Classification and severity progression measure of COVID-19 patients using pairs of multi-omic factors.

Early detection and effective treatment of severe COVID-19 patients remain two major challenges during the current pandemic. Analysis of molecular changes in blood samples of severe patients is one of the promising approaches to this problem. From thousands of proteomic, metabolomic, lipidomic, and transcriptomic biomarkers selected in other research, we identify several pairs of biomarkers that after additional nonlinear spline transformation are highly effective in classifying and predicting severe COVID-19 cases. The performance of these pairs is evaluated in-sample, in a cross-validation exercise, and in an out-of-sample analysis on two independent datasets. We further improve our classifier by identifying complementary pairs using hierarchical clustering. In a result, we achieve 96-98% AUC on the validation data. Our findings can help medical experts to identify small groups of biomarkers that after nonlinear transformation can be used to construct a cost-effective test for patient screening and prediction of severity progression.

Real-time emotion detection by quantitative facial motion analysis.

BACKGROUND: Research into mood and emotion has often depended on slow and subjective self-report, highlighting a need for rapid, accurate, and objective assessment tools. METHODS: To address this gap, we developed a method using digital image speckle correlation (DISC), which tracks subtle changes in facial expressions invisible to the naked eye, to assess emotions in real-time. We presented ten participants with visual stimuli triggering neutral, happy, and sad emotions and quantified their associated facial responses via detailed DISC analysis. RESULTS: We identified key alterations in facial expression (facial maps) that reliably signal changes in mood state across all individuals based on these data. Furthermore, principal component analysis of these facial maps identified regions associated with happy and sad emotions. Compared with commercial deep learning solutions that use individual images to detect facial expressions and classify emotions, such as Amazon Rekognition, our DISC-based classifiers utilize frame-to-frame changes. Our data show that DISC-based classifiers deliver substantially better predictions, and they are inherently free of racial or gender bias. LIMITATIONS: Our sample size was limited, and participants were aware their faces were recorded on video. Despite this, our results remained consistent across individuals. CONCLUSIONS: We demonstrate that DISC-based facial analysis can be used to reliably identify an individual's emotion and may provide a robust and economic modality for real-time, noninvasive clinical monitoring in the future.

Osteotropic Effect of Parenteral Obesity in Programmed Male Rats Fed a Calorically Differentiated Diet during Growth and Development.

The experiment was undertaken to assess whether the continuation or change of the parents' diet affects the previously programmed bone metabolism of the male offspring during its growth and development. A total of 16 male and 32 female Wistar rats were divided into groups and fed a standard (diet S) or high-energy (diet F). After the induction of obesity, the rats from groups S and F, as the parent generation, were used to obtain male offspring, which were kept with their mothers until the weaning day (21 days of age). In our earlier study, we documented the programming effects of the diet used in parents on the skeletal system of offspring measured on the weaning day. Weaned male offspring constitute one control group-parents and offspring fed the S diet. There were three experimental groups, where: parents received diet S and offspring were fed with the F diet; parents were treated with the diet F, while offspring received the S diet; and parents and offspring were fed with the diet F. The analyses were performed at 49 and 90 days of life. After sacrifice, cleaned-off soft tissue femora were assessed using peripheral quantitative computed tomography (pQCT), dual X-ray absorptiometry (DXA), and a three-point bending test. We observed that changing and continuation of nutrition, applied previously in parents, significantly influenced the metabolism of the bone tissue in male offspring, and the osteotropic effects differed, depending on the character of the nutrition modification and age. Additionally, an important conclusion of our study, regarding the previous, is that nutrition modification, affecting the metabolism of bone tissue, also depends on the sex.

Effect of bisphosphonates on selected markers of bone turnover in patients after total knee arthroplasty.

PURPOSE: Osteoporosis is a problem for many patients after total knee arthroplasty (TKA). The aseptic loosening of the prosthesis is also a significant problem. Therefore, in these patients, bisphosphonates (BPs) are used that, by influencing the level of bone turnover markers, reduce the risk of osteoporotic fractures and aseptic revisions in TKA. The purpose of the study was to assess whether the Pamifos® present in bone cement has any effect on the level of selected bone turnover markers and cytokines in patients after total knee arthroplasty. METHODS: The study group consisted of 30 women with degenerative changes of the knee joint, whose total knee prosthesis was stabilized with cement enriched with Pamifos®. The control group consisted of 30 women treated for degenerative changes of the knee joint without the use of bisphosphonate-enriched cement for prosthetic stabilization. RESULTS: In the study group, we found a decrease in tumour necrosis factor (TNF-α) levels 12 weeks after surgery, whereas the control group experienced an almost twofold increase in TNF-α level. The concentration of OPG, a natural RANKL antagonist, was highest in patients of the study group six weeks after surgery and was four times higher compared to the control group. Statistically significant differences were found in the RANKL level (P < 0.05). In the control group, there was a continuous increase in RANKL concentration from the first to the 12th week after surgery. The highest level of RANKL in patients of the study group was found six weeks after the surgery, and 12 weeks after knee arthroplasty, it was significantly lower. It was found that the concentration of osteocalcin (OC) in the study group was the lowest three weeks after the surgery, then it increased and remained at a similar level after 12 weeks. The concentrations of selected cytokines (IL-1ß, IL-2, IL-6, IL-10, IL-17AF) also showed statistically significant differences. CONCLUSIONS: The BP-stimulated increase in the level of OPG and the decrease in the level of RANKL, as well as the impact on the level of the analyzed interleukins in the bone microenvironment, may be an important element of the mechanisms limiting bone resorption. Therefore, the use of BP-enriched cement implants appears to be justified.

