bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from CDKN2A/B Homozygous Deletion Sensitizes IDH-Mutant Glioma to CDK4/6 Inhibition
Authors: Nasser Ali M. , Melamed Lisa , Wetzel Ethan A. , Chang Jenny Chia-Chen , Nagashima Hiroaki , Kitagawa Yosuke , Muzyka Logan , Wakimoto Hiroaki , Cahill Daniel P. , Miller Julie J.
Published: July 2024

AbstractPurpose:
Treatment paradigms for isocitrate dehydrogenase (IDH)–mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi).
Experimental Design:
Cell viability, proliferation assays, and flow cytometry were used to examine the pharmacologic effect of two distinct CDKi, palbociclib and abemaciclib, in multiple patient-derived IDH-mutant glioma lines. Isogenic models were used to directly investigate the influence of CDKN2A/B status on CDKi sensitivity. Orthotopic xenograft tumor models were used to examine the efficacy and tolerability of CDKi in vivo.
Results:
CDKi treatment leads to decreased cell viability and proliferative capacity in patient-derived IDH-mutant glioma lines, coupled with enrichment of cells in the G1 phase. CDKN2A inactivation sensitizes IDH-mutant glioma to CDKi in both endogenous and isogenic models with engineered CDKN2A deletion. CDK4/6 inhibitor administration improves survival in orthotopically implanted IDH-mutant glioma models.
Conclusions:
IDH-mutant gliomas with deletion of CDKN2A/B are sensitized to CDK4/6 inhibitors. These results support the investigation of the use of these agents in a clinical setting.
Data from MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance
Authors: Davis Lorraine N. , Walker Zachary J. , Reiman Lauren T. , Parzych Sarah E. , Stevens Brett M. , Jordan Craig T. , Forsberg Peter A. , Sherbenou Daniel W.
Published: July 2024

AbstractPurpose:
Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, are a cornerstone of multiple myeloma (MM) therapies, yet the disease inevitably becomes refractory. IMiDs exert cytotoxicity by inducing cereblon-dependent proteasomal degradation of IKZF1 and IKZF3, resulting in downregulation of the oncogenic transcription factors IRF4 and MYC. To date, clinical IMiD resistance independent of cereblon or IKZF1/3 has not been well explored. Here, we investigated the roles of IRF4 and MYC in this context.
Experimental Design:
Using bone marrow aspirates from patients with IMiD-naïve or refractory MM, we examined IKZF1/3 protein levels and IRF4/MYC gene expression following ex vivo pomalidomide treatment via flow cytometry and qPCR. We also assessed exvivo sensitivity to the MYC inhibitor MYCi975 using flow cytometry.
Results:
We discovered that although pomalidomide frequently led to IKZF1/3 degradation in MM cells, it did not affect MYC gene expression in most IMiD-refractory samples. We subsequently demonstrated that MYCi975 exerted strong anti-MM effects in both IMiD-naïve and -refractory samples. Unexpectedly, we identified a cluster of differentiation 8+ (CD8+ T) cells from patients with MM as crucial effectors of MYCi975-induced cytotoxicity in primary MM samples, and we discovered that MYCi975 enhanced the cytotoxic functions of memory CD8+ T cells. We lastly observed synergy between MYCi975 and pomalidomide in IMiD-refractory samples, suggesting that restoring MYC downregulation can re-sensitize refractory MM to IMiDs.
Conclusions:
Our study supports the concept that MYC represents an Achilles’ heel in MM across disease states and that MYCi975 may be a promising therapeutic for patients with MM, particularly in combination with IMiDs.
Data from Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification
Authors: Lorentzen Georgia M. , Łaniewski Paweł , Cui Haiyan , Mahnert Nichole D. , Mourad Jamal , Borst Matthew P. , Willmott Lyndsay , Chase Dana M. , Roe Denise J. , Herbst-Kralovetz Melissa M.
Published: July 2024

