bluuebunny/crossref_metadata_2025 huggingface dataset:
Optogenetic quantification of cardiac excitability and electrical coupling in intact hearts to explain cardiac arrhythmia initiation
Authors: Langen Judith S. , Boyle Patrick M. , Malan Daniela , Sasse Philipp
Published: February 2025

Increased cardiac excitability and reduced electrical coupling promote cardiac arrhythmia and can be quantified by input resistance (
R
m
), pacing threshold (
I
thr
), and cardiac space constant (λ). However, their measurement in the heart was not feasible because the required homogenous current injection cannot be performed with electrical stimulation. We overcame this problem by optogenetic current injection into all illuminated cardiomyocytes of mouse hearts in different action potential phases. Precisely triggered and patterned illumination enabled measuring
R
m
and λ, which both were smallest at diastole. Pharmacological and depolarization-induced reduction of inwardly rectifying K
+
currents (
I
K1
), gap junction block, and cardiac infarction reduced
I
thr
, showing the importance of high
I
K1
density and intact cardiomyocyte coupling for preventing arrhythmia initiation. Combining optogenetic current injection and computer simulations was used to classify pro- and anti-arrhythmic mechanisms based on their effects on
R
m
and
I
thr
and allowed to quantify
I
K1
inward rectification in the intact heart, identifying reduced
I
K1
rectification as anti-arrhythmic concept.
Atomic to nanoscale chemical fluctuations: The catalyst for enhanced thermoelectric performance in high-entropy materials
Authors: Wang Jingyi , Gao Haotian , Zhao Kunpeng , Wuliji Hexige , Zhao Binru , Ma Jie , Chen Xingyu , Zhang Jiawei , Sui Yanping , Wei Tian-Ran , Zhu Min , Shi Xun
Published: February 2025

High-entropy materials have expanded the frontier for discovering uncharted physicochemical properties. The phenomenon of chemical fluctuation is ubiquitous in high-entropy materials, yet its role in the thermoelectric field is often overlooked. Herein, we designed and synthesized a series of (Mg

0.94−
n

Yb
0.26
Sr
0.26
Zn

m

)(Mg

n

Cd
0.69
Zn

0.69−
m

Na

x

)(Sb
1.74
Ca
0.26
) samples characterized by ultrahigh configurational entropy. These samples exhibit a homogeneous single-phase structure at macroscopic and microscopic scales, yet display notable chemical fluctuations at the atomic to nanoscale. These fluctuations, along with the unusual atomic occupations, lead to an exceptionally low lattice thermal conductivity akin to that of amorphous materials. Combining the optimized carrier concentration and well-maintained carrier mobility, we ultimately achieved a high
zT
value of 1.2 at 750 kelvin, outperforming most previously reported AB
2
Sb
2
-type Zintls. This study underscores that the atomic to nanoscale chemical fluctuations are the crucial catalyst for the enhanced thermoelectric performance in high-entropy materials.
MSB2-activated pheromone pathway regulates fungal plasma membrane integrity in response to herbicide adjuvant
Authors: Pu Jianwei , Long Xiuju , Li Yifan , Zhang Jian , Qi Fei , Gao Jiangtao , Shen Qirong , Yu Zhenzhong
Published: February 2025

Glyphosate-based herbicides (GBHs) are used worldwide for weed management. However, GBHs pose a threat to soil fungal community, although fungi can degrade and use glyphosate as a nutrient source. How fungi respond to GBHs remains enigmatic. Here, we found that, not as in plants, the commercial GBH Roundup does not target the 5-enolpyruvyl-shikimate-3-phosphate synthase in the soil-derived fungus
Trichoderma guizhouense
, whereas it impairs fungal growth. We demonstrate that the herbicide adjuvant Triton CG-110 is more toxic to fungal cells than pure glyphosate. It limits nitrogen uptake, which induces the expression of proteinase YPS1 to catalyze the shedding of the MSB2 extracellular domain from the plasma membrane, leading to the activation of the MAPK TMK1 pheromone pathway. The downstream B2H2-type transcription factor STE12 directly regulates ergosterol biosynthesis, affecting membrane fluidity and stability. To our knowledge, this is the first evidence that the pheromone pathway is implicated in ergosterol biosynthesis and plasma membrane integrity.
Increased levels of lagging strand polymerase α in an adult stem cell lineage affect replication-coupled histone incorporation
Authors: Davis Brendon E. M. , Snedeker Jonathan , Ranjan Rajesh , Wooten Matthew , Barton Savannah Sáde , Blundon Joshua , Chen Xin
Published: February 2025

Stem cells display asymmetric histone inheritance, while nonstem progenitor cells exhibit symmetric patterns in the
Drosophila
male germ line. Here, we report that components involved in lagging strand synthesis, DNA polymerases α and δ, have substantially reduced levels in stem cells compared to progenitor cells, and this promotes local asymmetry of parental histone incorporation at the replication fork. Compromising Polα genetically induces the local replication-coupled histone incorporation pattern in progenitor cells to resemble that in stem cells, seen by both nuclear localization patterns and chromatin fibers. This is recapitulated using a Polα inhibitor in a concentration-dependent manner. The local old versus new histone asymmetry is comparable between stem cells and progenitor cells at both S phase and M phase. Together, these results indicate that developmentally programmed expression of key DNA replication components is important to shape stem cell chromatin. Furthermore, manipulating one crucial DNA replication component can induce replication-coupled histone dynamics in nonstem cells to resemble those in stem cells.
Heterogeneous crustal sources and recycling for silicic magmas in a Neoproterozoic continental arc in the western Yangtze block, South China
Authors: Zhu Yu , Lai Shao-cong , Zhu Ren-zhi , Liu Min , Zhang Fang-yi , Qin Jiang-feng , Yang Hang
Published: February 2025

