Miracle-dz/UniFAR-FTUs huggingface dataset:
Proinflammatory Cytokines Predict Brain Metabolite Concentrations in the Anterior Cingulate Cortex of Patients With Bipolar Disorder

Bipolar disorder (BD) is a severe psychiatric illness characterized by abnormalities in the immune/inflammatory function and in brain metabolism. Evidences suggest that inflammation may affect the levels of brain metabolites as measured by single-proton magnetic resonance spectroscopy (1H-MRS). The aim of the study was to investigate whether a wide panel of inflammatory markers (i.e., cytokines, chemokines, and growth factors) can predict brain metabolite concentrations of glutamate, myo-inositol, N-acetylaspartate, and glutathione in a sample of 63 bipolar patients and 49 healthy controls. Three cytokines influenced brain metabolite concentrations: IL-9 positively predicts glutamate, IL-1β positively predicts Myo-inositol, and CCL5 positively predicts N-acetylaspartate concentrations. Furthermore, patients showed higher concentrations of glutamate, Myo-inositol, and glutathione and lower concentrations of N-acetylaspartate in respect to healthy controls. Our results confirm that inflammation in BD alters brain metabolism, through mechanisms possibly including the production of reactive oxygen species and glia activation.
Immovable Object Meets Unstoppable Force? Dialogue Between Resident and Peripheral Myeloid Cells in the Inflamed Brain

Inflammation of the brain parenchyma is characteristic of neurodegenerative, autoimmune, and neuroinflammatory diseases. During this process, microglia, which populate the embryonic brain and become a permanent sentinel myeloid population, are inexorably joined by peripherally derived monocytes, recruited by the central nervous system. These cells can quickly adopt a morphology and immunophenotype similar to microglia. Both microglia and monocytes have been implicated in inducing, enhancing, and/or maintaining immune-mediated pathology and thus disease progression in a number of neuropathologies. For many years, experimental and analytical systems have failed to differentiate resident microglia from peripherally derived myeloid cells accurately. This has impeded our understanding of their precise functions in, and contributions to, these diseases, and hampered the development of novel treatments that could target specific cell subsets. Over the past decade, microglia have been investigated more intensively in the context of neuroimmunological research, fostering the development of more precise experimental systems. In light of our rapidly growing understanding of these cells, we discuss the differential origins of microglia and peripherally derived myeloid cells in the inflamed brain, with an analysis of the problems resolving these cell types phenotypically and morphologically, and highlight recent developments enabling more precise identification.
High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

Hematopoiesis is hosted, supported and regulated by a special bone marrow (BM) microenvironment known as “niche. ” BM niches have been classified based on micro-anatomic distance from the bone surface into “endosteal” and “central” niches. Whilst different blood vessels have been found in both BM niches in mice, our knowledge of the human BM architecture is much more limited. Here, we have used a combination of markers including NESTIN, CD146, and αSMA labeling different blood vessels in benign human BM. Applying immunohistochemical/immunofluorescence techniques on BM trephines and performing image analysis on almost 300 microphotographs, we detected high NESTIN expression in BM endothelial cells (BMECs) of small arteries (A) and endosteal arterioles (EA), and also in very small vessels we named NESTIN+ capillary-like tubes (NCLTs), not surrounded by sub-endothelial perivascular cells that occasionally reported low levels of NESTIN expression. Statistically, NCLTs were detected within 40 μm from bone trabecula, frequently found in direct contact to the bone line and spatially correlated with hematopoietic stem/progenitor cells. Our results support the expression of NESTIN in human BMECs of EA and A in accordance with the updated classification of murine BM micro-vessels. NCLTs for their peculiar characteristics and micro-anatomical localization have been here proposed as transitional vessels possibly involved in regulating human hematopoiesis.
Polysaccharide of Atractylodes macrocephala Koidz (PAMK) Alleviates Cyclophosphamide-induced Immunosuppression in Mice by Upregulating CD28/IP3R/PLCγ-1/AP-1/NFAT Signal Pathway

The polysaccharide of Atractylodes macrocephala Koidz (PAMK) is recognized as an immune enhancer, with anti-cancer, anti-tumour, lymphocyte-activating and lymphocytes proliferation-inducing effects. For investigating the mechanism that PAMK alleviates the decline in T cell activation induced by CTX, 24 6-week-old BALB/c female mice were randomly divided into four groups (C, PAMK, CTX, PAMK + CTX). The spleen index, splenocytes morphology and death, cytokine concentration, T cell activating factors (CD25, CD69, CD71), mRNA expression levels related to the CD28 signal pathway were detected. Furthermore, the lymphocytes of mice was isolated and cultured, and then the Th1/Th2 ratio, activating factors, mRNA levels related to the CD28 signal pathway were detected. The results showed that PAMK significantly improved the spleen index, alleviated abnormal splenocytes morphology and death, maintained the balance of Th1/Th2 cells, increased the levels of IL-2, IL-6, TNF-α, and IFN-γ, and increased the mRNA levels of CD28, PLCγ-1, IP3R, NFAT, and AP-1. In conclusion, PAMK increased cytokines levels and alleviated the decline in activation level of lymphocytes induced by CTX through CD28/IP3R/PLCγ-1/AP-1/NFAT signal pathway.
Palaeophytogeographical Patterns Across the Permian–Triassic Boundary

