Miracle-dz/UniFAR-FTUs huggingface dataset:
Strong maximum principle for fractional diffusion equations and an application to an inverse source problem

Abstract The strong maximum principle is a remarkable property of parabolic equations, which is expected to be partly inherited by fractional diffusion equations. Based on the corresponding weak maximum principle, in this paper we establish a strong maximum principle for time-fractional diffusion equations with Caputo derivatives, which is slightly weaker than that for the parabolic case. As a direct application, we give a uniqueness result for a related inverse source problem on the determination of the temporal component of the inhomogeneous term.
Evaluating Bacterial Pathogenesis Using a Model of Human Airway Organoids Infected with Pseudomonas aeruginosa Biofilms

Human airway organoids (HAOs) are an organotypic model of human airway mucociliary epithelium. The HAOs can closely resemble their origin organ in terms of epithelium architecture and physiological function. ABSTRACT Pseudomonas aeruginosa is one of the leading invasive agents of human pulmonary infection, especially in patients with compromised immunity. Prior studies have used various in vitro models to establish P. aeruginosa infection and to analyze transcriptomic profiles of either the host or pathogen, and yet how much those works are relevant to the genuine human airway still raises doubts. In this study, we cultured and differentiated human airway organoids (HAOs) that recapitulate, to a large extent, the histological and physiological features of the native human mucociliary epithelium. HAOs were then employed as a host model to monitor P. aeruginosa biofilm development. Through dual-species transcriptome sequencing (RNA-seq) analyses, we found that quorum sensing (QS) and several associated protein secretion systems were significantly upregulated in HAO-associated bacteria. Cocultures of HAOs and QS-defective mutants further validated the role of QS in the maintenance of a robust biofilm and disruption of host tissue. Simultaneously, the expression magnitude of multiple inflammation-associated signaling pathways was higher in the QS mutant-infected HAOs, suggesting that QS promotes immune evasion at the transcriptional level. Altogether, modeling infection of HAOs by P. aeruginosa captured several crucial facets in host responses and bacterial pathogenesis, with QS being the most dominant virulence pathway showing profound effects on both bacterial biofilm and host immune responses. Our results revealed that HAOs are an optimal model for studying the interaction between the airway epithelium and bacterial pathogens. IMPORTANCE Human airway organoids (HAOs) are an organotypic model of human airway mucociliary epithelium. The HAOs can closely resemble their origin organ in terms of epithelium architecture and physiological function. Accumulating studies have revealed the great values of the HAO cultures in host-pathogen interaction research. In this study, HAOs were used as a host model to grow Pseudomonas aeruginosa biofilm, which is one of the most common pathogens found in pulmonary infection cases. Dual transcriptome sequencing (RNA-seq) analyses showed that the cocultures have changed the gene expression pattern of both sides significantly and simultaneously. Bacterial quorum sensing (QS), the most upregulated pathway, contributed greatly to biofilm formation, disruption of barrier function, and subversion of host immune responses. Our study therefore provides a global insight into the transcriptomic responses of both P. aeruginosa and human airway epithelium.
The Extragalactic Ultra-high-energy Cosmic-Ray Dipole

We explore the possibility that the recently detected dipole anisotropy in the arrival directions of >8 EeV ultra-high-energy cosmic-rays (UHECRs) arises due to the large-scale structure. We assume that the cosmic-ray sources follow the matter distribution and calculate the flux-weighted UHECRs’ rms dipole amplitude taking into account the diffusive transport in the intergalactic magnetic field (IGMF). We find that the flux-weighted rms dipole amplitude is ∼8% before entering the Galaxy. The amplitude in the [4–8] EeV is only slightly lower ∼5%. The required IGMF is of the order of 5–30 nG, and the UHECR sources must be relatively nearby, within ∼300 Mpc. The absence of a statistically significant signal in the lower-energy bin can be explained if the same nuclei specie dominates the composition in both energy bins and diffusion in the Galactic magnetic field reduces the dipole of these lower-rigidity particles. Photodisintegration of higher-energy UHECRs could also reduce somewhat the lower-energy dipole.
13C Isotopic Fractionation of HC3N in Two Starless Cores: L1521B and L134N (L183)

