bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effects of GPVI Deletion and SYK Inhibition on Thrombus Organization and Platelet Adhesion in a Murine Jugular Puncture Wound Model
Authors: Storrie Brian , Pokrovskaya Irina D , Ball Kelly K. , Webb Michael W. 
Published: December 2024

Essential Points GPVI is the major collagen receptor in platelets as well as a receptor for fibrinogen/fibrin and signals intracellularly by activating SYK kinase.Deletion of GPVI in contrast to SYK inhibitor treatment has a mild but significant effect on jugular vein puncture wound bleeding cessation in the murine model. The SYK inhibitor was used at a concentration sufficient to inhibit ferric chloride induced occlusive clotting.Deletion of either GPVI or SYK inhibition inhibits the induction of a high platelet activation state at the collagen/thrombus interface and results in a thinning of the extravascular cap that leads to bleeding cessation in the jugular puncture wound model.The GPVI knockout has a profound effect on the tightness of platelet packing in a 5-min post puncture wound and affects thrombus structure in general through the formation of a very loose intravascular thrombus crown. In contrast, SYK inhibition has little effect on thrombus structure in general.The substantial effect of GPVI knockout on platelet adhesion and intravascular crowning of the puncture wound thrombus indicates a significant late role of GPVI in thrombus formation that is presumably mediated by GPVI-fibrinogen/fibrin interactions.These findings have clinical implications in terms of targeting GPVI to inhibit thrombosis. Is targeting the intracellular SYK pathway versus extracellular domains of GPVI safer? The SYK inhibitor Bi 1002494 is known to preferentially affect thrombosis versus hemostasis (van Eeuwijk et al, 2016; present work)
Literature Cited
Van Eeuwjk JM, Steger D, Lamb DJ, Kraft P, Beck S, Thielmann I, Keifer F, Walzog B, Stoll G, and Nieswandt B. 2916. The novel oral Syk Inhibitor, Bi 1002494, protects mice from arterial thrombosis and thromboinflammatory brain infarction. Arterscler Throm Vasc Biol 36:1247-1253.
BCL-2 Inhibitor Venetoclax Shows Synergistic Effects on CD8 T Cell Proliferation and Blast Death in Vitro When Combined with Anti PD-1 Checkpoint Inhibitor
Authors: Cho Hyun , Lind Evan F. , Pandita Ravina , Kosaka Yoko 
Published: December 2024

Background
Acute myeloid leukemia (AML) is a hematologic malignancy with significant heterogeneity characterized by various genetic mutations and translocations, rendering its treatment highly complicated. Of the numerous factors predicting prognosis, age plays a big role in determining the course of treatment (Juliusson et al. Blood 2009). Median age of 68 (NIH, 2024) poses a challenge to successful treatment induction with exponentially higher mortality rate in elderly patients (Walter et al. Journal of Clinical Oncology 2011) . Median survival rate 4.6 months and 1-year survival rate of 28% in patients age over 70 treated with cytarabine-based chemotherapy. BCL-2 inhibitors, such as venetoclax, have been recently approved for treating newly diagnosed and relapsed AML, improving outcomes for patients over 60 (Pollyea et al. Bone Marrow Transplant 2021). Although BCL-2 inhibition and its effects on T cell proliferation has been demonstrated in the past (Cheng et al. Oncogene 2004), the effects on CD 8 T cell proliferation when combined with checkpoint inhibitors, such as anti PD-1, are yet to be explored.
Methods
Splenocytes from a mouse model of AML with FLT3-ITD, TET2 mutations and wild type mice were collected for T cell proliferation assays. Treatment groups included: venetoclax alone and with azacitidine. On Day 3, the cells were harvested and stained for flow cytometry. CD 8 T cells were defined as CD3+CD8+CD4- and proliferation was quantified with Cell Trace Violet staining. AML blasts were defined as CD3-CD11b+.
Results
Flow cytometry analysis showed significantly increased CD8 T cell proliferation in venetoclax-treated murine AML groups in vitro, and more AML blast deaths when combined with anti PD-1 compared to the standard combination with azacitidine.
Conclusion
We found a higher population of proliferated CD 8 T cells and more blast deaths in venetoclax-treated groups when combined with anti PD-1, than azacitidine-combined groups. However, same analysis showed less T reg cell survival in azacitidine, warranting further investigation on the mechanism of the higher CD 8 T cell proliferation and increased blast deaths when Venetoclax is used with anti PD-1.
Sickle Cell Disease (SCD)-Related Stigma Among Indian SCD Patients - Findings of a Multicentric Study
Authors: Babu Bontha V , Jena Rabindra Kumar 
Published: December 2024

