bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid subsets impede the efficacy of anti-PD1 therapy in patients with advanced gastric cancer (WJOG10417GTR study)
Authors: Shoji Hirokazu , Kudo-Saito Chie , Nagashima Kengo , Imazeki Hiroshi , Tsugaru Kai , Takahashi Naoki , Kawakami Takeshi , Amanuma Yusuke , Wakatsuki Takeru , Okano Naohiro , Narita Yukiya , Yamamoto Yoshiyuki , Kizawa Rika , Muro Kei , Aoki Kazunori , Boku Narikazu 
Published: November 2024

BackgroundGastric cancer (GC) is one of the most common and deadly malignant diseases worldwide. Despite revolutionary advances, the therapeutic efficacy of anti-PD1/PDL1 monoclonal antibodies in advanced GC is still low due to the emergence of innate and acquired resistance to treatment. Myeloid cells represent the majority of human immune cells. Therefore, their increase, decrease, and abnormality could have a significant impact on the patient’s immune system and the progression of cancer, and reprogramming, inhibiting, and eliminating the tumor-supportive types may improve the immunological situation and efficacy of immunotherapy. However, the significance of myeloid cells in anti-PD1/PDL1 therapy remains unclear in GC. In the WJOG10417GTR study on GC, we sought to identify myeloid determinants that could predict anti-PD1 therapeutic efficacy and also serve as potential therapeutic targets.MethodsWe collected tumor tissues and peripheral blood from 96 patients with advanced GC before and 1 month after anti-PD1 nivolumab monotherapy, and the isolated whole leucocytes were analyzed by flow cytometry for various immune cell populations, including many myeloid subsets. Then, the relationship between the cellular levels and progression-free survival (PFS) or overall survival (OS) was statistically analyzed.ResultsWe found that high levels of several myeloid subsets expressing molecules that have been targeted in drug discovery but not yet approved for clinical use were significantly associated with shorter PFS/OS as compared with low levels: PDL1+and CTLA4+myeloid subsets within tumors at baseline, PDL1+, B7H3+and CD115+myeloid subsets in peripheral blood at baseline, and LAG3+, CD155+and CD115+myeloid subsets in peripheral blood at post-treatment.ConclusionsThis study revealed that these myeloid subsets are significant risk factors in nivolumab therapy for advanced GC. Targeting them may be useful as diagnostic biomarkers to predict potential anti-PD1 therapeutic efficacy, and also as therapeutic targets for accelerating the development of new drugs to improve clinical outcomes in immunotherapy for GC.
Clinical and mutational signatures ofCRB1-associated retinopathies: a multicentre study
Authors: Wang Mo-Ying , Gao Feng-Juan , Ju Yu-Qiao , Guo Lin-Ying , Duan Cong , Chang Qing , Zhang Ting , Xu Ge-Zhi , Du Hui , Zong Yuan , Huang Xin 
Published: November 2024

Background
To delineate the clinical and mutational signatures of patients withCRB1-associated retinopathies.

Methods
This multicentre retrospective cohort study involved 40 patients withCRB1mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype‒phenotype correlations of the patients were analysed.

Results
The mean age ofCRB1cohort was 27.33±14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients withCRB1mutations. These clinical signatures were notably more prevalent amongCRB1patients than among individuals in other IRD groups (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients.

Conclusions
Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update onCRB1-associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies.
FRED X flow diversion stenting for unruptured intracranial aneurysms: US multicenter post-market study
Authors: Hendrix Philipp , Hemmer Sina , Sioutas Georgios S , Field Nicholas C , Essibayi Muhammed Amir , Salem Mohamed M , Srinivasan Visish M , Custozzo Amanda , Karandish Alireza , Altschul David , Paul Alexandra R , Burkhardt Jan-Karl , Schirmer Clemens M , Goren Oded 
Published: November 2024

