bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFNγ mediates the resistance of tumor cells to distinct NK cell subsets
Authors: Hofman Tomáš , Ng Siu Wang , Garcés-Lázaro Irene , Heigwer Florian , Boutros Michael , Cerwenka Adelheid 
Published: July 2024

BackgroundImmune checkpoint blockade targeting the adaptive immune system has revolutionized the treatment of cancer. Despite impressive clinical benefits observed, patient subgroups remain non-responsive underscoring the necessity for combinational therapies harnessing additional immune cells. Natural killer (NK) cells are emerging tools for cancer therapy. However, only subpopulations of NK cells that are differentially controlled by inhibitory receptors exert reactivity against particular cancer types. How to leverage the complete anti-tumor potential of all NK cell subsets without favoring the emergence of NK cell-resistant tumor cells remains unresolved.MethodsWe performed a genome-wide CRISPR/Cas9 knockout resistance screen in melanoma cells in co-cultures with human primary NK cells. We comprehensively evaluated factors regulating tumor resistance and susceptibility by focusing on NK cell subsets in an allogenic setting. Moreover, we tested therapeutic blocking antibodies currently used in clinical trials.ResultsMelanoma cells deficient in antigen-presenting or the IFNγ-signaling pathways were depleted in remaining NK cell-co-cultured melanoma cells and displayed enhanced sensitivity to NK cells. Treatment with IFNγ induced potent resistance of melanoma cells to resting, IL-2-cultured and ADCC-activated NK cells that depended onB2Mrequired for the expression of both classical and non-classical MHC-I. IFNγ-induced expression of HLA-E mediated the resistance of melanoma cells to the NKG2A+KIR−and partially to the NKG2A+KIR+NK cell subset. The expression of classical MHC-I by itself was sufficient for the inhibition of the NKG2A−KIR+, but not the NKG2A+KIR+NK cell subset. Treatment of NK cells with monalizumab, an NKG2A blocking mAb, enhanced the reactivity of a corresponding subset of NK cells. The combination of monalizumab with lirilumab, blocking KIR2 receptors, together with DX9, blocking KIR3DL1, was required to restore cytotoxicity of all NK cell subsets against IFNγ-induced resistant tumor cells in melanoma and tumors of different origins.ConclusionOur data reveal that in the context of NK cells, IFNγ induces the resistance of tumor cells by the upregulation of classical and non-classical MHC-I. Moreover, we reveal insights into NK cell subset reactivity and propose a therapeutic strategy involving combinational monalizumab/lirilumab/DX9 treatment to fully restore the antitumor response across NK cell subsets.
LargeTRAPPC11gene deletions as a cause of muscular dystrophy and their estimated genesis
Authors: Kopčilová Johana , Ptáčková Hana , Kramářová Tereza , Fajkusová Lenka , Réblová Kamila , Zeman Jiří , Honzík Tomáš , Zdražilová Lucie , Zámečník Josef , Balážová Patrícia , Viestová Karin , Kolníková Miriam , Hansíková Hana , Zídková Jana 
Published: July 2024

BackgroundTransport protein particle (TRAPP) is a multiprotein complex that functions in localising proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in diseases affecting muscle, brain, eye and to some extent liver. We present three patients who are compound heterozygotes for a missense variant and a structural variant in theTRAPPC11gene.TRAPPC11structural variants have not yet been described in association with a disease. In order to reveal the estimated genesis of identified structural variants, we performed sequencing of individual breakpoint junctions and analysed the extent of homology and the presence of repetitive elements in and around the breakpoints.MethodsBiochemical methods including isoelectric focusing on serum transferrin and apolipoprotein C-III, as well as mitochondrial respiratory chain complex activity measurements, were used. Muscle biopsy samples underwent histochemical analysis. Next-generation sequencing was employed for identifying sequence variants associated with neuromuscular disorders, and Sanger sequencing was used to confirm findings.ResultsWe suppose that non-homologous end joining is a possible mechanism of deletion origin in two patients and non-allelic homologous recombination in one patient. Analyses of mitochondrial function performed in patients’ skeletal muscles revealed an imbalance of mitochondrial metabolism, which worsens with age and disease progression.ConclusionOur results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms. This knowledge is important for understanding the molecular nature of human diseases and allows us to improve strategies for identifying disease-causing mutations.
A FAC potential for autostructure
Authors: Badnell N. R. , Zhang C. Y. 
Published: July 2024

Abstract
We describe the implementation of the current Flexible Atomic Code (FAC) unique electron central potential within the autostructure code. We show that the two codes then give the same atomic data for all practical application purposes. However, autostructure has more flexible potential options which can lead to a more accurate description of atomic processes, especially in low-charged ions.

