Miracle-dz/UniFAR-FTUs huggingface dataset:
Shaping of Dendritic Cell Function by the Metabolic Micro-Environment

Nutrients are required for growth and survival of all cells, but are also crucially involved in cell fate determination of many cell types, including immune cells. There is a growing appreciation that the metabolic micro-environment also plays a major role in shaping the functional properties of dendritic cells (DCs). Under pathological conditions nutrient availability can range from a very restricted supply, such as seen in a tumor micro-environment, to an overabundance of nutrients found in for example obese adipose tissue. In this review we will discuss what is currently known about the metabolic requirements for DC differentiation and immunogenicity and compare that to how function and fate of DCs under pathological conditions can be affected by alterations in environmental levels of carbohydrates, lipids and amino acids as well as by other metabolic cues, including availability of oxygen, redox homeostasis and lactate levels. Many of these insights have been generated using in vitro model systems, which have revealed highly diverse effects of different metabolic cues on DC function. However, they also stress the importance of shifting toward more physiologically relevant experimental settings to be able to fully delineate the role of the metabolic surroundings in its full complexity in shaping the functional properties of DCs in health and disease.
The Microbiome–Metabolome Response in the Colon of Piglets Under the Status of Weaning Stress

Weaning is stressful for piglets involving nutritional, physiological, and psychological challenges, leading to an increase in the secretion of cortisol, changes in gut microbiome and metabolites, whereas the underlying relationships remain unclear. To elucidate this, 14 Meishan female piglets were divided into the weaning group and the suckling group at the age of 21 days paired by litter and body weight. After 48 h of experiment, weaned piglets had lower body weight, but higher salivary cortisol level than that of their suckling litter mates (P < 0.05). The composition of the colonic bacterial community and metabolites were different between the two groups, and the first predominant genus of the suckling and weaned piglets colonic microbiome were Bacteroides and Prevotellaceae-NK3B31 group respectively. The suckling piglets had higher proportions of phylum Bacteroidetes and Lentisphaerae, and genus Bacteroides and Lactobacillus in the colonic microbial community, but lower abundance of genus Prevotellaceae-NK3B31 group than that of the weaned piglets (P < 0.05). Accordingly, there were 15 colonic metabolites differed between the two groups, in which 2 metabolites (phenylacetic acid and phenol) negatively related to the abundant of Lactobacillus genus (P < 0.05), while 9 metabolites (acetic acid, arabitol, benzoic acid, caprylic acid, cholesterol, dihydrocholesterol, galactinol, glucose phenol, phenylacetic acid, and oxamic acid, glycerol, propionic acid) positively associated with the proportion of Prevotellaceae-NK3B31 group genus (P < 0.05). Furthermore, the salivary cortisol level negatively associated with the abundance of phylum Lentisphaerae, but positively associated with the phylum Bacteroidetes and the genus Prevotellaceae-NK3B31 group (P < 0.05) respectively. These results provide us with new insights into the cause of the gut microbiome and stress, and the contributions of gut microbiome in metabolic and physiological regulation in response to weaning stress.
The Metabolic Changes and Immune Profiles in Patients With COVID-19

To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33–59) were lymphocytes [2.5 × 109/L (IQR, 2.2–3.3)], and monocytes were 0.51 × 109/L (IQR, 0.45–0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 109/L (IQR, 0.36–0.64). Twenty-one severe patients had low PO2 [57 mmHg (IQR, 50–73)] and SO2 [90% (IQR, 86–93)] and high lactate dehydrogenase [580 U/L (IQR, 447–696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02–0.30)], and pro-BNP [498 pg/mL (IQR, 241–1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62–22.85) and 32.7 mg/L (IQR, 12.8–81.9), and a large number of RBC (46/μL (IQR, 4–242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9–10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 μmol/L (IQR, 131–256)]. In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils [6.5 × 109/L (IQR, 4.8–9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14–1.94)], C-reactive protein [66 mg/L (IQR, 25–114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I–III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.
A Multicenter Retrospective Study of 58 Patients With Primary Thyroid Diffuse Large B Cell Lymphoma

