Body Response Research Articles

Factors Affecting Neutrophil Functions During Sepsis: Human Microbiome and Epigenetics.

Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense anti-bacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation and play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There's a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps (NETs) is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis where dysbiosis may occur. We highlight the importance of deciphering neutrophil's functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for sepsis diagnostic method when used in combination with the cell-free DNA (cfDNA). Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cfDNA, could serve as biomarkers for the early detection of sepsis.

The Insight Meditation Enhanced Stress, Depression, and Anxiety Reduction in Working Professionals Like Medical Representatives Determined by Using Serum Cortisol Level and Electroencephalogram: A Qualitative Study

The Indian pharmaceutical industry is one of the fastest-growing sectors of the Indian economy and ranks among the top 15 drug-manufacturing countries globally. Among the fastest-growing industries in the world, the pharmaceutical industry has increased over the years. A pharmaceutical company appoints a medical representative to make their products easily reach healthcare specialists and then be used by the general public. The medical representatives construct a well- built network with doctors, clinical specialists, medical practitioners, paramedical experts, Dietitians and nutritionists, paediatricians, gynaecologists, psychiatrists, etc. The problem of stress is widespread in every job description, and it may affect directly or indirectly in the form of health issues and low productivity; the demands of achieving targets induced among medical representatives. Much of this credit goes to Medical Sales Representatives or Pharmaceutical Sales Representatives (also known as MR, PSR) who are solely responsible for the promotion of products among Physicians, Hospitals, and pharmacies and are accountable for sales results. They act as the face of the Pharma company contributing to a better quality of life for customers, building goodwill, and increasing the company’s market share. Pharmaceutical sales representatives (PSR) play a large role in helping an industry in a rapidly changing environment to achieve a new corporate vision and normally these medical representatives are in the highest stress position. Most pharmaceutical sales representatives experience significant job stress and unhappiness levels. Stress, depression, and anxiety are the most common psychiatric disorders all over the world. One of India's oldest meditation methods, vipassana also known as Insight meditation, helps a person become aware of things as they are. The goal of the Vipassana method, which aids in self-change via self-observation, is to finally arrive at a condition of inner and exterior peace and mental equilibrium. It is a process of "Self- exploration" to the normal base of the brain and body that removes mental smog and results in a healthier personality filled with love and empathy. Electroencephalography (EEG) is an efficient modality that helps to acquire brain signals corresponding to various states from the scalp surface area. These signals are generally categorized as delta, theta, alpha, beta, and gamma based on signal frequencies ranging from 0.1 Hz to more than 100 Hz. This paper primarily focuses on EEG signals and their characterization for various states of the human body. Beta wave induced the production of cortisol. Also, the beta wave is necessary for our everyday lives, such as thought, communicating, arguing, and problem-solving, during conscious mental work. This Beta wave can also lead to tension, anxiety, and restlessness as they enable us to think properly. Persistently elevated cortisol concentrations are associated with metabolic disorders. Cortisol is a vital hormone sometimes known as the stress hormone in humans, as it is involved in the body's natural response to physical or emotional stress. cortisol has effects on memory, mood, and neurological diseases. Cortisol is best known for mediating the body’s reaction to stress. This study aims to review the existing research and challenges of serum cortisol levels (cortisol is an indicator of stress) and EEG signals with the Insight meditation effect.

Discovery of the Clinical Candidate IDOR-1117-2520: A Potent and Selective Antagonist of CCR6 for Autoimmune Diseases.

Migration of immune cells to sites of inflammation is a critical step in the body's response to infections but also during autoimmune flares. Chemokine receptors, members of the GPCR receptors, are instrumental in directing specific cell types to their target organs. Herein, we describe a highly potent small molecule antagonist of the chemokine receptor CCR6, which came out of fine-tuned structural elaborations from a proprietary HTS hit. Three main issues in the parent chemical series-cytotoxicity, phototoxicity, and hERG, were successfully solved. Biological characterization demonstrated that compound 45 (IDOR-1117-2520) is a selective and insurmountable antagonist of CCR6. In vivo proof-of-mechanism studies in a mouse lung inflammation model using a representative compound from the chemical class of 45 confirmed that the targeted CCR6+ cells were efficiently inhibited from migrating into the bronchoalveoli. Finally, ADMET and physicochemical properties were well balanced and the preclinical package warranted progress in the clinic.