Graphic Abstract
Predictions of the missing excited vector heavy–light mesons: the mass difference method
Authors: Allosh M. , Hapareer Moustafa Ismail , Mustafa A. Sayed , Ismail Atef 
Published: July 2024

AbstractA prediction study for the not yet discovered $$c\overline{s}$$

c

s
¯

and $$b\overline{s}$$

b

s
¯

meson states of the $$1^{3}D_1$$

1
3

D
1

quantum numbers is conducted, denoted as $$D_s$$

D
s

and $$B_s$$

B
s

, respectively. By employing our method, both states of ground and excited vector mesons are considered, which predominantly correspond to the ground state vector mesons with quantum numbers $$n~ ^{2S+1}L_{J} = 1 ~ ^{3}S_1$$

n

2
S
+
1

L
J

=
1

3

S
1

and to the orbitally excited vector mesons with quantum numbers $$n~ ^{2\,S+1}L_{J} = 1~ ^{3}D_1$$

n

2

S
+
1

L
J

=
1

3

D
1

. The considered method depends on the difference in the masses for the relevant states from orbitally and ground state vector mesons. Theoretical calculations are in good agreements with newly published data.
The Influence of CdS on the Structural and Optical Properties of Nano ZnWO4
Authors: Heiba Zein K. , Farag Noura M. , Abozied Asmaa M. , Badawi Ali , Mohamed Mohamed Bakr 
Published: July 2024

We investigated the influence of CdS on the structural and optical properties of nano ZnWO4 for optical applications. (1−x)ZnWO4/xCdS (x; 0 to 0.25) heterojunctions were formed and the structure and microstructure of the ZnWO4 and CdS phases developed were investigated using Rietveld refinement analysis for synchrotron X-ray diffraction data. Phase analysis revealed the phase percentage of the CdS phase is always less than the nominated value (x), implying merging of some Cd and S into ZnWO4. Raman spectra showed CdS peaks, confirming the existence of CdS. Scanning electron microscopy showed two distinct morphologies: plate-like particles (ZnWO4 phase) and spherical shape (CdS phase). UV–vis diffuse measurements revealed enhancement of absorbance and reduction in reflectance and transmittance, in the range 300–56 nm, as the amount of CdS (x) increased in the (1−x)ZnWO4/xCdS system. Band gap of the ZnWO4 phase reduced from 4.0 eV for x = 0.0 to 3.9, 3.6, and 2.9 eV for x = 0.05, 0.1, and 0.25, respectively. The highest refractive index values were obtained as the amount of CdS reached 0.05. Impact of alloying on linear and nonlinear parameters and emitted photoluminescence spectra was studied. Upon loading ZnWO4 with CdS, the PL intensity is greatly quenched and the whole spectrum is red shifted, from 480 to 540 nm. CIE chromaticity diagrams show that ZnWO4 sample without any doping exhibits a blue color while the doped system reveals green-yellow colors.
A Multicenter Real-life Prospective Study of Axicabtagene Ciloleucel versus Tisagenlecleucel Toxicity and Outcomes in Large B-cell Lymphomas
Authors: Stella Federico , Chiappella Annalisa , Casadei Beatrice , Bramanti Stefania , Ljevar Silva , Chiusolo Patrizia , Di Rocco Alice , Tisi Maria C. , Carrabba Matteo G. , Cutini Ilaria , Martino Massimo , Dodero Anna , Bonifazi Francesca , Santoro Armando , Sorà Federica , Botto Barbara , Barbui Anna M. , Russo Domenico , Musso Maurizio , Grillo Giovanni , Krampera Mauro , Olivieri Jacopo , Ladetto Marco , Cavallo Federica , Massaia Massimo , Arcaini Luca , Pennisi Martina , Zinzani Pier L. , Miceli Rosalba , Corradini Paolo 
Published: July 2024

