Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Inhibition of Soluble Tumor Necrosis Factor Alters the Neuroinflammatory Response following Moderate Spinal Cord Injury in Mice

Simple Summary Blocking detrimental neuroinflammation and boosting a pro-regenerative environment are promising new therapeutic approaches in spinal cord injury (SCI). Selective blocking of the soluble (sol) form of the cytokine tumor necrosis factor (TNF) while maintaining the membrane-bound form of TNF (tmTNF) has shown beneficial effects in pre-clinical models of SCI. In the present study, we investigated the effects of selective solTNF inhibition on the spatio-temporal inflammatory response after SCI in mice. We found that the blocking of solTNF alleviated the pro-inflammatory response, altered microglial responses, increased myelin preservation, and improved functional outcomes. Altogether, this demonstrates that selective inhibition of solTNF holds translational potential after SCI. Abstract Clinical and animal model studies have implicated inflammation and glial and peripheral immune cell responses in the pathophysiology of spinal cord injury (SCI). A key player in the inflammatory response after SCI is the pleiotropic cytokine tumor necrosis factor (TNF), which exists both in both a transmembrane (tmTNF) and a soluble (solTNF) form. In the present study, we extend our previous findings of a therapeutic effect of topically blocking solTNF signaling after SCI for three consecutive days on lesion size and functional outcome to study the effect on spatio-temporal changes in the inflammatory response after SCI in mice treated with the selective solTNF inhibitor XPro1595 and compared to saline-treated mice. We found that despite comparable TNF and TNF receptor levels between XPro1595- and saline-treated mice, XPro1595 transiently decreased pro-inflammatory interleukin (IL)-1β and IL-6 levels and increased pro-regenerative IL-10 levels in the acute phase after SCI. This was complemented by a decrease in the number of infiltrated leukocytes (macrophages and neutrophils) in the lesioned area of the spinal cord and an increase in the number of microglia in the peri-lesion area 14 days after SCI, followed by a decrease in microglial activation in the peri-lesion area 21 days after SCI. This translated into increased myelin preservation and improved functional outcomes in XPro1595-treated mice 35 days after SCI. Collectively, our data suggest that selective targeting of solTNF time-dependently modulates the neuroinflammatory response by favoring a pro-regenerative environment in the lesioned spinal cord, leading to improved functional outcomes.
Chaotic attractors of atmospheric models

Abstract - In this paper we consider the theoretical results obtained for atmospheric models with chaotic dynamics. To define the notion of ‘climate’ for the real climate system we introduce the concept of ‘ideal climate model’. Starting from this concept we formulate problems that should be studied for the specific climate (or atmospheric) model under consideration. Further we give the analysis of the theoretical results for some widely used atmospheric models (barotropic, two-layer quasigeostrophic, a system of ‘primitive’ equations). In fact, most of the atmospheric and climate models are the results of some approximations to original systems (which are, in general, systems of partial differential equations). The problems of closeness for characteristics of original and approximating models are studied in the corresponding section of the paper. The central problem of the modern climate theory is the problem of the climate sensitivity to small perturbations of system parameters. In our paper we give the analysis of possible approaches to the solution of this problem. In particular, we consider the applicability of the fluctuation-dissipation theorem for the prediction of the system response to small perturbations of the external forcing. The results of numerical experiments with barotropic and two-layer quasigeostrophic atmospheric models, which were obtained along this line, are also presented.
Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature

Simple Summary Hepatocellular carcinoma is the third most prevalent cancer world-wide. This study aimed to reveal the metabolic signature of hepatocellular carcinoma compared to adjacent normal liver cells. To achieve this, metabolites were detected, analyzed, and quantified using targeted and non-targeted metabolomics. We found distinct metabolite signatures between both sample types. Targeted metabolomics identified distinct metabolites being specifically altered in hepatocellular tissue compared to adjacent liver, supporting the concept of metabolic reprogramming in hepatocellular carcinoma. Abstract Background: Hepatocellular carcinoma (HCC) is a major contributor to cancer-related morbidity and mortality burdens globally. Given the fundamental metabolic activity of hepatocytes within the liver, hepatocarcinogenesis is bound to be characterized by alterations in metabolite profiles as a manifestation of metabolic reprogramming. Methods: HCC and adjacent non-tumoral liver specimens were obtained from patients after HCC resection. Global patterns in tissue metabolites were identified using non-targeted 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy whereas specific metabolites were quantified using targeted liquid chromatography–mass spectrometry (LC/MS). Results: Principal component analysis (PCA) within our 1H-NMR dataset identified a principal component (PC) one of 53.3%, along which the two sample groups were distinctively clustered. Univariate analysis of tissue specimens identified more than 150 metabolites significantly altered in HCC compared to non-tumoral liver. For LC/MS, PCA identified a PC1 of 45.2%, along which samples from HCC tissues and non-tumoral tissues were clearly separated. Supervised analysis (PLS–DA) identified decreases in tissue glutathione, succinate, glycerol-3-phosphate, alanine, malate, and AMP as the most important contributors to the metabolomic signature of HCC by LC/MS. Conclusions: Together, 1H-NMR and LC/MS metabolomics have the capacity to distinguish HCC from non-tumoral liver. The characterization of such distinct profiles of metabolite abundances underscores the major metabolic alterations that result from hepatocarcinogenesis.
Effectiveness of Integrative Korean Medicine Treatment in Patients with Traffic-Accident-Induced Acute Low Back Pain and Mild Adult Scoliosis

We investigated the effectiveness of integrative Korean medicine treatment in patients with pre-existing scoliosis who received inpatient care for traffic-accident-induced acute LBP. We selected 674 patients diagnosed with scoliosis between 1 January 2015, and 30 June 2021, using lumbar spine (L-spine) imaging, across four Korean medicine hospitals in Korea for a retrospective chart review and sent them a questionnaire-based follow-up survey. The primary outcome was a numeric rating scale (NRS) score of LBP. The secondary outcomes were the Oswestry Disability Index (ODI), 5-level EuroQol 5-dimension (EQ-5D-5L), and patient global impression of change (PGIC) scores. In total, 101 patients responded to the follow-up survey. NRS scores decreased from 4.86 (4.71–5.02) to 3.53 (3.17–3.90) from admission to discharge, subsequently decreasing to 3.01 (2.64–3.38) (p < 0.001) at the last follow-up. Similarly, ODI scores decreased from 35.96 (33.08–38.85) to 22.73 (20.23–25.24) and 14.21 (11.74–16.67) (p < 0.001), respectively. Approximately 87.1% of patients were satisfied with their inpatient care. There were no significant differences in the degree of improvement according to the severity of scoliosis. Integrative Korean medicine treatment can improve pain, lumbar dysfunction, and quality of life in patients with traffic-accident-induced acute low back pain and pre-existing mild scoliosis.
Statistics of energetic electrons in the magnetotail reconnection

Magnetic reconnection has long been regarded as an important site for producing energetic electrons in solar terrestrial and astrophysical plasmas. The motivation of this paper is to provide the average properties of energetic electrons in reconnection region, which are crucial for understanding electron energization mechanism but are rarely known. We statistically analyzed the energetic electrons through 21 magnetotail reconnection events observed by Cluster spacecraft during the years of 2001–2005. Approximately 1200 data points with time resolution of 8 s have been collected for each spacecraft. Two parameters are examined: energetic electron rate (EER) and power law index. EER, which is defined as the ratio of the integrated energetic electron flux to the lower energy electron flux, is used to quantify the electron acceleration efficiency. We find that EER and energetic electron flux (EEF) are positively correlated with the power law index, i.e., the higher rate and flux generally corresponds to softer spectrum. This unexpected correlation is probably caused by some nonadiabatic heating/acceleration mechanisms that tend to soft the spectrum with high temperature. EER is much larger within the earthward flow than the tailward flow. It is positively correlated with the outflow speed Vx, while the correlation between EER and Bz is less clear. With the increment of earthward outflow speed, the occurrence rate of high EER also monotonically increases. We find that EER generally does not increase with the increment of perpendicular electric field |E⊥|, suggesting that adiabatic betatron and Fermi acceleration probably play minor roles in electron energization during magnetotail reconnection.
Long Term Outcome and Quality of Life of Intracranial Meningioma Patients Treated with Pencil Beam Scanning Proton Therapy

