bluuebunny/crossref_metadata_2025_split huggingface dataset:
MerTK signaling in human primary T cells modulates memory potential and improves recall response
Authors: Rahbech Anne , Kurzay Annina , Fresnillo Saló Sara , Seremet Tina , Debets Reno , Met Özcan , Peeters Marlies J W , thor Straten Per 
Published: October 2024

Abstract
Immune therapy using checkpoint inhibitors or adoptive cell transfer has revolutionized the treatment of several types of cancers. However, response to treatment is currently limited to a fraction of patients. Elucidation of immune modulatory mechanisms might optimize patient selection and present ways to modify anti-cancer immune responses. We recently discovered the expression and an important costimulatory role of TAM receptor MerTK signaling on activated human primary CD8+ T cells. Here we extend our study of the costimulatory role of MerTK expression in human CD8+ T cells. We uncover a clear link between MerTK expression and less differentiated Central Memory T cells based on an increased expression of CCR7, CD45RO, CD28, CD62L, and an altered metabolic profile. In addition, we observe an improved proliferative capacity and elevated expression of effector molecule IFNγ upon recall responses of MerTK-expressing cells in vitro. Finally, using gp100TCR-transduced T cells, we demonstrate how PROS1 treatment results in improved cytotoxicity and killing of tumors. Our findings describe a role of MerTK expression in T cells, which could be exploited in the search for improving immunotherapeutic approaches.
RE: The first living cervid species described in the 21st century and revalidation of Pudella (Artiodactyla)
Authors: Zijlstra Jelle S 
Published: October 2024

Abstract
The correct name combination for the Northern Pudu, which was recently assigned to the revalidated genus Pudella, is Pudella mephistophiles (de Winton, 1896). There has been confusion over the number of its holotype specimen; the correct specimen number of the holotype is BMNH 1896.1.28.6.
Cognitive and affective links between childhood adversity and psychological adjustment in emerging adults with chronic medical conditions
Authors: DeLone Alexandra M , Basile Nathan L , Chaney John M , Mullins Larry L , Sharkey Christina M 
Published: October 2024

Abstract

Objective
Childhood adversity has been linked to poor psychological adjustment and decreased emotion regulation (ER) abilities. The extended process model of ER outlines the pivotal role of cognitive appraisals in the generation and expression of emotion as well as the pursuit of ER. The aim of the current study is to examine whether illness-related cognitive appraisals (i.e., illness uncertainty and illness intrusiveness) and emotion dysregulation serially mediate the relationship between childhood adversity and psychological adjustment for emerging adults with chronic medical conditions (CMCs).

Methods
Participants included 557 undergraduate college students (Mage= 19.53 years, SD = 1.34) enrolled in a Midwestern public university with self-reported CMCs. Participants completed measures of adverse childhood experiences (ACEs), illness uncertainty, illness intrusiveness, emotion dysregulation, anxious symptoms, and depressive symptoms. A path analysis was conducted examining ACEs → cognitive appraisals (i.e., illness uncertainty, illness intrusiveness) → emotion dysregulation → depressive and anxious symptoms.

Results
The overall model was significant and predicted 63.5% of the variability in anxious symptoms and 60.2% of the variability in depressive symptoms. All anticipated direct and indirect paths were significant.

Conclusions
The current study indicates that greater childhood adversity is indeed associated with negative appraisals of one’s CMC, such as greater perceived uncertainty and intrusiveness. Negative illness-related cognitive appraisals thus may limit one’s ability to effectively employ adaptive strategies to regulate emotions, which could contribute to greater depressive and anxious symptoms.
High-throughput, low-cost FLASH: irradiation of Drosophila melanogaster with low-energy X-rays using time structures spanning conventional and ultrahigh dose rates
Authors: Hart Alexander , Dudzic Jan P , Clarke Jameson W , Eby Jonathan , Perlman Steve J , Bazalova-Carter Magdalena 
Published: October 2024

