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In geometric crystallography, there are 32 well-known point crystallographic groups, or A. V. Gadolin's 32 crystal classes, which make up a complete list of symmetry groups of crystal shapes whose internal structure is subordinate to one of the 230 Fedorov groups existing in . In 2022, the author constructed two point crystal structures located in whose possible external shapes have the symmetry groups and , respectively. However, the internal structure of the crystal was not taken into account in the considerations of these groups. The central result of the author's 2022 paper is as follows: if a possible external shape of an ideal crystal has an ordinary rotation of non-crystallographic order , then either or and in this case the external shape is a right prism of finite height. But only after the paper was published did the author notice that the proof of this result was incomplete, although the result itself is correct. The present paper provides a complete proof of this result without relying on the 2022 text. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease with various symptoms of differing severities and with the reported prominent involvement of neutrophil extracellular traps (NETs). The excitation of neutrophils, e.g., by interleukin 8 (IL-8) or lipopolysaccharide (LPS), leads to the citrullination of histones and the release of protein–DNA complexes into the extracellular space, where they are digested by DNases. Our aim was to explore data on the levels of protein-complexed DNAs neutrophil elastase–DNA (NE-DNA) and myeloperoxidase–DNA (MPO-DNA), citrullinated histones (citH2, citH3, citH4), and NET-degrading enzyme DNase I in the serum of psoriatic patients with varying severities of clinical symptoms assessed with the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores. The levels of factors were detected in 52 patients with psoriasis and 22 healthy volunteers by the enzyme-linked immunosorbent assay (ELISA). The results showed the elevated levels of NE-DNA, MPO-DNA, citH3, and DNase I in the patients with psoriasis compared to healthy volunteers (p < 0.05). Additionally, changes were noticed in the levels of NE-DNA, citH3, and DNase I, depending on the severity of symptoms (p < 0.05). In mild psoriasis (PASI < 10, BSA < 10, DLQI < 10), the suppressing activity of the enzyme caused the impaired ability to remove the physiological level of NETs, whereas in moderate to severe psoriasis (PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10), the enhanced activity of DNase I failed to remove NETs due to the observed overexpression. It may, thus, be concluded that the mechanism of action of NETs, which play an undeniable role in psoriatic diseases, seem to follow two different paths depending on the severity of disease, which may be crucial in selecting potential anti-NET treatment methods. [ABSTRACT FROM AUTHOR]

Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics. • Mares with bacterial endometritis exhibited a significantly higher relative abundance of endometrial proteins compared to clinically healthy mares. • The proteins upregulated in the secretome of mares with bacterial endometritis were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium (neutrophil extracellular trap (NET) formation pathway). • A total of 24 biomarkers for bacterial endometritis were identified. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B, complement C3a, or gelsolin and profilin. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and MPO) and two uncharacterized proteins with a high homology with cathelicidin families. [ABSTRACT FROM AUTHOR]

Plankton size spectra are important indicators of the ecosystem state, yet such measurements are typically biased by the available sampling methods. Here, we combined individual size measurement from two zooplankton imaging approaches— in situ observation by the Underwater Vision Profiler5 and Multinet-collection supplemented by ex situ imaging via Zooscan—obtained in the global ocean, to calculate zooplankton normalized biovolume size spectra (NBSS) for all organisms larger than 1 mm. The reconstructed NBSS combining both datasets resulted in increased biomass estimates by adding organisms poorly sampled by either of the methods. The optimal values measured by both methods are used to reconstruct the zooplankton biovolume and biomass distributions. The reconstructed slopes appeared steeper and closer to those measured only by the UVP5 (+7.6%) and flatter than those obtained only from the Multinet (−20%), particularly in tropical and temperate latitudes. The main difference in tropical and temperate NBSS from the two devices is due to the fragile rhizarians that were not accounted for when using net data. When possible, we suggest using in situ and ex situ technologies together, and we provide potential indications on how to correct for missing components of the community when only one method is available. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors are malignant neoplasms arising from neuroendocrine cells. These are increasingly recognized with rising incidence and encompass a diverse range of phenotypes. The large majority of these originate in the gastrointestinal tract however primary neuroendocrine tumors have also been reported to arise in a variety of organs such as lung, breast, prostate, and skin. Primary malignant paratesticular masses are often sarcomatous in origin and metastatic spread to the paratesticular region or scrotum is exceedingly rare. We report a fascinating case of a 56-year-old male who had an unusual initial presentation of paratesticular lesions on a background of an undescended testicle and an incidental umbilical nodule. After a combination of radiological and histopathological investigations, he was diagnosed with metastatic midgut neuroendocrine tumor.

