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Abstract Tumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.

Abstract Spatial and genomic heterogeneity of tumors are crucial factors influencing cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on somatic point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their localization in close to single-cell resolution by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors.

Abstract We continue our work on the light-front formulation of quarkonium γ ∗ γ transition form factors, extending the formalism to J PC = 2++ tensor meson states. We present an analysis of γ ∗ γ → χ c2 transition amplitude and the pertinent helicity form factors. Our relativistic formalism is based on the light-front quark-antiquark wave function of the quarkonium. We calculate the two-photon decay width as well as three independent γ ∗ γ transition form factors for J z = 0, 1, 2 as a function of photon virtuality Q 2. We compare our results for the two-photon decay width to the recently measured ones by the Belle and BES III collaborations. Even when including relativistic corrections, a very small Γ(λ = 0)/Γ(λ = 2) ~ 10 −3 ratio is found which is beyond present experimental precision. We also present the form factors as a function of photon virtuality and compare them to the sparse experimental data on the so-called off-shell width. The formalism presented here can be used for other 2++ mesons, excited charmonia or bottomonia or even light q q ¯ $$ q\overline{q} $$ -mesons.

Background: Yerba mate is a Paraguayan kind of herbal tea prepared from the dried and roasted leaves of trees called Ilex paraguariensis St. Hill. It is known for high content of polyphenols, methylxanthines and saponins. According to the studies products rich in those nutrients may have a positive influence on the humans cardiovascular health. Materials and methods: We reviewed publications obtained from PubMed and Google Scholar. Articles were selected based on keywords such “yerba mate’’, “Ilex paraguariensis’’, “cardiovascular diseases’’. For the final analysis, qualified articles were published from 2005 to 2024. Results: Confirming positive impact on serum lipid levels individuals using mate tea. Long – term positive influence on blood pressure. Moreover subjects with obesity took advantages of Yerba beverage by decreasing waist-to-hip ratio. Patients with diabetes were observed to have a significant reduction in fasting plasma glucose level and HbA1c concentration. Conclusions: Most of the cited researches support the hypothesis of benefits coming from drinking mate infusions for patients with elevated lipid serum levels, obesity, high blood pressure and type 2 diabetes mellitus. All of mentioned health issues can lead to the cardiovascular problems therefore using mate infusions can prevent CVDs. Taking everything into consideration, medical professionals might recommend Yerba mate tea for their patients especially as a replacement of a coffee.

Abstract: Introduction: Regular yoga practice positively affects physical and mental health, including stress reduction, emotional regulation, and cognitive enhancement. Recent research highlights yoga's potential to strengthen the nervous system's adaptability, promoting well-being and managing stress and anxiety. Aim of the study: This review aimed to demonstrate yoga's influence on nervous system adaptability and provide an overview of how yoga practices enhance neuroadaptation, highlighting benefits in improving neural resilience and adaptive capacities. Materials and methods: This paper analyzes current knowledge on the neurological consequences of excessive body weight. The review focused on clinical studies from 2018 to 2024, including review papers and meta-analyses. Literature was reviewed from PubMed and Google Scholar using keywords: “yoga,” “nervous system,” “stress,” “anxiety,” “depression,” “sleep problems,” “Alzheimer's disease,” “Parkinson's disease,” “epilepsy,” and “emotion regulation.” Discussion: Yoga significantly impacts the nervous system's adaptive capacity, improving mental and physical health. Regular practice enhances neuronal plasticity, aiding stress management and cognitive functions. Yoga breathing techniques reduce cortisol levels and increase certain neurotransmitters, regulating mood and autonomic nervous system function. The study did not explore different types of yoga on specific disorders, indicating a need for further research. Conclusions: This paper underscores yoga's role in enhancing the nervous system's adaptive capacity. Yoga shows promise in improving neural resilience and adaptive capacities, making it a valuable holistic healthcare approach. Understanding these benefits can guide healthcare professionals in integrating yoga into strategies to improve patient well-being, emphasizing its role in fostering physical and mental resilience.