Identifying the source characteristics of silicic magmas (SiO2 >65 wt%) is significant for revealing the nature of the crust and recycling processes under a continental arc zone. Herein, we present a comprehensive dataset of zircon U-Pb-Hf-O isotopes and whole-rock major and trace elements as well as Nd isotopes for two groups of Neoproterozoic silicic volcanic magmas from the Mianning area in the western Yangtze block (South China), in order to place systematic constraints on the heterogeneous crustal sources as well as crustal reworking and recycling processes of a Neoproterozoic continental magmatic arc during the evolution of the supercontinent Rodinia. The studied dacites and rhyolites, dated at ca. 815−811 Ma, are generally characterized by high SiO2 (66.87−80.02 wt%) but low MgO (0.11−0.81 wt%), Mg# (8.94−30.0), Cr (0.50−4.54 ppm), and Ni (1.10−4.98 ppm) contents, enriched light rare earth elements (LREEs) and large ion lithophile elements (LILEs; e.g., Rb, K), and depleted high field strength elements (HFSEs; e.g., Nb, Ta, Ti, and P), implying a source with continental crust affinity. Considering the contrasting whole-rock Nd and zircon Hf-O isotopic characteristics, these silicic volcanic rocks can be divided into two groups that originated from heterogeneous crustal sources. Group 1 dacites display relatively depleted whole-rock Nd (εNd[t] = +0.51 to +1.65) and zircon Hf (εHf[t] = +1.80 to +8.86) isotopes as well as submantle zircon O isotopes (δ18O = 3.95‰−4.63‰), and therefore, they were likely formed by recent melting of juvenile mafic arc lower crust, which was supplemented by mantle wedge melts metasomatized by predominantly subducted slab melts. Group 2 dacites and rhyolites have negative whole-rock εNd(t) (−4.05 to −2.12), low and variable zircon εHf(t) (−2.84 to +3.44), and highly variable zircon δ18O values (4.50‰−9.90‰), which could be derived from a relatively ancient and enriched crustal source heated by melts from juvenile lower crust or metasomatized mantle. We propose that the silicic volcanics in this study represent the simultaneous crustal melting of different magmatic reservoirs under a continental arc zone, which are responsible for the petrological and geochemical diversities of these Neoproterozoic silicic magmas. In combination with a compilation of previous data from nearby Neoproterozoic silicic igneous rocks, the diverse silicic magmas showing distinct Nd-Hf-O isotopes can be regarded as the products of primarily crustal reworking and recycling from heterogeneous crust-derived components (i.e., juvenile and ancient/evolved crust sources), and therefore, they preserve comprehensive information about crustal differentiation and enrichment in a continental arc setting.
Exploring B-meson properties using relativistic independent quarks
Authors: Behera S. , Panda S.
Published: February 2025

In this paper, we examine the radially excited states of B-mesons: [Formula: see text] and [Formula: see text]-mesons. Our investigation uses the relativistic independent quark model, which relies on a flavor-independent average potential expressed in the scalar and vector square root form. We make phenomenological fit the potential model parameters, [Formula: see text] [Formula: see text]GeV, [Formula: see text] [Formula: see text]GeV for calculation of 1S state of B-mesons: [Formula: see text] (5.329[Formula: see text]GeV), [Formula: see text] [Formula: see text], which aligns well with theoretical and experimental data. For higher radially excited states (2S, 3S, 4S, 5S), we adjust [Formula: see text] [Formula: see text]GeV while keeping “a” fixed, yielding results consistent with other theoretical models. With these parameters, we compute the pseudoscalar and vector meson decay constants, magnetic transition rates, non-leptonic decay widths, branching fractions, rare decay widths, and semileptonic decay widths and branching fractions of the B-mesons. Our findings show reasonable agreement with lattice QCD calculations, experimental results and other theoretical predictions. For instance, our predicted radiative decay width for [Formula: see text] (1S) [Formula: see text] [Formula: see text](1S)[Formula: see text], sensitive to the [Formula: see text] and [Formula: see text], mass difference, can aid in experimentally determining the [Formula: see text], mass. Predicted non-leptonic branching fractions, such as [Formula: see text] [Formula: see text] and [Formula: see text], align with PDG values of [Formula: see text] and [Formula: see text]. Additionally, we calculate the dileptonic decays of [Formula: see text] and [Formula: see text], which agrees with CMS, LHCb and PDG results. Our semileptonic decays of [Formula: see text] and [Formula: see text] mesons are computed and compared with PDG results. Furthermore, the results obtained for mass difference, [Formula: see text] and [Formula: see text], mixing parameters, [Formula: see text] and [Formula: see text], [Formula: see text] (0.1866 and 0.4993) of [Formula: see text] and [Formula: see text] oscillations, shows good agreement with PDG data, validating our model.
Isolated and group environment dependence of stellar mass and different star formation rates
Authors: Privatus Pius , Goswami Umananda Dev
Published: February 2025

