Miracle-dz/UniFAR-FTUs huggingface dataset:
Adapting Pediatric Sepsis Criteria for Benchmarking and Quality Control - The Search for the Holy Grail Continues.

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Effect of Brain Lesions on Voluntary Cough in Patients with Supratentorial Stroke: An Observational Study

Patients with stroke are known to manifest a decreased cough force, which is associated with an increased risk of aspiration. Specific brain lesions have been linked to impaired reflexive coughing. However, few studies have investigated whether specific stroke lesions are associated with impaired voluntary cough. Here, we studied the effects of stroke lesions on voluntary cough using voxel-based lesion-symptom mapping (VLSM). In this retrospective cross-sectional study, the peak cough flow was measured in patients who complained of weak cough (n = 39) after supratentorial lesions. Brain lesions were visualized via magnetic resonance imaging (MRI) at the onset of stroke. These lesions were studied using VLSM. The VLSM method with non-parametric mapping revealed that lesions in the sub-gyral frontal lobe and superior longitudinal and posterior corona radiata were associated with a weak cough flow. In addition, lesions in the inferior parietal and temporal lobes and both the superior and mid-temporal gyrus were associated with a weak peak cough flow during voluntary coughing. This study identified several brain lesions underlying impaired voluntary cough. The results might be useful in predicting those at risk of poor cough function and may improve the prognosis of patients at increased risk of respiratory complications after a stroke.
Interleukin-15 after Near-Infrared Photoimmunotherapy (NIR-PIT) Enhances T Cell Response against Syngeneic Mouse Tumors

Simple Summary Near infrared photoimmunotherapy is a newly developed and highly selective cancer treatment that employs a monoclonal antibody conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted near infrared photoimmunotherapy selectively induces rapid necrotic/immunogenic cell death only on target cancer cells and this induces antitumor host immunity including re-priming and proliferation of multi-chronal T-cells that can react with cancer-specific antigens. Interleukin-15 is a type-I cytokine that activates natural killer-, B- and T-cells while having minimal effect on regulatory T-cells that lack the interleukin-15 receptor. Therefore, interleukin-15 administration combined with cancer cell-targeted near infrared photoimmunotherapy could further inhibit tumor growth by increasing antitumor host immunity. In tumor-bearing immunocompetent mice receiving this combination therapy, significant tumor growth inhibition and prolonged survival was demonstrated compared with either single therapy alone, and tumor infiltrating CD8+ T-cells increased in number in combination-treated mice. Interleukin-15 enhances therapeutic effects of cancer-targeted near infrared photoimmunotherapy. Abstract Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted NIR-PIT induces rapid necrotic/immunogenic cell death (ICD) that induces antitumor host immunity including re-priming and proliferation of T cells. Interleukin-15 (IL-15) is a cytokine that activates natural killer (NK)-, B- and T-cells while having minimal effect on regulatory T cells (Tregs) that lack the IL-15 receptor. Here, we hypothesized that IL-15 administration with cancer cell-targeted NIR-PIT could further inhibit tumor growth by increasing antitumor host immunity. Three syngeneic mouse tumor models, MC38-luc, LL/2, and MOC1, underwent combined CD44-targeted NIR-PIT and short-term IL-15 administration with appropriate controls. Comparing with the single-agent therapy, the combination therapy of IL-15 after NIR-PIT inhibited tumor growth, prolonged survival, and increased tumor infiltrating CD8+ T cells more efficiently in tumor-bearing mice. IL-15 appears to enhance the therapeutic effect of cancer-targeted NIR-PIT.
Microbleeds and Medial Temporal Atrophy Determine Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study.