AbstractPurpose:
Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests.
Experimental Design:
Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n = 66) and non-malignant conditions (n = 108), and global untargeted metabolomics was performed. Using the metabolite data (n = 920), we completed a multivariate biomarker discovery analysis.
Results:
We analyzed grade 1/2 endometrioid carcinoma (n = 53) and other endometrial cancer subtypes (n = 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (P < 0.0001), tryptophan (P < 0.0001), and glutamate (P < 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q < 0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion.
Conclusions:
Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis.
Data from Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers
Authors: Son Ji , Zhang Yingao , Lin Heather , Mirallas Oriol , Alvarez Ballesteros Pablo , Nardo Mirella , Clark Natalie , Hillman R. Tyler , Campbell Erick , Holla Vijaykumar , Johnson Amber M. , Biter Amadeo B. , Yuan Ying , Cobb Lauren P. , Gershenson David M. , Jazaeri Amir A. , Lu Karen H. , Soliman Pamela T. , Westin Shannon N. , Euscher Elizabeth D. , Lawson Barrett C. , Yang Richard K. , Meric-Bernstam Funda , Hong David S.
Published: July 2024

AbstractPurpose:
We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
Experimental Design:
Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan–Meier method, and multivariable analysis was performed using the Cox proportional hazard model.
Results:
Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and lower grades (grade 1/2, 43.2% vs. 8.1%, all P < 0.0001). The highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n = 9/9), mesonephric-like ovarian (83.3%, n = 5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival [hazard ratio (HR) = 1.3; P = 0.001]. Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN (28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS + MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy [8.4 years [(95% confidence interval (CI), 5.5–12.0) vs. 5.5 years (95% CI, 4.6–6.6); HR = 0.67; P = 0.031], this effect did not persist in multivariable analysis.
Conclusions:
RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.
Data from Phase II Study to Determine the Antitumor Activity and Safety of Simlukafusp Alfa (FAP-IL2v) Combined with Atezolizumab in Esophageal Cancer
Authors: Prenen Hans , Deva Sanjeev , Keam Bhumsuk , Lindsay Colin R. , Lugowska Iwona , Yang James C. , Longo Federico , de Miguel Maria , Ponz-Sarvise Mariano , Ahn Myung-Ju , Gumus Mahmut , Champiat Stephane , Italiano Antoine , Salas Sébastien , Perets Ruth , Arslan Cagatay , Cho Byoung C. , Evers Stefan , Boetsch Christophe , Marbach Daniel , Dejardin David , Sleiman Nassim , Ardeshir Caroline , Richard Muriel , Charo Jehad , Kraxner Anton , Keshelava Nino , Teichgräber Volker , Moreno Victor
Published: July 2024

AbstractPurpose:
In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study evaluating the antitumor activity and safety of fibroblast activation protein–IL2 variant (FAP-IL2v) plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721).
Patients and Methods:
Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 to 1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor–naïve. Patients received FAP-IL2v 10 mg plus atezolizumab 1,200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks and then every 2 weeks plus atezolizumab 840 mg intravenously every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR).
Results:
In the response-evaluable population (N = 34), the best confirmed ORR was 20.6% [95% confidence interval (CI), 10.4–36.8], with a complete response seen in 1 patient and partial responses in 6 patients. The disease control rate was 44.1% (complete response = 2.9%; partial response = 17.6%; stable disease = 23.5%), and the median duration of response was 10.1 mon/ths (95% CI, 5.6–26.7). The median progression-free survival was 1.9 months (95% CI, 1.8–3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ORR of 26.7% for patients with PDL1-positive tumors (tumor area positivity cutoff ≥1%; n = 15) and 7.1% for patients with PDL1-negative tumors (tumor area positivity cutoff <1%; n = 14). Overall, the treatment combination was tolerable, and adverse events were consistent with the known safety profiles of each drug.
Conclusions:
FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.
Data from Antibody–Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients with Breast Cancer
Authors: Bardia Aditya , Sun Sheng , Thimmiah Nayana , Coates James T. , Wu Bogang , Abelman Rachel O. , Spring Laura , Moy Beverly , Ryan Phoebe , Melkonyan Mark N. , Partridge Ann , Juric Dejan , Peppercorn Jeffrey , Parsons Heather , Wander Seth A. , Attaya Victoria , Lormil Brenda , Shellock Maria , Nagayama Aiko , Bossuyt Veerle , Isakoff Steven J. , Tolaney Sara M. , Ellisen Leif W.
Published: July 2024

