Point Of No Return Research Articles

Early Rise and Persistent Inhibition of Electromyography during Failed Stopping.

Reactively canceling movements is a vital feature of the motor system to ensure safety. This behavior can be studied in the laboratory using the stop-signal task. There remains ambiguity about whether a "point-of-no-return" exists, after which a response cannot be aborted. A separate question concerns whether motor system inhibition associated with attempted stopping persists when stopping is unsuccessful. We address these two questions using electromyography (EMG) in two stop-signal task experiments. Experiment 1 (n = 24) involved simple right and left index finger responses in separate task blocks. Experiment 2 (n = 28) involved a response choice between the right index and pinky fingers. To evaluate the approximate point of no return, we measured EMG in responding fingers during the 100 msec preceding the stop signal and observed significantly greater EMG amplitudes during failed than successful stopping in both experiments. Thus, EMG before the stop signal differentiated success, regardless of whether there was a response choice. To address whether motor inhibition persists after failed stopping, we assessed EMG peak-to-offset durations and slopes (i.e., rate of EMG decline) for go, failed stop, and successful stop (partial response) trials. EMG peak-to-offset was shorter and steeper for failed stopping compared to go and successful stop partial response trials, suggesting motor inhibition persists even when failing to stop. These findings indicate EMG is sensitive to a "transition zone" at which the relative likelihood of stop failure versus success inverts and also suggest peak-to-offset time of response-related EMG activity during failed stopping reflects stopping-related inhibition.

Pathogenesis and potential reversibility of intestinal metaplasia - a milestone in gastric carcinogenesis.

Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of Helicobacter pylori; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. Helicobacter pylori eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy. Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after Helicobacter pylori eradication.

Prevención en el neonato de enfermedades que cursan con daño cerebral irreversible, derecho humano

Since the 1960s, my scientific activity has focused on the diagnosis and treatment of metabolic diseases, rare pathologies which, in some cases, cause irreversible brain damage. “Irreversible” is the word that should trigger all preventive efforts and ensure widespread screening. Its prevention implies early diagnosis and treatment. The fundamental objective was to detect avoidable hereditary diseases in newborns, which generally lead to irreversible mental retardation. In a short time, accompanied by the “luck of the bold”, we detected a first case of phenylketonuria and the pilot plan was set up, which led to its successive implementation throughout Spain and participation in specialised international meetings was initiated, as well as biochemical and genetic research, to contribute to scientific knowledge of such an important aspect of preventive medicine. As with any social, environmental or clinical phenomenon, it is necessary to apply treatment in time before the alteration that is to be avoided occurs, particularly when irreversible situations are involved. On several occasions I have referred to the need to act in a timely manner in order to stop the process at stages prior to the point of no return (ethics of time). Every day I feel more and more strongly, and I try to express it in this way, that the search for, dissemination and application of knowledge is the most beautiful task offered to man’s terrible perplexity, astonishment, doubt and fear. I remember that a few months after finishing my degree in Pharmacy, when I was starting to work in Prof. Santos Ruiz’s laboratory, I visited an institution for the mentally handicapped. There, on that day, many things in my life took root. Other things were erased by the force of that memory. And the feeling that it is necessary to contribute to alleviating and making the life of man, the only being aware of the great gift of life, more bearable, became more intense and urgent. In 2023, on the 75th anniversary of the Universal Declaration of Human Rights, I proposed to the United Nations, through its High Commissioner for Human Rights, Mr. Volker Turk, the recognition as a human right of the prevention of diseases that cause irreversible neurological damage and requested their help in the processing of this new human right. We then asked all governments, institutions and scientific societies to support the proposal to declare as a human right the prevention through neonatal screening of pathologies in which irreversible damage can be avoided through early treatment. It is now necessary to promote a conscious citizenship that is not a spectator of what is happening, but an actor for the progressive and urgent elimination of risks that affect humanity without further remedy. At last, human beings are gradually recognising that they are equal in dignity and can express themselves freely. Now we can. Now we must. The creative capacity that distinguishes the human species encourages us and gives us hope.

