Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural Killer Cells in Immunotherapy: Are We Nearly There?

Simple Summary Here, we review the last pre-clinical and clinical studies published in the last five years where natural killer (NK) cells have been administered as an immunotherapy option for the treatment of cancer patients. We describe studies administering NK cells alone and in combination with monoclonal antibodies that either promote antibody-dependent cell cytotoxicity or block immune checkpoint receptors. We review the use of genetically modified NK cells including chimeric antigen receptor (CAR)-modified NK cells and other modifications that can enhance the anti-tumor activity of NK cells. Moreover, we describe studies related to the antimicrobial activity of NK cells as we believe they demonstrate important lessons that we can learn and apply to improve the anti-tumor activity of NK cells. All these studies are described with the aim to find tips to improve the success of NK cells as an immunotherapy option in cancer patients. Abstract Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin an increasing number of clinical studies administering NK cells for the treatment of cancer patients. Unfortunately, even though transfused NK cells demonstrated safety, their observed efficacy was poor. In recent years, novel studies have emerged, combining NK cells with other immunotherapeutic agents, such as monoclonal antibodies, which might improve clinical efficacy. Moreover, genetically-modified NK cells aimed at arming NK cells with better efficacy and persistence have appeared as another option. Here, we review novel pre-clinical and clinical studies published in the last five years administering NK cells as a monotherapy and combined with other agents, and we also review chimeric antigen receptor-modified NK cells for the treatment of cancer patients. We then describe studies regarding the role of NK cells as anti-microbial effectors, as lessons that we could learn and apply in immunotherapy applications of NK cells; these studies highlight an important immunoregulatory role performed between T cells and NK cells that should be considered when designing immunotherapeutic strategies. Lastly, we highlight novel strategies that could be combined with NK cell immunotherapy to improve their targeting, activity, and persistence.
Virtual reality as a tool for balance research: Eyes open body sway is reproduced in photo-realistic, but not in abstract virtual scenes

Virtual reality (VR) technology is commonly used in balance research due to its ability to simulate real world experiences under controlled experimental conditions. However, several studies reported considerable differences in balance behavior in real world environments as compared to virtual environments presented in a head mounted display. Most of these studies were conducted more than a decade ago, at a time when VR was still struggling with major technical limitations (delays, limited field-of-view, etc.). In the meantime, VR technology has progressed considerably, enhancing its capacity to induce the feeling of presence and behavioural realism. In this study, we addressed two questions: Has VR technology now reached a point where balance is similar in real and virtual environments? And does the integration of visual cues for balance depend on the subjective experience of presence? We used a state-of-the-art head mounted VR system and a custom-made balance platform to compare balance when viewing (1) a real-world environment, (2) a photo-realistic virtual copy of the real-world environment, (3) an abstract virtual environment consisting of only spheres and bars (‘low presence’ VR condition), and, as reference, (4) a condition with eyes closed. Body sway of ten participants was measured in three different support surface conditions: (A) quiet stance, (B) stance on a sway referenced surface, and (C) surface tilting following a pseudo-random sequence. A 2-level repeated measures ANOVA and PostHoc analyses revealed no significant differences in body sway between viewing the real world environment and the photo-realistic virtual copy. In contrast, body sway was increased in the ‘low presence’ abstract scene and further increased with eyes closed. Results were consistent across platform conditions. Our results support the hypothesis that state of the art VR reached a point of behavioural realism in which balance in photo-realistic VR is similar to balance in a real environment. Presence was lower in the abstract virtual condition as compared to the photo-realistic condition as measured by the IPQ presence questionnaire. Thus, our results indicate that spatial presence may be a moderating factor, but further research is required to confirm this notion. We conceive that virtual reality is a valid tool for balance research, but that the properties of the virtual environment affects results.
Development of RisObIn.Com, a Screening Tool for Risk of Childhood Obesity in the Community

