Miracle-dz/UniFAR-FTUs huggingface dataset:
Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.
Probing the formation of the seeds of supermassive black holes with gravitational waves

The existence of black holes in the intermediate mass interval between one hundred and ten thousand solar masses, filling the gap between the stellar and the supermassive black holes is a key prediction to explain the origin of luminous QSOs at redshifts as large as seven. There is a sheer difficulty in forming giant black holes of billion suns in less than one billion years. This has led to the concept of seed black holes. They are high redshift intermediate mass black holes that formed during cosmic dawn. Seeds are a transient population, which later grew massive through episodes of accretion and mergers. In this chapter we explore the possibility of discovering seed black holes and track their growth across all cosmic epoch, by detecting the gravitational wave signal they emit at the time of their coalescence, when they pair to form close binaries. We show that the ESA LISA mission for the detection of low frequency gravitational waves will be paramount in granting this insight. Gravitational waves travel unimpeded through the cosmos and carry exquisite information on the masses and spins of the merging black holes. To this purpose we introduce key concepts on the gravitational wave emission from binaries, describing briefly their formation pathway during halo mergers and galaxy collisions.
Singularity resolution in quantum gravity

We examine the singularity resolution issue in quantum gravity by studying a new quantization of standard Friedmann-Robertson-Walker geometrodynamics. The quantization procedure is inspired by the loop quantum gravity program, and is based on an alternative to the Schr\"odinger representation normally used in metric variable quantum cosmology. We show that in this representation for quantum geometrodynamics there exists a densely defined inverse scale factor operator, and that the Hamiltonian constraint acts as a difference operator on the basis states. We find that the cosmological singularity is avoided in the quantum dynamics. We discuss these results with a view to identifying the criteria that constitute ``singularity resolution'' in quantum gravity.
Molecular Events in the Melanogenesis Cascade as Novel Melanoma-Targeted Small Molecules: Principle and Development

Simple Summary Melanin biosynthesis can be a unique pathway to identify novel anti-melanoma targeted molecules. In this approach, we specifically focused on the substrate of tyrosinase, which is highly expressed in malignant melanoma. Among the various forms of melanogenesis substrate synthesized, N-propionyl cysteaminylphenol was exploited to develop a melanoma-targeted chemo-immunotherapy drug because of its selective incorporation into melanoma cells and production of highly reactive molecules, which not only result in apoptotic cell death but also the generation of heat shock proteins by reacting with tyrosinase. Moreover, the drug was attached to magnetite nanoparticles in order to enable the heating of melanoma cells when they are exposed to an alternating magnetic field, which causes non-apoptotic cell death and further heat-shock protein generation (thermo-immunotherapy). Here, we review our synthesis of melanogenesis-based anti-melanoma molecules and development of selective chemo-thermo-immuno-therapy by combining these molecules with the magnetite-nanoparticles. We compare this strategy to other melanogenesis-based chemotherapy and thermal medicine systems, and discuss targeted therapies with immune checkpoint inhibitors for unresectable/metastatic melanoma. Abstract Malignant melanoma is one of the most malignant of all cancers. Melanoma occurs at the epidermo–dermal interface of the skin and mucosa, where small vessels and lymphatics are abundant. Consequently, from the onset of the disease, melanoma easily metastasizes to other organs throughout the body via lymphatic and blood circulation. At present, the most effective treatment method is surgical resection, and other attempted methods, such as chemotherapy, radiotherapy, immunotherapy, targeted therapy, and gene therapy, have not yet produced sufficient results. Since melanogenesis is a unique biochemical pathway that functions only in melanocytes and their neoplastic counterparts, melanoma cells, the development of drugs that target melanogenesis is a promising area of research. Melanin consists of small-molecule derivatives that are always synthesized by melanoma cells. Amelanosis reflects the macroscopic visibility of color changes (hypomelanosis). Under microscopy, melanin pigments and their precursors are present in amelanotic melanoma cells. Tumors can be easily targeted by small molecules that chemically mimic melanogenic substrates. In addition, small-molecule melanin metabolites are toxic to melanocytes and melanoma cells and can kill them. This review describes our development of chemo-thermo-immunotherapy based on the synthesis of melanogenesis-based small-molecule derivatives and conjugation to magnetite nanoparticles. We also introduce the other melanogenesis-related chemotherapy and thermal medicine approaches and discuss currently introduced targeted therapies with immune checkpoint inhibitors for unresectable/metastatic melanoma.
Growth of quotients of groups acting by isometries on Gromov hyperbolic spaces