Abstract 6002: Increased ferroptosis sensitivity and epithelial to mesenchymal transition of breast cancer cells overcoming chemotherapeutic mediated apoptotic caspase activation

Abstract The survival of cancer cells post chemotherapeutic treatment can lead to the presence of recurrent tumors and continues to be a barrier to effective cancer treatment. The majority of chemotherapeutics kill cells through the induction of executioner caspases and subsequent apoptotic death, and resistance to apoptosis can lead to the presence of anastatic cancer cells. Executioner caspase release was previously thought to be the point of no return from apoptotic cell death, however, it has been shown that removal of the reagent causing caspase release can lead to recovery of cells from apoptotic signaling, a phenomenon which has been termed ``Anastasis``. This presents a need for a better understanding of the underlying mechanisms behind cancer cell survival and the mechanisms that lead to cell recovery and recurrent tumors. We have hypothesized that when treated with chemotherapeutics, some cells will evade cell death even when executioner caspases have been activated. By identifying surviving anastatic cells and the pathways involved in their evasion of cell death, we hope to propose novel therapeutic strategies to prevent their survival. The novel CasExpress system, developed by the Denise Montell lab group, was used to identify and isolate a population of cells surviving caspase-3 activation as a result of chemotherapeutic treatment in Triple Negative Breast Cancer (TNBC) cell lines. The CasExpress system permanently labels these cells with GFP post caspase-3 activation. Analysis of this population of SUM159 anastatic cells, identified by their GFP expression, demonstrates that these cells have an increased resistance to further chemotherapeutic treatment, a decrease in levels of active caspase-3, an up-regulation of Cancer Stem Cell marker CD44, and a more mesenchymal phenotype. Furthermore, these “anastatic cells” express decreased levels of GPX-4, an enzyme that mitigates ferroptosis via lipid peroxide reduction, and are more sensitive to GPX-4 and xCT inhibitor mediated ferroptosis cell death.To investigate the link between Epithelial to Mesenchymal Transition (EMT) and ferroptosis mediated cell death, we used TGF-b to stimulate EMT in NMe mouse epithelial cells. We found that TGF-b induced EMT is associated with increased sensitivity to ferroptosis mediated by GPX-4 inhibition. Furthermore, the TGF-b induced EMT cells have a marked decrease in the expression of GPX4, similar to what was observed in the TNBC anastatic cells. These results indicate a potential link between EMT and an increased sensitivity to ferroptosis, and provide novel strategies for identifying and targeting chemotherapeutic resistant tumor cells. Citation Format: Rachel Hausman, Wells Brown, Paul McDonald, Shannon Awrey, Gongping Sun, Denise Montell, Shoukat Dedhar. Increased ferroptosis sensitivity and epithelial to mesenchymal transition of breast cancer cells overcoming chemotherapeutic mediated apoptotic caspase activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6002.

I'm the same, I'm the same, I'm trying to change: Investigating the role of human information behavior in view change

AbstractInformation is powerful; it can influence peoples' views and, in turn, their behavior. Much recent research and discussion on the role information plays in view change has focused on filter bubbles, echo chambers and misinformation and how they might influence what people think and how they act. However, no prior work has focused specifically on understanding the human information behavior (HIB) that drives and facilitates view change. We report findings from interviews with 18 people who recently changed views on issues they considered important. We found a tight symbiotic relationship between HIB and view change; passive information encountering sparked change, often spurring follow‐up active seeking and verification which progressed the change to a “point of no return,” supported making the change and reinforced the decision to change. When shared, information that contributed to the change sometimes sparked changes in others (as did expressing or debating the change), serving as an information encounter that perpetuated a cycle of HIB and view change. This understanding of the integral role of HIB in view change can inform policy and systems design to promote view change autonomy and a broader research agenda of understanding HIB to support democratic principles and values.

