bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates of bedrock canyon incision by megafloods, Channeled Scabland, eastern Washington, USA
Authors: Lehnigk Karin E. , Larsen Isaac J. , Lamb Michael P. , David Scott R. 
Published: April 2024

Abstract
Pleistocene outburst floods from the drainage of glacial Lake Missoula carved bedrock canyons into the Columbia Plateau in eastern Washington, USA, forming the Channeled Scabland. However, rates of bedrock incision by outburst floods are largely unconstrained, which hinders the ability to link flood hydrology with landscape evolution in the Channeled Scabland and other flood-carved landscapes. We used long profiles of hanging tributaries to reconstruct the pre-flood topography of the two largest Channeled Scabland canyons, upper Grand Coulee and Moses Coulee, and a smaller flood-eroded channel, Wilson Creek. The topographic reconstruction indicates floods eroded 67.8 km3, 14.5 km3, and 1.6 km3 of rock from upper Grand Coulee, Moses Coulee, and Wilson Creek, respectively, which corresponds to an average incision depth of 169 m, 56 m, and 10 m in each flood route. We simulated flood discharge over the reconstructed, pre-flood topography and found that high-water evidence was emplaced in each of these channels by flow discharges of 3.1 × 106 m3 s−1, 0.65–0.9 × 106 m3 s−1, and 0.65–0.9 × 106 m3 s−1, respectively. These discharges are a fraction of those predicted under the assumption that post-flood topography was filled to high-water marks for Grand and Moses Coulees. However, both methods yield similar results for Wilson Creek, where there was less erosion. Sediment transport rates based on these discharges imply that the largest canyons could have formed in only about six or fewer floods, based on the time required to transport the eroded rock from each canyon, with associated rates of knickpoint propagation on the order of several km per day. Overall, our results indicate that a small number of outburst floods, with discharges much lower than commonly assumed, can cause extensive erosion and canyon formation in fractured bedrock.
Characterization of accelerated approval status, trial endpoints and results, and recommendations in guidelines for oncology drug treatments from the National Comprehensive Cancer Network: cross sectional study
Authors: Mooghali Maryam , Mitchell Aaron P , Skydel Joshua J , Ross Joseph S , Wallach Joshua D , Ramachandran Reshma 
Published: April 2024

ObjectivesTo evaluate National Comprehensive Cancer Network (NCCN) guideline recommendations for oncology drug treatments that have been granted accelerated approval, and to determine whether recommendations are updated based on the results of confirmatory trials after approval and based on status updates from the US Food and Drug Administration (FDA).DesignCross sectional study.SettingUS FDA and NCCN guidelines.PopulationOncology therapeutic indications (ie, specific oncological conditions for which the drug is recommended) that have been granted accelerated approval in 2009-18.Main outcome measuresNCCN guideline reporting of accelerated approval status and postapproval confirmatory trials, and guideline recommendation alignment with postapproval confirmatory trial results and FDA status updates.Results39 oncology drug treatments were granted accelerated approval for 62 oncological indications. Although all indications were recommended in NCCN guidelines, accelerated approval status was reported for 10 (16%) indications. At least one postapproval confirmatory trial was identified for all 62 indications, 33 (53%) of which confirmed benefit; among these indications, NCCN guidelines maintained the previous recommendation or strengthened the category of evidence for 27 (82%). Postapproval confirmatory trials failed to confirm benefit for 12 (19%) indications; among these indications, NCCN guidelines removed the previous recommendation or weakened the category of evidence for five (42%). NCCN guidelines reflected the FDA's decision to convert 30 (83%) of 36 indications from accelerated to traditional approval, of which 20 (67%) had guideline updates before the FDA's conversion decision. NCCN guidelines reflected the FDA's decision to withdraw seven (58%) of 12 indications from the market, of which four (57%) had guidelines updates before the FDA's withdrawal decision.ConclusionsNCCN guidelines always recommend drug treatments that have been granted accelerated approval for oncological indications, but do not provide information about their accelerated approval status, including surrogate endpoint use and status of postapproval confirmatory trials. NCCN guidelines consistently provide information on postapproval trial results confirming clinical benefit, but not on postapproval trials failing to confirm clinical benefit. NCCN guidelines more frequently update recommendation for indications converted to traditional approval than for those approvals that were withdrawn.
Advancements in research on transcutaneous electrical acupoint stimulation for alleviating pelvic pain in women
Authors: Wang Yi Ling , Lu Xin Lei , Wang Shang , Chang Xiao Hong , Zhang Rong , Zhu Hong Lan 
Published: April 2024

