Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing Pretransplant and Posttransplant Therapy Response in Multiple Myeloma Patients

Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27–42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20–73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide.
The gravitational exclusion principle and null states in anti-de Sitter space

The holographic principle implies a vast reduction in the number of degrees of freedom of quantum gravity. This idea can be made precise in AdS3, where the the stringy or gravitational exclusion principle asserts that certain perturbative excitations are not present in the exact quantum spectrum. We show that this effect is visible directly in the bulk gravity theory: the norm of the offending linearized state is zero or negative. When the norm is negative, the theory is signalling its own breakdown as an effective field theory; this provides a perturbative bulk explanation for the stringy exclusion principle. When the norm vanishes the bulk state is null rather than physical. This implies that certain non-trivial diffeomorphisms must be regarded as gauge symmetries rather than spectrum-generating elements of the asymptotic symmetry group. This leads to subtle effects in the computation of one-loop determinants for Einstein gravity, higher spin theories and topologically massive gravity in AdS3. In particular, heat kernel methods do not capture the correct spectrum of a theory with null states. Communicated by S Ross
Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs

ABSTRACT Previous studies have indicated an association of fat mass and obesity-associated (FTO) with nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. This study aimed to decipher the complex role of FTO in hepatic lipid metabolism. We found that a decrease in N6-methyladenosine (m6A) RNA methylation in the liver of mice fed with a high-fat diet (HFD) was accompanied by an increase in FTO expression. Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes. Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1 (SREBF1) and carbohydrate responsive element binding protein (ChREBP), two master lipogenic transcription factors, by demethylating m6A sites. Knockdown of either SREBF1 or ChREBP attenuated the lipogenic effect of FTO, suggesting that they are bona fide effectors for FTO in regulating lipogenesis. Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta, while knockdown of FTO abrogated the lipogenic effect of insulin. Inhibition of FTO by entacapone decreased the expression of SREBF1, ChREBP, and downstream lipogenic genes, ameliorating liver steatosis in HFD-fed mice. Thus, our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategy for treating NAFLD.
The CGM and IGM at z ∼ 5: metal budget and physical connection

We present further results of a survey for absorption line systems in the spectra of four high redshift quasars (5.79 $\le$ z$_{\textrm{em}}$ $\le$ 6.13) obtained with the ESO Very Large Telescope X-Shooter. We identify 36 $\textrm{CIV}$ and 7 $\textrm{SiIV}$ systems with a $\ge$ 5$\sigma$ significance. The highest redshift $\textrm{CIV}$ and $\textrm{SiIV}$ absorbers identified in this work are at z = 5.80738 $\pm$ 0.00017 and z = 5.77495 $\pm$ 0.00038, respectively. We compute the comoving mass density of $\textrm{SiIV}$ ($\Omega_{\textrm{SiIV}}$) and find that it evolves from $\Omega_{\textrm{SiIV}}$ = 4.3$^{+2.1}_{-2.1}$ $\times$10$^{-9}$ at = 5.05 to $\Omega_{\textrm{SiIV}}$ = 1.4$^{+0.6}_{-0.4}$ $\times$10$^{-9}$ at = 5.66. We also measure $\Omega_{\textrm{CIV}}$ = 1.6$^{+0.4}_{-0.1}$ $\times$10$^{-8}$ at = 4.77 and $\Omega_{\textrm{CIV}}$ = 3.4$^{+1.6}_{-1.1}$ $\times$10$^{-9}$ at = 5.66. We classify our $\textrm{CIV}$ absorber population by the presence of associated $\textit{low}$ and/or $\textit{high ionisation}$ systems and compute their velocity width ($\Delta$v$_{90}$). We find that all $\textrm{CIV}$ systems with $\Delta$v$_{90}$ > 200 kms$^{-1}$ have associated $\textit{low ionisation}$ systems. We investigate two such systems, separated by 550 physical kpc along a line of sight, and find it likely that they are both tracing a multi-phase medium where hot and cold gas is mixing at the interface between the CGM and IGM. We further discuss the \textrm{MgII} systems presented in a previous work and we identify 5 $\textrm{SiII}$, 10 $\textrm{AlII}$, 12 $\textrm{FeII}$, 1 $\textrm{CII}$, 7 $\textrm{MgI}$ and 1 $\textrm{CaII}$ associated transitions. We compute the respective comoving mass densities in the redshift range 2 to 6, as allowed by the wavelength coverage.
Adaptation of a short and universal learning self-efficacy scale for clinical skills in Turkish

