Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryopreserved Human Natural Killer Cells Exhibit Potent Antitumor Efficacy against Orthotopic Pancreatic Cancer through Efficient Tumor-Homing and Cytolytic Ability (Running Title: Cryopreserved NK Cells Exhibit Antitumor Effect)

Pancreatic cancer is known to be highly aggressive, and desmoplasia-induced accumulation of extracellular matrix (ECM), which is a hallmark of many pancreatic cancers, severely restricts the therapeutic efficacy of both immunotherapeutics and conventional chemotherapeutics due to the ECM functioning as a major physical barrier against permeation and penetration. In the case of cell-based immunotherapeutics, there are several other bottlenecks preventing translation into clinical use due to their biological nature; for example, poor availability of cell therapeutic in a readily usable form due to difficulties in production, handling, shipping, and storage. To address these challenges, we have isolated allogeneic natural killer (NK) cells from healthy donors and expanded them in vitro to generate cryopreserved stocks. These cryopreserved NK cells were thawed to evaluate their therapeutic efficacy against desmoplastic pancreatic tumors, ultimately aiming to develop a readily accessible and mass-producible off-the-shelf cell-based immunotherapeutic. The cultured NK cells post-thawing retained highly pure populations of activated NK cells that expressed various activating receptors and a chemokine receptor. Furthermore, systemic administration of NK cells induced greater in vivo tumor growth suppression when compared with gemcitabine, which is the standard chemotherapeutic used for pancreatic cancer treatment. The potent antitumor effect of NK cells was mediated by efficient tumor-homing ability and infiltration into desmoplastic tumor tissues. Moreover, the infiltration of NK cells led to strong induction of apoptosis, elevated expression of the antitumor cytokine interferon (IFN)-γ, and inhibited expression of the immunosuppressive transforming growth factor (TGF)-β in tumor tissues. Expanded and cryopreserved NK cells are strong candidates for future cell-mediated systemic immunotherapy against pancreatic cancer.
Hallmarks of cancer: Tumor budding as a sign of invasion and metastasis in head and neck cancer

Invasion and metastasis are hallmarks of cancer. The concept of tumor budding at tumor‐host interface has been documented in many carcinomas. A growing body of evidence indicates that tumor budding is a sign of invasion and early step for metastasis of many epithelial cancers including head and neck squamous cell carcinoma (HNSCC). In addition, recent research has underlined the importance of tumor budding as a promising prognosticator in HNSCC. This review summarizes the findings regarding tumor budding in HNSCC and focuses on the role of tumor budding in invasion and metastasis. Also, we highlight the prognostic significance of tumor budding in HNSCC and its potential for improving clinical decision making in terms of recommending optimal individualized treatment for this patient population.
Understanding the local and global impacts of model physics changes: an aerosol example

This study demonstrates the use of a package of diagnostic techniques to understand the local and global responses to a given physics change within a general circulation model. Here, the package is applied to the case of a change in the aerosol climatology in the forecast model of the European Centre for Medium‐range Weather Forecasts. The largest difference between old and new climatologies is over the Sahara where, in particular, soil‐dust aerosol is reduced. Conventional diagnostics show that the change lead to improvements in local medium‐range forecast skill and reductions in seasonal‐mean errors throughout the globe. To study the local physics response, short‐range tendencies in weather forecasts are diagnosed. These tendencies are decomposed into the contributions from each physical process within the model. The resulting ‘initial tendency’ budget reveals how the local atmosphere responds to the aerosol change. The net tendencies also provide strong evidence to confirm that the new aerosol climatology is superior. Seasonal integrations demonstrate that the tropic‐wide response can be understood in terms of equatorial waves and their enhancement by diabatic processes. The so‐called ‘Rossby‐wave source’ is made applicable to general circulation models and used to understand how the tropical anomalies subsequently impact on the global circulation. The mean response in the extratropics is found to be a stationary wave field. Precipitation anomalies that are co‐located with extratropical divergent vorticity sources suggest the possibility for diabatic modification of the tropically forced Rossby‐wave response. Copyright © 2008 Royal Meteorological Society
Tomato GLR3.3 and GLR3.5 mediate cold acclimation-induced chilling tolerance by regulating apoplastic H2 O2 production and redox homeostasis.

