bluuebunny/crossref_metadata_2025 huggingface dataset:
SHRIMP U–Pb geochronology of Mesoproterozoic basement and overlying Ocoee Supergroup, NC–TN: dating diagenetic xenotime and monazite overgrowths on detrital minerals to determine the age of sedimentary deposition
Authors: Aleinikoff John N. , Southworth Scott , Fanning C. Mark
Published: February 2023

Sedimentary rocks of the Ocoee Supergroup crop out in the Appalachian Blue Ridge of western North Carolina and eastern Tennessee. This ∼12 km thick sequence of strata was mapped as nonconformably overlying Mesoproterozoic crystalline basement (about 1.20–1.02 Ga) and beneath the lower Cambrian Chilhowee Group, leading to the traditional interpretation that the Ocoee Supergroup was deposited between about 1.02 and 0.54 Ga. This interpretation was challenged by Unrug and Unrug (1990, Geology, 18: 1041–1045) and Unrug et al. (2000, Geological Society of America Bulletin. Vol. 112, pp. 982–996), who claimed that Paleozoic fossils were recovered from rocks of the Walden Creek Group (upper Ocoee), and thereby created a new tectonic model for the origin of Laurentia. To resolve the age controversy concerning the time of deposition of the Ocoee Supergroup, diagenetic xenotime overgrowths on detrital zircon and diagenetic monazite on detrital monazite were dated by the U–Pb method. Sensitive High Resolution Ion Microprobe ages of diagenetic xenotime from three samples of sandstone (Thunderhead Sandstone, Cades Sandstone, and Shields Formation) indicate that the Ocoee Supergroup was deposited in the interval of about 580–550 Ma. A sample of Sandsuck Formation (uppermost Ocoee) yielded xenotime overgrowths of about 410 Ma, probably related to post-depositional low-grade metamorphism. Various origins of xenotime overgrowths may be distinguished by trace element distributions. Ages and trace element concentrations of monazite overgrowths support the xenotime age results, although concordia systematics are complicated by high concentrations of common Pb and inheritance of ages (∼1.2 and 0.6 Ga). These age data support the observed field relations for a late Neoproterozoic depositional age of the Ocoee Supergroup.
The impact of Sino–US trade war on the co-movement between China’s stock market and global stock markets
Authors: Song Yuping , Sun Yankun , Ma Yue
Published: February 2023

Taking the Sino–US trade war as the background, we study the co-movement changes on horizontal return and volatility of the daily logarithmic return data of global stock indices from 2016 to January 23, 2020 from static and dynamic perspectives. Through static tools such as correlation coefficient matrices, complex networks, and Granger causality, it is found that the trade war has significantly strengthened the correlation between the Chinese stock market and the global stock market, and highlighted the position of the Hong Kong stock market. On dynamic analysis, the news impact surface shows the asymmetry of the co-movement for positive and negative news. The aDCC-EGARCH model is used to observe the dynamic co-movement changes between the Chinese stock market and the global stock market. It shows that trade conflicts have enhanced the co-movement between the Chinese stock market and the global stock market to varying degrees. At the same time, the Chinese stock market is strategically tilted towards the Asian market. Based on the research results in this paper, countries around the world need to pay more attention to the risk contagion between stock markets after the outbreak of the trade war. China’s inland markets should be alert to risk contagion from the Hong Kong market.
A Multi-Task Graph Neural Network with Variational Graph Auto-Encoders for Session-Based Travel Packages Recommendation
Authors: Zhu Guixiang , Cao Jie , Chen Lei , Wang Youquan , Bu Zhan , Yang Shuxin , Wu Jianqing , Wang Zhiping
Published: February 2023

Session-based travel packages recommendation aims to predict users’ next click based on their current and historical sessions recorded by Online Travel Agencies (OTAs). Recently, an increasing number of studies attempted to apply Graph Neural Networks (GNNs) to the session-based recommendation and obtained promising results. However, most of them do not take full advantage of the explicit latent structure from attributes of items, making learned representations of items less effective and difficult to interpret. Moreover, they only combine historical sessions (long-term preferences) with a current session (short-term preference) to learn a unified representation of users, ignoring the effects of historical sessions for the current session. To this end, this article proposes a novel session-based model named STR-VGAE, which fills subtasks of the travel packages recommendation and variational graph auto-encoders simultaneously. STR-VGAE mainly consists of three components:
travel packages encoder
,
users behaviors encoder
, and
interaction modeling
. Specifically, the
travel packages encoder
module is used to learn a unified travel package representation from co-occurrence attribute graphs by using multi-view variational graph auto-encoders and a multi-view attention network. The
users behaviors encoder
module is used to encode user’ historical and current sessions with a personalized GNN, which considers the effects of historical sessions on the current session, and coalesce these two kinds of session representations to learn the high-quality users’ representations by exploiting a gated fusion approach. The
interaction modeling
module is used to calculate recommendation scores over all candidate travel packages. Extensive experiments on a real-life tourism e-commerce dataset from China show that STR-VGAE yields significant performance advantages over several competitive methods, meanwhile provides an interpretation for the generated recommendation list.
A Geometric Multigrid Method for Space-Time Finite Element Discretizations of the Navier–Stokes Equations and its Application to 3D Flow Simulation
Authors: Anselmann Mathias , Bause Markus
Published: February 2023

