Miracle-dz/UniFAR-FTUs huggingface dataset:
A Real-Time Thermal Sensor System for Quantifying the Inhibitory Effect of Antimicrobial Peptides on Bacterial Adhesion and Biofilm Formation

The increasing rate of antimicrobial resistance (AMR) in pathogenic bacteria is a global threat to human and veterinary medicine. Beyond antibiotics, antimicrobial peptides (AMPs) might be an alternative to inhibit the growth of bacteria, including AMR pathogens, on different surfaces. Biofilm formation, which starts out as bacterial adhesion, poses additional challenges for antibiotics targeting bacterial cells. The objective of this study was to establish a real-time method for the monitoring of the inhibition of (a) bacterial adhesion to a defined substrate and (b) biofilm formation by AMPs using an innovative thermal sensor. We provide evidence that the thermal sensor enables continuous monitoring of the effect of two potent AMPs, protamine and OH-CATH-30, on surface colonization of bovine mastitis-associated Escherichia (E.) coli and Staphylococcus (S.) aureus. The bacteria were grown under static conditions on the surface of the sensor membrane, on which temperature oscillations generated by a heater structure were detected by an amorphous germanium thermistor. Bacterial adhesion, which was confirmed by white light interferometry, caused a detectable amplitude change and phase shift. To our knowledge, the thermal measurement system has never been used to assess the effect of AMPs on bacterial adhesion in real time before. The system could be used to screen and evaluate bacterial adhesion inhibition of both known and novel AMPs.
Neurogenic Bowel Dysfunction in Children and Adolescents

Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common cause of pediatric NBD). Many methods of conservative and medical management of NBD are reported, including relatively recently Transanal Irrigation (TAI). Based on the literature and personal experience, an expert group (pediatric urologists/surgeons/gastroenterologists with specific experience in NBD) focused on NBD in children and adolescents. A statement document was created using a modified Delphi method. The range of causes of pediatric NBD are discussed in this paper. The various therapeutic approaches are presented to improve clinical management. The population of children and adolescents with NBD is increasing, due both to the higher survival rate and better diagnosis. While NBD is relatively predictable in producing either constipation or fecal incontinence, or both, its various effects on each patient will depend on a wide range of underlying causes and accompanying comorbidities. For this reason, management of NBD should be tailored individually with a combined multidisciplinary therapy appropriate for the status of the affected child and caregivers.
Gene Module Analysis Reveals Cell-Type Specificity and Potential Target Genes in Autism’s Pathogenesis

Multiple genetic factors contribute to the pathogenesis of autism spectrum disorder (ASD), a kind of neurodevelopmental disorder. Genes were usually studied separately for their associations with ASD. However, genes associated with ASD do not act alone but interact with each other in a network module. The identification of these modules is the basis for the systematic understanding of the pathogenesis of ASD. Moreover, ASD is characterized by highly pathogenic heterogeneity, and gene modules associated with ASD are cell-type-specific. In this study, based on the single-nucleus RNA sequencing data of 41 post-mortem tissue samples from the prefrontal cortex and anterior cingulate cortex of 19 ASD patients and 16 control individuals, we applied sparse module activity factorization, a matrix decomposition method consistent with the multi-factor and heterogeneous characteristics of ASD pathogenesis, to identify cell-type-specific gene modules. Then, statistical procedures were performed to detect highly reproducible cell-type-specific ASD-associated gene modules. Through the enrichment analysis of cell markers, 31 cell-type-specific gene modules related to ASD were further screened out. These 31 gene modules are all enriched with curated ASD risk genes. Finally, we utilized the expression patterns of these cell-type-specific ASD-associated gene modules to build predictive models for ASD. The excellent predictive performance also proved the associations between these gene modules and ASD. Our study confirmed the multifactorial and cell-type-specific characteristics of ASD pathogeneses. The results showed that excitatory neurons such as L2/3, L4, and L5/6-CC play essential roles in ASD’s pathogenic processes. We identified the potential ASD target genes that act together in cell-type-specific modules, such as NRG3, KCNIP4, BAI3, PTPRD, LRRTM4, and LINGO2 in the L2/3 gene modules. Our study offers new potential genomic targets for ASD and provides a novel method to study gene modules involved in the pathogenesis of ASD.
Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.
GPCR-Based Bioactive Peptide Screening Using Phage-Displayed Peptides and an Insect Cell System for Insecticide Discovery

