Miracle-dz/UniFAR-FTUs huggingface dataset:
Past, present, and future of Lyme disease vaccines: antigen engineering approaches and mechanistic insights

ABSTRACT Introduction Transmitted by ticks, Lyme disease is the most common vector-borne disease in the Northern hemisphere. Despite the geographical expansion of human Lyme disease cases, no effective preventive strategies are currently available. Developing an efficacious and safe vaccine is therefore urgently needed. Efforts have previously been taken to identify vaccine targets in the causative pathogen (Borrelia burgdorferi sensu lato) and arthropod vector (Ixodes spp.). However, progress was impeded due to a lack of consumer confidence caused by the myth of undesired off-target responses, low immune responses, a limited breadth of immune reactivity, as well as by the complexities of the vaccine process development. Area covered In this review, we summarize the antigen engineering approaches that have been applied to overcome those challenges and the underlying mechanisms that can be exploited to improve both safety and efficacy of future Lyme disease vaccines. Expert opinion Over the past two decades, several new genetically redesigned Lyme disease vaccine candidates have shown success in both preclinical and clinical settings and built a solid foundation for further development. These studies have greatly informed the protective mechanisms of reducing Lyme disease burdens and ending the endemic of this disease.
Persistence of chronic inflammation after regular blood transfusion therapy in sickle cell anemia

Sickle cell anemia (SCA) is a hemoglobinopathy that causes major red blood cell (RBC) dysfunction; however, studies have also highlighted the signi ﬁ cant role of polymorphonuclear cells in SCA pathophysiology. 1-3 Patients with SCA have an increased leukocyte count at steady state and exhibit neutrophil activation markers, 4 including increased expression of adhesion molecules 5 such as the integrins Mac-1 (CD18/CD11b) and LFA-1 (CD18/CD11a), 6 increased expressions of activation proteins such as CD64, 7 and increased expression of aging markers such as CXCR4 high /CD62L low . 8 Hydroxyurea (HU) may also bene ﬁ t patients with SCA by suppressing neutrophil activation and cor-recting the dysregulated
THE LUMINOSITY FUNCTION AND INITIAL MASS FUNCTION FOR THE PLEIADES CLUSTER

In the best observed Pleiades cluster, the luminosity function(LF) and mass function(MF) for main sequence(MS) stars extended to are very similar to the initial luminosity function(ILF) and initial mass function(IMF) for field stars in the solar neighborhood showing a bump at log and a dip at log . This dip is equivalent to the Wielen dip appearing in the LF for the field stars. The occurence of these bump and dip is independent of adopted mass-luminosity relation(MLR) . and their characteristics could be explained by a time-dependent bimodal IMF. The model with this IMF gives a total cluster mass of brown dwarfs and white dwarfs if the upper mass limit of progenitor of white dwarf is greater than . The cluster age on the basis of LF for brightest stars is given by and all stars in the cluster lie along the single age sequence in the C-M diagram without showing a large dispersion from the sequence.
Econometric structural models : a model selection approach

Using a model selection approach, this thesis proposes a constructive data-and-theory-combined procedure to identify model structures in the framework of a linear simultaneous equations system based on observed data. A model structure is characterized by restrictions on the structural parameters. To identify these restrictions two issues have to be taken into account: the first is the problem of observational equivalence, i.e. different models may have an identical density function, henceforth data cannot differentiate such observationally equivalent models; the second is the identification of the restrictions on structural parameters. For the first problem we classify models into different observationally equivalent classes and give necessary and sufficient conditions for the uniqueness of observationally equivalent models. For the second problem we take an approach based on the information criterion and give a (strong) consistent criterion to identify the restrictions on the structural parameters. We apply this model selection criterion to cointegration systems and provide a unified approach to analyzing linear simultaneous equations systems and cointegration systems. The model selection criterion is also used to identify the encompassing relations among different structural models under mis-specification. Through constructive use of the model selection criterion, we may get the most parsimonious structural model that is compatible to the data among the models under investigation. However, all conclusions conducted from the model selection criterion are valid only asymptotically. Nevertheless, the relevance for practical applications of this criterion is demonstrated by some simulation studies.
Effect of incremental intensities on the spinal morphology and core muscle activation in competitive cyclists