With the increase in global population, the demand for aquatic products rises annually. As a sustainable industry, aquaculture offers a promising solution to address the growing demand for fish products. Meanwhile, intensifying and expanding sustainable aquaculture is essential for achieving the United Nations' global goal of the Decade of Action. Cage culture is a typical aquaculture method used globally. This culture method has the following advantages: (Ⅰ) Highly researched with a long history: cage culture has been in use since the 1970s. Cultivating high-value aquatic products through cage culture has become indispensable in aquaculture. (Ⅱ) The development prospects of cage culture are broad and include realization of the comprehensive breeding of different species. In the integrated multi-nutritive aquaculture (IMTA) system, cage culture enables a multi-species combination in which uneaten feed and nutrients from the excreted waste of one breeding species are used as food for other breeding species, thereby reducing nutrients released into the environment and increasing overall productivity. Net cage culture in shallow waters has grown exponentially in the past few decades. However, due to the limited space in nearshore areas and an increasing number of countries paying attention to the environmental problems caused by cage culture, the method has gradually shifted to deeper waters to ensure food security and safety. At the same time, alleviating environmental stress caused by nearshore cage culture and the expansion of the food production space are inevitable. Compared with nearshore aquaculture, the environmental conditions of offshore aquaculture are more complex, and the net cages are inevitably subjected to harsh sea conditions. To achieve the safe production of offshore aquaculture, it is crucial to study wind and wave resistance technology for use in culture net cages. As an essential part of net cages, the netting system is mainly used to maintain breeding space, protect the breeding species, prevent them from escaping, and protect them from predators. In the flow and wave field, the netting system bears most of the load on the farming facilities. Compared with other traditional marine structures, the nets have the mechanical characteristics of small scale and high flexibility. Under external force, the nets show large displacement and massive deformation, reducing breeding space and increasing the likelihood of damage to breeding species due to crowding. At the same time, the nets change the flow and wave field around the facility, affecting the distribution of the remaining bait, breeding species' excrement, and dissolved oxygen in the water. Currently, the lack of analysis technology for nets is a limitation in offshore cage culture engineering, which restricts the large-scale development of offshore cages. Therefore, research on the hydrodynamic characteristics of nets is vital for developing offshore cage culture. This study introduced primary methods for calculating the netting hydrodynamic loads and their applicability. Simultaneously, the predominant modeling techniques in the numerical calculation of the netting dynamic response were summarized and analyzed. Furthermore, a systematic review of studies relating to the wave flow field around net mesh was conducted. Finally, the current hot topics in the research of netting hydrodynamic characteristics were reviewed to provide a reference for designing and optimizing cages. Considering the influence of various parameters on the hydrodynamic loads on the nets is an effective way to improve the prediction accuracy for the loads, which is also a critical area of research that requires further investment. In order to restore the real force characteristics of nets, a database of the netting hydrodynamic coefficients should be established through experiments. Intelligent algorithms, such as digital twin technology, are used to construct prediction models and generate mapping relationships between multiple factors and the hydrodynamic coefficients of the nets. Moreover, databases and algorithms should be updated regularly to improve the accuracy of calculating the netting hydrodynamic load. For the dynamic response of the nets, the fluid-structure coupling of the flexible nets should be studied intensively in the future, focusing on the two-way coupling between the nets and the fluid and exploring direct numerical simulation methods. Meanwhile, considering computational accuracy, suitable algorithms, such as the submerged boundary method, should be selected, and parallel computational methods should be developed to improve computational efficiency. In terms of the flow and wave field around the nets, further research should be conducted to determine the effects of extreme waves, biofouling, fouling density, cultured fish species, fish size, fish number, fish swimming speed, and fish swimming status on the flow field in the net cages, which will be conducive to monitoring the health of fish, reducing the risk of fish diseases, and ensuring the sustainable development of cage culture. This study provides a reference for developing net hydrodynamic analysis for digitalization and precision. It also provides more information for the sustainable development of aquaculture.

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro‐tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF‐κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region‐specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16‐knockout reverses the pro‐tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region‐specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Cumulative evidence from several pre-clinical studies suggests that restoration of plasma DNase activity in a thrombo-inflammatory state may improve clinical outcomes. Following injury, hyperactivated immune cells release large amounts of granular proteins together with DNA, which often accumulate in the surrounding environment in so-called neutrophil extracellular traps (NETs). Degradation of excess NETs by systemic DNase administration offers a promising therapeutic approach to ameliorate inflammation and dissolve intravascular clots. In order to expand the therapeutic utility of human DNase I, a variant of the enzyme was developed that has both a prolonged systemic half-life and a higher catalytic activity compared to Dornase alfa (Pulmozyme®), the recombinant form of DNase I approved for inhaled therapy of cystic fibrosis. The hyperactive enzyme was "PASylated" by genetic fusion with a strongly hydrophilic and biodegradable PAS-polypeptide to increase its hydrodynamic volume and retard kidney filtration. A stable TurboCell™ CHO-K1-based cell line was generated which is suitable for the future production of PASylated DNase I according to good manufacturing practice (GMP). Furthermore, a robust bioprocess strategy was devised and an effective downstream process was developed. The final protein product is characterized by excellent purity, favorable physicochemical properties, a 14-fold higher DNA-degrading activity than Dornase alfa and a sustained pharmacokinetic profile, with a 22-fold slower clearance in rats. [ABSTRACT FROM AUTHOR]

Vascular permeability is temporarily heightened during inflammation, but excessive inflammation‐associated microvascular leakage can be detrimental, as evidenced in the inflamed lung. Formylated peptides regulate vascular leakage indirectly via formylated peptide receptor‐1 (FPR1)‐mediated recruitment and activation of neutrophils. Here we identify how the GTPase‐activating protein ARAP3 protects against formylated peptide‐induced microvascular permeability via endothelial cells and neutrophils. In vitro, Arap3−/− endothelial monolayers were characterised by enhanced formylated peptide‐induced permeability due to upregulated endothelial FPR1 and enhanced vascular endothelial cadherin internalisation. In vivo, enhanced inflammation‐associated microvascular leakage was observed in Arap3−/− mice. Leakage of plasma protein into the lungs of Arap3−/− mice increased within hours of formylated peptide administration. Adoptive transfer experiments indicated this was dependent upon ARAP3 deficiency in both immune and non‐immune cells. Bronchoalveolar lavages of formylated peptide‐challenged Arap3−/− mice contained neutrophil extracellular traps (NETs). Pharmacological inhibition of NET formation abrogated excessive microvascular leakage, indicating a critical function of NETs in this context. The observation that Arap3−/− mice developed more severe influenza suggests these findings are pertinent to pathological situations characterised by abundant formylated peptides. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

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One of the most relevant topics in web theory is linearization. A particular class of linearizable webs is the Grassmannizable web. Akivis gave a characterization of such a web, showing that Grassmannizable webs are equivalent to isoclinic and transversally geodesic webs. The obstructions given by Akivis that characterize isoclinic and transversally geodesic webs are computed locally, and it is difficult to give them an interpretation in relation to torsion or curvature of the unique Chern connection associated with a web. In this paper, using Nagy's web formalism, Frölisher—Nejenhuis theory for derivation associated with vector differential forms, and Grifone's connection theory for tensorial algebra on the tangent bundle, we find invariants associated with almost-Grassmann structures expressed in terms of torsion, curvature, and Nagy's tensors, and we provide an interpretation in terms of these invariants for the isoclinic, transversally geodesic, Grassmannizable, and parallelizable webs. [ABSTRACT FROM AUTHOR]

