bluuebunny/crossref_metadata_2025_split huggingface dataset:
P26.14.B VITAMIN D3 ENHANCES TEMOZOLOMIDE EFFICACY IN GLIOBLASTOMA CELLS WHILE PROTECTING NORMAL ASTROCYTES: INVESTIGATING THE EFFECTS OF ADJUNCTIVE THERAPY
Authors: Morelli M , Di Lorenzo F , Nannipieri F , Trasciatti S , Di Stefano A , Lessi F , Mazzanti C 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GB), the most aggressive brain tumor, poses challenges due to resistance to temozolomide (TMZ) and radiotherapy. Regorafenib (REGO) is used as second-line treatment for recurrences. Recent studies suggest potential benefits of using vitamin D, particularly cholecalciferol (VitD3), as adjunctive therapy in GB treatment, showing anti-proliferative effects and enhanced drug effectiveness. However, differences in the mechanisms of action between VitD3 and its active form, 1,25(OH)D3, require further investigation.

MATERIAL AND METHODS
Three commercial GB cell lines (U118, T98G, U87), and normal Human Brain Astrocytes (HBA) were treated for 48 hours with VitD3 and 1,25(OH)D3 at concentrations of 0, 3, 30, and 300 µM, and 0, 1, 10, and 100 nM, respectively along with TMZ and REGO at concentrations of 0, 10, 100, and 500 µM, and 0, 10, 20, 50 µM, respectively. Additionally, REGO with or without VitD3 was tested on tissue-derived primary cell cultures. Cellular responses to treatments in terms of cell proliferation were assessed using WST-1 and Crystal Violet assays.

RESULTS
VitD3 significantly reduced cell viability and proliferation in commercial tumor cell lines but not in healthy cell lines. Moreover, treatment with 10 and 100 µM of TMZ along with VitD3 resulted in an additional decrease in cell proliferation in commercial cell lines but not in healthy HBA. Conversely, REGO treatment did not further reduce proliferation with increasing VitD3 concentrations in tumor cell lines, HBA, or primary cultures. It is noteworthy that primary cultures exhibited greater resistance to REGO and/or VitD3 treatment compared to commercial cell lines. At all tested concentrations, 1,25(OH)D3 did not significantly reduce proliferation, either alone or with TMZ.

CONCLUSION
VitD3 unexpectedly enhances TMZ toxicity in tumor cell lines and may have a protective effect on healthy astrocytes in the presence of TMZ, suggesting potential as adjunctive therapy with existing TMZ chemotherapy, pending further understanding of the underlying molecular mechanisms. The efficacy of its active form requires testing at higher concentrations.
P27.27.A TUMOR TREATING FIELDS (TTFIELDS) THERAPY IN PATIENTS WITH GLIOBLASTOMA: LONG-TERM SURVIVAL RESULTS FROM TTFIELDS IN GERMANY IN ROUTINE CLINICAL CARE (TIGER) STUDY
Authors: Bähr O , Tabatabai G , Fietkau R , Goldbrunner R , Glas M 
Published: October 2024

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) therapy has demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) when applied with adjuvant temozolomide (TMZ) compared to TMZ alone in newly diagnosed glioblastoma (ndGBM). TTFields therapy delivers electric fields, through scalp-placed arrays, that disrupt cellular processes critical for cancer cell viability, is CE marked for WHO grade 4 glioma, and is a recommended treatment regimen for ndGBM. TTFields therapy was administered to &gt;25,000 patients, showing no systemic toxicities and mild to moderate skin reactions being the main therapy-related adverse event. Here, we report survival and safety data from the TIGER study, the largest prospective study investigating real-world use of TTFields therapy during routine clinical care in patients with ndGBM in Germany.

MATERIAL AND METHODS
TIGER (NCT03258021), a prospective, non-interventional, multicenter, medical device study, screened patients ≥18 years of age with histologically confirmed ndGMB from August 2017 to November 2019 in 81 participating centers in Germany who had clinical indication for TTFields therapy and were within the first 3 cycles of maintenance chemotherapy treatment. The analysis presented here focuses on patients that accepted TTFields therapy. Endpoints included OS, PFS, safety, and quality of life.