We present a parallelized geometric multigrid (GMG) method, based on the cell-based Vanka smoother, for higher order space-time finite element methods (STFEM) to the incompressible Navier–Stokes equations. The STFEM is implemented as a time marching scheme. The GMG solver is applied as a preconditioner for generalized minimal residual iterations. Its performance properties are demonstrated for 2D and 3D benchmarks of flow around a cylinder. The key ingredients of the GMG approach are the construction of the local Vanka smoother over all degrees of freedom in time of the respective subinterval and its efficient application. For this, data structures that store pre-computed cell inverses of the Jacobian for all hierarchical levels and require only a reasonable amount of memory overhead are generated. The GMG method is built for the
deal.II
finite element library. The concepts are flexible and can be transferred to similar software platforms.
Facile Sensors for Humidity Measurement of Indoor Environment
Authors: Fatima Sana
Published: February 2023

In this work, we present the fabrication of interdigitated capacitive and resistive humidity sensors for interior environment monitoring using pencil-on-paper technology. The production of the graphite pencil is done on paper, without the use of solvents or clean rooms, and with inexpensive, biodegradable ingredients. This strategy advances the creation of sensors for environmentally friendly electronics, resulting in zero environmental damage during either their creation or their disposal.
Regenerative Endodontic Management of an Immature Necrotic Premolar Using Advanced Platelet-Rich Fibrin
Authors: Hosseini Sepideh , Chitsaz Nazanin , Hamrah Mohammad Hassan , Maleki Donya , Taghizadeh Emad
Published: February 2023

Regenerative endodontic management is a feasible treatment for immature teeth with periapical radiolucency and necrotic pulp that simplifies continued root creation. Among the most prevalent health problems in an immature root is dental pulp necrosis, which is caused by caries, improper endodontic treatments, and trauma. Necrosis of the dental pulp can affect long-term tooth survival and preservation and serve as a source of bacteria infecting the periapical tissue and the maxillofacial space. Here, we report on the application of advanced platelet-rich fibrin plus (A-PRF+) therapy, as a regenerative endodontic treatment (RET), in a 12-year-old with necrotic pulp and asymptomatic apical periodontitis. Over a 24-month follow-up post-treatment, we observed resolving of symptoms and a complete root formation with considerable periapical healing.
Carbonic Anhydrase IX Controls Vulnerability to Ferroptosis in Gefitinib-Resistant Lung Cancer
Authors: Zhang Chen , Lu Xiyi , Liu Xinyin , Xu Jiali , Li Jun , Qu Tianyu , Dai Jiali , Guo Renhua
Published: February 2023

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI, such as gefitinib) in lung cancer continues to be a major problem. Recent studies have shown the promise of ferroptosis-inducing therapy in EGFR-TKI resistant cancer, but have not been translated into clinical benefits. Here, we identified carbonic anhydrase IX (CA9) was upregulated in gefitinib-resistant lung cancer. Then we measured the cell viability, intracellular reactive oxygen species (ROS) levels, and labile iron levels after the treatment of ferroptosis inducer erastin. We found that CA9 confers resistance to ferroptosis-inducing drugs. Mechanistically, CA9 is involved in the inhibition of transferrin endocytosis and the stabilization of ferritin, leading to resistance to ferroptosis. Targeting CA9 promotes iron uptake and release, thus triggering gefitinib-resistant cell ferroptosis. Notably, CA9 inhibitor enhances the ferroptosis-inducing effect of cisplatin on gefitinib-resistant cells, thus eliminating resistant cells in heterogeneous tumor tissues. Taken together, CA9-targeting therapy is a promising approach to improve the therapeutic effect of gefitinib-resistant lung cancer by inducing ferroptosis.
Quantifying Podocyte Number in a Small Sample Size of Glomeruli with CUBIC to Evaluate Podocyte Depletion of db/db Mice
Authors: Shi Jiaoyu , Hu Yuan , Shao Guangze , Zhu Yixiang , Zhao Zhonghua , Xu Yanyong , Zhang Zhigang , Wu Huijuan
Published: February 2023