BackgroundPelvic pain is a common complaint of discomfort in women, with an increasing incidence and seriously affecting patients’ quality of life. Its etiology involves multiple systems and disciplines, and therefore treatment modalities are diverse. Transcutaneous electrical acupoint stimulation (TEAS) therapy is a classic analgesic means, and electrical stimulation of local acupoints can achieve obvious analgesic effects. This review aims to discuss the application of TEAS for the treatment of various types of pelvic pain, the selection of optimal parameters and the renewal of equipment.MethodResultTEAS for treatment of pelvic pain in women has been reported mainly for endometriosis, pelvic inflammatory disease (PID), intrauterine adhesion (IUA), pelvic stasis syndrome, interstitial cystitis, primary dysmenorrhoea and other diseases. And for parameter selection, the most used of frequency is dilatational wave, the most used stimulation intensity is 10–20 mA, and the acupoint selection should be based on the specific conditions of the patient.ConclusionsThe analgesic mechanism of TEAS has not been fully elucidated, but the efficacy of the treatment is remarkable and there are no significant adverse effects. The selection of the parameters for TEAS and the combination of acupoints for different pains are still the main directions of future research.
Cytokine landscapes of pregnancy: mapping gestational immune phases
Authors: Dutta Sulagna , Sengupta Pallav , Liew Fong Fong 
Published: April 2024

BackgroundSynchronised physiological adaptations occur during pregnancy to achieve systemic, immune and neuroendocrine equilibrium in the mother’s body, allowing semiallogenic fetal growth.Main textDepending on the cytokine profile alterations occurring through pregnancy, the latter can be divided into three distinct phases. In the first immunological phase of pregnancy, proinflammatory cytokines promote inflammatory reactions needed for implantation. In the second phase, a possible change from proinflammatory to anti-inflammatory cytokines creates a symbiosis between maternal and fetal components, ensuring fetal development. In the third phase, inflammatory and cytolytic cytokines operate again to reinforce an inflammatory environment for parturition. The article offers a detailed account of immune adaptations during pregnancy and highlights the distinctive cytokine profiles that mark each phase.ConclusionBy providing a simplified depiction of pregnancy phases based on cytokine profiles, the article aims to inspire more research in reproductive immunology and improve the management of pregnancy-related inflammation and infection.
Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease
Authors: Gabriëls Ruben Y , van der Waaij Anne M , Linssen Matthijs D , Dobosz Michael , Volkmer Pia , Jalal Sumreen , Robinson Dominic , Hermoso Marcela A , Lub-de Hooge Marjolijn N , Festen Eleonora A M , Kats-Ugurlu Gursah , Dijkstra Gerard , Nagengast Wouter B 
Published: April 2024

Objective
Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI).

Design
Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab.

Results
FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6–78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo-800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells.

Conclusion
These results indicate the potential of FMI to determine the local distribution of drugs in the inflamed target tissue and identify drug target cells, providing new insights into targeted agents for their use in IBD.