It has long been recognized that terrestrial floras underwent major and long-lasting changes during the Permian and Triassic, some of which have been attributed to the end-Permian mass extinction. However, these changes are still poorly understood with regard to the late Permian and Early Triassic. In particular, the impact that ecological disturbances around the Permian–Triassic boundary had on the composition and palaeogeographical distribution of land plant communities needs to be scrutinized. We analyse this impact based on fossil floras from across the world, covering the Wuchiapingian to Ladinian time interval. The plant assemblages are assigned to biomes representing particular environmentally controlled community types. Variations in the distribution of biomes between stages indicate shifts in the environmental parameters affecting terrestrial floras, and provide insights into population turnover dynamics. A substantial shift towards increasing seasonality and a reduction of biome diversity occurs in the earliest Triassic and stabilised throughout the Middle Triassic. However, results also show that the stratigraphically and (palaeo-) geographically unequal distribution of sampled localities constitutes an important limitation for this kind of analysis.
Measurement Invariance of the Multidimensional Scale of Perceived Social Support Among Chinese and South Asian Ethnic Minority Adolescents in Hong Kong

Seven hundred adolescents (Chinese = 50%; South Asian ethnic minority = 50%) with mean age of 15.3 years (SD = 1.53). Multigroup confirmatory factor analysis was performed to assess measurement invariance of the MSPSS scale across Chinese and South Asian ethnic minority samples. Results show that the original three-factor structure of the MSPSS was supported in both samples. Measurement invariance was supported in terms of configural, metric, and partial scalar invariance. Given partial scalar invariance was achieved, the latent mean differences were compared across samples. Chinese adolescents had higher levels of all three types of social support when compared with their South Asian ethnic minority counterparts. The present study attempts to assess the measurement invariance of the MSPSS across ethnic groups in Asian society, which sheds light on future research that involves perceived social support among adolescents in Chinese culture contexts.
Effect of Pressures and Durations of Cupping Therapy on Skin Blood Flow Responses

Cupping therapy has been widely used in treating musculoskeletal impairments. However, there is no specific guideline on selecting the intensity of cupping therapy, including the pressure and duration. The objective of this study was to investigate the effect of different pressures and durations of cupping therapy on skin blood flow responses. A 2 × 2 factorial design, including two negative pressures at −225 and −300 mmHg and two durations at 5 and 10 min, was tested in 12 healthy participants. The four protocols of cupping therapy were tested in four different days. Skin blood flow was measured using laser Doppler flowmetry on the left triceps (the SJ12 acupoint). Skin blood flow after cupping therapy was expressed as a ratio of skin blood flow before cupping therapy. The results showed that −300 mmHg caused a significant increase in peak skin blood flow (16.7 ± 2.6 times) compared to −225 mmHg (11.1 ± 2.2 times, p < 0.05) under 5-min duration. The largest difference in skin blood flow is between −300 mmHg for 5 min (16.7 ± 2.6 times) and −225 mmHg for 10 min (8.1 ± 2.3 times, p < 0.01). Our findings demonstrated that a higher value (300 mmHg) of negative pressure is more effective on increasing skin blood flow compared to a lower value (225 mmHg). Also, a shorter duration (5 min) causes a larger peak and total skin blood flow compared to a longer duration (10 min). This study provides the first evidence showing the effect of pressures and durations of cupping therapy on skin blood flow responses.
Reciprocal Influence of Depressive Symptoms Between Mothers and Fathers During the First Postpartum Year: A Comparison Among Full-Term, Very Low, and Extremely Low Birth Weight Infants