Abstract Amyloid proteins are often associated with the onset of diseases, including Alzheimer’s, Parkinson’s and many others. However, there is a wide class of functional amyloids that are involved in physiological functions, e.g., formation of microbial biofilms or storage of hormones. Recent studies showed that an amyloid fibril could affect the aggregation of another protein, even from a different species. This may result in amplification or attenuation of the aggregation process. Insight into amyloid cross-interactions may be crucial for better understanding of amyloid diseases and the potential influence of microbial amyloids on human proteins. However, due to the demanding nature of the needed experiments, knowledge of such interactions is still limited. Here, we present PACT (Prediction of Amyloid Cross-interaction by Threading) - the computational method for the prediction of amyloid cross-interactions. The method is based on modeling of a heterogeneous fibril formed by two amyloidogenic peptides. The resulting structure is assessed by the structural statistical potential that approximates its plausibility and energetic stability. PACT was developed and first evaluated mostly on data collected in the AmyloGraph database of interacting amyloids and achieved high values of Area Under ROC (AUC=0.88) and F1 (0.82). Then, we applied our method to study the interactions of CsgA - a bacterial biofilm protein that was not used in our in-reference datasets, which is expressed in several bacterial species that inhabit the human intestines - with two human proteins. The study included alpha-synuclein, a human protein that is involved in Parkinson’s disease, and human islet amyloid polypeptide (hIAPP), which is involved in type 2 diabetes. In both cases, PACT predicted the appearance of cross-interactions. Importantly, the method indicated specific regions of the proteins, which were shown to play a central role in both interactions. We experimentally confirmed the novel results of the indicated CsgA fragments interacting with hIAPP based on the kinetic characteristics obtained with the ThT assay. PACT opens the possibility of high-throughput studies of amyloid interactions. Importantly, it can work with fairly long protein fragments, and as a purely physicochemical approach, it relies very little on scarce training data. The tool is available as a web server at https://pact.e-science.pl/pact/ . The local version can be downloaded from https://github.com/KubaWojciechowski/PACT .

Abstract We study the exclusive diffractive c c ¯ $$ c\overline{c} $$ photoproduction in ultraperipheral pA collisions. The formalism makes use of off-diagonal generalizations of the unintegrated gluon distribution, the so-called generalized transverse momentum dependent distributions (GTMDs). We present two different formulations. The first one is based directly on gluon GTMD parametrizations in momentum space. Another option is the calculation of the GTMD as a Fourier transform of the dipole-nucleon scattering amplitude N(Y, r → $$ \overrightarrow{r} $$ ⊥, b → $$ \overrightarrow{b} $$ ⊥). The latter approach requires some extra regularization discussed in the paper. Different dipole amplitudes from the literature are used. Compared to previous calculations in the literature, we integrate over the full phase space and therefore cross sections for realistic conditions are obtained. We present distributions in rapidity of c or c ¯ $$ \overline{c} $$ , transverse momentum of the c c ¯ $$ c\overline{c} $$ pair, four-momentum transfer squared as well as the azimuthal correlation between a sum and a difference of the c and c ¯ $$ \overline{c} $$ transverse momenta. The azimuthal correlations are partially due to the so-called elliptic gluon Wigner distribution. Different models lead to different modulations in the azimuthal angle. The modulations are generally smaller than 5%. They depend on the range of transverse momentum selected for the calculation.

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and cells’ ability to neutralize them by antioxidant systems. The role of oxidative stress in hypertrophic cardiomyopathy (HCM) is not fully understood. The aim of the study was to examine selected parameters of oxidative stress in patients with HCM compared to the control group. We enrolled 85 consecutive HCM patients and 97 controls without HCM. The groups were matched for sex, the body mass index, and age. Oxidative stress markers included superoxide dismutase (SOD), ceruloplasmin (CER), and lipofuscin (LPS). The median age of the HCM patients was 53 (40–63) years, and 41.2% of them were male. HCM patients, compared to the control ones, had significantly increased levels of CER and LPS. The areas under the receiver operating characteristics curves (AUC) indicated a good discriminatory power of CER (AUC 0.924, sensitivity 84%, and specificity 88%), an acceptable discriminatory power of LPS (AUC 0.740, sensitivity 66%, and specificity 72%), and poor discriminatory power of SOD (AUC 0.556, sensitivity 34%, and specificity 94%) for HCM detection. CER with good predictive strength, as well as LPS with acceptable predictive power, allows for HCM detection. The utility of SOD for HCM detection is limited.