The loss of podocyte is crucial for diagnosis and prognosis of diabetic kidney disease, whereas commonly two-dimensional methods for quantifying podocyte number existed with issues of low fidelity and accuracy. In this study, clear, unobstructed brain imaging cocktails and computational analysis (CUBIC), one of three-dimensional optical clearing approaches, was used which combines tissue clearing, immunolabeling, and a light-sheet microscope to image and evaluate podocytes in C57BL/6 (C57) and db/db mice. We discovered that 77 podocytes per glomerulus were in C57 mice. On the subject of db/db mice, there were 74 podocytes by the age of 8 w, 72 podocytes by the age of 12 w, and 66 podocytes by the age of 16 w, compared with 76 podocytes in the control group, suggesting that there was a significant decrease in podocyte number in db/db mice with the age of 16 w, showing a trend which positively correlated to the deterioration of kidney function. Sample size estimation using the PASS software revealed that taking 5%, 7.5%, and 10% of the mean podocyte number per glomerulus as the statistical allowable error and 95% as total confidence interval, 33, 15, and 9 glomeruli were independently needed to be sampled in C57 mice to represent the overall glomeruli to calculate podocyte number. Furthermore, in the control group of db/db mice, 36, 18, and 11 glomeruli were needed, compared with 46, 24, and 14 glomeruli in db/db mice by the age of 8 w, 43, 21, and 12 glomeruli by the age of 12 w, and 52, 27, and 16 by the age of 16 w. These findings indicated that precise quantification of podocyte number could judge the progression of diabetic kidney disease. In addition, a small number of glomeruli could be actually representative of the whole sample size, which indicated apparent practicability of CUBIC for clinical use.
Probiotic Properties of Exopolysaccharide-Producing Bacteria from Natto
Authors: Ngampuak Vongsathorn , Thongmee Acharawan , Pongpoungphet Napapan , Wongwailikhit Kanda , Kanchanaphum Panan
Published: February 2023

Natto is a traditional Japanese food made from soybeans fermented with Bacillus subtilis var. natto. It is also a famous food in Thailand. Potential probiotics were screened from natto. Bacillus subtilis strain VN5 produced the most quantity of exopolysaccharide (EPS), so it was selected to study the properties of microbial EPS and probiotics. The Fourier transform infrared spectrometer or FT-IR spectroscopy confirmed the presence of carboxyl and hydroxyl groups. The patterns of FT-IR and levans are similar. The basic properties of probiotics were revealed. The 90% of VN5 strain resisted lysozyme within 30 min. VN5 survived under acidic conditions (pH 1-6), and the survival rate in 0.3%, 0.5%, and 1% bile solutions for 24 h was 100%. Unfortunately, VN5 did not inhibit the growth of Escherichia coli, Staphylococcus aureus, and Salmonella typhi. Gamma hemolysis was determined in VN5 strain. The finding on Bacillus subtilis strain (VN5) from natto paves the way to a high potential, useful new strain of probiotics.
Hyper‐Mol: Molecular Representation Learning via Fingerprint‐Based Hypergraph
Authors: Cui Shicheng , Li Qianmu , Li Deqiang , Lian Zhichao , Hou Jun
Published: February 2023

With the development of artificial intelligence (AI) in the field of drug design and discovery, learning informative representations of molecules is becoming crucial for those AI‐driven tasks. In recent years, the graph neural networks (GNNs) have emerged as a preferred choice of deep learning architecture and have been successfully applied to molecular representation learning (MRL). Up‐to‐date MRL methods directly apply the message passing mechanism on the atom‐level attributes (i.e., atoms and bonds) of molecules. However, they neglect latent yet significant hyperstructured knowledge, such as the information of pharmacophore or functional class. Hence, in this paper, we propose Hyper‐Mol, a new MRL framework that applies GNNs to encode hypergraph structures of molecules via fingerprint‐based features. Hyper‐Mol explores the hyperstructured knowledge and the latent relationships of the fingerprint substructures from a hypergraph perspective. The molecular hypergraph generation algorithm is designed to depict the hyperstructured information with the physical and chemical characteristics of molecules. Thus, the fingerprint‐level message passing process can encode both the intra‐structured and inter‐structured information of fingerprint substructures according to the molecular hypergraphs. We evaluate Hyper‐Mol on molecular property prediction tasks, and the experimental results on real‐world benchmarks show that Hyper‐Mol can learn comprehensive hyperstructured knowledge of molecules and is superior to the state‐of‐the‐art baselines.
Which Gating System Can Prevent Addiction to Online Games?
Authors: Matheus Flobert , Jayadi Riyanto
Published: February 2023

The online game industry has increased time by time. Because of that, many addiction cases emerge in humans. In addition, some factors could make people addicted and mitigate or prevent the addiction. However, this addiction has already created some problems, such as skipping school (mild cases) to murder cases (huge cases). A gating system is a system that could prevent players from experiencing some content in the game after a specific limit has been reached. This study is aimed at identifying which gating systems in online games could make players more addicted and which systems are the most appropriate to mitigate or prevent addiction to online games. The study is done with a survey from online game communities with 458 samples in Indonesia. The result of the study shows that resource is the factor that affects addiction, and the stamina gating system is the one that affects resource as mitigation of addiction. This research shows that the stamina gating system will affect how players manage their resources in real life so that they will not be addicted to the game.
Solution of Nonlinear Fredholm Integral Equations on Almost

Z

⊥

-Contraction
Authors: Nallaselli Gunasekaran , Gnanaprakasam Arul Joseph , Mani Gunaseelan , Javed Khalil , Almalki Yahya
Published: February 2023

In this manuscript, we develop an orthogonal to basically

Z

-contraction and demonstrate various fixed point theorems of nonlinear Fredholm integral equation solutions in such a contraction. By using these ideas of discovering the fixed point theorems, we can also build the application of the Fredholm integral equation.
Effect of Public Expenditure on Economic Growth in the Case of Ethiopia
Authors: Mulugeta Emeru Girma
Published: February 2023