In this study, we explored the impact of isolated and group environments on stellar mass, star formation rate (SFR), and specific star formation rate (SSFR) using the catalog of group and cluster extracted from the Sloan Digital Sky Survey Data Release 12 (SDSS DR12) for [Formula: see text]. To mitigate the Malmquist bias, we partitioned the entire dataset into eighteen subsamples with a redshift bin size of [Formula: see text] and examined the environmental dependencies of these properties within each redshift bin. A strong correlation between environment, stellar mass, SFR, and SSFR was observed across nearly all redshift bins where by the relation is much stronger at lower redshift than higher redshift. The proportional of isolated and group galaxies within the bins was observed to vary with redshift where in the lower redshift bins [Formula: see text], the proportion of galaxies within the group environment exceeded that within the isolated environment. On the other hand, in the higher redshift bins [Formula: see text], the isolated environment’s galaxy fraction was found to be higher than that of the group environment. For the intermediate redshift bins [Formula: see text], an approximately equal proportion of galaxies was observed in both isolated and group environments.
Anisotropic models in magnetized Bianchi Type-III spacetimes via noether symmetries
Authors: Shair-a-Yazdan  , Iqbal Muhammad Jawed , Hickman Mark
Published: February 2025

This research paper is two-fold. In the first part, we study Noether and Killing symmetries in Bianchi Type-III spacetimes, along with the associated conservation laws. The study uses the Maple RIFSIMP package to transform a set of nonlinear differential equations into a simpler form called the reduced involutive form (RIF). This method generates a RIF tree, where each branch is solved to find the explicit forms of Noether symmetries. We also examine the Noether symmetry related to homothety and analyze this symmetry separately within each group. In the second part, we investigate the behavior of an anisotropic fluid under the influence of a magnetic field, which is assumed to be aligned along the z-axis. The anisotropic fluid model is consistent with the inherent anisotropy of Bianchi Type-III, which may be amplified by the presence of the magnetic field. We also study how this magnetic field affects the fluid’s physical properties and explore the conditions under which the fluid may approach isotropy.
Major and trace element geochemistry and 3.0 Ga Sm-Nd age for the gabbro-norite-anorthosite cumulates of the Mayurbhanj Complex (eastern India): Petrogenesis and implications for sulfide and Fe-Ti oxide mineralization
Authors: Bhattacharjee Chirasree , Mondal Sisir K. , Reisberg Laurie
Published: February 2025

The Archean Mayurbhanj Mafic Complex of the Singhbhum Craton in eastern India consists of a suite of gabbro-norite-anorthositic rocks with magnetitite ore bodies in the upper part. Petrography and whole-rock loss on ignition (LOI) values of 0.12 – 1.78 wt. % indicate negligible to minor local-scale secondary alteration of the rock suite. Petrology and the bulk-rock geochemistry of the rocks indicate pyroxene and plagioclase-controlled fractionation of the Fe-Ti-rich basaltic parental magma. The rocks show elevated rare earth element (REE) contents (LREE = 10-70 × chondrite, HREE = 10-30 × chondrite) with LREE enrichment. The enrichment of large ion lithophile elements (LILE), small negative Nb, Ta and Ti anomalies, weak positive Zr and Hf anomalies, and co-variations of various incompatible elements suggest minor incorporation of crustal components. The upper gabbro-anorthositic rock suite yields a bulk-rock Sm-Nd isochron age of 3022 ± 180 Ma, with an initial
143
Nd/
144
Nd ratio of 0.50849 ± 0.00017, corresponding to an ε
Nd(T)
value of -4.4±3.3. This value and the trace element geochemistry may indicate a metasomatized mantle source for the parental basaltic magma. Our study suggests that the parental basaltic magma might have originated from a metasomatized lithospheric mantle wedge in an active continental margin setting. The parental magma was emplaced within the early Archean tonalite-trondhjemite-granodiorite (TTG) dominated continental crust of the Singhbhum Craton. The contemporaneous Mesoarchean granitic plutons were formed by reworking of this older TTG-rich crust. The Mayurbhanj Mafic Complex and other time-equivalent Mesoarchean to Late Archean ultramafic-mafic intrusive and extrusive rocks in the Singhbhum and Dharwar Cratons in the Indian Shield represent a large-scale magmatic event likely related to the amalgamation of the supercontinent ‘Ur’. Rocks of similar age in different parts of this hypothetical supercontinent in the world have significant resource endowments of chromite, platinum group elements (PGE), Ti-V-Fe oxides and Ni-Cu sulfides, thus enhancing the exploration potential of the Mayurbhanj and equivalent mafic rock suites within the Indian cratons.
Algorithm xxxx: HDSDP: Software for Semidefinite Programming
Authors: Gao Wenzhi , Ge Dongdong , Ye Yinyu
Published: February 2025

HDSDP
is a numerical software solving semidefinite programming problems. The main framework of
HDSDP
resembles the dual-scaling interior point solver
DSDP
[Benson and Ye, 2008] and several new features, including a dual method based on the simplified homogeneous self-dual embedding, have been implemented. The embedding technique enhances the stability of the dual method , and several new heuristics and computational techniques are designed to accelerate its convergence. HDSDP aims to show how the dual-scaling algorithm benefits from the self-dual embedding, and it is developed in parallel to DSDP5.8. Numerical experiments over several classical benchmark datasets exhibit its robustness and efficiency, particularly its advantages on SDP instances featuring low-rank structure and sparsity.
HDSDP
is open-sourced under an MIT license and available at
https://github.com/Gwzwpxz/HDSDP
.
Unraveling Code Clone Dynamics in Deep Learning Frameworks
Authors: Assi Maram , Hassan Safwat , Zou Ying
Published: February 2025

