Miracle-dz/UniFAR-FTUs huggingface dataset:
PTK7-Targeting CAR T-Cells for the Treatment of Lung Cancer and Other Malignancies

In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the “on target off tumor” toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small-cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. In this study, we constructed three different PTK7-specific CAR (PTK7-CAR1/2/3), each comprising a humanized PTK7-specific single-chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain (CD3ζ-ICD) sequence, and then prepared the CAR T cells by lentivirus-mediated transduction of human activated T cells accordingly, and we sequentially evaluated their antigen-specific recognition and killing activity in vitro and in vivo. T cells transduced with all three PTK7-CAR candidates exhibited antigen-specific cytokine production and potent cytotoxicity against naturally expressing PTK7-positive tumor cells of multiple cancer types without mediating cytotoxicity of a panel of normal primary human cells; meanwhile, in vitro recursive cytotoxicity assays demonstrated that only PTK7-CAR2 modified T cells retained effective through multiple rounds of tumor challenge. Using in vivo xenograft models of lung cancers with different expression levels of PTK7, systemic delivery of PTK7-CAR2 modified T cells significantly prevented tumor growth and prolonged overall survival of mice. Altogether, our results support PTK7 as a therapeutic target suitable for CAR T-cell therapy that could be applied for lung cancers and many other solid cancers with PTK7 overexpression.
Training Emotion Recognition Accuracy: Results for Multimodal Expressions and Facial Micro Expressions

Nonverbal emotion recognition accuracy (ERA) is a central feature of successful communication and interaction, and is of importance for many professions. We developed and evaluated two ERA training programs—one focusing on dynamic multimodal expressions (audio, video, audio-video) and one focusing on facial micro expressions. Sixty-seven subjects were randomized to one of two experimental groups (multimodal, micro expression) or an active control group (emotional working memory task). Participants trained once weekly with a brief computerized training program for three consecutive weeks. Pre-post outcome measures consisted of a multimodal ERA task, a micro expression recognition task, and a task about patients' emotional cues. Post measurement took place approximately a week after the last training session. Non-parametric mixed analyses of variance using the Aligned Rank Transform were used to evaluate the effectiveness of the training programs. Results showed that multimodal training was significantly more effective in improving multimodal ERA compared to micro expression training or the control training; and the micro expression training was significantly more effective in improving micro expression ERA compared to the other two training conditions. Both pre-post effects can be interpreted as large. No group differences were found for the outcome measure about recognizing patients' emotion cues. There were no transfer effects of the training programs, meaning that participants only improved significantly for the specific facet of ERA that they had trained on. Further, low baseline ERA was associated with larger ERA improvements. Results are discussed with regard to methodological and conceptual aspects, and practical implications and future directions are explored.
A Longitudinal Study of Cattle Productivity in Intensive Dairy Farms in Central Ethiopia

Ethiopia is witnessing an emergence of intensive urban dairy farming. The aims of this study were to capture cattle productivity parameters in selected intensive dairy farms in and around Addis Ababa (Central Ethiopia). The study is a pre-requisite and baseline for further economic analysis of diseases such as bovine tuberculosis (BTB) and to assess some of the current challenges faced by farm owners for optimal animal performances. Hence, a 3-year longitudinal observational study was conducted for the first time in Ethiopia, in 24 dairy farms with intensive husbandry, including a total of 1,705 dairy animals. Herd characteristics, animal movement, and productivity parameters (fertility, morbidity, mortality) were recorded in a herd-book. Whereas, half the farms saw their animals increase in number over the 3 years, 37.5% (mainly large farms) saw their herd size decrease. Offtakes accounted for 76.6% of all animal exits. One hundred and ninety (11.1%) animals died of natural causes. Highest mortality was observed in young stock (13.9%). Overall, diseases were the leading cause for death (57.5%). The majority of calves (69%) that died, did so within the first week of life. Mean calving interval (CI) was 483.2 days. Successful conception after artificial insemination (AI) was 66.1% with Addis Ababa and smaller farms faring worst. Mean time interval from calving to first service was 152 days. Date of birth to first service was 592.2 days and date of birth to first calving was 794.7 days. In conclusion, the study showed sub-optimal productivity performances in intensive dairy cattle and highlighted some of the current gaps and challenges in urban dairy productivity.
A Novel Parasitic, Syndinean Dinoflagellate Euduboscquella triangula Infecting the Tintinnid Helicostomella longa

