bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assisted Reproduction and Discussion of Rare Cases in Monozygotic Twinning
Authors: Tan Yuge 
Published: June 2023

AbstractAssisted reproductive technology is a crucial factor that increases the incidence of monozygotic twinning in humans. This article discusses the impact of various indicators in assisted reproductive technology studies on pregnancy outcomes, especially studies with a large number of clinical cases. Furthermore, three rare cases in multiples pregnancy are discussed: fetus papyraceous of a pair of male monozygotic twins in a set of triplets, two pairs of sesquizygotic twins with sex-discordance, and rare conjoined triplets.
Laser Raman Induced Degradation of Macromolecular Carbon in Coals and Meteorites
Authors: Jakubek Ryan S. , Fries Marc D. 
Published: June 2023

AbstractMacromolecular carbon (MMC) is a polymeric solid form of carbon formed from numerous natural and anthropogenic processes. MMC is found in geologic samples, such as coals, meteorites, and metamorphic rocks, and the microstructure of the MMC provides details of the thermal history of the sample. Raman spectroscopy allows for a simple, quick examination of the MMC structure and thermal history of the rock. However, accurate Raman analysis necessitates that the Raman incident laser does not photodamage the MMC being measured. Here we examine, in detail, the effect of 532 and 488 nm laser irradiation on the structure of MMC in coals and meteorites. We show that photodegradation does affect the primary “G” and “D” Raman band peak positions, widths, absolute intensities, and relative intensities and we quantify changes with progressive irradiation. These results provide insight into the MMC structural changes that occur with photodegradation. We find that significant photodegradation occurs even with low laser powers (<200 μW). A literature survey of Raman MMC measurements shows that almost all publications use incident laser irradiances that would result in significant photodegradation of MMC within the accumulation time of a single Raman spectrum.
Assessing the Effect of the U.S. Vaccination Program on the Coronavirus Positivity Rate With a Multivariate Framework
Authors: Sanchez‐Vargas A. , Mendez‐Astudillo J. , López‐Vidal Y. , López‐Carr D. , Estrada F. 
Published: June 2023

AbstractThe factors influencing the incidence of COVID‐19, including the impact of the vaccination programs, have been studied in the literature. Most studies focus on one or two factors, without considering their interactions, which is not enough to assess a vaccination program in a statistically robust manner. We examine the impact of the U.S. vaccination program on the SARS‐CoV‐2 positivity rate while simultaneously considering a large number of factors involved in the spread of the virus and the feedbacks among them. We consider the effects of the following sets of factors: socioeconomic factors, public policy factors, environmental factors, and non‐observable factors. A time series Error Correction Model (ECM) was used to estimate the impact of the vaccination program at the national level on the positivity rate. Additionally, state‐level ECMs with panel data were combined with machine learning techniques to assess the impact of the program and identify relevant factors to build the best‐fitting models. We find that the vaccination program reduced the virus positivity rate. However, the program was partially undermined by a feedback loop in which increased vaccination led to increased mobility. Although some external factors reduced the positivity rate, the emergence of new variants increased the positivity rate. The positivity rate was associated with several forces acting simultaneously in opposite directions such as the number of vaccine doses administered and mobility. The existence of complex interactions, between the factors studied, implies that there is a need to combine different public policies to strengthen the impact of the vaccination program.
A Survey of Thunderstorms That Produce Megaflashes Across the Americas
Authors: Peterson Michael 
Published: June 2023