Deep Learning (DL)
frameworks play a critical role in advancing artificial intelligence, and their rapid growth underscores the need for a comprehensive understanding of software quality and maintainability. DL frameworks, like other systems, are prone to code clones. Code clones refer to identical or highly similar source code fragments within the same project or even across different projects. Code cloning can have positive and negative implications for software development, influencing maintenance, readability, and bug propagation. While the existing studies focus on studying clones in DL-based applications, to our knowledge, no work has been done investigating clones, their evolution and their impact on the maintenance of DL frameworks. In this paper, we aim to address the knowledge gap concerning the evolutionary dimension of code clones in DL frameworks and the extent of code reuse across these frameworks. We empirically analyze code clones in nine popular DL frameworks, i.e.,
TensorFlow
,
Paddle
,
PyTorch
,
Aesara
,
Ray
,
MXNet
,
Keras
,
Jax
and
BentoML
, to investigate (1) the characteristics of the long-term code cloning evolution over releases in each framework, (2) the short-term, i.e., within-release, code cloning patterns and their influence on the long-term trends, and (3) the file-level code clones within the DL frameworks. Our findings reveal that DL frameworks adopt four distinct cloning trends:
“Serpentine”
,
“Rise and Fall”
,
“Decreasing”
, and
“Stable”
and that these trends present some common and distinct characteristics. For instance, bug-fixing activities persistently happen in clones irrespective of the clone evolutionary trend but occur more in the
“Serpentine”
trend. Moreover, the within-release level investigation demonstrates that short-term code cloning practices impact long-term cloning trends. The cross-framework code clone investigation reveals the presence of
functional
and
architectural adaptation
file-level cross-framework code clones across the nine studied frameworks. We provide insights that foster robust clone practices and collaborative maintenance in the development of DL frameworks.
Intraoperative Supine Breast MRI for Residual Tumor Assessment after Breast-Conserving Therapy in Early-Stage Breast Cancer
Authors: Jirarayapong Jirarat , Portnow Leah H. , Jagadeesan Jayender , Kwait Dylan C. , Lan Zhou , Barbie Thanh U. , Mallory Melissa A. , Kim Leah , Golshan Mehra , Gombos Eva C.
Published: February 2025

Intraoperative supine breast MRI immediately after breast-conserving surgery in individuals with early-stage breast cancer yielded good accuracy in identifying residual tumor burden at resection margins.
Prophylactic caffeine mitigates systemic hypercapnia and headache during graded carbon dioxide exposure in healthy males and females: a randomized crossover trial
Authors: Ryan Benjamin J. , Mayer Thomas A. , Alba Billie K. , Bradbury Karleigh E. , Brazelton Shaun C. , Charkoudian Nisha , Connor K. Riley , Fry Benjamin A. , Giersch Gabrielle E.W , Gioscia-Ryan Rachel A. , Greenfield Andrew M. , Lieberman Harris R. , Seeley Afton D. , Sellers John H , Shevchik Joseph D. , Stein Jesse , Swenson Erik R. , Salgado Roy M.
Published: February 2025

Exposure to elevated inspired carbon dioxide (CO2) levels, an environmental threat in several occupational settings, is known to induce systemic hypercapnia and provoke headache. However, the impact of CO2 exposure dose on headache severity has not been determined, and countermeasures to mitigate systemic hypercapnia and headache during CO2 exposure are lacking. In this study, we first characterized respiratory responses and headache with graded CO2 exposure (sequential 12-minute stages of 0%, 2%, 4%, 6%, and 8% inspired CO2, all with 21% oxygen) during seated rest in 24 healthy males and females. As expected, graded CO2 exposure resulted in stepwise increases (41±3, 43±2, 46±2, 53±2, 65±1 mmHg; p<0.001) in end-tidal CO2 across the spectrum from normocapnia to severe hypercapnia. Headache increased (p<0.05) beginning at 4% inspired CO2 (1±2, 2±3, 8±8, 16±13, 32±20 mm on a 100 mm visual analog scale). Participants then completed the same graded CO2 exposure 1 hour following either caffeine (400 mg) or placebo supplementation in a randomized, double-blind, crossover manner (n=23). Caffeine increased ventilation and lowered end-tidal CO2 at inspired CO2 levels between 0% and 6% (p<0.05), corresponding with a leftward shift in the end-tidal CO2-ventilation response curve with unchanged slope. Caffeine substantially reduced headache during graded CO2 exposure, an effect that was most pronounced at 8% inspired CO2 (placebo: 25±15 mm, caffeine: 13±12 mm; p<0.05). Our novel findings establish prophylactic caffeine supplementation as a translational countermeasure to mitigate systemic hypercapnia and headache during CO2 exposure.
Evidence of a novel gene locus ARHGAP44 for longitudinal change in hemoglobin A1c levels among non-diabetic subjects from the Long Life Family Study
Authors: Wang Siyu , Lenzini Petra , Thygarajan Bharat , Lee Joseph H. , Vardarajan Badri N. , Yashin Anatoli , Miljkovic Iva , Daw E. Warwick , Lin Shiow J. , Patti Gary , Brent Michael , Zmuda Joseph M. , Perls Thomas T. , Christensen Kaare , Province Michael A. , An Ping
Published: February 2025