We observed the rotational lines of the normal species and three 13C isotopologues of HC3N at the 45 GHz band toward two low-mass starless cores, L1521B and L134N (L183), using the Nobeyama 45 m radio telescope in order to study the main formation pathways of HC3N in each core. The abundance ratios of the three 13C isotopologues in L1521B are derived to be [H13CCCN]:[HC13CCN]:[HCC13CN] = 0.98 (±0.14):1.00:1.52 (±0.16) ( ). The fractionation pattern is consistent with that at the cyanopolyyne peak in Taurus Molecular Cloud-1. This fractionation pattern suggests that the main formation pathway of HC3N is the neutral–neutral reaction between C2H2 and CN. On the other hand, their abundance ratios in L134N are found to be [H13CCCN]:[HC13CCN]:[HCC13CN] = 1.5 (±0.2):1.0:2.1 (±0.4) ( ), which are different from those in L1521B. From this fractionation pattern, we propose that the reaction between HNC and CCH is a possible main formation pathway of HC3N in L134N. We find out that the main formation pathways of the same molecule are not common even in similar physical conditions. We discuss the possible factors that could make a difference in the fractionation pattern between L134N and L1521B/TMC-1.
Comparison of fentanyl and nalbuphine as adjuvants to intrathecal 0.5% bupivacaine in lower limb surgeries: A randomised double-blind prospective study

Introduction: Local anaesthetics used in spinal anaesthesia have a limited duration of action. To prolong postoperative analgesia, adjuvants, mainly opioids, are used. As µ agonist drugs have side effects, other receptor agonists are considered. Nalbuphine is a safe and effective kappa agonist adjuvant. Aim: To compare the analgesic efficacy between fentanyl and nalbuphine adjuvants added to 3 mL of 0.5% intrathecal hyperbaric bupivacaine. Materials and Methods: This prospective, double-blind, comparative study was conducted in 60 patients of either sex belonging to the American Society of Anesthesiologists classes I and II aged 18–65 years undergoing lower limb surgery with entropy monitoring, randomly allocated into two groups. Group F (n = 30) received 0.5% hyperbaric bupivacaine (3 mL) + 25 µg (0.5 mL) fentanyl. Group N (n = 30) received 0.5% hyperbaric bupivacaine (3 ml) + 0.8 mg (0.5 mL) nalbuphine intrathecally. Hemodynamics, entropy, motor and sensory block characteristics, and complications were noted. Results: The nalbuphine group had a significantly longer two-segment regression time of sensory blockade and extended analgesia duration than the fentanyl group. Haemodynamics, entropy, time for onset of sensory and motor blockade and adverse effects were comparable in both groups. Conclusion: Nalbuphine prolongs sensory blockade and postoperative analgesia duration with minimal side effects and is a safe intrathecal adjuvant.
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Background Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non–small cell lung cancers (NSCLCs). Methods A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images. Results In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. Conclusions BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.
The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-β production in regulatory T-cells

Background Lymphocyte-specific protein tyrosine kinase (Lck) is a member of the Src family of tyrosine kinases. The significance of Lck inhibition in lung fibrosis has not yet been fully elucidated, even though lung fibrosis is commonly preceded by inflammation caused by infiltration of T-cells expressing Lck. In this study, we examined the effect of Lck inhibition in an experimental mouse model of lung fibrosis. We also evaluated the effect of Lck inhibition on the expression of TGF-β1, an inhibitory cytokine regulating the immune function, in regulatory T-cells (Tregs). Methods Lung fibrosis was induced in mice by intratracheal administration of bleomycin. A-770041, a Lck-specific inhibitor, was administrated daily by gavage. Tregs were isolated from the lung using a CD4+CD25+ Regulatory T-cell Isolation Kit. The expression of Tgfb on Tregs was examined by flow cytometry and quantitative polymerase chain reaction. The concentration of TGF-β in bronchoalveolar lavage fluid (BALF) and cell culture supernatant from Tregs was quantified by an enzyme-linked immunosorbent assay. Results A-770041 inhibited the phosphorylation of Lck in murine lymphocytes to the same degree as nintedanib. A-770041 attenuated lung fibrosis in bleomycin-treated mice and reduced the concentration of TGF-β in BALF. A flow-cytometry analysis showed that A-770041 reduced the number of Tregs producing TGF-β1 in the lung. In isolated Tregs, Lck inhibition by A-770041 decreased the Tgfb mRNA level as well as the concentration of TGF-β in the supernatant. Conclusions These results suggest that Lck inhibition attenuated lung fibrosis by suppressing TGF-β production in Tregs and support the role of Tregs in the pathogenesis of lung fibrosis.
Clinical and histopathological study of renal biopsy in Nepalese children: A single center experience