Simple Summary Meningiomas are one of the most common primary brain tumors. The current standard therapy for symptomatic or growing lesions includes surgery and/or radiotherapy. Pencil Beam Scanning Proton Therapy (PBS PT) is an alternative to conventional radiotherapy with unique dose deposition pattern and improved conformality. In this retrospective study, we assess the clinical outcome including the quality of life (QoL) of patients with intracranial meningiomas treated with PBS PT between 1997 and 2022 at the Centre for Proton Therapy of the Paul Scherrer Institute. In 200 patients, we observed a high local control and survival, especially in patients with grade 1 tumors as well as a low rate of high-grade toxicity and stable QoL over the years after treatment. This study shows that PBS PT is an adequate alternative to conventional radiotherapy in meningioma treatment. Abstract The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1–3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed. Acute and late side effects were classified according to CTCAE version 5.0. Time to event data were calculated. QoL was assessed descriptively by the EORTC-QLQ-C30 and BN20 questionnaires. With a median follow-up of 65 months (range: 3.8–260.8 months) the 5 year OS was 95.7% and 81.8% for WHO grade 1 and grade 2/3, respectively (p < 0.001). Twenty (10%) local failures were observed. Failures occurred significantly (p < 0.001) more frequent in WHO grade 2 or 3 meningioma (WHO grade 1: n = 7, WHO grade 2/3: n = 13), in patients with multiple meningiomas (p = 0.005), in male patients (p = 0.005), and when PT was initiated not as upfront therapy (p = 0.011). There were no high-grade toxicities in the majority (n = 176; 88%) of patients. QoL was assessed for 83 (41.5%) patients and for those patients PT did not impacted QoL negatively during the follow-up. In summary, we observed very few local recurrences of meningiomas after PBS PT, a stable QoL, and a low rate of high-grade toxicity.
Isoespintanol Antifungal Activity Involves Mitochondrial Dysfunction, Inhibition of Biofilm Formation, and Damage to Cell Wall Integrity in Candida tropicalis

The growing increase in infections caused by C. tropicalis, associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of fungal biofilms, the mitochondrial membrane potential (ΔΨm), and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.
Factors Associated with Return Visits by Elders within 72 Hours of Discharge from the Emergency Department

Elders have a higher rate of return visits to the emergency department (ED) than other patients. It is critical to understand the risk factors for return visits to the ED by elders. The aim of this study was to determine the factors associated with return visits to the ED by elders. This study retrospectively reviewed the hospital charts of elders who returned to the ED within 72 h after discharge from ED. The risk factors identified in the Triage Risk Screening Tool were applied in this study. Of the elders discharged from the ED, 8.64% made a return visit to the ED within 72 h. The highest revisit rate occurred within 24 h after discharge. Factors associated with return ED visits within 24 h by elders were difficulty walking and having discharge care needs. The factor associated with ED return visits within 24–48 h was polypharmacy. Difficulty walking, having discharge care needs, and hospitalization within the past 120 days were associated with return visits made within 48–72 h following discharge. Identifying the reasons for return visits to the ED and providing a continuous review of geriatric assessment and discharge planning could reduce unnecessary revisits.
Etiologies of Acute Bronchiolitis in Children at Risk for Asthma, with Emphasis on the Human Rhinovirus Genotyping Protocol