Glycated hemoglobin A1c (HbA1c) indicates average glucose levels over three months and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal change in circulating HbA1c (ΔHbA1c) are also associated with aging processes, cognitive performance, and mortality. We analyzed ΔHbA1c in 1,886 non-diabetic Europeans from the Long Life Family Study (LLFS) to uncover gene loci influencing ΔHbA1c. Using growth curve modeling adjusted for multiple covariates, we derived ΔHbA1c and conducted linkage-guided sequence analysis. Our genome-wide linkage scan identified a significant locus on 17p12. In-depth analysis revealed a gene locus ARHGAP44 (rs56340929, explaining 27% of the linkage peak) that was significantly associated with ΔHbA1c. Interestingly, RNA transcription of ARHGAP44 was also significantly associated with ΔHbA1c in the LLFS, and this discovery was replicable on the gene level in the Framingham Offspring Study (FOS). Taking together, we successfully identified a novel gene locus ARHGAP44 for ΔHbA1c in family members without T2D. Further follow-up studies using longitudinal omics data in large independent cohorts are warranted.
Health-related quality of life in patients with HR+/HER2− early breast cancer treated with ribociclib plus a nonsteroidal aromatase inhibitor: results from the NATALEE trial
Authors: Fasching Peter A. , Slamon Dennis , Nowecki Zbigniew , Kukielka-Budny Bozena , Stroyakovskiy Daniil , Yardley Denise A. , Huang Chiun-Sheng , Chan Arlene , Chia Stephen , Martín Miguel , Rugo Hope S. , Loi Sherene , Hurvitz Sara , Untch Michael , Afenjar Karen , Fresco Rodrigo , Danyliv Andriy , Ferrusi Ilia , Li Zheng , Hortobagyi Gabriel
Published: February 2025

Purpose: The phase 3 NATALEE trial reported a statistically significant invasive disease-free survival benefit with ribociclib plus nonsteroidal aromatase inhibitor (NSAI) versus an NSAI alone in stage II/III hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) early breast cancer (EBC). Here we report health-related quality of life (HRQOL) data from NATALEE. Patients and methods: Patients were randomized to receive ribociclib plus NSAI or NSAI alone. Patient-reported outcome scores (EORTC QLQ-C30 global health status and physical, social, and emotional functioning domains; EORTC QLQ-BR23 breast-symptoms scale; health on a visual analog scale of EQ-5D-5L; and the Hospital Anxiety and Depression Scale) were assessed. The prespecified primary HRQOL endpoint was physical functioning. Mean scores and time-categorical and prespecified linear-time repeated-measure models were used to evaluate HRQOL changes during treatment. Results: HRQOL was evaluated in all patients in the ribociclib plus NSAI (n = 2549) and NSAI alone (n = 2552) arms. Compliance was high in both arms (≈93%-97%). Mean scores did not differ meaningfully from baseline for any analyzed domain. Likewise, neither a meaningful change from baseline (in either treatment arm) nor a difference between arms was observed during treatment in the time-categorical, model-adjusted mean scores for any HRQOL domains—using published thresholds for interpreting longitudinal and between-group differences, with all values being within 0.5 SD of their baseline values. Linear-time regression analysis confirmed these findings. Conclusions: These analyses of NATALEE show that adding adjuvant ribociclib to an NSAI does not negatively impact HRQOL in patients with HR+/HER2− EBC.
Germline-Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking ATM to TP53 Synthetic Essentiality
Authors: Arafa Ali T. , Yadav Siddhartha , Marshall Catherine H. , Mauer Elizabeth , Huang Minxuan , Yilma Binyam , van der Pol Ymke , Fragkogianni Stamatina , Teslow Emily A. , Kellen Samuel , Boytim Ella , Luo Christine , Ludwig Megan , Zhang Weijie , Jayaraj Arockia , Armstrong Deborah K. , Isaacs William B. , Drake Justin M. , Nguyen Hai Dang , Huang R. Stephanie , Chao Calvin Y. , Lou Emil , Dehm Scott M. , Couch Fergus J. , Hwang Justin H. , Antonarakis Emmanuel S.
Published: February 2025

Background: Germline alterations in homologous recombination repair (gHRR) genes impact the pathogenesis, treatment options, and survival of cancer patients. However, distinct gHRR gene alterations may differentially impact treatment response and oncogenic signaling. Here we interrogated genomic and transcriptomic data and assessed clinical outcomes of patients with gHRR mutations across four BRCA-associated cancers (breast, ovarian, pancreatic, and prostate cancers) to identify therapeutic vulnerabilities. Methods: We assessed 24,309 patients undergoing matched tumor/normal next-generation DNA and RNA sequencing. Annotated gHRR gene variants (gBRCA1, gBRCA2, gPALB2, gATM, gCHEK2) were analyzed. Hazard ratios were used to assess survival outcomes comparing germline versus sporadic groups. Somatic alterations and their frequencies were compared across gHRR-altered groups. Differential gene expression and gene set enrichment analysis was used to compare transcriptomic profiles. Results: Somatic TP53 mutations were depleted in gATM carriers (p<0.05) across all four BRCA-associated cancers by up to 2.5-fold. Tumors with gBRCA1/2 mutations were associated with improved survival in ovarian cancer patients, and had consistent enrichment of TP53 mutations in all four cancers. gATM mutations displayed elevated p53 transcriptional activity in all four cancers, with significance reached in breast and prostate cancers (p<0.01). In breast, ovarian, and prostate cancers, gATM tumors demonstrated significantly increased inflammatory pathways (p<0.001). Finally, using gene-dependency data, we found that cell lines that were highly dependent on ATM were co-dependent on canonical p53 function. Conclusion: gATM-associated cancers appear to require intact p53 activity and this synthetic essentiality may be used to guide targeted therapies that perturb canonical TP53 function.
M4205 (IDRX-42) is a highly selective and potent inhibitor of relevant oncogenic driver and resistance variants of KIT in cancer
Authors: Esdar Christina , LInde Nina , Blum Andreas , Schieferstein Hanno , Drechsler Christine , Sherbetjian Eva , Petersson Carl , Ross Edith , Leuthner Birgitta , Grädler Ulrich , Dorsch Dieter , Blaukat Andree
Published: February 2025

