bluuebunny/crossref_metadata_2025 huggingface dataset:
A semi-tetrad decomposition of the Kerr spacetime
Authors: Hansraj C. , Goswami R. , Maharaj S. D.
Published: April 2023

In this paper we perform a semi-tetrad decomposition of the Kerr spacetime. We apply the 1+1+2 covariant method to the Kerr spacetime in order to describe its geometry outside the horizon. Comparisons are drawn between an observer belonging to the Killing frame and a ZAMO (zero angular momentum observer), a locally non-rotating observer in a zero angular momentum frame, and their resulting geometrical quantities that generate the evolution and propagation equations. This enhances the study of the Kerr geometry as the results are valid in the ergoregion from where energy can be extracted. Using this formalism allows us to present the kinematic and dynamic quantities in a transparent geometrical manner not present in alternate approaches. We find significant relationships between the properties of shear, vorticity and acceleration. Additionally we observe that in the Killing frame, the gravitational wave is a direct consequence of vorticity and in the ZAMO frame, the gravitational wave is a direct consequence of shear. To our knowledge, using the 1+1+2 formalism to investigate the Kerr spacetime is a novel approach, and this provides new insights into the spacetime geometry in an easier manner than alternate approaches. Furthermore we make corrections to earlier equations in the 1+1+2 formalism applied to the Kerr spacetime.
Probing geometric proca in metric-palatini gravity with black hole shadow and photon motion
Authors: Ghorani Elham , Puliçe Beyhan , Atamurotov Farruh , Rayimbaev Javlon , Abdujabbarov Ahmadjon , Demir Durmuş
Published: April 2023

Extended metric-Palatini gravity, quadratic in the antisymmetric part of the affine curvature, is known to lead to the general relativity plus a geometric Proca field. The geometric Proca, equivalent of the non-metricity vector in the torsion-free affine connection, qualifies to be a distinctive signature of the affine curvature. In the present work, we explore how shadow and photon motion near black holes can be used to probe the geometric Proca field. To this end, we derive static spherically symmetric field equations of this Einstein-geometric Proca theory, and show that it admits black hole solutions in asymptotically AdS background. We perform a detailed study of the optical properties and shadow of this black hole and contrast them with the observational data by considering black hole environments with and without plasma. As a useful astrophysical application, we discuss constraints on the Proca field parameters using the observed angular size of the shadow of supermassive black holes M87$$^*$$∗and Sgr A$$^*$$∗in both vacuum and plasma cases. Overall, we find that the geometric Proca can be probed via the black hole observations.
Comparing turbulent flow and bank erosion with controlled experiments in a field-scale meandering channel
Authors: Kozarek Jessica L. , Limaye Ajay B. , Arpin Eleanor
Published: April 2023

Bank erosion commonly occurs in alluvial rivers, shaping landscapes and riparian habitats and impacting water quality and infrastructure. Several models have been proposed that link shear stresses to bank erosion. However, data to test these hypotheses for characteristic geometries of meandering channels are sparse and technically challenging to acquire. Here we present results from a controlled experiment in a naturalistic channel to isolate the relationships between turbulent flow and nascent bank erosion. We ran the experiments at the Outdoor StreamLab (St Anthony Falls Laboratory, University of Minnesota) and gathered high-precision, contemporaneous measurements of the turbulent flow field and topography near a standardized, erodible bank at five locations along a single meander. The measurements show that the rate of bank erosion varied both along the channel and vertically and, local bank erosion was not correlated with any single hydrodynamic parameter. Upstream of the meander apex, erosion correlated with the near-bank time-averaged streamwise velocity magnitude while downstream of the apex, bank erosion correlated more strongly with near-bank turbulence parameters and depth. These results support field measurements that suggest that fluid shear contributions to outer bank erosion reflect multiple components of turbulent flow structure in river meanders.
SE Asia as part of Gondwana: a 1960s regional mapping project over Southern Thailand that lay behind the hypothesis
Authors: Ridd Michael F.
Published: April 2023

In the 1960s, anticipating the award of concessions in the Gulf of Thailand, BP carried out reconnaissance geological mapping over all of Southern Thailand including its Gulf islands.

The resulting eight geological maps at 1:250 000 scale provided a database that underpinned discussions of Thailand's place in global plate-tectonic reconstructions that were emerging at that time. In particular, new light was thrown on the Paleozoic succession, and important differences were found between the Upper Thai Peninsula and the Lower Peninsula (respectively, NW and SE of the prominent bend in the peninsula's outline). The Phuket Group of the Upper Peninsula is a very thick diamictite-bearing succession of possible Devonian to Early Permian age, apparently sourced in the west, a region now occupied by the Indian Ocean. That in turn suggested a possible Gondwana origin for SE Asia, a contentious concept at the time, but one that is now widely accepted.