ABSTRACT Cycling is a sport where cyclists predominantly adopt a sitting posture, with the trunk tilted forward. This posture requires a high volume of training and duration in several intensities of effort. This study aims to: 1) evaluate the behaviour of the thoracic and lumbar spine flexion and sacral inclination in the sagittal plane, the thoracic and lumbar spine flexion in the frontal plane, and the trunk torsion in the transverse plane; 2) compare the activation of the core muscles as the intensity of effort increases during an incremental test in cycling, and 3) identify which core muscle has a greater activation in each intensity zone. The spinal posture and the activation of the eight core muscles were evaluated in twelve competitive cyclists during incremental cycling intensities. Thoracic and lumbar spine flexion and sacral inclination statistically increased as the intensity of effort increased (Start < VT1 < VT2 < VO2max). A significant increase in muscle activation was observed in all core muscles evaluated as the intensity increased. The rectus abdominis showed statistically significant greater muscle activation than the other core muscles evaluated. In conclusion, as the intensity of effort in cycling increases, cyclists significantly increase the thoracic and lumbar spine flexion, the sacral inclination in the sagittal plane, the thoracic and lumbar spine flexion in the frontal plane, trunk rotation in the transverse plane, as well as the activation of the core muscles.
Recombinant human MG53 protein attenuates brain lesion size in a large animal model of traumatic brain injury

Administration of recombinant human MG53 (rhMG53) intravenously following a traumatic brain injury in swine led to decreased brain lesion size with localization to the injured region. rhMG53 has potential as a future therapy in treatment of TBI. #braininjury #TBI BACKGROUND MG53, a member of the tripartite motif (TRIM) protein family, plays an essential role in cell membrane repair and promotes cell survival. Recent studies show that systemic delivery of recombinant human MG53 (rhMG53) protein markedly attenuates tissue injury/inflammation, and facilitates healing. This study was performed to test whether intravenous administration of rhMG53 protein would decrease the lesion size in a clinically relevant large animal model of traumatic brain injury (TBI). METHOD Yorkshire swine (40–45 kg; n = 5/group) were subjected to controlled cortical impact TBI and randomized to either: (1) rhMG53 protein (2 mg/kg, intravenous) or (2) normal saline control. Hemodynamics, intracranial pressure, and brain oxygenation were monitored for 7 hours. Brains were then harvested and sectioned into 5-mm slices and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size. Blood-brain barrier permeability of MG53 in the brain was determined by Western blot and immunohistochemistry. Bcl-2 and phospho-GSK β levels were measured as makers of prosurvival pathway activation. RESULTS Hemodynamic parameters were similar in both groups, but the lesion size in the rhMG53-treated group (2,517 ± 525.4 mm3) was significantly (p < 0.05) smaller than the control group (3,646 ± 740.1 mm3). In the treated animals, rhMG53 was detected in the regions surrounding the TBI, but it was absent in the saline-treated control animals. Bcl-2 and phospho-GSK β levels in the brains were upregulated in the rhMG53-treated animals. CONCLUSION Intravenously administered rhMG53 localizes to the injured areas of the brain, with the treated animals demonstrating a significant attenuation in the brain lesion size following TBI.
Emergent Coordination of Heading in Soccer: Of Two Players and a Single Ball