We show that every non-elementary group $G$ acting properly and cocompactly by isometries on a proper geodesic Gromov hyperbolic space $X$ is growth tight. In other words, the exponential growth rate of $G$ for the geometric (pseudo)-distance induced by $X$ is greater than the exponential growth rate of any of its quotients by an infinite normal subgroup. This result generalizes from a unified framework previous works of Arzhantseva-Lysenok and Sambusetti, and provides an answer to a question of the latter.
Electrical Switching of Antiferromagnetic 
Mn2Au
 and the Role of Thermal Activation

Electrical manipulation of antiferromagnets with specific symmetries offers the prospect of creating novel, antiferromagnetic spintronic devices. Such devices aim to make use of the insensitivity to external magnetic fields and the ultrafast dynamics at the picosecond timescale intrinsic to antiferromagnets. The possibility to electrically switch antiferromagnets was first predicted for Mn2Au and then experimentally observed in tetragonal CuMnAs. Here, we report on the electrical switching and detection of the Neel order in epitaxial films of Mn2Au. The exponential dependences of the switching amplitude on the current density and the temperature are explained by a macroscopic thermal activation model taking into account the effect of the Joule heating in Hall cross devices and we observe that the thermal activation plays a key role in the reorientation process of the Neel order. Our model analysis shows that the electrically set Neel-state is long-term stable at room temperature, paving the way for practical applications in memory devices.
Non-Gaussianity of multiple photon-subtracted thermal states in terms of compound-Poisson photon number distribution parameters: theory and experiment

The multiphoton-subtracted thermal states are an interesting example of quantum states of light which are both classical and non-Gaussian. All the properties of such states can be described by just two parameters of compound-Poisson photon number distribution. The non-Gaussianity dependence on these parameters is calculated numerically and analytically. The loss of non-Gaussianity during the optical damping is also studied experimentally.
Radiation from the Relativistic Jet: A Role of the Shear Boundary Layer

Recent radio and optical large-scale jet observations suggest a two-component jet morphology, consisting of a fast central spine surrounded by a boundary layer with a velocity shear. We study radiation of electrons accelerated at such boundary layers as an option for standard approaches involving internal shocks in jets. The acceleration process in the boundary layer yields in a natural way a two-component electron distribution: a power-law continuum with a bump at the energy where energy gains equal radiation losses, followed by a cutoff. For such distributions, we derive the observed spectra of synchrotron and inverse Compton radiation, including Comptonization of synchrotron and cosmic microwave background photons. Under simple assumptions of energy equipartition between the relativistic particles and the magnetic field, the relativistic jet velocity at large scales, and a turbulent character of the shear layer, the considered radiation can substantially contribute to the jet radiative output. In the considered conditions the synchrotron emission is characterized by a spectral index of the radio-to-optical continuum being approximately constant along the jet. A characteristic feature of the obtained broadband synchrotron spectrum is an excess at X-ray frequencies, similar to the one observed in some objects by Chandra. As compared to the uniform jet models, the velocity shear across the radiating boundary region leads to a decrease and frequency dependence of the observed jet-counterjet radio brightness asymmetry. We conclude that a careful investigation of the observational data looking for the derived effects can allow us to evaluate the role of the boundary layer acceleration processes and/or impose constraints for the physical parameters of such layers in large-scale jets.
Dusty Debris around Solar-Type Stars: Temporal Disk Evolution

Using ISO-ISOPHOT, we carried out a survey of almost 150 stars to search for evidence of emission from dust orbiting young main-sequence stars, both in clusters and isolated systems. Over half of the detections are new examples of dusty stellar systems and demonstrate that such dust can be detected around numerous stars older than a few times 106 yr. Fluxes at 60 and either 90 or 100 μm for the new excess sources together with improved fluxes for a number of IRAS-identified sources are presented. Analysis of the excess luminosity relative to the stellar photosphere shows a systematic decline of this excess with stellar age consistent with a power-law index of -2.
Climatic niche divergence explains angiosperm diversification across clades in China

Diversification rates are critically important for understanding patterns of species richness among clades. However, the effects of climatic niche width on plant diversification rates remain to be elucidated. Based on the phylogenetic, climatic, and distributional information of angiosperms in China, a total of 26 906 species from 182 families were included in this study. We aimed to test relationships between diversification rate and climatic niche width and climatic niche width related variables (including climatic niche divergence, climatic niche position, geographic extent, and climatic niche evolutionary rate) using phylogenetic methods. We found that climatic niche divergence had the largest unique contribution to the diversification rate, while the unique effects of climatic niche width, climatic niche position, geographic extent, and climatic niche evolutionary rate on the diversification rate were negligible. We also observed that the relationship between diversification rate and climatic niche divergence was significantly stronger than the null assumption (artefactual relationship between diversification and clade‐level climatic niche width by sampling more species). Our study supports the hypothesis that wider family climatic niche widths explain faster diversification rates through a higher climatic niche divergence rather than through higher geographic extent, higher climatic niche evolutionary rate, or separated climatic niche position. Hence, the results provide a potential explanation for large‐scale diversity patterns within families of plants.
Forward Asteroseismic Modeling of Stars with a Convective Core from Gravity-mode Oscillations: Parameter Estimation and Stellar Model Selection