The emphasis of field mapping these days is on obtaining detailed data that necessarily means over areas of limited extent. But a very broad regional mapping project such as BP's in Thailand revealed stratigraphic and tectonic insights that could be revealed only from a wide-ranging regional study of this kind.
Photodarkening, Photobrightening, and the Role of Color Centers in Emerging Applications of Lanthanide-Based Upconverting Nanomaterials
Authors: Lee Changhwan , Schuck P. James
Published: April 2023

Upconverting nanoparticles (UCNPs) compose a class of luminescent materials that utilize the unique wavelength-converting properties of lanthanide (Ln) ions for light-harvesting applications, photonics technologies, and biological imaging and sensing experiments. Recent advances in UCNP design have shed light on the properties of local color centers, both intrinsic and controllably induced, within these materials and their potential influence on UCNP photophysics. In this review, we describe fundamental studies of color centers in Ln-based materials, including research into their origins and their roles in observed photodarkening and photobrightening mechanisms. We place particular focus on the new functionalities that are enabled by harnessing the properties of color centers within Ln-doped nanocrystals, illustrated through applications in afterglow-based bioimaging, X-ray detection, all-inorganic nanocrystal photoswitching, and fully rewritable optical patterning and memory.
Electrical pulse stimulation-induced muscle contraction alters the microRNA and mRNA profiles of circulating extracellular vesicles in mice
Authors: Kawanishi Noriaki , Tominaga Takaki , Suzuki Katsuhiko
Published: April 2023

Extracellular vesicles, such as exosomes, are secreted by skeletal muscle tissues and may play a role in physiological adaptations induced by exercise. Endurance exercise changes the microRNA (miRNA) profile of circulating extracellular vesicles; however, the effects of resistance exercise are unknown. In this study, we examined the effect of resistance exercise as electrical pulse stimulation (EPS)-induced muscle contraction on the miRNA and mRNA profiles of circulating extracellular vesicles in mice using a comprehensive RNA sequencing-based approach. EPS-induced muscle contraction resulted in changes in the miRNA profile of circulating extracellular vesicles. In particular, 90 min after EPS-induced muscle contraction, a considerable increase in expression of muscle-specific microRNAs, such as miR-1, miR-133, and miR-206, was observed. Furthermore, we found that the expression of 208 mRNAs was considerably altered immediately after EPS-induced muscle contraction and that of 267 mRNAs changed considerably after 90 min. Gene ontology enrichment analysis showed that mRNA expression changes in circulating extracellular vesicles after EPS-induced muscle contraction promoted angiogenesis and regulated the immune response. Changes in the properties of circulating extracellular vesicles owing to muscle contraction may play an important role in resistance exercise-induced physiological adaptations.
Vitamin D regulates microflora and ameliorates LPS-induced placental inflammation in rats
Authors: Ma Yantuanjin , Zhang Yuhang , He Qiuyue , Xu Tong , Huang Wei , Deng Xingli , Qian Yuan
Published: April 2023

Preeclampsia is a pregnancy-specific disease, which has become an essential cause of perinatal and neonatal death. Gut microflora becomes the regulator of host immunity through the metabolic pathway. Epidemiological studies provide convincing evidence that vitamin D supplementation can prevent the onset of preeclampsia. However, research on the microbial mechanisms and effective treatment strategies for placental inflammation induced by lipopolysaccharide is lacking. In this study, pregnant rats were induced by LPS to establish a rat model of preeclampsia. Sixteen-sequence analysis was used to determine the composition of microflora in feces. In addition, the protective effect of vitamin D supplementation on LPS-preeclampsia rats was evaluated. The results showed that the blood pressure and creatinine of pregnant rats in the LPS group were significantly higher than those in the control group. In addition, LPS disturbed the intestinal microbial community and reduced microbial diversity. Vitamin D supplementation improves the symptoms of preeclampsia, increases the abundance of intestinal beneficial flora, normalizes the level of inflammatory factors LPS-induced by inhibiting the TLR4/MYD88/NF-κB pathway, and effectively resists the disturbance of uterine spiral artery remodeling induced by LPS. This study established that vitamin D-mediated microbial mechanisms and their inhibition are potential therapeutic targets for the treatment of preeclampsia.
Improvement of Nutrient Uptake, Yield of Black Sesame (Sesamum indicum L.), and Alluvial Soil Fertility in Dyke by Spent Rice Straw from Mushroom Cultivation as Biofertilizer Containing Potent Strains of Rhodopseudomonas palustris
Authors: Khuong Nguyen Quoc , Thuc Le Vinh , Giang Cao Tien , Xuan Ly Ngoc Thanh , Thu Le Thi My , Isao Akagi , Jun-Ichi Sakagami
Published: April 2023