The discovery of new insecticides improves integrated pest management (IPM), but is usually a long high-risk process with a low probability of success. For over two decades, insect neuropeptides (NPs) and their G-protein coupled receptors (GPCRs) have been considered as biological targets for insect pest control, because they are involved in almost all physiological processes associated with insect life stages. A key roadblock to success has been the question of how large volume chemical libraries can be efficiently screened for active compounds. New genomic and proteomic tools have advanced and facilitated the development of new approaches to insecticide discovery. In this study, we report a novel GPCR-based screening technology that uses millions of short peptides randomly generated by bacteriophages, and a method using an insect Sf9 cell expression system. The fire ant is a good model system, since bioactive peptides have been identified for a specific GPCR. The novel small peptides could interfere with the target GPCR-ligand functions. Therefore, we refer to this new mechanism as “receptor interference” (RECEPTORi). The GPCR-based bioactive peptide screening method offers multiple advantages. Libraries of phage-displayed peptides (~109 peptides) are inexpensive. An insect cell-based screening system rapidly leads to target specific GPCR agonists or antagonists in weeks. Delivery of bioactive peptides to target pests can be flexible, such as topical, ingestion, and plant-incorporated protectants. A variety of GPCR targets are available, thus minimizing the development of potential insecticide resistance. This report provides the first proof-of-concept for the development of novel arthropod pest management strategies using neuropeptides, and GPCRs.
NFAT5 Is Involved in GRP-Enhanced Secretion of GLP-1 by Sodium

Gastrin, secreted by G-cells, and glucagon-like peptide-1 (GLP-1), secreted by L-cells, may participate in the regulation of sodium balance. We studied the effect of sodium in mice in vivo and mouse ileum and human L-cells, on GLP-1 secretion, and the role of NFAT5 and gastrin-releasing peptide receptor (GRPR) in this process. A high-sodium diet increases serum GLP-1 levels in mice. Increasing sodium concentration stimulates GLP-1 secretion from mouse ileum and L-cells. GRP enhances the high sodium-induced increase in GLP-1 secretion. High sodium increases cellular GLP-1 expression, while low and high sodium concentrations increase NFAT5 and GRPR expression. Silencing NFAT5 in L-cells abrogates the stimulatory effect of GRP on the high sodium-induced GLP-1 secretion and protein expression, and the sodium-induced increase in GRPR expression. GLP-1 and gastrin decrease the expression of Na+-K+/ATPase and increase the phosphorylation of sodium/hydrogen exchanger type 3 (NHE3) in human renal proximal tubule cells (hRPTCs). This study gives a new perspective on the mechanisms of GLP-1 secretion, especially that engendered by ingested sodium, and the ability of GLP-1, with gastrin, to decrease Na+-K+/ATPase expression and NHE3 function in hRPTCs. These results may contribute to the better utilization of current and future GLP-1-based drugs in the treatment of hypertension.
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PAhigh, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PAhigh at higher risk of progression and death.
Seroprevalence of SARS-CoV-2 Infection among Occupational Groups from the Bucaramanga Metropolitan Area, Colombia

The negative effects of coronavirus disease 2019 (COVID-19) pandemic have impacted the world economy due to the absence from work because of SARS-CoV-2 infection in workers, among other reasons. However, some economic areas are essential to society and people must continue working outside the home to support economic reactivation; their serological profile could be different from that of the global population. Cross-sectional study: Workers from health, construction, public transportation, public force, bike delivery messengers, independent or informal commerce areas, and residents of Bucaramanga or its metropolitan area were invited to participate. All participants self-completed a virtual survey and a blood test was taken to assess IgG and IgM with the ARC COV2 test. Seroprevalence was estimated considering a complex survey design, correcting for a finite population effect and adjusting for test performance. A total of 7045 workers were enrolled; 59.9% were women and most were residents of Bucaramanga and working in health occupations. The global adjusted seroprevalence was 19.5% (CI: 95% 18.6–20.4), being higher for Girón (27.9%; 95% CI: 24.5–31.30). Workers with multiple contact with people during working hours or using public transportation to go to work had a higher frequency of seropositivity for SARS-CoV-2. The seroprevalence among workers living in these four municipalities from the Colombian northeast area is still low.
Effects of Spatial Characteristics on the Spread of the Highly Pathogenic Avian Influenza (HPAI) in Korea

This paper examines the effects of regional characteristics on the spread of the highly pathogenic avian influenza (HPAI) during Korea’s 2016–2017 outbreak. A spatial econometric model is used to determine the effects of regional characteristics on HPAI dispersion using data from 162 counties in Korea. Results indicate the existence of spatial dependence, suggesting that the occurrence of HPAI in a county is significantly influenced by neighboring counties. We found that larger size poultry, including laying hens, breeders, and ducks are significantly associated with a greater incidence of HPAI. Among poultry, we found ducks as the greatest source of the spread of HPAI. Our findings suggest that those regions that are spatially dependent with respect to the spread of HPAI, such as counties that intensively breed ducks, should be the focus of surveillance to prevent future epidemics of HPAI.
Phenolic Content and Antioxidant Activity in Seeds of Common Bean (Phaseolus vulgaris L.)