We propose a methodological framework to perform forward asteroseismic modeling of stars with a convective core, based on gravity-mode oscillations. These probe the near-core region in the deep stellar interior. The modeling relies on a set of observed high-precision oscillation frequencies of low-degree coherent gravity modes with long lifetimes and their observational uncertainties. Identification of the mode degree and azimuthal order is assumed to be achieved from rotational splitting and/or from period spacing patterns. This paper has two major outcomes. The first is a comprehensive list and discussion of the major uncertainties of theoretically predicted gravity-mode oscillation frequencies based on linear pulsation theory, caused by fixing choices of the input physics for evolutionary models. Guided by a hierarchy among these uncertainties of theoretical frequencies, we subsequently provide a global methodological scheme to achieve forward asteroseismic modeling. We properly take into account correlations among the free parameters included in stellar models. Aside from the stellar mass, metallicity, and age, the major parameters to be estimated are the near-core rotation rate, the amount of convective core overshooting, and the level of chemical mixing in the radiative zones. This modeling scheme allows for maximum likelihood estimation of the stellar parameters for fixed input physics of the equilibrium models, followed by stellar model selection considering various choices of the input physics. Our approach uses the Mahalanobis distance instead of the often-used χ2 statistic and includes heteroscedasticity. It provides estimation of the unknown variance of the theoretically predicted oscillation frequencies.
Insensitivity of the distance ladder Hubble constant determination to Cepheid calibration modelling choices

Recent determination of the Hubble constant via Cepheid-calibrated supernovae by \citet{riess_2. 4_2016} (R16) find $\sim 3\sigma$ tension with inferences based on cosmic microwave background temperature and polarization measurements from $Planck$. This tension could be an indication of inadequacies in the concordance $\Lambda$CDM model. Here we investigate the possibility that the discrepancy could instead be due to systematic bias or uncertainty in the Cepheid calibration step of the distance ladder measurement by R16. We consider variations in total-to-selective extinction of Cepheid flux as a function of line-of-sight, hidden structure in the period-luminosity relationship, and potentially different intrinsic color distributions of Cepheids as a function of host galaxy. Considering all potential sources of error, our final determination of $H_0 = 73.3 \pm 1.7~{\rm km/s/Mpc}$ (not including systematic errors from the treatment of geometric distances or Type Ia Supernovae) shows remarkable robustness and agreement with R16. We conclude systematics from the modeling of Cepheid photometry, including Cepheid selection criteria, cannot explain the observed tension between Cepheid-variable and CMB-based inferences of the Hubble constant. Considering a `model-independent' approach to relating Cepheids in galaxies with known distances to Cepheids in galaxies hosting a Type Ia supernova and finding agreement with the R16 result, we conclude no generalization of the model relating anchor and host Cepheid magnitude measurements can introduce significant bias in the $H_0$ inference.
Relationship between Pain Intensity, Physical Factors, Pronociceptive Pain Modulation Profile and Psychological Vulnerability on Upper Limb Disability in Older Patients with Chronic Shoulder Pain

Background: Chronic shoulder pain is a very prevalent condition causing disability and functional impairment. The purpose of the study was to evaluate the relationship between pain intensity, physical variables, psychological vulnerability, pronociceptive pain modulation profile and disability in older people with chronic shoulder pain. Methods: A cross-sectional study was carried out. A total of 56 participants with non-specific chronic shoulder pain of the “Complejo Hospitalario Universitario” (Granada) and 56 healthy controls were included. The outcomes evaluated were pain intensity (visual analogue scale), physical factors (dynamometry for grip strength), psychological vulnerability (Fear-Avoidance Beliefs Questionnaire and Tampa Scale of Kinesiophobia), pronociceptive pain modulation profile (pain pressure algometry) and disability (Quick Disability Arm Shoulder Hand questionnaire). Results: Disability showed a positive correlation with pain and psychological vulnerability (p < 0.05) and a negative correlation with pronociceptive pain variables and dynamometry (p < 0.001). Psychological vulnerability also presented a strong negative correlation with proprioceptive pain variables and dynamometry and a positive correlation with pain (p < 0.05). In regard to the pronociceptive pain modulation profile, a strong negative correlation with pain (p < 0.001) and a positive moderate correlation with dynamometry (p < 0.001) were shown. Conclusions: Our results support a strong association between disability, psychological vulnerability and pronociceptive pain modulation profile in older adults with chronic shoulder pain.
The Attitude of King Saud University Medical Students Toward Online Distance Learning During the COVID-19 Pandemic