Background The performance of a clinical task depends on an individual’s skills, knowledge, and beliefs. However, there is no reliable and valid tool for measuring self-efficacy beliefs toward clinical skills in the Turkish language. This research work aims to study the linguistic equivalence, validity, and reliability of a Self-Efficacy Scale for Clinical Skills (L-SES). Materials and methods After reaching the original item pool of the scale, applying both forward and backward translation processes, and collecting responses of 11 experts from health professional sciences and educational sciences, the translation and adoption processes were completed. We randomly divided 651 medical students’ responses to a 15-item questionnaire into two datasets and conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) analyses. Results CFA validated the three-factor model, and the model fit indexes were found to have acceptable values. The item factor loads ranged from . 34 to . 84, and items in the scale explained 47% of the total variance. Cronbach’s alpha (.91), Spearman-Brown (.88), and Guttman Split-Half (.88) coefficients obtained within the scope of internal consistency reliability demonstrated that the scale had the desired internal consistency. Conclusion The Turkish version of the short and universal learning self-efficacy scale for clinical skills questionnaire is a valid and reliable scale for measuring medical students’ self-efficacy for clinical skills. Adopted questionnaires may have different factor structures when applied to two different cultures. We also discussed this issue as a hidden pattern in our study.
A nomogram based on CHADS2 score for predicting atrial fibrillation recurrence after cryoballoon ablation

As reported, CHADS2 scoring system moderately predicts the atrial fibrillation (AF) recurrence, a common event after cryoballoon ablation. We aimed to improve the diagnostic accuracy of the CHADS2 score by adding several routine auxiliary detection indicators into the scoring system and constructing a CHADS2 score‐based nomogram to predict AF recurrence in patients with paroxysmal AF undergoing cryoballoon ablation.
Lack of volume‐outcome association in ECMO bridge to heart transplantation

Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is increasingly used as a bridge to cardiac transplantation. As the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change elevated waitlist status for patients receiving mechanical circulatory support (MCS), we aimed to determine if a center's annual heart transplant volume was associated with ECMO‐support duration and posttransplant outcomes.
Extrachromosomal DNA (ecDNA): an origin of tumor heterogeneity, genomic remodeling, and drug resistance

The genome of cancer cells contains circular extrachromosomal DNA (ecDNA) elements not found in normal cells. Analysis of clinical samples reveal they are common in most cancers and their presence indicates poor prognosis. They often contain enhancers and driver oncogenes that are highly expressed. The circular ecDNA topology leads to an open chromatin conformation and generates new gene regulatory interactions, including with distal enhancers. The absence of centromeres leads to random distribution of ecDNAs during cell division and genes encoded on them are transmitted in a non-mendelian manner. ecDNA can integrate into and exit from chromosomal DNA. The numbers of specific ecDNAs can change in response to treatment. This dynamic ability to remodel the cancer genome challenges long-standing fundamentals, providing new insights into tumor heterogeneity, cancer genome remodeling, and drug resistance.
EVOLUTION OF THE SOLAR NEBULA AND PLANET GROWTH UNDER THE INFLUENCE OF PHOTOEVAPORATION

The recent development of a new minimum mass solar nebula, under the assumption that the giant planets formed in the compact configuration of the Nice model, has shed new light on planet formation in the solar system. Desch previously found that a steady state protoplanetary disk with an outer boundary truncated by photoevaporation by an external massive star would have a steep surface density profile. In a completely novel way, we have adapted numerical methods for solving propagating phase change problems to astrophysical disks. We find that a one-dimensional time-dependent disk model that self-consistently tracks the location of the outer boundary produces shallower profiles than those predicted for a steady state disk. The resulting surface density profiles have a radial dependence of with a power-law exponent that in some models becomes as large as ∼Σ(r) ∝ r−2.1. The evolutionary timescales of the model disks can be sped up or slowed down by altering the amount of far-ultraviolet flux or the viscosity parameter α. Slowing the evolutionary timescale by decreasing the incident far-ultraviolet flux, or similarly by decreasing α, can help to grow planets more rapidly, but at the cost of decreased migration timescales. Although they similarly affect relevant timescales, changes in the far-ultraviolet flux or α produce disks with drastically different outer radii. Despite their differences, these disks are all characterized by outward mass transport, mass loss at the outer edge, and a truncated outer boundary. The transport of mass from small to large radii can potentially prevent the rapid inward migration of Jupiter and Saturn, while at the same time supply enough mass to the outer regions of the disk for the formation of Uranus and Neptune.
Rapid Bactericidal Activity of SC5005 Combined with Docosahexaenoic Acid against Multidrug-Resistant Staphylococcus aureus Persisters and Biofilms