This study’s primary goal was to explain how Ethiopia’s economic growth affected government spending. The time series data utilized in the study were gathered between 1980 and 2018. The time series data were subjected to the Johansen cointegration test and the vector error correction model (VECM) in order to evaluate the short- and long-term correlations between public spending and economic growth in Ethiopia. According to the study, both long- and short-term economic growths are positively and significantly impacted by government spending on education. Long-term economic growth is negatively impacted by government expenditure on agriculture, while short-term effects are negatively impacted and considerable. In the long run, investment spending has a positive but negligible impact on economic growth; however, in the short run, it has a negative but large effect. Defense spending by the government has a positive and negligible effect on economic growth over the short and long terms. Both in the short and long terms, spending on health has a favorable and considerable impact on economic growth. According to the study, government spending on the education sector would help to foster the conditions that could result in higher labor force participation rates and, consequently, higher rates of economic growth. Aiming to establish a healthy and productive society that promotes economic progress, policy should focus on complementary measures to scale-up initiatives in the health sector.
House Dust Mite and Cat Dander Extract Induce Asthma-Like Histopathology with an Increase of Mucosal Mast Cells in a Guinea Pig Model
Authors: Ramos-Ramírez Patricia , Liu Jielu , Mogren Sofia , Gregory Joshua , Noreby Malin , Petrén Anne , Lei Ying , Olsson Henric , van Hage Marianne , Kervinen Jukka , Hellman Lars , Andersson Cecilia , Nilsson Gunnar , Adner Mikael
Published: February 2023

Background. Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Methods. Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Results. Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. Conclusions. We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.
TiO2/g-C3N4 Visible-Light-Driven Photocatalyst for Methylene Blue Decomposition
Authors: Hoa Dang Thi Ngoc , Tu Nguyen Thi Thanh , Thinh Huynh Quoc An , Van Thanh Son Le , Son Le Vu Truong , Quyen Nguyen Duc Vu , Son Le Lam , Tuyen Tran Ngoc , Thong Pham Le Minh , Diem Ly Hoang , Khieu Dinh Quang
Published: February 2023

In this work, graphitic carbon nitride (g-C3N4)/titanium dioxide (TiO2) nanoparticles with heterostructures were synthesized in situ from a mixture of melamine and peroxo-titanium complexes in a calcination process. The TiO2 nanoparticles are well-dispersed on the g-C3N4 nanosheets. The prepared TiO2/g-C3N4 composites have a heterostructure and excellent photocatalytic activity for decomposing methylene blue (MB) under visible light irradiation. The as-obtained g-C3N4 embroiled with TiO2 has a much larger surface area than its components (66.7 and 6.6 m2·g−1 for TiO2 and g-C3N4 against 95.5–143.8 m2·g−1 for the composite, respectively). It enhances the separation of photo-generated charge carriers. The TiO2/g-C3N4 photocatalytic degradation of MB was investigated in aqueous heterogeneous suspensions. The experimental kinetic data for the photocatalytic process follow the pseudo-first-order kinetic model. Furthermore, TiO2/g-C3N4 retains high photocatalytic activity after four reaction cycles. In addition to prompt removal of the color, the TiO2/g-C3N4 photocatalyst can oxidize MB almost completely to final oxidation products. The pathway of MB decomposition was also addressed. Additionally, the TiO2/g-C3N4 photocatalytic system was employed to eliminate other typical organic pigments, such as malachite green, methyl blue, and methyl red. The TiO2/g-C3N4 material, with remarkable dye degradability, is a promising catalyst in industrial textile treatment and can find applications in light-harvesting systems.
PRP19 Enhances Esophageal Squamous Cell Carcinoma Progression by Reprogramming SREBF1-Dependent Fatty Acid Metabolism
Authors: Zhang Guang-Cong , Yu Xiang-Nan , Guo Hong-Ying , Sun Jia-Lei , Liu Zhi-Yong , Zhu Ji-Min , Liu Tao-Tao , Dong Ling , Shen Xi-Zhong , Yin Jie
Published: February 2023

Lipid metabolism reprogramming is a recognized hallmark of cancer cells. Identification of the underlying regulators of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) could uncover potential therapeutic targets to improve treatment. Here, we demonstrated that pre-mRNA processing factor 19 (PRP19) mediates reprogramming of lipid metabolism in ESCC. Expression of PRP19 was significantly upregulated in multiple ESCC cohorts and was correlated with poor clinical prognosis. PRP19 promoted ESCC proliferation in vitro and in vivo. Upregulation of PRP19 enhanced fatty acid synthesis through sterol regulatory element-binding protein 1 (SREBF1), a major transcription factor of lipid synthase. Moreover, PRP19 enhanced the stability of SREBF1 mRNA in an N6-methyladenosine–dependent manner. Overall, this study shows that PRP19-mediated fatty acid metabolism is crucial for ESCC progression. Targeting PRP19 is a potential therapeutic approach to reverse metabolic reprogramming in patients with ESCC.