Background: Perinatal depression (PND) in mothers and fathers of very low and extremely low birth weight (VLBW and ELBW) infants has not been studied extensively. In particular, no studies investigated the reciprocal influence of depressive symptoms during the first 12 months postpartum. This study aimed at exploring the impact of the severity of prematurity on maternal and paternal PND during the first postpartum year; specifically, we used an Actor–Partner Interdependence Model (APIM) to test the interdependence of both partners on depressive symptoms. Methods: A total of 177 mothers and 177 fathers were recruited, divided into 38 couples with ELBW infants, 56 with VLBW, and 83 of full-term (FT) infants. PND was evaluated by the Edinburgh Postnatal Depression Scale (EPDS) at 3, 9, and 12 months postpartum (corrected age for preterm infants). Results: Maternal depressive symptoms at 3 months were positively related to those at 9 and 12 months in the 3 groups. Conversely, paternal depressive symptoms assessed at 3 months were positively related to those measured at 9 months for the ELBW group, 12 months for the VLBW group, 9 and 12 months for FT condition. Furthermore, a significantly positive partner effect was observed regarding the influence of 3 month maternal depressive symptoms on paternal depressive symptoms at 9 months, but only in the case of the VLBW group. Conclusion: Prematurity represents a very specific scenario in the transition to parenthood, leading to specific reactions in mothers and fathers, especially in high-risk conditions. Results should be deepened given the relevance of their clinical implications.
Functional and Genomic Characterization of Ligilactobacillus salivarius TUCO-L2 Isolated From Lama glama Milk: A Promising Immunobiotic Strain to Combat Infections

Potential probiotic or immunobiotic effects of lactic acid bacteria (LAB) isolated from the milk of the South American camelid llama (Lama glama) have not been reported in published studies. The aim of the present work was to isolate beneficial LAB from llama milk that can be used as potential probiotics active against bacterial pathogens. LAB strains were isolated from llama milk samples. In vitro functional characterization of the strains was performed by evaluating the resistance against gastrointestinal conditions and inhibition of the pathogen growth. Additionally, the adhesive and immunomodulatory properties of the strains were assessed. The functional studies were complemented with a comparative genomic evaluation and in vivo studies in mice. Ligilactobacillus salivarius TUCO-L2 showed enhanced probiotic/immunobiotic potential compared to that of other tested strains. The TUCO-L2 strain was resistant to pH and high bile salt concentrations and demonstrated antimicrobial activity against Gram-negative intestinal pathogens and adhesion to mucins and epithelial cells. L. salivarius TUCO-L2 modulated the innate immune response triggered by Toll-like receptor (TLR)-4 activation in intestinal epithelial cells. This effect involved differential regulation of the expression of inflammatory cytokines and chemokines mediated by the modulation of the negative regulators of the TLR signaling pathway. Moreover, the TUCO-L2 strain enhanced the resistance of mice to Salmonella infection. This is the first report on the isolation and characterization of a potential probiotic/immunobiotic strain from llama milk. The in vitro, in vivo, and in silico investigation performed in this study reveals several research directions that are needed to characterize the TUCO-L2 strain in detail to position this strain as a probiotic or immunobiotic that can be used against infections in humans or animals, including llama.
Coming Out to Parents in Lesbian and Bisexual Women: The Role of Internalized Sexual Stigma and Positive LB Identity

The experience of “coming out” (CO) to parents is often a crucial event in the lives of lesbian and bisexual (LB) women, associated with lower internalized sexual stigma (ISS) and higher positive LB identity. Few studies have compared the experiences of LB women in the CO process. Rather, most prior research has either: (1) not addressed bisexuality or eliminated bisexual individuals from the analysis; (2) combined bisexual women and bisexual men in the same sexual orientation group; or (3) examined bisexual participants alongside lesbian women and gay men, using a single monolithic measure. Thus, the present research aimed at investigating the role of ISS and positive LB identity in inhibiting or encouraging CO to parents in a sample of 241 lesbian women (Mage = 27.61, SD = 7.19) and 186 bisexual women (Mage = 25.23, SD = 5.81), aged 18–40 years. Most participants reported that they had already revealed their sexual orientation to their mother (69%) and their father (52%). More lesbian women had CO to both their mother and their father than had bisexual women. These lesbian women reported lower levels of ISS and higher levels of LB positive identity relative to bisexual women. On average, CO to mothers occurred at age 20 (SD = 5.54), while CO to fathers occurred at age 22 (SD = 5.63). LB women did not differ in the average age of CO to mothers or fathers, or in parental reactions to CO. Finally, ISS was found to affect the process of CO to both parents via positive identity (bootstrapping estimate = −0.26, SE = 0.08, 95% CI = −0.43, 0.11), whereas sexual orientation was not found to moderate the path from ISS to CO to both parents. The present study contributes to our understanding of the differences between LB women when developing their sexual orientation, highlighting the relevance of a positive LB identity for CO to parents. Research and clinical implications and directions for future research are discussed.
Gut Microbiota of Young Children Living in Four Brazilian Cities

