Background
Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. ...While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC.
Methods
NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed
in vitro
and
in vivo
and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity.
Results
HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression.
In vivo
experiments confirmed the efficacy of the therapy against both HLA
+
and HLA
−
CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control.
Conclusions
Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.
This paper reports the presence of the common dolphinfish, Coryphaena hippurus, in Argentinian waters for the first time, with a specimen collected by experienced sport fishermen near Mar del Plata ...(38°S). This finding also represents the first record of a species from the Coryphaenidae family in Argentinian waters. The collection of these specimens coincided with sightings of other rarely-seen pelagic and oceanic fish species during the same period, providing further evidence supporting the influx of subtropical fish species from warmer Brazilian waters. These observations highlight the need for continued monitoring of fish populations and their distribution and the ecological dynamics within the region.
Abstract Red seal inks from Korea (6), Japan (1) and China (6) were studied to investigate the feasibility of micro-attenuated total reflectance (ATR) FTIR spectroscopy as a tool in the forensic ...study of questioned documents involving seal inks. The technique was able to differentiate red seal inks of similar colors and different manufacturers. Blind testing has shown that micro-ATR FTIR can identify the origin of the red seal inks with accuracy. Data gathered were converted to a database for future reference. Also, the technique was also successful in determining the sequence of heterogeneous line intersection from a personal seal and a ballpoint pen. The results show that micro-ATR FTIR can be a valuable non-destructive tool for the objective analysis of questioned documents involving different red seal inks.
Microquasars (MQs) are binary systems composed by a star feeding mass to a compact object through an accretion disk. The compact object, usually a black hole, launches oppositely directed jets which ...are typically observed in our galaxy through their broadband electromagnetic emission. These jets are considered potential galactic neutrino sources. MQs can also have been formed by the first generations of stars in the universe, i.e., Population III (Pop III) stars, which are considered essential contributors to the ionization processes that took place during the period of ãcosmic reionizationå. In the present work, we develop a model that accounts for the main particle processes occurring within Pop III MQ jets, with the aim to obtain the diffuse neutrino flux at the Earth. We define different zones within the jets of Pop III MQs where particle interactions occur, and primary particles (i.e protons and electrons) are injected. We solve a transport equation for each zone, including the relevant cooling and escape processes, which include pγ and pp interactions. Once we obtain the primary particle distributions, we compute the pion and muon distributions, as well as the neutrino output produced by their decays. Finally, we obtain the diffuse neutrino flux by integration over the redshift, the line-of-sight angle, and the MQs lifetime. We find that, for a range of parameters suitable for Pop III MQ jets, the most relevant site for neutrino production in the jets is the base of the inner conical jet. Additionally, if protons accelerated at the forward shock formed at terminal jet region can escape from the outer shell, they would produce further neutrinos via pγ interactions with the cosmic microwave background (CMB). The latter contribution to the diffuse neutrino flux turns out to be dominant in the range 107GeV≲Eν≲109GeV, while the neutrinos produced in the inner jet could only account for a small fraction of the IceCube flux for Eν∼105 GeV. The co-produced multiwavelength photon background is also computed and it is checked to be in agreement with observations.
Solar thermal-driven heat engines for water pumping have been previously reviewed for some authors in the past century. However, some devices have not been treated as metal hydride-based systems or ...the pumping subsystems of solar thermal-driven reverse osmosis desalination systems. Following the typical classification given in the previous literature, in this work an update of the solar heat engines for water pumping based in thermodynamic methods (conventional and unconventional) is presented. Besides small remarks about systems previously quoted by other authors, new designs found in the literature are described. In general, the main characteristics of these systems is their low efficiency, low power output and, in the case of unconventional designs, its simplicity. This work in conjunction with previous review papers make up reference point for the knowledge of the use of solar thermal energy for liquid pumping purpose.