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation. [ABSTRACT FROM AUTHOR]

Purpose The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission tomography/computed tomography (PET/CT) cameras is well established. However, with the eventual retirement of older PET cameras and their replacement with newer, highly sensitive TOF PET/CT cameras, where SUV max measurements are reportedly higher, updated knowledge of normal SUV max range is needed and, to our knowledge, not previously reported. Our objectives are as follows: To establish normal Ga-68-dotatate TOF SUV max database for common structures and to aid the visual detection of abnormalities objectively. To compare SUV max values using the TOF and non-TOF algorithms. Methods Fifty consecutive patients referred routinely to our nuclear medicine service (20 men, 30 women; median age 55 years) with presumed neuroendocrine tumors underwent Ga-68-dotatate scans on a PET-CT camera having capability of reconstructing both TOF/non-TOF images. Region of interests (ROIs) were drawn around 24 normal structures as well as the primary lesion with abnormal radiotracer uptake and SUV max was measured. The same ROI was analyzed using both algorithms simultaneously and both TOF and non-TOF SUV max values were compared. Results Twelve hundred ROIs were evaluated. Non-TOF Ga-68-dotatate uptake in normal structures was in alignment with previously published studies. As compared to non-TOF, TOF images had better target to background ratios visually. TOF SUV max was higher for all structures except for lung and brain. TOF SUV max was more than double in adrenals/uncinate process of the pancreas; approximately 1.8 times in abnormal lesions, lymph nodes, pineal gland; and greater than 1.5 times in thyroid, breast, and pancreatic head. Conclusion Normal database of Ga-68-dotatate TOF SUV max is provided for common structures to aid visual detection of abnormalities objectively. Overall, TOF SUV max measures higher in identical ROIs, with abnormal lesions measuring approximately 1.8 times higher versus non-TOF technology. These findings need to be taken in consideration when comparing patient scans imaged on different PET/CT technologies. [ABSTRACT FROM AUTHOR]

Pathophysiology of severe COVID-19 is characterized by changes in the number, phenotype, and function of neutrophil granulocytes (NG). Among the effector antiviral mechanisms of NG, the neutrophil extracellular traps (NETs) are among the most important features. However, their excessive formation exacerbates inflammation in acute respiratory distress syndrome and contributes to microvascular thrombosis. Their detection and counting may be important in severity grading of COVID-19, for determining correlations with clinical outcome, assessing the risk of developing post-COVID syndrome, and, possibly, for monitoring future targeted therapy. Purpose of our study was to develop a new diagnostic integrative criterion to assess the severity of COVID-19 and the risk of complications in the post-COVID period, including post-COVID signs in peripheral blood. Peripheral blood (PB) samples were studied from 31 patients with acute COVID-19 of moderate (n = 15) and severe degrees (n = 16). Moreover, we observed 52 patients discharged from the hospital after severe COVID-19, with diagnosed post-COVID syndrome (PCS) over the period of 30 to 60 days, and 100 healthy volunteers. The parameters of routine blood counts (MicroCC-20Plus) were evaluated, the leukocyte formula was calculated in PC smears, taking into account the number of formed NETs, and NGs entering pathological apoptosis. Based on the obtained results, an integral diagnostic criterion was calculated using the formula:$$ IDK = \frac{\%\ unchanged\ NG}{\%NET + \%NG\ in\ apoptosis} $$A 8.5-fold decrease in IDK index (p < 0.05) was shown in the cases of moderate-severity course of the disease, and a 30-fold drop was seen in severe cases (p < 0.05) compared with appropriate values in the group of healthy individuals. It was also found that, in 88.5% of patients with PCS after the SARS-CoV-2 infection, no morphologically altered NG were detectable in PB samples. At the same time, in 11.5% of patients with PCS, we found NETs and cells with pathological apoptosis, whereas IDC of NG-PCS was 8 times less than in the comparison group, and did not differ from the parameters of patients with moderate COVID-19 (p > 0.05) thus requiring further dispensary observation of such patients. The data obtained in this study indicate that the developed integrative diagnostic criterion allows us to assess both the severity of COVID-19 over acute period, and the risk of post-COVID syndrome. It should be emphasized that the characteristic changes in NG detected in COVID-19 may be readily identified in PB and consistently monitored by the proposed integral diagnostic criterion. A significant decrease in IDC indicates the persisting hyper-activation of NG and a need for targeted immunotherapy aimed at modulating the NG dysfunction.

ABSTRACTThe mechanisms of Pythium insidiosum-antigen (PIA) immunotherapy activating a patient’s immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti-P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 (p

Astrocytes actively participate in neurotransmitter homeostasis by bidirectional communication with neuronal cells, a concept named the tripartite synapse, yet their role in dopamine (DA) homeostasis remains understudied. In the present study, we investigated the kinetic and molecular mechanisms of DA transport in cultured striatal astrocytes of adult rats. Kinetic uptake experiments were performed using radiolabeled [3H]-DA, whereas mRNA expression of the dopamine, norepinephrine, organic cation and plasma membrane monoamine transporters (DAT, NET, OCTs and PMAT) and DA receptors D1 and D2 was determined by qPCR. Additionally, astrocyte cultures were subjected to a 24 h treatment with the DA receptor agonist apomorphine, the DA receptor antagonist haloperidol and the DA precursor L-DOPA. [3H]-DA uptake exhibited temperature, concentration and sodium dependence, with potent inhibition by desipramine, nortriptyline and decynium-22, suggesting the involvement of multiple transporters. qPCR revealed prominent mRNA expression of the NET, the PMAT and OCT1, alongside lower levels of mRNA for OCT2, OCT3 and the DAT. Notably, apomorphine significantly altered NET, PMAT and D1 mRNA expression, while haloperidol and L-DOPA had a modest impact. Our findings demonstrate that striatal astrocytes aid in DA clearance by multiple transporters, which are influenced by dopaminergic drugs. Our study enhances the understanding of regional DA uptake, paving the way for targeted therapeutic interventions in dopaminergic disorders. [ABSTRACT FROM AUTHOR]