ABSTRACT Purpose: In many sports situations, two or more players need to coordinate their actions to make sure that one of them intercepts a ball or opponent. We considered how two soccer players head back a thrown ball. Two accounts for the joint decision making by both players were considered. These two accounts not only differ in their theoretical basis but also have vastly different implications for training practice. In a first account, players know their areas of responsibility for interception, and combine this with their prediction of the ball's landing location. In a second account, the coordination emerges from the unfolding dynamics of the system of informationally connected players and ball. According to this second account, especially for balls aimed in between the two players, both of the players may start moving and one player sees that the ball will be interceptable for the other player, and subsequently yields the interception. Methods: We instrumented soccer players and the ball with Kinexon sensors and had pairs of players head back the thrown ball. Results: In line with the second account, the results showed a fair number of instances where the player who intercepted the ball had to move the longest distance. Furthermore, considerable movement by both players was not an exception. Conclusion: The results can be taken as a first step towards an understanding of joint coordination as an emergent phenomenon.
Reduced Tripartite Motif-Containing Protein 29 Deteriorates the Severity of Severe Acute Pancreatitis

Objectives Severe acute pancreatitis (SAP) is the most serious subtype of acute pancreatitis, manifested as multiple-organ failure resulting in high morbidity and mortality. Based on the role of tripartite motif-containing protein 29 (TRIM29) in immune responses, we aimed to explore its effect on SAP. Methods Peripheral blood monocyte cells from the SAP or non-SAP patients, as well as bone marrow–derived macrophages from wild-type, TRIM29−/−, or stimulator of interferon genes (STING)−/− mice after injecting 50 mg/kg of cerulein to induce SAP, were isolated to analyze the role of TRIM29 and STING in the SAP. Results Tripartite motif-containing protein 29 was significantly reduced in SAP patients. Compared with wild-type mice, TRIM29 deficiency mice displayed more severe symptom of acute pancreatitis after cerulein injection, which were lost in TRIM29−/−STING−/− mice. Moreover, interferon and its related genes, as well as STING degradation, were decreased in TRIM29−/− mice. Conclusions Our study demonstrated that TRIM29 negatively regulated the severity of SAP by degrading STING at its downstream, suggesting that TRIM29 and STING might serve as therapeutic targets for SAP.
Zinc Kinetics Correlate With Length-for-Age z Scores in Bangladeshi Infants

Objectives: Stunting [length-for-age z score (LAZ) <−2] has multiple causes and is prevalent in areas with low dietary zinc (Zn) intake. Zinc kinetics from non-stunted infants were used in a published model for predicting linear growth; here, we directly measure zinc kinetics in stunted infants. Methods: Zinc kinetics were determined in 9-month-old Bangladeshi infants (n = 10), who were non-wasted [weight-for-length z score (WLZ) >−2], ranging in LAZ from −2.9 to −0.43. Stable isotopes were administered 2 hours after a meal as oral (70Zn) and intravenous (67Zn) tracers. After isotope administration, blood was sampled within 5 hours and all urine and feces were collected for 24 hours. Urine was sampled twice-daily out to 9 days. Data were analyzed by compartmental modeling. Daily zinc intake was estimated by the model as the sum of zinc used for growth plus that lost via urine and feces. Zinc absorbed (the amount required to maintain steady state) was the sum of zinc used for growth plus urine and endogenous fecal excretions. Results: The LAZ score correlated with serum zinc concentration (R = 0.77, P = 0.001), urinary zinc excretion (R = 0.66, P = 0.010), and fractional zinc absorption from calculated daily intake (R = 0.58, P = 0.030). In stunted infants (n = 8), the amount of zinc absorbed did not increase with calculated zinc intake unlike published values for non-stunted infants. Conclusions: Zinc kinetics in Bangladeshi infants correlate with LAZ and show that malabsorption of supplemental sources of zinc may occur in stunted infants.
Conduits in Vascular Pancreatic Surgery