The aim of the current research was to evaluate the effects of members of purple nonsulfur bacteria (PNSB), Rhodopseudomonas palustris strains of VNW02, TLS06, VNW64, and VNS89, mixed with spent rice straw (SRS) from mushroom cultivation as a carrier on promoting sesame growth and yield, and ameliorating the alluvial soil (AS) fertility in dykes. A 4 × 3 factorial experiment consisting of different levels of the solid PNSB biofertilizer mixture at 0, 3, 4, and 5 t·ha−1 (0, 1.81 × 108, 2.24 × 108, and 2.68 × 108 cells pot−1, respectively), and nitrogen (N) and phosphorus (P) inorganic fertilizer rates (100, 75, and 50 kg·N·ha−1; 60, 45, and 30 kg P2O5·ha−1, respectively) was performed in pots with the sesame variety of ADB1 in the dyked AS. The solid PNSB biofertilizer mixture at at least 3 t·ha−1 significantly enhanced the sesame seed yield by providing higher macronutrients for plants by increasing available N and soluble P concentrations in the soil. The solid PNSB biofertilizer mixture in addition to 75% of the recommended N and P fertilizers produced an equivalent yield in comparison to the utilized 100% of N and P inorganic fertilizers. The solid PNSB biofertilizer mixture in the SRS from the mushroom production reduced at least 25% of N and P chemical fertilizers for gaining the maximal seed yield and enriched soil characteristics for the sustainable black sesame cultivation in the dyked AS.
Decoupling Network for Closely Spaced Tx/Rx Antennas Using a Directional Coupler and Transmission Lines
Authors: Park Jeong-Hun , Roh Jeong-Eun , Lee Moon-Que
Published: April 2023

This paper presents an efficient decoupling network using a single directional coupler and transmission lines for closely spaced Tx/Rx antennas in single polarized radar applications. The isolation between both antennas can be enhanced by controlling the phase of the Tx leakage signal and the coupling coefficient of the directional coupler. Its structure provides no loss of Tx/Rx paths excepting minute loss due to the coupling of the directional coupler. The Tx leakage is more insensitive to the antenna impedance variation compared with a conventional monostatic system. The design process is as follows: First, closely separated Tx/Rx antennas were designed and their isolation (

I

a

) was extracted. Second, the directional coupler was designed with its coupling coefficient

=

I

a

. Finally, both were connected by transmission lines, of which phases were adjusted for the coupled and antenna-isolated signals with 180° phase difference. The Tx/Rx antennas without and with the decoupling network have 15-dB bandwidths of 23.98–24.43/23.98–24.50 GHz and 23.80–24.36/23.80–24.45 GHz, respectively. Gains of 8.17/8.39 and 8.72/8.73 dBi and efficiencies of 60.56%/60.77% and 63.0%/61.8% in the Tx/Rx antennas without and with the decoupling network were achieved at 24.1 GHz, respectively. The dimension of the proposed antenna is 1.62λ0

×

2.09λ0

×

0.0204λ0. The K-band antennas show a good Tx-Rx isolation of 29.3–67.9 dB which was superior at least 9 dB to the conventional antennas.
Comparison of General Use of Antibiotics between Medical and Nonmedical University Students of Lahore
Authors: Ayub Fiza , Khan Tahir Mehmood , Amin Muhammad Usman , Baig Mirza Rafi , Bukhsh Allah , Zaman Khadija , Afzal Asma , Bibi Sana , Javed Muhammad Umar , Naheed Fouzia , Alam Jamshaid , Ahmad Hafiz Ishfaq
Published: April 2023