Abstract
FLASH radiotherapy is an emerging technique in radiation oncology that may improve clinical outcomes by reducing normal tissue toxicities. The physical radiation characteristics needed to induce the radiobiological benefits of FLASH are still an active area of investigation. To determine the dose rate, range of doses and delivery time structure necessary to trigger the FLASH effect, Drosophila melanogaster were exposed to ultrahigh dose rate (UHDR) or conventional radiotherapy dose rate (CONV) 120-kVp X-rays. A conventional X-ray tube outfitted with a shutter system was used to deliver 17- to 44-Gy doses to third-instar D. melanogaster larvae at both UHDR (210 Gy/s) and CONV (0.2–0.4 Gy/s) dose rates. The larvae were then tracked through development to adulthood and scored for eclosion and lifespan. Larvae exposed to UHDR eclosed at higher rates and had longer median survival as adults compared to those treated with CONV at the same doses. Eclosion rates at 24 Gy were 68% higher for the UHDR group (P &lt; 0.05). Median survival from 22 Gy was &gt;22 days for UHDR and 17 days for CONV (P &lt; 0.01). Two normal tissue-sparing effects were observed for D. melanogaster irradiated with UHDR 120-kVp X-rays. The effects appeared only at intermediate doses and may be useful in establishing the dose range over which the benefits of FLASH can be obtained. This work also demonstrates the usefulness of a high-throughput fruit fly model and a low-cost X-ray tube system for radiobiological FLASH research.
High-fidelity Image Restoration of Large 3D Electron Microscopy Volume
Authors: Kreinin Yuri , Gunn Pat , Chklovskii Dmitri , Wu Jingpeng 
Published: October 2024

Abstract
Volume electron microscopy (VEM) is an essential tool for studying biological structures. Due to the challenges of sample preparation and continuous volumetric imaging, image artifacts are almost inevitable. Such image artifacts complicate further processing both for automated computer vision methods and human experts. Unfortunately, the widely used contrast limited adaptive histogram equalization (CLAHE) can alter the essential relative contrast information about some biological structures. We developed an image-processing pipeline to remove the artifacts and enhance the images without CLAHE. We apply our method to VEM datasets of a Microwasp head. We demonstrate that our method restores the images with high fidelity while preserving the original relative contrast. This pipeline is adaptable to other VEM datasets.
Intravital Microscopy With an Airy Beam Light Sheet Microscope Improves Temporal Resolution and Reduces Surgical Trauma
Authors: Stegmeyer Rebekka I , Stasch Malte , Olesker Daniel , Taylor Jonathan M , Mitchell Thomas J , Hosny Neveen A , Kirschnick Nils , Spickermann Gunnar , Vestweber Dietmar , Volkery Stefan 
Published: October 2024

Abstract
Intravital microscopy has emerged as a powerful imaging tool, which allows the visualization and precise understanding of rapid physiological processes at sites of inflammation in vivo, such as vascular permeability and leukocyte migration. Leukocyte interactions with the vascular endothelium can be characterized in the living organism in the murine cremaster muscle. Here, we present a microscopy technique using an Airy Beam Light Sheet microscope that has significant advantages over our previously used confocal microscopy systems. In comparison, the light sheet microscope offers near isotropic optical resolution and faster acquisition speed, while imaging a larger field of view. With less invasive surgery we can significantly reduce side effects such as bleeding, muscle twitching, and surgical inflammation. However, the increased acquisition speed requires exceptional tissue stability to avoid imaging artefacts. Since respiratory motion is transmitted to the tissue under investigation, we have developed a relocation algorithm that removes motion artefacts from our intravital microscopy images. Using these techniques, we are now able to obtain more detailed 3D time-lapse images of the cremaster vascular microcirculation, which allow us to observe the process of leukocyte emigration into the surrounding tissue with increased temporal resolution in comparison to our previous confocal approach.
Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda
Authors: Kasibante John , Irfanullah Eesha , Wele Abduljewad , Okafor Elizabeth C , Ssebambulidde Kenneth , Okurut Samuel , Kagimu Enock , Gakuru Jane , Rutakingirwa Morris K , Mugabi Timothy , Nuwagira Edwin , Jjunju Samuel , Mpoza Edward , Tugume Lillian , Nsangi Laura , Musibire Abdu K , Muzoora Conrad , Rhein Joshua , Meya David B , Boulware David R , Abassi Mahsa 
Published: October 2024