Background: Sickle Cell Disease (SCD) is the most prevalent hemoglobinopathy, affecting approximately 5% of the global population. Within India, the tribal population has been a primary focus of the national SCD program. Due to increased SCD-related awareness, SCD patients and their caregivers in these communities often face health-related stigma due to the multifaceted impact of the disease.
Methodology: This study was implemented in five tribal-dominated districts of India and initiated with exploratory qualitative data, followed by the development of an SCD-related stigma scale and measuring the stigma using the developed scale. In addition, the impact of stigma on Health-Related Quality of Life (HRQoL) and health care utilization. Initially, the study's framework for developing the stigma tool was rooted in Bronfenbrenner's Ecology of Human Development. Subsequently, quantitative surveys were conducted to measure the SCD-related stigma, HRQoL, which was measured through the Medical Outcome Study (MOS) 36-item short-form health survey (SF-36) for adult patients, SCD module and Family Impact Module (FIM) of Pediatric Quality of Life Inventory (PedsQL) for SCD pediatric patients and healthcare-seeking behavior of these patients and caregivers.
Results: The study identified four themes and several subthemes explaining the nature of stigma, its sources, and contributing factors. These themes - (i) perceived stigma, encompassing elements such as disclosure, self-isolation, and self-judgment; (ii) internalization of stigma; (iii) experienced stigma, specifically the impact of the disease on daily life; and the support systems required by patients. The framework underscored the varying degrees of stigma in different aspects of patients' lives and environments. The study also found a considerable negative impact of stigma on HRQoL. Healthcare-seeking behavior is also impacted due to stigma as well as health system-related factors. Poor treatment-seeking behavior is reported, and many patients have not sought appropriate SCD-related treatment, and a considerable number of patients did not report regular hydroxyureas therapy.
Conclusion: Our study, for the first time from India, measured the SCD-related stigma among SCD patients and their caregivers. As the national SCD program has been initiated and implemented in the primary health care system, these findings have considerable implications. Awareness generation activities and preventive measures are to be implemented by taking the stigma and its impact into consideration.
Space Disinfection Using TiO2 Photocatalyst Reduces the Incidence of Febrile Neutropenia in Cancer Patients
Authors: Iizuka Kazuhide , Ochiai Heihachiro , Iizuka Yoshikazu , Somei Junichi , Miura Katsuhiro , Nakamura Hideki , Nakayama Tomohiro , Hatta Yoshihiro , Takei Masami 
Published: December 2024