This research aims to determine acute bronchiolitis’ causative virus(es) and establish a viable protocol to classify the Human Rhinovirus (HRV) species. During 2021–2022, we included children 1–24 months of age with acute bronchiolitis at risk for asthma. The nasopharyngeal samples were taken and subjected to a quantitative polymerase chain reaction (qPCR) in a viral panel. For HRV-positive samples, a high-throughput assay was applied, directing the VP4/VP2 and VP3/VP1 regions to confirm species. BLAST searching, phylogenetic analysis, and sequence divergence took place to identify the degree to which these regions were appropriate for identifying and differentiating HRV. HRV ranked second, following RSV, as the etiology of acute bronchiolitis in children. The conclusion of the investigation of all available data in this study distributed sequences into 7 HRV-A, 1 HRV-B, and 7 HRV-C types based on the VP4/VP2 and VP3/VP1 sequences. The nucleotide divergence between the clinical samples and the corresponding reference strains was lower in the VP4/VP2 region than in the VP3/VP1 region. The results demonstrated the potential utility of the VP4/VP2 region and the VP3/VP1 region for differentiating HRV genotypes. Confirmatory outcomes were yielded, indicating how nested and semi-nested PCR can establish practical ways to facilitate HRV sequencing and genotyping.
A Personalized Approach to Determining the Caloric Needs of Children with Prader–Willi Syndrome Treated with Growth Hormone

Prader–Willi Syndrome (PWS) is the most frequent cause of genetic obesity. Early reports indicate that children with PWS require 20–40% fewer calories than healthy children to maintain adequate growth. Growth hormone treatment for children with PWS, approved in 2000, affects the body composition and probably affects energy requirements. This retrospective cross-sectional study analyzed the caloric intake in children with PWS aged from 6 months to 12 years old who underwent growth hormone treatment, comparing the patients’ caloric intake calculated from parent-recorded dietary intake versus the recommended caloric intake for healthy children, taking into account the age, sex, height, weight, and physical activity. We analyzed the data from 25 patients (13 (52%) boys; mean age, 6.72 ± 2.81 y; median age at starting growth hormone treatment, 1.4 y (IQR: 0.78–2.29); 17 (68%) normal weight and 8 (32%) overweight or obese). The mean daily energy intake was 1208 ± 186 kcal/d, representing 96.83% ± 18.66 of the recommended caloric intake for healthy children. The caloric intake in children with PWS treated with growth hormone was very similar to that recommended for healthy children; thus, we should rethink the dietary recommendations for these children.
Selected Nutrition and Management Strategies in Suckling Pigs to Improve Post-Weaning Outcomes

Simple Summary Weaning involves the removal of piglets from a sow, and on commercial farms, it usually occurs at between 3 and 5 weeks of age. Newly weaned piglets face physical, social, environmental, management and dietary challenges. Consequently, post-weaning, they often experience reduced feed intake, poor growth and, in some cases, diarrhoea. There are many interventions which can be employed on-farm during the suckling period to ease the transition at weaning for piglets. Strategies such as supervised farrowing, post-farrowing pain relief for sows, the use of nurse sows, cross-fostering, the administration of energy supplements/feed additives to piglets and liquid/dry creep feeding have been investigated. The objective of these strategies is to promote earlier feed exploration, increase early post-weaning feed intake and growth and improve intestinal maturity. This review focuses in particular on pain relief for sows, piglet management at birth, and the provision of supplementary milk/liquid feed and feed additives to suckling piglets. Carefully selected, these strategies have the potential to increase the lifetime growth and health of pigs from large litters. Abstract Weaning is a critical period in a pig’s life. Piglets are confronted with abrupt changes to their physical and social environment, as well as management and nutritional changes. Weaning has always been associated with a growth check and is frequently accompanied by post-weaning diarrhoea in piglets. However, rapid increases in litter size in the last decade have increased within-litter piglet weight variation, with piglets now generally lighter at weaning, making the challenges associated with weaning even greater. Many interventions can be employed during the suckling period to ease the weaning transition for piglets. Pre-weaning strategies such as supervised farrowing (assistance with suckling and oxytocin provision), the provision of pain relief to sows around farrowing, split-suckling, early oral supplementation with glucose, bovine colostrum, faecal microbiota transplantation, feed additives and solid and liquid creep feeding (milk and liquid feed) have all been investigated. The objective of these strategies is to stimulate earlier maturation of the digestive tract, improve immunity, reduce latency to the first feed post-weaning and increase early post-weaning feed intake and growth. This review focuses in particular on: (1) pain relief provision to sows around farrowing, (2)split-suckling of piglets, (3) pre-weaning provision of supplementary milk and/or liquid feed, (4) other strategies to stimulate earlier enzyme production (e.g., enzyme supplementation), (5) other nutritional strategies to promote improved gut structure and function (e.g., L-glutamine supplementation), and (6) other strategies to modulate gut microbiota (e.g., probiotics and prebiotics). Correctly implementing these strategies can, not only increase post-weaning growth and reduce mortality, but also maximise lifetime growth in pigs.
Positive Point-of-Care Influenza Test Significantly Decreases the Probability of Antibiotic Treatment during Respiratory Tract Infections in Primary Care