RESULTS
In this study, 710 assessed patients agreed to participate, with 583 (82%) opting for TTFields therapy, and 429 actually commencing the treatment. This patient population represents typical GBM patients, with a median age of 58 (range 19-82) and 64.1% being male. After a total follow-up of 56.2 months, the median OS and PFS were 19.6 months (95% CI, 17.9-22.4) and 10.2 months (95% CI, 9.4-11.4), respectively. The corresponding 1, 2, 3, and 4-year OS rates stood at 79.2%, 42.4%, 31.5%, and 27.7%, while the PFS rates were 42.0%, 23.2%, 19.9%, and 17.6%, respectively. Serious AEs were observed in 68% of patients, with only 0.5% being attributed to TTFields therapy.

CONCLUSION
TIGER is the largest prospective study to date on routine clinical practice in ndGBM. It reaffirms TTFields therapy’s positive safety profile, and its OS and PFS survival benefits are consistent with prior reports. It also reveals promising long-term survival rates.
Primary purulent bacterial pericarditis due to Streptococcus intermedius in the absence of an esophago-pericardial fistula
Authors: Patel Sahil M , Venkatesan Varshini , Simon Elaine , Hull Stephen 
Published: October 2024

Abstract
Purulent bacterial pericarditis is a rare and progressive infection with a high mortality. It is rarely due to Streptococcus intermedius, a commensal bacteria found in the oral cavity, gastrointestinal tract, and the genitourinary tract. Here we present a 71-year-old man with history of esophageal adenocarcinoma, status post distal esophagectomy and proximal gastrectomy 2 years prior, who developed cardiac tamponade secondary to primary S. intermedius purulent bacterial pericarditis in the absence of an esophago-pericardial fistula. We discuss the clinical manifestations of bacterial pericarditis and pericardial effusions, useful diagnostic tools, and explore possible mechanisms for S. intermedius pericarditis infection. This case highlights the importance of prompt suspicion, recognition, and intervention for bacterial pericarditis and cardiac tamponade in the setting of recent esophageal instrumentation. In addition, despite being rare, S. intermedius should be recognized as a possible pathogen in purulent bacterial pericarditis even with the absence of an esophago-pericardial fistula.
Palbociclib plus aromatase inhibitors in patients with metastatic breast cancer and cardiovascular diseases: real-world effectiveness
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Chen Connie , Makari Doris , Layman Rachel M , Rugo Hope S 
Published: October 2024

Abstract

Background
Patients with cardiovascular disease (CVD) comorbidities are often excluded from participating in breast cancer clinical trials. Consequently, data to inform treatment decisions for patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer (mBC) and CVD are limited.

Objective
We compared the effectiveness of first-line palbociclib plus an aromatase inhibitor (AI) vs an AI alone and evaluated palbociclib treatment patterns in patients with HR+/HER2− mBC and CVD in routine clinical practice.

Methods
Data from the Flatiron Health Analytic Database were captured for patients with HR+/HER2− mBC and CVD who initiated first-line treatment with palbociclib plus an AI or an AI alone between February 2015 and March 2020 (data cutoff: September 30, 2020). Overall survival (OS), real-world progression-free survival (PFS), and treatment patterns were evaluated.

Results
Of the 469 patients with identifiable CVD, 160 received palbociclib plus an AI, and 309 received an AI alone. After stabilized inverse probability treatment weighting, both median OS (40.7 vs 26.5 months; hazard ratio [HR], 0.732 [95% CI, 0.537-0.997]; P = .048) and median real-world PFS (20.0 vs 12.5 months; HR, 0.679 [95% CI, 0.512-0.900]; P = .007) were significantly prolonged in patients treated with palbociclib plus an AI vs an AI alone. Among patients with a documented palbociclib starting dose, 78.5% started palbociclib at 125 mg/day, and 38.6% experienced dose adjustment.

Conclusions
In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2– mBC and CVD.

