bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL
Authors: Coates Laura C , Landewé Robert , McInnes Iain B , Mease Philip J , Ritchlin Christopher T , Tanaka Yoshiya , Asahina Akihiko , Behrens Frank , Gladman Dafna D , Gossec Laure , Orbai Ana-Maria , Gottlieb Alice B , Warren Richard B , Ink Barbara , Bajracharya Rajan , Shende Vishvesh , Coarse Jason , Merola Joseph F 
Published: February 2024

ObjectivesTo assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors.MethodsPatients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52.ResultsA total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to ‍52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52.ConclusionsBimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.
Crossing the line: access to trauma care across state borders
Authors: Kumar Satvika , Song Jamie , Reilly Patrick M , Dickinson Edward T , Buckler David G , Haddad Diane N , Kaufman Elinore 
Published: February 2024

ObjectiveThis study investigates the challenge posed by state borders by identifying the population, injury, and geographic scope of areas of the country where the closest trauma center is out-of-state, and by collating state emergency medical services (EMS) policies relevant to cross-border trauma transport.MethodsWe identified designated levels I, II, and III trauma centers using data from American Trauma Society. ArcGIS was used to map the distance between US census block groups and trauma centers to identify the geographic areas for which cross-border transport may be most expedient. National Highway Traffic Safety Administration data were queried to quantify the proportion of fatal crashes occurring in the areas of interest. State EMS protocols were categorized by stance on cross-border transport.ResultsOf 237 596 included US census block groups, 18 499 (7.8%) were closest to an out-of-state designated level I or II trauma center. These census block groups accounted for 6.9% of the US population and 9.5% of all motor vehicle fatalities. With the inclusion of level III trauma centers, the number of US census block groups closest to an out-of-state designated level I, II, or III trauma center decreased to 13 690 (5.8%). These census block groups accounted for 5.1% of the US population and 7.1% of all motor vehicle fatalities. Of the 48 contiguous states, 30 encourage cross-border transport, 2 discourage it, 12 are neutral, and 4 leave it to local discretion.ConclusionCross-border transport can expedite access to care in at least 5% of US census block groups. While few states discourage this practice, more robust policy guidance could reduce delays and enhance care.Level of EvidenceIII, Epidemiological.
Outcomes of patients with traumatic brain injury after stress ulcer prophylaxis: a retrospective multicenter study
Authors: McGraw Constance , Briscoe Abigale , Reynolds Cassandra , Carrick Matthew , Palacio Carlos H , Waswick William , Miller April , Trujillo Laura , Bar-Or David 
Published: February 2024

BackgroundStress ulcers in patients with traumatic brain injury (TBI) and spinal cord injury (SCI) present significant morbidity and mortality risks. Despite the low reported stress ulcer rates, stress ulcer prophylaxis (SUP) is widely administered in neurocritical care. It was hypothesized that universal SUP administration may not be associated with reduced rates of complications across all neurocritical care patients.MethodsThis retrospective study encompassed neurocritical care patients aged ≥18 with moderate or severe TBI or SCI, admitted to the intensive care unit (ICU) between October 2020 and September 2021, across six level I trauma centers. Exclusions included patients with an ICU stay <2 days, prior SUP medication use, and pre-existing SUP diagnoses. The primary exposure was SUP, with the primary outcome being clinically significant gastrointestinal bleeds (CSGIBs). Secondary outcomes included pneumonia and in-hospital mortality. Patients were stratified by admission Glasgow Coma Scale (GCS) groups.ResultsAmong 407 patients, 83% received SUP, primarily H2 receptor antagonists (88%) and proton pump inhibitors (12%). Patients on SUP were significantly younger, had lower admission GCS scores, higher Injury Severity Scores, longer ICU stays, and higher rates of mechanical ventilation than non-SUP patients. Overall, CSGIBs were rare (1%) and not significantly different between the SUP and non-SUP groups (p=0.06). However, CSGIBs exclusively occurred in patients with GCS scores of 3–8, and SUP was associated with a significantly lower rate of CSGIBs in this subgroup (p=0.03). SUP was also linked to significantly higher pneumonia rates in both GCS 3–8 and GCS 9–12 patients.ConclusionsThis study highlights the low incidence of CSGIBs in neurocritical trauma patients and suggests potential benefits of SUP, particularly for those with severe neurological impairment. Nevertheless, the increased risk of pneumonia associated with SUP in these patients warrants caution. Further research is crucial to refine SUP guidelines for neurocritical care patients and inform optimal strategies.Level of evidenceLevel III, retrospective.
Evolution of an interacting fermion–antifermion pair in the near-horizon of the BTZ black hole
Authors: Guvendi Abdullah 
Published: February 2024