BackgroundThe Flow Re-direction Endoluminal Device (FRED) X is a next generation flow-diverting stent for treating intracranial aneurysms. Its surface modification (X technology) aims to minimize device thrombogenicity. Early post-market multicenter data from the US are lacking.MethodsWe conducted a retrospective multicenter analysis of consecutive FRED X procedures performed to treat unruptured intracranial aneurysms at four US centers (March 2022 to January 2024). Cases with ruptured aneurysms or extracranial aneurysm location were excluded (n=10). We assessed patient and aneurysm characteristics, antithrombotic management, safety events, and both clinical and angiographic (effectiveness) outcomes.ResultsIn this cohort, 101 patients underwent FRED X stenting for 117 aneurysms. Most aneurysms were saccular in shape (95.7%) and located at the C6–C7 segments of the internal carotid artery (72.6%). Thromboembolic events occurred in 5.9% of the cases, leading to one instance of permanent procedure related morbidity (1.0%). No procedure related mortality (0%) was observed. Device related issues were recorded in 2.0% of cases. At the 6 month follow-up, complete aneurysm occlusion was achieved in 58% of aneurysms. At the last available follow-up (6–12 months), 74.8% of aneurysms were adequately occluded.ConclusionsFRED X stenting for unruptured intracranial aneurysms demonstrated low rates of neurological morbidity and periprocedural complications. Early aneurysm occlusion rates were appropriate, but further mid-term and long term follow-up is required. These findings support the early safety and effectiveness of the FRED X device for intracranial aneurysm treatment.
Watch Out for the Inherent Vulnerabilities in Developing Multi-tenant Cloud-FPGA: Communication Protocols
Authors: Liu Ziyu , Luo Yukui , Zhang Yuheng , Duan Shijin , Xu Xiaolin 
Published: November 2024

As FPGAs are being deployed in the cloud infrastructure for acceleration, the technology of multi-tenant FPGA has emerged as a topic of interest. This development has drawn considerable attention to its security issues. While previous research primarily focused on the security of applications, there has been limited exploration of the vulnerabilities inherent in FPGA IPs. In our work, we examine the vulnerabilities of two widely used data transmission protocols in modern FPGAs: the Advanced eXtensible Interface (AXI) and Peripheral Component Interconnect Express (PCIe). Our experiments, conducted with commercial FPGA development kits, launched fault injection attacks through the shared power distribution network (PDN). Through non-invasive electromagnetic (EM) trace measurement, we characterize the voltage fluctuation across various attack patterns. Subsequently, we simulate real-world data transfers using two crafted datasets with different statistical characteristics. The experimental results demonstrate the unique security vulnerabilities of the current AXI and PCIe protocols in the context of a multi-tenant cloud-FPGA. In response to such vulnerability, we further propose two defense strategies: InChAXI that utilizes integrity checking for AXI-based data, and FCPCIe that employs frequency scaling for PCIe-based data. The performance evaluation demonstrates that our proposed defenses can significantly reduce the fault injections on the AXI-based data transmission by 705 times with small overheads – 0.5% in hardware footprint and 7.9% in latency, respectively. On the other hand, FCPCIe effectively prevents the fault injection attack during the PCIe-based data transmission by reducing the user clock frequency, while incurring a 10.13% overhead on data throughput.
SPIRIT: Scalable and Persistent In-Memory Indices for Real-Time Search
Authors: Akram Shoaib , Hasnat Adnan 
Published: November 2024

Today, real-time search over big microblogging data requires low indexing and query latency. Online services, therefore, prefer to host inverted indices in memory. Unfortunately, as datasets grow, indices grow proportionally, and with limited DRAM scaling, the main memory faces high pressure. Also, indices must be persisted on disks as building them is computationally intensive. Consequently, it becomes necessary to frequently move on-heap index segments to storage, slowing down indexing. Reading storage-resident index segments requires filesystem calls and disk accesses during query evaluation, leading to high and unpredictable tail latency.
This work exploits hybrid DRAM and scalable non-volatile memory (NVM) to offer dynamically growing and instantly searchable (i.e., real-time) persistent indices in on-heap memory. We implement SPIRIT, a real-time text inversion engine over hybrid memory. SPIRIT exploits the byte-addressability of hybrid memory to enable direct access to the index on a pre-allocated heap, eliminating expensive block storage accesses and filesystem calls during live operation. It uses an in-memory segment descriptor table to offer: ① instant segment availability to query evaluators upon fresh ingestion, ② low-overhead segment movement across memory tiers transparent to query evaluators, and ③ decoupled segment movement into NVM from their visibility to query evaluators, enabling different policies for mitigating NVM latency. SPIRIT accelerates compaction with zero-copy merging. It supports volatile, graceful shutdown, and crash-consistent indexing modes. The latter two modes offer instant recovery using persistent pointers.
SPIRIT with hybrid memory and strong crash consistency guarantees exhibits many orders of magnitude better tail response times and query throughout than the state-of-the-art Lucene search engine. Compared against a highly optimized non-real-time evaluation of Lucene with liberal DRAM size, on average, across six query workloads, SPIRIT still delivers 2.5 × better (real-time) query throughput. Our work applies to other services that will benefit from direct on-heap access to large persistent indices.
PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability
Authors: Jasani Neel , Xu Xiaonan , Posorske Benjamin , Kim Yumi , Wang Kaizhen , Vera Olga , Tsai Kenneth Y. , DeNicola Gina M. , Karreth Florian A. 
Published: November 2024