The prevalence of childhood overweight has increased considerably in the past three decades and there is evidence that childhood obesity can persist into adulthood. A simple tool to identify relevant risk factors may alert families and prevent overweight and obesity. This study aims to develop a pre-school screening tool to assess the risk of childhood obesity. Child anthropometric measurements and several risk factors for childhood obesity factors were obtained. The effect of the variables on the outcome of obesity (defined as increased anthropometry-estimated adiposity) was assessed by binary logistic regression analyses. The identified variables were submitted for expert panel validation and combined for the tool development. A total of 304 children were included. Eight items were included in the tool. A higher score of the tool indicates a greater risk for obesity in childhood with the cutoff point set at 0. The tool sensitivity for obesity was 95%, specificity was 74.4%, the positive predictive value was 37.3%, and negative predictive value was 98.9%. The Risk of childhood Obesity In the Community (RisObIn.Com) tool is proposed to be a comprehensive tool to identify children at high risk for late childhood obesity at admission to primary school. Further studies are needed to assess the performance of the tool.
Effects of Oxygen and Glucose on Bone Marrow Mesenchymal Stem Cell Culture

This study determines whether the viability of mesenchymal stem cell (MSC) in vitro is most sensitive to oxygen supply, energetic substrate supply, or accumulation of lactate. Mouse unmodified (wild type (WT)) and erythropoietin (EPO) gene‐modified MSC is cultured for 7 days in normoxic (21%) and anoxic conditions. WT‐MSC is cultured in anoxia for 45 days in high and regular glucose media and both have similar viability when compared to their normoxic controls at 7 days. Protein production of EPO‐MSC is unaffected by the absence of oxygen. MSC doubling time and post‐anoxic exposure is increased (WT: 32.3–73.3 h; EPO: 27.2–115 h). High glucose leads to a 37% increase in cell viability at 13 days and 17% at 30 days, indicating that MSC anoxic survival is affected by supply of metabolic substrate. However, after 30 days, little difference in viability is found, and at 45 days, complete cell death occurs in both the conditions. This death cannot be attributed to lack of glucose or lactate levels. MSC stemness is retained for both osteogenic and adipogenic differentiations. The absence of oxygen increases the doubling time of MSC but does not affect their viability, protein production, or differentiation capacity.
The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration

Objective Toxic metals are suspected to play a role in the pathogenesis of age-related macular degeneration. However, difficulties in detecting the presence of multiple toxic metals within the intact human retina, and in separating primary metal toxicity from the secondary uptake of metals in damaged tissue, have hindered progress in this field. We therefore looked for the presence of several toxic metals in the posterior segment of normal adult eyes using elemental bioimaging. Methods Paraffin sections of the posterior segment of the eye from seven tissue donors (age range 54–74 years) to an eye bank were examined for toxic metals in situ using laser ablation-inductively coupled plasma-mass spectrometry, a technique that detects multiple elements in tissues, as well as the histochemical technique of autometallography that demonstrates inorganic mercury, silver, and bismuth. No donor had a visual impairment, and no significant retinal abnormalities were seen on post mortem fundoscopy and histology. Results Metals found by laser ablation-inductively coupled plasma-mass spectrometry in the retinal pigment epithelium and choriocapillaris were lead (n = 7), nickel (n = 7), iron (n = 7), cadmium (n = 6), mercury (n = 6), bismuth (n = 5), aluminium (n = 3), and silver (n = 1). In the neural retina, mercury was present in six samples, and iron in one. Metals detected in the optic nerve head were iron (N = 7), mercury (N = 7), nickel (N = 4), and aluminium (N = 1). No gold or chromium was seen. Autometallography demonstrated probable inorganic mercury in the retinal pigment epithelium of one donor. Conclusion Several toxic metals are taken up by the human retina and optic nerve head. Injury to the retinal pigment epithelium from toxic metals could damage the neuroprotective functions of the retinal pigment epithelium and allow toxic metals to enter the outer neural retina. These findings support the hypothesis that accumulations of toxic metals in the retina could contribute to the pathogenesis of age-related macular degeneration.
Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus

Background Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea. Methods This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs). Results After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs. Conclusion SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.
Fluctuating shear during resistance exercise