Long-term thermal stress induces hepatic injury and alters the thermotolerance response in Hong Kong catfish (Clarias fuscus)

Global climate change has a significant impact on fish survival and the aquaculture industry. Even highly adaptable organisms like Siluriformes fish are susceptible to these effects. This study investigates the consequences of extreme high temperature on Hong Kong catfish (Clarias fuscus), a species known for its long-term habitation in tropical and subtropical regions. In this study, C. fuscus were cultivated for 90 days at high temperature (HT, 34 °C) and normal temperature (NT, 26 °C), followed by subjecting the two groups to high temperature stress (34 °C) and temperature recovery (26 °C). The hepatic histology, biochemical, and transcriptomic characteristics of the species were examined before acute high temperature stress (NT-C, HT-C), after acute high temperature stress (NT-T, HT-T), and after temperature recovery (NT-R, HT-R). The histological analysis revealed that long-term heat stress damaged the liver tissue of C. fuscus. Furthermore, significant damage was observed in the liver tissues of the NT group under acute high temperature stress, while no further damage was observed in the HT group. The biochemical analysis showed that 90 days of heat stress altered the body's immune and oxidative balance, resulting in an increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and a decrease in malondialdehyde (MDA) content. Upon acute heat stress, the liver function of the NT group was disordered and unable to produce enough total-bilirubin (T-BIL), while the aspartate aminotransferase (AST) activity of the HT group was more susceptible to being affected. Long-term heat stress led to significant changes in gene expression, with the NT group showing three times more differentially expressed genes (DEGs) identified in the liver compared to the HT group under acute heat stress conditions. Analysis of DEG enrichment during the same treatment period in both groups revealed significant differences in amino acid metabolism and lipid metabolism pathways. These results suggest that long-term heat stress caused liver tissue damage in C. fuscus, altering immune and oxidative balance, enzyme activity sensitivity, as well as the body's response to acute heat stress pathways and intensity. This study lays the groundwork for future investigations into fish adaptability to sudden temperature changes and aquaculture strategies to mitigate heat stress in fish facing extreme temperatures.

Pain of Threatened Self: Explicit and Implicit Self-Esteem, Cortisol Responses to a Social Threat and Pain Perception.

Background: Rejection, injustice, and exclusion from meaningful interpersonal relationships are often extremely painful and stress-generating experiences. This study aimed to define the role of explicit and implicit self-esteem in pain perception as a component of the physiological-psychological system that regulates the body's response to stress associated with the threat of social rejection. Methods: In total, 360 individuals participated in this study. The measurement of cortisol in saliva, the assessment of pain thresholds using thermal stimuli, the IAT to assess implicit self-esteem, and a questionnaire on global self-esteem and social pain were used. The study included three measurements: baseline and 15 and 45 min after the application of a laboratory socially threatening stimulus (the Trier Social Stress Test). Results: People experiencing chronic social pain (CSP) are more likely to have fragile self-esteem, higher pain thresholds, and tend to experience reduced pain tolerance in situations of acute social threat than people without CSP experience. In people with CSP and fragile self-esteem, after the introduction of a social threat, an increase in pain tolerance was observed along with a longer-lasting increase in cortisol levels. Conclusions: Fragile self-esteem, along with feelings of chronic exclusion, injustice, and rejection, may prolong stress reactions and produce a hypoalgesic effect.