Objectives: We analyze successes and failures of pushing the boundaries in vascular pancreatic surgery to establish safety of conduit reconstructions. Background: Improved systemic control from chemotherapy in pancreatic cancer is increasing the demand for surgical solutions of extensive local vessel involvement, but conduit-specific data are scarce. Methods: We identified 63 implanted conduits (41% autologous vessels, 37% allografts, 18% PTFE) in 56 pancreatic resections of highly selected cancer patients between October 2013 and July 2020 from our prospectively maintained database. Assessed parameters were survival, perioperative complications, operative techniques (anatomic and extra-anatomic routes), and conduit patency. Results: For vascular reconstruction, 25 arterial and 38 venous conduits were utilized during 39 pancreatoduodenectomies, 14 distal pancreatectomies, and 3 total pancreatectomies. The median postoperative survival was 2 years. A Clavien-Dindo grade ≥IIIa complication was apparent in 50% of the patients with a median Comprehensive Complication Index of 29.6. The 90-day mortality in this highly selected cohort was 9%. Causes of mortality were conduit related in 3 patients, late postpancreatectomy hemorrhage in 1 patient, and early liver metastasis in 1 patient. Image-based patency rates of conduits were 66% and 45% at postoperative days 30 and 90, respectively. Conclusions: Our perioperative mortality of vascular pancreatic surgery with conduits in the arterial or venous system is 9%. Reconstructions are technically feasible with different anatomic and extra-anatomic strategies, while identifying predictors of early conduit occlusion remains challenging. Optimizing reconstructed arterial and venous hemodynamics in the context of pancreatic malignancy will enable long-term survival in more patients responsive to chemotherapies.
Age impacts left atrial functional remodeling in athletes

Aim Age-associated changes in cardiac filling and function are well known in the general population. Yet, the effect of aging on left atrial (LA) function, and its interaction with left ventricular (LV) adaptation, remain less described when combined with high-intensity chronic training. We aimed to analyze the effects of aging on LA and LV functions in trained athletes. Methods and results Ninety-five healthy highly-trained athletes referred for resting echocardiography were included. Two groups of athletes were retrospectively defined based on age: young athletes aged <35 years (n = 54), and master athletes aged ≥35 years (n = 41). All subjects were questioned about their sports practice. Echocardiographic analysis of LV systolic and diastolic functions (2D-echo, 3D-echo, and Doppler), as well as LA 2D dimensions and phasic deformations assessed by speckle tracking, were analyzed. Master athletes (mean age = 46.3 ± 8.3 years, mean duration of sustained training = 13.7 ± 8.9 years) exhibited significantly stiffer LV and LA with reduced LV early diastolic functional parameters (ratio E/A, peak e’, and ratio e’/a’), LA reservoir and conduit strain, whereas LA volume, LA contractile strain and LV peak a’ were higher, compared to young athletes. Multivariate regression analysis confirmed that age was predictive of peak e’, LA reservoir strain and LA conduit strain, independently of training variables. LA phasic strains were strongly associated with LV diastolic function. Conclusions Regardless of chronic sports practice, master athletes exhibited age-related changes in LA function closely coupled to LV diastolic properties, which led to LV filling shifts to late diastole.
Therapeutic induction of Bcl2‐associated athanogene 3‐mediated autophagy in idiopathic pulmonary fibrosis