Trial registration number

NCT04112212
.
Spontaneous delayed migration or shortening after pipeline embolization device treatment of intracranial aneurysm: incidence, management, and risk factors
Authors: Dong Linggen , Wang Chao , Wei Dachao , Peng Qichen , Wu Xinzhi , Chen Xiheng , Li Mingtao , Li Tong , Liu He , Zhao Yang , Duan Ran , Jin Weitao , Zhang Yukun , Wang Yang , Lv Ming 
Published: April 2024

BackgroundStudies reporting spontaneous delayed migration or shortening (SDMS) after treatment with the Pipeline Embolization Device (PED) are limited. This study aimed to evaluate the incidence of SDMS after PED treatment, propose management strategies, and identify the risk factors contributing to its occurrence.MethodsWe retrospectively reviewed consecutive patients with an intracranial aneurysm (IA) treated with PEDs at three institutions. SDMS was classified as type I or II based on whether the PED covered the aneurysm neck.ResultsThe total cohort comprised 790 patients. SDMS was identified in 24 (3.04%) patients. Eighteen of the 24 patients had type I SDMS and did not require retreatment, while the remaining six patients had type II SDMS and all received retreatment. Multivariate logistic regression showed that the difference between the proximal and distal parent artery diameters (DPAD) (adjusted OR 2.977; 95% CI 1.054 to 8.405; P=0.039) and device tortuosity index (DTI) (adjusted OR 8.059; 95% CI 2.867 to 23.428; P<0.001) were independent predictors of SDMS after PED treatment, while the difference in length (DL) (adjusted OR 0.841; 95% CI 0.738 to 0.958; P=0.009) and PED plus coiling (adjusted OR 0.288; 95% CI 0.106 to 0.785; P=0.015) were protective factors.ConclusionThe incidence of SDMS after PED treatment of IA was 3.04%. For patients with type I SDMS with incomplete aneurysm occlusion we recommend continuous imaging follow-up while, for patients with type II SDMS, we recommend aggressive retreatment. The DPAD and DTI were independent risk predictors of SDMS after PED treatment, while the DL and PED plus coiling were protective factors.
Comparative responses of Lohmann Select Leghorn-lite and Shaver Heritage White Leghorn hens when fed diets containing fine and coarse oat hulls
Authors: Mills Alisha , Maina Anderson N. , Kiarie Elijah G. 
Published: April 2024

A standard commercial mash (control), or a mixture of control and fine (FOH) or coarse oat hulls (COH) at a ratio of 80:20 w/ w were fed to 57-week old Lohmann Select Leghorn-lite (LSL) and 44-week old Shavers Heritage White Leghorns (SHW) for 28 days. There was no ( P > 0.05) strain and diet interaction or diet effects on egg production indices (EP) and feed intake (FI). However, LSL hens had similar ( P > 0.05) FI but higher ( P > 0.05) EP than SHW. There was no strain and diet interaction observed on apparent retention of gross energy (ARGE) and gizzard weight ( P > 0.05). However, the control hens had higher ARGE, and lighter gizzards compared to oat hull-fed hens ( P < 0.01). In addition, COH hens had higher ARGE and heavier gizzards compared to FOH hens. The SHW hens exhibited greater jejunal crypt depth ( P = 0.011) compared to LSL hens. An interaction ( P = 0.041) between strain and diets on ceca digesta short chain fatty acids (SCFA) was such that oat hulls reduced SCFA in LSL but not in SHW hens. In conclusion, despite differences in age, relative to predecessors the modern hen is adaptable to ingestion of structural material rich insoluble fiber without negative impact on egg production and feed intake.
The effects of plant growth-promoting bacteria on seed germination and seedling growth in Crassocephalum rubens
Authors: Ou Jr-Chi , Lin Yu-Heng , Rho Hyungmin 
Published: April 2024