Purpose of Review: This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT). Recent Findings: Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. Summary: PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

The central idea in this text consists of identifying the importance of the home concept in the life of human beings, proposing two references: the oikos as a place and the oikos as an affective niche, showing the transformations that this concept has had with the presence of the virtuality, as one of the most determining aspects today, when interpreting new conditions of inhabiting the world today in virtuality, as an aesthetic of existence. The methodological approach is qualitative since the object of study is an aspect of the human being that is neither tangible nor measurable, but rather reflective and interpretable. The present investigation was developed from the hermeneutical method, based on the understanding and interpretation of texts, where it is very important to "apply the text to our context. Hence, the interpretive act includes putting ourselves in front of the text, exposing ourselves to it, so that it speaks to us, tells us something (for our lives). That is why Gadamer spoke of an "application", and Ricoeur of an "approximation", as necessary as distancing, with respect to the text. [ABSTRACT FROM AUTHOR]

In this paper, convergences of a filter and a net have been characterized through ideal on topological spaces. Furthermore, we characterized the local function in an ideal topological space in terms of convergence of filter. Using Zorn's Lemma, we have found a maximal element in the collection of all proper ideals on a nonempty set which is called maximal ideal. We provide a convenient characterization of maximal ideals. We also consider simple properties of the image of an ideal, a net and various local functions under a homeomorphism. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors ranging from genetics, alcohol use, gall stones, and ductal obstruction caused by calcification or neutrophil extracellular traps. Acute pancreatitis is also characterized by immune cell infiltration of neutrophils and M1 macrophages. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. This receptor can be found on a variety of cell types from endothelial cells to resident and infiltrating immune cells leading to production of pro-inflammatory cytokines as well as immune cell activation and maturation resulting in the furthering of pancreatic damage during acute pancreatitis. In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition. [ABSTRACT FROM AUTHOR]

Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse; however, their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na+‐dependent and Na+‐independent transporters. Uptake of radiolabelled dopamine was time‐, temperature‐ and concentration‐dependent and was inhibited by decynium‐22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. Twenty‐four‐hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L‐DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine‐tuning of existing therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: Central pancreatectomy (CP) offers parenchymal preservation compared to conventional distal pancreato-splenectomy for pancreatic neck and body tumours. However, it is associated with more morbidity. This study is aimed at evaluating the peri-operative and long-term functional outcomes, comparing central and distal pancreatectomies (DPs). Methods: Retrospective analysis of patients undergoing pancreatic resections for low-grade malignant or benign tumours in pancreatic neck and body was performed (from January 2007 to December 2022). Preoperative imaging was reviewed for all cases, and only patients with uninvolved pancreatic tail, whereby a CP was feasible, were included. Peri-operative outcomes and long-term functional outcomes were compared between CP and DP. Results: One hundred twenty-two (5.2%) patients, amongst the total of 2304 pancreatic resections, underwent central or distal pancreatectomy for low-grade malignant or benign tumours. CP was feasible in 55 cases, of which 23 (42%) actually underwent CP and the remaining 32 (58%) underwent DP. CP group had a significantly longer operative time [370 min (IQR 300–480) versus 300 min (IQR 240–360); p = 0.002]; however, the major morbidity (43.5% versus 37.5%; p = 0.655) and median hospital stay (10 versus 11 days; p = 0.312) were comparable. The long-term endocrine functional outcome was favourable for the CP group [endocrine insufficiency rate was 13.6% in central versus 42.8% in distal (p = 0.046)]. Conclusion: Central pancreatectomy offers better long-term endocrine function without any increased morbidity in low malignant potential or benign pancreatic tumours of neck and body region. [ABSTRACT FROM AUTHOR]

Inverse Dynamics is routinely used in biomechanics for the estimation of loading in the musculoskeletal system but there are problems with the terms and definitions and even official recommendations introduce artificial and incorrect mechanical constructs to justify arbitrary and inappropriate terms. These terminology problems lead to further confusion and misinterpretations rather than to standardisation of mechanically correct nomenclature and accurate interpretation of joint loading. The perspective in this paper exposes some of the flawed foundational premises of these constructs and makes recommendations for accurate reporting of inverse dynamics outcomes and musculoskeletal loading. The inverse dynamics approach is based on free body diagrams that include the actual forces as applied ('Actual Forces' approach) or the replacement of actual forces with an equivalent resultant force and moment ('Resultant Moments' approach). Irrespective of the approach used to model the muscle and other forces, the inverse dynamics outputs always include the joint reaction forces representing the interactions with adjacent segments. The different terms suggested to distinguish the calculated joint reaction forces from the two approaches such as 'net joint force', 'resultant force', 'intersegmental force' and 'bone-on-bone force' are inappropriate, misleading and confusing. It is recommended to refer to joint reaction forces as Total or Partial when using an Actual Forces or a Resultant Moments approach, respectively. [ABSTRACT FROM AUTHOR]

Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors. [ABSTRACT FROM AUTHOR]

Abstract The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro‐tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF‐κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region‐specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16‐knockout reverses the pro‐tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region‐specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC.

In this response to Diamond is a scientist's best friend, Ron Oostdam argues that diamond open access is morally worth striving for, but may be difficult to achieve.

Abstract Background Neutrophil extracellular trap (NET) has been implicated in the pathology of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the specific contributions of NLRP3, a NET-associated molecule, to EAE pathogenesis and its regulatory role in NET formation remain unknown. Methods To investigate the detrimental effect of NETs supported by NLRP3 in MS pathogenesis, we induced EAE in WT and NLRP3 KO mice and monitored the disease severity. At the peak of the disease, NET formation was assessed by flow cytometry, immunoblotting, and immunofluorescence staining. To further identify the propensity of infiltrated neutrophils, NET-related chemokine receptors, degranulation, ROS production, and PAD4 expression levels were evaluated by flow cytometry. In some experiments, mice were injected with DNase-1 to eliminate the formed NETs. Results Our data revealed that neutrophils significantly infiltrate the brain and spinal cord and form NETs during EAE pathogenesis. NLRP3 significantly elevates NET formation, primarily in the brain. NLRP3 also modulated the phenotypes of brain-infiltrated and circulating neutrophils, augmenting CXCR2 and CXCR4 expression, thereby potentially enhancing NET formation. NLRP3 facilitates NET formation in a ROS-dependent and PAD4-independent manner in brain-infiltrated neutrophils. Finally, NLRP3-supported NET formation exacerbates disease severity, triggering Th1 and Th17 cells recruitment. Conclusions Collectively, our findings suggest that NLRP3-supported NETs may be an etiological factor in EAE pathogenesis, primarily in the brain. This study provides evidence that targeting NLRP3 could be a potential therapeutic strategy for MS, specifically by attenuating NET formation.

The concept of a basis having a sequence of elements in a topological vector space is extended to a concept of a directed basis having a net of elements in a topological vector space. This article provides a generalization of the classical result which states that every basis in a complete metrizable topological vector space is a Schauder basis.

Jennie Garcia-Olivares,1 Brittney Yegla,1 Frank P Bymaster,2 Jami Earnest,1 Jennifer Koch,1 Chungping Yu,1 Jonathan Rubin1 1Supernus Pharmaceuticals, Inc., Rockville, MD, USA; 2Bymaster Neuroscience Consulting, Green Cove Springs, FL, USACorrespondence: Jennie Garcia-Olivares, Supernus Pharmaceuticals, Inc., 9715 Key West Avenue, Rockville, MD, 20850, USA, Fax +1 301-560-5542, Email jgarciaolivares@supernus.comBackground: Viloxazine ER (viloxazine extended-release capsules; Qelbree®), a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment, has known activity as a norepinephrine (NE) transporter (NET) inhibitor. In vitro studies have also shown direct pharmacological effects on specific serotonin (5-HT) receptors, but not on the serotonin transporter (SERT). An in vivo microdialysis study in rats showed viloxazine (50 mg/kg i.p.) increased extracellular 5-HT, NE, and dopamine (DA) in the prefrontal cortex (PFC), a key brain region in ADHD pathology. This study evaluated whether these effects occur at clinically relevant concentrations.Methods: Microdialysis experiments were conducted in freely-moving, Sprague-Dawley rats (males, 8 weeks). Viloxazine (1, 3, 10, 30 mg/kg) was administered intraperitoneally to establish the dose range in rats at which viloxazine plasma concentrations aligned with those of individuals with ADHD administered therapeutic doses of viloxazine ER. Concentrations of unbound viloxazine, NE, 5-HT, DA, and NE and 5-HT metabolites (3,5-dihydroxyphenylglycol [DHPG] and 5-hydroxyindoleacetic acid [5-HIAA]) were measured in PFC interstitial fluid. After identifying a therapeutically relevant dose (30 mg/kg), the experiment was repeated using 30 and 50 mg/kg viloxazine (as 50 mg/kg increased NE, 5-HT, and DA in prior studies).Results: Viloxazine unbound (free drug) plasma concentrations in rats at 30 mg/kg were comparable to free drug concentrations in individuals with ADHD taking clinically effective doses (based on validated population PK models). Viloxazine 30 mg/kg significantly increased extracellular NE, 5-HT, and DA PFC levels compared to vehicle. Concomitant decreases in DHPG, but not 5-HIAA, support the inhibitory effect of viloxazine on NET but not SERT.Conclusion: At clinically relevant concentrations, viloxazine increases PFC NE, DA, and 5-HT. Prefrontal augmentation of 5-HT does not appear to result from 5-HT reuptake inhibition but may be related to activation of 5-HT neurons. The potential therapeutic role of serotonergic effects in ADHD treatment merits further exploration.Plain Language Summary: Viloxazine ER (Qelbree®) is a non-stimulant, FDA-approved treatment for ADHD in children and adults. Viloxazine and other ADHD medications are thought to work by increasing two signaling molecules, called norepinephrine and dopamine, in a brain area called the prefrontal cortex. The prefrontal cortex is important in ADHD as it helps control impulsive behavior, attention, hyperactivity, and learning. A third signaling molecule called serotonin may also be important for ADHD. Previous experiments in rats have shown that viloxazine increases norepinephrine, dopamine, and serotonin in the prefrontal cortex. To better understand how viloxazine increases serotonin and if the increase occurs at the same doses used to treat ADHD, we did another microdialysis study in rats. Our study showed that viloxazine increases norepinephrine, dopamine, and serotonin in the prefrontal cortex at doses used to treat ADHD in humans. We showed that viloxazine increases norepinephrine and dopamine levels in the neuron where these signaling molecules work by blocking the way that they are recycled back into the nerve space. However, viloxazine does not block the serotonin recycling mechanism, meaning viloxazine works differently than selective serotonin reuptake inhibitor (SSRI) medications (often used in depression). Additional studies are needed to determine exactly how viloxazine increases serotonin in the brain and whether this increase plays a role in treating ADHD. These additional studies will also help us understand how viloxazine acts differently than other ADHD medications. Keywords: viloxazine, microdialysis, prefrontal cortex, serotonin, NET, ADHD

Kratom (Mitragyna speciosa Korth) is a tropical plant originating from Southeast Asia that predominantly contains alkaloid compounds and can potentially maintain levels of monoamine compounds in the body to treat depression. The study aimed to examine the potential of 8 alkaloid compounds in kratom as antidepressants towards four target proteins: Serotonin Transporter (SERT), Dopamine Transporter (DOPAT), Leucine Transporter (LEUT), and Monoamine Oxidase (MAO) via molecular docking. The Pyrx program is used with exhaustiveness 106 as the protocol, and the grid is adapted to the active site of each receptor. The affinity values ​​of the alkaloid compounds in kratom are mitragynine, 7-hydroxy mitragynine, speciociliatine, paynantheine, speciogynine, corynantheidine, mitraciliatine, and 9-hydroxycorynantheidine, for MAO were -7.1, -6.1, -5.7, -6.7, -5.7, -7.7, -5.7, and -5.7 kcal/ mole. All compounds bind to amino acid residues in the target protein through hydrogen and pi (π) bonds. All the tested alkaloid compounds have the potential to be re-uptake inhibitors SERT, DOPAT, LEUT, and Monoamine Oxidase (MAO).

Psoriasis is an inflammatory skin disease with various symptoms of differing severities and with the reported prominent involvement of neutrophil extracellular traps (NETs). The excitation of neutrophils, e.g., by interleukin 8 (IL-8) or lipopolysaccharide (LPS), leads to the citrullination of histones and the release of protein–DNA complexes into the extracellular space, where they are digested by DNases. Our aim was to explore data on the levels of protein-complexed DNAs neutrophil elastase–DNA (NE-DNA) and myeloperoxidase–DNA (MPO-DNA), citrullinated histones (citH2, citH3, citH4), and NET-degrading enzyme DNase I in the serum of psoriatic patients with varying severities of clinical symptoms assessed with the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores. The levels of factors were detected in 52 patients with psoriasis and 22 healthy volunteers by the enzyme-linked immunosorbent assay (ELISA). The results showed the elevated levels of NE-DNA, MPO-DNA, citH3, and DNase I in the patients with psoriasis compared to healthy volunteers (p < 0.05). Additionally, changes were noticed in the levels of NE-DNA, citH3, and DNase I, depending on the severity of symptoms (p < 0.05). In mild psoriasis (PASI < 10, BSA < 10, DLQI < 10), the suppressing activity of the enzyme caused the impaired ability to remove the physiological level of NETs, whereas in moderate to severe psoriasis (PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10), the enhanced activity of DNase I failed to remove NETs due to the observed overexpression. It may, thus, be concluded that the mechanism of action of NETs, which play an undeniable role in psoriatic diseases, seem to follow two different paths depending on the severity of disease, which may be crucial in selecting potential anti-NET treatment methods.

Backgrounds Venous Thromboembolism (VTE) is a disease entity comprising Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). VTE events increase the mortality rate of patients with cancer receiving platinum-based chemotherapy. Soluble P-Selectin, Neutrophil Extracellular Traps (NET), and myeloperoxidase (MPO) are risk factors associated with DVT in malignancy patients receiving platinum-based chemotherapy. The purpose of this study was to determine the role of soluble P-selectin, NET, and MPO as risk factors for DVT in patients with malignancy receiving platinum-based chemotherapy. Patients and Methods This study used a case-control design (matched pair case-control study) based on age and gender. The case group consisted of subjects with DVT, whereas the control group consisted of subjects without DVT. The subjects were 31 in each case and control groups. Soluble P-selectin, NET, and MPO levels were measured in each group. Results The mean age of case group was 50.26±12.15 years meanwhile in control group was 52.81±11.64 years. In the case group, 71% of the subjects were female, whereas 51.6% of the control group were male. Most subjects, either in the case group (71%) or the control group (71%), used carboplatin. In the case group, cervix malignancy was the most common malignancy (32.3%), whereas in the control group, it was nasopharyngeal malignancy (25.8%). High soluble P-selectin level was a risk factor for DVT (OR 3.38, CI 1.180 – 9.780, p=0.02). A high NET level was also a risk factor for DVT (OR 2.88, CI 1.026-8.074, p=0.04). The high MPO levels in this study could not be proven as a risk factor. Conclusions Soluble P-selectin and NET are risk factors that play a role in the pathophysiology of DVT through the pathomechanism of immunothrombosis induced by endothelial injury and activation of monocytes and neutrophils due to the use of platinum-based chemotherapy.

Introduction: Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment. Methodology: We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a nonprogression group (n=33). Clinical datawere compared between the two groups. Results: A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively. Conclusion: The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular trap (NET) has been implicated in the pathology of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the specific contributions of NLRP3, a NET-associated molecule, to EAE pathogenesis and its regulatory role in NET formation remain unknown. Methods: To investigate the detrimental effect of NETs supported by NLRP3 in MS pathogenesis, we induced EAE in WT and NLRP3 KO mice and monitored the disease severity. At the peak of the disease, NET formation was assessed by flow cytometry, immunoblotting, and immunofluorescence staining. To further identify the propensity of infiltrated neutrophils, NET-related chemokine receptors, degranulation, ROS production, and PAD4 expression levels were evaluated by flow cytometry. In some experiments, mice were injected with DNase-1 to eliminate the formed NETs. Results: Our data revealed that neutrophils significantly infiltrate the brain and spinal cord and form NETs during EAE pathogenesis. NLRP3 significantly elevates NET formation, primarily in the brain. NLRP3 also modulated the phenotypes of brain-infiltrated and circulating neutrophils, augmenting CXCR2 and CXCR4 expression, thereby potentially enhancing NET formation. NLRP3 facilitates NET formation in a ROS-dependent and PAD4-independent manner in brain-infiltrated neutrophils. Finally, NLRP3-supported NET formation exacerbates disease severity, triggering Th1 and Th17 cells recruitment. Conclusions: Collectively, our findings suggest that NLRP3-supported NETs may be an etiological factor in EAE pathogenesis, primarily in the brain. This study provides evidence that targeting NLRP3 could be a potential therapeutic strategy for MS, specifically by attenuating NET formation. [ABSTRACT FROM AUTHOR]

Thrombosis is a well‐known cardiovascular disease (CVD) complication that has caused death in many patients with cancer. Oral bacteria have been reported to contribute to systemic diseases, including CVDs, and tumor metastasis. However, whether oral bacteria‐induced thrombosis induces tumor metastasis remains poorly understood. In this study, the cariogenic oral bacterium Streptococcus mutans was used to examine thrombosis in vitro and in vivo. Investigation of tumor metastasis to the lungs was undertaken by intravenous S. mutans implantation using a murine breast cancer metastasis model. The results indicated that platelet activation, aggregation, and coagulation were significantly altered in S. mutans‐stimulated endothelial cells (ECs), with elevated neutrophil migration, thereby inducing thrombosis formation. Streptococcus mutans stimulation significantly enhances platelet and tumor cell adhesion to the inflamed ECs. Furthermore, S. mutans‐induced pulmonary thrombosis promotes breast cancer cell metastasis to the lungs in vivo, which can be reduced by using aspirin, an antiplatelet drug. Our findings indicate that oral bacteria promote tumor metastasis through thrombosis formation. Oral health management is important to prevent CVDs, tumor metastasis, and their associated death. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine tumours (NETs) are relatively rare gastrointestinal neoplasms. Many NETs have a favourable prognosis, but some show aggressive features and poor long-term survival. A relatively higher incidence of small lesions amenable to endoscopic resection has been noted. The aim of this review is to present a thorough review of the literature to assist clinicians in the endoscopic management of neuroendocrine tumours (rectal, gastric, duodenal, pancreatic and oesophageal NETs), to highlight novel endoscopic therapeutic techniques of resection. A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs. [ABSTRACT FROM AUTHOR]

Astrocytes are crucial in the regulation of neurotransmitter homeostasis, and while their involvement in the dopamine (DA) tripartite synapse is acknowledged, it necessitates a more comprehensive investigation. In the present study, experiments were conducted on primary astrocyte cultures from the striatum and cortex of neonatal rats. The pharmacological intricacies of DA uptake, including dependence on time, temperature, and concentration, were investigated using radiolabelled [3H]-DA. The mRNA expression of transporters DAT, NET, PMAT, and OCTs was evaluated by qPCR. Notably, astrocytes from both brain regions exhibited prominent mRNA expression of NET and PMAT, with comparatively lower expression of DAT and OCTs. The inhibition of DA uptake by the DAT inhibitor, GBR12909, and NET inhibitors, desipramine and nortriptyline, impeded DA uptake in striatal astrocytes more than in cortical astrocytes. The mRNA expression of NET and PMAT was significantly upregulated in cortical astrocytes in response to the DA receptor agonist apomorphine, while only the mRNA expression of NET exhibited changes in striatal astrocytes. Haloperidol, a DA receptor antagonist, and L-DOPA, a DA precursor, did not induce significant alterations in transporter mRNA expression. These findings underscore the intricate and region-specific mechanisms governing DA uptake in astrocytes, emphasizing the need for continued exploration to unravel the nuanced dynamics of astrocytic involvement in the DA tripartite synapse. [ABSTRACT FROM AUTHOR]

In the case of neuroendocrine tumors (NETs), additional resection should be considered if the pathological examination shows positive for lymphovascular invasion, but there is not enough evidence on the long-term prognosis. Among patients with a NET G1 < 1 cm in diameter which was confined to the submucosal layer and treated endoscopically at our hospital between January 2005 and December 2021, 44 (27.8%) with vascular invasion were enrolled to investigate the lymph node/distant metastasis rate and the recurrence/mortality rate. Twelve patients were placed in the additional resection group (two with lymph node metastasis), and 32 were placed in the no additional treatment group (five with death from other causes). No distant metastasis, recurrence, or current death was observed in either group. There was also no recurrence of or death due to primary tumor among the patients with positive vascular invasion after endoscopic treatment of a NET G1 tumor < 1 cm in diameter. Colostomy was required in 75% of the patients who underwent an additional resection. Moreover, there were some cases of lymph node metastasis. The decision to perform an additional surgical resection should take into account the patient􀁠s wishes in terms of quality of life and the recurrence rate. How to stratify patients for follow-up remains an issue for future study. [ABSTRACT FROM AUTHOR]

This study investigates heat stress in 17 Indian cities during the post‐COVID‐19 lockdown period. The study compares thermal comfort experienced during the COVID‐19 lockdown against that experienced during post‐lockdown, which has not been previously studied. The analysis utilizes daily and monthly climate data from 1991 to 2022 obtained from the Langley Research Centre's official website. The net effective temperature (NET) and thermo‐hygrometric index (THI) were employed to assess heat stress in cities. The findings indicate a sudden increase in heat stress levels during the post‐lockdown period, particularly in cities like Lucknow, Chandigarh, Patna, Kolkata, Ahmadabad, Jodhpur, Guwahati, and Delhi. Moreover, there is a noticeable decline in the number of comfortable days for both THI and NET in certain cities, such as Delhi, Chandigarh, Bhopal, Ahmadabad, and Jodhpur, in 2021 and 2022. This analysis also reveals an overall rise in the number of torrid and very hot days, with significant increases recorded in 2022 compared to 2020. With a few exceptions, most cities show rising trends in THI and NET, causing Indian cities to experience more torrid and very hot months. This study clarifies the effect of the COVID‐19 lockdown on bioclimatic comfort and offers important guidance for future studies in this field. [ABSTRACT FROM AUTHOR]

To combat climate change, carbon dioxide must be prevented from entering the atmosphere or even removed from it. Biochar is one potential practice to sequester carbon, but its climate change mitigation potential depends on a multitude of parameters. Differentiating areas of low and high climate change mitigation through biochar addition is key to maximize its potential and effectively use the available feedstock for its production. This study models the realistic application of 1 metric tonne (t) per hectare (ha) of forest harvest residue derived biochar over the climatically and pedologically diverse agricultural area of British Columbia, Canada, and provides a framework and assumptions for reproducibility in other parts of the world. The model accounts for the direct (input of organic carbon) and indirect (enhanced plant biomass) effects of biochar on soil organic carbon stock, its impact on nitrous oxide emissions from soils, and the avoided emissions from the reduced lime requirement due to biochar's alkalinization potential. Impacts are modelled over 20‐year time horizon to account for the duration and magnitude variation over time of biochar effect on plant biomass and nitrous oxide emissions from soil and conform to the IPCC GWP 20‐year time horizon reporting. The results show that a single application of 1 t of biochar per ha−1 can mitigate between 3 and 5 t CO2e ha−1 over a 20‐year time frame. Applied to the 746,000 ha of agricultural land of British Columbia this translate to the mitigation of a total of 2.5 million metric tonnes (Mt) CO2e over a 20‐year time frame. Further, the results identify agricultural areas in the Lower Mainland region (the southwestern corner of British Columbia) as the area maximizing climate change mitigation potential through biochar addition due to a combination of relative high temperature, high precipitation, and crops with high nitrogen requirement. [ABSTRACT FROM AUTHOR]

The large number of thermal indices introduced in the literature poses a challenge to identify the appropriate one for a given application. The aim of this study was to examine the effectiveness of widely used indices in quantifying the thermal environment for operational weather applications within a Mediterranean climate. Eight indices (six simple and two thermo-physiological) were considered, i.e., apparent temperature, heat index, humidex, net effective temperature (NET), physiologically equivalent temperature (PET), universal thermal climate index (UTCI), wet-bulb globe temperature, and wind chill temperature. They were estimated using hourly meteorological data between 2010 and 2021, recorded in 15 stations from the Automatic Weather Station Network of the National Observatory of Athens in the Athens metropolitan area, Greece. The statistical analysis focused on examining indices' sensitivity to variations of the thermal environment. NET, PET, and UTCI were evaluated as suitable for operational use, assessing both cool and warm environments, and extending their estimations to the entire range of their assessment scales. NET and PET often tended to classify thermal perception in the negative categories of their scales, with 63% of NET and 56% of PET estimations falling within the range of cool/slightly cool to very cold. UTCI estimations in the negative categories accounted for 25.8% (p < 0.001), while most estimations were classified in the neutral category (53.1%). The common occasions of extreme warm conditions in terms of both air temperature (Tair) and NET was 77.7%, Tair and UTCI 64.4%, and Tair and PET 33.6% (p < 0.001). According to the indices considered and the method followed, NET and UTCI satisfied sufficiently the requirements for operational use in the climate conditions of the Mediterranean climate. [ABSTRACT FROM AUTHOR]

Background: Narrative exposure therapy (NET) is a recommended intervention for people with multiple trauma histories; however, research is lacking into its use with people experiencing psychosis, many of whom report multiple trauma histories. Objective: This study aimed to explore experiences of NET in early intervention in psychosis (EIP) services. Method: Eight clinicians and four experts with lived experience (experts by experience) of psychosis and multiple trauma were interviewed on a single occasion using two versions (clinician and expert by experience) of a semi-structured interview schedule. Data was analysed using thematic analysis. Results: Five overarching themes were generated, relating to fear and avoidance of memories, importance of trust, organizing memories and making new meaning, reconnecting with emotions, and considerations when delivering NET in EIP. Conclusions: Directly addressing the impact of multiple trauma in people experiencing first episode psychosis is frightening and emotive, but helps to address painful memories and organize them into a personal narrative. Increases in distress and anomalous experiences were carefully considered by clinicians, but typically outweighed by the benefits of NET. Challenges were comparable to those described in non-psychosis research. Implications for clinical practice and future research are outlined. [ABSTRACT FROM AUTHOR]

Background: Early-Onset (EO) pancreatic neuroendocrine tumor (Pan- NET) is a rare disease, but whether it is clinically different from lateonset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LOPanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. Methods: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. Results: Overall 383 patients were included, 107 (27.9%) with EOPanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P<0.001) but had similar pathology features such as tumor grade (P=0.6), size (2.2 Vs. 2.3 cm, P=0.5) and stageof disease (P=0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P<0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%-28%) and 17% (95% CI 13%-23%), in EO-PanNET and LO-PanNET (P=0.3). Five-year disease-specific survivalwas 99%(95%CI 98%-100%)with no difference with respect to PanNET onset time (P=0.26). Conclusions: In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasma gondii, responsible for causing toxoplasmosis, is a prevalent food and waterborne pathogen worldwide. It commonly infects warmblooded animals and affects more than a third of the global human population. Once ingested, the parasite enters the host's small intestine and rapidly disseminates throughout the body via the bloodstream, infiltrating various tissues. Leukocyte-driven responses are vital against T. gondii, with neutrophils playing a dual role: swiftly recruited to infection sites, releasing inflammatory mediators, and serving as a replication hub and Trojan horses, aiding parasite spread. Neutrophils from various hosts release extracellular traps (NETs) against the protozoan. However, gaps persist regarding the mechanisms of NETs production to parasite and their significance in infection control. This study investigates the interplay between human neutrophils and T. gondii, exploring dynamics, key molecules, and signaling pathways involved in NETs production upon protozoan challenge. Methods and Results: Using confocal and electron microscopy, live cell imaging, pharmacological inhibitors, and DNA quantification assays, we find that human neutrophils promptly release both classical and rapid NETs upon pathogen stimulation. The NETs structure exhibits diverse phenotypes over time and is consistently associated with microorganisms. Mechanisms involve neutrophil elastase and peptidylarginine deiminase, along with intracellular calcium signaling and the PI3K pathway. Unexpectedly, human traps do not diminish viability or infectivity, but potentially aid in capturing parasites for subsequent neutrophil phagocytosis and elimination. Discussion: By revealing NETs formation mechanisms and their nuanced impact on T. gondii infection dynamics, our findings contribute to broader insights into host-pathogen relationships. [ABSTRACT FROM AUTHOR]