Miracle-dz/UniFAR-FTUs huggingface dataset:
Egg-adaptive mutations of human influenza H3N2 virus are contingent on natural evolution

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine.
Dissipation regimes for short wind waves

[1] The dissipation processes affecting short wind waves of centimeter and decimeter scales are investigated experimentally in laboratory. The processes include damping due to molecular viscosity, generation of capillary waves, microbreaking, and breaking. The observations were made in a large wind wave tank for a wide range of fetches and winds, using a laser sheet and a high-resolution video camera. The work aims at constructing a comprehensive picture of dissipative processes in the short wind wave field, to find for which scales particular dissipative mechanism may become important. Four distinct regimes have been identified. For capillary-gravity wave fields, i.e., for dominant waves with scales below 4 cm, viscous damping is found to be the main dissipation mechanism. The gravity-capillary wave fields with dominant wavelength less than 10 cm usually exhibit a train of capillary ripples at the crest wavefront, but no wave breaking. For such waves, the main dissipation process is molecular viscosity occurring through nonlinear energy cascade toward high-frequency motions. Microscale breaking takes place for waves longer than 10 cm and manifests itself in a very localized surface disruption on the forward face of the crest. Such events generate turbulent motions in water and thus enhance wave dissipation. Plunging breaking, characterized by formation of a crest bulge, a microjet hitting the water surface and a splash-up, occurs for short gravity waves of wavelength exceeding 20 cm. Macroscale spilling breaking is also observed for longer waves at high winds. In both cases, the direct momentum transfer from breaking waves to the water flow contributes significantly to wave damping.
Shadowing effects on J/ψ and Υ production at energies available at the CERN Large Hadron Collider

Proton-nucleus collisions have been used as a intermediate baseline for the determination of cold medium effects. They lie between proton-proton collisions in vacuum and nucleus-nucleus collisions which are expected to be dominated by hot matter effects. Modifications of the quark densities in nuclei relative to those of the proton are well established although those of the gluons in the nucleus are not well understood. We focus on the effect of these on quarkonium production in proton-lead collisions at the LHC at a center of mass energy of 5.02 TeV.
Advances in therapeutic targeting of immune checkpoints receptors within the CD96-TIGIT axis: clinical implications and future perspectives

ABSTRACT Introduction The development of therapeutic antibodies targeting immune checkpoint molecules (ICMs) that induce long-term remissions in cancer patients has revolutionized cancer immunotherapy. However, a major drawback is that relapse after an initial response may be attributed to innate and acquired resistance. Additionally, these treatments are not beneficial to all patients. Therefore, the discovery and targeting of novel ICMs and their combination with other immunotherapeutics are urgently needed. Areas covered There has been increasing evidence of the CD96-TIGIT axis as ICMs in cancer immunotherapy in the last five years. This review will highlight and discuss the current knowledge about the role of CD96 and TIGIT in hematological and solid tumor immunotherapy in the context of empirical studies and clinical trials, and provide a comprehensive list of ongoing cancer clinical trials on the blockade of these ICMs, as well as the rationale behind combinational therapies with anti-PD-1/PD-L1 agents, chemotherapy drugs, and radiotherapy. Moreover, we share our perspectives on anti-CD96/TIGIT-related combination therapies. Expert opinion CD96-TIGIT axis regulates anti-tumor immune responses. Thus, the receptors within this axis are the potential candidates for cancer immunotherapy. Combining the inhibition of CD96-TIGIT with anti-PD-1/PD-L1 mAbs and chemotherapy drugs has shown relatively effective results in the context of preclinical studies and tumor models.
A plant‐derived glucocorticoid receptor modulator with potency to attenuate the side effects of glucocorticoid therapy

Continuous efforts have been made to move towards maintaining the beneficial anti‐inflammatory functions of glucocorticoids (GCs) while minimizing side effects. Here, we investigated the selective glucocorticoid receptor (GR) modulator‐like properties of a plant‐derived compound caesaldekarin e (CA‐e).
Optimizing laboratory-based surveillance networks for monitoring multi-genotype or multi-serotype infections