Staphylococcus aureus can form persister cells and biofilms, making the treatment difficult and often leading to recurrent infections. In an effort to discover new anti-staphylococcal agents, we observed that oleic acid enhances the activity of a new antibacterial agent, SC5005, against S. aureus and MRSA strains. ABSTRACT Staphylococcus aureus can form persister cells and biofilms, making the treatment difficult and often leading to recurrent infections. In an effort to discover new anti-staphylococcal agents, we observed that oleic acid enhances the activity of a new antibacterial agent, SC5005, against S. aureus and MRSA strains. Subsequent studies showed that saturated or trans-form unsaturated fatty acids did not potentiate SC5005’s antibacterial activity. SC5005 only exhibits synergistic bactericidal activity with cis-form unsaturated fatty acids with 16 to 22 carbon atoms. In particular, docosahexaenoic acid (DHA) could reduce the MIC of SC5005 to the subng/mL range against different MRSA strains, including those resistant to second- and third-line antibiotics. However, we did not detect any significant shift in SC5005’s cytotoxicity toward four different mammalian cell lines, suggesting that the synergy of DHA and SC5005 is highly selective. Most importantly, this combination demonstrated fast-killing activity, completely eradicating MRSA USA300 planktonic and persister cells within 10 and 30 min, respectively, and removing nearly 98% of MRSA biofilms within 1 min. Together, our findings suggest that the combination of SC5005 and DHA has great potential as a new therapeutic for the treatment of infections caused by multidrug-resistant (MDR) S. aureus biofilms.
Long-term X-ray spectral variability in AGN from the Palomar sample observed by Swift

We present X-ray spectral variability of 24 local active galactic nuclei (AGN) from the Palomar sample of nearby galaxies, as observed mainly by Swift. From hardness ratio measurements, we find that 18 AGN with low accretion rates show hardening with increasing count rate, converse to the softer-when-brighter behaviour normally observed in AGN with higher accretion rates. Two AGN show softening with increasing count rate, two show more complex behaviour, and two do not show any simple relationship. Sufficient data were available for the spectra of 13 AGN to be summed in flux-bins. In nine of these sources, correlated luminosity-dependent changes in the photon index (? ) of a power-law component are found to be the main cause of hardness variability. For six objects, with a low accretion rate as a fraction of the Eddington rate (m? Edd), ? is anticorrelated with m? Edd, i.e. ‘harder-when-brighter’ behaviour is observed. The three higher m? Edd-rate objects show a positive correlation between ? and m? Edd. This transition from harder-when-brighter at low m? Eddto softer-when-brighter at high m? Edd can be explained by a change in the dominant source of seed-photons for X-ray emission from cyclo-synchrotron emission from the Comptonizing corona itself to thermal seed-photons from the accretion disc. This transition is also seen in the ‘hard state’ of black hole X-ray binaries (BHXRBs). The results support the idea that low-ionization nuclear emission-line regions are analogues of BHXRBs in the hard state and that Seyferts are analogues of BHXRBs in either the high-accretion rate end of the hard state or in the hard-intermediate state.
TOWARD PRECISION SUPERMASSIVE BLACK HOLE MASSES USING MEGAMASER DISKS

Megamaser disks provide the most precise and accurate extragalactic supermassive black hole (BH) masses. Here we describe a search for megamasers in nearby galaxies using the Green Bank Telescope (GBT). We focus on galaxies where we believe that we can resolve the gravitational sphere of influence of the BH and derive a stellar or gas dynamical measurement with optical or NIR observations. Since there are only a handful of super massive BHs that have direct BH mass measurements from more than one method, even a single galaxy with a megamaser disk and a stellar dynamical BH mass would provide necessary checks on the stellar dynamical methods. We targeted 87 objects from the Hobby–Eberly Telescope Massive Galaxy Survey, and detected no new maser disks. Most of the targeted objects are elliptical galaxies with typical stellar velocity dispersions of 250 km s−1 and distances within 130 Mpc. We discuss the implications of our non-detections, whether they imply a threshold X-ray luminosity required for masing, or possibly reflect the difficulty of maintaining a masing disk around much more massive ( ≳ 10 8 ? > M ⊙ ? > ) BHs at a low Eddington ratio. Given the power of maser disks for probing BH accretion and demographics, we suggest that future maser searches should endeavour to remove remaining sample biases, in order to sort out the importance of these covariant effects.
Near-Infrared Evidence for a Sudden Temperature Increase in Eta Carinae