AbstractWe previously observed that long‐horizontal lightning flashes exceeding 100 km in length, known as “megaflashes,” occur preferentially in certain thunderstorms. In this study, we develop a cluster feature approach for automatically documenting the evolutions of thunderstorm systems from continuous lightning observations provided by the Geostationary Lightning Mapper (GLM) on NOAA's Geostationary Operational Environmental Satellites (GOES). We apply this methodology to GOES‐16 GLM observations from 2018 to mid‐2022 to improve our understanding of megaflash‐producing storms. We find that megaflashes occur in long‐lived (median: 14 hr) storms that grow to exceptional sizes (median: 11,984 km2) while they propagate across long distances (median: 622 km) compared to ordinary storms. The first megaflashes are typically produced within 15 min of the storm reaching its peak intensity and extent. However, most megaflashes occur ≥13 hr after the initial megaflash activity, and are sufficiently close to convection to suggest initiation in the thunderstorm core (where GLM has difficulty detecting faint early light sources from megaflashes). Megaflashes generated outside of convection are rare, accounting for 2.7% of the sample using a 50 km convective distance threshold, but also tend to be larger than normal megaflashes, possibly due to having direct access to electrified stratiform clouds through which megaflashes propagate.
Embracing Uncertainty to Resolve Polar Wander: A Case Study of Cenozoic North America
Authors: Gallo L. C. , Domeier M. , Sapienza F. , Swanson‐Hysell N. L. , Vaes B. , Zhang Y. , Arnould M. , Eyster A. , Gürer D. , Király Á. , Robert B. , Rolf T. , Shephard G. , van der Boon A. 
Published: June 2023

AbstractOur understanding of Earth's paleogeography relies heavily on paleomagnetic apparent polar wander paths (APWPs), which represent the time‐dependent position of Earth's spin axis relative to a given block of lithosphere. However, conventional approaches to APWP construction have significant limitations. First, the paleomagnetic record contains substantial noise that is not integrated into APWPs. Second, parametric assumptions are adopted to represent spatial and temporal uncertainties even where the underlying data do not conform to the assumed distributions. The consequences of these limitations remain largely unknown. Here, we address these challenges with a bottom‐up Monte Carlo uncertainty propagation scheme that operates on site‐level paleomagnetic data. To demonstrate our methodology, we present an extensive compilation of site‐level Cenozoic paleomagnetic data from North America, which we use to generate a high‐resolution APWP. Our results demonstrate that even in the presence of substantial noise, polar wandering can be assessed with unprecedented temporal and spatial resolution.
The 2016 Menyuan Earthquake: The Largest Self‐Arrested Crustal Earthquake Ever Observed
Authors: Xu Duyuan , Gong Wenzheng , Zhang Zhenguo , Xu Jiankuan , Yu Houyun , Chen Xiaofei 
Published: June 2023

AbstractThe 2016 Mw 5.9 Menyuan earthquake occurred near the Haiyuan fault system in the northeastern Tibetan plateau. Although some kinematic properties of this event have been investigated, more dynamic properties still need to be clarified. First, we use the empirical Green's function method to obtain this event's apparent source time functions (ASTFs), which present a bell shape with a duration of 3s and corresponding smooth spectra. We then conduct dynamic rupture simulations, which are well constrained by the seismic and geodetic observations, to explore more in‐depth source properties. The results show that the characteristics of ASTFs can be explained by the self‐arresting rupture model, which implies that the rupture propagation of this event may spontaneously terminate before reaching the barriers. This result suggests that the initial conditions when this earthquake nucleated may have controlled the rupture process. Our work contributes to understanding the stopping mechanism of some moderate earthquake ruptures.
Is legislation to prevent genetic discrimination necessary in Japan? An overview of the current policies and public attitudes
Authors: Muto Kaori , Nagai Akiko , Ri Izen , Takashima Kyoko , Yoshida Sachie 
Published: June 2023