Objective. To compare the knowledge of antibiotic resistance between medical and nonmedical university students of Lahore. Methodology. An observational cross‐sectional survey‐based study was conducted among students of Lahore, Pakistan, from November 12, 2021, to December 13, 2021. The convenience sampling method was used to select students. Descriptive analysis and chi‐square test were performed using Statistical Package for Social Sciences version 25.0. Results. 52.9% medical and 42.25% nonmedical students knew about antibiotics. 24.1% medical and 18.3% nonmedical students do not take antibiotics without a prescription. 40.6% medical and only 19.3% nonmedical students knew about the course of antibiotics. Medical students let the minor ailments recover naturally compared to nonmedical students who visit the doctor more often. Both groups complete the course of antibiotics without a significant difference. 49% medical and 27.9% nonmedical students knew that bacteria can develop resistance against antibiotics. Most nonmedical students responded that antibiotics can work even after resistance. Medical students have better knowledge about the relationship of resistance with overuse and misuse. Conclusion. The knowledge of antibiotics and compliance to therapy of the nonmedical students were less than those of the medical students. Medical students were aware of the pattern of taking antibiotics because of their educational background. There is a dire need for awareness regarding antibiotic use in this group to conserve treatment options for future use.
Research Progress on Mesenchymal Stem Cells for the Treatment of Diabetes and Its Complications
Authors: Zhang Jiarui , Zheng Yongqin , Huang Lichenlu , He Jundong
Published: April 2023

Diabetes mellitus (DM) is a chronic disease that threatens human health. Although many drugs are available to treat DM, various complications caused by DM are unavoidable. As an emerging treatment for DM, mesenchymal stem cells (MSCs) have shown many advantages and are gradually gaining public attention. This review summarizes the clinical studies on the use of MSCs to treat DM and the potential mechanisms of complications such as pancreatic dysfunction, cardiovascular lesions, renal lesions, neurological lesions, and trauma repair. This review focuses on the research progress on MSC-mediated secretion of cytokines, improvements in the microenvironment, repair of tissue morphology, and related signaling pathways. At present, the sample sizes in clinical studies of MSCs in treating DM are small, and there is a lack of standardized quality control systems in the preparation, transportation, and infusion methods, so we need to conduct more in-depth studies. In conclusion, MSCs have shown superior potential for use in the treatment of DM and its complications and will hopefully become a novel therapeutic approach in the future.
Angiopoietin-2–Dependent Spatial Vascular Destabilization Promotes T-cell Exclusion and Limits Immunotherapy in Melanoma
Authors: Park Ha-Ram , Shiva Anahita , Cummings Portia , Kim Seoyeon , Kim Sungsoo , Lee Eunhyeong , Leong Alessandra , Chowdhury Subrata , Shawber Carrie , Carvajal Richard , Thurston Gavin , An Joon-Yong , Lund Amanda W. , Yang Hee Won , Kim Minah
Published: April 2023

T-cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T-cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T-cell infiltration to the tumor core. The spatial regulation of ANGPT2 in whole tumor cross-sections was analyzed in conjunction with T-cell distribution, vascular integrity, and response to immunotherapy in syngeneic murine melanoma models. T-cell exclusion was associated with ANGPT2 upregulation and elevated vascular leakage at the periphery of human and murine melanomas. Both pharmacologic and genetic blockade of ANGPT2 promoted CD8+ T-cell infiltration into the tumor core, exerting antitumor effects. Importantly, the reversal of T-cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 immune checkpoint blockade therapy in immunogenic, therapy-responsive mouse melanomas, but it also rendered nonresponsive tumors susceptible to immunotherapy. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T-cell infiltration to the tumor core, coincided with spatial TIE2 signaling activation and increased vascular integrity at the tumor periphery where endothelial expression of adhesion molecules was reduced. These data highlight ANGPT2/TIE2 signaling as a key mediator of T-cell exclusion and a promising target to potentiate immune checkpoint blockade efficacy in melanoma.

Significance:

ANGPT2 limits the efficacy of immunotherapy by inducing vascular destabilization at the tumor periphery to promote T-cell exclusion.
Tackling Osimertinib Resistance in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Blaquier Juan Bautista , Ortiz-Cuaran Sandra , Ricciuti Biagio , Mezquita Laura , Cardona Andrés Felipe , Recondo Gonzalo
Published: April 2023

The current landscape of targeted therapies directed against oncogenic driver alterations in non–small cell lung cancer (NSCLC) is expanding. Patients with EGFR-mutant NSCLC can derive significant benefit from EGFR tyrosine kinase inhibitor (TKI) therapy, including the third-generation EGFR TKI osimertinib. However, invariably, all patients will experience disease progression with this therapy mainly due to the adaptation of cancer cells through primary or secondary molecular mechanisms of resistance. The comprehension and access to tissue and cell-free DNA next-generation sequencing have fueled the development of innovative therapeutic strategies to prevent and overcome resistance to osimertinib in the clinical setting. Herein, we review the biological and clinical implications of molecular mechanisms of osimertinib resistance and the ongoing development of therapeutic strategies to overcome or prevent resistance.
Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma
Authors: Kelly William , Diaz Duque Adolfo Enrique , Michalek Joel , Konkel Brandon , Caflisch Laura , Chen Yidong , Pathuri Sarath Chand , Madhusudanannair-Kunnuparampil Vinu , Floyd John , Brenner Andrew
Published: April 2023

Purpose:

Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity.