AbstractIn this study, we investigate the evolution of a composite system comprising a fermion–antifermion pair engaged in Cornell-type non-minimal interaction in the near-horizon region of a BTZ black hole. Our exploration involves the derivation of an exact solution for the covariant two-body Dirac equation, derived from quantum electrodynamics through the action principle. To commence our analysis, we formulate the relevant equation, resulting in a $$4\times 4$$

4
×
4

dimensional matrix equation that governs the relative motion of the fermion–antifermion pair. Notably, we demonstrate that this matrix equation results in an exactly solvable wave equation, enabling us to determine the relativistic frequency modes for this spinless static composite system. Our findings unveil a temporal decay in these modes, with the decay time explicitly dependent on both the inter-particle interaction and the spacetime parameters. Our comprehensive examination extends to a detailed analysis of the system’s evolution, shedding light on the influence of inter-particle interaction on the evolution of a fermion–antifermion pair in the near-horizon region of the BTZ black hole.
Designs of the divider and special multiplier optimizing T and CNOT gates
Authors: Fan Ping , Li Hai-Sheng 
Published: February 2024

AbstractQuantum circuits for multiplication and division are necessary for scientific computing on quantum computers. Clifford + T circuits are widely used in fault-tolerant realizations. T gates are more expensive than other gates in Clifford + T circuits. But neglecting the cost of CNOT gates may lead to a significant underestimation. Moreover, the small number of qubits available in existing quantum devices is another constraint on quantum circuits. As a result, reducing T-count, T-depth, CNOT-count, CNOT-depth, and circuit width has become the important optimization goal. We use 3-bit Hermitian gates to design basic arithmetic operations. Then, we present a special multiplier and a divider using basic arithmetic operations, where ‘special’ means that one of the two operands of multiplication is non-zero. Next, we use new rules to optimize the Clifford + T circuits of the special multiplier and divider in terms of T-count, T-depth, CNOT-count, CNOT-depth, and circuit width. Comparative analysis shows that the proposed multiplier and divider have lower T-count, T-depth, CNOT-count, and CNOT-depth than the current works. For instance, the proposed 32-bit divider achieves improvement ratios of 40.41 percent, 31.64 percent, 45.27 percent, and 65.93 percent in terms of T-count, T-depth, CNOT-count, and CNOT-depth compared to the best current work. Further, the circuit widths of the proposed n-bit multiplier and divider are 3n. I.e., our multiplier and divider reach the minimum width of multipliers and dividers, keeping an operand unchanged.
Van der Waals black holes in rainbow gravity
Authors: Oubagha R. , Hamil B. , Merad M. , Lütfüoğlu B. C. 
Published: February 2024

Recently, Rajagopal et al. presented an asymptotically AdS black hole metric whose thermodynamics qualitatively mimics the behavior of the Van der Waals fluid by treating the cosmological constant as a thermodynamic pressure. In some studies in the literature, authors have discussed the effects of deformed algebras such as generalized and extended uncertainty principles on the thermal quantities of these black holes. In this paper, we considered another deformation, the rainbow gravity formalism, and we investigated its impact on the Van der Waal black hole thermodynamics. To this end, we first generated the modified lapse and mass functions, and then we derived the modified thermal quantities such as thermodynamic volume, Hawking temperature, entropy, and specific heat functions. Finally, we explored the thermodynamics of a black hole, which mimics the thermodynamics of an ideal gas, under the influence of the rainbow gravity formalism.
Quality Competition Among Internet Service Providers
Authors: Scherrer Simon , Tabaeiaghdaei Seyedali , Perrig Adrian 
Published: February 2024

