bluuebunny/crossref_metadata_2025 huggingface dataset:
Equatorial Pacific pCO2 Interannual Variability in CMIP6 Models
Authors: Wong Suki C. K. , McKinley Galen A. , Seager Richard
Published: December 2022

The El Niño‐Southern Oscillation (ENSO) in the equatorial Pacific is the dominant mode of global air‐sea carbon dioxide (CO2) flux interannual variability (IAV). Air‐sea CO2 fluxes are driven by the difference between atmospheric and surface ocean pCO2, with variability of the latter driving flux variability. Previous studies found that models in Coupled Model Intercomparison Project Phase 5 (CMIP5) failed to reproduce the observed ENSO‐related pattern of CO2 fluxes and had weak pCO2 IAV, which were explained by both weak upwelling IAV and weak mean vertical dissolved inorganic carbon (DIC) gradients. We assess whether the latest generation of CMIP6 models can reproduce equatorial Pacific pCO2 IAV by validating models against observations‐based data products. We decompose pCO2 IAV into thermally and non‐thermally driven anomalies to examine the balance between these competing anomalies, which explain the total pCO2 IAV. The majority of CMIP6 models underestimate pCO2 IAV, while they overestimate sea surface temperature IAV. Insufficient compensation of non‐thermal pCO2 to thermal pCO2 IAV in models results in weak total pCO2 IAV. We compare the relative strengths of the vertical transport of temperature and DIC and evaluate their contributions to thermal and non‐thermal pCO2 anomalies. Model‐to‐observations‐based product comparisons reveal that modeled mean vertical DIC gradients are biased weak relative to their mean vertical temperature gradients, but upwelling acting on these gradients is insufficient to explain the relative magnitudes of thermal and non‐thermal pCO2 anomalies.
Targeting PEA3 transcription factors to mitigate small cell lung cancer progression
Authors: Shia David W. , Choi WooSuk , Vijayaraj Preethi , Vuong Valarie , Sandlin Jenna M. , Lu Michelle M. , Aziz Adam , Marin Caliope , Aros Cody J. , Sen Chandani , Durra Abdo , Lund Andrew J. , Purkayastha Arunima , Rickabaugh Tammy M. , Graeber Thomas G. , Gomperts Brigitte N.
Published: December 2022

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide—the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC.
Striatal connectopic maps link to functional domains across psychiatric disorders
Authors: Mulders Peter C. R. , van Eijndhoven Philip F. P. , van Oort Jasper , Oldehinkel Marianne , Duyser Fleur A. , Kist Josina D. , Collard Rose M. , Vrijsen Janna N. , Haak Koen V. , Beckmann Christian F. , Tendolkar Indira , Marquand Andre F.
Published: December 2022

Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum—a central hub in motor, cognitive, affective and reward-related brain circuits—and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.
Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia
Authors: Ravandi Farhad , Kreitman Robert J. , Tiacci Enrico , Andritsos Leslie , Banerji Versha , Barrientos Jacqueline C. , Bhat Seema A. , Blachly James S. , Broccoli Alessandro , Call Timothy , Chihara Dai , Dearden Claire , Demeter Judit , Dietrich Sasha , Else Monica , Epperla Narendranath , Falini Brunangelo , Forconi Francesco , Gladstone Douglas E. , Gozzetti Alessandro , Iyengar Sunil , Johnston James B. , Jorgensen Jeffrey , Juliusson Gunnar , Lauria Francesco , Lozanski Gerard , Parikh Sameer A. , Park Jae H. , Polliack Aaron , Quest Graeme , Robak Tadeusz , Rogers Kerry A. , Saven Alan , Seymour John F. , Tadmor Tamar , Tallman Martin S. , Tam Constantine S. , Thompson Philip A. , Troussard Xavier , Zent Clive S. , Zenz Thorsten , Zinzani Pier Luigi , Wörmann Bernhard , Rai Kanti , Grever Michael
Published: December 2022

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.
The influence of patient race on the outcome of endodontic treatments: a pooled analysis of one-year recall data from four cone beam computed tomography outcome studies
Authors: Patel Neha , Scambler Sasha , Ranjbari Mohammadreza , Alhammad Mohammad , Bakhsh Abdulaziz A. , Mannocci Francesco
Published: December 2022

Objectives The aim of this pooled data analysis was to establish if there is an association between a patient's race and the proportion of successful outcomes of endodontic treatments, and if so, what factors may determine this association.