Abstract Background Exaggerated fibroblast proliferation is a well‐known feature in idiopathic pulmonary fibrosis (IPF) which may be – in part – due to insufficient autophagy, a lysosome dependent cellular surveillance pathway. Bcl2‐associated athanogene 3 (BAG3) is a pivotal co‐chaperone of the autophagy pathway. Here, we studied whether therapeutic modulation of BAG3‐mediated autophagy can rescue insufficient autophagy and impact IPF fibroblast proliferation. Methods Primary interstitial fibroblasts or precision cut lung slices (PCLS) of IPF lungs were treated with (1) the antifibrotic drug pirfenidone (Pirf), (2) the demethylating agent 5‐azacytidine (Aza), (3) the BAG3 modulator cantharidin (Ctd). Autophagy flux was measured following pretreatment with the autophagy inhibitors or by GFP‐RFP‐LC3B transfection followed by drug treatments. Proliferation was measured by 5‐bromo‐2′‐deoxyuridine assay. BAG3, filamin C (FLNC), proliferating‐cell‐nuclear‐antigen (PCNA), collagen1A1 (COL1A1) and autophagy proteins were assessed by immunoblotting or immunofluorescence. Loss of function experiments were performed by siRNA mediated knockdown of BAG3. Results In comparison with healthy donors, increased BAG3 protein was observed in IPF lung homogenates and IPF fibroblasts. In addition, the substrate of BAG3‐mediated autophagy, FLNC, was increased in IPF fibroblasts, implying insufficient activation of BAG3‐dependent autophagy. Therapeutic modulation of this pathway using Aza and Ctd alone or in combination with the IPF therapy drug Pirf rescued the insufficient BAG3‐mediated autophagy and decreased fibroblast proliferation. Such effects were observed upon therapeutic modulation of BAG3 but not upon knock down of BAG3 per se in IPF fibroblasts. Similarly, PCLS of IPF patients showed a significant decrease in collagen deposition in response to these drugs, either alone or in a more potent form in combination with Pirf. Conclusions Our study reveals that repurposing drugs that modulate autophagy regulating proteins render therapeutic benefits in IPF. Fine tuning of this pathway may hence signify a promising therapeutic strategy to ameliorate antifibrotic properties and augment the efficacy of current IPF therapy.
Membrane lipid renovation in Pseudomonas aeruginosa ‐ implications for phage therapy?

Abstract Pseudomonas aeruginosa is an important Gram‐negative pathogen with intrinsic resistance to many clinically used antibiotics. It is particularly troublesome in nosocomial infections, immunocompromised patients, and individuals with cystic fibrosis. Antimicrobial resistance (AMR) is a huge threat to global health, with a predicted 10 million people dying from resistant infections by 2050. A promising therapy for combatting AMR infections is phage therapy. However, more research is required to investigate mechanisms that may influence the efficacy of phage therapy. An important overlooked aspect is the impact of membrane lipid remodelling on phage binding ability. P. aeruginosa undergoes changes in membrane lipids when it encounters phosphorus stress, an environmental perturbation that is likely to occur during infection. Lipid changes include the substitution of glycerophospholipids with surrogate glycolipids and the over‐production of ornithine‐containing aminolipids. Given that membrane lipids are known to influence the structure and function of membrane proteins, we propose that changes in the composition of membrane lipids during infection may alter phage binding and subsequent phage infection dynamics. Consideration of such effects needs to be urgently prioritised in order to develop the most effective phage therapy strategies for P. aeruginosa infections.
Basic symptoms of schizophrenia are related to symptoms of traumatic stress: A pivotal role of sensitization. An observational study

Introduction: Subjective cognitive deficits have been broadly reported in schizophrenia and described by Huber as basic symptoms. It remains unclear however to what extent they may be related to psychosocial stressors including trauma. Methods: We assessed basic symptoms using the Frankfurt Complaint Questionnaire (FCQ) in a sample of 40 patients with schizophrenia. Trauma-related symptoms were assessed concurrently using the Trauma Symptom Checklist-40, symptoms of dissociation using the Dissociative Experiences Scale, and sensitization phenomena using the Complex Partial Seizure-like Symptoms Inventory and Limbic System Checklist-33. Psychotic symptoms were measured by Health of the Nation Outcome Scales. The dosage of antipsychotic medication was assessed in terms of equivalents of chlorpromazine, and antidepressant medication in terms of equivalents of fluoxetine. Spearman correlations were performed to explore the relationship between FCQ and other trauma-related measures. To determine the relative contributions of trauma-related symptoms to basic symptoms a linear regression analysis was performed. Results: The results showed that higher levels of basic symptoms of schizophrenia were associated with greater levels of symptoms of dissociation, traumatic stress, and sensitization or kindling-like processes in schizophrenia. Among the trauma-related variables, sensitization phenomena assessed with Complex Partial Seizure-like Symptoms Inventory were closely associated with basic symptoms. Discussion: These results indicate that basic symptoms measured by FCQ might be related to trauma. The potential of trauma to influence neurodevelopmental hypotheses of schizophrenia is discussed.