Aerobic exercise enhances flow-mediated dilatation (FMD), an index of endothelial function, but this favourable effect is abolished when it mechanically attenuates shear rate (SR) (Tinken et al., 2009). These findings suggest that an exercise-induced increase in SR rather than systemic cardiovascular changes is a crucial stimulus for the improvement of endothelial function (Green, Hopman, Padilla, Laughlin, & Thijssen, 2017). In contrast, resistance exercise, an important component of health-promoting exercise programmes, decreases FMD in both active (Gonzales, Thompson, Thistlethwaite, & Scheuermann, 2011) and inactive limbs (Morishima, Tsuchiya, Iemitsu, & Ochi, 2018). The mechanism responsible for the acute attenuation of FMD after resistance exercise remains unclear, but changes in the SR profile and in the haemodynamic parameters during resistance exercise are speculated to provide key information that can help in elucidating thesemechanisms. In this regard, in this issue of Experimental Physiology Thomas and colleagues (2020) tested the acute effect of resistance exercise on the SR profile in active and inactive limbs in young adults. Thomas et al. (2020) explored the acute effects of resistance exercise (three sets of 10 isotonic repetitions of bicep curls or knee extensions, with ∼5min rest between sets) on the blood flow (BF) and SR in the brachial and superficial femoral arteries. Doppler and blood pressure (BP) measurements were performed before and for 3 min after each set. Systolic and diastolic BPs increased to a similar extent after the upper limb (UL) and lower limb (LL) exercises (systolic BP, +36–38 mmHg; diastolic BP, +23–24 mmHg). In the active limb, anterograde SR was
Ruptured unilateral anterior lenticonus with congenital hypertrophy of retinal pigment epithelium: A rare association

Best-corrected visual acuity was 20/40 in the right eye (OD) and 20/1200 in OS. Slit lamp biomicroscopy revealed OD anterior lenticonus [Fig. 1] and OS ruptured anterior lens capsule [Fig. 2] with dense heterogeneous lenticular opacity in a circular pattern [Fig. 3]. Fundoscopy OD showed Congenital Hypertrophy of Retinal Pigment Epithelium (CHRPE) [Fig. 4] and OS was hazy, with normal B scan. Systemic evaluation revealed microcystic hematuria and bilateral moderate sensorineural hearing loss. He underwent OS cataract extraction with IOL implantation. On follow-up, till 4 months the patient is maintaining the best-corrected visual acuity of 20/30. He has been started on ACE inhibitors by the nephrologist.
Effects of Unloaded vs. Ankle-Loaded Plyometric Training on the Physical Fitness of U-17 Male Soccer Players

The aim of this study was to compare the impact of two differing plyometric training programs (loaded plyometrics (with 2.5% of body mass placed above the ankle joint) vs. unloaded plyometrics), performed biweekly for 10 weeks, on the physical fitness of elite junior male soccer players. Participants aged 16.0 ± 0.5 years were randomly assigned between unloaded plyometrics (UP; n = 12), loaded plyometrics (LP; n = 14) and control (C; n = 12) groups. Two-way analyses of performance (group x time) were assessed by 40-m sprint times; 9–3–6–3–9 m sprints with 180° turns (S180°); 9–3–6–3–9 m sprints with backward and forward running (SBF); and 4 × 5 m sprints (S4 × 5 m); four jump tests; measures of static and dynamic balance; repeated change of direction tests and the Yo-Yo intermittent recovery test. Both LP and UP enhanced sprinting performance relative to C (p < 0.05) but performance increased more in LP relative to UP (p < 0.05) in all sprints except 40 m. Change of direction times were also significantly shortened by LP relative to UP (p < 0.05) and C (p < 0.01) in all tests, with no significant differences between UP and C. Jumps heights increased similarly in both LP and UP relative to C (p < 0.05), with no significance between LP and UP. LP and UP also enhanced repeated change of direction scores relative to C (p < 0.01) with greater changes in LP than in UP (p < 0.01). Finally, LP enhanced some balance scores relative to UP (p < 0.05) and C (p < 0.05). We conclude that the introduction of 10 weeks of in-season loaded plyometrics into the regimen of U17 male soccer players yields gains in several physical performance scores relative to either unloaded plyometrics or the control training regimen.
Ketogenic diet induces autophagy to alleviate bleomycin-induced pulmonary fibrosis in murine models