AbstractGenetic discrimination (GD) has not been discussed in East Asia as extensively as in Europe and North America. Influenced by UNESCO’s universal declaration in 1997, the Japanese government took a stringent approach toward GD by releasing the Basic Principles on Human Genome Research in 2000. However, Japanese society has mostly been ignoring the prevention of GD for decades, and the principle of prohibiting GD was never adhered to in any of the Japanese laws. We conducted anonymous surveys among the general adult population in 2017 and 2022 to explore their experiences of GD and attitudes toward laws carrying penalties to prevent GD in Japan. In both years, approximately 3% of the respondents had experienced some unfavorable treatment regarding their genetic information. They showed higher recognition of the benefits of using genetic information and lower recognition of concerns about using genetic information and GD in 2022 than in 2017. However, the awareness regarding the need for legislation with penalties on GD had increased over the five-year period. In 2022, the framework of a bill to promote genomic medicine and prevent GD without any relevant penalties was released by the Bipartisan Diet Members Caucus. Considering that the absence of regulations may be a barrier to obtaining genomic medicine, as the initial step toward making the prohibition of GD more effective, legislation that no form of GD will be tolerated may stimulate education and awareness regarding respect for the human genome and its diversity.
piRT-IFC: Physics-informed real-time impedance flow cytometry for the characterization of cellular intrinsic electrical properties
Authors: Luan Xiaofeng , Liu Pengbin , Huang Di , Zhao Haiping , Li Yuang , Sun Sheng , Zhang Wenchang , Zhang Lingqian , Li Mingxiao , Zhi Tian , Zhao Yang , Huang Chengjun 
Published: June 2023

AbstractReal-time transformation was important for the practical implementation of impedance flow cytometry. The major obstacle was the time-consuming step of translating raw data to cellular intrinsic electrical properties (e.g., specific membrane capacitance Csm and cytoplasm conductivity σcyto). Although optimization strategies such as neural network-aided strategies were recently reported to provide an impressive boost to the translation process, simultaneously achieving high speed, accuracy, and generalization capability is still challenging. To this end, we proposed a fast parallel physical fitting solver that could characterize single cells’ Csm and σcyto within 0.62 ms/cell without any data preacquisition or pretraining requirements. We achieved the 27000-fold acceleration without loss of accuracy compared with the traditional solver. Based on the solver, we implemented physics-informed real-time impedance flow cytometry (piRT-IFC), which was able to characterize up to 100,902 cells’ Csm and σcyto within 50 min in a real-time manner. Compared to the fully connected neural network (FCNN) predictor, the proposed real-time solver showed comparable processing speed but higher accuracy. Furthermore, we used a neutrophil degranulation cell model to represent tasks to test unfamiliar samples without data for pretraining. After being treated with cytochalasin B and N-Formyl-Met-Leu-Phe, HL-60 cells underwent dynamic degranulation processes, and we characterized cell’s Csm and σcyto using piRT-IFC. Compared to the results from our solver, accuracy loss was observed in the results predicted by the FCNN, revealing the advantages of high speed, accuracy, and generalizability of the proposed piRT-IFC.
hMOF induces cisplatin resistance of ovarian cancer by regulating the stability and expression of MDM2
Authors: Cai Mingbo , Xu Sulong , Jin Yuxi , Yu Jingjing , Dai Shan , Shi Xiao-Jing , Guo Ruixia 
Published: June 2023

