Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of cold chain interruptions on the shelf-life of fluid pasteurised skim milk at the consumer stage

This study aimed to verify the effect of time and temperature abuse on bacterial numbers in fluid pasteurized skim milk by simulating the real-life scenario, which usually occurs when cold chain is interrupted by consumers prior to consumption that affect the shelf-life of milk. Total three trials were carried out in this study. Thermal abuse was simulated with temperature fluctuations from 5 °C. In the first trial, the information about holding the milk samples for 8 hours at three different temperatures of 15 °C, 20 °C and 25 °C was obtained using a data logger to predict the effect of temperature abuse on the milk microbial quality. Further, in the second and third trial, the effect of temperature abuse on bacterial numbers was examined by holding milk at 5 °C and then shifts temperature to 25 °C for 8 h and 6 h. The pH was monitored during storage. The total bacterial count was examined by the Standard Plate Count (SPC). The mean air temperature had the greatest impact on milk temperature. It took 3.0 h, 3.9 h and 4.2 h to warm up when exposed to the temperatures of 15 °C, 20 °C and 25 °C, respectively. The holding time of 8 h at 25 °C showed that bacterial numbers (1 x 105 CFU mL-1) were higher after 14 days of storage, but control samples at 5 °C (< 1 x 104 CFU mL-1) were still within the acceptable level (5 x 104 CFU mL-1). A holding time of 6 h at 25 oC showed much higher bacterial numbers (1 x 109 CFU mL-1) compared to control samples (1 x 107 CFU mL-1) which were held at 5 °C for 11 days. The pH of the milk decreased with increasing bacterial growth during the extended storage time. The results show that temperature abuse has a significant effect on milk microbial stability and shelf life. It is important to maintain the milk temperature at 5 °C or less as the bacterial growth directly depend on increasing temperature and holding time, which pose the potential risk of microbial hazards leading to foodborne illness. Thus, consumers must understand the factors associated with the safe handling of milk to keep it safe to use before the expiry date.
Distinct ground state and activated state modes of firing in forebrain neurons

Neuronal firing patterns have significant spatiotemporal variability with no agreed upon theoretical framework. Using a combined experimental and modeling approach, we found that spike interval statistics can be described by discrete modes of activity. Of these, a “ground state” (GS) mode of low-rate spiking is universal among forebrain excitatory neurons and characterized by irregular spiking at neuron-specific rates. In contrast, “activated state” (AS) modes consist of spiking at characteristic timescales and regularity that are specific to neuron populations in a given region and brain state. The majority of spiking is contributed by GS mode, while neurons can transiently switch to AS spiking in response to stimuli or in coordination with population activity patterns. We hypothesize that GS spiking serves to maintain a persistent backbone of neuronal activity while AS modes support communication functions.
Investigation of the impact of stool collection methods on the metabolomics analysis/profiles of infant fecal samples

Metabolomic studies are important to understand microbial metabolism and interaction between the host and the gut microbiome. Although there have been efforts to standardize sample processing in metabolomic studies, infant samples are mostly disregarded. In birth cohort studies, the use of diaper liners is prevalent and its impact on fecal metabolic profile remains untested. In this study, we compared metabolite profiles of fecal samples collected as solid stool and those collected from stool saturated liner. One infant’s stool sample was collected in triplicate for solid stool and stool saturated liner. Comprehensive metabolomics analysis of the fecal samples was performed using NMR, UPLC and DI-MS. The total number, identities and concentrations of the metabolites were determined and compared between stool sample collection methods (stool vs. liner). The number and identity of metabolites did not differ between collection methods for NMR and DI-MS when excluding metabolites with a coefficient of variation (CV) > 40%. NMR analysis demonstrated lowest bias between collection methods, and lowest technical precision between triplicates of the same method followed by DI-MS then UPLC. Concentrations of many metabolites from stool and stool saturated liner differed significantly as revealed by Bland-Altman plots and t-tests. Overall, a mean bias of 10.2% in the Bland-Altman analysis was acceptable for some metabolites confirming mutual agreement but not for others with a wide range of bias (−97-117%). Consequently, stool and stool-saturated liner could be used interchangeably only for some select metabolite classes e.g. amino acids. Differences between the metabolomic profiles of solid stool samples and stool saturated liner samples for some important molecules e.g., ethanol, fumarate, short chain fatty acids and bile acids, indicate the need for standardization in stool collection method for metabolomic studies performed in infants.
Distributionally Robust, Skeptical Binary Inferences in Multi-label Problems