Methodology Data collected from four prospective clinical outcome studies were pooled. Patients were recalled 12 months after the completion of the treatment. Treatment outcome was determined by clinical findings and cone beam computed tomography examination. Statistical analysis included the description of categorical and continuous variables and simple binary logistic regression models, chi-squared tests and Kruskal-Wallis tests.

Results Data from 301 patients were available. Of these patients, 43 were Black (14.3%), 50 were from a Non-Black Minority Ethnic (NBME) group (16.6%) and 208 were white (69.1%). The risk of an unfavourable outcome was higher in teeth with short root canal fillings (OR = 3.36; p = 0.002), when a preoperative radiolucency was present (OR = 2.59; p = 0.019) and when an intra-operative root canal perforation was detected (OR = 5.25; p = 0.016).

Multiple regression models showed that Black (OR = 2.28; p = 0.05) and NBME patients (OR = 3.07; p = 0.008) had a higher risk of an unfavourable result compared to white patients.

Conclusions Black and NBME patients had a significantly higher failure rate of root canal treatments compared to white patients. All other known pre-, intra- and post-operative risk factors for root canal treatment failure were present in similar proportions in BME and white patients.
Structure-function studies reveal ComEA contains an oligomerization domain essential for transformation in gram-positive bacteria
Authors: Ahmed Ishtiyaq , Hahn Jeanette , Henrickson Amy , Khaja Faisal Tarique , Demeler Borries , Dubnau David , Neiditch Matthew B.
Published: December 2022

An essential step in bacterial transformation is the uptake of DNA into the periplasm, across the thick peptidoglycan cell wall of Gram-positive bacteria, or the outer membrane and thin peptidoglycan layer of Gram-negative bacteria. ComEA, a DNA-binding protein widely conserved in transformable bacteria, is required for this uptake step. Here we determine X-ray crystal structures of ComEA from two Gram-positive species,Bacillus subtilisandGeobacillus stearothermophilus, identifying a domain that is absent in Gram-negative bacteria. X-ray crystallographic, genetic, and analytical ultracentrifugation (AUC) analyses reveal that this domain drives ComEA oligomerization, which we show is required for transformation. We use multi-wavelength AUC (MW-AUC) to characterize the interaction between DNA and the ComEA DNA-binding domain. Finally, we present a model for the interaction of the ComEA DNA-binding domain with DNA, suggesting that ComEA oligomerization may provide a pulling force that drives DNA uptake across the thick cell walls of Gram-positive bacteria.
Focus image scanning microscopy for sharp and gentle super-resolved microscopy
Authors: Tortarolo Giorgio , Zunino Alessandro , Fersini Francesco , Castello Marco , Piazza Simonluca , Sheppard Colin J. R. , Bianchini Paolo , Diaspro Alberto , Koho Sami , Vicidomini Giuseppe
Published: December 2022

To date, the feasibility of super-resolution microscopy for imaging live and thick samples is still limited. Stimulated emission depletion (STED) microscopy requires high-intensity illumination to achieve sub-diffraction resolution, potentially introducing photodamage to live specimens. Moreover, the out-of-focus background may degrade the signal stemming from the focal plane. Here, we propose a new method to mitigate these limitations without drawbacks. First, we enhance a STED microscope with a detector array, enabling image scanning microscopy (ISM). Therefore, we implement STED-ISM, a method that exploits the working principle of ISM to reduce the depletion intensity and achieve a target resolution. Later, we develop Focus-ISM, a strategy to improve the optical sectioning and remove the background of any ISM-based imaging technique, with or without a STED beam. The proposed approach requires minimal architectural changes to a conventional microscope but provides substantial advantages for live and thick sample imaging.
How ornithopters can perch autonomously on a branch
Authors: Zufferey Raphael , Tormo-Barbero Jesus , Feliu-Talegón Daniel , Nekoo Saeed Rafee , Acosta José Ángel , Ollero Anibal
Published: December 2022

Flapping wings produce lift and thrust in bio-inspired aerial robots, leading to quiet, safe and efficient flight. However, to extend their application scope, these robots must perch and land, a feat widely demonstrated by birds. Despite recent progress, flapping-wing vehicles, or ornithopters, are to this day unable to stop their flight. In this paper, we present a process to autonomously land an ornithopter on a branch. This method describes the joint operation of a pitch-yaw-altitude flapping flight controller, an optical close-range correction system and a bistable claw appendage design that can grasp a branch within 25 milliseconds and re-open. We validate this method with a 700 g robot and demonstrate the first autonomous perching flight of a flapping-wing robot on a branch, a result replicated with a second robot. This work paves the way towards the application of flapping-wing robots for long-range missions, bird observation, manipulation, and outdoor flight.
Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations
Authors: Farag Mina , Cohen Samuel R. , Borcherds Wade M. , Bremer Anne , Mittag Tanja , Pappu Rohit V.
Published: December 2022