AbstractPurpose:
The antibody–drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule.
Patients and Methods:
In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or sequential (N = 23) schedule. Outcome measures included safety, tolerability, preliminary efficacy, and establishment of a recommended phase 2 dose.
Results:
We hypothesized that tumor-selective delivery of TOP1i via SG would reduce nontumor toxicity and create a temporal window, enabling sequential dosing of SG and PARP inhibition. In vitro, sequential SG followed by TZP delayed TOP1 cleavage complex clearance, increased DNA damage, and promoted apoptosis. In the clinical trial, sequential SG/TZP successfully met primary objectives and demonstrated median progression-free survival (PFS) of 7.6 months without dose-limiting toxicities (DLT), while concurrent dosing yielded 2.3 months PFS and multiple DLTs including severe myelosuppression.
Conclusions:
While SG dosed concurrently with TZP is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG followed by TZP proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies.
Associations of Immune Checkpoint Predictive Biomarkers (MHC-I and MHC-II) with Clinical and Molecular Features in a Diverse Breast Cancer Cohort
Authors: Sun Xiaopeng , Kennedy Laura C. , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda , Perou Charles M. , Troester Melissa A. , Balko Justin M. , Reid Sonya A.
Published: July 2024

Purpose:

Immunotherapy (IO) in triple-negative breast cancer (TNBC) has improved survival outcomes, with promising improvements in pCR rates among early high-risk hormone receptor (HR)+/HER2− breast cancers. However, biomarkers are needed to select patients likely to benefit from IO. MHC-I and tumor-specific MHC-II (tsMHC-II) expression are candidate biomarkers for PD-(L)1 checkpoint inhibition but existing data from clinical trials included limited racial/ethnic diversity.

Experimental Design:

We performed multiplexed immunofluorescence assays in the Carolina Breast Cancer Study (CBCS; n = 1,628, 48% Black, 52% non-Black). Intrinsic subtype and P53 mutant-like status were identified using RNA-based multigene assays. We ranked participants based on tumoral MHC-I intensity (top 33% categorized as “MHC-Ihigh”) and MHC-II+ (≥5% of tumor cells as tsMHC-II+). MHC-I/II were evaluated in association with clinicopathological features by race.

Results:

Black participants had higher frequency of TNBC (25% vs. 12.5%, P ≤ 0.001) and basal-like (30% vs. 14%, P ≤ 0.001) tumors overall, and higher frequency of basal-like (11% vs. 5.5%, P = 0.002) and TP53 mutant tumors (26% vs. 17%, P = 0.002) among HR+/HER2−. The frequency of tsMHC-II+ was higher in HR+/HER2− Black participants (7.9% vs. 4.9%, P = 0.04). Black participants also had higher frequency of MHC-Ihigh (38.7% vs. 28.2%, P < 0.001), which was significant among HR+/HER2− (28.2% vs. 22.1%, P = 0.02).

Conclusions:

In this diverse study population, MHC-I and MHC-II tumor cell expression were more highly expressed in HR+/HER2− tumors from Black women, underscoring the importance of diverse and equitable enrollment in future IO trials.
NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance
Authors: Mowery Yvonne M. , Luke Jason J.
Published: July 2024

Neutrophil extracellular trap (NET)osis via lytic neutrophil death or neutrophil activation is associated with standard cancer therapies, notably including radiotherapy; is immunosuppressive; and may enhance metastasis and treatment resistance. This emerging area of research should be prioritized in drug development and standard of care treatment paradigms including radiation therapy, chemotherapy, and immunotherapy.

See related article by Teijeira et al., p. 4131
Supplementary Table 2 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: July 2024

Experimental data userd in the article including Olink, CyTOF populational frequencies, Serology and TCRseq beta chain.
Figure S3 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: July 2024

Supplemental Figure 3. Graphical abstract. Top boxes show a simplified trial design including 3 treatments composed by the combination of BV with I, N and I+N. We investigated the differences between responders and non-responders using standardized assays through the CIMAC’s network (ELISA, Olink, CYTOF and TCRseq). Bottom boxes summarize the main findings associated with specific treatments and treatment associated response or resistance.
Figure 4 from Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
Authors: Gonzalez-Kozlova Edgar , Huang Hsin-Hui , Jagede Opeyemi A. , Tuballes Kevin , Del Valle Diane M. , Kelly Geoffrey , Patel Manishkumar , Xie Hui , Harris Jocelyn , Argueta Kimberly , Nie Kai , Barcessat Vanessa , Moravec Radim , Altreuter Jennifer , Duose Dzifa Y. , Kahl Brad S. , Ansell Stephen M. , Yu Joyce , Cerami Ethan , Lindsay James R. , Wistuba Ignacio I. , Kim-Schulze Seunghee , Diefenbach Catherine S. , Gnjatic Sacha
Published: July 2024