In this paper, we consider the problem of making dis-tributionally robust, skeptical inferences for the multi-label problem, or more generally for Boolean vectors. By distributionally robust, we mean that we consider sets of probability distributions, and by skeptical we understand that we consider as valid only those inferences that are true for every distribution within this set. Such inferences will provide partial predictions whenever the considered set is sufﬁciently big. We study in particular the Hamming loss case, a common loss function in multi-label problems, showing how skep-tical inferences can be made in this setting. We also perform some experiments demonstrating the interest of our results.
Towards Improving Electoral Forecasting by Including Undecided Voters and Interval-valued Prior Knowledge

Increasing numbers of undecided voters constitute a severe challenge for conventional pre-election polls in multi-party systems. While these polls only provide the still pondering individuals with the options to either state a precise party or to drop out, we suggest to regard their valuable information in a set-valued way. The resulting consideration set, listing all the options the individual is still pondering between, can be interpreted under epistemic imprecision. Within this paper we extend the already existing approaches including this valuable information, by making first steps to utilize interval-valued prior information. Including background information is common in election forecasting while we focus on realistically obtainable and credible interval-valued prior information about transition probabilities from the undecided to the eventual choice. We introduce two approaches utilizing this intervalvalued information, weighting the credibility against the precision of the results. For the first approach, we narrow the most cautious and wide so-called Dempster bounds by deploying the prior information on the transition probabilities as new worst and best case scenarios for each party. The second approach applies if these interval-valued results are still too wide for useful application. We hereby narrow them towards a good guess of the eventual choice, estimated by a further model-based source of information making use of the covariates. These single-valued estimates on the individual level are regarded as realizations of an underlying probability distribution, which we combine with the prior knowledge in a Bayesian way. The approach can thus be seen as an attempt to combine two, for the needed outcome by themselves inadequate, sources of information to obtain more concise results. We conduct a simulation study showing the applicability and virtues of the new approaches and compare them to conventional ones.
Mathematics Disability vs. Learning Disability: A 360 Degree Analysis

A fundamental issue for research in mathematics disability (MD) and reading disability (RD) is: If these disabilities are clearly distinct, why is there so high a level of comorbidity, together with the converse; if these disabilities are so similar, why are there clear differences in underlying causes and aetiology? In order to address this puzzle, we introduce the “360 degree analysis” (360DA) framework and apply it to the overlap between RD and MD. The 360DA process starts by analyzing the issue from four perspectives: theoretical, developmental, affective, and pedagogical. Under 360DA, these analyses are then integrated to provide insights for theory, and for individual assessment and support, together with directions for future progress. The analyses confirm extensive similarities between arithmetic and reading development in terms of rote learning, executive function (EF), and affective trauma, but also major differences in terms of the conceptual needs, the motor coordination needs, and the methods of scaffolding. In terms of theory, commonalities are interpreted naturally in terms of initial general developmental delay followed by domain-independent affective trauma following school failure. Dissociations are interpreted in terms of cerebellar vs. hippocampal learning networks, sequential vs. spatial processing, and language vs. spatial scaffolding, with a further dimension of the need for accurate fixation for reading. The framework has significant theoretical and applied implications.
Clostridium butyricum Supplement Can Ameliorate the Intestinal Barrier Roles in Broiler Chickens Experimentally Infected With Clostridium perfringens