Adaptive responses of feeding and swimming behaviors in black rockfish, Sebastes schlegelii, under starvation at juvenile and young stages

Starvation is a ubiquitous stress that many fish species have to cope with. To investigate the behavioral responses under this pressure in the fry stage, black rockfish (Sebastes schlegelii) at juvenile (29 days of age, 15.2 ± 1.0 mm in total length) and young (51 days of age, 40.3 ± 1.2 mm in total length) stages were starved for 12 and 21 days, respectively. During these two periods of starvation, the starved and routinely fed individuals (serving as the control group) were sampled to be analyzed the variations in growth, survival, feeding activity, swimming ability (cruise and burst), and diet transition process. The results indicated that juveniles were more sensitive to hunger, and the point of no return (PNR) was approximately 5.5 days (19 ℃ in water temperature). In contrast, the young fish had a significantly higher tolerance to starvation because the survival rate after 21 days of starvation was still higher than 99% (20 ℃). The total length and body weight of juveniles and young fish showed different degrees of negative growth. After the starvation for 1 day, the juveniles’ feeding activity on shrimps increased significantly (p < 0.05), while their cruising speed and time changed insignificantly. Similar results were observed in young fish been starved for 1–3 days. With the prolongation of starvation, however, both the feeding and cruising activities of black rockfish became significantly lower than those of the control groups (p < 0.05). The burst swimming ability did not seem to be affected by starvation time. Although the short-term starvation would not increase the young fish’s predation on shrimp, it might be serviceable for improving their feeding vitality. These behavioral results would help us understand the adaptive processes and response mechanisms of fish under starvation.

Allometric Growth Pattern and Hunger Tolerance of Hemibarbus maculatus Bleeker Larvae.

To clarify the allometric growth pattern and hunger tolerance of Hemibarbus maculatus Bleeker larvae, the morphological lengths of their functional organs were measured continuously and their primary feeding rates under a state of starvation were studied. A control group and starvation group were set up for this study, and 10 larvae were sampled from each group every day in order to study their allometric growth pattern and starvation tolerance. The results indicated that the Hemibarbus maculatus larvae opened their mouths for feeding at 4 days after hatching, and that the yolk sac disappeared completely at 11 days after hatching. The Hemibarbus maculatus larvae preferentially developed their heads, fins, and eyes, related to the functions of feeding, balancing, and swimming, in order to cope with complex environments. The growth inflection points for the head length, pectoral fin length, dorsal fin length, eye diameter, eye spacing, snout length, and body height were characterized by total lengths of 10.93 mm, 11.67 mm, 11.67 mm, 13.17 mm, 16.53 mm, 15.13 mm, and 15.13 mm, respectively. Prior to and following the inflection point, positive allometric growth was observed in all organs. After the inflection point, the dorsal fin continued to maintain positive allometric growth, while the others changed to isometric allometric growth. A growth inflection point was not observed for trunk length or the lengths of the tail and anal fins. The trunk length always maintained negative allometry, while the tail and anal fin lengths were reversed. The growth inflection point of the tail length was at a total length of 13.68 mm. Before and after the growth inflection point, negative and isometric allometric growths were observed, respectively. According to the relationship between the total length and number of days after hatching, the growth inflection point of the Hemibarbus maculatus larvae was concentrated at TL = 10.93-16.53 mm, which was observed 14-20 days after hatching. The point of no return for the Hemibarbus maculatus larvae was 12-13 days after hatching, and the ratio of days after hatching in the mixed trophic period to the endotrophic period was 1.75, indicating that the larvae had strong hunger tolerance. Therefore, when considering a water temperature of 22.66 ± 1.56 °C, 4-5 days after hatching is the best time to cultivate in the pond, and it should not be carried out later than 12 days after hatching.

Unpacking the point of no return under drought in poplar: insight from stem diameter variation.