Objective To explore the attitudes of medical students at King Saud University (KSU) toward online distance learning during the COVID-19 pandemic and to examine the effects of gender, academic year and level of computer skills on student attitudes toward distance learning. Methods A previously validated questionnaire was distributed to participants via WhatsApp using a stratified random sampling method. Data were analyzed using SPSS version 26.0 statistical software. Means and standard deviations were used to examine quantitative variables, while frequencies and percentages were used to examine qualitative variables. Results Our study included 533 students; 71.9% of participants were satisfied with online classes, while 59.6% struggled to receive explanations due to limitations to face-to-face interactions. Two-thirds of participants thought that online classes were more convenient because of their flexibility with respect to location. A similar proportion (65.3%) believed that in situations of distance learning, it was difficult to meet and work with friends. The majority (88.7%) of participants agreed that distance learning saved time and effort spent traveling to campus. Finally, most participants 355 (66.6%), favored blended learning, while only 111 (20.8%) of participants preferred in-class learning. Students in preclinical years had more negative attitudes regarding face-to-face interactions (66.5% vs 54.9%, P=0.027) and meeting with friends (69.3% vs 58.7%, P=0.026) than did students in clinical years. Gender and level of computer skills did not affect students’ attitudes toward distance learning (P > 0.05). Conclusion The majority of student participants felt that online distance learning was an effective option during the pandemic, but they preferred to preserve face-to-face teaching as a concurrent option. Attitudes toward certain aspects of distance learning were more negative among students in preclinical years than among students in clinical years. We did not find any effects of gender or level of computer skills on student attitudes toward distance learning.
The Impact of Magnetic Fields on Thermal Instability

Cold ($T\sim 10^{4} \ \mathrm{K}$) gas is very commonly found in both galactic and cluster halos. There is no clear consensus on its origin. Such gas could be uplifted from the central galaxy by galactic or AGN winds. Alternatively, it could form in situ by thermal instability. Fragmentation into a multi-phase medium has previously been shown in hydrodynamic simulations to take place once $t_\mathrm{cool}/t_\mathrm{ff}$, the ratio of the cooling time to the free-fall time, falls below a threshold value. Here, we use 3D plane-parallel MHD simulations to investigate the influence of magnetic fields. We find that because magnetic tension suppresses buoyant oscillations of condensing gas, it destabilizes all scales below $l_\mathrm{A}^\mathrm{cool} \sim v_\mathrm{A} t_\mathrm{cool}$, enhancing thermal instability. This effect is surprisingly independent of magnetic field orientation or cooling curve shape, and sets in even at very low magnetic field strengths. Magnetic fields critically modify both the amplitude and morphology of thermal instability, with $\delta \rho/\rho \propto \beta^{-1/2}$, where $\beta$ is the ratio of thermal to magnetic pressure. In galactic halos, magnetic fields can render gas throughout the entire halo thermally unstable, and may be an attractive explanation for the ubiquity of cold gas, even in the halos of passive, quenched galaxies.
The stellar cusp around the Milky Way’s central black hole

The existence of stellar cusps in dense clusters around massive black holes is a fundamental, decades-old prediction of theoretical stellar dynamics. Yet, observational evidence has been difficult to obtain. With a new, improved analysis of high-angular resolution images of the central parsecs of the Galactic Center, we are finally able to provide the first solid evidence for the existence of a stellar cusp around the Milky Way’s massive black hole. The existence of stellar cusps has a significant impact on predicted event rates of phenomena like tidal disruptions of stars and extreme mass ratio inspirals.
Rotation in young massive star clusters

Hydrodynamical simulations of turbulent molecular clouds show that star clusters form from the hierarchical merger of several sub-clumps. We run smoothed-particle hydrodynamics simulations of turbulence-supported molecular clouds with mass ranging from 1700 to 43000 Msun. We study the kinematic evolution of the main cluster that forms in each cloud. We find that the parent gas acquires significant rotation, because of large-scale torques during the process of hierarchical assembly. The stellar component of the embedded star cluster inherits the rotation signature from the parent gas. Only star clusters with final mass ~1000 Msun) star clusters. This might provide a key observational test for the hierarchical assembly scenario.