A tintinnid species, Helicostomella longa, infected by the parasitic dinoflagellate Euduboscquella triangula n. sp. was discovered from the southern coast of Korea in August of 2015 and 2016. Parasite morphology and development were analyzed by observation of live cells and protargol-stained specimens. The parasite was determined to be a new species in the genus Euduboscquella based on morphological and molecular data. A representative sequence of the novel species clustered in Euduboscquella group I. The morphological and developmental features of E. triangula were distinguished from those of its congeners by: (1) numerous shallow and intertwining grooves on an inconspicuous shield; (2) sporocytes initially forming a short chain, but separating after the second or third division regardless of spore type; (3) production of motile mushroom-shaped dinospores, non-motile spherical spores, and non-motile triangular spores. Dinospores were formed by ca. 28% of infections, while both non-motile spherical and triangular spores occurred at a frequency of ca. 36%. All spore types showed completely identical 18S rDNA sequences. Parasite prevalence was 15.5 and 8.3% on 17 and 24 August of 2015, respectively, with infection intensity on both dates being 1.3.
Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

Diabetic vascular complications (DVC) including macrovascular and microvascular lesions, have a significant impact on public health, and lead to increased patient mortality. Disordered intercellular cascades play a vital role in diabetic systemic vasculopathy. Exosomes participate in the abnormal signal transduction of local vascular cells and mediate the transmission of metabolic disorder signal molecules in distant organs and cells through the blood circulation. They can store different signaling molecules in the membrane structure and release them into the blood, urine, and tears. In recent years, the carrier value and therapeutic effect of exosomes derived from stem cells have garnered attention. Exosomes are not only a promising biomarker but also a potential target and tool for the treatment of DVC. This review explored changes in the production process of exosomes in the diabetic microenvironment and exosomes’ early warning role in DVC from different systems and their pathological processes. On the basis of these findings, we discussed the future direction of exosomes in the treatment of DVC, and the current limitations of exosomes in DVC research.
CMV Infection Is Directly Related to the Inflammatory Status in Chronic Heart Failure Patients

High levels of inflammation play an important role in chronic heart failure (CHF). Patients with CHF have elevated levels of pro-inflammatory cytokines circulating systemically, mainly TNF and IL-6. However, there are almost no studies that relate these levels to the functional status of patients in CHF, much less to their CMV serostatus. In this study, patients with CHF (n=40; age=54.9 ± 6.3; New York Heart Association functional classification (NYHA, I-III) and healthy controls (n=40; age=53.5 ± 7.1) were analyzed. The serum concentrations of nine pro- and anti-inflammatory cytokines were measured by Luminex® xMap Technology and the basal level of mRNA expression of some immune molecules was quantified by TaqMan™ Array in CD4+ T-lymphocytes. The concentration of these cytokines in culture supernatants in response to anti-CD3 and LPS was also measured. The percentage of CD28null T-cells was determined, as well as the antibody titer against CMV. We found a higher concentration of all cytokines studied in CHF serum compared to healthy controls, as well as a direct correlation between functional status in CHF patients and levels of inflammatory cytokines. Moreover, the highest cytokine concentrations were found in patients with higher concentrations of lymphocytes lacking CD28 molecule. The cytokine production was much higher in CMV+ patients, and the production of these cytokines was found mainly in the T-lymphocytes of CMV+ patients in response to anti-CD3. Anti-CMV antibody levels were positively correlated with cytokine levels. The baseline expression of specific mRNA of the main molecules involved in the Th1 response, as well as molecules related to the CD4+CD28 null subset was higher in CMV+ patients. The cytokine concentrations are higher in CHF CMV+ patients and these concentrations are related to the production of antibodies against CMV. These high levels of cytokines are also associated with the more differentiated CD28null lymphocyte populations. All this, together with the dynamics of the pathology itself, makes CMV+ patients present a worse functional status and possibly a worse evolution of the pathology.
Predictive Equation for Angle Opening Distance at 750 μm After Laser Peripheral Iridotomy in Primary Angle Closure Suspects

Aim: The aim of this study was to investigate the changes in anterior segment parameters as assessed by ultrasound biomicroscopy (UBM) after laser peripheral iridotomy (LPI) and to propose a prediction equation for the width of the angle after LPI. Design: This was a prospective study. Participants: The participants included 100 subjects with primary angle closure suspect (PACS). Methods: Anterior segment UBM parameters were measured, whereas AOD750 was chosen to indicate the width of the angle associated with gonioscopic angle closure, as found in a prior study. Main Outcome Measures: Angle parameters, iris parameters, anterior chamber parameters and ciliary body parameters. Results: All angle parameters increased after LPI, including the mean angle opening distance at 750 μm (AOD750), mean angle opening distance at 500 μm from the scleral spur (AOD500), mean angle opening distance at 750 μm from the scleral spur (AOD750), and mean angle recess area at 750 μm from the scleral spur (ARA750). Among iris parameters and ciliary body parameters, the iris thickness at 2,000 μm (IT2000), iris curvature (IC), and trabecular-ciliary process distance (ICPD) were reduced after LPI. The final equation consisted of four parameters: anterior chamber depth (ACD), iris thickness at 750 μm from the scleral spur (IT750), AOD750, and lens vault (LV). This equation explained 42.7% of the variability in the angle opening indicator AOD750 after LPI, whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached the highest a maximum of 68.6%. Conclusions: There was an increase in angle opening and iris flattening after LPI. An equation involving four angle parameters was constructed, this equation which could explained 42.7% of the variability in the angle opening indicator AOD750 after LPI whereas in the plateau iris configuration subgroup, the accuracy of the prediction equation reached a maximum of 68.6%.
Active Inference and Cooperative Communication: An Ecological Alternative to the Alignment View