Background/Purpose
Febrile neutropenia (FN) is life-threatening condition, and airborne microorganisms have been identified as one of the potential transmission routes. Therefore, air disinfection using laminar air flow (LAF) unit with high-efficiency particulate air (HEPA) filter is recommended to prevent infection in patients undergoing intense chemotherapy. However, HEPA filters are expensive and not available in sufficient numbers. Recently, TiO2-photocatalyzed reactions have garnered attention because of their strong oxidative degradation ability against various bacteria, fungi, and viruses. In this study, we investigated the effect of spatial sterilization using a photocatalyst device, which is inexpensive and easy to install and maintain, on the incidence of FN and the causative microorganisms in patients undergoing cancer treatment.
Methods
The space disinfection device which equipped a mechanism that irradiates photocatalytic platinum-added titanium dioxide with 405 nm wavelength LED (LED-TiO2 device) is exhibits a strong oxidative degradation effect. In a previous study, the LED-TiO2 device inactivated aerosolized SARS-Cov-2 viruses in a 120-L acrylic box in 20 minutes. LED-TiO2 device was installed per 21.5-35 m³ in hospital rooms to investigate changes in the incidence of FN and the number of airborne microorganisms.
Results
Airborne microorganisms in the hospital rooms matched those responsible for nosocomial infections. The incidence of nosocomial infections showed a decreasing trend in the After group compared with that in the before group, but the difference was not significant (Figure 1c; 13/32 versus 5/23, P = 0.160). However, the incidence of FN was significantly reduced after installation of the LED-TiO2 device (9/13 vs 2/12, P=0.015). Among the FN cases, pneumonia occurred in 4/13 patients before group and 0/12 patients after group (P = 0.096). In addition, When G-CSF was not administered due to AML/MDS or induction of remission therapy, there was a significant decrease between the Before and After groups (7/8 versus 2/8, P = 0.041). The LED-TiO2 device decreased the number of airborne microorganisms in patient-free rooms by approximately 75% after 2 hours (P&lt;0.001). When patient was in the room, the number of airborne microorganisms increased with medical procedure. However, after 20 minutes after procedure, the number of airborne microorganisms was approximately 50% lower than without the device room (p=0.019).
Conclusions
The LED-TiO2 device successfully achieved spatial disinfection in hospital rooms, and reduced the incidence of FN. Spatial disinfection using photocatalysts is considered an effective new infection prevention measure in patients with severe neutropenia undergoing cancer treatment.
TIFAB modulates metabolic pathways in KMT2A::MLLT3−induced AML through HNF4A
Authors: Wang Yang , Xiu Yan , Dong Qianze , Zhao Jinming , Neumbo Kelao , Miyagi Masaru , Borcherding Nicholas , Fu Lin , De Celis Havana , Pintozzi Nicolas , Starczynowski Daniel T. , Zhao Chen 
Published: December 2024

Abstract
Tumor necrosis factor (TNF) receptor–associated factor (TRAF)–interacting protein with forkhead-associated domain B (TIFAB), an inhibitor of NF-κB signaling, plays critical roles in hematopoiesis, myelodysplastic neoplasms, and leukemia. We previously demonstrated that Tifab enhances KMT2A::MLLT3–driven acute myeloid leukemia (AML) by either upregulating Hoxa9 or through ubiquitin-specific peptidase 15–mediated downregulation of p53 signaling. In this study, we show that Tifab deletion in KMT2A::MLLT3–induced AML impairs leukemia stem/progenitor cell (LSPC) engraftment, glucose uptake, and mitochondrial function. Gene set enrichment analysis reveals that Tifab deletion downregulates MYC, HOXA9/MEIS1, mTORC1 signaling, and genes involved in glycolysis and oxidative phosphorylation. By comparing genes upregulated in TIFAB-overexpressing LSPCs with those downregulated upon Tifab deletion, we identify hepatocyte nuclear factor 4 alpha (Hnf4a) as a key TIFAB target, regulated through the inhibition of NF-κB component RelB, which suppresses Hnf4a in leukemia cells. HNF4A, a nuclear receptor involved in organ development, metabolism, and tumorigenesis, rescues the metabolic defects caused by Tifab deletion and enhances leukemia cell engraftment. Conversely, Hnf4a knockdown attenuates TIFAB-mediated enhancement of LSPC function. These findings highlight the critical role of the TIFAB-HNF4A axis in KMT2A::MLLT3–induced AML and uncover a novel regulator in leukemia biology.
Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia
Authors: Heyman Benjamin M. , Opat Stephen S. , Wahlin Björn E. , Dimopoulos Meletios-Athanasios C. , Castillo Jorge J. , Tedeschi Alessandra , Tam Constantine S. , Buske Christian , Owen Roger G. , Leblond Véronique , Trotman Judith , Barnes Gisoo , Chan Wai Y. , Schneider Jingjing , Allewelt Heather , Cohen Aileen , Matous Jeffrey V. 
Published: December 2024