Investigation on similitude method for dynamic response of high-speed train body considering thickness distortion

Small-scale model test is an economical and efficient method to study the collision process analysis and crashworthiness design of full-scale high-speed trains. For high-speed trains, the vehicle body thickness of scaled train models is too small to be processed, resulting in thickness distortion. Although the distorted model can predict dynamic responses of the full-scale model, there are some errors in predicting the dynamic response parameters. This article proposes a new similitude distortion method to improve the prediction accuracy of the high-speed train body distorted model. First, the complete similitude relationship for train collisions was derived using dimensional analysis. According to the Buckingham π theory, the theoretical expression between prediction coefficient and distortion coefficient was obtained when the high-speed train thickness distortion occurred. Then, based on a full-scale high-speed train body prototype, the benchmark model and distorted model were established. Numerical simulation was used to explore the relationship between prediction coefficient and distortion coefficient. Finally, the distorted similar model was established using the similitude distortion method. The accuracy and feasibility of this approach were verified by comparing and analysing the dynamic response curves obtained by numerical simulations between the distorted similar model and prototype. The errors of the maximum displacement and deceleration were 2.70% and 8.26%. The results show that the similitude distortion method is reliable to relate dynamic responses of scaled models to the prototype when the vehicle body thickness distorts.

Abstract PO4-03-06: Body mass index and response to neoadjuvant chemo-immunotherapy among women with primary triple negative breast cancer

Abstract Background: Elevated body mass index (BMI) is associated with lower rates of pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with breast cancer. The addition of PD-1 receptor inhibition with pembrolizumab to neoadjuvant chemotherapy is now considered the standard of care for patients with stage II or III triple negative breast cancer (TNBC) based on results from the KEYNOTE-522 (KN-522) trial. In other cancer types such as melanoma and lung cancer, patients with overweight/obesity have better survival outcomes following treatment with immunotherapy compared to patients with normal weight, despite a higher incidence of any-grade immune-related adverse events (irAEs). Whether BMI is associated with differential response and toxicity in patients with TNBC treated with neoadjuvant chemo-immunotherapy is unknown. Methods: Patients with stage II-III TNBC treated with neoadjuvant chemotherapy plus pembrolizumab per the KN-522 regimen from 8/2021 – 9/2022 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Patient characteristics, tumor characteristics, treatments, surgical pathology information, and irAEs were abstracted from medical records. pCR was defined as absence of invasive or in situ carcinoma in breast and axillary node tissue surgical specimens. BMI was categorized per standard definitions: underweight/normal weight < 25 kg/m2, overweight 25-29.9 kg/m2, and obese >=30 kg/m2. Wilcoxon rank sum tests, Pearson’s chi-squared tests, and Kendall rank correlation tests were used to test associations between variables. Results: 143 patients were included in this study. 57 patients (39.8%) were underweight/normal weight, 46 (32.2%) were overweight, and 40 (28.0%) were obese. Overall, 79/143 patients (55.2%) experienced a pCR. Among patients with a pCR, median BMI was 26.3 kg/m2 (interquartile range [IQR] 23.1-30.5 kg/m2); among patients without a pCR, median BMI was 26.1 kg/m2 (IQR 23.6-30.0 kg/m2; p >0.9). There was no significant association between BMI category and pCR (p=0.9). Overall, 63/143 (44%) of patients experienced an irAE; 42 (29.4%) required treatment for an irAE. There were no associations between BMI and the incidence (p=0.5) or frequency (p=0.7) of irAEs. Conclusions: In this TNBC cohort treated with neoadjuvant chemo-immunotherapy, BMI was not associated with rates of pCR or irAEs. These findings highlight the divergent impact of BMI on immunotherapy response across cancer types. Confirmatory studies in independent cohorts are needed. Citation Format: Sherry Shen, Sara Myers, Yuan Chen, Stephanie Downs-Canner, Nour Abuhadra, Tiffany Traina, Mark Robson, Neil Iyengar. Body mass index and response to neoadjuvant chemo-immunotherapy among women with primary triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-06.

Materials Strategies to Overcome the Foreign Body Response.

The foreign body response (FBR) is an immune-mediated reaction that can occur with most biomaterials and biomedical devices. The FBR initiates a deterioration in the performance of implantable devices, representing a longstanding challenge that consistently hampers their optimal utilization. Over the last decade, significant strides are achieved based on either hydrogel design or surface modifications to mitigate the FBR. This review delves into recent material strategies aimed at mitigating the FBR. Further, the authors look forward to future novel anti-FBR materials from the perspective of clinical translation needs. Such prospective materials hold the potential to attenuate local immune responses, thereby significantly enhancing the overall performance of implantable devices.