Plant GLUTAMATE RECEPTOR-LIKE (GLR) genes play important roles in plant development and immune response. However, the functions of GLRs in abiotic stress response remain unclear. Here we show that cold acclimation at 12°C induced the transcripts of GLR3.3 and GLR3.5 with increased tolerance against a subsequent chilling at 4 °C. Silencing of GLR3.3 or/and GLR3.5 or application of the antagonist of ionotropic glutamate receptor 6,7-dinitroquinoxaline-2,3-dione (DNQX), all compromised the acclimation-induced increases in the transcripts of RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1), activity of NADPH oxidase, the accumulation of apoplastic H2 O2 and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), resulting in an attenuated chilling tolerance, the effect, however, was rescued by foliar application of H2 O2 or GSH. Both RBOH1-silenced and glutathione biosynthesis genes, γ-GLUTAMYLCYSTEINE SYNTHETASE (GSH1)- and GLUTATHIONE SYNTHETASE (GSH2)-cosilenced plants had decreased chilling tolerance with reduced GSH/GSSG ratio. Moreover, application of DNQX had little effects on the GSH/GSSG ratio and the tolerance in RBOH1-silenced plants and GSH1- and GSH2-cosilenced plants. These findings unmasked the functional hierarchy of GLR-H2 O2 -Glutathione cascade and shed new light on cold response pathway in tomato plants.
Stable multicharged localized optical vortices in cubic–quintic nonlinear media

We investigate analytically and numerically the stability of multiply-charged two-dimensional bright vortex solitons in media with focusing cubic and defocusing quintic nonlinearities. A vortex soliton becomes robust with respect to symmetry-breaking azimuthal perturbations in the self-defocusing regime above some critical beam power when its radial profile flattens. A stable high-power vortex has nearly homogeneous energy distribution across the beam with a rather sharp boundary. The dynamics of a slightly perturbed stable vortex soliton is found to be similar to oscillations of a liquid stream having a surface tension. We propose an explanation of stabilization of vortex solitons in media with competing nonlinearities based on the idea of sustaining effective surface tension.
A Sustainable Career Perspective of Work Ability: The Importance of Resources across the Lifespan

In this study, we examine employees’ perceptions of their work ability from a sustainable career perspective. Specifically, we investigate the role of a person’s perceived current fit (i.e., autonomy, strengths use and needs-supply fit), and future fit with their job as resources that affect perceived work ability, defined as the extent to which employees feel capable of continuing their current work over a longer time period. In addition, we test whether meaningfulness of one’s work mediates this relationship, and we address the moderating role of age. Our hypotheses were tested using a sample of 5205 employees working in diverse sectors in Belgium. The results of multi-group Structural Equation Modelling (SEM) provide mixed evidence for our hypotheses. While all four resources were significantly and positively related to perceived meaningfulness, only needs-supply fit was positively related to perceived work ability. Strengths use, on the other hand, was also significantly related to perceived work ability, yet in a negative way. These findings underscore the importance of distinguishing between several types of resources to understand their impact upon perceived work ability. Interestingly, the relationship between future-orientedness of the job and perceived work ability was moderated by age, with the relationship only being significant and positive for middle-aged and senior workers. This suggests an increasingly important role of having a perspective of future fit with one’s job as employees grow older. Contrary to our expectations, meaningfulness did not mediate the relationships between resources and perceived work ability. We discuss these findings and their implications from the perspective of sustainable career development.
The Relationship Between Depression and Frailty in Community-Dwelling Older People: A Systematic Review and Meta-Analysis of 84,351 Older Adults.

OBJECTIVES In this study we investigated the correlation between depression and frailty in older adults. Additionally, correlations among study designs (prospective vs. cross-sectional), regions, depression indices, frailty indices, covariance corrections, and sexes were explored to support the analysis. METHODS A systematic literature review and meta-analysis were conducted. A total of 84,351 older adults, all 65 years of age or older, were analyzed. Both authors independently extracted and examined retrieved articles. Searched keywords included "depression" or "depressive"; "frailty" or "frail"; and "older people," "elderly," "geriatric," or "senior. " Articles published between January 2000 and December 2016 were searched. A literature quality assessment was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic REVIEWS AND META-ANALYSES: Systematic literature searches were conducted on the Embase, PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases, and collected studies were analyzed using a random effects model. RESULTS Fourteen studies on people 65 years of age or older were collected, and a correlation analysis was conducted for depression and frailty. According to the meta-analysis, the risk for frailty due to depression was nonsignificant among the subgroups for study design (p for heterogeneity = .149), region (p = .429), depression criteria (p = .934), covariate adjustment (p = .702), and frailty criteria (p = .661). Notably, the risk for frailty due to depression was significantly higher in men than in women (pooled odds ratios for men and women: 4.76 and 2.25, respectively; Qbetween χ2 = 9.93, p = .002). CONCLUSION Older adults with depression are more prone to frailty than are those without depression. Regardless of study design, region, depression index, frailty index, and covariance corrections, no significant differences were observed in the results of studies on depression and frailty in older adults. The only factor that had a significant influence was sex; older men with depression were at a higher risk for frailty than were older women with depression. CLINICAL RELEVANCE Depression and frailty are pertinent health concerns related to geriatric syndromes. Because older adults with depression have a high risk for frailty, nursing personnel should use a depression index as early as possible to screen for depression and further reduce the occurrence of frailty in older adults. Furthermore, based on the aforementioned differences between the sexes, special attention should be paid to older men with depression to reduce their risk for frailty.
Increased Soluble CrkL in Serum of Breast Cancer Patients Is Associated with Advanced Disease

Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.
Cancer Chemotherapy drug wastage in a tertiary care hospital in India-A three-month prospective and one-year retrospective study.

This study prospectively quantified wastage of cancer chemotherapeutic drugs in oncology unit to find the associated cost in three months. Retrospective analysis of drug usage for 12 months was also conducted to determine the expected drug loss in one year. The effect of vial sharing was evaluated under the assumption of sharing. A significant drug wastage of 19.72% (95% CI, 14.52%-24.93%) in three months and 17.14% [95% CI 14.69%-19.59%] in one year occurred in our oncology unit. Number of vials purchased (r = 0.362, p < 0.01), weight (r = -0.146, p < 0.01) and body surface area (r = -0.26, p < 0.01) correlated with the drug wasted. Vial sharing assumption showed a 9% (95% CI, 2.5%-15.5%) reduction in cost in one year.
Moment theories for a $d$-dimensional dilute granular gas of Maxwell molecules

Various systems of moment equations – consisting of up to $(d+3)(d^{2}+6d+2)/6$ moments – in a general dimension $d$ for a dilute granular gas composed of Maxwell molecules are derived from the inelastic Boltzmann equation by employing the Grad moment method. The Navier–Stokes-level constitutive relations for the stress and heat flux appearing in the system of mass, momentum and energy balance equations are determined from the derived moment equations. It has been shown that the moment equations only for the hydrodynamic field variables (density, velocity and granular temperature), stress and heat flux – along with the time-independent value of the fourth cumulant – are sufficient for determining the Navier–Stokes-level constitutive relations in the case of inelastic Maxwell molecules, and that the other higher-order moment equations do not play any role in this case. The homogeneous cooling state of a freely cooling granular gas is investigated with the system of the Grad $(d+3)(d^{2}+6d+2)/6$-moment equations and its various subsystems. By performing a linear stability analysis in the vicinity of the homogeneous cooling state, the critical system size for the onset of instability is estimated through the considered Grad moment systems. The results on critical system size from the presented moment theories are found to be in reasonably good agreement with those from simulations.
Robust Low-Rank Tensor Recovery with Rectification and Alignment

Low-rank tensor recovery in the presence of sparse but arbitrary errors is an important problem with many practical applications. In this work, we propose a general framework that recovers low-rank tensors, in which the data can be deformed by some unknown transformations and corrupted by arbitrary sparse errors. We give a unified presentation of the surrogate-based formulations that incorporate the features of rectification and alignment simultaneously, and establish worst-case error bounds of the recovered tensor. In this context, the state-of-the-art methods ‘RASL’ and ‘TILT’ can be viewed as two special cases of our work, and yet each only performs part of the function of our method. Subsequently, we study the optimization aspects of the problem in detail by deriving two algorithms, one based on the alternating direction method of multipliers (ADMM) and the other based on proximal gradient. We provide convergence guarantees for the latter algorithm, and demonstrate the performance of the former through in-depth simulations. Finally, we present extensive experimental results on public datasets to demonstrate the effectiveness and efficiency of the proposed framework and algorithms.
Differences in protein profiles between Malassezia pachydermatis strains obtained from healthy and infected dogs