A specific, robust threshold for drought-induced tree mortality is needed to improve the prediction of forest dieback. Here, we tested the relevance of continuous measurements of stem diameter variations for identifying such a threshold, their relationship with hydraulic and cellular damage mechanisms, and the influence of growth conditions on these relationships. Poplar saplings were grown under well-watered, water-limited, or light-limited conditions and then submitted to a drought followed by rewatering. Stem diameter was continuously measured to investigate two parameters: the percentage loss of diameter (PLD) and the percentage of diameter recovery (DR) following rewatering. Water potentials, stomatal conductance, embolism, and electrolyte leakage were also measured, and light microscopy allowed investigating cell collapse induced by drought. The water release observed through loss of diameter occurred throughout the drought, regardless of growth conditions. Poplars did not recover from drought when PLD reached a threshold and this differed according to growth conditions but remained linked to cell resistance to damage and collapse. Our findings shed new light on the mechanisms of drought-induced tree mortality and indicate that PLD could be a relevant indicator of drought-induced tree mortality, regardless of the growth conditions.

Up the stairway leading down. Towards the prospects of an american-centric modeling of world development

The modern world has changed, continuing to transform in a crisis-like manner in all significant parameters. The fact that the former world system has passed the point of no return is a geopolitical reality. The objective need to reformat the world order is an immutable imperative of the time. The geopolitical status of the US as a hegemon is becoming a thing of the past. The key centers of power are shifting towards non-Western countries. But the reliance on power dominance has not disappeared from the US foreign policy strategy.

Temporal gene signature of myofibroblast transformation in Peyronie's disease: first insights into the molecular mechanisms of irreversibility.

Transformation of resident fibroblasts to profibrotic myofibroblasts in the tunica albuginea is a critical step in the pathophysiology of Peyronie's disease (PD). We have previously shown that myofibroblasts do not revert to the fibroblast phenotype and we suggested that there is a point of no return at 36hours after induction of the transformation. However, the molecular mechanisms that drive this proposed irreversibility are not known. Identify molecular pathways that drive the irreversibility of myofibroblast transformation by analyzing the expression of the genes involved in the process in a temporal fashion. Human primary fibroblasts obtained from tunica albuginea of patients with Peyronie's disease were transformed to myofibroblasts using transforming growth factor beta 1 (TGF-β1). The mRNA of the cells was collected at 0, 24, 36, 48, and 72hours after stimulation with TGF-β1 and then analyzed using a Nanostring nCounter Fibrosis panel. The gene expression results were analyzed using Reactome pathway analysis database and ANNi, a deep learning-based inference algorithm based on a swarm approach. The study outcome was the time course of changes in gene expression during transformation of PD-derived fibroblasts to myofibroblasts. The temporal analysis of the gene expression revealed that the majority of the changes at the gene expression level happened within the first 24hours and remained so throughout the 72-hour period. At 36hours, significant changes were observed in genes involved in MAPK-Hedgehog signaling pathways. This study highlights the importance of early intervention in clinical management of PD and the future potential of new drugs targeting the point of no return. The use of human primary cells and confirmation of results with further RNA analysis are the strengths of this study. The study was limited to 760 genes rather than the whole transcriptome. This study is to our knowledge the first analysis of temporal gene expression associated with the regulation of the transformation of resident fibroblasts to profibrotic myofibroblasts in PD. Further research is warranted to investigate the role of the MAPK-Hedgehog signaling pathways in reversibility of PD.