Patients and Methods:

We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS).

Results:

A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56).

Conclusions:

In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.
A Phase I/II Trial of HER2 Vaccine–Primed Autologous T-Cell Infusions in Patients with Treatment Refractory HER2–Overexpressing Breast Cancer
Authors: Disis Mary L. , Dang Yushe , Coveler Andrew L. , Childs Jennifer S. , Higgins Doreen M. , Liu Ying , Zhou Jing , Mackay Sean , Salazar Lupe G.
Published: April 2023

Purpose:

High levels of type I T cells are needed for tumor eradication. We evaluated whether the HER2-specific vaccine–primed T cells are readily expanded ex vivo to achieve levels needed for therapeutic infusion.

Patients and Methods:

Phase I/II nonrandomized trial of escalating doses of ex vivo–expanded HER2-specific T cells after in vivo priming with a multiple peptide–based HER2 intracellular domain (ICD) vaccine. Vaccines were given weekly for a total of three immunizations. Two weeks after the third vaccine, patients underwent leukapheresis for T-cell expansion, then received three escalating cell doses over 7- to 10-day intervals. Booster vaccines were administered after the T-cell infusions. The primary objective was safety. The secondary objectives included extent and persistence of HER2-specific T cells, development of epitope spreading, and clinical response. Patients received a CT scan prior to enrollment and 1 month after the last T-cell infusion.

Results:

Nineteen patients received T-cell infusions. Treatment was well tolerated. One month after the last T-cell infusion, 82% of patients had significantly augmented T cells to at least one of the immunizing epitopes and 81% of patients demonstrated enhanced intramolecular epitope spreading compared with baseline (P < 0.05). There were no complete responses, one partial response (6%), and eight patients with stable disease (47%), for a disease control rate of 53%. The median survival for those with progressive disease was 20.5 months and for responders (PR+SD) was 45.0 months.

Conclusions:

Adoptive transfer of HER2 vaccine–primed T cells was feasible, was associated with minimal toxicity, and resulted in an increased overall survival in responding patients.

See related commentary by Crosby et al., p. 3256
The Emerging Role of Circulating Tumor DNA in Non-Colorectal Gastrointestinal Cancers
Authors: Lee Michael S. , Kaseb Ahmed O. , Pant Shubham
Published: April 2023

Assays to detect circulating tumor DNA (ctDNA) have multiple clinically important applications in management of multiple types of gastrointestinal cancers. Different methodologies of ctDNA detection have varying sensitivities and potential applications in different contexts. For patients with localized cancers treated for curative intent, ctDNA detection is associated with prognosis in multiple cancer types, and persistent detection of ctDNA after surgical resection is highly concerning for minimal residual disease (MRD) and forebodes impending radiographic and clinical recurrence. CtDNA assays for comprehensive genomic profiling enable genotyping of cancers in the absence of tumor tissue data, and longitudinal testing can also characterize clonal evolution and emergence of putative resistance mechanisms upon treatment with targeted agents. These applications have proven instructive in patients with HER2-amplified gastric and esophageal cancers and in patients with FGFR2 fusion cholangiocarcinomas. In this review, we summarize data supporting the role of ctDNA as a novel predictive and prognostic biomarker and potential impacts on current management of patients with pancreatic, gastroesophageal, and hepatobiliary cancers.
First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: April 2023

Purpose:

Nectin-4 is an emerging biomarker for cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first nectin-4 targeting antibody–drug conjugate for treating advanced urothelial carcinoma (UC). A PET imaging method to noninvasively quantify nectin-4 expression level would potentially help to select patients most likely to respond to EV and predict the response.

Experimental Design:

In this study, we designed a bicyclic peptide-based nectin-4 targeting radiotracer 68Ga-N188. Initially, we performed preclinical evaluations of 68Ga-N188 in UC cell lines and xenograft mouse models. Next, we performed the translational study in healthy volunteers and a pilot cohort of patients with advanced UC on uEXPLORER total-body PET/CT.

Results:

In the preclinical study, 68Ga-N188 showed high affinity to nectin-4, specific uptake in a nectin-4(+) xenograft mouse model, and suitable pharmacokinetic and safety profiles. In the translational study, 2 healthy volunteers and 14 patients with advanced UC were enrolled. The pharmacokinetic profile was determined for 68Ga-N188, and the nectin-4 relative expression level in different organs was quantitatively imaged.