Trial Registration
NCT05361655 (ClinicalTrials.gov)
Climate action on the mind: a longitudinal study of Americans’ psychosocial drivers of high-impact climate behaviors
Authors: Rakhimov Rakhim , Aweko Scovia , Thulin Erik 
Published: October 2024

Abstract
Widespread adoption of high-impact climate-positive behaviors can significantly reduce greenhouse gas emissions. To motivate these behaviors, social scientists and policymakers need to understand people’s psychological and social (psychosocial) factors to create an environment that encourages widespread adoption. Past longitudinal survey research has focused on tracking changes in broad climate change beliefs and attitudes, risk perceptions, and climate policy support. While behavioral and psychological research has identified key beliefs and attitudes as enabling conditions, this work tends to study a single snapshot in time, often in a narrow population, not allowing for the identification of trends. In the present paper, we launch the annual Climate Action on the Mind (CAM) longitudinal survey, which aims to track key psychosocial factors shown to be important enablers of climate behaviors. Our work focuses on behaviors relevant to households in the United States, such as installing solar panels and driving an electric vehicle. The paper introduces the first two waves of the CAM survey from December 2021 (n = 2031) and June 2023 (n = 1528), quota-matched to represent the US adult population on key demographics. Our research offers novel insights into how the enabling psychological conditions for high-impact climate-positive behaviors are shifting in the United States, helping to inform the development of future communication strategies, interventions, and climate policy.
Stomatal closure as a driver of minimum leaf conductance declines at high temperature and vapor pressure deficit in Quercus
Authors: Zailaa Joseph , Scoffoni Christine , Brodersen Craig R 
Published: October 2024

Abstract
Rising global temperatures and vapor pressure deficits (VPDs) are increasing plant water demand and becoming major drivers of large-scale plant mortality. Controlling transient leaf water loss after stomatal closure (minimum stomatal conductance [gmin]) is recognized as a key trait determining how long plants survive during soil drought. Yet, substantial uncertainty remains regarding how gmin responds to elevated temperatures and VPD and the underlying mechanisms. We measured gmin in 24 Quercus species from temperate and Mediterranean climates to determine whether gmin was sensitive to a coupled temperature and VPD increase. We also explored mechanistic links to phenology, climate, evolutionary history, and leaf anatomy. We found that gmin in all species exhibited a nonlinear negative temperature and VPD dependence. At 25 °C (VPD = 2.2 kPa), gmin varied from 1.19 to 8.09 mmol m−2 s−1 across species but converged to 0.57 ± 0.06 mmol m−2 s−1 at 45 °C (VPD = 6.6 kPa). In a subset of species, the effect of temperature and VPD on gmin was reversible and linked to the degree of stomatal closure, which was greater at 45 °C than at 25 °C. Our results show that gmin is dependent on temperature and VPD, is highly conserved in Quercus species, and is linked to leaf anatomy and stomatal behavior.
Art for health’s sake or health for art’s sake: Disentangling the bidirectional relationships between arts engagement and mental health
Authors: Mak Hei Wan , Hu Yang , Bu Feifei , Bone Jessica K , Fancourt Daisy 
Published: October 2024

Abstract
Increasing evidence links arts engagement with mental health, but the directionality of the link remains unclear. Applying a novel approach to causal inference, we used nonrecursive instrumental variable models to analyze two waves of data from the United Kingdom Household Longitudinal Study (n = 17,927). Our findings reveal bidirectional causal relationships between arts engagement (arts participation, cultural attendance, and heritage visits) and mental health (GHQ-12 mental distress and SF-12 Mental Component Summary mental well-being). After adjusting for time 1 measures and identifying confounders, cultural attendance and heritage visits were reciprocally associated with mental distress and mental well-being, while arts participation was only reciprocally associated with mental well-being. The bidirectional effects between arts engagement and mental health are modest but clearly demonstrated not only from mental health to arts but also from arts to mental health. Our findings indicate that previous evidence of an association between arts engagement and mental health is due to bidirectional causal effects. Interventions that boost arts participation, cultural attendance, and heritage visits may help break the negative feedback loop and enhance mental health.
A beautiful face is good when we’re judged by others, a moral character is better
Authors: Baum Julia , Abdel Rahman Rasha 
Published: October 2024