ABSTRACT Malassezia pachydermatis causes infections of the skin and mucous membranes, especially in individuals with metabolic, hormonal, and immunological disorders. The search for M. pachydermatis properties that differentiate isolates from healthy and infected animals may result in the identification of typically commensal and potentially pathogenic strains within the entire species. We aimed to determine and compare protein profiles of M. pachydermatis strains isolated from 30 dogs with clinical symptoms of otitis externa and 34 dogs without symptoms of any disease. Two-dimensional gel electrophoresis was applied, and proteins distinguishing the two groups of strains were identified by liquid chromatography coupled with tandem mass spectrometry. Significant differences were found between potentially pathogenic and commensal isolates. The most significant finding was the presence of nicotinamide adenine dinucleotide phosphate (NADP)-dependent mannitol dehydrogenase and ketol-acid reductoisomerase among M. pachydermatis strains obtained from dogs with otitis externa. Nevertheless, it is not clear whether they are associated directly with the pathogenicity or they play the role of fungal allergen. On the basis of these findings, we can conclude that there may be two distinct groups of M. pachydermatis strains—one typically commensal and the other with properties that enhance the infection process. These results may be used for more precise diagnosis and identification of potentially pathogenic strains in the future.
A Decomposition Method for Object-Oriented Systems Based on Iterative Analysis of the Directed Weighted Graph

Aiming at the problem of how to acquire components from existing systems, this paper proposes a decomposition method for object-oriented systems based on iterative analysis of the directed weighted graph. This method uses the directed weighted graph as the representation of object-oriented systems, and an iterative algorithm for analyzing the independence of sub-graphs at different granularity levels. Those highly independent ones are chosen as candidate components. Experimental results show that this method is effective and can improve the existing decomposition methods in terms of accuracy.
Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis

This study aimed to determine whether autologous orthobiologic tissue source affects pain and functional outcomes in patients with symptomatic knee osteoarthritis (OA) who received microfragmented adipose tissue (MFAT) or bone marrow aspirate concentrate (BMAC) injection. We retrospectively reviewed prospectively collected data from patients who received BMAC or MFAT injection for symptomatic knee OA. Patients completed baseline and follow‐up surveys. Each survey included the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, Emory Quality of Life (EQOL) questionnaire, and Visual Analog Scale (VAS) for pain. The follow‐up responses were compared with baseline for all patients and between BMAC and MFAT groups. A total of 110 patients met inclusion criteria, with 76 patients (BMAC 41, MFAT 35) and 106 knees (BMAC 58, MFAT 48) having appropriate follow‐up data. The BMAC group included 17 females and 24 males, with a mean age of 59 ± 11 years. The MFAT group included 23 females and 12 males, with a mean age of 63 ± 11 years. Minimum follow‐up time was 0.5 years. Mean follow‐up time was 1.80 ± 0.88 years for BMAC and 1.09 ± 0.49 years for MFAT. Both groups had significant improvement in EQOL, VAS, and all KOOS parameters preprocedure versus postprocedure (p < .001). There was not a significant difference when comparing postprocedure scores between groups (p = .09, .38, .63, .94, .17, .15, .70, respectively). These data demonstrate significant improvement in pain and function with both MFAT and BMAC injections in patients with symptomatic knee OA without a significant difference in improvement when comparing the two autologous tissue sources. Stem Cells Translational Medicine 2019;8:1149–1156
Improving the quality of foods available in a rural kibbutz cafeteria in Israel to align with a freshly prepared Mediterranean-style diet through a community culinary coaching programme

Abstract Objective: To examine the impact of a community culinary coaching programme (CCCP) on cafeteria food alignment with a freshly prepared Mediterranean-style diet, and diners’ consumption habits and satisfaction. Design: A non-randomized, controlled, community-based participatory research programme. CCCP included eight 90 min coaching sessions with a community steering committee, 22 h of kitchen staff training, 12 h of pre-school staff training and 30 h of education for diners; control communities received no intervention. Outcomes, measured before and 12 months after programme initiation, included cafeteria food alignment with a freshly prepared Mediterranean-style diet through a food items list derived from the cafeteria food purchasing software, and adult diners’ consumption habits and satisfaction through questionnaires. Setting: Communal cafeterias of rural kibbutzim. Participants: Intervention: kibbutz with 493 adults and 214 children. Control: Two kibbutzim with a total of 487 adults and 206 children. Results: Intervention cafeteria food improved significantly in all Mediterranean index categories except nuts (legumes, wholegrain products, fish, MUFA/SFA P < 0·0001; fruits, vegetables P < 0·001; processed meats P = 0·004), and in the proportion of ultra-processed and unprocessed or minimally processed foods categories of the NOVA classification (−22 %, P < 0·001 and +7 %, P < 0·001, respectively), compared with the control community. The intervention group’s satisfaction was significantly improved in twenty-five (83 %) out of the thirty satisfaction items, compared with twelve (40 %) in the control group. No changes were identified in diners’ consumption habits in either intervention or control communities. Conclusions: CCCP might be useful in improving alignment of cafeteria food with a freshly prepared Mediterranean-style diet.