Cancer antigen detection and T-cell clonal dynamics associated with treatment and response. A, Heatmap showing cancer antigen detection by ELISA for all samples. The color represents the log10 scale antibody titers. Positive detection is considered above levels of 2 (pink), whereas negative detection is represented by the color black. The top rows of the figure show the treatment group, best overall response, and time. The figure is separated into nonresponders (left) and responders (right). Each column box is hierarchically clustered for simplicity. B, Pie charts showing the association of NY-ESO-1 presence (left column) and nondetection (middle column). Boxplots (right column) show all titer levels for nonresponders and responders. C, Boxplots showing the standardized absolute clonal diversity index calculated using Immunarch R package. The clonal diversity changes are shown over four time points (Baseline, C2D1, Restaging, and off-study) per treatment arm. The P value from the Wilcoxon rank test is shown on top of the boxes. The y-axis is identical for all three treatment arms. There was no statistical difference between the treatments due to the observed large variances (patient heterogeneity). D, Boxplots showing an increase in clonal overlap over time for all three treatments. P values were estimated using the Wilcoxon rank test. E, Clonal expansion was stratified into unique and expanded clones (black and orange, respectively). The stacked barplot shows the average percent of each clonal expansion class over time and per treatment arm. There were no statistical differences identified between treatment arms. F, Boxplots showing the percent abundance of only expanded clones shown for responders and nonresponders over time. There were no significant differences between these two groups except for C2D1 using the Wilcoxon rank test. G, Clonal diversity boxplots comparing responders and nonresponders. Overall, responders had a higher diversity, yet it did not reach statistical significance.
Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension
Authors: Muntner Paul , Jaeger Byron C. , Foti Kathryn , Ghazi Lama , Bundy Joshua D. , Chen Ligong , Safford Monika M.
Published: July 2024

BACKGROUND:

The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130–139 mm Hg, or diastolic blood pressure, 80–89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk.

METHODS:

We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension.

RESULTS:

Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%–5.9%) and 2.9% (95% CI, 2.7%–3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs.

CONCLUSIONS:

Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.
Antiplatelet Therapy and Platelet Activity Testing for Neurointerventional Procedures
Authors: Fukuda Keiko A , Beaman Charles , Szeder Viktor
Published: July 2024

The management of antiplatelet medications in neurointerventional procedures remains a subject of considerable variability and debate. This review article explores the diverse clinical practices and the impact of different antiplatelet regimens and platelet activity testing on patient outcomes in neurointerventional treatments. While much of the evidence around antiplatelet therapies largely stems from randomized trials in cardiac and peripheral vascular diseases, their application in neurointerventional settings requires nuanced consideration. Various assays exist to assess individual platelet function, yet the optimal assay, thresholds, and agents remain uncertain due to interpatient variability in medication responsiveness. Expert consensus groups have attempted to standardize antiplatelet management, which is summarized for elective and emergent neurointerventional procedures. Clopidogrel, a commonly used antiplatelet, faces challenges such as genetic variability in metabolism and drug–drug interactions, impacting its effectiveness. Other agents, such as ticagrelor and prasugrel, offer alternatives with different mechanisms of action and potential advantages. Additionally, short‐acting intravenous P2Y
12
inhibitors, such as cangrelor, and glycoprotein IIb/IIIa inhibitors provide options for acute bridging therapy in neurointerventional cases. Despite advancements, significant gaps persist in understanding the optimal antiplatelet management for neurovascular procedures. While platelet function testing is commonly used, its clinical utility and standardization remain an area of investigation. This review underscores the need for further multicenter studies to delineate best practices and optimize patient outcomes in neurointerventional settings.
Improving laminar fMRI specificity by reducing macrovascular bias revealed by respiration effects
Authors: Chai Yuhui , Morgan A. Tyler , Handwerker Daniel A. , Li Linqing , Huber Laurentius , Sutton Bradley P. , Bandettini Peter A.
Published: July 2024