AbstractHistone acetyltransferase human males absent on the first (hMOF) is a member of MYST family which participates in posttranslational chromatin modification by controlling the acetylation level of histone H4K16. Abnormal activity of hMOF occurs in multiple cancers and biological alteration of hMOF expression can affect diverse cellular functions including cell proliferation, cell cycle progression and embryonic stem cells (ESCs) self-renewal. The relationship between hMOF and cisplatin resistance was investigated in The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) database. Lentiviral-mediated hMOF-overexpressed cells or hMOF-knockdown cells were established to investigate its role on cisplatin-based chemotherapy resistance in vitro ovarian cancer cells and animal models. Furthermore, a whole transcriptome analysis with RNA sequencing was used to explore the underlying molecular mechanism of hMOF affecting cisplatin-resistance in ovarian cancer. The data from TCGA analysis and IHC identification demonstrated that hMOF expression was closely associated with cisplatin-resistance in ovarian cancer. The expression of hMOF and cell stemness characteristics increased significantly in cisplatin-resistant OVCAR3/DDP cells. In the low hMOF expressing ovarian cancer OVCAR3 cells, overexpression of hMOF improved the stemness characteristics, inhibited cisplatin-induced apoptosis and mitochondrial membrane potential impairment, as well as reduced the sensitivity of OVCAR3 cells to cisplatin treatment. Moreover, overexpression of hMOF diminished tumor sensitivity to cisplatin in a mouse xenograft tumor model, accompanied by decrease in the proportion of cisplatin-induced apoptosis and alteration of mitochondrial apoptosis proteins. In addition, opposite phenotype and protein alterations were observed when knockdown of hMOF in the high hMOF expressing ovarian cancer A2780 cells. Transcriptomic profiling analysis and biological experimental verification orientated that MDM2-p53 apoptosis pathway was related to hMOF-modulated cisplatin resistance of OVCAR3 cells. Furthermore, hMOF reduced cisplatin-induced p53 accumulation by stabilizing MDM2 expression. Mechanistically, the increased stability of MDM2 was due to the inhibition of ubiquitinated degradation, which resulted by increased of MDM2 acetylation levels by its direct interaction with hMOF. Finally, genetic inhibition MDM2 could reverse hMOF-mediated cisplatin resistance in OVCAR3 cells with up-regulated hMOF expression. Meanwhile, treatment with adenovirus expressing shRNA of hMOF improved OVCAR3/DDP cell xenograft sensitivity to cisplatin in mouse. Collectively, the results of the study confirm that MDM2 as a novel non-histone substrate of hMOF, participates in promoting hMOF-modulated cisplatin chemoresistance in ovarian cancer cells. hMOF/MDM2 axis might be a potential target for the treatment of chemotherapy-resistant ovarian cancer.
Antibiotics in the clinical pipeline as of December 2022
Authors: Butler Mark S. , Henderson Ian R. , Capon Robert J. , Blaskovich Mark A. T. 
Published: June 2023

AbstractThe need for new antibacterial drugs to treat the increasing global prevalence of drug-resistant bacterial infections has clearly attracted global attention, with a range of existing and upcoming funding, policy, and legislative initiatives designed to revive antibacterial R&D. It is essential to assess whether these programs are having any real-world impact and this review continues our systematic analyses that began in 2011. Direct-acting antibacterials (47), non-traditional small molecule antibacterials (5), and β-lactam/β-lactamase inhibitor combinations (10) under clinical development as of December 2022 are described, as are the three antibacterial drugs launched since 2020. Encouragingly, the increased number of early-stage clinical candidates observed in the 2019 review increased in 2022, although the number of first-time drug approvals from 2020 to 2022 was disappointingly low. It will be critical to monitor how many Phase-I and -II candidates move into Phase-III and beyond in the next few years. There was also an enhanced presence of novel antibacterial pharmacophores in early-stage trials, and at least 18 of the 26 phase-I candidates were targeted to treat Gram-negative bacteria infections. Despite the promising early-stage antibacterial pipeline, it is essential to maintain funding for antibacterial R&D and to ensure that plans to address late-stage pipeline issues succeed.
Patterns in soil microbial diversity across Europe
Authors: Labouyrie Maëva , Ballabio Cristiano , Romero Ferran , Panagos Panos , Jones Arwyn , Schmid Marc W. , Mikryukov Vladimir , Dulya Olesya , Tedersoo Leho , Bahram Mohammad , Lugato Emanuele , van der Heijden Marcel G. A. , Orgiazzi Alberto 
Published: June 2023