Significance:

Upregulation of pre-mRNA processing factor 19 (PRP19) contributes to esophageal squamous cell carcinoma progression by reprogramming SREBF1-dependent fatty acid metabolism, identifying PRP19 as a potential prognostic biomarker and therapeutic target.
Molecular Evolution of Classic Hodgkin Lymphoma Revealed Through Whole-Genome Sequencing of Hodgkin and Reed Sternberg Cells
Authors: Maura Francesco , Ziccheddu Bachisio , Xiang Jenny Z. , Bhinder Bhavneet , Rosiene Joel , Abascal Federico , Maclachlan Kylee H. , Eng Kenneth Wha , Uppal Manik , He Feng , Zhang Wei , Gao Qi , Yellapantula Venkata D. , Trujillo-Alonso Vicenta , Park Sunita I. , Oberley Matthew J. , Ruckdeschel Elizabeth , Lim Megan S. , Wertheim Gerald B. , Barth Matthew J. , Horton Terzah M. , Derkach Andriy , Kovach Alexandra E. , Forlenza Christopher J. , Zhang Yanming , Landgren Ola , Moskowitz Craig H. , Cesarman Ethel , Imielinski Marcin , Elemento Olivier , Roshal Mikhail , Giulino-Roth Lisa
Published: February 2023

The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS cells. Using this approach, we now report the whole-genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events leading to cHL. We identified alterations in driver genes not previously described in cHL, APOBEC mutational activity, and the presence of complex structural variants including chromothripsis. We found that high ploidy in cHL is often acquired through multiple, independent chromosomal gains events including whole-genome duplication. Evolutionary timing analyses revealed that structural variants enriched for RAG motifs, driver mutations in B2M, BCL7A, GNA13, and PTPN1, and the onset of AID-driven mutagenesis usually preceded large chromosomal gains. This study provides a temporal reconstruction of cHL pathogenesis.

Significance:

Previous studies in cHL were limited to coding sequences and therefore not able to comprehensively decipher the tumor complexity. Here, leveraging cHL whole-genome characterization, we identify driver events and reconstruct the tumor evolution, finding that structural variants, driver mutations, and AID mutagenesis precede chromosomal gains.

This article is highlighted in the In This Issue feature, p. 171
APRRX1Signature Identifies TIM-3 and VISTA as Potential Immune Checkpoint Targets in a Subgroup of Microsatellite Stable Colorectal Cancer Liver Metastases
Authors: Nygaard Vigdis , Ree Anne Hansen , Dagenborg Vegar Johansen , Børresen-Dale Anne-Lise , Edwin Bjørn , Fretland Åsmund Avdem , Grzyb Krzysztof , Haugen Mads H. , Mælandsmo Gunhild M. , Flatmark Kjersti
Published: February 2023

Disease recurrence and drug resistance are major challenges in the clinical management of patients with colorectal cancer liver metastases (CLM), and because tumors are generally microsatellite stable (MSS), responses to immune therapies are poor. The mesenchymal phenotype is overrepresented in treatment-resistant cancers and is associated with an immunosuppressed microenvironment. The aim of this work was to molecularly identify and characterize a mesenchymal subgroup of MSS CLM to identify novel therapeutic approaches. We here generated a mesenchymal gene expression signature by analysis of resection specimens from 38 patients with CLM using ranked expression level of the epithelial-to-mesenchymal transition–related transcription factor PRRX1. Downstream pathway analysis based on the resulting gene signature was performed and independent, publicly available datasets were used to validate the findings. A subgroup comprising 16% of the analyzed CLM samples were classified as mesenchymal, or belonging to the PRRX1high group. Analysis of the PRRX1 signature genes revealed a distinct immunosuppressive phenotype with high expression of immune checkpoints HAVCR2/TIM-3 and VISTA, in addition to the M2 macrophage marker CD163. The findings were convincingly validated in datasets from three external CLM cohorts. Upregulation of immune checkpoints HAVCR2/TIM-3 and VISTA in the PRRX1high subgroup is a novel finding, and suggests immune evasion beyond the PD-1/PD-L1 axis, which may contribute to poor response to PD-1/PD-L1–directed immune therapy in MSS colorectal cancer. Importantly, these checkpoints represent potential novel opportunities for immune-based therapy approaches in a subset of MSS CLM.

Significance:

CLM is an important cause of colorectal cancer mortality where the majority of patients have yet to benefit from immunotherapies. In this study of gene expression profiling analyses, we uncovered novel immune checkpoint targets in a subgroup of patients with MSS CLMs harboring a mesenchymal phenotype.
Differential Diagnosis of Pulmonary Veno-Occlusive Disease and/or Pulmonary Capillary Hemangiomatosis after Identification of Two Novel EIF2AK4 Variants by Whole-Exome Sequencing
Authors: Park Jong Eun , Chang Sung-A , Jang Shin Yi , Lee Kyung Soo , Kim Duk-Kyung , Ki Chang-Seok
Published: February 2023