Dry bean (Phaseolus vulgaris L.) is one of the most important pulses consumed in the world. Total phenolic content, total flavonoid content, total monomeric anthocyanin content and antioxidant capacity were determined, using ferric reducing antioxidant power and free radical scavenging activity, in 255 lines grown under the same environmental conditions. For all parameters analysed, there was a wide range of variability, with differences always above one order of magnitude. Phenolic compounds in beans with coloured coats were found to be more efficient antioxidants than those with completely white coats, and samples with more strongly coloured coats (red, cream, black, pink and brown) showed the highest antioxidant capacities. Based on the strong correlation detected between the variables, total phenolic content can be considered an appropriate indicator of antioxidant activity. The results provide a robust database for selecting those lines of greater functional and nutritional interest in terms of cultivation for direct consumption, for inclusions in food formulations or for use in future breeding programs.
Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses

Simple Summary Despite the unprecedented clinical benefit of immunotherapy in melanoma, some patients still do not respond to treatment, arguing the need for novel therapeutic targets. The aim of this study was to investigate the therapeutic potential of two understudied proteins, Ropporin-1 (ROPN1) and 1B (ROPN1B). We confirmed that these proteins are widely expressed in melanoma patients using gene data derived from public datasets, and protein data derived from 61 patient tumours. Moreover, these proteins were able to evoke strong immune responses in 104 melanoma patients. These findings therefore suggest that ROPN1 and ROPN1B may be valuable targets for immunotherapy, alone or in combination with existing treatments. Abstract Antibodies that block immune regulatory checkpoints (programmed cell death 1, PD-1 and cytotoxic T-lymphocyte-associated antigen 4, CTLA-4) to mobilise immunity have shown unprecedented clinical efficacy against cancer, demonstrating the importance of antigen-specific tumour recognition. Despite this, many patients still fail to benefit from these treatments and additional approaches are being sought. These include mechanisms that boost antigen-specific immunity either by vaccination or adoptive transfer of effector cells. Other than neoantigens, epigenetically regulated and shared antigens such as NY-ESO-1 are attractive targets; however, tissue expression is often heterogeneous and weak. Therefore, peptide-specific therapies combining multiple antigens rationally selected to give additive anti-cancer benefits are necessary to achieve optimal outcomes. Here, we show that Ropporin-1 (ROPN1) and 1B (ROPN1B), cancer restricted antigens, are highly expressed and immunogenic, inducing humoral immunity in patients with advanced metastatic melanoma. By multispectral immunohistochemistry, 88.5% of melanoma patients tested (n = 54/61) showed ROPN1B expression in at least 1 of 2/3 tumour cores in tissue microarrays. Antibody responses against ROPN1A and ROPN1B were detected in 71.2% of melanoma patients tested (n = 74/104), with increased reactivity seen with more advanced disease stages. Thus, ROPN1A and ROPN1B may indeed be viable targets for cancer immunotherapy, alone or in combination with other cancer antigens, and could be combined with additional therapies such as immune checkpoint blockade.
A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis

Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.
Exploring the Potential Application of Matrimid® and ZIFs-Based Membranes for Hydrogen Recovery: A Review

Hydrogen recovery is at the center of the energy transition guidelines promoted by governments, owing to its applicability as an energy resource, but calls for energetically nonintensive recovery methods. The employment of polymeric membranes in selective gas separations has arisen as a potential alternative, as its established commercial availability demonstrates. However, enhanced features need to be developed to achieve adequate mechanical properties and the membrane performance that allows the obtention of hydrogen with the required industrial purity. Matrimid®, as a polyimide, is an attractive material providing relatively good performance to selectively recover hydrogen. As a consequence, this review aims to study and summarize the main results, mechanisms involved and advances in the use of Matrimid® as a selective material for hydrogen separation to date, delving into membrane fabrication procedures that increase the effectiveness of hydrogen recovery, i.e., the addition of fillers (within which ZIFs have acquired extraordinary importance), chemical crosslinking or polymeric blending, among others.
Dexamethasone in Patients Hospitalized with COVID-19: Whether, When and to Whom

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9–65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0–13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1–79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1–50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9–20.6) in subjects <70 years, 27.0 (95%CI 18.5–49.8) in men, and 16.2 (95%CI 13.2–20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.
The wasp-waisted hysteresis loop and exchange bias in multiferroic BaNiF4

Multiferroic BaNiF4 has been fabricated by hydrothermal method. The bifurcation between zero field cooling (ZFC) and field cooling (FC) temperature dependent magnetization (M-T) curves starts at 150 K, indicating the 2D antiferromagnetic (FM) transition. A further upturn of magnetization has been observed below 68 K in FC M-T curve, corresponding to the emergence of 3D AFM structure. Wasp-waisted hysteresis loop was observed under 130 K, which is explained by that the AFM aligned net spins from the canting of neighboring AFM spins due to Dzyaloshinskii-Moriya interaction can be easily aligned by the magnetic field. Exchange bias effect was detected below 70 K, which has been interpreted by the magnetization pinned by the spontaneous polarization through magnetoelectric coupling.