AbstractFactors driving microbial community composition and diversity are well established but the relationship with microbial functioning is poorly understood, especially at large scales. We analysed microbial biodiversity metrics and distribution of potential functional groups along a gradient of increasing land-use perturbation, detecting over 79,000 bacterial and 25,000 fungal OTUs in 715 sites across 24 European countries. We found the lowest bacterial and fungal diversity in less-disturbed environments (woodlands) compared to grasslands and highly-disturbed environments (croplands). Highly-disturbed environments contain significantly more bacterial chemoheterotrophs, harbour a higher proportion of fungal plant pathogens and saprotrophs, and have less beneficial fungal plant symbionts compared to woodlands and extensively-managed grasslands. Spatial patterns of microbial communities and predicted functions are best explained when interactions among the major determinants (vegetation cover, climate, soil properties) are considered. We propose guidelines for environmental policy actions and argue that taxonomical and functional diversity should be considered simultaneously for monitoring purposes.
Integrated quantum optical phase sensor in thin film lithium niobate
Authors: Stokowski Hubert S. , McKenna Timothy P. , Park Taewon , Hwang Alexander Y. , Dean Devin J. , Celik Oguz Tolga , Ansari Vahid , Fejer Martin M. , Safavi-Naeini Amir H. 
Published: June 2023

AbstractThe quantum noise of light, attributed to the random arrival time of photons from a coherent light source, fundamentally limits optical phase sensors. An engineered source of squeezed states suppresses this noise and allows phase detection sensitivity beyond the quantum noise limit (QNL). We need ways to use quantum light within deployable quantum sensors. Here we present a photonic integrated circuit in thin-film lithium niobate that meets these requirements. We use the second-order nonlinearity to produce a squeezed state at the same frequency as the pump light and realize circuit control and sensing with electro-optics. Using 26.2 milliwatts of optical power, we measure (2.7 ± 0.2)% squeezing and apply it to increase the signal-to-noise ratio of phase measurement. We anticipate that photonic systems like this, which operate with low power and integrate all of the needed functionality on a single die, will open new opportunities for quantum optical sensing.
Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner
Authors: Tang Tianyu , Huang Xing , Lu Minghao , Zhang Gang , Han Xu , Liang Tingbo 
Published: June 2023

AbstractCancer cell metabolism contributes to the establishment of an immunosuppressive tumor microenvironment. Aberrant expression of CD73, a critical enzyme in ATP metabolism, on the cell surface results in the extracellular accumulation of adenosine, which exhibits direct inhibitory effects on tumor-infiltrating lymphocytes. However, little is known about the influence of CD73 on negative immune regulation-associated signaling molecules and transduction pathways inside tumor cells. This study aims to demonstrate the moonlighting functions of CD73 in immunosuppression in pancreatic cancer, an ideal model characterized by complex crosstalk among cancer metabolism, immune microenvironment, and immunotherapeutic resistance. The synergistic effect of CD73-specific drugs in combination with immune checkpoint blockade is observed in multiple pancreatic cancer models. Cytometry by time-of-flight analysis shows that CD73 inhibition reduces tumor-infiltrating Tregs in pancreatic cancer. Tumor cell-autonomous CD73 is found to facilitate Treg recruitment, in which CCL5 is identified as a significant downstream effector of CD73 using integrated proteomic and transcriptomic analyses. CD73 transcriptionally upregulates CCL5 through tumor cell-autocrine adenosine–Adora2a signaling-mediated activation of the p38–STAT1 axis, recruiting Tregs to pancreatic tumors and causing an immunosuppressive microenvironment. Together, this study highlights that CD73–adenosine metabolism transcriptionally controls pancreatic cancer immunosuppression in a tumor-autonomous and -autocrine manner.
Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates
Authors: Chen Xinhong , Wolfe Damien A. , Bindu Dhanesh Sivadasan , Zhang Mengying , Taskin Naz , Goertsen David , Shay Timothy F. , Sullivan Erin E. , Huang Sheng-Fu , Ravindra Kumar Sripriya , Arokiaraj Cynthia M. , Plattner Viktor M. , Campos Lillian J. , Mich John K. , Monet Deja , Ngo Victoria , Ding Xiaozhe , Omstead Victoria , Weed Natalie , Bishaw Yeme , Gore Bryan B. , Lein Ed S. , Akrami Athena , Miller Cory , Levi Boaz P. , Keller Annika , Ting Jonathan T. , Fox Andrew S. , Eroglu Cagla , Gradinaru Viviana 
Published: June 2023

AbstractDelivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.