Background Glomerular diseases are important causes of morbidity and mortality among children in developing countries. Renal biopsy is the gold standard for determining histological diagnosis, prognosis, and therapy options. This study aimed to investigate the clinical, histopathological, and direct immunofluorescence findings of renal biopsy results in Nepalese children under 18 years old. Methods In this retrospective cross-sectional study, the available data from children who had undergone kidney biopsy between 2016 and the end of 2020 were evaluated. Demographic data, indications of biopsy, histopathologic findings, and direct immunofluorescence findings were collected and presented. Results The mean age of the patients was 12.14 ± 4.07 years. Male/female ratio was 1:1. The majority of biopsy cases were aged between 11–15 years of age. The most common indication for biopsy in children was nephrotic syndrome (68.25%). Lupus nephritis with 28 cases (22.22%) had the highest frequency in overall renal biopsies. Minimal change disease (MCD) with 22 cases (17.46%) followed by Ig A nephropathy with 16 cases (12.69%) were the most frequent primary glomerulonephritis. Lupus nephritis showed full house positivity, and MCD showed full house negativity in all Direct immunofluorescence (DIF) parameters, whereas immunoglobulin A nephropathy showed 100% positivity in Ig A in DIF. Conclusions Nephrotic syndrome was the most common indication for renal biopsy. The most common primary glomerulonephritis was MCD, while secondary glomerulonephritis was lupus nephritis. Clinical data, light microscopy, and direct DIF played an integral role in the overall final diagnosis.
Luminous Infrared Galaxies with the Submillimeter Array. V. Molecular Gas in Intermediate to Late-stage Mergers

We present new high-resolution ALMA (13CO J = 1−0 and J = 2−1) and CARMA (12CO and 13CO J = 1−0) observations of two luminous infrared galaxies (LIRGs), Arp 55 and NGC 2623. The new data are complementary to published and archival submillimeter array observations of 12CO J = 2−1 and J = 3−2. We perform a Bayesian likelihood non-local thermodynamic equilibrium analysis to constrain the molecular gas physical conditions such as temperature, column, and volume densities and the [12CO]/[13CO] abundance ratio. For Arp 55, an early/intermediate-staged merger, the line measurements are consistent with cold (∼10–20 K), dense (> cm−3) molecular gas. For NGC 2623, the molecular gas is warmer (∼110 K) and less dense ( cm−3). Because Arp 55 is an early/intermediate stage merger, while NGC 2623 is a merger remnant, the difference in physical conditions may be an indicator of merger stage. Comparing the temperature and volume density of several LIRGs shows that the molecular gas, averaged over ∼kiloparsec scales, of advanced mergers is in general warmer and less dense than early/intermediate stage mergers. We also find that the [12CO]/[13CO] abundance ratio of NGC 2623 is unusually high (>250) when compared with the Milky Way; however, it follows a trend seen with other LIRGs in the literature. This high [12CO]/[13CO] value is very likely due to stellar nucleosynthesis enrichment of the interstellar medium. On the other hand, Arp 55 has a more Galactic [12CO]/[13CO] value with the most probable [12CO]/[13CO] value being 20–30. We measure the CO-to-H2 conversion factor, , to be ∼0.1 and ∼0.7 (3 × 10−4/ ) M⊙ (K km s−1 pc2)−1 for Arp 55 and NGC 2623, respectively. Because Arp 55 is an early/intermediate-stage merger, this suggests that the transition from a Galactic conversion factor to a LIRG value happens at an even earlier merger stage.
Sound velocity and tidal deformability in compact stars

The sound velocity vs and dimensionless tidal deformability Λ are analyzed using the pseudo-conformal model we developed before. In contrast to the conclusion obtained in the previous works in the literature, our model with the upper bound of the sound velocity vs=1/3, the so-called conformal sound velocity, set in at a density relevant to compact stars ≳2n0 where n0 is the normal nuclear matter density, can accommodate all presently established nuclear matter and compact-star properties including the maximum star-mass constraint ≃2.3 M⊙. This observation is associated with a possible emergence of pseudoconformal structure in compact star matter—in which the trace of energy-momentum tensor is a nearly density-independent nonzero constant—brought in by a topology change at 2.0≲n1/2/n0≲4.0 commensurate with a possible change of degrees of freedom from hadrons.
Boletus dermatitis: first report in France of flagellate erythema after consumption of Porcini mushrooms

6. Lis-Święty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al. Localized scleroderma: clinical and epidemiological features with emphasis on adulthoodversus childhood-onset disease differences. J Eur Acad Dermatol Venereol 2017; 31: 1595-603. 7. Bernstein JE, Medenica M, Soltani K. Coexistence of localized bullous pemphigoid, morphea, and subcorneal pustulosis. Arch Dermatol 1981; 117: 725-7. 8. Iskandarli M, Gerceker Turk B, Yaman B, Unal I. Rare association of morphea with vesicular pemphigoid. G Ital Dermatol Venereol 2016; 151: 562-3. 9. Sacher C, König C, Scharffetter-Kochanek K, et al. Bullous pemphigoid in a patient treated with UVA-1 phototherapy for disseminated morphea. Dermatology 2001; 202: 54-7.
Examination of genotype × environment interactions by GGE biplot analysis in spring durum wheat