Conclusions:

A clear correlation between PET SUV value and nectin-4 expression was observed, supporting the application of 68Ga-N188 PET as a companion diagnostic tool for optimizing treatments that target nectin-4.

See related commentary by Jiang et al., p. 3259
Supplementary Table S3 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Probes for genes with specific expression alterations in malignant GISTs with KIT Δ557–558.
Supplementary Table S2 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Summary of WGS, methylation and expression data.
Supplementary Table S1 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Genes for expression signatures.
Supplementary Figure S6 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Visualization of methylation status in GISTs.
Supplementary Figure S5 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

SVs and expression levels of DMD in 30 GIST samples.
Supplementary Figure S4 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Comparison of somatic mutational landscape between malignant and less malignant GISTs with and without KIT Δ557–558.
Supplementary Data S5 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Expression data of probes used for the volcano plot comparing between malignant GISTs carrying KIT Δ557–558 and other GISTs.
Supplementary Data S3 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

CNAs identified in the 30 GIST cases in our study cohort.
Supplementary Data S1 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

SVs identified in the 30 GIST cases in our study cohort.
Supplementary Figure S3 from Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557–558 Deletion Mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Kaplan-Meier curves.
The Spectrum of Biopsy-Proven Kidney Diseases, Causes, and Renal Outcomes in Acute Kidney Injury Patients
Authors: Abuduwupuer Zulihumaer , Lei Qunjuan , Liang Shaoshan , Xu Feng , Liang Dandan , Yang Xue , Liu Xumeng , Zeng Caihong
Published: April 2023

Introduction: Acute kidney injury (AKI) is a group of highly heterogeneous, complicated clinical syndromes. Although kidney biopsy plays an irreplaceable role in evaluating complex AKI, a few studies have focused on the clinicopathology of AKI biopsies. This study analyzed the pathological disease spectrum, causes, and renal outcomes of biopsied AKI patients. Methods: We retrospectively included 2,027 AKI patients who underwent kidney biopsies at a national clinical research center of kidney diseases from 2013 through 2018. To compare the biopsied AKI cases without and with coexisting glomerulopathy, patients were classified into acute tubular/tubulointerstitial nephropathy-associated AKI (ATIN-AKI) and glomerular disease-associated AKI (GD-AKI) groups. Results: Of 2,027 biopsied AKI patients, 65.1% were male, with a median age of 43 years. A total of 1,590 (78.4%) patients had coexisting GD, while only 437 (21.6%) patients had ATIN alone. The AKI patients with GD mainly (53.5%) manifested as stage 1 AKI, while most ATIN-AKI patients (74.8%) had stage 3 AKI. In the ATIN-AKI group, 256 (58.6%) patients had acute interstitial nephritis (AIN), and 77 (17.6%) had acute tubular injury (ATI). ATIN-AKI was mainly caused by drugs in 85.5% of AIN and 63.6% of ATI cases, respectively. In AKI patients with coexisting GD, the leading pathological diagnoses in over 80% of patients were IgA nephropathy (IgAN, 22.5%), minimal change disease (MCD, 17.5%), focal segmental glomerulosclerosis (FSGS, 15.3%), lupus nephritis (LN, 11.9%), membranous nephropathy (MN, 10.2%), and ANCA-associated vasculitis (AAV, 4.7%). A total of 775 patients were followed up within 3 months after renal biopsy; ATIN-AKI patients achieved statistically higher complete renal recovery than the GD-AKI patients (83.5% vs. 70.5%, p < 0.001). Conclusions: Most biopsied AKI patients have coexisting GD, while ATIN alone is seen less frequently. ATIN-AKI is mainly caused by drugs. In GD-AKI patients, IgAN, MCD, FSGS, LN, MN, and AAV are the leading diagnoses. Compared to AKI patients without GD, patients with GD suffer from worse renal function recovery.
Cellular Senescence: Ageing and Androgenetic Alopecia
Authors: Deng Yongqiong , Wang Mengxue , He Yuxin , Liu Fuming , Chen Lingna , Xiong Xia
Published: April 2023

Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long been thought to be driven by genetic and androgen predisposition. However, increasingly, data proposed ageing and AGA are intimately linked. Elevated senescent cell burden and androgen and oxidative stress-induced senescence mechanisms in ageing may be initial targets to improve AGA. This review summarizes the biological links between ageing and AGA, with special focus on cellular senescence. In addition, we discuss the potential therapeutic strategies for improving cellular senescence in AGA, such as inhibiting dermal papilla cells and hair follicle stem cells senescence driven by androgen and reactive oxygen species, removing senescent cell, and reducing senescence-associated secretory phenotype (SASP).
Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System
Authors: Wu Qiwen , Chen Jingmei , Hua Tingyu , Cai Jinyan
Published: April 2023