Functional MRI (fMRI) time series are inherently susceptible to the influence of respiratory variations. While many studies treat respiration as a source of noise in fMRI, this study employs natural respiratory variations during high resolution (0.8 mm) fMRI at 7T to formulate a respiration effect related map and then use this map to reduce macrovascular bias for a more laminar-specific fMRI measurement. Our results indicate that respiratory-related signal changes are modulated by breath phase (breathing in/out or in the transition between breath in and out) during fMRI acquisition, with distinct patterns across various brain regions. We demonstrate that respiration maps generated from normal fMRI runs, such as task-oriented sessions, closely resemble those from deep-breath and breath-hold experiments. These maps show a significant correlation with the macro-vasculature automatically segmented based on susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) images. Most crucially, by removing voxels most responsive to respiratory variations, we can refine high-resolution fMRI measurements to be more layer-specific, improving the accuracy of laminar fMRI analysis.
Synopsis of the Castniidae (Lepidoptera) of Costa Rica
Authors: GARCÍA-DÍAZ JOSÉ DE JESÚS , ESPINOZA-SANABRIA BERNARDO A. , WORTHY ROBERT , GONZÁLEZ JORGE M. , JANZEN DANIEL H. , HALLWACHS WINNIE
Published: July 2024

Based on an exhaustive review of the bibliography, and consultation of entomological collections around the world, we present an illustrated catalog with 16 Castniidae taxa present in Costa Rica. Corybantes veraguana veraguana (Westwood, 1877) is recorded for the first time in the country and new records are reported for rare and little-known species such as Athis analibiae (Espinoza-Sanabria & González, 2005), Athis delecta (Schaus, 1911) and Mirocastnia pyrrhopygoides smalli Miller, 1980. A taxonomic catalog of each taxon is included, as well as general information on geographic distribution, biogeography, ecology, seasonality, flight habits, material examined, and illustrations of males and females for all those taxa known from more than one specimen from Costa Rica.
Winter Targeted Observing Periods during the Year of Polar Prediction in the Southern Hemisphere (YOPP-SH)
Authors: Bromwich David H. , Gorodetskaya Irina V. , Carpentier Scott , Alexander Simon , Bazile Eric , Heinrich Victoria J. , Massonnet Francois , Powers Jordan G. , Carrasco Jorge F. , Cayette Arthur , Choi Taejin , Chyhareva Anastasiia , Colwell Steven R. , Cordeira Jason M. , Cordero Raul R. , Doerenbecher Alexis , Durán-Alarcón Claudio , French W. John R. , Gonzalez-Herrero Sergi , Guyot Adrien , Haiden Thomas , Hirasawa Naohiko , Imazio Paola Rodriguez , Kawzenuk Brian , Krakovska Svitlana , Lazzara Matthew A. , Litell Mariana Fontolan , Manning Kevin W. , Norris Kimberley , Park Sang-Jong , Ralph F. Martin , Rowe Penny M. , Sun Qizhen , Vitale Vito , Wille Jonathan D. , Zhang Zhenhai , Zou Xun
Published: July 2024

The Year of Polar Prediction in the Southern Hemisphere (YOPP-SH) held seven targeted observing periods (TOPs) during the 2022 austral winter to enhance atmospheric predictability over the Southern Ocean and Antarctica. The TOPs of 5–10-day duration each featured the release of additional radiosonde balloons, more than doubling the routine sounding program at the 24 participating stations run by 14 nations, together with process-oriented observations at selected sites. These extra sounding data are evaluated for their impact on forecast skill via data denial experiments with the goal of refining the observing system to improve numerical weather prediction for winter conditions. Extensive observations focusing on clouds and precipitation primarily during atmospheric river (AR) events are being applied to refine model microphysical parameterizations for the ubiquitous mixed-phase clouds that frequently impact coastal Antarctica. Process studies are being facilitated by high-time-resolution series of observations and forecast model output via the YOPP Model Intercomparison and Improvement Project (YOPPsiteMIIP). Parallel investigations are broadening the scope and impact of the YOPP-SH winter TOPs. Studies of the Antarctic tourist industry’s use of weather services show the scope for much greater awareness of the availability of forecast products and the skill they exhibit. The Sea Ice Prediction Network South (SIPN South) analysis of predictions of the sea ice growth period reveals that the forecast skill is superior to the sea ice retreat phase.
Should We Conserve Entropy or Energy when Computing CAPE with Mixed-Phase Precipitation Physics?
Authors: Peters John M.
Published: July 2024