Crassocephalum rubens, a herb with potential anticancer properties, encounters challenges in production efficiency due to small seed size and elevated temperatures in cultivation areas. Our study investigates the effects of seed pelleting and plant growth-promoting bacteria (PGPB) on germination and seedling growth across temperature variations in Taiwan. Pelleted seeds demonstrate superior germination percentages linked to enhanced seed quality. Elevated temperature, particularly at 30/25 °C, enhanced germination performance, with the highest final germination percentage observed in pelleted seeds treated with water. Unexpectedly, PGPB strains— Klebsiella sp. KsGRB10 and Bacillus sp. BsGFB04—exhibited limited impact on germination rates, showing a marginal increase in seedling growth under 25/20 °C and 30/25 °C, respectively. Air temperature fluctuations influenced seedling vigor, leaf color, and physiological parameters. Remarkably, inoculation with BsGFB04 and KsGRB10 enhanced C. rubens’ tolerance to high-temperature stress conditions. Diurnal measurements in week 4, under 25/20 °C, reveal that PGPB inoculation decreased stomatal conductance and transpiration rate while maintaining the quantum yield of PSII, indicating potentially improved water-use efficiency. This study provides crucial insights into the interplay among PGPB, environmental stress, and the physiology of a wild species, paving the way for further research in the domestication of C. rubens for medicinal herb mass production.
Spring wheat agronomic and quality responses to a genotype × environment × N source and management systems approach
Authors: Wang Zhijie , Strydhorst Sheri , Hao Xiying , Hernandez Ramirez Guillermo , Semach Greg , Holzapfel Chris , Enns Jessica , Thompson Laurel , Beres Brian L. 
Published: April 2024

Yield and quality improvements in Canada Western Red Spring (CWRS) wheat ( Triticum aestivum L.) are increasingly difficult to attain, which behooves a systems approach to unlock genotype (G) × environment (E) × management (M) synergies. This 25 site-year study was designed to assess a G × E × M systems approach to improve CWRS agronomics, quality, and N use efficiency (NUE). The investigation consisted of genetics (AAC Viewfield vs. AC Stettler), N source (untreated urea; urea + urease inhibitor, N-(n-butyl) thiophosphoric triamide (NBPT); urea + nitrification inhibitor, nitrapyrin; urea + dual-inhibitor (NBPT + dicyandiamide); and polymer-coated) and N timing/placement (all-banded at planting, two-split applications and three-split applications), deployed across diverse soil zones in western Canada. Differential yield responses were observed between cultivars as AAC Viewfield produced superior yield over AC Stettler (+4.3%) in black and grey soils, while yield attainment was similar in dark brown soils. Genetic improvement over AC Stettler seemed most apparent in water abundant environments; however, AC Stettler was often superior in drier conditions. All N sources produced comparable outcomes for yield, quality, NUE, and net returns. In black and grey soils, adopting either all-banded or two-splits improved grain yield due to augmented seedling vigor, heads per plant, and N recovery. The timing of split-applications introduces more risk to yield and is likely attributed to a poorly developed source:sink relationship in the critical growth period if applied late to optimize grain protein. This highlights the complexity of the system and balance needed to harness the potential synergy between G, E, and M components.
Statistical modeling and denoising of microseismic signal for dropping ambient noise in wavelet domain
Authors: Kim Kyong-Il , Pak Myong-Il 
Published: April 2024

Dropping the ambient noise from microseismic signals is very important for disaster monitoring such as a rockburst and early warning system using microseismic monitoring techniques in the mine and coal mines. Currently, it is still a challenge to remove high and low-frequency noise simultaneously without losing the useful information of microseismic signal. The aim of this paper is to remove the low-frequency noise contained in microseismic signal effectively, while preserving the useful signal information by using a stochastic approach. We first statistically model the wavelet coefficients in the approximation subband of noisy microseismic signal. In addition, we evaluate qualitatively and quantitatively the fitness of Gauss–Laplace mixture distribution and the statistical modeling of data. Then, we propose a novel denoising algorithm to remove the ambient noise effectively from the noisy microseismic signals in wavelet domain. This algorithm removes the low-frequency noise by using a stochastic approach and the high-frequency noise by using a traditional wavelet thresholding method. The low-frequency noise is removed by using a closed-form shrinkage function based on Gauss–Laplace mixture distribution, while the high-frequency noise is removed by using a threshold function combined with Garrote and hyperbolic threshold functions. Next, we evaluated the ambient denoising performance of our novel denoising algorithm by comparing it with various denoising methods with different test signals. Experimental results show that the ambient denoising performance of the proposed method is better than the other seven existing methods.
Stabilizing Tumor-Resident Mast Cells Restores T-Cell Infiltration and Sensitizes Sarcomas to PD-L1 Inhibition
Authors: Panagi Myrofora , Mpekris Fotios , Voutouri Chrysovalantis , Hadjigeorgiou Andreas G. , Symeonidou Chloe , Porfyriou Eleni , Michael Christina , Stylianou Andreas , Martin John D. , Cabral Horacio , Constantinidou Anastasia , Stylianopoulos Triantafyllos 
Published: April 2024

