dimer. Overall, we provide a detailed study on the Nsp9 dimer of SARS-CoV-2 that may aid in the development of new strategies for the treatment and prevention of COVID-19.
Changes in shoulder outcomes using ultrasonographic assessment of breast cancer survivors: a prospective longitudinal study with 6-month follow-up
Authors: Gala-Alarcón Paula , Prieto-Gómez Virginia , Bailón-Cerezo Javier , Yuste-Sánchez María José , Arranz-Martín Beatriz , Torres-Lacomba María
Published: November 2021

This study aimed to describe changes in supraspinatus tendon thickness, acromiohumeral distance, and the presence of fluid in the subacromial bursa as measured by ultrasound, as well as shoulder range of motion and strength, perceived shoulder disability, and health-related quality of life in women before and after breast cancer treatment. Women who underwent surgery for unilateral breast cancer who did not suffer from shoulder pain or difficulty performing activities of daily living in the 6 months prior to surgery were included. One pre-surgical (A0) and three post-surgical assessments at 7–10 days (A1), 3 months (A2), and 6 months (A3) after surgery were carried out. The thickness of the supraspinatus tendon on the affected side decreased between post-surgical (A1) and 6-month (A3) follow-up assessments (p = 0.029), although the minimal detectable change was not reached. The active range of motion of the affected shoulder decreased after surgery. Strength changes were observed in both shoulders after surgery. The intensity of shoulder pain increased between post-surgical and 6-month follow-up assessments. Shoulder function was decreased at the post-surgical assessment and increased throughout the follow-ups. Health-related quality of life declined after surgery. A trend of decreasing thickness of the supraspinatus tendon of the affected shoulder was observed. Detecting these possible structural changes early would allow for early or preventive treatment.
Microstructure and phase composition of bronze Montefortino helmets discovered Mediterranean seabed to explain an unusual corrosion
Authors: Armetta Francesco , Saladino Maria Luisa , Scherillo Antonella , Caponetti Eugenio
Published: November 2021

Two Monterfortino helmets, recovered in the Mediterranean seabed, show unusual features with respect to the more common helmets of the same period and found in underwater environments. Hence, they were investigated by a multi-analytical approach, which allowed us to identify the compounds constituting the helmets and to make some considerations about their metallurgy, although all the metal was converted to degradation products. The helmets, originally made in bronze, have maintained their original shape because of copper sulphides formation. The observed differences in composition between the two helmets were attributed to the position modification, of one of them, into the seabed along centuries. For the first time, a microstructural investigation permits to reconstruct the history of the aging processes involved in the total oxidation of roman bronze helmet metal.
Three-dimensional morphological analysis of spermatogenesis in aged mouse testes
Authors: Nakano Taito , Nakata Hiroki , Kadomoto Suguru , Iwamoto Hiroaki , Yaegashi Hiroshi , Iijima Masashi , Kawaguchi Shohei , Nohara Takahiro , Shigehara Kazuyoshi , Izumi Kouji , Kadono Yoshifumi , Mizokami Atsushi
Published: November 2021

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.
Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan
Authors: Matsumoto Naomi , Kubo Toshihide , Nakamura Kazue , Mitsuhashi Toshiharu , Takeuchi Akihito , Tsukahara Hirokazu , Yorifuji Takashi
Published: November 2021

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda–mu–sigma) method based on yearly height and weight information (age 1.5–15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.
Excessive application of chemical fertilizer and organophosphorus pesticides induced total phosphorus loss from planting causing surface water eutrophication
Authors: Liu Liyuan , Zheng Xiangqun , Wei Xiaocheng , Kai Zhang , Xu Yan
Published: November 2021