BACKGROUND The cognitive trajectories in normal aging may be affected by medial temporal atrophy (MTA) and amyloid burden, as well as vascular pathologies such as cortical microbleeds (CMB) and white matter hyperintensities (WMH). OBJECTIVE We addressed here the role of imaging markers in their prediction in a real-world situation. METHODS We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, MTA estimated with the Schelten's scale, number of CMB, and WMH evaluated with the Fazekas score at inclusion and follow-up, visual rating of amyloid PET and glucose hypometabolism at follow-up, and APOE genotyping. Regression models were built to explore the association between the continuous cognitive score (CCS) and imaging parameters. RESULTS The number of strictly lobar CMB at baseline (4 or more) was related to a 5.5-fold increase of the risk of cognitive decrement. This association persisted in multivariable models explaining 10.6% of the CCS decrease variance. MTA, and Fazekas score at baseline and amyloid positivity or abnormal FDG PET, were not related to the cognitive outcome. The increase of right MTA at follow-up was the only correlate of CCS decrease both in univariate and multivariable models explaining 9.2% of its variance. CONCLUSION The present data show that the accumulation of more than four CMB is associated with significant cognitive decrement over time in highly educated elderly persons. They also reveal that the progressive deterioration of cognitive performance within the age-adjusted norms is also related to the increase of visually assessed MTA.
Natural History of Growing Sporadic Vestibular Schwannomas: An Argument for Continued Observation Despite Documented Growth in Select Cases

Objective: Definitive treatment of sporadic vestibular schwannoma (VS) following documented growth is common practice at most centers in the United States. However, as a natural extension of this paradigm, very little evidence exists surrounding the natural history of growing tumors. The primary objective of the current work was to describe the natural history of sporadic VS following documentation of initial tumor growth. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients diagnosed with sporadic VS between January 1, 2001 and December 31, 2015 who elected continued observation despite having volumetric growth ≥20% of original tumor volume on interval magnetic resonance imaging (MRI). Main Outcome Measure: Survival free of subsequent volumetric growth. Results: Of 361 patients undergoing observation with serial imaging during the study period, 85 patients met inclusion criteria at a median age of 66 years (interquartile ranges [IQR] 55–71). Within this cohort, 40 patients demonstrated subsequent volumetric growth at a median of 1.7 years (IQR 1.0–2.6) from the date of initial MRI that documented growth. The median volumetric growth was 43% (IQR 28–57), and the median growth rate was 0.026 cm3 per year (IQR 0.009–0.107). Survival free of subsequent volumetric growth rates (95% CI; number still at risk) at 1, 2, 3, 4, and 5 years were 93% (87–99; 75), 67% (58–79; 45), 54% (43–67; 29), 44% (33–59; 19), and 41% (30–56; 12), respectively. Conclusions: In a cohort exclusively comprised of sporadic VS with documented growth, over 40% of tumors demonstrated no subsequent volumetric growth after 5 years of continued MRI surveillance. These data challenge the supposition that once growth occurs, all tumors will exhibit sustained growth. Continued observation after documented growth of sporadic VS is a reasonable consideration in appropriately selected cases.
Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion

Supplemental Digital Content is available in the text Abstract Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma. Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy. This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12–26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04). Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.
Seasonality of mood and affect in a large general population sample

Mood and behaviour are thought to be under considerable influence of the seasons, but evidence is not unequivocal. The purpose of this study was to investigate whether mood and affect are related to the seasons, and what is the role of neuroticism in this association. In a national internet-based crowdsourcing project in the Dutch general population, individuals were invited to assess themselves on several domains of mental health. ANCOVA was used to test for differences between the seasons in mean scores on the Positive and Negative Affect Schedule (PANAS) and Quick Inventory of Depressive Symptomatology (QIDS). Within-subject seasonal differences were tested as well, in a subgroup that completed the PANAS twice. The role of neuroticism as a potential moderator of seasonality was examined. Participants (n = 5,282) scored significantly higher on positive affect (PANAS) and lower on depressive symptoms (QIDS) in spring compared to summer, autumn and winter. They also scored significantly lower on negative affect in spring compared to autumn. Effect sizes were small or very small. Neuroticism moderated the effect of the seasons, with only participants higher on neuroticism showing seasonality. There was no within-subject seasonal effect for participants who completed the questionnaires twice (n = 503), nor was neuroticism a significant moderator of this within-subjects effect. The findings of this study in a general population sample participating in an online crowdsourcing study do not support the widespread belief that seasons influence mood to a great extent. For, as far as the seasons did influence mood, this only applied to highly neurotic participants and not to low-neurotic participants. The underlying mechanism of cognitive attribution may explain the perceived relation between seasonality and neuroticism.
Enhanced Magnetic Properties of Co-Doped BiFeO3 Thin Films via Structural Progression