Abstract Aim of the Study Ketogenic diet (KD) has been identified as an effective strategy in treating multiple diseases. KD is capable of inducing autophagy which is an important therapeutic target for pulmonary fibrosis (PF). This study aimed to investigate the effect of KD treatment on PF progression. Materials and Methods: Intratracheal instillation of bleomycin (BLM, 5 mg/kg) to establish PF model in male Kunming mice fed either KD or standard diet. The survival of mice was recorded every day for 3 weeks. The pulmonary tissues were weighed on day 21 and the pulmonary index was calculated. The histopathological changes of pulmonary tissues were analyzed by hematoxylin and eosin staining and Masson staining, and the collagen deposition by hydroxyproline assay. Then the content of proinflammatory factors in pulmonary tissues was measured using enzyme-linked immunosorbent assay, and the expression of profibrogenic cytokines, autophagy markers and PI3K/AKT/mTOR pathway-related proteins in pulmonary tissues using western blotting or immunohistochemistry. Results: KD treatment significantly restored the BLM-induced increase of pulmonary index and had a tendency to increase the survival rate of PF mice. Furthermore, KD treatment restored the BLM-induced damage of alveolar structure, infiltration of inflammatory cells and collagen deposition and decreased hydroxyproline content. In addition, the BLM-induced secretion of tumor necrosis factor-alpha, interleukin-6 and interleukin-1β and expression of transforming growth factor β1, phospho-Smad2/3, connective tissue growth factor, α-smooth muscle actin and collagen type III alpha 1 chain were inhibited by KD. KD treatment also up-regulated the expression of light chain 3 II/I and Beclin1 and down-regulated the expression of p62, phospho-AKT, phospho-mTOR and phospho-p70S6K, suggesting that KD induced autophagy and suppressed the BLM-induced activation of PI3K/AKT/mTOR signaling pathway. Conclusions: These findings indicate that KD can alleviate PF in vivo by regulating autophagy and PI3K/AKT/mTOR signaling pathway, which provides a novel therapeutic strategy for PF.
Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts.

OBJECTIVES Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. METHODS Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). RESULTS The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. CONCLUSIONS The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.
Turkey Meat. Seasonal Effect on Meat Quality and on Dead on Arrival Index in a Commercial Plant

The objective of this study was to determine the incidence of Pale, Soft, Exudative (PSE) meat and to characterize the Dark, Fim, Dry (DFD) meat as well as the Dead on Arrival (DOA) index in a commercial turkey slaughterhouse in southern Brazil during the summer and winter seasons. The journeys (n=64) were over a distance of 36 ± 20 km and took approximately 95 ± 20 min. Color (L*) and pH distribution of turkey breast meat (n=5,352) were evaluated from different farms (n=64) during the 2015-2016 years. The pH, water-holding capacity, color (L*, a*, b*) were used to establish cutoff values for DFD meat (L* < 44.0 and pH > 5.90) and presented correlation among them. The L* value was the highest during the summer (P<0.01), indicating the highest incidence of PSE meat (28.35 %), and lowest during winter, observing the highest incidence of DFD meat (10.3 %). Finally, the obtained summer DOA index was 0.23 % higher in relation to winter.
Effects of Dialectal Code-Switching on Speech Modules: A Study Using Egyptian Arabic Broadcast Speech

The intra-utterance code-switching (CS) is deﬁned as the alternation between two or more languages within the same ut-terance. Despite the fact that spoken dialectal code-switching (DCS) is more challenging than CS, it remains largely unexplored. In this study, we describe a method to build the ﬁrst spoken DCS corpus. The corpus is annotated at the token-level minding both linguistic and acoustic cues for dialectal Arabic. For detailed analysis, we study Arabic automatic speech recognition (ASR), Arabic dialect identiﬁcation (ADI), and nat-ural language processing (NLP) modules for the DCS corpus. Our results highlight the importance of lexical information for discriminating the DCS labels. We observe that the performance of different models is highly dependent on the degree of code-mixing at the token-level as well as its complexity at the utterance-level.