Abstract
Overexpression of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. Here, we found that PHGDH is universally increased in melanoma cells and required for melanomagenesis. Although PHGDH amplification explained PHGDH overexpression in a subset of melanomas, oncogenic BRAFV600E also promoted PHGDH transcription through mTORC1-mediated translation of ATF4. Importantly, depletion of PHGDH in genetic mouse melanoma models blocked tumor formation. In addition to BRAFV600E-mediated upregulation, PHGDH was further induced by exogenous serine restriction. Surprisingly, BRAFV600E inhibition diminished serine restriction–mediated PHGDH expression by preventing ATF4 induction. Consequently, melanoma cells could be specifically starved of serine by combining BRAFV600E inhibition with exogenous serine restriction, which promoted cell death in vitro and attenuated melanoma growth in vivo. In summary, this study identified that PHGDH is essential for melanomagenesis and regulated by BRAFV600E, revealing a targetable vulnerability in BRAFV600E-mutant melanoma.
Significance: BRAFV600E promotes the expression of the serine synthesis enzyme PHGDH, which is required for melanoma formation, and can be targeted to sensitize melanoma to dietary serine restriction, providing a melanoma cell–specific treatment strategy.
Preclinical Characterization of XB002, an Anti–Tissue Factor Antibody–Drug Conjugate for the Treatment of Solid Tumors
Authors: Kantak Seema , Faggioni Raffaella , Cai Allen G. , Bhatti Maryam M. , Li Jing , Vainshtein Inna , Cheng Jackie , Mendelsohn Brian A. , Gaudreault Jacques , Migone Thi-Sau , Theunissen Jan-Willem 
Published: November 2024

Abstract
Tissue factor (TF) is overexpressed in various cancers and is typically associated with poor clinical outcomes. XB002 is an anti-TF antibody–drug conjugate designed to selectively deliver a cytotoxic payload to TF-expressing tumors while minimizing TF-related adverse events, particularly bleeding. The conjugate consists of a zovodotin linker–payload attached to a mAb (clone 25A3) that binds TF with high affinity (KD = 0.86 nmol/L). In vitro coagulation assays confirmed that 25A3 does not interfere with the clotting cascade; even at a concentration of 100 nmol/L, it did not affect the activation of coagulation factor X or thrombin generation. XB002 demonstrated efficient internalization in TF-expressing cancer cell lines, exhibiting potent cytotoxicity at subnanomolar concentrations. In the HPAF-II xenograft model, a regimen of XB002 (1.5 mg/kg, i.v.) administered once weekly for two weeks achieved complete tumor regression, with no detectable tumor growth up to five weeks after the second dose. In murine patient-derived xenograft models, a single dose of XB002 (10 mg/kg, i.v.) inhibited tumor growth across multiple cancer models, including bladder, cervical, gastric, head and neck squamous cell carcinoma, and non–small cell lung cancers. Remarkably, complete tumor regression was observed in the cervical cancer and head and neck squamous cell carcinoma models within 30 days of treatment. In nonhuman primate studies, XB002 demonstrated favorable pharmacokinetics with exposure in the desired therapeutic range and no signs of bleeding or neutropenia. Collectively, these data highlight XB002’s broad-spectrum antitumor activity and strongly support its further clinical development.
The Surge in Human Papillomavirus Vaccine Rejection in Nigeria
Authors: Otorkpa Oche Joseph , Onifade Adefunmilola Adebola , Otorkpa Chinenye Oche 
Published: November 2024