The rapidly increasing resolution of global atmospheric reanalysis and climate model datasets necessitates finding methods for computing convective available potential energy (CAPE) both efficiently and accurately. To this end, this article compares two common methods for computing CAPE which conserve either energy or entropy. Inaccuracies in these computations arise from both physical and numerical errors. For instance, computing CAPE with entropy conserved results in physical errors from nonequilibrium phase transitions but minimizes numerical errors because solutions are analytic at each height. In contrast, computing CAPE with energy conserved avoids these physical errors, but accumulates numerical errors that are grid-resolution-dependent because the numerical integration of a differential equation is required. Analysis of CAPE computed with large databases of soundings from the tropical Amazon and midlatitude storm environments shows that physical errors from the entropy method are typically 1%–3% as large as CAPE, which is comparable to the numerical errors from conserving energy with grid spacing of 25 and 250 m using explicit first-order and second-order integration schemes, respectively. Errors in entropy-based CAPE calculations are also insensitive to vertical grid spacing, in contrast to energy-based calculations whose error strongly scales with the grid spacing. It is shown that entropy-based methods are advantageous when intercomparing datasets with differing vertical resolution because they produce accurate and reasonably fast results that are insensitive to grid resolution, whereas a second-order energy-based method is advantageous when analyzing data with a consistent vertical resolution because of its superior computational efficiency.

Significance Statement

Convective available potential energy (CAPE) is a measure of instability in the atmosphere that helps forecasters and researchers understand when and where thunderstorms will form. The purpose of this article is to identify the most efficient and accurate methods for computing CAPE. Two methods are considered here, one that relates to the entropy (a measure of thermodynamic disorder) of an air parcel and one that relates to the energy of an air parcel. Results indicate that the entropy method is most accurate and insensitive to the resolution of the data used for the calculation (which can vary considerably), whereas the energy method uses the least computation time.
Path Tracking Controller Design of Automated Parking Systems via NMPC with an Instructible Solution
Authors: Chen Liang , Qin Zhaobo , Hu Manjiang , Bian Yougang , Peng Xiaoyan
Published: July 2024

Parking difficulties have become a social issue that people have to solve. Automated parking system is practicable for quick par operations without a driver which can also greatly reduces the probability of parking accidents. The paper proposes a Lyapunov-based nonlinear model predictive controller embedding an instructable solution which is generated by the modified rear-wheel feedback method (RF-LNMPC) in order to improve the overall path tracking accuracy in parking conditions. Firstly, A discrete-time RF-LNMPC considering the position and attitude of the parking vehicle is proposed to increase the success rate of automated parking effectively. Secondly, the RF-LNMPC problem with a multi-objective cost function is solved by the Interior-Point Optimization, of which the iterative initial values are described as the instructable solutions calculated by combining modified rear-wheel feedback to improve the performance of local optimal solution. Thirdly, the details on the computation of the terminal constraint and terminal cost for the linear time-varying case is presented. The closed-loop stability is verified via Lyapunov techniques by considering the terminal constraint and terminal cost theoretically. Finally, the proposed RF-LNMPC is implemented on a self-driving Lincoln MKZ platform and the experiment results have shown improved performance in parallel and vertical parking conditions. The Monte Carlo analysis also demonstrates good stability and repeatability of the proposed method which can be applied in practical use in the near future.
Vibration Control of the Rail Grinding Vehicle with Abrasive Belt Based on Structural Optimization and Lightweight Design
Authors: Fan Wengang , Zhang Shuai , Wu Zhiwei , Liu Yi , Yu Jiangnan
Published: July 2024

As a new grinding and maintenance technology, rail belt grinding shows significant advantages in many applications. The dynamic characteristics of the rail belt grinding vehicle largely determines its grinding performance and service life. In order to explore the vibration control method of the rail grinding vehicle with abrasive belt, the vibration response changes in structural optimization and lightweight design are respectively analyzed through transient response and random vibration simulations in this paper. Firstly, the transient response simulation analysis of the rail grinding vehicle with abrasive belt is carried out under operating conditions and non-operating conditions. Secondly, the vibration control of the grinding vehicle is implemented by setting vibration isolation elements, optimizing the structure, and increasing damping. Thirdly, in order to further explore the dynamic characteristics of the rail grinding vehicle, the random vibration simulation analysis of the grinding vehicle is carried out under the condition of the horizontal irregularity of the American AAR6 track. Finally, by replacing the Q235 steel frame material with 7075 aluminum alloy and LA43M magnesium alloy, both vibration control and lightweight design can be achieved simultaneously. The results of transient dynamic response analysis show that the acceleration of most positions in the two working conditions exceeds the standard value in GB/T 17426-1998 standard. By optimizing the structure of the grinding vehicle in three ways, the average vibration acceleration of the whole car is reduced by about 55.1% from 15.6 m/s2 to 7.0 m/s2. The results of random vibration analysis show that the grinding vehicle with Q235 steel frame does not meet the safety conditions of $$3\sigma$$