Background: Primary thyroid diffuse large B cell lymphoma (DLBCL) is a rare type of extranodal lymphoma; optimal treatment methods and the key prognostic factors have not been established. Methods: The clinical data of 58 patients with primary thyroid DLBCL from January 2007 to December 2017 were collected. The Kaplan–Meier method and log-rank tests were used for the survival analysis. Cox regression analysis was performed to evaluate the prognostic factors. Results: The follow-up time was 6–120 months; 5-year overall survival (OS) and progression-free survival (PFS) were 73 and 61%, respectively. Single-factor analysis showed that IPI, Ki-67, treatment modalities, Hans classification, Myc/Bcl-2 protein co-expression, and administration of rituximab had a significant effect on the 5-year OS and PFS (P < 0.05), while age, sex, Bcl-2 protein expression, Myc protein expression, tumor stage, tumor size, Hashimoto's thyroiditis, and B symptoms were not associated with prognosis (P > 0.05). Multivariate risk regression analysis revealed that Myc/Bcl-2 protein co-expression, treatment modalities, and rituximab were independent prognostic factors (P < 0.05). Conclusions: Patients with primary thyroid DLBCL who received combination chemotherapy with radiotherapy had a better prognosis. Surgical treatment alone was not associated with the prognosis and is used only for diagnosis. Rituximab could improve the survival time of patients.
Brain Metastases From Lung Adenocarcinoma May Preferentially Involve the Distal Middle Cerebral Artery Territory and Cerebellum

Although whole-brain radiation therapy (WBRT) is the mainstay of treatment for brain metastases (BMs), the concept of saving eloquent cortical lesions has been promoted. If BMs from lung cancer are spatially biased to certain regions, this approach can be justified more. We evaluated whether BMs from lung cancer show a preference for certain brain regions and if their distribution pattern differs according to the histologic subtype of the primary lung cancer. In this retrospective study, 562 BMs in 80 patients were analyzed (107 BMs from small cell carcinoma, 432 from adenocarcinoma, and 23 from squamous cell carcinoma). Kernel density estimation was performed to investigate whether BM spatial patterns differed among lung cancer subtypes. Further, we explored more detailed subregions where BMs from adenocarcinomas occur frequently using one-way analysis of variance. Finally, we divided our cohort into those with fewer (≤10) and more (>10) BMs and evaluated whether this biased pattern was maintained across limited and extensive stages. For small cell carcinoma, BMs were biased to the cerebellum, but this did not reach statistical significance. For adenocarcinoma, BMs were found more frequently near the distal middle cerebral artery (MCA) territory and cerebellum than in other arterial territories (p < 0.01). The precentral and postcentral gyri were the most significant subregions within the distal anterior cerebral artery (ACA) and MCA territories (p < 0.01). Crus I and Lobule VI were significant regions within the cerebellum (p < 0.01). Regardless of the number of BMs, the affinity to the distal MCA territory and cerebellum was maintained. The present data confirm that BMs from lung adenocarcinoma may preferentially involve the distal MCA territory and cerebellum.
Examining the Relationships Between Job Characteristics, Emotional Regulation and University Teachers’ Well-Being: The Mediation of Emotional Regulation

This study investigated the associations between university teachers’ emotional job demands, teaching support, and well-being, and examined the mediating effect of emotional regulation strategies (i.e., reappraisal and suppression) in the job demands-resources (JD-R) model. The results of a survey of 643 university teachers in mainland China indicated that emotional job demands and teaching support, which facilitated teachers’ use of reappraisal strategies, had desirable effects on their well-being. Reappraisal was beneficial to teachers’ well-being, and suppression was harmful. These findings support the mediation role of emotional regulation, and evidence the applicability of the JD-R model to a higher education context.
European Portuguese-Learning Infants Look Longer at Iambic Stress: New Data on Language Specificity in Early Stress Perception

The ability to perceive lexical stress patterns has been shown to develop in language-specific ways. However, previous studies have examined this ability in languages that are either clearly stress-based (favoring the development of a preference for trochaic stress, like English and German) or syllable-based (favoring the development of no stress preferences, like French, Spanish, and Catalan) and/or where the frequency distributions of stress patterns provide clear data for a predominant pattern (like English and Hebrew). European Portuguese (EP) is a different type of language, which presents conflicting sets of cues related to rhythm, frequency, and stress correlates that challenge existing accounts of early stress perception. Using an anticipatory eye movement (AEM) paradigm implemented with eye-tracking, EP-learning infants at 5–6 months demonstrated sensitivity to the trochaic/iambic stress contrast, with evidence of asymmetrical perception or preference for iambic stress. These results are not predicted by the rhythmic account of developing stress perception, and suggest that the language-particular phonological patterns impacting the frequency of trochaic and iambic stress, beyond lexical words with two or more syllables, together with the prosodic correlates of stress, drive the early acquisition of lexical stress. Our findings provide the first evidence of sensitivity to stress patterns in the presence of segmental variability by 5–6 months, and highlight the importance of testing developing stress perception in languages with diverse combinations of rhythmic, phonological, and phonetic properties.
FFT-Based Methods for Computational Contact Mechanics

