Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy

Interferon-gamma (IFN-γ) has been identified as a crucial factor in determining the responsiveness to immunotherapy. Produced primarily by natural killer (NK) and T cells, IFN-γ promotes activation, maturation, proliferation, cytokine expression, and effector function in immune cells, while simultaneously inducing antigen presentation, growth arrest, and apoptosis in tumor cells. However, tumor cells can hijack the IFN-γ signaling pathway to mount IFN-γ resistance: rather than increasing antigenicity and succumbing to death, tumor cells acquire stemness characteristics and express immunosuppressive molecules to defend against antitumor immunity. In this review, we summarize the potential mechanisms of IFN-γ resistance occurring at two critical stages: disrupted signal transduction along the IFNG/IFNGR/JAK/STAT pathway, or preferential expression of specific interferon-stimulated genes (ISGs). Elucidating the molecular mechanisms through which tumor cells develop IFN-γ resistance help identify promising therapeutic targets to improve immunotherapy, with broad application value in conjugation with targeted, antibody or cellular therapies.
Effects of coal-derived compound fertilizers on soil bacterial community structure in coal mining subsidence areas

The land damaged by coal mining can be recovered to healthy condition through various reclamation methods. Fertilization is one of the effective methods to improve soil fertility and microbial activity. However, the effects of coal-derived compound fertilizers (SH) on bacterial communities in coal mining subsidence areas still remain unclear. Here, we studied the effects on the nutrient characteristics and bacterial communities in fertilizer-reclaimed soil (CK, without fertilizer; CF, common compound fertilizers; SH, coal-derived compound fertilizers) in coal mining subsidence areas and we applied SH with four different nitrogen application rates (90, 135, 180, and 225 kg/hm2). The results showed that the application of SH significantly increased the contents of available nitrogen (AN), available phosphorus (AP), available potassium (AK), total phosphorus (TP) and soil organic matter (SOM) compared with CK, as well as the bacterial richness (Chao1) and diversity (Shannon) in reclaimed soil that increased first and then decreased with the increase of nitrogen application. Under the same nitrogen application rate (135 kg/hm2), the nutrient content, Chao1 and Shannon of SH2 treatments were higher than those of CF treatment. Meanwhile, SH increased the relative abundance of Proteobacteria, Actinobacteria and Gemmatimonadetes. LEfSe analysis indicated that the taxa of Acidobacteria and Actinobacteria were significantly improved under SH treatments. Canonical correspondence analysis (CCA) and Variance partitioning analysis (VPA) showed that SOM was the most important factor affecting the change of bacterial community structure in reclaimed soil. In conclusion, application of SH can not only increase nutrient content and bacterial diversity of reclaimed soil, but also improve bacterial community structure by increasing bacterial abundance.
Multiple sclerosis lesion segmentation: revisiting weighting mechanisms for federated learning

Background and introduction Federated learning (FL) has been widely employed for medical image analysis to facilitate multi-client collaborative learning without sharing raw data. Despite great success, FL's applications remain suboptimal in neuroimage analysis tasks such as lesion segmentation in multiple sclerosis (MS), due to variance in lesion characteristics imparted by different scanners and acquisition parameters. Methods In this work, we propose the first FL MS lesion segmentation framework via two effective re-weighting mechanisms. Specifically, a learnable weight is assigned to each local node during the aggregation process, based on its segmentation performance. In addition, the segmentation loss function in each client is also re-weighted according to the lesion volume for the data during training. Results The proposed method has been validated on two FL MS segmentation scenarios using public and clinical datasets. Specifically, the case-wise and voxel-wise Dice score of the proposed method under the first public dataset is 65.20 and 74.30, respectively. On the second in-house dataset, the case-wise and voxel-wise Dice score is 53.66, and 62.31, respectively. Discussions and conclusions The Comparison experiments on two FL MS segmentation scenarios using public and clinical datasets have demonstrated the effectiveness of the proposed method by significantly outperforming other FL methods. Furthermore, the segmentation performance of FL incorporating our proposed aggregation mechanism can achieve comparable performance to that from centralized training with all the raw data.
Metabolic decline in an insect ear: correlative or causative for age-related auditory decline?