We present and contrast two accounts of cooperative communication, both based on Active Inference, a framework that unifies biological and cognitive processes. The mental alignment account, defended in Vasil et al., takes the function of cooperative communication to be the alignment of the interlocutor's mental states, and cooperative communicative behavior to be driven by an evolutionarily selected adaptive prior belief favoring the selection of action policies that promote such an alignment. We argue that the mental alignment account should be rejected because it neglects the action-oriented nature of cooperative communication, which skews its view of the dynamics of communicative interaction. We introduce our own conception of cooperative communication, inspired by a more radical ecological interpretation of the active inference framework. Cooperative communication, on our ecological conception, serves to guide and constrain the dynamics of the cooperative interaction via the construction and restructuring of shared fields of affordances, in order to reach the local goals of the joint actions in which episodes of cooperative communication are embedded. We argue that our ecological conception provides a better theoretical standpoint to account for the action-oriented nature of cooperative communication in the active inference framework.
Clinical Characteristics, Prognosis, and Gender Disparities in Young Patients With Acute Myocardial Infarction

Background: Young people hold a stable or increasing percentage of patients with acute myocardial infarction (AMI) in many countries. However, data on clinical characteristics and outcomes of young AMI patients were insufficient. This study aimed to analyze clinical characteristics, prognosis, and gender disparities in patients aged ≤45 years with AMI. Methods: A total of 24,125 patients from China Acute Myocardial Infarction registry were included in this study. Clinical characteristics, managements, and in-hospital and 2-year outcomes were compared between patients aged ≤45 years and those aged >45 years. Predictors of all-cause death were obtained using multivariate regression models. Gender disparities of AMI were analyzed among young patients. Results: Of 24,125 patients, 2,042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged >45 years, young patients were more often male, current smokers, and more likely to have medical history of hyperlipidemia. Smoking (72.1%) was the major modifiable risk factor in patients aged ≤45 years. Young patients received more evidence-based medications and had significantly lower risk of both in-hospital and 2-year adverse events than older patients. Education level and left ventricular ejection fraction were independent predictors of 2-year mortality in young patients. Moreover, symptom onset to admission time of young women was significantly longer than that of young men. Young women were less likely to receive percutaneous coronary intervention and suffered higher risk of in-hospital adverse events than young men (adjusted odds ratio for death: 5.767, 95% confidence interval 1.580–21.049, p = 0.0080; adjusted odds ratio for the composite of death, re-infarction, and stroke: 3.981, 95% confidence interval 1.150–13.784, p = 0.0292). Young women who survived at discharge had a higher 2-year cumulative incidence of death (3.8 vs 1.4%, plog−rank = 0.0412). Conclusions: Patients aged ≤45 years constituted a non-negligible proportion of AMI patients, with higher prevalence of smoking and hyperlipidemia but better care and prognosis compared with older patients. There were significant gender disparities of managements and outcomes in young patients. More efforts to improve quality of care in young women are needed.
Visual Impairments Are Associated With Retinal Microvascular Density in Patients With Parkinson’s Disease

Objective This study aimed to evaluate retinal microvascular density in patients with Parkinson’s disease (PD) and its correlation with visual impairment. Methods This cross-sectional study included 24 eyes of 24 patients with PD and 23 eyes of 23 healthy controls. All participants underwent ophthalmic examination, visual evoked potential (VEP) test, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and optical coherence tomography angiography (OCTA) examination. The correlation between retinal microvascular density and visual parameter was evaluated using Spearman correlation analysis, and the area under receiver operating characteristic curve (AUROC) was calculated. Results Parkinson’s disease patients had prolonged P100 latency (P = 0.041), worse vision-related quality of life (composite score and 3 of 12 subscales in NEI VFQ-25), and decreased vessel density (VD) in all sectors of 3-mm-diameter region (all P < 0.05) compared with healthy controls. There were no statistical differences in the ganglion cell-inner plexiform layer (GCIPL) thickness and retinal nerve fiber layer (RNFL) thickness between the two groups. A negative correlation was found between P100 latency and nasal and superior sectors of macular VD in a 3-mm-diameter region (r = −0.328, P = 0.030; r = −0.302, and P = 0.047, respectively). Macular VD in a 3-mm-diameter region showed diagnostic capacities to distinguish PD patients from healthy controls (AUROCs, ranging from 0.655 to 0.723). Conclusion This study demonstrated that decreased retinal microvascular density was correlated with visual impairment in PD patients. Retinal microvasculature change may occur earlier than visual decline and retinal structure change and has the potential to be a promising diagnostic marker for early PD.
The Hunger Games: Aggregatibacter actinomycetemcomitans Exploits Human Neutrophils As an Epinephrine Source for Survival