Abstract
Moral beauty, reflected in one’s actions, and facial beauty both affect how we’re judged. Here, we investigated how moral and facial beauty interactively affect social judgments and emotional responses, employing event-related brain potentials. Participants (all female) associated positive, neutral, or negative verbal information with faces scoring high or low on attractiveness and performed ratings of the faces as manipulation checks. In a separate test phase, the faces were presented again, and participants made valenced social judgments of the persons. Results show a dominance of moral beauty in valenced social judgments as well as ERPs related to reflexive and evaluative emotional responses (early posterior negativity, EPN, late positive potential, LPP), whereas facial attractiveness mattered little. In contrast, facial attractiveness affected visual processing (N170). Similarly, relatively shallow impressions of attractiveness and likability that require no knowledge about the person were influenced by both facial attractiveness and social-emotional information. This pattern of dominant effects of social-emotional information regardless of attractiveness shows that when it comes to our emotional responses and social judgments, moral beauty is what matters most, even in the face of physical beauty.
Disgust-specific impairment of facial emotion recognition in Parkinson’s disease patients with mild cognitive impairment
Authors: Chiang Ke-Wei , Tan Chun-Hsiang , Hong Wei-Pin , Yu Rwei-Ling 
Published: October 2024

Abstract
This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson’s disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing “disgust,” compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and “disgust” FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing “disgust” and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.
Adaptation of a sleep hygiene intervention for individuals with poor sleep and their companions: Results of a randomized controlled pilot trial
Authors: Mindlis Irina , Millar Brett M , Chkhaidze Ana , Fernández Sedano Brandon , Noel Jovanka , Revenson Tracey A 
Published: October 2024

Abstract
Sleep is a major health issue for young adults. While sleep hygiene interventions have small-to-moderate effects, better outcomes might be achieved by delivering interventions individually to those reporting sleep difficulties, or in the presence of a supportive other or companion. To examine the feasibility, acceptability, and initial effects of an adapted sleep hygiene intervention for young adults with poor sleep, we conducted an ORBIT Phase IIb pilot randomized controlled trial (n = 51). Young adults with poor sleep were randomized to receive a sleep hygiene intervention individually or with a companion. Sleep patterns were measured at baseline and 4 weeks. Participants completed daily dairies and wore wearable devices for the month following the intervention. Attrition at follow-up was minimal (3.9%), and missing rates were low for diary data (8%), and in line with prior studies for wearable devices (14%). Participants expressed high levels of satisfaction with the study, with no differences between study arms. Significant effects were found postintervention for all participants, indicating improved sleep quality (t = 6.14, P &lt; .001), greater sleep duration (t = 3.8, P &lt; .001), and reduced daytime sleepiness (t = 2.13, P = .039). There were no significant differences in sleep efficiency pre and postintervention, or between study arms for any sleep outcome based on self-reported and objective data. Results from this pilot provide evidence for the feasibility and acceptability of a sleep hygiene intervention for young adults and lay the groundwork for a larger, fully powered study.
Investigating the existence of an osmotic barrier between xylem fibers and vessels in sugar maple (Acer saccharum) using microCT
Authors: Robinson James A , Rennie Matt , Clearwater Mike J , Holland Daniel J , van den Berg Abby , Watson Matthew J 
Published: October 2024

Abstract
Sugar maples (Acer saccharum Marshall) develop elevated stem pressures in springtime through the compression and expansion of gas bubbles present within xylem fibers. The stability of this gas within the fibers is hypothesized to be due to the elevated sugar concentration of maple sap and the presence of an osmotic barrier between fibers and vessels. Without this osmotic barrier, gas bubbles are predicted to dissolve rapidly. In this work, we investigated the existence of this osmotic barrier. We quantified the fraction of the xylem occupied by gas-filled fibers using synchrotron-based microCT. After imaging fresh stem segments, we perfused them with either a 2% sucrose solution or water, imaging again following perfusion. In this way we directly observed how total gas present in the fibers changed when an osmotic pressure difference should be present, with the 2% sucrose solution, and when it is absent, with the water. Following a first round of perfusion, we perfused stem segments with the other perfusate, repeating this multiple times to observe how switching perfusates affected gas-filled fibers. We found that perfusing stem segments with water resulted in a significant reduction in the xylem fiber gas, but perfusing stem segments with a sucrose solution did not significantly reduce the gas in the fibers. These results support the hypothesis that an osmotic barrier exists between fibers and vessels.
Photosynthetic temperature responses in leaves and canopies: why temperature optima may disagree at different scales
Authors: Kumarathunge Dushan P , Medlyn Belinda E , Drake John E , De Kauwe Martin G , Tjoelker Mark G , Aspinwall Michael J , Barton Craig V M , Campany Courtney E , Crous Kristine Y , Yang Jinyan , Jiang Mingkai 
Published: October 2024