Total phosphorus (TP) loss from planting was one of the resources causing agricultural non-point source pollution. It is significant to clarify the factors influencing TP loss, as well as explore the relationship between TP loss from planting and surface water eutrophication for making recommendations on the reduction of environmental pollution. In this study, the minimum and maximum of average TP loss was appeared in Qinghai and Shandong province with the TP loss of 7.7 × 102 t and 7.5 × 103 t from 2012 to 2014, respectively. The results of structural equation model (SEM) indicating that the effect of anthropogenic drivers on TP loss was more important than natural conditions due to the higher path coefficient of anthropogenic drivers (0.814) than that of natural conditions (0.130). For anthropogenic drivers, the path coefficients of usage of fertilizer and pesticides, which was often excessively applied in China, were 0.921 and 0.909, respectively causing they the two dominant factors affecting TP loss. Annual precipitation and relative humidity, which were belongs to natural conditions, increased TP loss by enhancing leaching and surface runoff. However, light duration could reduce TP loss by promoting crop growth and increasing TP absorption of crops, with a path coefficient of − 0.920. TP loss of each province in per unit area from planting was significantly correlated with TP concentration of its surface water (p < 0.05), suggesting that TP loss from planting was the main factor causing surface water eutrophication. This study targeted presented three proposals to reduce the TP loss from planting, including promotion of scientific fertilization technologies, restriction of organophosphorus pesticides, and popularization of water saving irrigation technologies. These findings as well as suggestions herein would provide direction for the reduction of TP loss from planting.
A study on the impact of the users’ characteristics on the performance of wearable fall detection systems
Authors: Santoyo-Ramón José Antonio , Casilari-Pérez Eduardo , Cano-García José Manuel
Published: November 2021

Wearable Fall Detection Systems (FDSs) have gained much research interest during last decade. In this regard, Machine Learning (ML) classifiers have shown great efficiency in discriminating falls and conventional movements or Activities of Daily Living (ADLs) based on the analysis of the signals captured by transportable inertial sensors. Due to the intrinsic difficulties of training and testing this type of detectors in realistic scenarios and with their target audience (older adults), FDSs are normally benchmarked against a predefined set of ADLs and emulated falls executed by volunteers in a controlled environment. In most studies, however, samples from the same experimental subjects are used to both train and evaluate the FDSs. In this work, we investigate the performance of ML-based FDS systems when the test subjects have physical characteristics (weight, height, body mass index, age, gender) different from those of the users considered for the test phase. The results seem to point out that certain divergences (weight, height) of the users of both subsets (training ad test) may hamper the effectiveness of the classifiers (a reduction of up 20% in sensitivity and of up to 5% in specificity is reported). However, it is shown that the typology of the activities included in these subgroups has much greater relevance for the discrimination capability of the classifiers (with specificity losses of up to 95% if the activity types for training and testing strongly diverge).
Epidemiological associations with genomic variation in SARS-CoV-2
Authors: Rahnavard Ali , Dawson Tyson , Clement Rebecca , Stearrett Nathaniel , Pérez-Losada Marcos , Crandall Keith A.
Published: November 2021

SARS-CoV-2 (CoV) is the etiological agent of the COVID-19 pandemic and evolves to evade both host immune systems and intervention strategies. We divided the CoV genome into 29 constituent regions and applied novel analytical approaches to identify associations between CoV genomic features and epidemiological metadata. Our results show that nonstructural protein 3 (nsp3) and Spike protein (S) have the highest variation and greatest correlation with the viral whole-genome variation. S protein variation is correlated with nsp3, nsp6, and 3′-to-5′ exonuclease variation. Country of origin and time since the start of the pandemic were the most influential metadata associated with genomic variation, while host sex and age were the least influential. We define a novel statistic—coherence—and show its utility in identifying geographic regions (populations) with unusually high (many new variants) or low (isolated) viral phylogenetic diversity. Interestingly, at both global and regional scales, we identify geographic locations with high coherence neighboring regions of low coherence; this emphasizes the utility of this metric to inform public health measures for disease spread. Our results provide a direction to prioritize genes associated with outcome predictors (e.g., health, therapeutic, and vaccine outcomes) and to improve DNA tests for predicting disease status.
Overview of Antiviral Drug Discovery and Development: Viral Versus Host Targets
Authors: Li Guangdi , De Clercq Erik
Published: November 2021

Over the past fifty years, a great number of viral and host targets have been explored for the discovery of antiviral agents against human viral infections. Most antivirals have been designed to target viral proteins such as viral polymerases, viral proteases, and viral structural proteins. Alternative drug targets are human proteins (e.g. receptors, co-receptors, kinases) that are indispensable for the viral life cycle. This chapter aims to provide a comprehensive overview of 20 viral proteins and 12 host factors targeted by approved and novel antiviral agents. Advantages and disadvantages of viral versus host targets are highlighted, shedding light on the discovery of effective antiviral drugs against human infectious diseases worldwide.
Small-molecule and Synthetically Derived Antivirals for Ebola Virus and Other Filoviruses
Authors: Iversen Patrick , Bixler Sandra , Kane Christopher D. , Warren Travis K.
Published: November 2021