Abstract
Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN. Logistic regression was performed between PN symptom resolution and several predictors. Health-related quality of life (HRQOL) was assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Forty-nine patients with PN symptoms were included (zanubrutinib treated, n = 27; ibrutinib treated, n = 22). Overall, 35 patients (71.4%) experienced resolution of PN symptoms, with a median time to resolution of 10.1 months (range, 1-46.8). In cohort 1 (MYD88 mutation), the median time to PN symptom resolution was 4.6 months (range, 1.1-46.8) with zanubrutinib and 14.1 months (range, 1-44) with ibrutinib. Logistic regression demonstrated a significant relationship between PN symptom resolution and both major response and lower baseline anti–myelin-associated glycoprotein antibody levels. Patients with PN symptom resolution had greater improvement in HRQOL. Physical functioning improved in patients with PN symptom resolution and was unchanged in patients without resolution. Improvements observed in PN symptoms may be in response to a reduction in immunoglobulin M. Although further investigation is required, this analysis supports the potential use and further exploration of Bruton tyrosine kinase inhibitors to treat PN symptoms in patients with WM. This trial was registered at www.clinicaltrials.gov as #NCT03053440.
Nailfold videocapillaroscopy – a novel method for the assessment of hemodynamic incoherence on the ICU
Authors: Kintrup Sebastian , Listkiewicz Lukasz , Arnemann Philip-Helge , Wagner Nana-Maria 
Published: December 2024

Abstract
Background
Loss of hemodynamic coherence is a phenomenon in critically ill patients. Due to inflammatory events and endothelial remodeling, macro- and microhemodynamics are decoupled from each other, resulting in microcirculatory disturbances and end organ ischemia despite adequate vital parameters. So far, quantification of perfusion of vessels with < 100 μm diameter on the intensive care unit (ICU) was regularly performed with incident darkfield (IDF) microscopy. Nailfold videocapillaroscopy (NVC), however, is an established and easy method for visualization of the microcirculation in chronic diseases. We here evaluated NVC in critically ill patients and compared its use with consensus microcirculatory assessment of IDF-microscopy.

Methods
A new score, the capillary microcirculation (CapMic) score summarizing the microcirculation of the nail fold at four regions of digitus III, IV and V in a number between 0 (= no microcirculation) and 1 (= completely preserved microcirculation) was first established in 10 healthy volunteers and compared to the Microangiopathy Evolution Score (MES) standardized for NVC in chronic diseases. Then, n = 60 critically ill patients were recruited from a surgical ICU. Consensus-defined IDF scores and NCV data were compared at a single time point.

Results
Evaluation of the CapMic score in 10 healthy volunteers at rest and under iatrogenic limb ischemia showed robust changes (0.80 ± 0.03 vs. 0.51 ± 0.12, p < 0.001). In critically ill patients, the IDF microscopy parameters “proportion of perfused vessels” (PPV) and “microvascular flow index” (MFI) inversely correlated with the MES (Spearman’s R = -0.590, p < 0.001; Spearman’s R = −0.585, p < 0.001). There was a positive correlation between PPV and the CapMic score (Spearman’s R = 0.714, p < 0.001) and between MFI and the CapMic score (Spearman’s R = 0.711, p < 0.001) and an inverse correlation between MES and the CapMic score (Spearman’s R = −0.610, p < 0.001). Both sublingual and nailfold microcirculation deteriorated under rising norepinephrine- and crystalloid volume-requirements.

Conclusion
NVC-imaging provides comparable information on the microcirculation in critically ill patients compared to sublingual IDF microscopy. NCV could represent a new, additional method for diagnosing microcirculatory parameters on the ICU.
Analysis of Huanglongbing transmission model with vector preferences and heterogeneous environments
Authors: Luo Youquan , Tang Shuimei , Zhang Fumin , Liu Yujiang , Gao Shujing 
Published: December 2024