3
σ

. By changing frame material, the maximum vibration stress of the vehicle can be reduced from 240.7 MPa to 160.0 MPa and the weight of the grinding vehicle is reduced by about 21.7% from 1500 kg to 1175 kg. The modal analysis results indicate that the vibration control of the grinding vehicle can be realized by optimizing the structure and replacing the materials with lower stiffness under the premise of ensuring the overall strength. The study provides the basis for the development of lightweight, diversified and efficient rail grinding equipment.
Impact Force Localization and Reconstruction via ADMM-based Sparse Regularization Method
Authors: Wang Yanan , Chen Lin , Liu Junjiang , Qiao Baijie , He Weifeng , Chen Xuefeng
Published: July 2024

In practice, simultaneous impact localization and time history reconstruction can hardly be achieved, due to the ill-posed and under-determined problems induced by the constrained and harsh measuring conditions. Although $$\ell_{1}$$

ℓ
1

regularization can be used to obtain sparse solutions, it tends to underestimate solution amplitudes as a biased estimator. To address this issue, a novel impact force identification method with $$\ell_{p}$$

ℓ
p

regularization is proposed in this paper, using the alternating direction method of multipliers (ADMM). By decomposing the complex primal problem into sub-problems solvable in parallel via proximal operators, ADMM can address the challenge effectively. To mitigate the sensitivity to regularization parameters, an adaptive regularization parameter is derived based on the K-sparsity strategy. Then, an ADMM-based sparse regularization method is developed, which is capable of handling $$\ell_{p}$$

ℓ
p

regularization with arbitrary p values using adaptively-updated parameters. The effectiveness and performance of the proposed method are validated on an aircraft skin-like composite structure. Additionally, an investigation into the optimal p value for achieving high-accuracy solutions via $$\ell_{p}$$

ℓ
p

regularization is conducted. It turns out that $$\ell_{0.6}$$

ℓ

0.6

regularization consistently yields sparser and more accurate solutions for impact force identification compared to the classic $$\ell_{1}$$

ℓ
1

regularization method. The impact force identification method proposed in this paper can simultaneously reconstruct impact time history with high accuracy and accurately localize the impact using an under-determined sensor configuration.
Intelligent Diagnosis Method for Typical Co-frequency Vibration Faults of Rotating Machinery Based on SAE and Ensembled ResNet-SVM
Authors: Zhang Xiancheng , Pan Xin , Zeng Hao , Zhou Haofu
Published: July 2024

Intelligent fault diagnosis is an important method in rotating machinery fault diagnosis and equipment health management. To deal with co-frequency vibration faults, a type of typical fault in rotating machinery, this paper proposes a fault diagnosis method based on the stacked autoencoder (SAE) and ensembled ResNet-SVM. Furthermore, the time- and frequency-domain features of several co-frequency vibration faults are summarized based on the mechanism analysis and calculated using actual vibration data. To realize and validate the high-precision diagnosis method of rotating equipment with co-frequency faults proposed in this study, the following three criteria are required: First, to improve the effectiveness and robustness of the ensembled model and the sliding window using data augmentation, adding noise, autoencoder (AE) and SAE methods are analyzed in terms of principle and practical effects. Second, ResNet is used as the feature extractor for the ensembled ResNet-SVM model. Feature extraction is carried out twice, and the extracted co-frequency fault features are more comprehensive. Finally, the data augmentation method and ensemble ResNet-SVM are combined for fault diagnosis and compared with other methods. The experimental results show that the accuracy of the proposed method can exceed 99.9%.
Velocity-Incorporated Wear Model of Rolling Guide Shoe Material Selection
Authors: Chen Longye , Yan Lingyu , Liu Chengliang , Zhang Zhinan
Published: July 2024