De-obstruction of bladder outlet in humans reverses organ remodelling by normalizing the expression of key transcription factors

BackgroundBenign prostatic hyperplasia in elderly males often causes bladder outlet obstruction termed benign prostatic obstruction (BPO). BPO induces lower urinary tract symptoms and quantifiable urodynamic alterations in bladder function. When conservative medical treatments are exhausted, surgical interventions like transurethral resection of the prostate (TURP) are employed for bladder outlet de-obstruction. Elucidating the molecular changes in the human bladder resulting from BPO and their reversal post-de-obstruction is pivotal for defining the “point of no return”, when the organ deterioration becomes irreversible. In this study we carried out a comprehensive molecular and urodynamic characterization of the bladders in men with BPO before TURP and 3 months after the relief of obstruction.MethodsWe report integrated transcriptome and proteome analysis of bladder samples from male patients with BPO before and 3 months after de-obstruction surgery (TURP). mRNA and protein profiles were correlated with urodynamic findings, specifically voiding detrusor pressure (PdetQmax) before TURP. We delineated the molecular classifiers of each group, pointing at the different pre-TURP bladder status.ResultsAge-matched patients with BPO without DO were divided into two groups based on the PdetQmax values recorded by UDI before de-obstruction: high and medium pressure (HP and MP) groups. Three months after de-obstruction surgery, the voiding parameters PdetQmax, Qmax and RV were significantly improved in both groups, without notable inter-group differences in the values after TURP. Patients with high PdetQmax showed less advanced remodeling and inflammatory changes than those with lower values. We detected significant dysregulation of gene expression, which was at least partially reversed by de-obstruction in both patients’ groups. Transcription factor SOX21 and its target thrombospondin 4 (THBS4) demonstrated normalization post-TURP.ConclusionsOur findings reveal substantial yet incomplete reversal of cell signalling pathways three months after TURP, consistent with improved urodynamic parameters. We propose a set of biomarker genes, indicative of BPO, and possibly contributing to the bladder changes. This study unveils the stages of progressive obstruction-induced bladder decompensation and offers insights into selecting an optimal intervention point to mitigate loss of contractility.

ERCC1 abundance is an indicator of DNA repair-apoptosis decision upon DNA damage

DNA repair is essential for successful propagation of genetic material and fidelity of transcription. Nucleotide excision repair (NER) is one of the earliest DNA repair mechanisms, functionally conserved from bacteria to human. The fact that number of NER genes vary significantly between prokaryotes and metazoans gives the insight that NER proteins have evolved to acquire additional functions to combat challenges associated with a diploid genome, including being involved in the decision between DNA repair and apoptosis. However, no direct association between apoptosis and NER proteins has been shown to date. In this study, we induced apoptosis with a variety of agents, including oxaliplatin, doxorubicin and TRAIL, and observed changes in the abundance and molecular weight of NER complex proteins. Our results showed that XPA, XPC and ERCC1 protein levels change during DNA damage-induced apoptosis. Among these, ERCC1 decrease was observed as a pre-mitochondria depolarisation event which marks the “point of no return” in apoptosis signalling. ERCC1 decrease was due to proteasomal degradation upon lethal doses of oxaliplatin exposure. When ERCC1 protein was stabilised using proteasome inhibitors, the pro-apoptotic activity of oxaliplatin was attenuated. These results explain why clinical trials using proteasome inhibitors and platinum derivatives showed limited efficacy in carcinoma treatment and also the importance of how deep understanding of DNA repair mechanisms can improve cancer therapy.

Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.

Acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity in western countries, and, because of translational relevance of animal models, APAP is mechanistically the most studied drug. This review covers intracellular signaling events starting with drug metabolism and the central role of mitochondrial dysfunction involving oxidant stress and peroxynitrite. Mitochondria-derived endonucleases trigger nuclear DNA fragmentation, the point of no return for cell death. In addition, adaptive mechanisms that limit cell death are discussed including autophagy, mitochondrial morphology changes, and biogenesis. Extensive evidence supports oncotic necrosis as the mode of cell death; however, a partial overlap with signaling events of apoptosis, ferroptosis, and pyroptosis is the basis for controversial discussions. Furthermore, an update on sterile inflammation in injury and repair with activation of Kupffer cells, monocyte-derived macrophages, and neutrophils is provided. Understanding these mechanisms of cell death led to discovery of N-acetylcysteine and recently fomepizole as effective antidotes against APAP toxicity.