Biomolecular condensates form via coupled associative and segregative phase transitions of multivalent associative macromolecules. Phase separation coupled to percolation is one example of such transitions. Here, we characterize molecular and mesoscale structural descriptions of condensates formed by intrinsically disordered prion-like low complexity domains (PLCDs). These systems conform to sticker-and-spacers architectures. Stickers are cohesive motifs that drive associative interactions through reversible crosslinking and spacers affect the cooperativity of crosslinking and overall macromolecular solubility. Our computations reproduce experimentally measured sequence-specific phase behaviors of PLCDs. Within simulated condensates, networks of reversible inter-sticker crosslinks organize PLCDs into small-world topologies. The overall dimensions of PLCDs vary with spatial location, being most expanded at and preferring to be oriented perpendicular to the interface. Our results demonstrate that even simple condensates with one type of macromolecule feature inhomogeneous spatial organizations of molecules and interfacial features that likely prime them for biochemical activity.
Significant contributions of combustion-related sources to ammonia emissions
Authors: Chen Zhi-Li , Song Wei , Hu Chao-Chen , Liu Xue-Jun , Chen Guan-Yi , Walters Wendell W. , Michalski Greg , Liu Cong-Qiang , Fowler David , Liu Xue-Yan
Published: December 2022

Atmospheric ammonia (NH3) and ammonium (NH4+) can substantially influence air quality, ecosystems, and climate. NH3 volatilization from fertilizers and wastes (v-NH3) has long been assumed to be the primary NH3 source, but the contribution of combustion-related NH3 (c-NH3, mainly fossil fuels and biomass burning) remains unconstrained. Here, we collated nitrogen isotopes of atmospheric NH3 and NH4+ and established a robust method to differentiate v-NH3 and c-NH3. We found that the relative contribution of the c-NH3 in the total NH3 emissions reached up to 40 ± 21% (6.6 ± 3.4 Tg N yr−1), 49 ± 16% (2.8 ± 0.9 Tg N yr−1), and 44 ± 19% (2.8 ± 1.3 Tg N yr−1) in East Asia, North America, and Europe, respectively, though its fractions and amounts in these regions generally decreased over the past decades. Given its importance, c-NH3 emission should be considered in making emission inventories, dispersion modeling, mitigation strategies, budgeting deposition fluxes, and evaluating the ecological effects of atmospheric NH3 loading.
Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration
Authors: Xia Yu , Duca Sierra , Perder Björn , Dündar Friederike , Zumbo Paul , Qiu Miaoyan , Yao Jun , Cao Yingxi , Harrison Michael R. M. , Zangi Lior , Betel Doron , Cao Jingli
Published: December 2022

The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked byptx3aandcol12a1bexpression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells andpdgfra+hapln1a+mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reducednrg1expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
Anomalous inapplicability of nacre-like architectures as impact-resistant templates in a wide range of impact velocities
Authors: Zhang Xiao , Wu Kaijin , Ni Yong , He Linghui
Published: December 2022

Nacre is generally regarded as tough body armor, but it was often smashed by predators with a certain striking speed. Nacre-like architectures have been demonstrated to dissipate abundant energy by tablets sliding at static or specific low-speed loads, but whether they’re still impact-resistant templates in a wide range of impact velocities remains unclear. Here, we find an anomalous phenomenon that nacre-like structures show superior energy-dissipation ability only in a narrow range of low impact velocities, while they exhibit lower impact resistance than laminated structures when impact velocity exceeds a critical value. This is because the tablets sliding in nacre-like structure occurs earlier and wider at low impact velocities, while it becomes localized at excessive impact velocities. Such anomalous phenomenon remains under different structural sizes and boundary conditions. It further inspires us to propose a hybrid architecture design strategy that achieves optimal impact resistance in a wide range of impact velocities.
Element-wise representations with ECNet for material property prediction and applications in high-entropy alloys
Authors: Wang Xinming , Tran Nguyen-Dung , Zeng Shuming , Hou Cong , Chen Ying , Ni Jun
Published: December 2022