Neuralgic amyotrophy(NA), is a rare and highly variable neurological disorder of unknown aetiology that causes serious diagnostic problems. We described a case of NA with atrophy of the brachialis muscle in order to enrich clinicians’ knowledge about this disorder and to help them in the proper diagnosis of NA. A 21-year-old man presented with sudden, severe pain in the right biceps muscle. The man had consultations with several doctors and physiotherapists. Three magnetic resonance imaging (MRI) examinations, a nerve conduction study (NCS) and needle electromyography (EMG) were performed. Only after 6 months, based on medical history, physical examination and ultrasound imaging (USI), the physiotherapist suggested NA, which was later on confirmed by a neurologist. This case description of NA showed a variety of symptoms that made it difficult to establish an accurate diagnosis for a longer period of time. The diagnostic procedure, as well as the prolonged time between the onset of symptoms and diagnosis, indicates the need for further education of clinicians to better understand the symptoms of NA.

Introduction and purpose: Apples are a widely consumed fruit globally and are known to be a great source of nutrition. Studies have shown that apples contain high levels of antioxidants, dietary fiber, and vitamins that contribute to numerous health benefits. This paper aims to provide a comprehensive review of the impact of apples on human health. State of knowledge: The paper reviews the current literature on the health benefits of apples, focusing on their impact on various health conditions such as cancer, cardiovascular diseases, diabetes, and obesity. Additionally, it examines the role of apples in improving intestinal, immune, and cognitive function. The paper also discusses the potential mechanisms by which apples exert their health benefits, such as high levels of flavonoids, polyphenols, and dietary fiber. Summary: In conclusion, the vast body of evidence reviewed in this paper supports the notion that consuming apples regularly can contribute to better health outcomes. They may help reduce the risk of chronic diseases, such as cancer, cardiovascular diseases, and diabetes, as well as promote healthy gut microbiota and immune function. Despite the controversy surrounding the use of pesticides in apple cultivation, the benefits of consuming apples outweigh the risks. Therefore, it is highly recommended to include apples as part of a balanced and nutritious diet to promote optimal health and wellbeing. As the saying goes, "An apple a day keeps the doctor away".

Introduction and purpose: The human body hosts a diverse ecosystem of commensal microbes, known as the human microbiome. This review aims to asses the current state of knowledge regarding the effectiveness, mechanisms of action, and potential benefits of probiotic supplementation in patients with inflammatory bowel diseases. Materials and methods: A literature review was conducted using the “PubMed” and “Google Scholar” databases with the keywords “Probiotics”, “Gut Microbiome”, “Probiotics and the treatment of Crohns Disease”, “Probiotics and the treatment of Colitis Ulcerosa”. State of knowledge: Dysbiosis is known to disrupt the function of the intestinal mucosis and has been associated with chronic tissue inflammation. The use of probiotics is a promising method to improve the state of gut microbiota. It is known that the gut microbiome is disrupted in inflammatory bowel diseases. Summary: The use of probiotics in Ulcerative Colitis is supported by a significant amount of evidence supporting its effectiveness. In the case of Crohn’s Disease there is a lack of evidence to definitively determine whether the use of probiotics yields therapeutic benefits. Therefore there is a need for further research in this area.

Abstract Spatial transcriptomics maps gene expression across tissues, posing the challenge of determining the spatial arrangement of different cell types. However, spatial transcriptomics spots contain multiple cells. Therefore, the observed signal comes from mixtures of cells of different types. Here, we propose an innovative probabilistic model, Celloscope, that utilizes established prior knowledge on marker genes for cell type deconvolution from spatial transcriptomics data. Celloscope outperforms other methods on simulated data, successfully indicates known brain structures and spatially distinguishes between inhibitory and excitatory neuron types based in mouse brain tissue, and dissects large heterogeneity of immune infiltrate composition in prostate gland tissue.

Abstract Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp.

Abstract Background Osteoarthritis (OA) is one of the most commonly recorded diseases in clinical practice. Vibration therapy has been suggested for the treatment of knee OA. The purpose of the study was to determine the impact of vibrations of variable frequency and low amplitude on pain perception and mobility in patients suffering from knee OA. Methods Thirty-two participants were allocated into two groups – Group 1 (oscillatory cycloidal vibrotherapy-OCV) and Group 2—control (sham therapy). The participants were diagnosed with moderate degenerative changes in the knee (grade II based on the Kellgren-Lawrence (KL) Grading Scale). Subjects received 15 sessions of vibration therapy and sham therapy respectively. Pain, range of motion, and functional disability were assessed through Visual Analog Scale (VAS), Laitinen questionnaire, goniometer (ROM – range of motion), timed up and go test (TUG) and Knee Injury and Osteoarthritis Outcome Score (KOOS). Measurements were taken at baseline, after the last session and four weeks after the last session (follow up). T-test and U-Mann Whitney test compare baseline characteristics. The Wilcoxon and ANOVA tests compared mean VAS, Laitinen, ROM, TUG and KOOS. The significant P-value was less than 0.05. Results After 3 weeks (15 sessions) of vibration therapy, reduced the sensation of pain and improved mobility was recorded. There was a more significant improvement in the vibration therapy group than the control group in pain alleviation on VAS scale (p