WHAT ABOUT THIS?: Quick Somatic Rescue Techniques when Stressed

When threats are perceived, our thoughts and body respond almost immediately with defense reactions that may negatively affect us and others we know. Described are approaches that can interrupt negative stress responses and allow us to become calmer and less reactive by utilizing a set of somatic and breathing practices that assist in raising self-awareness as well as moderating the triggers and interrupting the cascades of stress reactions. Each of the specific practices can be introduced quickly, even in situations in which mental health first aid is indicated. For example, the practices introduce the S.O.S 1™ technique, an adapted Nyingma stress reduction exercise, and several breathing exercises, such as box breathing, sniff and sniff breathing, humming, and toning. The various practices are aimed at reducing or stopping over-reactive thoughts and body responses as well as increasing a sense of safety and control that allows you to think more clearly about difficult situations.

Exploring the tidal responses of ocean worlds with PyALMA3

Observations of the tidal response of celestial bodies quantified by the Love numbers are highly relevant in planetary geophysical investigations because they provide unique insight into the interior structures. For example, the high sensitivity of tidal deformations to the properties of the oceans detected beneath the icy surfaces of some moons is of paramount importance for investigations of their habitability. We present here PyALMA3, a software framework developed in Python devoted to the computation of planetary Love numbers. PyALMA3 is based on ALMA3, a previous version developed in Fortran. Conversion to Python significantly improves the accessibility and portability of the software. We tested PyALMA3 by applying it to the exploration of the tidal responses of Europa and the other Galilean moons. We show that accurate modeling of effects such as the viscoelastic deformations of ice and the water density gradient in the ocean (variations of 2−3% on the real part of k2) will be important in the context of geophysical investigations that will be conducted by future missions targeting icy moons, such as Europa Clipper and JUICE.

Meta-analysis reveals that the effects of precipitation change on soil and litter fauna in forests depend on body size.

Anthropogenic climate change is altering precipitation regimes at a global scale. While precipitation changes have been linked to changes in the abundance and diversity of soil and litter invertebrate fauna in forests, general trends have remained elusive due to mixed results from primary studies. We used a meta-analysis based on 430 comparisons from 38 primary studies to address associated knowledge gaps, (i) quantifying impacts of precipitation change on forest soil and litter fauna abundance and diversity, (ii) exploring reasons for variation in impacts and (iii) examining biases affecting the realism and accuracy of experimental studies. Precipitation reductions led to a decrease of 39% in soil and litter fauna abundance, with a 35% increase in abundance under precipitation increases, while diversity impacts were smaller. A statistical model containing an interaction between body size and the magnitude of precipitation change showed that mesofauna (e.g. mites, collembola) responded most to changes in precipitation. Changes in taxonomic richness were related solely to the magnitude of precipitation change. Our results suggest that body size is related to the ability of a taxon to survive under drought conditions, or to benefit from high precipitation. We also found that most experiments manipulated precipitation in a way that aligns better with predicted extreme climatic events than with predicted average annual changes in precipitation and that the experimental plots used in experiments were likely too small to accurately capture changes for mobile taxa. The relationship between body size and response to precipitation found here has far-reaching implications for our ability to predict future responses of soil biodiversity to climate change and will help to produce more realistic mechanistic soil models which aim to simulate the responses of soils to global change.

The Relationship between Sport and Stress in Medical Faculty Student Students Malang Muhammadiyah University

Medical students are prone to experiencing stress during the lecture period due to the demands of the learning process. Women experience stress more easily than men due to a higher body response to stress. Exercise is known to help reduce stress because it stimulates the release of endorphins in the body. The purpose of this study was to determine whether there is a relationship between sports activity and stress in female students at the Faculty of Medicine, University of Muhammadiyah Malang. The research was conducted in January 2021 with a sample of 127 people and was taken using the technique of purposive sampling, that is, female students who are sampled must comply with the inclusion and exclusion criteria. Data was collected using a questionnaire (Godin-Shepard). Leisure Time Physical Activity and Depression, Anxiety, and Stress Scale (THAT)-21 The results of data analysis using the Kruskal-Wallis test show a value of p = 0.614 (p > 0.05), which indicates that there is no relationship between sports activity and stress levels in female students at the Faculty of Medicine, University of Muhammadiyah Malang