Necrotic enteritis (NE), caused by Clostridium perfringens, is an economically important disease in the broiler. Among normal flora in the broiler intestinal region, Clostridium butyricum has been identified as a probiotic agent that reduces the susceptibility of broilers to C. perfringens. However, the effects of C. butyricum supplement on broiler intestinal integrity during NE are largely unknown. In this study, we investigated the effects of C. butyricum on the growth performance, intestinal morphology and barrier function, and the functions of immune-related cytokines under NE in broilers. Chickens were divided into five groups: control group (NC), supplement C. butyricum only group (CB), NE-infected group (PC), supplement C. butyricum from Day 14 (NECB1) to Day 22 NE-infected group, and supplement C. butyricum from Day 1 (NECB2) to Day 22 NE-infected group. The results showed that there were significantly decreased average daily weight gain and increased feed conversion rate in the infected group (PC) compared with the C. butyricum-supplemented groups (NECB1 and NECB2) through the diet. Histopathological observation on the Hematoxylin–Eosin staining avian small intestine sections revealed that supplementation of C. butyricum (NECB1 and NECB2) could increase the intestinal villus height/crypt depth and lessen the intestinal damage under NE. ELISA and Limulus test showed that broilers infected with NE (PC) had higher serum IgA and lipopolysaccharide content; however, after C. butyricum supplementation (NECB1 and NECB2), they returned to a normal level. Furthermore, real-time PCR and Western blot results indicated that compared with PC, supplementing C. butyricum (NECB1 and NECB2) could initialize the expressions of genes related to the intestinal barrier-associated molecules (such as CLDN-1, CLDN-3, OCLN, MUC2, ZO-1, and CLDN5), cytokines (such as IL-10, IL-6, and TGFB1), and C. perfringens plc gene expression. Moreover, the results detected by the Ussing chamber suggested that C. butyricum (NECB1 and NECB2) could amend the decrease in conductivity value and short-circuit current value caused by NE. In addition, NECB2 significantly reduced the upregulation of fluorescein isothiocyanate–dextran flux caused by the NE disease. In conclusion, these findings suggest that dietary supplementation of C. butyricum in broilers with NE improved chicken growth performance, intestinal integrity and barrier function, and immunological status. Notably, no statistical difference was observed with the addition of C. butyricum on day 1 or day 14.
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens and cellular debris. Microglia emerge from early erythromyeloid progenitors of the yolk sac and enter the developing brain before the establishment of a fully mature blood–brain barrier. In physiological conditions, during brain development, microglia contribute to CNS homeostasis by supporting cell proliferation of neural precursors. In post-natal life, such cells contribute to preserving the integrity of neuronal circuits by sculpting synapses. After a CNS injury, microglia change their morphology and down-regulate those genes supporting homeostatic functions. However, it is still unclear whether such changes are accompanied by molecular and functional modifications that might contribute to the pathological process. While comprehensive transcriptome analyses at the single-cell level have identified specific gene perturbations occurring in the “pathological” microglia, still the precise protective/detrimental role of microglia in neurological disorders is far from being fully elucidated. In this review, the results so far obtained regarding the role of microglia in neurodegenerative disorders will be discussed. There is solid and sound evidence suggesting that regulating microglia functions during disease pathology might represent a strategy to develop future therapies aimed at counteracting brain degeneration in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.
Secondhand Smoke Decreased Excitability and Altered Action Potential Characteristics of Cardiac Vagal Neurons in Mice

Background: Secondhand smoke (SHS), a major indoor pollutant, is a significant risk factor for cardiovascular morbidity and mortality including arrhythmias and sudden cardiac death. Exposure to SHS can produce autonomic imbalance, as evidenced by reduced heart rate variability (HRV)—a clinical metric of cardiac vagal regulation. Currently, the mechanisms through which SHS changes the vagal preganglionic neuronal inputs to the heart to produce this remains unknown. Objectives: To characterize the effect of SHS on both the excitability and action potential (AP) characteristics of anatomically identified cardiac vagal neurons (CVNs) in the nucleus ambiguus and examine whether SHS alters small conductance calcium-activated potassium (SK) channel activity of these CVNs. Methods: Adult male mice were exposed to four weeks of filtered air or SHS (3 mg/m3) 6 h/day, 5 day/week. Using patch-clamp recordings on identified CVNs in brainstem slices, we determined neuronal excitability and AP characteristics with depolarizing step- and ramp-current injections. Results: Four weeks of SHS exposure reduced spiking responses to depolarizing current injections and increased AP voltage threshold in CVNs. Perfusion with apamin (20 nM) magnified these SHS-induced effects, suggesting reduced SK channel activity may serve to minimize the SHS-induced decreases in CVNs excitability. Medium afterhyperpolarization (a measurement of SK channel activity) was smaller in the SHS group, further supporting a lower SK channel activity. AP amplitude, rise rate, fast afterhyperpolarization amplitude (a measurement of voltage-gated channel activity), and decay rate were higher in the SHS group at membrane voltages more positive to 0 mV, suggesting altered inactivation properties of voltage-dependent channels underlying APs. Discussion: SHS exposure reduced neuronal excitability of CVNs with compensatory attenuation of SK channel activity and altered AP characteristics. Neuroplasticity of CVNs could blunt regulatory cardiac vagal signaling and contribute to the cardiovascular consequences associated with SHS exposure, including reduced HRV.
Tailorable Stimulated Brillouin Scattering Laser Based on Silicon Ring Waveguides

Stimulated Brillouin scattering (SBS) lasers based on silicon waveguides with large SBS gain, have been widely used in frequency tunable laser emission, mode-locked pulse laser, low-noise oscillator, optical gyroscope, and other fields. However, current SBS lasers still need long waveguide lengths to realize Brillouin laser output, which increases the waveguide losses and is not conductive to be integrated. In this paper, we propose a silicon ring waveguide, in order to tune the frequency of the phonon field of SBS laser based on the silicon substrate of the ring cavity. The simulation results exhibit that the tailorable forward SBS effect is realized in the silicon-based optical waveguide with a large SBS gain up to 1.90 W-1m-1. Particularly, with the mutual restraint between photoelastic and moving boundary effects, the tunable phonon frequencies emitting from 1 to 15 GHz are realized through the conversion among higher order modes by modifying the widths of the ring cavity. Therefore, this silicon waveguide based on ring cavity will provide a new technical scheme for designing tunable SBS lasers by tuning the ring widths. In addition, this enhanced and broadband acoustic radiation will pave the way for hybrid integration in silicon-based optical waveguide, micro-electromechanical system, and CMOS signal processing technology.
Conditional Deletion of EphA4 on Cx3cr1-Expressing Microglia Fails to Influence Histopathological Outcome and Blood Brain Barrier Disruption Following Brain Injury