Abstract
Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into &lt; 100 mg/dl (72%, n = 641) and ≥ 100 mg/dl (28%, n = 249). We described baseline clinical variables and 18-week mortality by CSF protein groups. Those with CSF protein ≥ 100 mg/dl were more likely to present with Glasgow coma scale score &lt; 15 (P &lt; .01), self-reported seizures at baseline (P = .02), higher CD4 T-cell count (P &lt; .001), and higher CSF white blood cells (P &lt; .001). Moreover, those with a baseline CSF protein ≥ 100 mg/dl also had a lower baseline CSF fungal burden (P &lt; .001) and a higher percentage of sterile CSF cultures at day 14 (P = .02). Individuals with CSF protein ≥ 100 mg/dl demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules, pro-inflammatory cytokines, T-helper cell type 1 and 17 cytokines, and immune-exhaustion marker (P &lt; .05). 18-week mortality risk in individuals with a CSF protein &lt; 100 mg/dl was 34% higher (unadjusted Hazard Ratio 1.34; 95% Confidence Interval, 1.05–1.70; P = .02) than those with CSF protein ≥ 100 mg/dl. In HIV-associated cryptococcal meningitis, individuals with baseline CSF protein ≥ 100 mg/dl more frequently presented with neurological symptoms, higher CSF inflammatory cytokines, reduced fungal burden, and lower mortality risk. The findings underscore the prognostic significance of baseline CSF protein levels in predicting disease severity and mortality risk in cryptococcal meningitis.
A correlation between sunspot observations and solar Ca ii H&K activity proxies
Authors: Ferreira R R , Gonçalves B F O , do Nascimento J -D , Castro M 
Published: October 2024

ABSTRACT
The magnetic phenomena on the solar surface have been the subject of several investigations over the last 400 yr. An early indicator of solar magnetic activity was sunspot counting. Currently, the main sunspot indicators are the international sunspot number, the sunspot group number, the total sunspot area, and the photometric sunspot index. Several improvements in observational techniques have allowed magnetic activity to be measured using solar/stellar spectra. Standard spectroscopic activity indicators are the $S_{\rm MW}$ index, based on the Ca ii H&K emission lines, and the chromospheric component $R^{\prime }_{\rm HK}$ index. In this context, we present a correlation between sunspot observations and solar Ca ii H&K activity proxies. We present our comparisons between the spectroscopic chromospheric activity proxies ($S_{\rm MW}$ and $R^{\prime }_{\rm HK}$) and the sunspot indicators over the last decades, using solar measurements (spectroscopic and spot proxy) performed on the same day. In general, our results indicate a linear fit between the chromospheric proxies and sunspot indicators. In addition, using the long-term sunspot group number records, we estimate an average spectroscopic proxy along the solar Maunder minimum (MM) phase, corresponding to $\mathinner {\langle {S_{\rm MW}}\rangle } = 0.167 \pm 0.013$ and $\mathinner {\log \langle {R^{\prime }_{\rm HK}}\rangle } = -4.913 \pm 0.363$. The estimated variability is $\sigma _{S_{\rm MW}} = 1.137 \times 10^{-7}$ and $\sigma _{\log R^{\prime }_{\rm HK}} = 2.704 \times 10^{-6}$. Our linear regression analysis, applied annually, suggests that the variability level of the chromospheric activity in the MM phase is significantly lower than in the normal period of activity and that this could be the result of linear regression on annually averaged data, combined with minimal sunspot activity during the solar MM phase. Further observations of MM analogues will be needed to test this hypothesis.
scTWAS Atlas: an integrative knowledgebase of single-cell transcriptome-wide association studies
Authors: Mai Jialin , Qian Qiheng , Gao Hao , Fan Zhuojing , Zeng Jingyao , Xiao Jingfa 
Published: October 2024