Insights on Microsomal Prostaglandin E2 Synthase 1 (mPGES-1) Inhibitors using Molecular Dynamics and MM/PBSA Calculations

Background: Despite being a normal body response against invading agents, inflammation, when exaggerated, needs to be controlled to minimize damage to the body. There are several drugs in clinical use against inflammation and other inflammatory conditions. Still, side effects often limit the use of these drugs, such as gastrointestinal effects generated by COX-1 inhibitors and cardiovascular effects by COX-2 inhibitors. Thus, exploring new targets such as mPGES-1 may lead to discovering agents that are more selective against inflammation and generate fewer side effects. Objectives: Here, docking, molecular dynamics, and MM-PBSA studies were performed on a dataset of known mPGES-1 inhibitors to identify helpful information and discover new mPGES-1 inhibitors. Methods: Molecular docking in GOLD software was used to obtain the complexes used in Molecular dynamics simulations (GROMACS software), performed to generate the RMSD, RMSF, Rg, SASA, and H-bond plots to predict the complexes' stability. The most stable conformation was analyzed regarding the most important interactions of the compounds. Finally, MM-PBSA calculations using the tool g_mmpbsa in GROMACS software were performed to determine de-binding affinity, interaction parameters, and per-residue contribution. Results: The main findings of this work were that the molecular dynamics simulation was able to find the open conformation of mPGES-1, which showed a greater preference on compounds in this region, consisting of residues known as "gateways". All compounds showed stability and stable complex formation with mPGES-1, as demonstrated by the results of RMSD, RMSF, Rg, SASA, and H-bond plots generated in a molecular dynamics simulation at 100 ns. The molecular dynamics identified three preferential sites of interaction for the compounds. Thus, the docking and dynamics protocols showed greater affinity of these compounds for cavity-02, interacting with Leu85, Pro81, Gln134, Cys137, Ala138, and Ala141. On the other hand, compound 09 preferred the cavity-03 of the protein, interacting mainly with His72 through Hbond. In addition, MM-PBSA calculations showed binding energies of up to -220,113 KJ/mol for compound 04. Furthermore, MM-PBSA could identify which electrostatic interactions are the most prevalent in the complex formation of the compounds with the highest affinity (04 and 07). Still, the van der Waals interactions are the most important for the others. Finally, the energy contribution per-residue revealed Lys120, Arg122, Arg126, and Tyr130 as the most important for the formation of the complexes. Conclusion: Design mPGES-1 inhibitors based on the residues Leu85, Pro81, Gln134, Cys137, Ala138, and Ala141, in addition to Lys120, Arg122, Arg126, and Tyr130 can provide new promising drugs useful against diseases involving inflammatory conditions.

Time delays between physiological signals in interpreting the body's responses to intermittent hypoxia in obstructive sleep apnea.

Intermittent hypoxia, the primary pathology of obstructive sleep apnea (OSA), causes cardiovascular responses resulting in changes in hemodynamic parameters such as stroke volume (SV), blood pressure (BP), and heart rate (HR). However, previous studies have produced very different conclusions, such as suggesting that SV increases or decreases during apnea. A key reason for drawing contrary conclusions from similar measurements may be due to ignoring the time delay in acquiring response signals. By analyzing the signals collected during hypoxia, we aim to establish criteria for determining the delay time between the onset of apnea and the onset of physiological parameter response. &#xD;Approach. We monitored oxygen saturation (SpO2), transcutaneous oxygen pressure (TcPO2), and hemodynamic parameters SV, HR, and BP, during sleep in 66 patients with different OSA severity to observe body's response to hypoxia and determine the delay time of above parameters. Data were analyzed using the Kruskal-Wallis test, Quade test. and Spearman test.&#xD;Main Results. We found that simultaneous acquisition of various parameters inevitably involved varying degrees of response delay (7.12 - 25.60 seconds). The delay time of hemodynamic parameters was significantly shorter than that of SpO2 and TcPO2 (p < 0.01). OSA severity affected the response delay of SpO2, TcPO2, SV, MBP, and HR (p < 0.05). SV delay time was negatively correlated with the apnea-hypopnea index (r = -0.4831, p < 0.0001).&#xD;Significance. The real body response should be determined after removing the effect of delay time, which is the key to solve the problem of drawing contradictory conclusions from similar studies. The methods and important findings presented in this study provide key information for revealing the true response of the cardiovascular system during hypoxia, indicating the importance of proper signal analysis for correctly interpreting the cardiovascular hemodynamic response phenomena and exploring their physiological and pathophysiological mechanisms.