Filoviruses—Ebola virus (EBOV), Marburg virus, and Sudan virus—are human pathogenic viruses, outbreaks of which have been associated with high case fatality rates. No antivirals have been approved to combat filovirus disease. Multiple experimental therapeutics have been shown to protect nonhuman primates against filovirus infection, and recent EBOV outbreaks have provided opportunities for clinical efficacy evaluations of promising investigational products. This chapter provides a comprehensive review of small molecules and other synthetic entities that have shown potential as therapeutic agents to combat filovirus disease. Summarized results are intended to convey key results from in vitro, in vivo, or clinical antiviral assessments; known mechanism(s) of action; and other relevant pharmacological characterizations of therapeutic candidates.
Receptors on Primary Phagocytes as Therapeutic Targets Against Highly Pathogenic Emerging Viruses
Authors: Perez-Zsolt Daniel , Martinez-Picado Javier , Izquierdo-Useros Nuria
Published: November 2021

Highly pathogenic Ebola and Marburg filoviruses infect myeloid phagocytes, but viral attachment and entry occur through a complex series of events involving the interaction of several viral and host components. This chapter focuses on what is currently known about the cellular pathways exploited by filoviruses to gain access into myeloid phagocytes. These antigen-presenting cells are located at the mucosal portals of viral entry, and upon pathogen encounter, migrate to secondary lymphoid tissues to induce antiviral immunity. However, once infected, myeloid phagocytes may also contribute to systemic viral dissemination. Here we discuss the current therapeutic agents available for blocking filoviral entry into these cells as a strategy to limit viral dissemination and disease progression, which might trigger protective immune responses. The development of a combined therapy targeting the precise host factors that confer susceptibility to filoviral entry may also lead to a new generation of broad-spectrum antivirals with potential clinical applicability.
Development of magnetic solid phase extraction based on magnetic chitosan–graphene oxide nanoparticles and deep eutectic solvents for the determination of flavonoids by high performance liquid chromatography
Authors: Jafari Zahra , Hadjmohammadi Mohammad Reza
Published: November 2021

Fe3O4–CS–GO–MSPE-DES was used for the extraction and determination of some flavonoids. CS–GO was synthesized and immobilized on the inner surface of Fe3O4. The method can be directly used in relatively complicated samples. The method is effective, sensitive and has wide LDRs.
Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group A streptococcus
Authors: Madge Harrison Y. R. , Huang Wenbin , Gilmartin Lachlan , Rigau-Planella Berta , Hussein Waleed M. , Khalil Zeinab G. , Koirala Prashamsa , Santiago Viviene S. , Capon Robert J. , Toth Istvan , Stephenson Rachel J.
Published: November 2021

The presence of a cyclic peptide is as part of a physically-mixed group A Streptococcus vaccine for the induction of a strong, balanced Th1/Th2 immune response.
Reactive oxygen species-scavenging hollow MnO2 nanozymes as carriers to deliver budesonide for synergistic inflammatory bowel disease therapy
Authors: Qiu Huiqiang , Gong Hengtai , Bao Yuheng , Jiang Hong , Tong Weijun
Published: November 2021

Hollow MnO2 nanozyme carriers loaded with budesonide can simultaneously scavenge excessive ROS and deliver anti-inflammatory drugs, resulting in synergistic IBD therapy.
AgCu@CuO aerogels with peroxidase-like activities and photoelectric responses for sensitive biosensing
Authors: Li Jinli , Wu Yu , Qin Ying , Liu Mingwang , Chen Guojuan , Hu Liuyong , Gu Wenling , Zhu Chengzhou
Published: November 2021

AgCu@CuO aerogel-based materials were innovatively designed with enzyme-like activity and photoelectric property, which can be used for xanthine oxidase activity detection with high sensitivity.
Correction methods for first-principles calculations of the solution enthalpy of gases and compounds in liquid metals
Authors: Gil Junhyoung , Oda Takuji
Published: November 2021

Correction methods for the first-principles calculation of the solution enthalpy of gases and compounds in liquid metals are proposed. With correction, accuracy similar to precise experiments is achieved.
Future greenhouse gas emissions from metal production: gaps and opportunities towards climate goals
Authors: Yokoi Ryosuke , Watari Takuma , Motoshita Masaharu
Published: November 2021