Low-temperature plasma production is possible as a result of photoionization using high-intensity extreme ultraviolet (EUV) and soft X-ray (SXR) pulses. Plasma of this type is also present in outer space, e.g., aurora borealis. It also occurs when high-velocity objects enter the atmosphere, during which period high temperatures can be produced locally by friction. Low-temperature plasma is also formed in an ambient gas surrounding the hot laser-produced plasma (LPP). In this work, a special system has been prepared for investigation of this type of plasma. The LPP was created inside a chamber filled with a gas under a low pressure, of the order of 1–50 mbar, by a laser pulse (3–9 J, 1–8 ns) focused onto a gas puff target. In such a case, the SXR/EUV radiation emitted from the LPP was partially absorbed in the low-density gas. In this case, high- and low-temperature plasmas (Te ~100 eV and ~1 eV, respectively) were created locally in the chamber. Investigation of the EUV-induced plasmas was performed mainly using spectral methods in ultraviolet/visible (UV/VIS) light. The measurements were performed using an echelle spectrometer, and additionally, spatial–temporal measurements were performed using an optical streak camera. Spectral analysis was supported by the PGOPHER numerical code.

Abstract Prokineticin 1 (PROK1) is a pleiotropic factor secreted by endocrine glands; however, its role has not been studied in the corpus luteum (CL) during pregnancy in any species. The present study aimed to investigate the contribution of PROK1 in regulating processes related to porcine CL function and regression: steroidogenesis, luteal cell apoptosis and viability, and angiogenesis. The luteal expression of PROK1 was greater on Days 12 and 14 of pregnancy compared to Day 9. PROK1 protein expression during pregnancy increased gradually and peaked on Day 14, when it was also significantly higher than that on Day 14 of the estrous cycle. Prokineticin receptor 1 (PROKR1) mRNA abundance increased on Days 12 and 14 of pregnancy, whereas PROKR2 elevated on Day 14 of the estrous cycle. PROK1, acting via PROKR1, stimulated the expression of genes involved in progesterone synthesis, as well as progesterone secretion by luteal tissue. PROK1–PROKR1 signaling reduced apoptosis and increased the viability of luteal cells. PROK1 acting through PROKR1 stimulated angiogenesis by increasing capillary-like structure formation by luteal endothelial cells and elevating angiogenin gene expression and VEGFA secretion by luteal tissue. Our results indicate that PROK1 regulates processes vital for maintaining luteal function during early pregnancy and the mid-luteal phase.

Abstract Antimicrobial peptides emerge as compounds that can alleviate the global health hazard of antimicrobial resistance, prompting a need for novel computational approaches to peptide generation. Here, we propose HydrAMP, a conditional variational autoencoder that learns lower-dimensional, continuous representation of peptides and captures their antimicrobial properties. The model disentangles the learnt representation of a peptide from its antimicrobial conditions and leverages parameter-controlled creativity. HydrAMP is the first model that is directly optimized for diverse tasks, including unconstrained and analogue generation and outperforms other approaches in these tasks. An additional preselection procedure based on ranking of generated peptides and molecular dynamics simulations increases experimental validation rate. Wet-lab experiments on five bacterial strains confirm high activity of nine peptides generated as analogues of clinically relevant prototypes, as well as six analogues of an inactive peptide. HydrAMP enables generation of diverse and potent peptides, making a step towards resolving the antimicrobial resistance crisis.

In the spring of 2017, amateur metal detectorists discovered a Late Bronze Age hoard near the village of Kaliska, Poland. Comprising over 120 artefacts, it is one of the most impressive Bronze Age finds within Pomerania. The authors discuss the hoard's contents and context, as well as its chronology. Keywords: Poland, Late Bronze Age, bronze hoard, bronze-age metalwork, Introduction Kaliska is a small village near the town of Bialy Bor, Szczecinek County, West Pomeranian Voivodeship, Poland. It is situated between the hilly moraines of Pojezierze Szczecineckie and the [...]