Internet service providers (ISPs) have a variety of quality attributes that determine their attractiveness for data transmission, ranging from quality-of-service metrics such as jitter to security properties such as the presence of DDoS defense systems. ISPs should optimize these attributes in line with their profit objective, i.e., maximize revenue from attracted traffic while minimizing attribute-related cost, all in the context of alternative offers by competing ISPs. However, this attribute optimization is difficult not least because many aspects of ISP competition are barely understood on a systematic level, e.g., the multi-dimensional and cost-driving nature of path quality, and the distributed decision making of ISPs on the same path.
In this paper, we improve this understanding by analyzing how ISP competition affects path quality and ISP profits. To that end, we develop a game-theoretic model in which ISPs (i) affect path quality via multiple attributes that entail costs, (ii) are on paths together with other selfish ISPs, and (iii) are in competition with alternative paths when attracting traffic. The model enables an extensive theoretical analysis, surprisingly showing that competition can have both positive and negative effects on path quality and ISP profits, depending on the network topology and the cost structure of ISPs. However, a large-scale simulation, which draws on real-world data to instantiate the model, shows that the positive effects will likely prevail in practice: If the number of selectable paths towards any destination increases from 1 to 5, the prevalence of quality attributes increases by at least 50%, while 75% of ISPs improve their profit.
A Foundation for Real-time Applications onFunction-as-a-Service
Authors: Duc Nguyen Hai , Chien Andrew A. 
Published: February 2024

Serverless (or Function-as-a-Service) compute model enables new applications with dynamic scaling. However, all current Serverless systems are best-effort, and as we prove this means they cannot guarantee hard real-time deadlines, rendering them unsuitable for such real-time applications.
We analyze a proposed extension of the Serverless model that adds a guaranteed invocation rate to the serverless model called Real-time Serverless. This approach aims to meet real-time deadlines with dynamically allocated function invocations. We first prove that the Serverless model does not support real-time guarantees. Next, we analyze Real-time Serverless, showing it can guarantee application real-time deadlines for rate-monotonic real-time workloads. Further, we derive bounds on the required invocation rate to meet any set of workload runtimes and periods. Subsequently, we explore an application technique, pre-invocation, and show that it can reduce the required guaranteed invocation rate. We derive bounds for the feasible rate guarantee reduction, and corresponding overhead in wasted compute resources. Finally, we apply the theoretical results to improve the experience quality of a distributed virtual reality/ augmented reality application as well as simplify the application design and resource management.
Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials
Authors: Svanberg Teglgaard Rebecca , Marquart Hanne Vibeke , Hartling Hans Jakob , Bay Jakob Thaning , da Cunha-Bang Caspar , Brieghel Christian , Faitová Tereza , Enggaard Lisbeth , Kater Arnon P. , Levin Mark-David , Kersting Sabina , Ostrowski Sisse Rye , Niemann Carsten U. 
Published: February 2024

Abstract

Purpose:
Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function. Therefore, we investigated innate immune phenotypes and function in patients with CLL before and during targeted treatment.

Experimental Design:
Baseline and consecutive blood samples were collected from patients with CLL treated with acalabrutinib (n = 17) or ibrutinib+venetoclax (n = 18) in clinical trials. Innate immune function was assessed by TruCulture, a whole-blood ligand-stimulation assay quantifying cytokine release in response to standardized stimuli. Innate immune phenotypes were characterized by flow cytometry. As a proxy for infections, we mapped antimicrobial use before and during treatment.

Results:
At baseline, patients with CLL displayed impaired stimulated cytokine responses to the endotoxin lipopolysaccharide (LPS) along with deactivated monocytes, enrichment of myeloid-derived suppressor cells and metamyelocytes, and elevated (unstimulated) proinflammatory cytokines. Two/three cycles of acalabrutinib or ibrutinib normalized LPS-stimulated responses, in parallel with decreased duration of infections. Innate immune profiles and elevated proinflammatory cytokines further normalized during longer-term acalabrutinib or ibrutinib+venetoclax, paralleled by decreased infection frequency.

Conclusions:
Innate immune impairment and infection susceptibility in patients with CLL were restored in parallel during targeted therapy. Thus, targeted treatment may reduce the risk of infections in CLL, as currently under investigation in the PreVent-ACaLL phase 2 trial of acalabrutinib+venetoclax for high-risk CLL (NCT03868722).
Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study
Authors: Else Tobias , Jonasch Eric , Iliopoulos Othon , Beckermann Kathryn E. , Narayan Vivek , Maughan Benjamin L. , Oudard Stephane , Maranchie Jodi K. , Iversen Ane B. , Goldberg Cynthia M. , Fu Wei , Perini Rodolfo F. , Liu Yanfang , Linehan W. Marston , Srinivasan Ramaprasad 
Published: February 2024

Abstract

Purpose:
Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel–Lindau (VHL) disease–associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease–associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas].

Patients and Methods:
Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor &gt;3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety.

Results:
All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1–46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was –4.2 mm per year (range, –7.9 to –0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred.