Abstract
Understanding how canopy-scale photosynthesis responds to temperature is of paramount importance for realistic prediction of the likely impact of climate change on forest growth. The effects of temperature on leaf-scale photosynthesis have been extensively documented but data demonstrating the temperature response of canopy-scale photosynthesis are relatively rare, and the mechanisms that determine the response are not well quantified. Here, we compared leaf- and canopy-scale photosynthesis responses to temperature measured in a whole-tree chamber experiment and tested mechanisms that could explain the difference between leaf and crown scale temperature optima for photosynthesis. We hypothesized that (i) there is a large contribution of non-light saturated leaves to total crown photosynthesis, (ii) photosynthetic component processes vary vertically through the canopy following the gradient in incident light and (iii) seasonal temperature acclimation of photosynthetic biochemistry has a significant role in determining the overall temperature response of canopy photosynthesis. We tested these hypotheses using three models of canopy radiation interception and photosynthesis parameterized with leaf-level physiological data and estimates of canopy leaf area. Our results identified the influence of non-light saturated leaves as a key determinant of the lower temperature optimum of canopy photosynthesis, which reduced the temperature optimum of canopy photosynthesis by 6–8 °C compared with the leaf scale. Further, we demonstrate the importance of accounting for within-canopy variation and seasonal temperature acclimation of photosynthetic biochemistry in determining the magnitude of canopy photosynthesis. Overall, our study identifies key processes that need to be incorporated in terrestrial biosphere models to accurately predict temperature responses of whole-tree photosynthesis.
Long-read transcriptomics of Ostreid herpesvirus 1 uncovers a conserved expression strategy for the capsid maturation module and pinpoints a mechanism for evasion of the ADAR-based antiviral defence
Authors: Rosani Umberto , Bortoletto Enrico , Zhang Xiang , Huang Bo-Wen , Xin Lu-Sheng , Krupovic Mart , Bai Chang-Ming 
Published: October 2024

Abstract
Ostreid herpesvirus 1 (OsHV-1), a member of the family Malacoherpesviridae (order Herpesvirales), is a major pathogen of bivalves. However, the molecular details of the malacoherpesvirus infection cycle and its overall similarity to the replication of mammalian herpesviruses (family Orthoherpesviridae) remain obscure. Here, to gain insights into the OsHV-1 biology, we performed long-read sequencing of infected blood clams, Anadara broughtonii, which yielded over one million OsHV-1 long reads. These data enabled the annotation of the viral genome with 78 gene units and 274 transcripts, of which 67 were polycistronic mRNAs, 35 ncRNAs, and 20 natural antisense transcripts (NATs). Transcriptomics and proteomics data indicate preferential transcription and independent translation of the capsid scaffold protein as an OsHV-1 capsid maturation protease isoform. The conservation of this transcriptional architecture across Herpesvirales likely indicates its functional importance and ancient origin. Moreover, we traced RNA editing events using short-read sequencing and supported the presence of inosine nucleotides in native OsHV-1 RNA, consistent with the activity of adenosine deaminase acting on dsRNA 1 (ADAR1). Our data suggest that, whereas RNA hyper-editing is concentrated in specific regions of the OsHV-1 genome, single-nucleotide editing is more dispersed along the OsHV-1 transcripts. In conclusion, we reveal the existence of conserved pan-Herpesvirales transcriptomic architecture of the capsid maturation module and uncover a transcription-based viral counter defence mechanism, which presumably facilitates the evasion of the host ADAR antiviral system.