Abstract
In October 2023, Nigeria integrated the single-dose human papillomavirus (HPV) vaccine into its routine immunization program, aiming to protect 7.7 million girls aged 9 to 14 years. This milestone in the fight against HPV-related cancers, especially cervical cancer, faces significant challenges due to high vaccine rejection rates driven by misinformation and cultural barriers. Despite the vaccine’s proven safety and efficacy, uptake remains low. This communication highlights the urgent need for a comprehensive public health education campaign to address these barriers. Proposed strategies include leveraging digital health technologies, integrating HPV education into school curricula, training community health workers, engaging religious and cultural leaders, and launching media campaigns featuring personal narratives. Implementing these evidence-based interventions is crucial for dispelling myths, misconceptions, and skepticism surrounding HPV vaccines. This will enhance acceptance and uptake, ultimately reducing cervical cancer mortality in Nigeria.
Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans
Authors: Sokoloff Lara J. , Wu Jingyi , Eberly Lauren A. , Nathan Ashwin S. , Julien Howard M. , Kobayashi Taisei J. , Damrauer Scott M. , Groeneveld Peter W. , Tsai Jack , Khatana Sameed Ahmed M. 
Published: November 2024

BACKGROUND:
Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization.

METHODS:
Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease–related specialists. Secondary outcomes included cardiovascular disease–related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest.

RESULTS:
Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease–related specialists (4.3% [95% CI, 2.5%–6.1%] and 14.1% [95% CI, 12.5%–15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations.

CONCLUSIONS:
Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.
Burn Period: A Use-Inspired Metric to Track Wildfire Risk across Arizona and New Mexico in the Southwest United States
Authors: Crimmins Michael A. , Maxwell Charles , Ferguson Daniel B. , Frisvold George B. 
Published: November 2024

Abstract
Numerous tools and indices exist for wildland fire managers to anticipate and track changes in wildfire risk driven by variability in weather and climate conditions at hourly to seasonal scales. However, in working closely with Southwest U.S. managers, we learned of a simple meteorological metric being informally used, but not widely accessible in existing tools or information products, to gauge short-term changes in wildfire risk. This metric, termed “Burn Period” (BP), is the local count of hours per day with relative humidity values equal to or less than 20%. Our collaboration led to the development of an experimental tool called the “Burn Period Tracker” to ease access and promote the use of BP values for planning and response. This study is a climatological analysis of BP values at 124 fire weather stations across Arizona and New Mexico for the period 2000–22 to aid in interpretation and understanding of this use-inspired metric. BP values reflect the strong seasonality in temperature and moisture deficit–driven wildfire risk across the Southwest United States, with risk climbing through the arid spring season, peaking in June, and then falling rapidly with the onset of the summer monsoon in July. Regression analyses show that short-term variability in BP values is driven by variability in low-level atmospheric moisture in all months with strongest relationships during the summer after the onset of the monsoon. This study highlights the utility of BP as a short-term wildfire planning tool as well as an example of collaborative weather and climate services development.
Widening of Wind Stress Anomalies Amplifies ENSO in a Warming Climate
Authors: Stuivenvolt-Allen Jacob , Fedorov Alexey V. , Fu Minmin , Heede Ulla 
Published: November 2024

Abstract
Climate change simulations generally indicate the strengthening of El Niño–Southern Oscillation (ENSO) sea surface temperature (SST) variability through the twenty-first century, yet a robust physical mechanism explaining this change across different models is still lacking, and the projections for ENSO amplitude exhibit a large spread. Most commonly, changes in the background state of the tropical Pacific are invoked to explain these changes of ENSO. Here, we show that changes in the structure of wind stress anomalies associated with ENSO are potentially as important as these background state changes. Specifically, changes in the magnitude, meridional width, and zonal structure of wind stress anomalies can explain approximately 53% of the intermodel variance in the projected change of ENSO magnitude through the twenty-first century as well as 43% in ENSO periodicity changes. Among these changes in the wind structure, the meridional widening of wind anomalies plays the most important role. To demonstrate that these changes are indeed critical, we develop a hybrid model of ENSO based on the Community Earth System Model, version 2, which incorporates a dynamical ocean coupled to a simplified statistical atmosphere within the tropical Pacific. In the absence of external forcing and corresponding mean-state changes, the imposed changes in wind stress anomalies in this hybrid model result in an increase of ENSO amplitudes of nearly 10% along the equator. Our results are also theoretically supported by a recharge-oscillator model that incorporates the meridional wind structure. Thus, changes in the structure of wind stress anomalies, together with changes in the mean state, likely play a critical role in the projected strengthening of ENSO.