Abstract
This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs. 89.3%, P = 0.0017) and neurotoxicity (9.9% vs. 32.2%, P &lt; 0.0001) but also superior progression-free survival (PFS) at 1 year (46.5% vs. 34.1%, P = 0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs. 22.7%, P = 0.0059). Differences in overall survival and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, P &lt; 0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients.
Significance: The findings of this study on 485 patients with relapsed/refractory large B-cell lymphoma treated with commercial axi-cel and tisa-cel indicate axi-cel’s superior PFS after propensity score weighting. The predictive utility of CAR-HEMATOTOX in assessing not only toxicity but also outcomes across both CAR T-cell products may guide future risk-stratified management strategies.
A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That mTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC
Authors: Goto Yusuke , Koshizuka Keiichi , Ando Toshinori , Izumi Hiroki , Wu Xingyu , Sato Kuniaki , Ishikawa Tomohiko , Ford Kyle , Feng Xiaodong , Wang Zhiyong , Arang Nadia , Allevato Michael M. , Kishore Ayush , Mali Prashant , Gutkind J. Silvio 
Published: July 2024

Abstract

The comprehensive genomic analysis of the head and neck squamous cell carcinoma (HNSCC) oncogenome revealed the frequent loss of p16INK4A (CDKN2A) and amplification of cyclin D1 genes in most human papillomavirus–negative HNSCC lesions. However, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown modest effects in the clinic. The aberrant activation of the PI3K/mTOR pathway is highly prevalent in HNSCC, and recent clinical trials have shown promising clinical efficacy of mTOR inhibitors (mTORi) in the neoadjuvant and adjuvant settings but not in patients with advanced HNSCC. By implementing a kinome-wide CRISPR/Cas9 screen, we identified cell-cycle inhibition as a synthetic lethal target for mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergism in HNSCC-derived cells in vitro and in vivo. Remarkably, we found that an adaptive increase in cyclin E1 (CCNE1) expression upon palbociclib treatment underlies the rapid acquired resistance to this CDK4/6 inhibitor. Mechanistically, mTORi inhibits the formation of eIF4G–CCNE1 mRNA complexes, with the consequent reduction in mRNA translation and CCNE1 protein expression. Our findings suggest that mTORi reverts the adaptive resistance to palbociclib. This provides a multimodal therapeutic option for HNSCC by cotargeting mTOR and CDK4/6, which in turn may halt the emergence of palbociclib resistance.

Significance:
A kinome-wide CRISPR/Cas9 screen identified cell-cycle inhibition as a synthetic lethal target of mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergistic effects in HNSCC. Mechanistically, mTORis inhibited palbociclib-induced increase in CCNE1.
Navigating Problematic Bauhaus Inheritances: Critiques, Implications, and Questions from the Bauhaus of the Seas NEB Lighthouse
Authors: Torretta Nicholas B. , Pestana Mariana , Duarte Frederico , Predroso-Roussado Cristiano , Seixas Luisa Metelo , Nisi Valentina , Nunes Nuno Jardim 
Published: July 2024

Abstract
In 2020, Europe announced the New European Bauhaus (NEB). While the initiative intends to achieve EU sustainability goals, framing it under the name of the Bauhaus brings various challenges and issues to the fore. In this article, we analyze the critiques of the original Bauhaus and the NEB to understand the challenges that the NEB lighthouse project Bauhaus of the Seas Sails (BoSS) inherits by adhering to the Bauhaus vision and name. We unveil the problematic dynamics of Eurocentric modernity's myths of universalism and better living through technology and on the Bauhaus's and NEB's position in global power structures. Instead of assuming a tabula rasa approach and replicating problematic structures unknowingly, we bring these three aspects to BoSS to find questions as orientation points to help steer away from problematic aspects inherited by reanimating the Bauhaus name and its legacy.
Characteristics of Gravity Waves in Opposing Phases of the QBO: A Reanalysis Perspective with ERA5
Authors: Pahlavan Hamid A. , Wallace John M. , Fu Qiang , Alexander M. Joan 
Published: July 2024