The projected GHG emissions cannot reach the climate goal under any SSP. Further efforts on lowering per capita in-use metal stocks and GHG emission intensity of metal production and promoting recycling are the key to achieve the climate goal.
Uptake, translocation, and transformation of silver nanoparticles in plants
Authors: Huang Danyu , Dang Fei , Huang Yingnan , Chen Ning , Zhou Dongmei
Published: November 2021

This article reviews the plant uptake of silver nanoparticles (AgNPs) that occurred in soil systems and the in planta fate of Ag.
Vesicle-based artificial cells: materials, construction methods and applications
Authors: Lu Yao , Allegri Giulia , Huskens Jurriaan
Published: November 2021

The construction of artificial cells using a giant vesicle model helps to explore and mimic complex biological processes and cell functions of natural cell systems. Various materials and fabrication processes for giant vesicles are reviewed here.
Computational design of thermoelectric alloys through optimization of transport and dopability
Authors: Qu Jiaxing , Balvanz Adam , Baranets Sviatoslav , Bobev Svilen , Gorai Prashun
Published: November 2021

We develop a computational framework to guide the systematic optimization of transport properties and dopability of thermoelectric alloys.
A four-component domino reaction for the synthesis of novel bridgehead nitrogen-containing pyrido[1,2-d][1,4]diazepines
Authors: Wang Rui , Zhang Wei , Tang Ying , Qi Ze-Hui , Yu Yuan-Hui , Tan Hong-Bo , Tang Dian-Yong , Xu Zhi-Gang , Chen Zhong-Zhu
Published: November 2021

An efficient methodology for the synthesis of a new family of novel bridgehead nitrogen-containing pyrido[1,2-d][1,4]diazepines has been described and its mechanism has been proposed, which follows a ring-closure and ring-cleavage pathway.
Modified boehmite: a choice of catalyst for the selective conversion of glycerol to five-membered dioxolane
Authors: Barik Manas , Mishra Jyotiranjan , Dabas Shilpa , Chinnaraja Eswaran , Subramanian Saravanan , Subramanian Palani S.
Published: November 2021

The catalytic activity of WO3@boehmite for the acetalization of glycerol with aromatic aldehydes is described in this article. The catalyst is selective towards dioxolane (up to 96%) with excellent conversion (up to 100%) in selective substrates.
DNA nanostructures directed by RNA clamps
Authors: Lyu Jiazhen , Yang Mei , Zhang Chong , Luo Yongbo , Qin Tong , Su Zhaoming , Huang Zhen
Published: November 2021

DNA chains can be folded rationally by using DNA staples, and the programmed structures are of great potential in nanomaterial studies.
Ferromagnetic barrier induced large enhancement of tunneling magnetoresistance in van der Waals perpendicular magnetic tunnel junctions
Authors: Zhang Xiaolin , Yang Baishun , Guo Xiaoyan , Han Xiufeng , Yan Yu
Published: November 2021

Schematics of TMR effect of FGT/CrI3/FGT and FGT/ScI3/FGT vdW MTJs.
Upconversion nanoparticle-assisted cationic and radical/cationic hybrid photopolymerization using sulfonium salts
Authors: Meng Xiaoyan , Li Longji , Huang Yaoxin , Deng Xin , Liu Xiaoxuan , Li Zhiquan
Published: November 2021

Several sulfonium salts as unimolecular photoinitiators can efficiently initiate UCNP-assisted direct cationic and radial/cationic photopolymerization under 980 nm NIR light irradiation.
Vinyl sulfonyl chemistry-driven unidirectional transport of a macrocycle through a [2]rotaxane
Authors: David Arthur H. G. , García–Cerezo Pablo , Campaña Araceli G. , Santoyo–González Francisco , Blanco Victor
Published: November 2021

The pH- and chemically-driven unidirectional transport of a macrocycle through a [2]rotaxane based on the vinyl sulfonyl groups is reported.
Rapid antibacterial activity of anodized aluminum-based materials impregnated with quaternary ammonium compounds for high-touch surfaces to limit transmission of pathogenic bacteria
Authors: Jann Jessica , Drevelle Olivier , Chen X. Grant , Auclair-Gilbert Myriam , Soucy Gervais , Faucheux Nathalie , Fortier Louis-Charles
Published: November 2021

Anodized aluminum-based antibacterial materials impregnated with biocidal compounds for high-touch surfaces applications to limit transmission of pathogenic bacteria.