Primary activating mutations in KIT (exons 9/11) are key driver alterations in about 80% of gastrointestinal stromal tumors (GIST). Imatinib, a small molecule tyrosine kinase inhibitor, is used successfully as first-line therapy for unresectable metastatic or recurrent GIST patients, but secondary resistance mutations in the KIT kinase domains frequently occur. Currently approved later-line therapies target these mutations incompletely with limited clinical benefit. M4205, a kinome-selective KIT inhibitor, was designed to address this high unmet medical need by inhibiting all relevant KIT driver and resistance mutations. Compared to imatinib, M4205 shows stronger antitumor activity in preclinical GIST models driven by oncogenic KIT driver mutations. M4205 demonstrates clinically relevant efficacy in a range of preclinical GIST models expressing different secondary KIT resistance mutations. The kinase selectivity profile of M4205 is superior to registered standard of care and investigational agents. M4205, now IDRX-42, is currently being investigated in a Phase 1 first-in-human study in participants with GIST.
Figure 2 from Acetalax and Bisacodyl for the Treatment of Triple-Negative Breast Cancer: A Combined Molecular and Preclinical Study
Authors: Reinhold William C. , Marangoni Elisabetta , Elloumi Fathi , Montagne Remi , Varma Sudhir , Wang Yanghsin , Rezai Keyvan , Morriset Ludivine , Dahmani Ahmed , El Botty Rania , Huguet Léa , Mizunuma Makito , Takebe Naoko , Huguet Samuel , Luna Augustin , Pommier Yves
Published: February 2025

Implication of the mitochondrial pathways in cellular responses to Acetalax assessed by CRISPR (Achilles project, DepMap MIT) survival comparisons with Acetalax activity [GDSC_MGH-Sanger, −log10(IC50M)]. A, Schematic of the GSEA analysis workflow used to generate B. B, GSEA used to determine enriched categories of 18,121 genes from the comparison of CRISPR survival with Acetalax [−log10(IC50M)] activity for TNBC cell lines. N is the number of genes in the category. All nominal P values for these categories are less than 1 × 10−7. C, Scatter plots of Acetalax activity (x-axis) vs. CRISPR survival for three representative genes, NDUFS1, CYCS, and ATP5ME (y-axes) as specific examples from the B analysis. Each circle is a breast cell line, with the TNBC cell lines in red. The correlation type is Pearson. The red line is the regression line. Plots were generated using CellMinerCDB using Select Tissues\To include “Breast”. D, Levels of significant correlation in breast cancer cell lines for mitochondrial categories as compared with Acetalax activity in the breast cell line subset. The correlation between Acetalax activity and CRISPR gene survival data were generated from CellMinerCDB with the selection of “Breast” as the “To include” category. act, activity.
Fluxos produtivos globais da saúde: elementos para a construção do mapa dos complexos industriais da saúde no mundo
Authors: Antas Junior Ricardo Mendes
Published: February 2025

O artigo parte do pressuposto de que os circuitos espaciais produtivos apresentam dinâmicas globais, conforme assevera Milton Santos (1988), construídas pela articulação entre lugares e regiões das diferentes formações socioespaciais que constituem o atual sistema mundo. Essa dinâmica transfronteiriça se estabelece pela imposição das temporalidades hegemônicas dos agentes globais, especificamente aquelas que usam a simultaneidade instrumental para fins de acumulação capitalista. Na produção industrial, essa prática espacial das empresas se atinge, entre outros modos, pela troca de insumos produtivos entre países que detêm os mesmos ramos industriais, e aqui tratamos daqueles que constituem o complexo industrial da saúde. É por meio da análise desses fluxos de insumos produtivos e produtos acabados que se podem criar indicadores e estimar os países detentores de tais complexos.
An Extended Refutation of Doctrinal Correlates in John 8–9
Authors: Terian Abraham
Published: February 2025

The doctrinal continuum between ancestral merits and rewards and punishments is well established in Second Temple Judaism and is discernible in John 8–9. Following Philo of Alexandria’s questioning of these doctrinal correlates, the Johannine chapters are subjected to a theological-rhetorical analysis focused on the transitional passage (9:1–5). The passage is here seen not as an introduction to a new theme but as corollary to the preceding chapter(s), having a duo-directional significance, linking a two-part refutation of invariably related doctrines: ancestral merits and rewards and punishments. The rejection or refutation of the latter affirms the rejection or refutation of the former, and vice versa. The Johannine chapters in question have a thematic and dialectical connection; they constitute a substantial part of the broader, interrelated polemic of the Fourth Gospel.
Jesus’s Solidarity with Human Mortality and Perfection of Sonship in the Epistle to the Hebrews
Authors: Lee Jihye
Published: February 2025