Conjugation of IL-33 to Microporous Annealed Particle Scaffolds Enhances Type 2-Like Immune Responses in Vitro and in Vivo.

The inflammatory foreign body response (FBR) is the main driver of biomaterial implant failure. Current strategies to mitigate the onset of a FBR include modification of the implant surface, release of anti-inflammatory drugs, and cell-scale implant porosity. The microporous annealed particle (MAP) scaffold platform is an injectable, porous biomaterial composed of individual microgels which are annealed in situ to provide a structurally stable scaffold with cell-scale microporosity. MAP scaffold does not induce a discernible foreign body response in vivo and, therefore, can be used a "blank canvas" for biomaterial-mediated immunomodulation. Damage associated molecular patterns (DAMPs), such as IL-33, are potent regulators of type 2 immunity that play an important role in tissue repair. In this manuscript, we conjugate IL-33 to the microgel building-blocks of MAP scaffold to generate a bioactive material (IL33-MAP) capable of stimulating macrophages in vitro via a ST-2 receptor dependent pathway and modulating immune cell recruitment to the implant site in vivo which indicates an upregulation of a type 2-like immune response and downregulation of a type 1-like immune response. This article is protected by copyright. All rights reserved.

Random dynamic response analysis of an asphalt concrete core wall dam on deep overburden with double random factors

The spatial variability of material parameters and the randomness of ground motion are factors that influence the seismic response of a dam. To obtain more reliable seismic response results, it is crucial to study the influence of various uncertain factors on the response to earthquakes. In this paper, the K-L series expansion method and LH sampling technique are combined to characterize the spatial correlation of material parameters using a Gaussian autocorrelation function. This allows for the simulation of random fields of material parameters. By improved the Clough-Penzien power spectrum model and incorporating the concept of a random function, it becomes possible to generate nonstationary random ground motion that accurately reflects the site conditions. Taking an asphalt concrete core dam on deep overburden as an example, a random dynamic response analysis was conducted, considering various random factors. Statistical analysis and distribution testing were conducted on the horizontal acceleration and vertical permanent deformation responses. The process of the evolution of the probability density of the horizontal acceleration at the top of the dam was determined using the generalized probability density evolution method. This method helps to reveal the influence of various random factors on the response of the dam body. The research results show that among the spatial variability of material parameters and the randomness of ground motions, the randomness of ground motions is the main influencing factor of the random response results of the dam body. The mean response of two random factors is significantly larger than that of a single random factor. When considering dual random factors simultaneously, the complexity of the random factors increases, resulting in statistical properties that differ from those of single random factors. Therefore, to obtain more reliable random seismic response results, it is necessary to consider both the spatial variability of material parameters and the randomness of ground motions.

[Infections and fever].

Fever can be due to infectious or noninfectious causes and results from the body's natural response to exogenous or endogenous pyrogens. Laboratory tests including complete blood count, differential blood count, C‑reactive protein, erythrocyte sedimentation rate and procalcitonin do not have sufficient sensitivity and specificity to definitively detect or rule out an infectious (bacterial, viral, parasitic) cause of fever. Blood cultures should be carried out when bacteremic or septic illnesses are suspected. Fever is not always present in infections and can be absent, especially in older and immunocompromised patients. If fever is suspected, core temperatures should be taken, e.g., rectally, orally or invasively. Depending on the clinical situation, infectious causes must be excluded as the most likely cause of an acutely occurring fever. The investigation of long-standing fever (fever of unknown origin, FUO) can be complex and some infectious diseases should first be ruled out, whereby asyndromic classification often helps to clarify the cause of the fever.