One leading hypothesis for why we lose our hearing as we age is a decrease in ear metabolism. However, direct measurements of metabolism across a lifespan in any auditory system are lacking. Even if metabolism does decrease with age, a question remains: is a metabolic decrease a cause of age-related auditory decline or simply correlative? We use an insect, the desert locust Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that auditory organ metabolism decreases with age as measured fluorometrically. Next, we measured the individual auditory organ’s metabolic rate and its sound-evoked nerve activity and found no correlation. We found no age-related change in auditory nerve activity, using hook electrode recordings, and in the electrophysiological properties of auditory neurons, using patch-clamp electrophysiology, but transduction channel activity decreased. To further test for a causative role of the metabolic rate in auditory decline, we manipulated metabolism of the auditory organ through diet and cold-rearing but found no difference in sound-evoked nerve activity. We found that although metabolism correlates with age-related auditory decline, it is not causative. Finally, we performed RNA-Seq on the auditory organs of young and old locusts, and whilst we found enrichment for Gene Ontology terms associated with metabolism, we also found enrichment for a number of additional aging GO terms. We hypothesize that age-related hearing loss is dominated by accumulative damage in multiple cell types and multiple processes which outweighs its metabolic decline.
Commentary: A tribute to Dr. Paul Berg (1926–2023) American biochemist, Nobel Laureate and discoverer of recombinant DNA technology, vaccine and genetic engineering

The world of human molecular genetics, virology and immunology has lost one of the pillars in the study of recombinant DNA technology and vaccine and genetic engineering with the passing of Paul Berg. Inventor of one of the most powerful and trusted tools in the armamentarium of modern molecular biology, Paul Berg was the first biochemist-geneticist to incorporate DNA from the bacterium Escherichia coli into the potentially cancer-causing DNA polyoma tumor virus SV40, as was reported by his laboratory in late 1972 in the now classic paper in the Proceedings of the National Academy of Science United States (Jackson et al., 1972). Berg thereby created the first DNA molecule made from different parts of the genome of different organisms. This type of molecule became known as “hybrid DNA” or “recombinant DNA” with the idea to use the modified SV40 as a viral vector to carry “foreign” or “intelligent and strategically designed” genetic information into animal cells. Berg also discovered, and in part characterized transfer RNA (tRNA) and showed that amino acids needed to be activated before being attached to tRNA and before their assembly into proteins. Berg also was the first to purify the enzyme that carried out the formation of acetyl CoA, made deep inroads into our understanding of “activated acetate” and mechanisms related to fatty acid activation and polymerization and was the first to characterize the distribution of CpG dinucleotides in the human genome that distinguishes two distinct classes of eukaryotic gene promoters (Saxonov et al., 2006). Berg’s novel recombinant DNA discoveries are the basis for the biotechnology industry today worth hundreds of billions of dollars, that involve technologies capable of the editing of heritable genes in humans and the genetic engineering of new therapeutic treatments for many diseases and of vaccines, like the OPEN ACCESS
What Happens When We Hear?

What happens when we hear? Where does the sound go when it enters our ears? Our ears sense the vibrations of the air and convert them into electrical signals the brain can process. But that is only the start. The brain uses tens of thousands of nerve cells to hear even the quietest or simplest sound. With those nerve cells, the brain is solving a never-ending puzzle: figuring out what is going on in the world. To do that, the brain must separate out sounds that are occurring at the same time, recognize them, and describe them in lots of ways, such as how loud a sound is and where it is coming from. This article gives an overview of how the ears and brain work together, so we can live in a world of sound.
Japanese Predicate Argument Structure Analysis by Comparing Candidates in Different Positional Relations between Predicate and Arguments

Therefore, we propose a Japanese predicate argument structure analysis model that gathers the most likely candidates from all the groups and then selects the ﬁnal candidate amongst them. We can account for candidates with less priority before making a ﬁnal decision to perform global optimization. Experimental results show that our model outperforms deterministic models.
SSVEP detection assessment by combining visual stimuli paradigms and no-training detection methods