Monitoring of Thermal Runaway in Commercial Prismatic High-Energy Lithium-Ion Battery Cells via Internal Temperature Sensing

The temperature of a lithium-ion battery is a crucial parameter for understanding the internal processes during various operating and failure scenarios, including thermal runaway. However, the internal temperature is comparatively higher than the surface temperature. This particularly affects cells with a large cross-section, which is due to heat development within the cell and lower heat dissipation due to a poorer ratio of volume to surface area. This paper presents an approach that enables real-time monitoring of the behavior of a commercial prismatic high-energy battery cell (NMC811/C, 95 Ah, Contemporary Amperex Technology Co., Limited (Ningde, China)) in the event of thermal runaway induced by overcharging. The internal cell temperature is investigated by the subsequent integration of two hard sensors between the two jelly rolls and additional sensors on the surface of the aluminum housing of the battery cell. The sensor’s signals show a significant increase in the temperature gradient between the temperature in the core of the cell and the cell casing surface until the onset of venting and thermal runaway of the battery. The data enable a detailed investigation of the behavior of the battery cell and the comparatively earlier detection of the point of no return in the event of thermal runaway.

Comparison of the Expansion and End of The World in The Qur'an and New Science

Comparison of the expansion and end of the world in the Qur’an and new science is one of the important issue and this comparison is quite vital to be considered. In this article, according to the scientific information of the Quran, which corresponds to the findings of contemporary scientists, we have investigated black holes. Black holes form when a star uses up all its fuel. A black hole is a point of space with so much gravity and density that even light cannot escape. This attraction is so strong that it compresses all matter into a small space. According to the theory of general relativity, matter that is compressed enough can bend space-time and form a black hole. The black hole's point of no return is called the event horizon. Black holes do not reflect any light. But they can be identified based on the effects they have on the materials and objects around them. Fourteen centuries ago, when science and astronomy were still very primitive, the fact that the sun and the stars will one day lose their light has been stated in numerous Quranic verses.

Annular Remodeling predicts Outcome in Isolated Severe Tricuspid Regurgitation: A Registry-based Echocardiographic Analysis.

Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodeling in isolated severe sTR (isoTR). A total of 36,000 patients from the longitudinal echocardiographic database of our tertiary center were screened for severe isoTR [vena contracta (VC)≥7mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were reread, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined the primary endpoint.216 patients fulfilled the inclusion criteria. Severe TR was predominant, only few were classified in the new grades massive [n=23(10%)] and torrential TR [n=4(2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31%(n=67). Multivariate Cox regression analysis revealed no association of VC, EROA, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (p<0.001), indexed right atrial dimensions (p=0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (TADI:p=0.002) and TV annulus diameter systole index (TASI:p=0.001) were significantly associated with outcome. Severe isolated TR in absence of AF is a rare finding with grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodeling leading to a "point of no return" with dismal outcome.

New therapeutic modalities for rare diseases

Genetic Diseases affect about 2 % to 3 % of all live births. It has been reported that genetic disorders can account for up to 22 % of infant deaths. Despite this significant effort to create new therapies, treatment is available only for about 5 % of these diseases due to undiscovered etiology or rapid progression to the point of no return. Efforts for new and effective etiology-targeted treatment methods for rare genetic disorders have significantly increased in recent years. Gene-targeted novel treatments such as gene replacement therapy and gene editing, mainly gene-targeted, have significant potential to be the primary treatment modalities in the future.