With the aid of laboratory typing techniques, infectious disease surveillance networks have the opportunity to obtain powerful information on the emergence, circulation, and evolution of multiple genotypes, serotypes or other subtypes of pathogens, informing understanding of transmission dynamics and strategies for prevention and control. The volume of typing performed on clinical isolates is typically limited by its ability to inform clinical care, cost and logistical constraints, especially in comparison with the capacity to monitor clinical reports of disease occurrence, which remains the most widespread form of public health surveillance. Viewing clinical disease reports as arising from a latent mixture of pathogen subtypes, laboratory typing of a subset of clinical cases can provide inference on the proportion of clinical cases attributable to each subtype (i.e., the mixture components). Optimizing protocols for the selection of isolates for typing by weighting specific subpopulations, locations, time periods, or case characteristics (e.g., disease severity), may improve inference of the frequency and distribution of pathogen subtypes within and between populations. Here, we apply the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework to simulate and optimize hand foot and mouth disease (HFMD) surveillance in a high-burden region of western China. We identify laboratory surveillance designs that significantly outperform the existing network: the optimal network reduced mean absolute error in estimated serotype-specific incidence rates by 14.1%; similarly, the optimal network for monitoring severe cases reduced mean absolute error in serotype-specific incidence rates by 13.3%. In both cases, the optimal network designs achieved improved inference without increasing subtyping effort. We demonstrate how the DIOS framework can be used to optimize surveillance networks by augmenting clinical diagnostic data with limited laboratory typing resources, while adapting to specific, local surveillance objectives and constraints.
Algorithmic theory of numbers, graphs and convexity

How to Round Numbers Preliminaries: On Algorithms Involving Numbers Diophantine Approximation, Problems Lattices, Bases, and the Reduction Problem Diophantine Approximation and Rounding What is a Real Number How to Round a Convex Body Preliminaries: Inputting a Set Algorithmic Problems on Convex Sets The Ellipsoid Method Rational Polyhedra Some Other Algorithmic Problems on Convex Sets Integer Programming in Fixed Dimension Some Applications in Combinatorics Cuts and Joins Chromatic Number, Cliques and Perfect Graphs Minimizing a Submodular Function.
Male fertility in Pyricularia oryzae: Microconidia are spermatia

Abstract Sexual reproduction in Ascomycetes is well described in several model organisms such as Neurospora crassa or Podospora anserina. Deciphering the biological process of sexual reproduction (from the recognition between compatible partners to the formation of zygote) can be a major advantage to better control sexually reproducing pathogenic fungi. In Pyricularia oryzae, the fungal pathogen causing blast diseases on several Poaceae species, the biology of sexual reproduction remains poorly documented. Besides the well‐documented production of asexual macroconidia, the production of microconidia was seldom reported in P. oryzae, and their role as male gamete (i.e., spermatia) and in male fertility has never been explored. Here, we characterised the morphological features of microconidia and demonstrated that they are bona fide spermatia. Contrary to macroconidia, microconidia are not able to germinate and seem to be the only male gametes in P. oryzae. We show that fruiting body (perithecium) formation requires microconidia to get in contact with mycelium of strains of opposite mating type, to presumably fertilise the female gametes.
Numerical investigation on red blood cell flow based on unstructured grid

Prediction of blood cell flow is known as the difficult research by reason of the complexity of blood vessel. In this study, considering the complex structure of blood vessels, a mechanical model for red blood cell (RBC) based on unstructured grid has been established to study the flow characteristics of RBCs in complex blood vessels. In the model, the strain‐energy function by Skalak is employed to model the shear elasticity and surface‐area conservation of the membrane, and the hinge spring is used to describe the forces originating from local bending of the membrane. The immersed boundary method is utilized to couple the interphase force. Using the model, the stretching test of RBC is compared with the experiment data, and the good agreement verified the validation of the present model. The morphology of red blood cell and the blood viscosity in micro‐vessel are studied. RBCs move with a symmetric shape (parachute shape) in small blood vessels, and the buckling instability is observed when the RBC flow slowly through a micro‐vessel or a converging–diverging capillary. When the vessel diameter is around 10 μm, the reverse Fahraeus‐Lindqvist effect is presented. The blood apparent viscosity shows linear increase with the blood hematocrit. In addition, Malaria infection can make the RBC deformability decreased and the blood apparent viscosity increased.
Homological characterisation of Lambda-ranks

If G is a pro-p, p-adic, Lie group and if $\Lambda(G)$ denotes the Iwasawa algebra of G then we present a formula for determining the $\Lambda(G)$-rank of a finitely generated $\Lambda(G)$-module. This is given in terms of the G homology groups of the module. We explore some consequences of this for the structure of $\Lambda(G)$-modules.
Comparison of maternal and neonatal gut microbial community and function in a porcine model