Abstract
Single-cell transcriptome-wide association studies (scTWAS) is a new method for conducting TWAS analysis at the cellular level to identify gene-trait associations with higher precision. This approach helps overcome the challenge of interpreting cell-type heterogeneity in traditional TWAS results. As the field of scTWAS rapidly advances, there is a growing need for additional database platforms to integrate this wealth of data and knowledge effectively. To address this gap, we present scTWAS Atlas (https://ngdc.cncb.ac.cn/sctwas/), a comprehensive database of scTWAS information integrating literature curation and data analysis. The current version of scTWAS Atlas amasses 2,765,211 associations encompassing 34 traits, 30 cell types, 9 cell conditions and 16,470 genes. The database features visualization tools, including an interactive knowledge graph that integrates single-cell expression quantitative trait loci (sc-eQTL) and scTWAS associations to build a multi-omics level regulatory network at the cellular level. Additionally, scTWAS Atlas facilitates cross-cell-type analysis, highlighting cell-type-specific and shared TWAS genes. The database is designed with user-friendly interfaces and allows for easy browsing, searching, and downloading of relevant information. Overall, scTWAS Atlas is instrumental in exploring the genetic regulatory mechanisms at the cellular level and shedding light on the role of various cell types in biological processes, offering novel insights for human health research.
Magnesium and boron isotope evidence for the generation of arc magma through serpentinite-mélange melting
Authors: Qiao Xin-Yue , Xiong Jia-Wei , Chen Yi-Xiang , De Hoog Jan C M , Pearce Julian , Huang Fang , Zhao Zi-Fu , Chen Kun 
Published: October 2024

ABSTRACT
Serpentinites play a crucial role in mass transport and volatile recycling in subduction zones, yet the mechanism for their contribution to the formation of arc magma remains elusive. Here, we investigate this issue by examining the magnesium (Mg) and boron (B) isotope compositions of volcanic rocks and forearc serpentinites from the South Sandwich Island arc. The volcanic rocks display δ26Mg values ranging from −0.25‰ to −0.06‰ and δ11B values ranging from +9.6‰ to +16.5‰, while the forearc serpentinites exhibit δ26Mg values of −0.21‰ to −0.02‰ and δ11B values of +5.2‰ to +9.8‰. Given the substantial contrast in both Mg and B contents between mantle rocks and fluids, the combined heavy Mg–B isotope compositions of volcanic rocks pose a challenge to traditional arc formation models, i.e. flux melting of depleted subarc mantle metasomatized by slab-derived fluids. Although an alternative model involving flux melting of dehydrated serpentinites can partly account for the heavy Mg isotope compositions of arc magmas, it is difficult to simultaneously explain the B isotope and trace-element compositions. Instead, these distinct compositions can be adequately explained by partial melting of a serpentinite-dominated mélange beneath the volcanic arc. Given that arc magmas exhibiting coupled heavy Mg–B isotope compositions are increasingly reported, we propose that serpentinite-mélange melting represents an effective and geochemically self-consistent mechanism for transferring signatures of subducted slabs to the overlying mantle source. This process can be significant in subduction zones with prominent forearc mantle erosion or those involving considerable amounts of slab-hosted serpentinite.
Real-world outcomes in patients with brain metastases secondary to HR+/HER2− MBC treated with abemaciclib and local intracranial therapy
Authors: Gathirua-Mwangi Wambui , Martin Holly , He Dan , Zheng Shen , Sheffield Kristin M , John Jincy , Yamazawa Erika , Rybowski Sarah , Brastianos Priscilla K 
Published: October 2024

Abstract

Background
Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2−) MBC with brain metastases diagnosis before abemaciclib initiation.