When developing deep learning models for accurate property prediction, it is sometimes overlooked that some material physical properties are insensitive to the local atomic environment. Here, we propose the elemental convolution neural networks (ECNet) to obtain more general and global element-wise representations to accurately model material properties. It shows better prediction in properties like band gaps, refractive index, and elastic moduli of crystals. To explore its application on high-entropy alloys (HEAs), we focus on the FeNiCoCrMn/Pd systems based on the data of DFT calculation. The knowledge from less-principal element alloys can enhance performance in HEAs by transfer learning technique. Besides, the element-wise features from the parent model as universal descriptors retain good accuracy at small data limits. Using this framework, we obtain the concentration-dependent formation energy, magnetic moment and local displacement in some sub-ternary and quinary systems. The results enriched the physics of those high-entropy alloys.
Novel time-domain NMR-based traits for rapid, label-free Olive oils profiling
Authors: dos Santos Vasco Rafael , Goncalves Victor , Deng Peishan , Ribeiro Ana Cristina , Teigao Mariana Maia , Dias Bárbara , Mendes Pinto Inês , Gallo Juan , Peng Weng Kung
Published: December 2022

Olive oil is one of the oldest and essential edible oils in the market. The classification of olive oils (e.g. extra virgin, virgin, refined) is often influenced by factors ranging from its complex inherent physiochemical properties (e.g. fatty acid profiles) to the undisclosed manufacturing processes. Therefore, olive oils have been the target of adulteration due to its profitable margin. In this work, we demonstrate that multi-parametric time-domain NMR relaxometry can be used to rapidly (in minutes) identify and classify olive oils in label-free and non-destructive manner. The subtle differences in molecular microenvironment of the olive oils induce substantial changes in the relaxation mechanism in the time-domain NMR regime. We demonstrated that the proposed NMR-relaxation based detection (AUC = 0.95) is far more sensitive and specific than the current gold-standards in the field i.e. near-infrared spectroscopy (AUC = 0.84) and Ultraviolet-visible spectroscopy (AUC = 0.73), respectively. We further show that, albeit the inherent complexity of olive plant natural phenotypic variations, the proposed NMR-relaxation based traits may be a viable mean (AUC = 0.71) in tracing the regions of origin for olive trees, in agreement with their geographical orientation.
Photonic crystals umbrella for thermal desalination: simulation study
Authors: Sayed Hassan , Aly Arafa H. , Krauss Thomas F.
Published: December 2022

For sustainable water desalination, there is a worldwide push towards solar thermal desalination with the objective to limit the amount of consumed energy in other desalination technologies and maximize the resulting freshwater from saline water. Here, we demonstrate a photonic crystals solar umbrella that covers the saline water surface, demanding to absorb all the incident electromagnetic wave and remit it as greater wavelengths in the range of mid-infrared (MIR) to be highly absorbed and localized close to the water surface. The temperature of the saline water with a refractive index of 1.3326 is reached to $$45^\circ \mathrm{C}$$

45
∘

C

after one hour of illumination with the incident power intensity equal 680 $$(\mathrm{w}/{\mathrm{m}}^{2})$$

(
w
/

m

2

)

. Hence, by adding one-dimensional PCs the surface temperature is reached $$77^\circ \mathrm{C}$$

77
∘

C

. Also, by adding 2D PCs to allow the vapor to flow up through the pores of the structure with the diameter of the pore equal to 500 nm, the surface temperature is reached $$100^\circ \mathrm{C}$$

100
∘

C

after three hour of illumination. Thus, the effective use of electromagnetic waves and warmth localization at the surface of saline water is accomplished by radiative coupling with the effect of 2D PCs. We design the considered structure by using COMSOL multiphysics which based on the finite element method (FEM).
Association of labour duration in spontaneous deliveries with low neonatal Apgar scores and foetal acidosis: the Japan Environment and Children’s Study
Authors: Murata Tsuyoshi , Yasuda Shun , Imaizumi Karin , Isogami Hirotaka , Fukuda Toma , Kyozuka Hyo , Yamaguchi Akiko , Sato Akiko , Ogata Yuka , Shinoki Kosei , Hosoya Mitsuaki , Yasumura Seiji , Hashimoto Koichi , Nishigori Hidekazu , Fujimori Keiya ,   The Japan Environment, Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Nakamura Hiroshige , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: December 2022