Abstract Our knowledge of the difference in maternal and neonatal gut microbiota composition is not fully understood. Using the Bama miniature pig model, the bacterial community in the feces from sows and piglets was analyzed on an IonS5TMXL platform targeting the single-end reads strategy. Results revealed that the maternal and neonatal bacteria profile in the pig model was distinct. Compared with the piglets, sows had higher proportions of bacteria in Spirochetes, Clostridiales, and Spirochaetales (p < 0.10) and had a lower abundance of bacteria in Tyzzerella (p < 0.05) and Alistipes (p < 0.10). Meanwhile, the proportions of bacteria in Oscillibacter and the index of Chao1, Shannon, and observed_species increased in the sows compared with those in the piglets (p < 0.05). Moreover, the abundance of bacteria associated with the human disease was higher (p < 0.05) and the population of bacteria associated with cellular processes was lower (p < 0.05) in the piglets compared with those in the sows. Collectively, the diversity and beneficial bacteria populations in the sow fecal microbiota exhibit more than those in the piglets. This study indicates that maternal fecal microbiota may be a beneficial source of transplanted bacteria to promote healthy function in neonates.
Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex‐specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)–associated cirrhosis by small RNA‐sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty‐five (64 up‐regulated, 1 down‐regulated) and 12 (6 up‐regulated, 6 down‐regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix–receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex‐specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex‐specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV‐associated cirrhosis are distinct between the males and females and suggest a potential role of sex‐specific biomarkers and molecular mechanisms in disease development and progression.
What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study

Abstract Background and Aims As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients’ preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. Methods This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. Results IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medication’s long-term effects. Furthermore, participants extensively discussed the mental impact of IBD and their need for more psychological guidance, support, and improved information and communication with healthcare workers regarding their disease and emotional wellbeing. The following five characteristics were identified during the attribute grading as most important: prevent surgery, long-term clinical remission, improved quality of life [QoL], occurrence of urgency and improved labour rate. Conclusions This study suggests that IBD drug development and treatment decision-making are needed to improve IBD symptoms and adverse events that significantly impact IBD patients’ QoL. Furthermore, this study underlines patients’ need for a shared decision-making process in which their desired treatment outcomes and uncertainties are explicitly discussed and considered.
THE ACCRETION RATE INDEPENDENCE OF HORIZONTAL BRANCH OSCILLATION IN XTE J1701-462

We study the temporal and energy spectral properties of the unique neutron star low-mass X-ray binary XTE J1701-462. Assuming the horizontal branch/normal branch (HB/NB) vertex as a reference position of the accretion rate, the horizontal branch oscillation (HBO) of the HB/NB vertex is roughly 50 Hz. It indicates that the HBO is independent of the accretion rate or the source intensity. The spectral analysis shows in the HB/NB vertex and in the NB/flaring branch (FB) vertex, which implies that different accretion rates may be produced in the HB/NB and NB/FB vertex. The Comptonization component could be fitted by a constrained broken power law or nthComp. Unlike GX 17+2, the frequencies of HBO positively correlate with the inner disk radius, which contradict with the prediction of the Lense–Thirring precession model. XTE J1701-462, both in the Cyg-like phase and in the Sco-like phase, follows a positive correlation between the break frequency of broadband noise and the characteristic frequency of HBO, which is called the W–K relation. An anticorrelation between the frequency of HBO and photon energy is observed. Moreover, the rms of HBO increases with photon energy until ∼10 keV. We discuss the possible origin of HBO from the corona in XTE J1701-462.
Green synthesis aspects of (R)-(-)-mandelic acid; a potent pharmaceutically active agent and its future prospects

Abstract (R)-(-)-mandelic acid is an important carboxylic acid known for its numerous potential applications in the pharmaceutical industry as it is an ideal starting material for the synthesis of antibiotics, antiobesity drugs and antitumor agents. In past few decades, the synthesis of (R)-(-)-mandelic acid has been undertaken mainly through the chemical route. However, chemical synthesis of optically pure (R)-(-)-mandelic acid is difficult to achieve at an industrial scale. Therefore, its microbe mediated production has gained considerable attention as it exhibits many merits over the chemical approaches. The present review focuses on various biotechnological strategies for the production of (R)-(-)-mandelic acid through microbial biotransformation and enzymatic catalysis; in particular, an analysis and comparison of the synthetic methods and different enzymes. The wild type as well as recombinant microbial strains for the production of (R)-(-)-mandelic acid have been elucidated. In addition, different microbial strategies used for maximum bioconversion of mandelonitrile into (R)-(-)-mandelic acid are discussed in detail with regard to higher substrate tolerance and maximum bioconversion. Highlights Mandelonitrile, mandelamide and o-chloromandelonitrile can be used as substrates to produce (R)-(-)-mandelic acid by enzymes. Three enzymes (nitrilase, nitrile hydratase and amidase) are systematically introduced for production of (R)-(-)-mandelic acid. Microbial transformation is able to produce optically pure (R)-(-)-mandelic acid with 100% productive yield. Graphical Abstract
Dual-energy Computed Tomographic Pulmonary Angiography Accurately Estimates Lobar Perfusion Before Lung Volume Reduction for Severe Emphysema

Purpose: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR). Materials and Methods: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded. Results: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance (P<0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, −0.01, mean r 2 0.64; P<0.0001). Individual lobar comparisons demonstrated moderate correlation (r=0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P<0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index. Conclusions: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR.