Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy

Induction of apoptosis represents a promising therapeutic approach to drive tumor cells to death. however, this poses challenges due to the intricate nature of cancer biology and the mechanisms employed by cancer cells to survive and escape immune surveillance. furthermore, molecules released from apoptotic cells and phagocytes in the tumor microenvironment (TME) can facilitate cancer progression and immune evasion. apoptosis is also a pivotal mechanism in modulating the strength and duration of anti-tumor T-cell responses. combined strategies including molecular targeting of apoptosis, promoting immunogenic cell death, modulating immunosuppressive cells, and affecting energy pathways can potentially overcome resistance and enhance therapeutic outcomes. thus, an effective approach for targeting apoptosis within the TME should delicately balance the selective induction of apoptosis in tumor cells, while safeguarding survival, metabolic changes, and functionality of T cells targeting crucial molecular pathways involved in T-cell apoptosis regulation. enhancing the persistence and effectiveness of T cells may bolster a more resilient and enduring anti-tumor immune response, ultimately advancing therapeutic outcomes in cancer treatment. this review delves into the pivotal topics of this multifaceted issue and suggests drugs and druggable targets for possible combined therapies

Sound Regular Corecursion in coFJ

The aim of the paper is to provide solid foundations for a programming paradigm natively supporting the creation and manipulation of cyclic data structures. To this end, we describe coFJ, a Java-like calculus where objects can be infinite and methods are equipped with a codefinition (an alternative body). We provide an abstract semantics of the calculus based on the framework of inference systems with corules. In coFJ with this semantics, FJ recursive methods on finite objects can be extended to infinite objects as well, and behave as desired by the programmer, by specifying a codefinition. We also describe an operational semantics which can be directly implemented in a programming language, and prove the soundness of such semantics with respect to the abstract one

A model-based opinion dynamics approach to tackle vaccine hesitancy

: Uncovering the mechanisms underlying the diffusion of vaccine hesitancy is crucial in fighting epidemic spreading. Toward this ambitious goal, we treat vaccine hesitancy as an opinion, whose diffusion in a social group can be shaped over time by the influence of personal beliefs, social pressure, and other exogenous actions, such as pro-vaccine campaigns. We propose a simple mathematical model that, calibrated on survey data, can predict the modification of the pre-existing individual willingness to be vaccinated and estimate the fraction of a population that is expected to adhere to an immunization program. This work paves the way for enabling tools from network control towards the simulation of different intervention plans and the design of more effective targeted pro-vaccine campaigns. Compared to traditional mass media alternatives, these model-based campaigns can exploit the structural properties of social networks to provide a potentially pivotal advantage in epidemic mitigation

A Real-Time Spectroscopic Sensor for Monitoring Laser Welding Processes

In this paper we report on the development of a sensor for real time monitoring of laser welding processes based on spectroscopic techniques. The system is based on the acquisition of the optical spectra emitted from the laser generated plasma plume and their use to implement an on-line algorithm for both the calculation of the plasma electron temperature and the analysis of the correlations between selected spectral lines. The sensor has been patented and it is currently available on the market

Plasma Plume Oscillations Monitoring during Laser Welding of Stainless Steel by Discrete Wavelet Transform Application

The plasma optical radiation emitted during CO2 laser welding of stainless steel samples has been detected with a Si-PIN photodiode and analyzed under different process conditions. The discrete wavelet transform (DWT) has been used to decompose the optical signal into various discrete series of sequences over different frequency bands. The results show that changes of the process settings may yield different signal features in the range of frequencies between 200 Hz and 30 kHz. Potential applications of this method to monitor in real time the laser welding processes are also discussed

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

CircRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs. Among the 4362 circRNAs potentially encoding proteins with a unique primary structure and 1179 encoding proteins with a novel domain composition, 183 were differentially expressed in cancer. In particular, eight were associated with prognosis in acute myeloid leukemia. The functional classification of the dysregulated circRNA-encoded polypeptides showed an enrichment in the heme and cancer signaling, DNA-binding, and phosphorylation processes, and disclosed the roles of some circRNA-based effectors in cancer

The role of the general practictioner in the management of urinary calculi

Background: The prevalence of kidney stones tends to increase worldwide due to dietary and climate changes. Disease management involves a high consumption of healthcare system resources which can be reduced with primary prevention measures and prophylaxis of recurrences. In this field, collaboration between general practitioners (GPs) and hospitals is crucial. Methods: a panel composed of general practitioners and academic and hospital clinicians expert in the treatment of urinary stones met with the aim of identifying the activities that require the participation of the GP in the management process of the kidney stone patient. Results: Collaboration between GP and hospital was found crucial in the treatment of renal colic and its infectious complications, expulsive treatment of ureteral stones, chemolysis of uric acid stones, long-term follow-up after active treatment of urinary stones, prevention of recurrence and primary prevention in the general population. Conclusions: The role of the GP is crucial in the management and prevention of urinary stones. Community hospitals which are normally led by GPs in liaison with consultants and other health professional can have a role in assisting multidisciplinary working as extended primary care

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research