This study evaluated the association between labour duration (LD) and incidence of low neonatal Apgar scores and foetal acidosis. Data of 37,682 women with full-term singleton spontaneous vaginal deliveries from the Japan Environment and Children’s Study were analysed. Women were classified according to the median LD as nulliparous (< 10 or ≥ 10 h) or multiparous (< 5 or ≥ 5 h) and further into five subcategories: nulliparous (< 10.0, 10.0–12.9, 13.0–15.9, 16.0–18.9, and ≥ 19 h) and multiparous (< 5.0, 5.0–7.9, 8.0–10.9, 11.0–13.9, and ≥ 14.0 h). Multiple logistic regression models were used to determine odds ratios (ORs) for outcomes in women with over-median LD. Over-median LD exhibited no statistically significant association with low neonatal Apgar scores. The adjusted ORs for both umbilical artery (UmA-pH) < 7.2 and < 7.1 were increased in nulliparous women with over-median LD, whereas only the adjusted OR for UmA-pH < 7.2 was increased in multiparous women with over-median LD. Moreover, this association manifested as a plateau in nulliparous women with LD ≥ 13 h and without dose-dependent association in multiparous women.
Complex selective manipulations of thermomagnetic programmable matter
Authors: Irisarri Josu , Ezcurdia Iñigo , Sandua Xabier , Galarreta-Rodriguez Itziar , Pérez-Landazabal Jose Ignacio , Marzo Asier
Published: December 2022

Programmable matter can change its shape, stiffness or other physical properties upon command. Previous work has shown contactless optically controlled matter or magnetic actuation, but the former is limited in strength and the latter in spatial resolution. Here, we show an unprecedented level of control combining light patterns and magnetic fields. A mixture of thermoplastic and ferromagnetic powder is heated up at specific locations that become malleable and are attracted by magnetic fields. These heated areas solidify on cool down, and the process can be repeated. We show complex control of 3D slabs, 2D sheets, and 1D filaments with applications in tactile displays and object manipulation. Due to the low transition temperature and the possibility of using microwave heating, the compound can be manipulated in air, water, or inside biological tissue having the potential to revolutionize biomedical devices, robotics or display technologies.
Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer
Authors: Lee Jeeyeon , Park Nora Jee-Young , Park Ho Yong , Kim Wan Wook , Kang Byeongju , Keum Heejung , Kim Hye Jung , Kim Won Hwa , Chae Yee Soo , Lee Soo Jung , Lee In Hee , Park Ji-Young , Jung Jin Hyang
Published: December 2022

The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells. A total of 144 patients with breast cancer and diffuse microcalcifications were classified into the reduced mass with no change in residual microcalcification (RESMIN, n = 49) and non-RESMIN (n = 95) groups. Five specimens were prospectively evaluated to assess the presence of viable cancer cells around the microcalcification. Tumor responses to NAC were significantly better with high pCR rates in the RESMIN group (p = 0.005 and p = 0.002). The incidence of human epidermal growth factor receptor 2-positive and triple-negative breast cancers was significantly high in the RESMIN group (p = 0.007). Although five (10.2%) patients had locoregional recurrence in the RESMIN group, no local recurrence in the breast was reported. Although pCR was highly estimated, residual cancers, including ductal carcinoma in situ, remained in 80% cases. Therefore, given the weak scientific evidence available currently, complete removal of residual microcalcifications should be considered for oncologic safety.
The expression pattern of pyroptosis-related genes predicts the prognosis and drug response of melanoma
Authors: Zhou Bin , Sha Shanshan , Tao Juan , Li Jun , Shen Chen , Zhu Jinjin , Tan Lulu , Dong Liyun , Huang Changzheng
Published: December 2022

Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+ T cells, CD8+ T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 (SLC31A2) and collagen type 4 alpha 5 chain (COL4A5) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.
Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma
Authors: Yuan Xianggui , Yu Teng , Huang Yurong , Jiang Huawei , Xu Xiaohua , Liang Yun , Qian Wenbin
Published: December 2022

Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3–4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.
New fossil assemblages from the Early Ordovician Fezouata Biota
Authors: Saleh Farid , Vaucher Romain , Vidal Muriel , Hariri Khadija El , Laibl Lukáš , Daley Allison C. , Gutiérrez-Marco Juan Carlos , Candela Yves , Harper David A. T. , Ortega-Hernández Javier , Ma Xiaoya , Rida Ariba , Vizcaïno Daniel , Lefebvre Bertrand
Published: December 2022