Aims. Eta Car's ultra-violet, optical, and X-ray light curves and its spectrum suggest a physical change in its stellar wind over the last decade. It was proposed that the mass-loss rate decreased by a factor of about 2 in the last 15 years. We complement these recent results by investigating the past evolution and the current state of eta Car in the near-infrared (IR). Methods. We present JHKL photometry of eta Car obtained at SAAO Sutherland from 2004-2013 with the Mk II photometer at the 0.75-m telescope and JHKs photometry with SIRIUS at the 1.4-m IRSF telescope from 2012-2013. The near-IR light curves since 1972 are analyzed. Results. The long-term brightening trends in eta Car's JHKL light curves were discontinuous around the 1998 periastron passage. After 1998, the star shows excess emission above the extrapolated trend from earlier dates, foremost in J and H, and the blueward, cyclical progression in its near-IR colors is accelerated. The near-IR color evolution is strongly correlated with the periastron passages. After correcting for the secular trend we find that the color evolution matches an apparent increase in blackbody temperature of an optically thick near-IR emitting plasma component from about 3500 to 6000 K over the last 20 years. Conclusions. We suggest that the changing near-IR emission may be caused by variability in optically thick bremsstrahlung emission. Periastron passages play a key role in the observed excess near-IR emission after 1998 and the long-term color evolution. We thus propose as a hypothesis that angular momentum transfer (via tidal acceleration) during periastron passages leads to sudden changes in eta Car's atmosphere resulting in a long-term decrease in the mass-loss rate.
SELF-SUSTAINED ASYMMETRY OF LEPTON-NUMBER EMISSION: A NEW PHENOMENON DURING THE SUPERNOVA SHOCK-ACCRETION PHASE IN THREE DIMENSIONS

During the stalled-shock phase of our three-dimensional, hydrodynamical core-collapse simulations with energy-dependent, three-flavor neutrino transport, the lepton-number flux (νe minus ) emerges predominantly in one hemisphere. This novel, spherical-symmetry breaking neutrino-hydrodynamical instability is termed LESA for “Lepton-number Emission Self-sustained Asymmetry. ” While the individual νe and fluxes show a pronounced dipole pattern, the heavy-flavor neutrino fluxes and the overall luminosity are almost spherically symmetric. Initially, LESA seems to develop stochastically from convective fluctuations. It exists for hundreds of milliseconds or more and persists during violent shock sloshing associated with the standing accretion shock instability. The νe minus flux asymmetry originates predominantly below the neutrinosphere in a region of pronounced proto-neutron star (PNS) convection, which is stronger in the hemisphere of enhanced lepton-number flux. On this side of the PNS, the mass accretion rate of lepton-rich matter is larger, amplifying the lepton-emission asymmetry, because the spherical stellar infall deflects on a dipolar deformation of the stalled shock. The increased shock radius in the hemisphere of less mass accretion and minimal lepton-number flux ( flux maximum) is sustained by stronger convection on this side, which is boosted by stronger neutrino heating due to . Asymmetric heating thus supports the global deformation despite extremely nonstationary convective overturn behind the shock. While these different elements of the LESA phenomenon form a consistent picture, a full understanding remains elusive at present. There may be important implications for neutrino-flavor oscillations, the neutron-to-proton ratio in the neutrino-heated supernova ejecta, and neutron-star kicks, which remain to be explored.
Cyclin-Dependent Kinase 5 Regulates cPLA2 Activity and Neuroinflammation in Parkinson’s Disease

Abstract Hyperactivation of cyclin-dependent kinase 5 (Cdk5) by p25, contributes to neuroinflammation causing neurodegeneration in Parkinson’s disease (PD) and Alzheimer’s disease. However, the mechanism by which Cdk5 induces neuroinflammation in the PD brain is largely unexplored. Here, we show that Cdk5 phosphorylates cytosolic phospholipase A2 (cPLA2) at Thr-268 and Ser-505 sites lead to its activation and generation of eicosanoid products. Mutational studies using site-directed mutagenesis and molecular simulations show that the architecture of the protein changes on each single-point mutation. Interestingly, double mutations also led to a severe decline in the activity of cPLA2 and to the disruption of its translocation to the plasma membrane. Further, the brain lysates of transgenic PD mouse models show hyperactivation of Cdk5, resulting in enhanced phosphorylation of Thr-268 and Ser-505 of cPLA2 and its heightened activity, confirming the findings observed in the cell culture model of PD. These phosphorylation sites of cPLA2 and Cdk5 could be explored as the future therapeutic targets against neuroinflammation in PD. Further, conjoint transcriptomic analysis of the publicly available human PD datasets strengthens the hypothesis that genes of the arachidonic acid, prostaglandin synthesis, and inflammatory pathways are significantly upregulated in the case of PD patients compared with that of healthy control subjects.
Critical mingling and universal correlations in model binary active liquids

Ensembles of driven or motile bodies moving along opposite directions are generically reported to self-organize into strongly anisotropic lanes. Here, building on a minimal model of self-propelled bodies targeting opposite directions, we first evidence a critical phase transition between a mingled state and a phase-separated lane state specific to active particles. We then demonstrate that the mingled state displays algebraic structural correlations also found in driven binary mixtures. Finally, constructing a hydrodynamic theory, we single out the physical mechanisms responsible for these universal long-range correlations typical of ensembles of oppositely moving bodies.