Conclusions:
Belzutifan continued to show robust activity and manageable safety in VHL disease–associated pNETs.
Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma
Authors: Wehrli Marc , Guinn Samantha , Birocchi Filippo , Kuo Adam , Sun Yi , Larson Rebecca C. , Almazan Antonio J. , Scarfò Irene , Bouffard Amanda A. , Bailey Stefanie R. , Anekal Praju Vikas , Montero Llopis Paula , Nieman Linda T. , Song Yuhui , Xu Katherine H. , Berger Trisha R. , Kann Michael C. , Leick Mark B. , Silva Harrison , Salas-Benito Diego , Kienka Tamina , Grauwet Korneel , Armstrong Todd D. , Zhang Rui , Zhu Qingfeng , Fu Juan , Schmidts Andrea , Korell Felix , Jan Max , Choi Bryan D. , Liss Andrew S. , Boland Genevieve M. , Ting David T. , Burkhart Richard A. , Jenkins Russell W. , Zheng Lei , Jaffee Elizabeth M. , Zimmerman Jacquelyn W. , Maus Marcela V. 
Published: February 2024

Abstract

Purpose:
Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell–engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).

Experimental Design:
Using a suite of in vitro, in vivo, and ex vivo patient-derived models containing cancer cells and CAF, we examined the ability of mesoFAP CAR-TEAM cells to target PDAC cells and CAF within the TME. We developed and used patient-derived ex vivo models, including patient-derived organoids with patient-matched CAF and patient-derived organotypic tumor spheroids.

Results:
We demonstrated specific and significant binding of the TEAM to its respective antigens (CD3 and FAP) when released from mesothelin-targeting CAR T cells, leading to T-cell activation and cytotoxicity of the target cell. MesoFAP CAR-TEAM cells were superior in eliminating PDAC and CAF compared with T cells engineered to target either antigen alone in our ex vivo patient-derived models and in mouse models of PDAC with primary or metastatic liver tumors.

Conclusions:
CAR-TEAM cells enable modification of tumor stroma, leading to increased elimination of PDAC tumors. This approach represents a promising treatment option for pancreatic cancer.
Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test
Authors: Alimena Stephanie , Stephenson Briana Joy K. , Webber James W. , Wollborn Laura , Sussman Chad B. , Packard Daniel George , Williams Marta , Comrie Cameron Elizabeth , Wang Joyce Y. , Markert Tahireh , Spiegel Julia , Rodriguez Carmen B. , Lightfoot Maya , Graye Amia , O'Connor Sean , Elias Kevin M. 
Published: February 2024

Abstract

Serum miRNAs are promising biomarkers for several clinical conditions, including ovarian cancer. To inform equitable implementation of these tests, we investigated the effects of race, ethnicity, and socioeconomic status on serum miRNA profiles. Serum samples from a large institutional biobank were analyzed using a custom panel of 179 miRNA species highly expressed in human serum, measured using the Abcam Fireplex assay via flow cytometry. Data were log-transformed prior to analysis. Differences in miRNA by race and ethnicity were assessed using logistic regression. Pairwise t tests analyzed racial and ethnic differences among eight miRNAs previously associated with ovarian cancer risk. Pearson correlations determined the relationship between mean miRNA expression and the social deprivation index (SDI) for Massachusetts residents. Of 1,586 patients (76.9% white, non-Hispanic), compared with white, non-Hispanic patients, those from other racial and ethnic groups were younger (41.9 years ± 13.2 vs. 51.3 ± 15.1, P &lt; 0.01) and had fewer comorbidities (3.5 comorbidities ± 2.7 vs. 4.6 ± 2.8, P &lt; 0.01). On logistic regression, miRNAs predicted race and ethnicity at an AUC of 0.69 (95% confidence interval, 0.66–0.72), which remained consistent when stratified by most comorbidities. Among eight miRNAs previously associated with ovarian cancer risk, seven significantly varied by race and ethnicity (all P &lt; 0.01). There were no significant differences in SDI for any of these eight miRNAs. miRNA expression is significantly influenced by race and ethnicity, which remained consistent after controlling for confounders. Understanding baseline differences in biomarker test characteristics prior to clinical implementation is essential to ensure instruments perform comparably across diverse populations.

Prevention Relevance:
This study aimed to understand factors affecting miRNA expression, to ensure we create equitable screening tests for ovarian cancer that perform well in diverse populations. The goal is to ensure that we are detecting ovarian cancer cases earlier (secondary prevention) in women of all races, ethnic backgrounds, and socioeconomic means.