Computational contact mechanics seeks for numerical solutions to contact area, pressure, deformation, and stresses, as well as flash temperature, in response to the interaction of two bodies. The materials of the bodies may be homogeneous or inhomogeneous, isotropic or anisotropic, layered or functionally graded, elastic, elastoplastic, or viscoelastic, and the physical interactions may be subjected to a single field or multiple fields. The contact geometry can be cylindrical, point (circular or elliptical), or nominally flat-to-flat. With reasonable simplifications, the mathematical nature of the relationship between a surface excitation and a body response for an elastic contact problem is either in the form of a convolution or correlation, making it possible to formulate and solve the contact problem by means of an efficient Fourier-transform algorithm. Green's function inside such a convolution or correlation form is the fundamental solution to an elementary problem, and if explicitly available, it can be integrated over a region, or an element, to obtain influence coefficients (ICs). Either the problem itself or Green's functions/ICs can be transformed into a space-related frequency domain, via a Fourier transform algorithm, to formulate a frequency-domain solution for contact problems. This approach converts the original tedious integration operation into multiplication accompanied by Fourier and inverse Fourier transforms, and thus a great computational efficiency is achieved. The conversion between ICs and frequency-response functions facilitate the solutions to problems with no explicit space-domain Green's function. This paper summarizes different algorithms involving the fast Fourier transform (FFT), developed for different contact problems, error control, as well as solutions to the problems involving different contact geometries, different types of materials, and different physical issues. The related works suggest that (i) a proper FFT algorithm should be used for each of the cylindrical, point, and nominally flat-flat contact problems, and then (ii) the FFT-based algorithms are accurate and efficient. In most cases, the ICs from the 0-order shape function can be applied to achieve satisfactory accuracy and efficiency if (i) is guaranteed.
Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19

SARS-CoV-2 infection has recently been declared a pandemic. Some patients showing severe symptoms exhibit drastic inflammation and airway damage. In this study, we re-analyzed published scRNA-seq data of COVID-19 patient bronchoalveolar lavage fluid to further classify and compare immunological features according to the patient’s disease severity. Patients with severe symptoms showed DNA damage and apoptotic features of epithelial cells. Our results suggested that epithelial damage was associated with neutrophil infiltration. Myeloid cells of severe patients showed higher expression of proinflammatory cytokines and chemokines such as CXCL8. As a result, neutrophils were abundant in lungs of patients from the severe group. Furthermore, recruited neutrophils highly expressed genes related to neutrophil extracellular traps. Neutrophil-mediated inflammation was regulated by glucocorticoid receptor expression and activity. Based on these results, we suggest that severe COVID-19 symptoms may be determined by differential expression of glucocorticoid receptors and neutrophils.
CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression

Objectives: This study compared neurofilament light chain (NFL) levels in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with levels in patients with other neurological diseases and healthy controls and assessed correlations between NFL levels and clinical indicators of sALS. Methods: We used enzyme-linked immunosorbent assays to determine the NFL levels in the CSF of 45 patients with sALS, 21 patients with other central nervous system diseases (OCNSDs), 18 with immune-mediated peripheral neuropathy (IMPN), 14 with non-immune-mediated peripheral neuropathy (NIMPN), and 19 healthy controls (HCs). Results: The median NFL levels in the CSF of the sALS, OCNSD, IMPN, NIMPN, and HC groups were 6510, 5372, 4320, 1477, and 756 pg/mL, respectively. The CSF NFL levels did not differ significantly among the sALS, IMPN, and OCNSD groups, but were significantly higher than those of the NIMPN and HC groups. The NFL CSF levels were significantly higher in the NIMPN group than the HCs. There was a negative correlation between the NFL level and ALS function score (ALSFRS-R), and a positive correlation with the disease progression rate in patients with sALS. Conclusion: CSF NFL may not be sufficient to distinguish ALS from other central nervous system diseases or peripheral neuropathy, but it predicts ALS severity and progression.
Social Cognition in a Research Domain Criteria Perspective: A Bridge Between Schizophrenia and Autism Spectra Disorders

Schizophrenia and autism spectra disorders are currently conceptualized as distinct clinical categories. However, the relationship between these two nosological entities has been revisited in recent years due to the evidence that they share some important clinical and neurobiological features, putting into question the nature and the extent of their commonalities and differences. In this respect, some core symptoms that are present in both disorders, such as social cognitive deficits, could be a primary target of investigation. This review briefly summarizes the commonalities and overlapping features between schizophrenia and autism spectra disorders in social cognitive functions, considering this construct in a Research Domain Criteria perspective. The clinical manifestation of deficits in social cognition are similar in schizophrenia spectrum disorders and autism spectrum disorders, and brain areas that appear to be altered in relation to these impairments are largely shared; however, the results of various studies suggest that, in some cases, the qualitative nature of these alterations may be different in the two spectra. Moreover, relevant differences could be present at the level of brain networks and connections. More research is required in this field, regarding molecular and genetic aspects of both spectra, to better define the neurobiological mechanisms involved in social cognition deficits, with the objective of developing specific and targeted treatments.
Keys to Expanding the Rural Healthcare Workforce in Kyrgyzstan