Abstract

Purpose:
To explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling the activity of cancer-associated fibroblasts (CAF) to overcome tumor microenvironment (TME) abnormalities, enhancing the efficacy of immune-checkpoint inhibitors in sarcoma.

Experimental Design:
We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti–PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurposed phase II clinical trial.

Results:
Inhibition of MC activation with ketotifen successfully suppressed CAF proliferation and stiffness of the extracellular matrix accompanied by an increase in vessel perfusion in fibrosarcoma and osteosarcoma as indicated by ultrasound shear wave elastography imaging. The improved tissue oxygenation increased the efficacy of chemoimmunotherapy, supported by enhanced T-cell infiltration and acquisition of tumor antigen–specific memory. Importantly, the effect of ketotifen in reducing tumor stiffness was further validated in sarcoma patients, highlighting its translational potential.

Conclusions:
Our study suggests the targeting of MCs with clinically administered drugs, such as antihistamines, as a promising approach to overcome resistance to immunotherapy in sarcomas.
Abstract CT155: Trial in progress: A phase Ia/Ib, an open-label, multicenter study of ZL-1310 to evaluate the safety, tolerability, and pharmacokinetics in subjects with small cell lung cancer
Authors: Dowlati Afshin , Spira Alexander , Shen Xiaodong , Fu Yinjia , Pan Yiyuan , Liu Linda , Zhou Renke , Wu Yi-Long 
Published: April 2024

Abstract
Background: ZL-1310, a novel antibody-drug conjugate (ADC) targeting delta-like protein 3 (DLL3) with a camptothecin derivative as its payload via a protease-cleavable linker, employs TMALIN® (Tumor Microenvironment Activable LINker-payload) ADC technology platform. DLL3, an inhibitory Notch pathway ligand and a validated target for directed therapy, is highly expressed in more than 80% of patients with small cell lung cancer (SCLC) and also has variable expression in other neuroendocrine (NE) tumors. There remains an unmet medical need for 2nd-line SCLC, as the standard of care chemotherapy has a modest response rate of ~25%. ZL-1310 is designed to minimize payload toxicity and improve anti-tumor effectiveness.
Methods: This is an open-label, multiple-dose, phase 1 study of ZL-1310 administered to subjects with relapsed/refractory (r/r) metastatic SCLC who have progressed after at least one platinum-based chemotherapy regimen. The study consists of two parts: Part 1 (dose escalation) and Part 2 (dose expansion). In Part 1, the Bayesian optimal interval (BOIN) design is employed for dose escalation, while in Part 2, patients will be randomized into two cohorts with different doses of ZL-1310 to further define safety and preliminary antitumor activity. The major inclusion criteria are as follows: (1) Subjects must have histologically or cytologically confirmed metastatic or extensive-stage SCLC with no more than 3 prior regimens in the r/r setting. (2) Subjects must have at least one measurable target lesion as defined by RECIST v1.1. (3) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The major exclusion criteria include: (1) Prior exposure to DLL3-targeted therapy. (2) Subjects with symptomatic or uncontrolled brain metastasis requiring concurrent treatment, impaired major organ functions, active autoimmune disease, or active infections.Part 1 Dose Escalation is recruiting subjects in the US and China.
Citation Format: Afshin Dowlati, Alexander Spira, Xiaodong Shen, Yinjia Fu, Yiyuan Pan, Linda Liu, Renke Zhou, Yi-Long Wu. Trial in progress: A phase Ia/Ib, an open-label, multicenter study of ZL-1310 to evaluate the safety, tolerability, and pharmacokinetics in subjects with small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT155.