Introduction Brain-Computer Interfaces (BCI) based on Steady-State Visually Evoked Potentials (SSVEP) have great potential for use in communication applications because of their relatively simple assembly and in some cases the possibility of bypassing the time-consuming training stage. However, among multiple factors, the efficient performance of this technology is highly dependent on the stimulation paradigm applied in combination with the SSVEP detection algorithm employed. This paper proposes the performance assessment of the classification of target events with respect to non-target events by applying four types of visual paradigms, rectangular modulated On-Off (OOR), sinusoidal modulated On-Off (OOS), rectangular modulated Checkerboard (CBR), and sinusoidal modulated Checkerboard (CBS), with three types of SSVEP detection methods, Canonical Correlation Analysis (CCA), Filter-Bank CCA (FBCCA), and Minimum Energy Combination (MEC). Methods We set up an experimental protocol in which the four types of visual stimuli were presented randomly to twenty-seven participants and after acquiring their electroencephalographic responses to five stimulation frequencies (8.57, 10.909, 15, 20, and 24 Hz), the three detection methods were applied to the collected data. Results The results are conclusive, obtaining the best performance with the combination of either OOR or OOS visual stimulus and the FBCCA as a detection method, however, this finding contrasts with the opinion of almost half of the participants in terms of visual comfort, where the 51.9% of the subjects felt more comfortable and focused with CBR or CBS stimulation. Discussion Finally, the EEG recordings correspond to the SSVEP response of 27 subjects to four visual paradigms when selecting five items on a screen, which is useful in BCI navigation applications. The dataset is available to anyone interested in studying and evaluating signal processing and machine-learning algorithms for SSVEP-BCI systems.
Umbilical cord blood derived cellular therapy: advances in clinical development

While cord blood (CB) is primarily utilized in allogeneic hematopoietic cell transplantation (HCT), the development of novel cell therapy products from CB is a growing and developing field. Compared to adult blood, CB is characterized by a higher percentage of hematopoietic stem cells (HSCs) and progenitor cells, less mature immune cells that retain a high capacity of proliferation, and stronger immune tolerance that requires less stringent HLA-matching when used in the allogenic setting. Given that CB is an FDA regulated product and along with its unique cellular composition, CB lends itself as a readily available and safe starting material for the development of off-the-shelf cell therapies. Moreover, non-hematologic cells such as mesenchymal stem cell (MSCs) residing in CB or CB tissue also have potential in regenerative medicine and inflammatory and autoimmune conditions. In this review, we will focus on recent clinical development on CB-derived cellular therapies in the field of oncology, including T-cell therapies such as chimeric antigen receptor (CAR) T-cells, regulatory T-cells, and virus-specific T-cells; NK-cell therapies, such as NK cell engagers and CAR NK-cells; CB-HCT and various modifications; as well as applications of MSCs in HCT.
Professional identity of pre-service teachers: actual and designated identity profiles and their relationship to teacher education programs

In this study, we investigated the professional identities of 490 pre-service teachers (PSTs) at the University of Hamburg, Germany. By distributing 100 percentage points, the PSTs assessed the relevance of the roles of subject specialist (SS), didactician (DD), and pedagogue (PD) for themselves currently (actual identity) and for an ideal teacher in different school types (designated identity). A theory-based non-hierarchical cluster analysis distinguished seven profiles: three main role profiles, three dual role profiles, and one balanced profile. The distribution of the PSTs’ actual identities across these seven profiles showed expectedly large interindividual diversity. The most frequent actual identity profiles were those for which the DD and PD roles were particularly relevant (dual role PD/DD profile and balanced profile). The distribution of PSTs across profiles supported the hypothesis that actual identity is related to the type of teacher education program being followed: upper secondary education PSTs were more strongly characterized by profiles that emphasized the SS role (main role SS and dual role SS/DD profiles) than the other PSTs, and special education PSTs were more strongly characterized by profiles that emphasized the PD role (main role PD profile, dual role PD/DD, and PD/SS profiles) than the other PSTs. The designated identities, on the other hand, showed greater consensus among the PSTs. The profiles that best characterized PSTs were the dual role PD/DD profile and the balanced profile. In contrast, the two main role SS and DD profiles and the dual role PD/SS profile were irrelevant as designated identities. A comparison of PSTs’ actual identities with their designated identities showed that a third of the PSTs had the same profile. The diversity of professional identities and the factors in teacher training that influence them should be investigated more closely.
Fast algorithm to calculate generalized centroid of interval type-2 fuzzy set

The relationship between the switch point on the membership function and the generalized centroid in an interval type-2 fuzzy set is discussed.A close form representation of the switch point for calculating the endpoint of the generalized centroid is provided in both discrete and continuous conditions.Then an opposite direction searching method for computing the switch point is proposed.The convergence of the switch point is proved.Experimental result shows that the approach is computationally faster than the commonly used Enhanced Karnik-Mendel method without loosing numeric precision.
Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels

Chronic cerebral hypoperfusion (CCH) is increasingly recognized as a common cognitive impairment-causing mechanism. However, no clinically effective drugs to treat cognitive impairment due to CCH have been identified. An abnormal distribution of neural oscillations was found in the hippocampus of CCH rats. By releasing various neurotransmitters, distinct afferent fibers in the hippocampus influence neuronal oscillations in the hippocampus. Enriched environments (EE) are known to improve cognitive levels by modulating neurotransmitter homeostasis. Using EE as an intervention, we examined the levels of three classical neurotransmitters and the dynamics of neural oscillations in the hippocampus of the CCH rat model. The results showed that EE significantly improved the balance of three classical neurotransmitters (acetylcholine, glutamate, and GABA) in the hippocampus, enhanced the strength of theta and slow-gamma (SG) rhythms, and dramatically improved neural coupling across frequency bands in CCH rats. Furthermore, the expression of the three neurotransmitter vesicular transporters—vesicular acetylcholine transporters (VAChT) and vesicular GABA transporters (VGAT)—was significantly reduced in CCH rats, whereas the expression of vesicular glutamate transporter 1 (VGLUT1) was abnormally elevated. EE partially restored the expression of the three protein levels to maintain the balance of hippocampal afferent neurotransmitters. More importantly, causal mediation analysis showed EE increased the power of theta rhythm by increasing the level of VAChT and VGAT, which then enhanced the phase amplitude coupling of theta-SG and finally led to an improvement in the cognitive level of CCH. These findings shed light on the role of CCH in the disruption of hippocampal afferent neurotransmitter balance and neural oscillations. This study has implications for our knowledge of disease pathways.
Sjögren’s syndrome: novel insights from proteomics and miRNA expression analysis

Introduction Sjögren’s syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS. Methods This systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard. Results and discussion Out of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.
Association between preoperative diagnosis of sarcopenia and postoperative pneumonia in resectable esophageal squamous cell carcinoma patients: a retrospective cohort study

Background Postoperative outcomes for patients suffering from resectable esophageal squamous cell carcinoma (ESCC) are related to sarcopenia. In patients with resectable ESCC, this study investigated the link between sarcopenia and postoperative pneumonia. Methods The McKewon procedure was the only one used to treat resectable ESCC patients from January 2018 to December 2021 in this retrospective analysis. Sarcopenia was assessed using skeletal muscles at L3 and planning CT scans. It was defined when PMI was below 6.36 cm2/m2 and 3.92 cm2/m2 for men and women, separately. Analyses of multivariate and univariate logistic regression were applied for identifying the risk factors for postoperative pneumonia. Results The study included 773 patients with resectable ESCC in total. Sarcopenia was an independent risk factor for postoperative pneumonia in individuals with resectable ESCC based on univariate and multivariate analysis (P < 0.05). The stratified analysis indicated that neither of the clinical outcomes in the logistic regression model were affected by gender, age, BMI, smoking, or pre-albumin (P for interaction > 0.006). Conclusion Following the McKewon procedure, patients with resectable ESCC who were sarcopenic had a higher postoperative pneumonia rate. To prevent the development of postoperative pneumonia during the perioperative period, it may be important to control the incidence of sarcopenia.
Five blueberry anthocyanins and their antioxidant, hypoglycemic, and hypolipidemic effects in vitro

The dual epidemic of obesity and diabetes mellitus is becoming an important worldwide public health issue. “Diabesity” is the term used to describe the combined detrimental health effects of both diabetes mellitus and obesity/overweight. Currently, food-derived bioactive compounds are suggested to alleviate diabesity. Blueberries are rich in bioactive anthocyanins, which are associated with contributing to preventing obesity and diabetes mellitus. However, the accurate active compounds and the underlying mechanism are still unclear. The objective of this study was to investigate the beneficial effects of blueberry anthocyanin on diabesity. In total, five anthocyanins (delphinidin-3-O-galactoside, delphinidin-3-O-glucoside, petunidin-3-O-galactoside, petunidin-3-O-glucoside, and malvidin-3-O-galactoside) were isolated from rabbiteye blueberry (Vaccinium virgatum) cultivar “Garden blue. ” All these anthocyanins exhibited oxygen radical absorbance capacity (ORAC), scavenging power of ABTS+, and DPPH-free radical and inhibitory activity of α-glucosidase in vitro. Moreover, some compounds improved glucose uptake and attenuated lipid accumulation in high glucose and oleic acid-treated HepG2 cells. All these results suggest that blueberry anthocyanins have potential antioxidant, hypoglycemic, and hypolipidemic effects, which may benefit the treatment of diabesity.