Objective/Background: This study assessed Kyrgyzstan's progress with developing its rural primary care workforce and prioritized next steps to build on its current momentum. Kyrgyzstan has improved rural health care since 1997 through the implementation of family medicine, retraining of rural doctors and nurses, and other efforts. Attrition, emigration, urbanization, and population growth are threatening these hard-won advances. In response, Kyrgyzstan is now educating family medicine residents at rural sites and improving salaries. This study explores other steps to strengthen its rural health care, especially its rural generalists. Methods: This was an observational study using a two-phase survey process. To access the current status of Kyrgyzstan's rural health care system, we surveyed key stakeholders within that system using a draft version of the new World Health Organization Rural Pathways Checklist. To prioritize next steps, we asked rural FM residents to rank the relative importance of 31 possible future actions to support Kyrgyzstan's rural primary care workers. Results: Doctors and nurses involved in teaching rural health workers identified that Kyrgyzstan has made good progress with rural professional support and upskilling of existing health workers through education. They saw the least progress with selection of health workers and monitoring. The rural family medicine residents' top ten suggestions for rural recruitment and retention all involved improving working conditions (providing housing, internet, basic medical equipment, protected time off, better salaries, and more respect) and improving clinic efficiency (switching clinic scheduling from walk-in based to appointment based, optimizing the roles of clinical team members, and decreasing low-value clinic visits). Conclusions: The WHO Rural Pathways Checklist helped to evaluate Kyrgyzstan's current efforts to promote rural primary care. The priorities listed above from the next generation of potential rural family doctors could help guide future steps to promote rural health in Kyrgyzstan and the Former Soviet Union.
No Evidence That Homologs of Key Circadian Clock Genes Direct Circadian Programs of Development or mRNA Abundance in Verticillium dahliae

Many organisms harbor circadian clocks that promote their adaptation to the rhythmic environment. While a broad knowledge of the molecular mechanism of circadian clocks has been gained through the fungal model Neurospora crassa, little is known about circadian clocks in other fungi. N. crassa belongs to the same class as many important plant pathogens including the vascular wilt fungus Verticillium dahliae. We identified homologs of N. crassa clock proteins in V. dahliae, which showed high conservation in key protein domains. However, no evidence for an endogenous, free-running and entrainable rhythm was observed in the daily formation of conidia and microsclerotia. In N. crassa the frequency (frq) gene encodes a central clock protein expressed rhythmically and in response to light. In contrast, expression of Vdfrq is not light-regulated. Temporal gene expression profiling over 48 h in constant darkness and temperature revealed no circadian expression of key clock genes. Furthermore, RNA-seq over a 24 h time-course revealed no robust oscillations of clock-associated transcripts in constant darkness. Comparison of gene expression between wild-type V. dahliae and a ΔVdfrq mutant showed that genes involved in metabolism, transport and redox processes are mis-regulated in the absence of Vdfrq. In addition, VdΔfrq mutants display growth defects and reduced pathogenicity in a strain dependent manner. Our data indicate that if a circadian clock exists in Verticillium, it is based on alternative mechanisms such as post-transcriptional interactions of VdFRQ and the WC proteins or the components of a FRQ-less oscillator. Alternatively, it could be that whilst the original functions of the clock proteins have been maintained, in this species the interactions that generate robust rhythmicity have been lost or are only triggered when specific environmental conditions are met. The presence of conserved clock genes in genomes should not be taken as definitive evidence of circadian function.
Changes in Population Age-Structure Obscure the Temperature-Size Rule in Marine Cyanobacteria

The temperature-size Rule (TSR) states that there is a negative relationship between ambient temperature and body size. This rule has been independently evaluated for different phases of the life cycle in multicellular eukaryotes, but mostly for the average population in unicellular organisms. We acclimated two model marine cyanobacterial strains (Prochlorococcus marinus MIT9301 and Synechococcus sp. RS9907) to a gradient of temperatures and measured the changes in population age-structure and cell size along their division cycle. Both strains displayed temperature-dependent diel changes in cell size, and as a result, the relationship between temperature and average cell size varied along the day. We computed the mean cell size of new-born cells in order to test the prediction of the TSR on a single-growth stage. Our work reconciles previous inconsistent results when testing the TSR on unicellular organisms, and shows that when a single-growth stage is considered the predicted negative response to temperature is revealed.