Aggregatibacter actinomycetemcomitans is a gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. Previously, our group identified catecholamines and iron as the signals that activate the QseBC two-component system in A. actinomycetemcomitans, necessary for the organism to acquire iron as a nutrient to survive in the anaerobic environment. However, the source of catecholamines has not been identified. It has been reported that mouse neutrophils can release catecholamines. In periodontitis, large infiltration of neutrophils is found at the subgingival pocket; hence, we wanted to test the hypothesis that A. actinomycetemcomitans exploits human neutrophils as a source for catecholamines. In the present study, we showed that human neutrophils synthesize, store, and release epinephrine, one of the three main types of catecholamines. Human neutrophil challenge with A. actinomycetemcomitans induced exocytosis of neutrophil granule subtypes: secretory vesicles, specific granules, gelatinase granules, and azurophilic granules. In addition, by selectively inhibiting granule exocytosis, we present the first evidence that epinephrine is stored in azurophilic granules. Using QseC mutants, we showed that the periplasmic domain of the QseC sensor kinase is required for the interaction between A. actinomycetemcomitans and epinephrine. Finally, epinephrine-containing supernatants collected from human neutrophils promoted A. actinomycetemcomitans growth and induced the expression of the qseBC operon under anaerobic conditions. Based on our findings, we propose that A. actinomycetemcomitans promotes azurophilic granule exocytosis by neutrophils as an epinephrine source to promote bacterial survival.
Mini-Review of Studies Testing the Cardiorespiratory Hypothesis With Near-Infrared Spectroscopy (NIRS): Overview and Perspectives

The cardiorespiratory hypothesis (CH) is one of the hypotheses used by researchers to explain the relationship between cardiorespiratory fitness and cognitive performance during executive functions. Despite the indubitable beneficial effect of training on brain blood flow and function that may explain the link between physical fitness and cognition and the recognition of the near-infrared spectroscopy (NIRS) as a reliable tool for measuring brain oxygenation, few studies investigated the CH with NIRS. It is still not well understood whether an increase in brain flow by training is translated into an increase in cerebral oxygenation. Thus, the objective of this mini-review was to summarize main results of studies that investigated the CH using the NIRS and to propose future research directions.
Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin

Depression is a common and debilitating mood disorder that increases in prevalence during pregnancy. Worldwide, 7 to 12% of pregnant women experience depression, in which the associated risk factors include socio-demographic, psychological, and socioeconomic variables. Maternal depression could have psychological, anatomical, and physiological consequences in the newborn. Depression has been related to a downregulation in serotonin levels in the brain. Accordingly, the most commonly prescribed pharmacotherapy is based on selective serotonin reuptake inhibitors (SSRIs), which increase local serotonin concentration. Even though the use of SSRIs has few adverse effects compared with other antidepressants, altering serotonin levels has been associated with the advent of anatomical and physiological changes in utero, leading to defects in craniofacial development, including craniosynostosis, cleft palate, and dental defects. Migration and proliferation of neural crest cells, which contribute to the formation of bone, cartilage, palate, teeth, and salivary glands in the craniofacial region, are regulated by serotonin. Specifically, craniofacial progenitor cells are affected by serotonin levels, producing a misbalance between their proliferation and differentiation. Thus, it is possible to hypothesize that craniofacial development will be affected by the changes in serotonin levels, happening during maternal depression or after the use of SSRIs, which cross the placental barrier, increasing the risk of craniofacial defects. In this review, we provide a synthesis of the current research on depression and the use of SSRI during pregnancy, and how this could be related to craniofacial defects using an interdisciplinary perspective integrating psychological, clinical, and developmental biology perspectives. We discuss the mechanisms by which serotonin could influence craniofacial development and stem/progenitor cells, proposing some transcription factors as mediators of serotonin signaling, and craniofacial stem/progenitor cell biology. We finally highlight the importance of non-pharmacological therapies for depression on fertile and pregnant women, and provide an individual analysis of the risk–benefit balance for the use of antidepressants during pregnancy