Hybrid Materials for Vascular Applications: A Preliminary In Vitro Assessment

The production of biomedical devices able to appropriately interact with the biological environment is still a great challenge. Synthetic materials are often employed, but they fail to replicate the biological and functional properties of native tissues, leading to a variety of adverse effects. Several commercial products are based on chemically treated xenogeneic tissues: their principal drawback is due to weak mechanical stability and low durability. Recently, decellularization has been proposed to bypass the drawbacks of both synthetic and biological materials. Acellular materials can integrate with host tissues avoiding/mitigating any foreign body response, but they often lack sufficient patency and impermeability. The present paper investigates an innovative approach to the realization of hybrid materials that combine decellularized bovine pericardium with polycarbonate urethanes. These hybrid materials benefit from the superior biocompatibility of the biological tissue and the mechanical properties of the synthetic polymers. They were assessed from physicochemical, structural, mechanical, and biological points of view; their ability to promote cell growth was also investigated. The decellularized pericardium and the polymer appeared to well adhere to each other, and the two sides were distinguishable. The maximum elongation of hybrid materials was mainly affected by the pericardium, which allows for lower elongation than the polymer; this latter, in turn, influenced the maximum strength achieved. The results confirmed the promising features of hybrid materials for the production of vascular grafts able to be repopulated by circulating cells, thus, improving blood compatibility.

Self-supervised learning of T cell receptor sequences exposes core properties for T cell membership.

The T cell receptor (TCR) repertoire is an extraordinarily diverse collection of TCRs essential for maintaining the body's homeostasis and response to threats. In this study, we compiled an extensive dataset of more than 4200 bulk TCR repertoire samples, encompassing 221,176,713 sequences, alongside 6,159,652 single-cell TCR sequences from over 400 samples. From this dataset, we then selected a representative subset of 5 million bulk sequences and 4.2 million single-cell sequences to train two specialized Transformer-based language models for bulk (CVC) and single-cell (scCVC) TCR repertoires, respectively. We show that these models successfully capture TCR core qualities, such as sharing, gene composition, and single-cell properties. These qualities are emergent in the encoded TCR latent space and enable classification into TCR-based qualities such as public sequences. These models demonstrate the potential of Transformer-based language models in TCR downstream applications.

Exploring the impact of arginine-supplemented immunonutrition on length of stay in the intensive care unit: A retrospective cross-sectional analysis.

Arginine-supplemented enteral immunonutrition has been designed to optimize outcomes in critical care patients. Existing formulas may be isocaloric and isoproteic, yet differ in L-arginine content, energy distribution, and in source and amount of many other specialized ingredients. The individual contributions of each may be difficult to pinpoint; however, all cumulate in the body's response to illness and injury. The study objective was to compare health outcomes between different immunonutrition formulas. Real-world data from October 2015 -February 2019 in the PINC AI™ Healthcare Database (formerly the Premier Healthcare Database) was reviewed for patients with an intensive care unit (ICU) stay and ≥3 days exclusive use of either higher L-arginine formula (HAF), or lower L-arginine formula (LAF). Multivariable generalized linear model regression was used to check associations between formulas and ICU length of stay. 3,284 patients (74.5% surgical) were included from 21 hospitals, with 2,525 receiving HAF and 759 LAF. Inpatient mortality (19.4%) and surgical site infections (6.2%) were similar across groups. Median hospital stay of 17 days (IQR: 16) did not differ by immunonutrition formula. Median ICU stay was shorter for patients receiving HAF compared to LAF (10 vs 12 days; P<0.001). After adjusting for demographics, visit, severity of illness, and other clinical characteristics, associated regression-adjusted ICU length of stay for patients in the HAF group was 11% shorter [0.89 (95% CI: 0.84, 0.94; P<0.001)] compared to patients in the LAF group. Estimated adjusted mean ICU length of stay was 9.4 days (95% CI: 8.9, 10.0 days) for the HAF group compared to 10.6 days (95% CI: 9.9, 11.3 days) for the LAF group (P<0.001). Despite formulas being isocaloric and isoproteic, HAF use was associated with significantly reduced ICU length of stay, compared to LAF. Higher arginine immunonutrition formula may play a role in improving health outcomes in primarily surgical critically ill patients.