The Fezouata Biota (Morocco) is a unique Early Ordovician fossil assemblage. The discovery of this biota revolutionized our understanding of Earth’s early animal diversifications—the Cambrian Explosion and the Ordovician Radiation—by suggesting an evolutionary continuum between both events. Herein, we describe Taichoute, a new fossil locality from the Fezouata Shale. This locality extends the temporal distribution of fossil preservation from this formation into the upper Floian, while also expanding the range of depositional environments to more distal parts of the shelf. In Taichoute, most animals were transported by density flows, unlike the in-situ preservation of animals recovered in previously investigated Fezouata sites. Taichoute is dominated by three-dimensionally preserved, and heavily sclerotized fragments of large euarthropods—possibly representing nektobenthic/nektic bivalved taxa and/or hurdiid radiodonts. Resolving whether this dominance reflects a legitimate aspect of the original ecosystem or a preservational bias requires an in-depth assessment of the environmental conditions at this site. Nevertheless, Taichoute provides novel preservational and palaeontological insights during a key evolutionary transition in the history of life on Earth.
A soft supernumerary hand for rehabilitation in sub-acute stroke: a pilot study
Authors: Trompetto Carlo , Catalano Manuel G. , Farina Alessandro , Grioli Giorgio , Mori Laura , Ciullo Andrea , Pittaluga Matteo , Rossero Martina , Puce Luca , Bicchi Antonio
Published: December 2022

In patients with subacute stroke, task specific training (TST) has been shown to accelerate functional recovery of the upper limb. However, many patients do not have sufficient active extension of the fingers to perform this treatment. In these patients, here we propose a new rehabilitation technique in which TST is performed through a soft robotic hand (SoftHand-X). In short, the extension of the robotic fingers is controlled by the patient through his residual, albeit minimal, active extension of the fingers or wrist, while the patient was required to relax the muscles to achieve full flexion of the robotic fingers. TST with SoftHand-X was attempted in 27 subacute stroke patients unable to perform TST due to insufficient active extension of the fingers. Four patients (14.8%) were able to perform the proposed treatment (10 daily sessions of 60 min each). They reported an excellent level of participation. After the treatment, both clinical score of spasticity and its electromyographic correlate (stretch reflex) decreased. In subacute stroke patients, TST using SoftHand-X is a well-accepted treatment, resulting in a decrease of spasticity. At present, it can be applied only in a small proportion of the patients who cannot perform conventional TST, though extensions are possible.
Quantitative environmental DNA metabarcoding shows high potential as a novel approach to quantitatively assess fish community
Authors: Tsuji Satsuki , Inui Ryutei , Nakao Ryohei , Miyazono Seiji , Saito Minoru , Kono Takanori , Akamatsu Yoshihisa
Published: December 2022

The simultaneous conservation of species richness and evenness is important to effectively reduce biodiversity loss and keep ecosystem health. Environmental DNA (eDNA) metabarcoding has been used as a powerful tool for identifying community composition, but it does not necessarily provide quantitative information due to several methodological limitations. Thus, the quantification of eDNA through metabarcoding is an important frontier of eDNA-based biomonitoring. Particularly, the qMiSeq approach has recently been developed as a quantitative metabarcoding method and has attracted much attention due to its usefulness. The aim here was to evaluate the performance of the qMiSeq approach as a quantitative monitoring tool for fish communities by comparing the quantified eDNA concentrations with the results of fish capture surveys. The eDNA water sampling and the capture surveys using the electrical shocker were conducted at a total of 21 sites in four rivers in Japan. As a result, we found significant positive relationships between the eDNA concentrations of each species quantified by qMiSeq and both the abundance and biomass of each captured taxon at each site. Furthermore, for seven out of eleven taxa, a significant positive relationship was observed between quantified DNA concentrations by sample and the abundance and/or biomass. In total, our results demonstrated that eDNA metabarcoding with the qMiSeq approach is a suitable and useful tool for quantitative monitoring of fish communities. Due to the simplicity of the eDNA analysis, the eDNA metabarcoding with qMiSeq approach would promote further growth of quantitative monitoring of biodiversity.
Deep kernel learning of dynamical models from high-dimensional noisy data
Authors: Botteghi Nicolò , Guo Mengwu , Brune Christoph
Published: December 2022