Co3+ doping in BiFeO3 is expected to be an effective method for improving its magnetic properties. In this work, pristine BiFeO3 (BFO) and doped BiFe1-xCoxO3 (BFCxO, x = 0.01, 0.03, 0.05, 0.07 and 0.10) composite thin films were successfully synthesized by a sol–gel technique. XRD and Raman spectra indicate that the Co3+ ions are substituted for the Fe3+ ion sites in the BFO rhombohedral lattice. Raman vibration of oxygen octahedron is obviously weakened due to the lattice distortion induced by the size mismatch between two B-site cations (Fe3+ and Co3+ ions), which has an impact on the magnetic properties of BFCxO. SEM images reveal a denser agglomeration in Co-doped samples. TEM results indicate that the average size of grains is reduced due to the Co3+ substitution. XPS measurements illustrate that the replacement of Fe3+ with Co3+ effectively suppresses the generation of oxygen defects and increases the concentration of Fe3+ ions at the B-site of perovskite lattice. Vibrating sample magnetometer (VSM) measurements show that the remanent magnetization (Mr) of BFC0.07O (3.6 emu/cm3) and the saturation magnetization (Ms) of BFC0.10O (48.84 emu/cm3) thin film both increase by approximately two times at room temperature, compared with that of the pure BFO counterpart.
Systemic lupus erythematosus and varicella‐like rash following COVID‐19 in a previously healthy patient

Emerging reports show that coronavirus disease 2019 (COVID‐19) may lead to autoimmune and autoinflammatory diseases. However, COVID‐19 triggered systemic lupus erythematosus (SLE) has never been reported to our knowledge. COVID‐19 also has associated cutaneous manifestations. Here we present a case of SLE with antiphospholipid antibody syndrome in a previously healthy patient with COVID‐19, who subsequently developped a varicella‐like exanthem on the trunk. The disease resulted in death of the patient. The pathophysiological mechanisms resulting in overlapping disorders in our patient remain unknown, adding to the growing mystery of this virus and raising questions about the nature of its link with cutaneous, autoimmune, and autoinflammatory manifestations. Sharing the images of this case may benefit physicians dealing with similar patients during this pandemic.
Serine Protease-Mediated Cutaneous Inflammation: Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers

Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development.
Tumor microenvironment-triggered charge reversal polymetformin-based nanosystem co-delivered doxorubicin and IL-12 cytokine gene for chemo-gene combination therapy on metastatic breast cancer.

Cancer metastasis is the leading cause of high mortality and disease recurrence in breast cancer. In this study, a novel tumor microenvironment charge reversal polymetformin (PMet)-based nanosystem co-delivered doxorubicin (DOX) and plasmid encoding IL-12 gene (pIL-12) was developed for chemo-gene combination therapy on metastatic breast cancer. Cationic PMet was readily self-assembled into micelles for DOX physical encapsulation and pIL-12 complexation, and a hyaluronidase-sensitive thiolated hyaluronic acid (HA-SH) was then collaboratively assembled to the pIL-12/DOX-PMet micelleplexes, abbreviated as HA/pIL-12/DOX-PMet. DOX/pIL-12 loaded in HA/pIL-12/DOX-PMet micelleplexes presented prolonged circulation in blood, efficient accumulation in tumors and internalization in tumor cells via CD44 receptor-mediated tumor specific-targeting, and DOX/pIL-12 co-released in endo/lysosomes tumor microenvironment followed by HAase-triggered HA-SH de-shielding from HA/pIL-12/DOX-PMet micelleplexes. Moreover, HA/PMet micelleplexes displayed excellent pIL-12 transfection and IL-12 expression in tumors of 4T1 tumor-bearing mice. Importantly, HA/pIL-12/DOX-PMet micelleplexes synergistically enhanced the NK cells and tumor infiltrated cytotoxic T lymphocytes, modulate the polarization from protumor M2 macrophages to activated anti-tumor M1 macrophages, concomitant decreasing the immunosuppressive regulatory T (Treg) cells, accompanied with the increased in the cytokines expression of IL-12, IFN-γ and TNF-α, consequently showing an improved anti-tumor and anti-metastasis activity in 4T1 breast cancer lung metastasis mice model. In conclusion, the tumor microenvironment charge reversal HA/PMet nano system holds great promise for DOX/pIL-12 co-delivery and exploitation in chemo-gene combination therapy on metastatic breast cancer.
The Combined Algae Test for the Evaluation of Mixture Toxicity in Environmental Samples