In relation to the discussion on the concept of perfection in Hebrews, the author’s emphasis on Jesus’s solidarity with human mortality has been considered as simple reference to the precondition of his Christological role and his sympathetic character, which shares human weaknesses. However, the substantial connection between the discussions on sonship in Heb 12 and on the Son in Heb 1–2 suggests a fresh reading of the text’s emphasis on Jesus’s mortality along with his role as ἀρχηγός of other sons. The author of Hebrews presents the notion that human mortality is a divinely designed opportunity for the sons of God to acquire the discipline necessary to be prepared to become the heirs of the eternal inheritance. The one who totally entrusts his own life to the Father is the genuinely obedient son, and this true obedience is cultivated when the sons choose obedience on the occasion of the test, i.e., “fear of death,” which is unaffectedly derived from the status of mortality.
Body condition index of Bombina variegata variegata (Linneus,1758) in different habitats
Authors: Trenti Matteo , Sacchi Roberto , Romano Antonio , Endrizzi Sonia
Published: February 2025

Understanding how threatened amphibians respond to alternative environments, such as human made site and human exploited landscape is a crucial point of view for future conservation projects, primarily thought that these environments are growing both in number and importance. There are a lot of population traits for evaluating the population’s status, such as the abundance, recruitment and survival rate, all methods very dispendious of an effort level. Here we investigated the influence of environmental variables on the physiological body condition of Bombina variegata (yellow-bellied toad) in three different habitat typologies, Natural, Mountain pasture and Agricultural, in the Province of Trento, Northern Italy. These habitats differ in their genesis, development and maintenance. The natural sites are unaffected by human impact, the Mountain pasture pond are semi-natural environments whose maintenance, however, depends on human intervention (periodic removal of substrate to prevent silting) and subject to cows trampling, in the end the agricultural sites are artificial cemented tank used by farmer as water reservoir. The species shows decreasing trend following the IUCN assessment but it has a fairly well distribution in the study area. We used the Scaled Mass Index (SMI), considering snout-vent length and body weight of toads, as a measure of the population’s body condition. SMI was calculated for 932 male toads belonging to 9 populations that were monitored for 5 consecutive years. We found that toads in Natural Habitat had significantly better body condition than those in both Mountain pasture habitat () and Agricultural one (), indicating that Natural habitat provided particularly higher quality habitat. SMI allows for the assessment of individuals persisting in disturbed environments, providing valuable information on environmental suitability, which is a primary objective of conservation.
“The Significance of the Local Church”
Authors: Tyson Catherine
Published: February 2025

Since the start of the war in Ukraine, Patriarch Kirill, head of the Russian Orthodox Church (ROC), has faced criticism for providing religious justification for Russia’s invasion. This study provides foundational research on how the war and the patriarch’s statements are impacting attitudes toward church attendance at ROC parishes in France and the U.S. Based on twenty-seven qualitative interviews across seven parishes, this research explores the central reasons churchgoers hold for continuing to attend ROC parishes, despite many disagreeing with the patriarch’s stance on the war. Reasons for staying center around viewing the local church as a place of worship and community.
Make space! Creating Church with Newcomers
Authors: Felter Kirsten Donskov , Berg Berit Weigand , Hansen Heine Lokjaer
Published: February 2025

In the Evangelical Lutheran Church of Denmark, demographic changes call for new strategies to integrate groups of newcomers in already existing parishes. In 2019, Skalborg, a rapidly growing parish on the outskirts of the city of Aalborg, together with the independent organization Kirkefondet and Centre for Pastoral Education and Research, initiated the project ‘Church with Newcomers’ that seeks to involve new citizens actively in creating relevant forms of church in a new city district. The evaluation of the project team made clear that openness and inclusiveness were seen as core qualities of the project that indicated that this was church. The article explores how the collaborative design and culture of the project team have contributed to realizing the project’s aim. We argue that working with space-making practices may point to fruitful ways of realizing participatory ecclesiology in a changing folk church setting.
Possible behavioral hierarchy in the food handling by Messor arenarius ants
Authors: Warburg Ittai
Published: February 2025

Messor arenarius ants are seed harvesters, that feed mainly on seeds or plant parts. This species inhabits mainly deserts in the Middle East and North Africa. In Israel, M. arenarius ants can be found in the Negev Desert and also in the Coastal Plain. This research focuses on the food-handling stages of those ants. Using food choice experiments, ants were given choices, to select between whole-wheat seeds and halves of wheat seeds cut longitudinally. In first collection rounds, the proportion of cases in which ants touched both food items using their antennae was significantly higher than forelegs touches. Similar findings were obtained in further collection rounds, when the sand or the soil at the food collection points was swept or changed after each collection round. These findings indicate a hierarchy between the food handling by the antennae and the food handling by the forelegs in M. arenarius ants. It seems that those ants smell food items by their antennae, which contain contact chemoreceptors, and afterward feel those food items by their forelegs, which contain mechanoreceptors.
The Imminent Data Desert: The Future of Stratospheric Monitoring in a Rapidly Changing World
Authors: Salawitch Ross J. , Smith Jessica B. , Selkirk Henry , Wargan Krzysztof , Chipperfield Martyn P. , Hossaini Ryan , Levelt Pieternel F. , Livesey Nathaniel J. , McBride Laura A. , Millán Luis F. , Moyer Elisabeth , Santee Michelle L. , Schoeberl Mark R. , Solomon Susan , Stone Kane , Worden Helen M.
Published: February 2025