This work proposes a stochastic variational deep kernel learning method for the data-driven discovery of low-dimensional dynamical models from high-dimensional noisy data. The framework is composed of an encoder that compresses high-dimensional measurements into low-dimensional state variables, and a latent dynamical model for the state variables that predicts the system evolution over time. The training of the proposed model is carried out in an unsupervised manner, i.e., not relying on labeled data. Our learning method is evaluated on the motion of a pendulum—a well studied baseline for nonlinear model identification and control with continuous states and control inputs—measured via high-dimensional noisy RGB images. Results show that the method can effectively denoise measurements, learn compact state representations and latent dynamical models, as well as identify and quantify modeling uncertainties.
Role of poly(ADP-ribose) polymerase-1 in regulating human islet cell differentiation
Authors: Dadheech Nidheesh , Srivastava Abhay , Shah Rashmi G. , Shah Girish M. , Gupta Sarita
Published: December 2022

Poly(ADP-ribose) polymerase-1 (PARP1), a fundamental DNA repair enzyme, is known to regulate β cell death, replication, and insulin secretion. PARP1 knockout (KO) mice are resistant to diabetes, while PARP1 overactivation contributes to β cell death. Additionally, PARP1 inhibition (PARPi) improves diabetes complications in patients with type-2 diabetes. Despite these beneficial effects, the use of PARP1 modulating agents in diabetes treatment is largely neglected, primarily due to the poorly studied mechanistic action of PARP1 catalytic function in human β cell development. In the present study, we evaluated PARP1 regulatory action in human β cell differentiation using the human pancreatic progenitor cell line, PANC-1. We surveyed islet census and histology from PARP1 wild-type versus KO mice pancreas in a head-to-head comparison with PARP1 regulatory action for in-vitro β cell differentiation following either PARP1 depletion or its pharmacological inhibition in PANC-1-differentiated islet cells. shRNA mediated PARP1 depleted (SiP) and shRNA control (U6) PANC-1 cells were differentiated into islet-like clusters using established protocols. We observed complete abrogation of new β cell formation with absolute PARP1 depletion while its inhibition using the potent inhibitor, PJ34, promoted the endocrine β cell differentiation and maturation. Immunohistochemistry and immunoblotting for key endocrine differentiation players along with β cell maturation markers highlighted the potential regulatory action of PARP1 and augmented β cell differentiation due to direct interaction of unmodified PARP1 protein elicited p38 MAPK phosphorylation and Neurogenin-3 (Ngn3) re-activation. In summary, our study suggests that PARP1 is required for the proper development and differentiation of human islets. Selective inhibition with PARPi can be an advantage in pushing more insulin-producing cells under pathological conditions and delivers a potential for pilot clinical testing for β cell replacement cell therapies for diabetes.
A novel small molecule inhibitor of human Drp1
Authors: Rosdah Ayeshah A. , Abbott Belinda M. , Langendorf Christopher G. , Deng Yali , Truong Jia Q. , Waddell Helen M. M. , Ling Naomi X. Y. , Smiles William J. , Delbridge Lea M. D. , Liu Guei-Sheung , Oakhill Jonathan S. , Lim Shiang Y. , Holien Jessica K.
Published: December 2022

Mitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and is known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, the specificity of Mdivi-1 towards human Drp1 has not been definitively proven and there have been numerous issues reported with its use including off-target effects. In our hands Mdivi-1 showed varying binding affinities toward human Drp1, potentially impacted by compound aggregation. Herein, we sought to identify a novel small molecule inhibitor of Drp1. From an initial virtual screening, we identified DRP1i27 as a compound which directly bound to the human isoform 3 of Drp1 via surface plasmon resonance and microscale thermophoresis. Importantly, DRP1i27 was found to have a dose-dependent increase in the cellular networks of fused mitochondria but had no effect in Drp1 knock-out cells. Further analogues of this compound were identified and screened, though none displayed greater affinity to human Drp1 isoform 3 than DRP1i27. To date, this is the first small molecule inhibitor shown to directly bind to human Drp1.
How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation
Authors: Halecker S. , Hansen S. , Krabben L. , Ebner F. , Kaufer B. , Denner J.
Published: December 2022