Effect of starvation on physiological and survival traits of Mimachlamys varia (Linneaus, 1758)

In order to better understand Mimachlamys varia (Linneaus, 1758) response to nutritional stress, a controlled-condition experiment was conducted. Two scallop batches (i.e. juveniles and adults) were completely food-deprived for 3 months. Changes in mass and energy content of tissues (adductor muscle, digestive gland, rest of the soft tissues), as well as stable carbon and nitrogen isotope ratios of the adductor muscle were monitored weekly. Both batches exhibited a 3-phase response to starvation. For adults, phase 1, was characterized by a fast loss in mass, an δ15N-enrichment, a stable calorific power, and a low mortality, corresponding to a transitional stage associated with protein-storage consumption. Phase 2 (day 28–42) exhibited a stabilization of mass and δ15N values, coinciding with a digestive gland calorific power drop and an acceleration in mortality. This corresponds to a “protein sparing” stage where highly energetic fuel such as lipids, which are stored especially in the digestive gland in pectinids, are consumed in priority. Juveniles exhibited a distinct response characterized by a significant mass loss and an increase in calorific power during the first phase (day 0–28). This body weight decrease may involve the remobilization of low-caloric biochemical compounds (e.g. proteins) using the structure as internal fuel, thus limiting somatic maintenance costs. During the second month, body mass and calorific power stabilized, indicating a “protein sparing” stage. In a third phase for both age classes, mass decreased again together with a sharp increase in mortality: essential structure was ultimately remobilized. The survival rate of juveniles was higher than that of adults during the first two months of the experiment (97% and 64%, respectively). Although the time required for starvation to deplete of half the cohort is higher for juveniles than for mature individuals, increase in mortality rate after reaching the “Point of No Return”, (e.g. the beginning of the last phase) was higher in juveniles than in adults. These results highlight the potential impacts of starvation at the population level, beyond the direct impact on individual survival. For instance, individuals may not effectively contribute to reproduction during the spawning period if exposed to a prolonged winter starvation episode. In particular, since highly energetic compounds stored in the digestive gland are often used as fuel to initiate gametogenesis in pectinids. Similarly, decrease in somatic weight in juveniles may delay their sexual maturity and hence their ability to contribute to population reproductive potential.

Regarding the resilience of market entities on the example of enterprises in the extractive industry

The last period (starting with the pandemic) cataclysms determined the importance for the macro- and microeconomies resilience as the ability of ecosystems, business, society to cope with shocks and continue to function in approximately the same way. The topic of resilience is extremely important for mining companies, because they cannot afford any relocation and industrial repurposing. The goal of this work is to clarify the essence of resilience and identify the factors that determine it for subjects of the market system. Research methods: general scientific – abstraction, analysis, synthesis, observation, generalization; the microcosm-system approach, which is an extension of the world-system approach to microeconomics; cumulative cost curves; single-factor production functions; methods of mathematical and statistical analysis; Zipf-Pareto law. The base of observations is the global coking coal market, production and economic indicators of the Ukrainian iron ore mining company. It is shown that the unprofitability of industrial and commercial activity is a necessary but not sufficient condition for the microcosm-economy to lose resilience. The loss of resilience is a process whose active actors, along with the direct subjects of the market, are their owners, the state and other subjects and authorities. The final stage of resilience loss occurs after the market subject crosses a certain point of no return. A model of a certain market is a cumulative cost curve. The final part of the cumulative cost curve`s graph, where the elements with the worst economic characteristics (high-risk group) are located, is significantly non-linear. The rank of the element position on the curve mathematically determines with the Zipf-Pareto law the cost value and identify the zone of market entities profitable functioning according with the market price of products. The application of the logit-regression model makes it possible to estimate the probability of a market subject's profitability loss at its inherent cost and the confidence interval of prices observed during a certain period. The risk degree of resilience loss is determined not only by the factors of the market itself, but also by the production function characteristic of the subject of market activity. The article provides an example of a one-factor logarithmic production function of a Ukrainian iron ore mining company.

A multicentric and nationwide predictive study role of T cell sub-population in the prevalence and prognosis of cryoglobulinemia among genotype 4 chronic hepatitis C patients.

The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.