The programming effect of parenteral obesity on the structural and mechanical properties of femora in female rats fed a varied calorie diet during puberty.

The study was aimed to ascertain whether continuation or change in the offspring of the diet consumed by the parents modulates, in later life, the previously programmed bone metabolism. We used adult Wistar rats (16 males; 32 females), divided into groups that were fed either a standard (diet S) or a high-energy (diet F). After 90 days of obesity induction, the rats were submitted to obtain female offspring from parents S and F. The offspring stayed with their mothers until 21 days of age (weaning day). Our previous studies have proved the programming effects of parental obesity on the skeletal system of their offspring at the age of 21 days. Weaned female offspring were divided into groups: S/S-parents and offspring fed the S diet; S/F-parents fed the S diet and offspring fed the F diet; F/S-parents fed the diet F and offspring with the diet S; F/F-parents and offspring fed the F diet (F/F). After sacrifice, isolated femurs were assessed by peripheral quantitative computed tomography and by a three-point bending test. The bones were examined at 49 and 90 days of life. We found that nutritional programming has a significant influence on the development and metabolism of the skeletal system in females during growth and maturity. Moreover, the modification of nutrition alters the metabolism of bone tissue, and the osteotropic effects vary depending on the nature of the change, as well as the stage of development. Reducing the caloric content of the diet inhibits the mineralization and decreases the mechanical strength of the bones while increasing the caloric content of the diet has a beneficial osteotropic effect.

Lipoic acid (LA) dose-dependently protects bone losses in the mandible of rats during the development of osteopenia by inhibiting oxidative stress and promoting bone formation.

Our study was carried out to evaluate the effect of lipoic acid (LA) on the densitometric properties, structure and mechanical strength of the mandible of Wistar rats with developing osteopenia. The study used 42 sham-operated (SHO) and ovariectomized (OVX) rats. The OVX rats were randomly divided (n = 6) onto two controls treated subcutaneously with physiological saline (OVX-PhS) and 17ß-estradiol (OVX-E2), respectively, and onto four experimental OVX groups that received LA in the doses of 12.5, 25, 50 and 100 mg/kg/day for 28 days. The results demonstrated that the lack of estrogen brought about osteopenic bone changes, especially in the trabecular compartment. In addition, while the usage of LA in the doses of 12.5 and 25 LA had no effect in OVX rats, the dose of 100 effectively inhibited osteopenic changes of the mandible. This dose maintained structural, densitometric and mechanical parameters at levels like that in the SHO and OVX-E2 groups by inhibiting the destructive influence of oxidative stress. Dose 50, however, was revealed to be the most effective. It not only inhibited atrophic changes and the influence of oxidative stress, but also stimulated the formation of mandibular bone tissue. Our results suggest that the administration of LA is effective in preventing atrophic changes in the mandibular bone tissue in conditions of ovarian hormone deficiency and suggest its potential in the therapy of osteoporosis.

Evaluation of long-term surgical treatment outcomes of thoraco-lumbar spinal fractures - follow-up period of over 10 years.

INTRODUCTION AND OBJECTIVE: Agricultural accidents often result in spinal injuries, particularly in fractures of the thoraco-lumbar spine. Surgical treatment of thoraco-lumbar fractures continues to comprise a major medical problem. The aim of this study was to assess and compare the long-term effects of surgical treatments of thoracic and lumbar spinal fractures treated with transpedicular stabilization, combined with posterior interbody spinal fusion (PLIF, also known as spondylodesis) or Daniaux reconstruction. MATERIAL AND METHODS: A retrospective analysis was conducted on 66 patients with a thoracic or lumbar spinal fracture (Th10-L3) type A in the AO classification system, operated in 2000-2005. All patients underwent a short segment transpedicular stabilization, which in 36 patients was combined with posterior interbody spinal fusion, and in 30 other patients combined with Daniaux reconstruction. Radiological assessment was performed based on X-ray imaging. A lateral X-ray image of the spine was used to measure the vertebral wedging angle of the fractured vertebrae, the height ratio of the anterior to posterior vertebral body, and the angle of segmental kyphotic deformation. Subjective long-term assessment of the patient was conducted using the Oswestry Instability Score. The results were analyzed for statistical significance. RESULTS: In both groups, similar improvements in all measured parameters were observed. Despite all patients losing some of the correction in the long-term, this loss was significantly smaller following Daniaux reconstruction. CONCLUSIONS: Spinal stabilization combined with vertebral reconstruction allows for long-term and improved treatment results for thoraco-lumbar fracture than posterior interbody spinal fusion (spondylodesis).