This study explores the capability of machine learning techniques (MLTs) in predicting IAQ in apartments. Sensor data from kitchen air monitoring were used to determine the conditions in the living room. The analysis was based on several air parameters—temperature, relative humidity, CO2 concentration, and TVOC—recorded in five apartments. Multiple input–multiple output prediction models were built. Linear (multiple linear regression and multilayer perceptron (MLP)) and nonlinear (decision trees, random forest, k-nearest neighbors, and MLP) methods were investigated. Five-fold cross-validation was applied, where four apartments provided data for model training and the remaining one was the source of the test data. The models were compared using performance metrics (R2, MAPE, and RMSE). The naive approach was used as the benchmark. This study showed that linear MLTs performed best. In this case, the coefficients of determination were highest: R2 = 0.94 (T), R2 = 0.94 (RH), R2 = 0.63 (CO2), R2 = 0.84 (TVOC, based on the SGP30 sensor), and R2 = 0.92 (TVOC, based on the SGP30 sensor). The prediction of distinct indoor air parameters was not equally effective. Based on the lowest percentage error, best predictions were attained for indoor air temperature (MAPE = 1.57%), relative humidity (MAPE = 2.97%RH), and TVOC content (MAPE = 0.41%). Unfortunately, CO2 prediction was loaded with high error (MAPE = 20.83%). The approach was particularly effective in open-kitchen apartments, and they could be the target for its application. This research offers a method that could contribute to attaining effective IAQ control in apartments.

The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed 85 heart transplant candidates who were hospitalized at our institution for right heart catheterization. Ten milliliters of coronary sinus blood was collected to measure oxidative/antioxidative markers. The median age was 58 (50–62) years, and 90.6% of them were male. The one-year mortality rate was 40%. Multivariable logistic regression analysis revealed that ceruloplasmin (OR = 1.342 [1.019–1.770], p = 0.0363; per unit decrease), catalase (OR = 1.053 [1.014–1.093], p = 0.0076; per unit decrease), and creatinine (OR = 1.071 [1.002–1.144], p = 0.0422; per unit increase) were independently associated with one-year mortality. Ceruloplasmin, catalase, and creatinine had areas under the curve of 0.9296 [0.8738–0.9855], 0.9666 [0.9360–0.9971], and 0.7682 [0.6607–0.8756], respectively. Lower ceruloplasmin and catalase in the coronary sinus, as well as higher creatinine in peripheral blood, are independently associated with one-year mortality in patients with advanced HF. Catalase and ceruloplasmin have excellent prognostic power, and creatinine has acceptable prognostic power, allowing the distinction of one-year survivors from nonsurvivors.

Here the authors discover that SET1 complexes function as transcription anti-termination factors that bind to CpG islands and protect low to moderately transcribed genes from the pervasive termination activity of the ZC3H4 complex.

Remote robotic interventions and maintenance tasks are frequently required in hazardous environments. Particularly, missions with a redundant mobile manipulator in the world’s most complex machine, the CERN Large Hadron Collider (LHC), are performed in a sensitive underground environment with radioactive or electromagnetic hazards, bringing further challenges in safety and reliability. The mission’s success depends on the robot’s hardware and software, and when the tasks become too unpredictable to execute autonomously, the operators need to make critical decisions. Still, in most current human-machine systems, the state of the human is neglected. In this context, a novel 3D Mixed Reality (MR) human-robot interface with the Operator Monitoring System (OMS) was developed to advance safety and task efficiency with improved spatial awareness, advanced manipulator control, and collision avoidance. However, new techniques could increase the system’s sophistication and add to the operator’s workload and stress. Therefore, for operational validation, the 3D MR interface had to be compared with an operational 2D interface, which has been used in hundreds of interventions. With the 3D MR interface, the execution of precise approach tasks was faster, with no increased workload or physiological response. The new 3D MR techniques improved the teleoperation quality and safety while maintaining similar effects on the operator. The OMS worked jointly with the interface and performed well with operators with varied teleoperation backgrounds facing a stressful real telerobotic scenario in the LHC. The paper contributes to the methodology for human-centred interface evaluation incorporating the user’s physiological state: heart rate, respiration rate and skin electrodermal activity, and combines it with the NASA TLX assessment method, questionnaires, and task execution time. It provides novel approaches to operator state identification, the GUI-OMS software architecture, and the evaluation of the 3D MR techniques. The solutions can be practically applied in mission-critical applications, such as telesurgery, space robotics, uncrewed transport vehicles and semi-autonomous machinery.