The combined algae test is a 96‐well plate‐based algal toxicity assay with the green algae Raphidocelis subcapitata that combines inhibition of 24‐h population growth rate with inhibition of photosynthesis detected after 2 and 24 h with pulse‐amplitude modulated (PAM) fluorometry using a Maxi‐Imaging PAM. The combined algae test has been in use for more than a decade but has had limitations due to incompatibilities of the measurements of the 2 biological endpoints on the same microtiter plates. These limitations could be overcome by increasing growth rates and doubling times on black, clear‐bottom 96‐well plates by application of dichromatic red/blue light‐emitting diode illumination. Different robotic dosing approaches and additional data evaluation methods helped to further expand the applicability domain of the assay. The combined algae test differentiates between nonspecifically acting compounds and photosynthesis inhibitors, such as photosystem II (PSII) herbicides. The PSII herbicides acted immediately on photosynthesis and showed growth rate inhibition at higher concentrations. If growth was a similar or more sensitive endpoint than photosynthesis inhibition, this was an indication that the tested chemical acted nonspecifically or that a mixture or a water sample was dominated by chemicals other than PSII herbicides acting on algal growth. We fingerprinted the effects of 45 chemicals on photosynthesis inhibition and growth rate and related the effects of the single compounds to designed mixtures of these chemicals detected in water samples and to the effects directly measured in water samples. Most of the observed effects in the water samples could be explained by known photosystem II inhibitors such as triazines and phenylurea herbicides. The improved setup of the combined algae test gave results consistent with those of the previous method but has lower costs, higher throughput, and higher precision. Environ Toxicol Chem 2020;39:2496–2508. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Baseline SUVmax of 18F-FDG PET-CT indicates prognosis of extranodal natural killer/T-cell lymphoma

Supplemental Digital Content is available in the text Abstract To evaluate the prognostic value of the baseline SUVmax of 18F-FDG PET-CT in extranodal natural killer/T-cell lymphoma (NKTCL) patients. From January 2010 to December 2015, 141 extranodal NKTCL patients with staging 18F-FDG PET-CT scan were divided into two group based on SUVmax cutoff value obtained from operating characteristic (ROC) curves. All the patients received radiotherapy, chemotherapy or chemoradiation. Survival analysis was performed on the basis of SUVmax. The median baseline SUVmax of the tumors was 11.67 (range 2.6–34.6). The ROC curves showed that the optimal cutoff of the baseline SUVmax was 9.65. The patients were divided into two groups: low SUV group (SUVmax < 9.65) and high SUV group (SUVmax ≥ 9.65). Patients in high SUV group were more likely to have invasive disease outside the nasal cavity (P < .001), poorer ECOG scores (P = .012) and higher LDH levels (P = .034). The univariate survival analyses indicated that high SUVmax was a poor prognostic factor for overall survival (OS, P = .038), progression free survival (PFS, P = .006) and distant relapse free survival (DRFS, P = .001), but not for local recurrence free survival (LRFS, P > .05). These results were consistent with that of the survival analyses using the Kaplan–Meier method. The multivariate survival analyses showed that the baseline SUVmax was no longer a prognostic factor for OS (HR 1.99, 95% CI 0.81–4.88, P = .135), but it still indicated worse PFS (HR 2.6, 95% CI 1.24–5.46, P = .012) and DRFS (HR 4.58, 95% CI 1.83–11.46, P = .001) independent of other variables. For extranodal NKTCL patients, a higher baseline SUVmax of 18F-FDG PET-CT was associated with more aggressive clinical features. An SUVmax ≥ 9.65 was an independent poor prognostic factor for DRFS and PFS. Thus, the baseline SUVmax may be a valuable tool to help identify patients with a high risk of disease progression.