Abstract
Gravity waves dispersing upward through the tropical stratosphere during opposing phases of the QBO are investigated using ERA5 data for 1979–2019. Log–log plots of two-sided zonal wavenumber–frequency spectra of vertical velocity, and cospectra representing the vertical flux of zonal momentum in the tropical lower stratosphere, exhibit distinctive gravity wave signatures across space and time scales ranging over two orders of magnitude. Spectra of the vertical flux of momentum are indicative of a strong dissipation of westward-propagating gravity waves during the easterly phase and vice versa. This selective “wind filtering” of the waves as they disperse upward imprints the vertical structure of the zonal flow on the resolved wave spectra, characteristic of (re)analysis and/or free-running models. The three-dimensional structures of the gravity waves are documented in composites of the vertical velocity field relative to grid-resolved tropospheric downwelling events at individual reference grid points along the equator. In the absence of a background zonal flow, the waves radiate outward and upward from their respective reference grid points in concentric rings. When a zonal flow is present, the rings are displaced downstream relative to the source and they are amplified upstream of the source and attenuated downstream of it, such that instead of rings, they assume the form of arcs. The log–log spectral representation of wind filtering of equatorial waves by the zonal flow in this paper can be used to diagnose the performance of high-resolution models designed to simulate the circulation of the tropical stratosphere.
Genetic deletion of JAM-C in preleukemic cells rewires leukemic stem cell gene expression program in AML
Authors: Grenier Julien M. P. , Testut Céline , Bal Matthieu , Bardin Florence , De Grandis Maria , Gelsi-Boyer Véronique , Vernerey Julien , Delahaye Marjorie , Granjeaud Samuel , Zemmour Christophe , Spinella Jean-François , Chavakis Triantafyllos , Mancini Stéphane J. C. , Boher Jean-Marie , Hébert Josée , Sauvageau Guy , Vey Norbert , Schwaller Jürg , Hospital Marie-Anne , Fauriat Cyril , Aurrand-Lions Michel 
Published: July 2024

AbstractThe leukemic stem cell (LSC) score LSC-17 based on a stemness–related gene expression signature is an indicator of poor disease outcome in acute myeloid leukemia (AML). However, it is not known whether “niche anchoring” of LSC affects disease evolution. To address this issue, we conditionally inactivated the adhesion molecule JAM-C (Junctional Adhesion Molecule-C) expressed by hematopoietic stem cells (HSCs) and LSCs in an inducible mixed-lineage leukemia (iMLL)-AF9–driven AML mouse model. Deletion of Jam3 (encoding JAM-C) before induction of the leukemia–initiating iMLL-AF9 fusion resulted in a shift from long-term to short-term HSC expansion, without affecting disease initiation and progression. In vitro experiments showed that JAM-C controlled leukemic cell nesting irrespective of the bone marrow stromal cells used. RNA sequencing performed on leukemic HSCs isolated from diseased mice revealed that genes upregulated in Jam3-deficient animals belonged to activation protein-1 (AP-1) and tumor necrosis factor α (TNF-α)/NF-κB pathways. Human orthologs of dysregulated genes allowed to identify a score that was distinct from, and complementary to, the LSC-17 score. Substratification of patients with AML using LSC-17 and AP-1/TNF-α genes signature defined 4 groups with median survival ranging from &lt;1 year to a median of “not reached” after 8 years. Finally, coculture experiments showed that AP-1 activation in leukemic cells was dependent on the nature of stromal cells. Altogether, our results identify the AP-1/TNF-α gene signature as a proxy of LSC anchoring in bone marrow niches, which improves the prognostic value of the LSC-17 score. This trial was registered at www.ClinicalTrials.gov as #NCT02320656.
Risk of transformation by frontline management in follicular and marginal zone lymphomas: a US population–based analysis
Authors: Florindez Jorge A. , Chihara Dai , Reis Isildinha M. , Lossos Izidore S. , Alderuccio Juan Pablo 
Published: July 2024

Abstract
Follicular lymphoma (FL) and marginal zone lymphoma (MZL) often have long overall survival (OS), however, high-grade transformation (HGT) to diffuse large B-cell lymphoma markedly reduces survival. The roles of upfront treatment vs observation on the incidence and outcome of HGT remain unclear. Thus, we analyzed a Surveillance, Epidemiology, and End Results database to address this question. Patients diagnosed with FL grades 1 to 2 or MZL between 2000 and 2020 were included. Fine-Gray models estimated the impact of covariates on HGT cumulative incidence and lymphoma-specific survival (LSS) and Cox regression on OS. HGT occurred in 4.2% of 23 384 patients with FL and 2.5% of 20 530 patients with MZL. The 5- and 10-year HGT cumulative incidence rates were 2.80% and 4.87% for FL, and 1.74% and 2.95% for MZL, respectively, which are notably lower than in earlier studies. The annual HGT incidence rate peaked in the first 2 years, then steadily declined over 2 decades for FL and all MZL subtypes. In FL, upfront observation vs treatment increases HGT risk (sub-distribution hazard ratio [SHR], 1.23; 95% confidence interval [CI], 1.09-1.40; P &lt; .001) and barely affects OS (hazard ratio [HR], 0.95; 95% CI, 0.90-0.99; P = .03). Conversely, upfront observation was associated with lower HGT risk in nodal (SHR, 0.71; 95% CI, 0.53-0.94; P = .01) and extranodal (SHR, 0.64; 95% CI, 0.48-0.86; P = .003) MZL and did not affect survival in extranodal disease (HR, 0.94; 95% CI, 0.97-1.02; P = .15). HGT was associated with decrease in LSS across all histologies. Upfront treatment reduced the risk of HGT only in FL but not MZL.
The wolf in sheep’s clothing: vasovagal syncope in acute aortic dissection
Authors: Donner Viviane , Beuret Hadrien , Savoy Simon , Ribordy Vincent , Sadeghi Christine D. 
Published: July 2024