AbstractThe world citrus industry is confronting an unprecedented challenge from citrus Huanglongbing (HLB). With no resistant commercial citrus varieties or curable chemicals currently available, HLB remains the top threat to the world citrus industry. In this paper, two dynamic models of citrus HLB are proposed based on the preference and diffusion of citrus psyllids. The first model is a single-patch model of HLB with vector preference. The basic reproduction number of the model is calculated, and dynamic properties of the single-patch model, including the existence and local stability of the disease-free equilibrium, are analyzed. By sensitivity analysis, the parameters that have a significant impact on the basic reproduction number are identified. Numerical simulations are conducted to demonstrate that the preference of citrus psyllids is not conducive to disease prevention. Considering the diffusion of citrus psyllids between two patches, a two-patch diffusion model of HLB with preference is formulated. The global basic reproduction number of the diffusion model is determined, and the global stability of the disease-free equilibrium is established under certain conditions. Finally, numerical simulation results explore how the preference behavior of the vector and the coupling strength between two patches affect the HLB transmission.
Innovative sterile male release strategies for Aedes mosquito control: progress and challenges in integrating evidence of mosquito population suppression with epidemiological impact
Authors: Rahul Arya , Reegan Appadurai Daniel , Shriram A. N. , Fouque Florence , Rahi Manju 
Published: December 2024

Abstract
Background
Aedes mosquitoes pose a significant global threat as vectors for several debilitating arboviruses, including dengue, Zika, yellow fever, and chikungunya. Their unique breeding habits, behavior, and daytime activity complicate control efforts, prompting the search for innovative solutions. The sterile insect technique (SIT) and incompatible insect technique (IIT) are promising new techniques under investigation. This review synthesizes findings from field trials on SIT and/or IIT for Aedes mosquito control.

Methods
A scoping review was conducted through comprehensive searches on Scopus, Web of Science, MEDLINE, PubMed, and preprint repositories up to April 25, 2024. Studies were initially screened for relevance based on their titles and abstracts, followed by a full-text review conducted by two independent extractors. Only field trials with control groups were included, with the final assessment focusing on trials reporting epidemiological outcomes. Data were abstracted into templates, emphasizing study design, intervention details, and outcomes. The review adhered to the PRISMA-ScR guidelines.

Results
The search identified 21 field trials in various countries against Aedes mosquitoes. These trials employed diverse methodologies and mosquito release strategies, achieving varying levels of mosquito population suppression. Notably, two SIT and two Wolbachia-based IIT trials reported epidemiological outcomes, including reductions in dengue incidence and associated risk ratios. However, the reliance on national surveillance data for assessing dengue incidence suggests caution due to the potential underreporting of subclinical cases.

Conclusions
The review underscores the promise of SIT and IIT for controlling Aedes mosquito populations, citing successful reductions in mosquito densities and dengue transmission. However, it calls for more rigorous study designs and standardized methodologies, as well as the adoption of comprehensive frameworks to accurately assess the effectiveness of these interventions. Future research should focus on bridging gaps in real-world effectiveness by addressing factors such as feasibility, acceptability, scalability, and cost, which are crucial for guiding their successful large-scale deployment in any country.
The interplay of forgiveness by God and self-forgiveness: a longitudinal study of moderating effects on stress overload in a religious Canadian sample
Authors: Skalski-Bednarz Sebastian Binyamin 
Published: December 2024

Abstract
Background
A consistent link between self-forgiveness and well-being has been established, yet a full understanding of self-forgiveness and its correlates, particularly in relation to forgiveness by God, remains limited, especially given that most existing data are cross-sectional. This study sought to address this gap by investigating the interplay between self-forgiveness and perceived forgiveness by God in reducing stress overload among religious individuals over time.

Methods
This study involved 211 religious individuals in Canada, 55% of whom were female. Through multilevel analyses, the research examined the between-person, within-person, and cross-level effects of these forms of forgiveness on stress across three waves conducted over a total 12-month period.

Results
The findings suggested that the effectiveness of self-forgiveness in mitigating stress may be significantly influenced by the perception of forgiveness by God, with the greatest stress reduction occurring when forgiveness by God was perceived at higher levels.

Conclusions
These findings highlight the potential value of incorporating spiritual dimensions into psychological approaches to stress management, offering insights into the complex relationships between different forms of forgiveness and their impact on mental health of religious individuals. Future research is encouraged to further explore these dynamics across diverse cultural and religious contexts.