Abstract Drosophila has a massive number of members and a wide range of habitats. Different natural conditions make it possible to find diverse Drosophila populations, although several types of ...Drosophila are cosmopolitan. Drosophila diversity is characterized by morphological variations. The structural similarity of an individual can be used to determine various kinship relations between organisms. This research aimed to determine the relation between Drosophila from three regions in East Java, Indonesia, namely Malang, Mojokerto, and Pasuruan, based on similarities in morphological characteristics. Samples were taken from these three areas, and observations were carried out from January to May 2023 at the Genetics Laboratory, Biology Department, FMIPA UM. Identification of Drosophila is based on an identification key consisting of 52 traits. Drosophila was purified to the third generation to achieve a homogeneity of 87.5%. The kinship relation is sought by calculating the association coefficient and similarity index as a reference in preparing the dendrogram. The dendrogram illustrates that Drosophila from Malang had a closer relationship with Drosophila from the Pasuruan area than from the Mojokerto area. Drosophila kinship relations are influenced by internal and external factors, which include gene flow, mobility, distance, and natural conditions.
Summary
Background
Mast cells (MCs) play a key role in allergic diseases through the release of inflammatory mediators, which are responsible of allergic symptoms. Mastocytosis is characterized by an ...abnormal proliferation and accumulation of mast cells, in which mediators are released intermittingly or continuously. Despite these clinical similarities, few studies have addressed the presence of allergic symptoms in mastocytosis patients, including anaphylaxis.
Objective
A prospective evaluation was carried out to study the prevalence of allergic diseases in patients with mastocytosis and their impact on the natural history of mastocytosis.
Methods
A questionnaire was given to 210 patients with mastocytosis to evaluate the history of asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop® infant (aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done to 72 patients.
Results
The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Total IgE level was significantly higher in patients with allergy as compared with patients without allergy (median 58 vs. 16.5 kU/L, P<0.0001). Anaphylactic symptoms were present in 36 patients (22%), in nine the allergen was identified. Males had more allergy and anaphylactic symptoms than females (61.5% vs. 38.5% and 72% vs. 28%, respectively).
Conclusions
Allergic diseases coexist in patients with mastocytosis with similar frequency as compared with the general population. Anaphylactic symptoms are more prevalent in males with mastocytosis and in patients with elevated IgE.
Capsule summary
The prevalence of allergy in mastocytosis is similar to the general population. Anaphylactic symptoms are more prevalent in males and in patients with elevated IgE. The coexistence of atopy does not influence mastocytosis‐associated symptoms.
The hapuku wreckfish Polyprion oxygeneios is recorded for the first time in Argentinian waters. Four specimens were caught off Mar del Plata (38degreesS, Argentina) in depths between 60 and 260 m ...during austral summer (three by sport fishers and one in a research cruise). Up to the present, this species was consistently misidentified with its congener, the common wreckfish P. americanus, off Argentina. These records represent a connection between previous records from Brazil and the more austral circumglobal distribution of the species.
ObjectivesWe developed (a) a survey to investigate the knowledge of childhood health experts on public policies and behavioural insights (BI), as well as its use in Latin American and the Caribbean ...countries (LACs), and (b) an intervention (randomised controlled trial) to test the influence of nudges on the effect of a simulated public health programme communication.Participants and settingsA total of 2003 LACs childhood health professionals participated in the study through a Hispanic online platform.Primary and secondary outcomesWe used regression models analysing expertise-related information, individual differences and location. We extracted several outcome variables related to (a) ‘Public Policy Knowledge Index’ based on the participants’ degree of knowledge on childhood health public policies and (b) BI knowledge, perceived effectiveness and usefulness of a simulated public programme communication. We also analysed a ‘Behavioural Insights Knowledge Index’ (BIKI) based on participants’ performance in BI questions.ResultsIn general, health professionals showed low BI knowledge (knowledge of the term BI: χ2=210.29, df=1 and p<0.001; BIKI: χ2=160.5, df=1 and p<0.001), and results were modulated by different factors (age, academic formation, public policy knowledge and location). The use of BI principles for the communication of the public programme revealed higher impact and clarity ratings from professionals than control messages.ConclusionsOur findings provide relevant knowledge about BI in health professionals to inform governmental and non-governmental organisations’ decision-making processes related with childhood public policies and BI designs.
Successful 54 Gbit/s on–off keying (OOK) transmission over 2.2 km of multimode OM4 fibre is demonstrated. The decisive advantages of the single mode over multimode vertical cavity surface emitting ...laser (VCSEL) in transmission experiments are shown.