Background: Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. Pulmonary arterial hypertension (PAH) and PVOD/PCH are clinically similar, but there is a risk of drug-induced pulmonary edema when PCH patients receive the PAH therapy. Therefore, early diagnosis of PVOD/PCH is important. Objectives: We report the first case in Korea of PVOD/PCH in a patient carrying compound heterozygous pathogenic variants in the EIF2AK4 gene. Case Description and Method: A 19-year-old man who was previously diagnosed with idiopathic PAH suffered from dyspnea on exertion for 2 months. He had a reduced lung diffusion capacity for carbon monoxide (25% predicted). Chest computed tomography images showed diffusely scattered ground-glass opacity nodules in both lungs with an enlarged main pulmonary artery. For the molecular diagnosis of PVOD/PCH, whole-exome sequencing was performed for the proband. Results: Exome sequencing identified two novel EIF2AK4 variants, c.2137_2138dup (p.Ser714Leufs*78) and c.3358-1G>A. These two variants were classified as pathogenic variants according to the 2015 American College of Medical Genetics and Genomics guidelines. Conclusions: We identified two novel pathogenic variants (c.2137_2138dup and c.3358-1G>A) in the EIF2AK4 gene. Identification of possible pathogenic gene variants by whole-exome sequencing or panel sequencing is recommended as a guide to adequate treatment of patients with pulmonary hypertension.
Genetic Variants in SRD5A2 in a Spectrum of DSD Patients from Australian Clinics Highlight Importance of Genetic Testing alongside Typical First-Line Investigations
Authors: Robevska Gorjana , Hanna Chloe , van den Bergen Jocelyn , Welch John , Couper Jennifer , Harris Shannon , Joshi Kriti , Brown Justin , Sabin Matthew , Sinclair Andrew , O’Connell Michele , Ayers Katie
Published: February 2023

Introduction: Steroid 5-alpha reductase deficiency (5α-R2D) is a rare condition caused by genetic variants that reduce the activity of the enzyme that converts testosterone into dihydrotestosterone. The clinical spectrum of 5α-R2D is known to overlap with other 46,XY differences of sex development (DSD) such as androgen insensitivity or gonadal dysgenesis. However, the clinical trajectories of the aetiologies can differ, with 5α-R2D presenting its own challenges. Methods: In this study, we have collated clinical information for five individuals with variants in SRD5A2 identified using research genetic testing in an Australian paediatric setting. Results: We describe how a genetic finding resolved or confirmed a diagnosis for these individuals and how it guided clinical management and family counselling. Conclusion: This work highlights the importance of early genetic testing in children born with 46,XY DSD where it complements traditional first-line testing.
Molecular and Chromosomal Evolution of DsTc1_5 and DsPogo_8 Elements (Tc1-Mariner) in Species of the Dichotomius Genus (Coleoptera: Scarabaeidae): Contributions to the Speciation Process
Authors: Amorim Igor C. , Costa Rafaelle G.C. , Mota Liliane L. , Xavier Crislaine , Wallau Gabriel L. , Moura Rita C.
Published: February 2023

In Dichotomius genus, transposable elements (TE) have been related to chromosome remodeling, genomic evolution, and, possibly, to the speciation process. The objective of this study was to verify the interpopulational and interspecific conservation/variation of Tc1-Mariner elements (possibly autonomous) in Dichotomius species, aiming to identify possible contributions in the speciation process of this group. The analysis was performed on four species of Dichotomius, belonging to the Selenocopris subgenus. We verified the presence of the DsPogo_8 and DsTc1_5 elements by PCR and sequencing. We also isolated and sequenced the 28S and 16S rRNA genes aiming at the phylogenetic reconstruction of the analyzed species. Chromosomal mapping of TEs DsTc1_5 and DsPogo_8 was performed by fluorescent in situ hybridization. The results revealed the presence of the elements in the different species analyzed, except for DsTc1_5 in D. (S.) geminatus. These results suggest a vertical inheritance, with the presence of these elements in the common ancestor of these species. In the analyzed species, the nucleotide similarity of DsTc1_5 was higher than that of the 28S and 16S rRNA genes, suggesting the occurrence of horizontal transfer. The phylogenetic tree indicated that the absence of DsTc1_5 in D. (S.) geminatus is related to stochastic loss of this TE. Chromosomal mapping revealed dispersed signals, with predominance in euchromatic regions and wide variation in the chromosomal localization pattern of DsTc1_5 and DsPogo_8, both interpopulational and interspecific. This variation indicates that DsTc1_5 and DsPogo_8 may have contributed to prezygotic and postzygotic isolation, thus contributing to the speciation of these species.
Impact of Hysterotomy Closure Technique on Subsequent Cesarean Scar Defects Formation: A Systematic Review
Authors: Genovese Fortunato , Schiattarella Antonio , D’Urso Gisella , Vitale Salvatore Giovanni , Carugno Jose , Verzì Giovanna , D’Urso Valentina , Iacono Elisa , Siringo Stefano , Leanza Vito , Palumbo Marco
Published: February 2023