Programming Effect of the Parental Obesity on the Skeletal System of Offspring at Weaning Day.

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.

Bone losses in obese, ovariectomized rats appear to be independent from sclerostin-induced inhibition of the Wnt/ß-catenin pathway.

INTRODUCTION: Overweight and obesity, as well as a gonadal function, are pivotal factors influencing bone tissue metabolism. MATERIAL AND METHODS: The aim of the study was to determine the effect of dietary induced obesity (DIO) on bone tissue metabolism in sham-operated (SHO) or ovariectomized (OVX) adult female Wistar rats. Additionally, the influence of DIO in SHO or OVX on the concentration of sclerostin in the blood serum was analyzed. After SHO or OVX, the rats were placed in groups (n=8) and either received a standard diet (11.5 MJ/kg) (SHO-CON; OVX-CON) or a high-energy diet (17.6 MJ/kg) (SHO-FAT; OVX-FAT). The experiment lasted for 90 days and allowed for the establishment of osteopenia in OVX females and obesity in the rats that had received the high-energy diet. RESULTS: The results of the study demonstrate that obesity or/and ovariectomy increases the resorption of femora and tibiae, hence decreasing the densitometric and mechanical parameters affecting the bone structure in adult females rats. The strongest osteodegenerative effect was seen in the OVX-FAT females. Interestingly, the degree of bone tissue degradation caused exclusively by ovariectomy was similar to that found in the obese sham-operated rats. CONCLUSIONS: Bone losses invoked by DIO seem to be independent from the Wnt/ß-catenin pathway inhibition induced by sclerostin. While further study is necessary, the obtained results suggest that the usage of sclerostin anti-body in the treatment of osteoporosis can be ineffective, and in obese patients the undertaking of such therapy should be reassessed.

[THE ROLE OF PHILOSOPHICAL REFLECTIONS OF STANISLAW ZAREMBA IN THE CONTEXT OF A DISPUTE ON THE FOUNDATIONS OF THE THEORY OF RELATIVITY]. / ROLA REFLEKSJI FILOZOFICZNYCH STANISLAWA ZAREMBY W KONTEKSCIE SPORU O PODSTAWY TEORII WZGLEDNOSCI.

The aim of this paper is to present the philosophical background of Stanislaw Zaremba's critique of Einstein's theory of relativity. In the 1920s, Zaremba was the most prominent Polish opponent of this theory. His papers influenced some discussions related to Einstein's theory, especially in France and in Poland. This paper takes also into account the development of Zaremba's critique. The analysis of his papers shows that he never became a follower of the Einstein's theory of relativity. Such a statement compels us to confront it with the previous interpretations of Zaremba's thought.

Natural killer-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia: intracellular cytokine expression and relationship with clinical outcome.

The clinical significance of NK-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia (CLL) is still a subject of controversy. There are few previous descriptions that this cell population can be qualitatively or quantitatively deficient in CLL patients. In the present study we investigated the clinical value of CD3+/CD16+ CD56+ cells as predictors of disease progression. We assessed the frequencies of CD3+/CD16+CD56+ cells by the flow cytometry in a group of 300 CLL patients. The percentage of CD3+/CD16+CD56+ cell population expressed as the percentage of CD3+ lymphocyte compartment showed an inverse correlation with ZAP-70 and CD38. Additionally, the CD3+/CD16+CD56+ showed an inverse correlation with LPL/ADAM29 ratio. Likewise, the ability of these cells to cytokine expression correlated with ZAP-70 expression. A positive correlation between percentage CD3+/CD16+CD56+ cells and TFS was found. The decreased percentage of these cells was associated with higher death risk in CLL patients. Furthermore, the percentage of CD3+/CD16+CD56+ cells was significantly decreased in patients who showed progression of disease. This study suggests that assessment of CD3+/CD16+ CD56+ cells may be helpful in determining a worsening of clinical course. Monitoring of these cell numbers and function may provide useful information for determining disease activity. Especially, it could be intormative to look at these cells in patients with stage 0 CLL. For this patient group immunological control and dysfunction are probably important factors.