To ensure an accurate selection of rolling guide shoe materials, an analysis of the intricate relationship between linear speed and wear is imperative. Finite element simulations and experimental measurements are employed to evaluate four distinct types of materials: polyurethane, rubber, polytetrafluoroethylene (PTFE), and nylon. The speed-index of each material is measured, serving as a preparation for subsequent analysis. Furthermore, the velocity-wear factor is determined, providing insights into the resilience and durability of the material across varying speeds. Additionally, a wear model tailored specifically for viscoelastic bodies is explored, which is pivotal in understanding the wear mechanisms within the material. Leveraging this model, wear predictions are made under higher speed conditions, facilitating the choice of material for rolling guide shoes. To validate the accuracy of the model, the predicted degree of wear is compared with experimental data, ensuring its alignment with both theoretical principles and real-world performance. This comprehensive analysis has verified the effectiveness of the model in the selection of materials under high-speed conditions, thereby offering confidence in its reliability and ensuring optimal performance.
Inflammatory response of leptomeninges to a single cortical spreading depolarization
Authors: Karan Anna A. , Gerasimov Konstantin A. , Spivak Yulia S. , Suleymanova Elena M. , Vinogradova Lyudmila V.
Published: July 2024

Background

Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges.

Methods

A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR.

Results

Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression.

Conclusion

A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack.
Antimicrobial efficacy of nano-particles for crop protection and sustainable agriculture
Authors: Jali Pallavi , Acharya Srinivas , Mahalik Gyanranjan
Published: July 2024

Plant diseases cause colossal crop loss worldwide and are the major yield constraining component in agriculture. Nanotechnology, which has the possible to revolutionize numerous fields of science, innovation, drug, and agriculture. Nanotechnology can be utilized for combating the plant infectious diseases and nano-materials can be utilized as transporter of dynamic elements of pesticides, host defense etc. to the pathogens. The analysis of diseases, finding of pathogens may turn out to be substantially more precise and fast with the utilization of nanosensors. As worldwide demand for food production raises against an evolving atmosphere, nanotechnology could reasonably alleviate numerous challenges in disease managing by diminishing chemical inputs and advancing quick recognition of pathogens. The major goal of this review is to increase growth and productivity using supplements with nanoparticles. (i.e., metals, metal oxides, and carbon) to treat crop diseases and make agricultural practices more productive and sustainable. Prominently, this improved crop may not only be straight connected to the diminished occurrence of pathogenic microorganisms, yet in might possibly add nutritional benefits of the nanoparticles themselves, particularly for the micronutrients important for generating host resistance.
Treatment strategy for compartment syndrome at multiple regions due to injuries caused by a tree fall: a case report
Authors: Miura Tomotaka , Miyake Takahito , Okada Hideshi , Oiwa Hideaki , Mizuno Yosuke , Kitagawa Yuichiro , Fukuta Tetsuya , Okamoto Haruka , Shiba Masato , Kanda Norihide , Yoshida Takahiro , Yoshida Shozo , Ogura Shinji
Published: July 2024

Background

Compartment syndrome commonly occurs in patients with forearm and lower leg fractures. Compartment syndromes of the gluteal and thigh muscles are less common. It is imperative that compartment syndrome be diagnosed and treated with fasciotomy as soon as possible. However, there are few reports on the diagnosis and treatment strategies for compartment syndromes that occur simultaneously in multiple anatomical regions or in the ipsilateral gluteal region and thigh.

Case presentation

We report on a 76-year-old man who was obliquely crushed under a tree extending from the right forearm to the left groin. He was brought to our emergency room, where he was diagnosed with compartment syndrome of the right forearm and left lower leg and crush syndrome. Emergency fasciotomy was performed. On the day after admission, swelling and tightness of the left gluteal thigh became apparent, and intracompartmental pressures were elevated, which led to an additional diagnosis of these compartment syndromes. A fasciotomy was performed, the gluteal skin incision was made according to the Kocher–Langenbeck approach (one of the posterior approaches for hip fractures), and the thigh was approached by extending the incision laterally. This surgical approach enabled the decompression of the compartments through a single incision and allowed for easier wound treatment and closure.

Conclusion

This case highlights the diagnosis and treatment of compartment syndrome in four anatomical regions. Extension of the Kocher–Langenbeck approach to the lateral thigh can be a useful surgical approach for ipsilateral gluteal and thigh compartment syndrome.