This study aimed to analyse clinical and laboratory findings in primary care patients with respiratory tract infections to distinguish the group more likely to receive antibiotic treatment. The study group consisted of 631 patients (264 males; 367 females) with a median age of 48 years (IQR 36–63 years). Analysed groups included patients treated with antibiotics (n = 269 patients; 43%) and those who recovered without antibiotic treatment (n = 362 patients; 57%). Patients receiving antibiotics were older (median 51 vs. 47 years; p = 0.008) and more commonly developed fever (77% vs. 25%, p < 0.0001) and cough (63% vs. 30%; p = 0.0014). Moreover, they more frequently presented wheezing and crackles upon physical examination (28% vs. 4% and 9% vs. 0.3%; p < 0.0001 and p < 0.0001, respectively). They also had more comorbidities and came to more follow-up visits (median of 4 vs. 3 and 2 vs. 1, p < 0.0001 and p < 0.0001, respectively). Patients receiving symptomatic therapy more often had positive point-of-care tests (POCTS)—20% vs. 7%; p = <0.0001. Multivariate analysis in our cohort found comorbidities complexity (odds ratio—OR 2.62; 95% confidence interval—1.54–4.46), fever (OR 32.59; 95%CI 19.15–55.47), crackles (OR 26.35; 95%CI 2.77–250.81) and the number of visits (OR 4.15; 95%CI 2.39–7.20) as factors increasing the probability of antibiotic treatment. Positive influenza POCTS reduced the risk of antibiotic therapy (OR 0.0015; 95%CI 0.0001–0.0168).
How Dog Behavior Influences Pet Owner’s Perceptions of Dog Preference for Dental Chews

Simple Summary Most studies on dog food and treat preferences focus on owner reports about the product and how much the dog consumes. The aim of this study was to examine dog behavior and engagement in a home-environment with eight different dental chews. Owners submitted a video of their dogs which was analyzed to investigate any relationship between coded dog behavior and owner survey responses for preference among the chew types. Owner-reported dog preference related more to the video coded behavior than their own preference providing some preliminary guidance on what factors might relate to product preference and purchase and how analysis of in-home behavior may better guide pet product research. Abstract American pet owners spend billions of dollars on food and treats so it is important to understand what products they want and what they think their dog would enjoy. This study analyzed video recordings of dogs engaging in dental chews in their home environment and compared the observed appetitive behaviors to owner preference and owner-reported dog preference. Overall, appetitive behavior differed significantly between some dental chews. Owner preference for the chews correlated significantly with dog appetitive behavior, but the effect was small (r (702) = 0.22, p = 0.001), whereas owner-reported dog preference correlated significantly with dog appetitive behavior and showed a moderate effect size (r (702) = 0.43, p = 0.001)—similar in magnitude to findings when parents are asked to report on their children’s behavior. By merging objective behavioral observation of owner-recorded videos with their survey responses, we were able to preliminarily parse out what factors owners may use to assess preference and encourage the future use of in-home video recordings to better understand dog and owner engagement and interaction with pet products.