Recent studies have demonstrated that gut microbiota development is influenced by human biogeographic factors such as race, ethnicity, diet, lifestyle or culture-specific variations, and other environmental influences. However, biogeographic variation in gut microbiota assembly remains largely unexplored in Latin America. In this paper, we compared food recall information and microbiota composition of toddlers living in geographically separated urban populations within four states of Brazil. 16S RNA gene sequencing revealed that alpha diversity was similar between the four different populations. Gut microbiota compositions were dominated by members of the phyla Firmicutes and Bacteroidetes, resembling a more adult-like microbiota as compared with those of Western European toddlers of similar age. These findings suggest that inter-individual and nutrition-induced differences were apparent in the fecal microbiota. We conclude that urban dietary pattern plays a larger role in influencing the gut microbiota composition than do biogeographic factors.
Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

The circulatory neutrophil and brain tissue-resident microglia are two important immune cells involved in neuroinflammation. Since neutrophils that infiltrate through the brain vascular vessel may affect the immune function of microglia in the brain, close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and immunological aftermaths that follow. This study aimed to observe how morphology and function of both neutrophils and microglia are converted in the inflamed brain. To directly investigate cellular responses of neutrophils and microglia, LysMGFP/+ and CX3CR1GFP/+ mice were used for the observation of neutrophils and microglia, respectively. In addition, low-dose lipopolysaccharide (LPS) was utilized to induce acute inflammation in the central nervous system (CNS) of mice. Real-time observation on mice brain undergoing neuroinflammation via two-photon intravital microscopy revealed various changes in neutrophils and microglia; namely, neutrophil infiltration and movement within the brain tissue increased, while microglia displayed morphological changes suggesting an activated state. Furthermore, neutrophils seemed to not only actively interact with microglial processes but also exhibit reverse transendothelial migration (rTEM) back to the bloodstream. Thus, it may be postulated that, through crosstalk with neutrophils, macrophages are primed to initiate a neuroinflammatory immune response; also, during pathogenic events in the brain, neutrophils that engage in rTEM may deliver proinflammatory signals to peripheral organs outside the brain. Taken together, these results both show that neuroinflammation results in significant alterations in neutrophils and microglia and lay the pavement for further studies on the molecular mechanisms behind such changes.
Hybrid EEG-fNIRS BCI Fusion Using Multi-Resolution Singular Value Decomposition (MSVD)

Brain-computer interface (BCI) multi-modal fusion has the potential to generate multiple commands in a highly reliable manner by alleviating the drawbacks associated with single modality. In the present work, a hybrid EEG-fNIRS BCI system—achieved through a fusion of concurrently recorded electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) signals—is used to overcome the limitations of uni-modality and to achieve higher tasks classification. Although the hybrid approach enhances the performance of the system, the improvements are still modest due to the lack of availability of computational approaches to fuse the two modalities. To overcome this, a novel approach is proposed using Multi-resolution singular value decomposition (MSVD) to achieve system- and feature-based fusion. The two approaches based up different features set are compared using the KNN and Tree classifiers. The results obtained through multiple datasets show that the proposed approach can effectively fuse both modalities with improvement in the classification accuracy.
Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Burkholderia pseudomallei Infection in A549 Cells

Burkholderia pseudomallei is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of B. pseudomallei with its hosts is complex, and cellular response to B. pseudomallei infection in humans still remains to be elucidated. In this study, transcriptomic profiling of B. pseudomallei-infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a P-value < 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2α (p-eIF2α) and ATF4 were verified to be increasing over time during the EI stage, suggesting that B. pseudomallei infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between B. pseudomallei and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of B. pseudomallei infections in humans.
Barriers and Opportunities for Implementation of Outcome-Based Spread Payments for High-Cost, One-Shot Curative Therapies

Background: The challenging market access of high-cost one-time curative therapies has inspired the development of alternative reimbursement structures, such as outcome-based spread payments, to mitigate their unaffordability and answer remaining uncertainties. This study aimed to provide a broad overview of barriers and possible opportunities for the practical implementation of outcome-based spread payments for the reimbursement of one-shot therapies in European healthcare systems. Methods: A systematic literature review was performed investigating published literature and publicly available documents to identify barriers and implementation opportunities for both spreading payments and for implementing outcome-based agreements. Data was analyzed via qualitative content analysis by extracting data with a reporting template. Results: A total of 1,503 publications were screened and 174 were included. Main identified barriers for the implementation of spread payments are reaching an agreement on financial terms while considering 12-months budget cycles and the possible violation of corresponding international accounting rules. Furthermore, outcome correction of payments is currently hindered by the need for additional data collection, the lack of clear governance structures and the resulting administrative burden and cost. The use of spread payments adjusted by population- or individual-level data collected within automated registries and overseen by a governance committee and external advisory board may alleviate several barriers and may support the reimbursement of highly innovative therapies. Conclusion: High-cost advanced therapy medicinal products pose a substantial affordability challenge on healthcare systems worldwide. Outcome-based spread payments may mitigate the initial budget impact and alleviate existing uncertainties; however, their effective implementation still faces several barriers and will be facilitated by realizing the required organizational changes.