Introduction: The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section scar. It is associated with obstetrical complications such as caesarean scar, ectopic pregnancy, uterine rupture, and the placenta accreta spectrum. Women with cesarean scar defects are frequently asymptomatic but may also experience abnormal vaginal bleeding, chronic pelvic pain, and infertility. Methods: This systematic review aims to determine the best hysterotomy closure technique to prevent subsequent development of uterine scar defects. An electronic search in Medline, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov was performed from January 2001 until December 2020 for studies evaluating hysterotomy closure techniques. Results: Our systematic search strategy identified 1,781 titles. Six studies fulfilled inclusion criteria and were included in the final analysis. The results supported the superiority of the double-layer closure over the single-layer closure. Conclusions: Hysterotomy closure with continuous running sutures in two layers represents a suitable option to prevent cesarean scar defect formation. Particularly, the first layer should include the decidua and the second layer should overlap the first.
Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2
Authors: Chen Yue-e , Ren Fu-le , Gu Xing , Zhang Hong-jun , Li Wen-jie , Yang Han , Shang Fen-qing
Published: February 2023

Introduction: The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta. Methods: This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization. Results: Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30–51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta. Conclusion: Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.
Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency
Authors: Abreu Nélia , Pereira Vítor Magno , Pestana Madalena , Jasmins Luís
Published: February 2023

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic diseases and is caused by mutations in the SERPINA1 gene. The homozygous Pi*Z variant is responsible for the majority of the classic severe form of alpha-1 antitrypsin deficiency, which is characterized by markedly decreased levels of serum alpha-1 antitrypsin (AAT) with a strong predisposition to lung and liver disease. The diagnosis and early treatment of AATD-associated liver disease are challenges in clinical practice. In this review, the authors aim to summarize the current evidence of the non-invasive methods in the assessment of liver fibrosis, as well as to elucidate the main therapeutic strategies under investigation that may emerge in the near future.
Infants with Congenital Adrenal Hyperplasia Exhibit Thalamic Discrepancies in Early Brain Structure
Authors: Rajagopalan Vidya , Overholtzer Lloyd N. , Kim William S. , Wisnowski Jessica L. , Pickering Trevor A. , Fraga Nicole R. , Javier Joyce , Mackintosh Liza , Mirzaian Christine , Geffner Mitchell E. , Kim Mimi S.
Published: February 2023

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) have prenatal and postnatal hormonal imbalances. To characterize the ontogeny of reported brain and behavior changes in older children with CAH, we aimed to study the brain structure in infants with CAH compared to healthy controls. Methods: We performed neuroimaging in 16 infants with classical CAH due to 21-hydroxylase deficiency (8 males, gestational age 38.2 ± 1.7 weeks, post-conceptional age [PCA] 42.2 ± 3.0 weeks) and 14 control infants (9 males, gestational age 38.5 ± 1.8 weeks, PCA 42.5 ± 2.4 weeks) utilizing 3-Tesla magnetic resonance imaging. Regional brain volumes were adjusted for PCA and sex, along with an additional adjustment for total brain volume (TBV), for group comparisons by regression analyses (mean, 95% confidence interval [CI]). The degree to which each brain region was differentiated between CAH and control infants was examined by relaimpo analyses, adjusting for all other brain regions, PCA, and sex. Results: Infants with CAH had significantly smaller thalamic volumes (8,606 mm3, 95% CI [8,209, 9,002]) compared to age-matched control infants (9,215 mm3, 95% CI [8,783, 9,647]; β = −609; p = 0.02) which remained smaller after further adjustment for TBV. Upon further adjustment for TBV, the temporal lobe was larger in infants with CAH (66,817 mm3, CI [65,957, 67,677]) compared to controls (65,616 mm3, CI [64,680, 66,551]; β = 1,202, p = 0.03). The brain regions most differentiated between CAH versus controls were the thalamus (22%) and parietal lobe (10%). Conclusions: Infants with CAH exhibit smaller thalamic regions from early life, suggesting a prenatal influence on brain development in CAH. Thalamic emergence at 8–14 weeks makes the region particularly vulnerable to changes in the intrauterine environment, with potential implications for later maturing brain regions. These changes may take time to manifest, meriting longitudinal study through adolescence in CAH.
Genetic relationships of the Yucatan black hairless pig with Iberian breeds using single nucleotide polymorfisms
Authors: Lemus-Flores Clemente , Bugarín Prado Job Oswaldo , Valdivia Bernal Roberto , Segura Correa José Candelario , Sansor-Nah Raúl
Published: February 2023

To conduct ex-situ creole pig conservation programs, it is essential to determine which breeding animals will be used, preferentially those with a more significant Iberian genetic component to preserve their origin. This study used a Yucatan black hairless pigs (YBHP) subpopulation to estimate its genetic diversity and population structure. One hundred four adult pigs were selected for the absence of hair, black skin (without spots), black hoof, and straight snout. The porcine-GGP-50K chip was used for SNP genotyping in YBHP, and information on Iberian and Yucatán hairless pigs from the United States (USYU) was taken from databases. All analysis was performed using PLINK v1.9 and v2.1 software. Inbreeding and fixation index values were lower in YBHP, with high observed heterozygosity and allogamy index values, which agree with those obtained in the populations of Canarias and Chato Murciano. According to the clusters generated by the “Genome-Wide Identity by State” analysis, four groups were identified, one of which included pigs from Guadyerbas, USYU, and YBHP. Between populations, YBHP was closely related to the hairless pigs from Guadyerbas, USYU, and Canarias. Principal component analysis showed the same result. According to the results obtained from the runs of homozygosity investigation, aimed to get pools consensus of regions of overlapping, 119 SNPs associated with genes and biological processes were identified. The BMP7 and NSUN2 genes were associated with epithelial cell differentiation, morphogenesis, and epithelial development. For nutrient metabolism: energy, the HADHA, PPARA, ADD1/SREBF1, and FAT1genes were identified.
Uma conversa virtual com Ronaldo Correia de Brito
Authors: Palmeira Natasha Belfort
Published: February 2023