Patients and Methods
A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2− MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date).

Results
Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively.

Conclusion
In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.
The effect of π-spacer on D-A'-π-a system organic dyes for dye-sensitized solar cells (DSSCs) technology: a computational approach”
Authors: Sanama Michael Kennedy , Abubakari Ismail , Numbury Surendra Babu 
Published: October 2024

Abstract
The globe is consuming more energy as a result of population growth and economic development. One of the most important forms of renewable energy for human usage is solar energy. By modifying the π-spacers, four D-A'-π-A of novel organic dye molecules (D1–D4) have been created in this study. To evaluate the optoelectronic capabilities and photovoltaic qualities of four D-A'-π-A new organic dyes created molecules, density functional theory (DFT) and time-dependent DFT (TD-DFT) theory methodologies through the B3LYP and 6-311G basis set have been employed. To ascertain the effect of developed π-spacer on enhancing intramolecular charge transfer (ICT) and enhancing light-absorbing capacities, a number of crucial factors, including molecular geometry, energy bandgap and light-harvesting efficiency (LHE), have been studied. Based on the available data, D4 outperforms the other four developed organic dye molecules, with energy bandgap of 1.4896 and 1.4253 eV for gas and solvent phase, respectively, regeneration driving forces (ΔGreg) of 0.0469 and 0.0300 eV for the gas phase and solvent phase, respectively, and open-circuit voltages (Voc) of 0.6427 and 0.5953 eV for the gas phase and solvent phase, respectively. Additionally, the maximum absorption wavelengths (λmax) for the gas phase and solvent phase are 932.03 and 1013.81 nm, respectively. Consequently, it was found that the D4 dye molecule was a more promising option for the use of dye-sensitized solar cells (DSSCs) technology hence advised for more practical research to provide efficient advancements in the D-A'-π-A system organic dye for the production of sustainable energy.
Impaired sleep-dependent memory consolidation in pediatric narcolepsy type 1
Authors: Maski Kiran , Heckler Gillian , Worhach Jennifer , Mylonas Dimitrios , Wang Grace , Szilagyi Klara , Zhang Bo , Diniz Behn Cecilia , Scammell Thomas E , Stickgold Robert 
Published: October 2024

Abstract

Study Objectives
Disrupted nighttime sleep is common in pediatric narcolepsy type 1, yet its cognitive impact is unknown. As N2 sleep spindles are necessary for sleep-dependent memory consolidation, we hypothesized that narcolepsy type 1 impairs memory consolidation via N2 sleep fragmentation and N2 sleep spindle alterations.

Methods
We trained 28 pediatric narcolepsy type 1 participants and 27 healthy controls (HCs) on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. We extracted wake and sleep stage bout numbers and N2 spindle characteristics from the polysomnogram and conducted mixed model analysis of sleep-dependent memory consolidation to identify group differences.

Results
Narcolepsy type 1 participants had shorter N2 bout durations and associated shorter N2 spindles versus HC, but other N2 spindle features were similar. Narcolepsy type 1 participants had worse memory performance postsleep than HCs after adjusting for age and gender (mean memory consolidation HC: −3.1% ± 18.7, NT1: −15.6 ± 24.8, main effect group × time of testing F = 5.3, p = .03). We did not find significant relationships between sleep-dependent memory consolidation and N2 spindle characteristics. Notably, increased N1% was associated with worse sleep-dependent memory consolidation with results driven by the narcolepsy type 1 group.

Conclusions
Sleep-dependent memory consolidation is mildly impaired in youth with narcolepsy type 1 and findings may be attributed to increases in N1 sleep. Further studies are needed to determine if these findings are generalizable and reversible with sleep-based therapies.