Porcine cytomegalovirus (PCMV), that is actually a porcine roseolovirus (PRV), is a common herpesvirus in domestic pigs and wild boars. In xenotransplantation, PCMV/PRV has been shown to significantly reduce the survival time of pig kidneys and hearts in preclinical trials with different non-human primates. Furthermore, PCMV/PRV has been transmitted in the first pig to human heart xenotransplantation and contributed to the death of the patient. Although transmitted to the recipient, there is no evidence that PCMV/PRV can infect primate cells including human cells. PCMV/PRV is closely related to the human herpesviruses 6 and 7, and only distantly related to the human CMV (HCMV). Antiviral drugs used for the treatment of HCMV are less effective against PCMV/PRV. However, there are well described strategies to eliminate the virus from pig facilities. In order to detect the virus and to eliminate it, highly sensitive detection methods and the knowledge of how, where and when to screen the donor pigs is required. Here, a comparative testing of organs from pigs of different ages using polymerase chain reaction (PCR)-based and immunological methods was performed. Testing young piglets, PCMV/PRV was detected effectively by PCR in blood, bronchoalveolar lavage fluid, tonsils and heart. In adult animals, detection by PCR was not successful in most cases, because the virus load was below the detection limit or the virus was in its latent stage. Therefore, detection of antibodies against selected recombinant proteins corresponding to epitopes detected by nearly all infected animals in a Western blot assay is advantageous. By contrast, immunological testing is not beneficial in young animals as piglets might have PCMV/PRV-specific antibodies obtained from their infected mother via the colostrum. Using a thoughtful combination of PCR-based and immunological methods, detection of PCMV/PRV in donor pigs for xenotransplantation is feasible and a controlled elimination of the virus by early weaning or other methods is possible.
Integrated analysis of Hashtgerd plain deformation, using Sentinel-1 SAR, geological and hydrological data
Authors: Khoshlahjeh Azar Mahdi , Shami Siavash , Nilfouroushan Faramarz , Salimi Maryam , Ghayoor Bolorfroshan Mahdieh , Reshadi Mir Amir Mohammad
Published: December 2022

Due to its proximity to Tehran, the Hashtgerd catchment in Iran is an important region that has experienced alarming subsidence rates in recent years. This study estimated the ground surface deformation in the Hashtgerd plain between 2015 and 2020 using Sentinel-1 SAR data and InSAR technique. The average LOS displacement of the ascending and descending tracks was − 23 cm/year and − 22 cm/year, respectively. The central area of the plain experienced the greatest vertical subsidence, with a more than − 100 cm cumulative displacement. The Karaj-Qazvin railway and highway that pass through this area have been damaged by subsidence, according to an analysis of profiles drawn along the transportation lines. The southern sections of Hashtgerd city have experienced a total displacement of − 30 cm/year over the course of about 6 years. The relationship between changes in groundwater level and subsidence rate in this region was examined using piezometer and precipitation data. Geoelectric sections and piezometric well logs were also utilized to investigate the geological characteristics of the Hashtgerd aquifer. According to the findings, the leading causes of subsidence were uncontrolled groundwater abstraction. This research highlights the need to comprehend the spatial distribution of confined aquifers and their effect on subsidence, which can aid in the development of a suitable management strategy to restore these aquifers.
A few-shot approach for COVID-19 screening in standard and portable chest X-ray images
Authors: Cores Daniel , Vila-Blanco Nicolás , Pérez-Alarcón María , Martínez-de-Alegría Anxo , Mucientes Manuel , Carreira María J.
Published: December 2022

Reliable and effective diagnostic systems are of vital importance for COVID-19, specifically for triage and screening procedures. In this work, a fully automatic diagnostic system based on chest X-ray images (CXR) has been proposed. It relies on the few-shot paradigm, which allows to work with small databases. Furthermore, three components have been added to improve the diagnosis performance: (1) a region proposal network which makes the system focus on the lungs; (2) a novel cost function which adds expert knowledge by giving specific penalties to each misdiagnosis; and (3) an ensembling procedure integrating multiple image comparisons to produce more reliable diagnoses. Moreover, the COVID-SC dataset has been introduced, comprising almost 1100 AnteroPosterior CXR images, namely 439 negative and 653 positive according to the RT-PCR test. Expert radiologists divided the negative images into three categories (normal lungs, COVID-related diseases, and other diseases) and the positive images into four severity levels. This entails the most complete COVID-19 dataset in terms of patient diversity. The proposed system has been compared with state-of-the-art methods in the COVIDGR-1.0 public database, achieving the highest accuracy (81.13% ± 2.76%) and the most robust results. An ablation study proved that each system component contributes to improve the overall performance. The procedure has also been validated on the COVID-SC dataset under different scenarios, with accuracies ranging from 70.81 to 87.40%. In conclusion, our proposal provides a good accuracy appropriate for the early detection of COVID-19.