Understanding the complex action mechanism of appetite regulation peptides can significantly impact therapeutic options in the treatment of obesity and other metabolic diseases. Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide, closely related to the occurrence of obesity, playing a central role in food intake and energy expenditure. In the central nervous system, α-MSH is cleaved from proopiomelanocortin and then released into different hypothalamic regions to act on melanocortin 3/4 receptor-expressing neurons, lowering food intake, and raising energy expenditure via appetite suppression and sympathetic nervous system. Furthermore, it can increase the transmission of some anorexigenic hormones (e.g., dopamine) and interact with other orexigenic factors (e.g., agouti-related protein, neuropeptide Y) to influence food reward rather than merely feeding behavior. Therefore, α-MSH is a critical node of the hypothalamus in transmitting appetite suppression signals and is a key component of the central appetite-regulating circuits. Herein, we describe the role of α-MSH in appetite suppression in terms of specific receptors, effector neurons, sites of action, and the interaction with other appetite-relative peptides, respectively. We focus on the role of α-MSH in obesity. The status of research on α-MSH-related drugs is also discussed. With the intention of illuminating a new approach for targeting α-MSH in the hypothalamus as a strategy to manage obesity, we hope to further understand the direct or indirect mechanisms by which α-MSH exerts its appetite-regulating effects.
Hypertension in Patients Treated With In-Center Maintenance Hemodialysis: Current Evidence and Future Opportunities: A Scientific Statement From the American Heart Association
Authors: Bansal Nisha , Artinian Nancy T. , Bakris George , Chang Tara , Cohen Jordana , Flythe Jennifer , Lea Janice , Vongpatanasin Wanpen , Chertow Glenn M. ,   on behalf of the American Heart Association Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular and Stroke Nursing; and Council on Epidemiology and Prevention
Published: April 2023

Nearly 500 000 individuals are treated with maintenance hemodialysis for kidney failure in the United States, and roughly half will die of cardiovascular causes. Hypertension, an important and modifiable risk factor for cardiovascular disease, is observed in >80% of patients treated with maintenance hemodialysis. The pathophysiology of hypertension in patients treated with maintenance hemodialysis is multifactorial and differs from that seen in other patient populations. Factors that contribute to hypertension in patients treated with hemodialysis include volume overload, arterial stiffness, enhanced activity of the sympathetic nervous and renin-angiotensin-aldosterone systems, endothelial dysfunction, and use of erythropoietin-stimulating agents. This scientific statement reviews the current evidence on defining, diagnosing, and treating hypertension in patients treated with maintenance hemodialysis and highlights opportunities for future investigation, including studies on blood pressure targets and treatment strategies.
Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030
Authors: Pu Liyuan , Wang Li , Zhang Ruijie , Zhao Tian , Jiang Yannan , Han Liyuan
Published: April 2023

Background:

We projected global trends in ischemic stroke from 2020 to 2030 according to age, sex, and socio-demographic index (SDI) quintile.

Methods:

Estimated annual percentage changes (EAPCs) were used to project trends in the incidence of deaths from and disability-adjusted life years (DALYs) due to ischemic stroke between 2020 and 2030. EAPCs were computed using generalized additive models and data from the Global Burden of Disease study during the 1990 to 2019 period.

Results:

The global age-standardized incidence rate of ischemic stroke was projected to increase to 89.32 per 100 000 population in 2030 (EAPC=0.89), whereas the associated global age-standardized death and DALY rates were projected to decrease to 18.28 (EAPC, −3.58) and 500.37 per 100 000 (EAPC=−1.75), respectively, in 2030. The projections indicated a higher age-standardized incidence rate of ischemic stroke among women than among men in 2030 (90.70 versus 87.64 per 100 000). The incidence rate of ischemic stroke was projected to increase across all age groups and SDI quintiles between 2020 and 2030. At the national level, the greatest increase in the age-standardized incidence rate of ischemic stroke between 2020 and 2030 was projected to occur in Cyprus (EAPC=4.16), followed by Palestine (EAPC=3.50) and South Africa (EAPC=2.64). Additionally, the projections suggested increases in the age-standardized death and DALY rates due to ischemic stroke for countries in low-SDI quintiles (EAPC=3.68 and EAPC=5.30, respectively).