Abstract
Background
The presentation of acute aortic dissection can pose a challenge for emergency physicians, as it may occur without pain. Atypical presentations can lead to significant delays in diagnosis and increased mortality rates.

Case description
Our case illustrates that isolated painless syncope can be a rare presenting symptom of acute aortic dissection type A. What is unique about our case is the limited extension of the dissection tear and the availability of Holter monitoring during the syncopal episode.

Conclusion
This constellation provides insight into the pathophysiological mechanism of the syncope in this patient. Mechanisms of syncope related to acute aortic dissection are diverse. We show that vasovagal activation not related to pain can be the underlying mechanism of syncope in acute aortic dissection type A. Although excessive vasovagal tone in the setting of aortic dissection has been hypothesized in the past, it has never been as clearly illustrated as in the present case. This also highlights the challenge in risk stratification of syncope in the emergency department.
The effect of air pollution on selected immune system parameters, 8-isoprostane, and alpha-1-antitrypsin of people living in environmentally distinct regions
Authors: Jiřík Vítězslav , Machaczka Ondřej , Riedlová Petra , Kramná Dagmar , Siemiatkowski Grzegorz , Ośródka Leszek , Krajny Ewa , Ambrož Antonín , Topinka Jan , Rössner Pavel 
Published: July 2024

Abstract
Background
Air pollution is associated with adverse health effects, especially on the respiratory and cardiovascular systems, but according to recent research, even in cognitive health, metabolic, and immune systems. The objective was to analyse the effect of long-term exposure to air pollution on selected immune system parameters, 8-isoprostane a parameter of oxidative stress, and alpha-1-antitrypsin a protease inhibitor.

Methods
The number of 381 probands aged 35–65 from two differently polluted regions was included. Lifetime exposures to PM10, PM2.5, NO2, B(a)P, and benzene for each proband were calculated based on historical pollutant concentrations observed. The selected blood parameters were analysed in relation to independent variables (air pollutants, socioeconomic factors, etc.) using multiple regression. Possible covariates were determined. In its end, the study was conceived as a case–control study, and the odds ratio was quantified, expressing the strength of the association of the monitored parameters with the region.

Results
The average lifetime exposures to air pollution were significantly different between the two regions. Significant effects of the region were observed on IgM, IL-6, 8-isoprostane, and alpha-1-antitrypsin levels. The strongest positive association was observed between 8-isoprostane levels and benzene, PM2.5, PM10 and B(a)P. Odds ratio was 3.21 (95%CI 1.61–6.38). A significant negative association between all pollutants and IgM levels was observed even with covariate adjustment. Odds ratio was 1.80 (95%CI 1.15–2.82). A significant negative association between the alpha-1-antitrypsin levels and PM10, PM2.5, and benzene was found, independent of smoking as a covariate factor. Odds ratio was 1.77 (95%CI 1.09–2.87). In the case of IL-6, a significant effect of especially sleep as a covariate was observed. After covariates adjustment, a significant positive association between the IL-6 levels and PM10 and benzene was only observed. The odds ratio was 1.95 (95%CI 1.28–2.97).

Conclusions
The study confirmed that long-term exposure to air pollutants is associated with reduced levels of the protease inhibitor alpha-1-antitrypsin and decreased immune system performance by IgM. Furthermore, long-term exposure to air pollutants was associated with increased oxidative stress in humans, measured by 8-isoprostane levels. Residents who live in an industrial, environmentally polluted region showed elevated levels of IL-6.