Não há.
No gume da prosa
Authors: Palmeira Natasha Belfort
Published: February 2023

Não há.
Introduction: Art's Histories Without Art History
Authors: Cabañas Kaira Marie
Published: February 2023

The introductory text situates the therapeutic practices of Gina Ferreira and Lula Wanderley in relation to the work of Brazilian modernist artist Lygia Clark. Ferreira is a social psychologist who uses the arts—for instance, photography and film—for the socialization and treatment of psychiatric patients. Wanderley is an artist who brings creativity into the realm of psychiatric care. Both have significantly expanded the sites and amplified the applications of Clark's Estruturação do self (Structuration of the self) therapy sessions by working in public psychiatric hospitals and clinics in Rio de Janeiro and with marginalized populations. In “Lend Me Your Eyes,” Gina Ferreira offers a poetic account of both Lygia Clark's practice and how communication became a “‘therapeutic’ possibility” for the artist. These thoughts frame Ferreira's narration of her clinical care of a client (patient) named Pedro. In “The Silence That Words Hold,” Lula Wanderley describes his artistic engagement with psychiatry and his use of Clark's therapy with clients such as Rosa. The two articles compelling attest to how Clark's Estruturação do self resonates beyond the institutionalized spaces of the art museum and the academy.
Low Vision Impairs Implicit Sensorimotor Adaptation in Response to Small Errors, But Not Large Errors
Authors: Tsay Jonathan S. , Tan Steven , Chu Marlena A. , Ivry Richard B. , Cooper Emily A.
Published: February 2023

Successful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (e.g., where you see your hand after reaching vs. where you expected it to be). Individuals with low vision experience challenges with visuomotor control, but whether low vision disrupts motor adaptation is unknown. To explore this question, we assessed individuals with low vision and matched controls with normal vision on a visuomotor task designed to isolate implicit adaptation. We found that low vision was associated with attenuated implicit adaptation only for small visual errors, but not for large visual errors. This result highlights important constraints underlying how low-fidelity visual information is processed by the sensorimotor system to enable successful implicit adaptation.
Two new species of Xanthagaricus from Punjab, Pakistan
Authors: HAQNAWAZ MUHAMMAD , NIAZI ABDUL REHMAN , KHALID ABDUL NASIR
Published: February 2023

Many basidiomata collected during a fungal survey of the Indus Riverbed revealed two new taxa in the genus Xanthagaricus. Phylogenetic analyses of the Internal Transcribed Spacers (ITS) & ribosomal Large Subunit (28S) have confirmed that these new species (namely Xanthagaricus punjabensis & Xanthagaricus kotadduensis) form a separate clade with a strong bootstrap value from the closest species of Xanthagaricus. The closest taxon to Xanthagaricus punjabensis is X. Thailandensis, while Xanthagaricus kotadduensis is closely related to X. omanicus. Xanthagaricus punjabensis is unique due to its umbonate disc, dull orange to light yellow lamellae, gray rhizomorphic mycelial mat at the base of stipe, presence of annulus, globose to subglobose basidiospore, narrowly utriform to utriform cheilocystidia, and clavate to broadly clavate caulocystidia. Our second new taxon, X. Kotadduensis, can be characterized by the absence of annulus, utriform to knobbed cheilocystidia, and oblong caulocystidia. Our results strongly support the placement of the new taxa within the genus Xanthagaricus and provide a unique insight into the phylogenetic relationships within this genus. With this addition, the number of known species of Xanthagaricus from Pakistan becomes three.
Omorgus (Omorgus) khandesh (Coleoptera: Scarabaeoidea: Trogidae), a new species from India, along with an annotated catalogue of the Oriental and Palearctic species of the subgenus Omorgus Erichson, 1847
Authors: STRÜMPHER WERNER P. , KALAWATE APARNA S.
Published: February 2023

A new species of keratin beetle from Western India, Omorgus (Omorgus) khandesh Strümpher & Kalawate, new species, is described and illustrated. The new species is morphologically most similar to O. (O.) rimulosus (Haaf, 1957). The latter is redescribed and illustrated to enable accurate recognition of both species. Based on this work the following taxonomic changes are proposed: Three species are transferred from the subgenus Afromorgus Scholtz, 1986 to the nominotypical subgenus: O. (O.) inclusus (Walker 1858), O. (O.) maissouri (Haaf, 1945a) and O. (O.) rimulosus (Haaf, 1957). Lastly, we include an annotated catalogue of the species of the nominotypical subgenus Omorgus known from the Oriental and Palaearctic regions.