Conclusions:

The projections indicated that the incidence rate of ischemic stroke will increase both sexes, all age groups, and all SDI quintiles and in some countries between 2020 and 2030. Furthermore, countries with a low SDI should be aware of potential increases in the age-standardized death and DALY due to ischemic stroke.
Sex and Racial Disparity in Outcome of Aneurysmal Subarachnoid Hemorrhage in the United States: A 20-Year Analysis
Authors: Schupper Alexander J. , Hardigan Trevor A. , Mehta Amol , Yim Benjamin , Yaeger Kurt A. , De Leacy Reade , Fifi Johanna T. , Mocco J , Majidi Shahram
Published: April 2023

Background:

Aneurysmal subarachnoid hemorrhage is associated with high rate of morbidity and mortality. We aimed to assess prognostic impact of sex, race, and ethnicity in these patients.

Methods:

Nationwide Inpatient Sample (2000–2019) was used to identify patients presenting with aneurysmal subarachnoid hemorrhage as primary diagnosis. Patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities, type of the hospital, and treatment modality used for aneurysm repair were extracted. The previously validated Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale was used to estimate the clinical severity. Discharge destination and in-hospital mortality was used as outcome measured. The impact of race/ethnicity and sex on clinical outcome was analyzed using multivariate regression models.

Results:

A total of 161 086 patients with aneurysmal subarachnoid hemorrhage were identified. Mean age was 55.0±13.8 years. Sixty-nine percent of the patients were female, 60% White patients, and 17% Black patients. There was no difference in the Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale score between the 2 sexes. Women had significantly lower odds of good clinical outcome (defined as discharge to home or acute rehabilitation facility; RR, 0.83 [95% CI, 0.74–0.94];
P
=0.004). Hispanic patients (RR, 1.12 [95% CI, 1.07–1.17];
P
<0.001) had higher odds of excellent clinical outcome compared with White patients, and lower risk of mortality were observed in Black patients (RR, 0.73 [95% CI, 0.66–0.81]) and Hispanic patients (RR, 0.78 [95% CI, 0.70–0.86]) compared with the White patients.

Conclusions:

In this nationally representative study, women were less likely to have excellent outcomes following aneurysmal subarachnoid hemorrhage, and White patients had disproportionately higher likelihood of worse clinical outcomes. Lower rates of mortality were seen among Black and Hispanic patients.
Deep Learning Algorithm Enables Cerebral Venous Thrombosis Detection With Routine Brain Magnetic Resonance Imaging
Authors: Yang Xiaoxu , Yu Pengxin , Zhang Haoyue , Zhang Rongguo , Liu Yuehong , Li Haoyuan , Sun Penghui , Liu Xin , Wu Yu , Jia Xiuqin , Duan Jiangang , Ji Xunming , Yang Qi
Published: April 2023

Background:

Cerebral venous thrombosis (CVT) is a rare cerebrovascular disease. Routine brain magnetic resonance imaging is commonly used to diagnose CVT. This study aimed to develop and evaluate a novel deep learning (DL) algorithm for detecting CVT using routine brain magnetic resonance imaging.

Methods:

Routine brain magnetic resonance imaging, including T1-weighted, T2-weighted, and fluid-attenuated inversion recovery images of patients suspected of CVT from April 2014 through December 2019 who were enrolled from a CVT registry, were collected. The images were divided into 2 data sets: a development set and a test set. Different DL algorithms were constructed in the development set using 5-fold cross-validation. Four radiologists with various levels of expertise independently read the images and performed diagnosis within the test set. The diagnostic performance on per-patient and per-segment diagnosis levels of the DL algorithms and radiologist’s assessment were evaluated and compared.

Results:

A total of 392 patients, including 294 patients with CVT (37±14 years, 151 women) and 98 patients without CVT (42±15 years, 65 women), were enrolled. Of these, 100 patients (50 CVT and 50 non-CVT) were randomly assigned to the test set, and the other 292 patients comprised the development set. In the test set, the optimal DL algorithm (multisequence multitask deep learning algorithm) achieved an area under the curve of 0.96, with a sensitivity of 96% (48/50) and a specificity of 88% (44/50) on per-patient diagnosis level, as well as a sensitivity of 88% (129/146) and a specificity of 80% (521/654) on per-segment diagnosis level. Compared with 4 radiologists, multisequence multitask deep learning algorithm showed higher sensitivity both on per-patient (all
P
<0.05) and per-segment diagnosis levels (all
P
<0.001).

Conclusions:

The CVT-detected DL algorithm herein improved diagnostic performance of routine brain magnetic resonance imaging, with high sensitivity and specificity, which provides a promising approach for detecting CVT.