Erythropoietin-producing human hepatocellular receptors play a major role in central nervous system injury. Preclinical and clinical studies revealed the upregulation of erythropoietin-producing human hepatocellular A4 (EphA4) receptors in the brain after acute traumatic brain injury. We have previously reported that Cx3cr1-expressing cells in the peri-lesion show high levels of EphA4 after the induction of controlled cortical impact (CCI) injury in mice. Cx3cr1 is a fractalkine receptor expressed on both resident microglia and peripheral-derived macrophages. The current study aimed to determine the role of microglial-specific EphA4 in CCI-induced damage. We used Cx3cr1CreER/+ knock-in/knock-out mice, which express EYFP in Cx3cr1-positive cells to establish microglia, EphA4-deficient mice following 1-month tamoxifen injection. Consistent with our previous findings, induction of CCI in wild-type (WT) Cx3cr1CreER/+EphA4+/+ mice increased EphA4 expression on EYFP-positive cells in the peri-lesion. To distinguish between peripheral-derived macrophages and resident microglia, we exploited GFP bone marrow-chimeric mice and found that CCI injury increased EphA4 expression in microglia (TMEM119+GFP–) using immunohistochemistry. Using Cx3cr1CreER/+EphA4 f/f (KO) mice, we observed that the EphA4 mRNA transcript was undetected in microglia but remained present in whole blood when compared to WT. Finally, we found no difference in lesion volume or blood-brain barrier (BBB) disruption between WT and KO mice at 3 dpi. Our data demonstrate a nonessential role of microglial EphA4 in the acute histopathological outcome in response to CCI.
Metabolic Modifications, Inflammation, and Cancer Immunotherapy

Cancer immunotherapy has accomplished significant progresses on treatment of various cancers in the past decade; however, recent studies revealed more and more heterogeneity in tumor microenvironment which cause unneglectable therapy resistance. A central phenomenon in tumor malignancy is metabolic dysfunctionality; it reprograms metabolic homeostasis in tumor and stromal cells thus affecting metabolic modifications on specific proteins. These posttranslational modifications include glycosylation and palmitoylation, which usually alter the protein localization, stability, and function. Many of these proteins participate in acute or chronic inflammation and play critical roles in tumorigenesis and progression. Therefore, targeting these metabolic modifications in immune checkpoints and inflammation provides an attractive therapeutic strategy for certain cancers. In this review, we summarize the recent progresses on metabolic modifications in this field, focus on the mechanisms on how glycosylation and palmitoylation regulate innate immune and inflammation, and we further discuss designing new immunotherapy targeting metabolic modifications. We aim to improve immunotherapy or targeted-therapy response and achieve more accurate individual therapy.
Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications

Owing to retained hepatic phenotypes and functions, human three-dimensional (3D) hepatic models established with diverse hepatic cell types are thought to recoup the gaps in drug development and disease modeling limited by a conventional two-dimensional (2D) cell culture system and species-specific variability in drug metabolizing enzymes and transporters. Primary human hepatocytes, human hepatic cancer cell lines, and human stem cell–derived hepatocyte-like cells are three main hepatic cell types used in current models and exhibit divergent hepatic phenotypes. Primary human hepatocytes derived from healthy hepatic parenchyma resemble in vivo–like genetic and metabolic profiling. Human hepatic cancer cell lines are unlimitedly reproducible and tumorigenic. Stem cell–derived hepatocyte-like cells derived from patients are promising to retain the donor’s genetic background. It has been suggested in some studies that unique properties of cell types endue them with benefits in different research fields of in vitro 3D modeling paradigm. For instance, the primary human hepatocyte was thought to be the gold standard for hepatotoxicity study, and stem cell–derived hepatocyte-like cells have taken a main role in personalized medicine and regenerative medicine. However, the comprehensive review focuses on the hepatic cell type variety, and corresponding applications in 3D models are sparse. Therefore, this review summarizes the characteristics of different cell types and discusses opportunities of different cell types in drug development, liver disease modeling, and liver transplantation.