The Atmospheric Chemistry Experiment-Fourier Transform Spectrometer (ACE-FTS) on SCISAT-1 and Microwave Limb Sounder (MLS) on NASA’s Aura satellite have contributed significantly to understanding the impacts of human activities on the stratospheric ozone layer. The two-decade-long data record from these instruments has allowed quantification of ozone depletion caused by human-released ozone-depleting substances, the effects of extreme natural events like major volcanic eruptions including Hunga in 2022, as well as events amplified by human-caused climate change such as wildfires that inject material into the stratosphere, as happened over Australia in early 2020. Both platforms are nearing the end of their operational lifetimes, and their decommissioning will cause a substantial gap in the measurement of critical atmospheric components, including water vapor, inorganic chlorine species, and tracers of stratospheric transport. This upcoming “data desert” poses significant challenges for monitoring the recovery of the ozone layer and assessing the effects on stratospheric composition of future extreme events, threats posed by increases in space debris from satellite burn-up, and the possible injection of stratospheric aerosol to mitigate global warming. The lack of confirmed future missions that can provide daily near-global profile measurements of stratospheric composition highlights the need for observational strategies to bridge this impending gap. This paper discusses the essential role of ACE-FTS and MLS in advancing our understanding of the stratosphere, the impact of data loss after the cessation of one or both instruments, and the urgency of developing strategies for mitigating the impact of these observational losses at a time marked by dramatic changes in the stratosphere due to human and natural factors.
Impacts of Background Conditions on the Evolutionary Disparities between Greenland and Euro-Atlantic Blocking
Authors: Zhang Wenqi , Wang Lin , Luo Dehai , Yao Yao , Luo Binhe , Simmonds Ian , Semenov Vladimir
Published: February 2025

In this paper, we investigate the contrasting evolutionary behaviors and weather impacts of Greenland blocking and Euro-Atlantic blocking. The comprehensive analysis reveals that Greenland blocking is characterized by substantial amplitude, a prolonged lifespan, and notable westward movement, accompanied by significant warming over western Greenland and cooling over eastern North America and northern Europe. In contrast, Euro-Atlantic blocking remains quasi stationary, has a shorter duration, and features a smaller amplitude, resulting in only mild cooling over southern Europe. We elucidate the dynamic mechanism behind the evolution of these two types of blockings using the nonlinear multiscale interaction model of atmospheric blocking from the perspective of the meridional gradient of potential vorticity PVy. Here, atmospheric blocking is conceptualized as a wave packet comprising an envelope and a carrier wave. In contrast to Euro-Atlantic blocking, the wave packet envelope (WPE) of Greenland blocking displays a greater degree of nonlinearity and weaker high-order dispersion under weak background zonal wind and PVy conditions. This fosters the amplification and sustainability of the WPE, contributing to its large amplitude and extended lifespan. Greenland blocking also shows pronounced westward movement due to its large amplitude and the weak background PVy condition. The Euro-Atlantic blocking exhibits quasi-stationary and small-amplitude behaviors due to strong zonal wind and PVy conditions. Our findings indicate that the discrepancy in system dispersion, i.e., the relative velocity of the WPE and the carrier wave, between Greenland blocking and Euro-Atlantic blocking is negligible. The results emphasize that the variance in their evolutionary behaviors primarily stems from disparities in their WPEs.
A Systematic Review of Attribution Theory Applied to Crisis Events in Communication Journals: Integration and Advancing Insights
Authors: Ji Yingru , Tao Weiting , Wan Chang
Published: February 2025

Research on communication in crises across individual, organizational, and societal levels has expanded significantly, with attribution theory frequently used to explain how people interpret these crises. However, research in the three levels of crises has developed independently, limiting theoretical advancement. This study systematically reviews 133 attribution theory based communication articles in crisis situations, showing that responsibility attribution can be integrated into a unified framework. Attribution theories are most commonly integrated with situational crisis communication theory, framing theory, and image repair theory—three communication theories developed over three decades ago, primarily focusing on content effects. This study calls for modernizing attribution-related communication theories and testing media effects beyond content influence in today’s rapidly changing media environment. Additionally, it advocates for adopting a multi-agent approach to responsibility attribution and emphasizing treatment responsibility attribution. Further insights into research contexts and methodologies are provided to advance scholarly knowledge and suggest directions for future research.
Producing images and making judgement: The ongoing use of epistemic technologies in expert work
Authors: Lindberg Kajsa , Tyskbo Daniel , Styhre Alexander
Published: February 2025

The increased use of advanced technologies generating new data and information, including algorithmic technologies and AI, has led to a renewed interest in the role of technologies in knowledge work. Some of these technologies act as epistemic technologies, a term derived from the work of Knorr Cetina (1999) on how sciences make knowledge. While previous studies provide important insights into how the outcomes of the technologies are used in expert work, the work needed to produce the outcomes in the first place is often overlooked and separated from use. The generation of new data and information is instead treated as both black-boxed and de-contextualized. To highlight the work required to generate meaningful outcomes, and address the challenges posed by opaque algorithms, we present a longitudinal in-depth study of the medical imaging technologies of the Robotic X-ray and iMRI, used in combination with surgery. The study illustrates how technologies become epistemic through use: new data was produced by means of interactions within a relational and heterogeneous assemblage of people, technologies and devices. Through trained judgement, the experts made the data useful and possible to act upon in each specific situation. The study contributes to research into the use of algorithmic technologies in knowledge work by showing how opaque algorithms can be complemented by contextualized information, making it possible to interrogate and make trained judgements, not only in relation to outcomes, but also their production. We conclude that epistemic technologies are involved in the ongoing construction of knowledge, during both the production and use of outcomes, and that enacting the technologies as epistemic includes a situational and material awareness.