A study was conducted to examine the effects of genotype × environment interaction (GEI) on grain yield, its components, and quality characteristics using genotype main effect (G) plus genotype × environment interaction (GE) (GGE) biplot analysis. Significant differences were observed among cultivars in grain yield, yield components, and quality traits and the relationship between yield components was used to identify three groups. Positive correlations were found between quality parameters and yield components, whereas correlations of quality parameters with yield and yield components were negative. The GGE biplot indicated that E6 (single irrigated location at Diyarbakir) was an ideal environment for all traits and E5 (rainfed locations at Diyarbakir) was a highly efficient model for quality parameters. The biplot analysis showed that Zenit was the best cultivar in terms of yield and quality and Zuhre was efficient for quality parameters only and hence these two genotypes can be recommended to Southeastern Anatolia Region in Turkey.
Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre‐clinical pooled analysis, with focus on cerebral hemodynamics

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t‐MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal‐level data from three experimental series were combined in a study population of 104 t‐MCAO rats (45 in HDT15 group and 59 in flat position group). Co‐primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non‐ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3, 95% CI 9.1–54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10–16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5–19.18, p = 0.0002). Mean cerebral perfusion in the non‐ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI −1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t‐MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non‐ischemic areas.
Prefoldin 6 promotes glioma progression via the AKT signalling pathway

Gliomas are one of the most aggressive primary tumours, accounting for 81% of malignant brain tumours, and are associated with a significant mortality. Therefore, the elucidation of the molecular mechanism underlying glioma progression and identification of promising treatment targets are necessary. Here, the expression of prefoldin (PFDN) 6 in human glioma tissues and cell lines was evaluated using immunohistochemistry and quantitative polymerase chain reaction. Celigo and CCK‐8 assays were performed for assessing cell viability. Flow cytometry was used to analyse apoptosis and cell cycle distribution. Wound‐healing and transwell assays were performed to observe cell migration. Lastly, xenograft models were developed for the in vivo validation of the results, and a human phospho‐kinase array was used to explore the downstream signalling pathways. PFDN6 was upregulated in gliomas, and PFDN6 overexpression was significantly correlated with a low survival rate, estimated glomerular filtration rate (EGFR) expression, and tumour grade and recurrence. Moreover, PFDN6 knockdown significantly attenuated cell proliferation and migration, induced apoptosis, and blocked cell cycle progression in the G2 phase, which was further confirmed in the in vivo experiments. Mechanistically, the effects of PFDN6 may be mediated via the AKT signalling pathway. In conclusion, we showed that PFDN6 promotes glioma development by activating AKT signalling and emphasised the potential of PFDN6 as a crucial target in glioma therapy.
The association between OCD and Shame: A systematic review and meta‐analysis

Abstract Background Due to rumination and self‐criticism over unwanted obsessions and repetitive rituals, shame is a common emotion experienced by individuals with obsessive–compulsive disorder (OCD). Shame is also theorized to have relevance to unacceptable thoughts in OCD. However, empirical research looking at the relationship between OCD and shame is still emerging and findings have been mixed. Objectives Our review systematically examines the association of shame with OCD and unacceptable thoughts. Methods The last updated search was conducted across five databases between 27 and 29 February 2022. The final selection included 20 papers, 18 of which were used in the primary meta‐analysis to calculate pooled effect sizes between OCD and shame measures using a random effects model. In a separate analysis, three papers were used to calculate pooled effect sizes between shame and OCD symptom dimensions also using a random effects model. Results The meta‐analyses identified a significant, moderate and positive correlation between total OCD and shame scores r = . 352, 95% CI [0.260, 0.438]. In addition, significant, weak and positive relationships were found between shame and three OCD symptom dimensions: unacceptable thoughts r = . 252, 95% CI [−0.467, 0.9708], harm obsessions r = . 224, CI [−0.190, 0.638] and symmetry concerns r = . 200, CI [−0.108, 0.509]. Limitations Shame measures in the reviewed studies were not specific to OCD, and between‐study variance in the analyses examining unacceptable thoughts was significant. Conclusions Our findings support a medium positive relationship between shame and OCD. As shame in OCD can be a barrier to seeking treatment and impair quality of life, it is imperative to address this emotion through psychoeducation, assessment and treatment.
Metal-insulator transition in holography

We exhibit an interaction-driven metal-insulator quantum phase transition in a holographic model. Use of a helical lattice enables us to break translation invariance while preserving homogeneity. The metallic phase is characterized by a sharp Drude peak and a d.c. resistivity that increases with temperature. In the insulating phase the Drude spectral weight is transferred into a `mid-infrared' peak and to energy scales of order the chemical potential. The d.c. resistivity now decreases with temperature. In the metallic phase, operators breaking translation invariance are irrelevant at low energy scales. In the insulating phase, translation symmetry breaking effects are present at low energies. We find the near horizon extremal geometry that captures the insulating physics.