New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.

CRISPR-Cas3 and type I restriction-modification team up against blaKPC-IncF plasmid transfer in Klebsiella pneumoniae.

OBJECTIVE: We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks. METHODS: 932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and blaKPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems. RESULTS: We found a significant inverse correlation between the presence of CRISPR and R-M systems and blaKPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in blaKPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder blaKPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of blaKPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity. CONCLUSIONS: Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP.

Comparative imaging study of patients with persistent olfactory dysfunction due to mild COVID-19 using structural and functional MRI.

INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging. MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function. RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively. CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.

Update in imaging tests used for the localization of parathyroid pathology.

Preoperative localization of parathyroid pathology, generally a parathyroid adenoma, can be difficult in some cases due to the anatomical variants that these glands present. The objective of this review is to analyse the different imaging techniques used for preoperative localization of parathyroid pathology (scintigraphy, ultrasound, CT, MRI and PET). There is great variability between the different tests for the preoperative localization of parathyroid pathology. The importance of knowing the different diagnostic options lies in the need to choose the most suitable test at each moment and for each patient for an adequate management of primary hyperparathyroidism (PHP) with surgical criteria.

Crosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity.

The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103+ dendritic cells, and IgA+ plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8+ T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8+ T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-ß, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.

Synthesis and Physicochemical Characterization of Gelatine-Based Biodegradable Aerogel-like Composites as Possible Scaffolds for Regenerative Medicine.

Regenerative medicine is an interdisciplinary field aiming at restoring pathologically damaged tissues and whole organs by cell transplantation in combination with proper supporting scaffolds. Gelatine-based ones are very attractive due to their biocompatibility, rapid biodegradability, and lack of immunogenicity. Gelatine-based composite hydrogels, containing strengthening agents to improve their modest mechanical properties, have been demonstrated to act as extracellular matrices (ECMs), thus playing a critical role in "organ manufacturing". Inspired by the lysyl oxidase (LO)-mediated process of crosslinking, which occurs in nature to reinforce collagen, we have recently developed a versatile protocol to crosslink gelatine B (Gel B) in the presence or absence of LO, using properly synthesized polystyrene- and polyacrylic-based copolymers containing the amine or aldehyde groups needed for crosslinking reactions. Here, following the developed protocol with slight modifications, we have successfully crosslinked Gel B in different conditions, obtaining eight out of nine compounds in high yield (57-99%). The determined crosslinking degree percentage (CP%) evidenced a high CP% for compounds obtained in presence of LO and using the styrenic amine-containing (CP5/DMAA) and acrylic aldehyde-containing (CPMA/DMAA) copolymers as crosslinking agents. ATR-FTIR analyses confirmed the chemical structure of all compounds, while optical microscopy demonstrated cavernous, crater-like, and labyrinth-like morphologies and cavities with a size in the range 15-261 µm. An apparent density in the range 0.10-0.45 g/cm3 confirmed the aerogel-like structure of most samples. Although the best biodegradation profile was observed for the sample obtained using 10% CP5/DMAA (M3), high swelling and absorption properties, high porosity, and good biodegradation profiles were also observed for samples obtained using the 5-10% CP5/DMAA (M4, 5, 6) and 20% CPMA/DMAA (M9) copolymers. Collectively, in this work of synthesis and physicochemical characterization, new aerogel-like composites have been developed and, based on their characteristics, which fit well within the requirements for TE, five candidates (M3, M4, M5, M6, and M9) suitable for future biological experiments on cell adhesion, infiltration and proliferation, to confirm their effective functioning, have been identified.

A botanical extract blend of Mangifera indica and Sphaeranthus indicus combined with resistance exercise training improves muscle strength and endurance over exercise alone in young men: a randomized, blinded, placebo-controlled trial.

Resistance exercise training (RET) is used to improve muscular strength and function. This study tested the hypothesis that RET alongside daily supplementation of a Sphaeranthus indicus and Mangifera indica extract blend (SMI) would augment bench press (BP) and leg extension (LE) strength and repetitions to failure (RTF) compared to RET alone. Ninety-nine men (age 22 ± 3) completed the trial after randomization into one of four groups: (A1) 425 mg SMI plus one RET set; (A2) 850 mg SMI plus one RET set; (P1) placebo plus one RET set; and (P2) placebo plus two RET sets. RET sets were 6-8 BP and LE repetitions at 80% of a progressive one repetition maximum (1-RM), performed 3x/week for 8 weeks. Strength and RTF were evaluated at baseline and days 14, 28, and 56 while serum values of total testosterone (TT), free testosterone (FT), and cortisol (C) values were evaluated at baseline and day 56. RET significantly (p < 0.05) increased 1-RM, RTF, and T measures above baselines regardless of group assignment, but the increases were greater in the supplemented groups. At week 8, A1 bench pressed more than P1 (71.5.5 ± 17.5 kg vs. 62.0 ± 15.3 kg, p = 0.003), while A2 pressed 13.8 ± 3.0 kg more (95% CI 5.7-21.8, p < 0.001) than P1 and 9.9 ± 13.0 kg more (95% CI 1.7-18.2, p = 0.01) than P2. Also at week 8, the mean LE 1-RM of A1 (159.4 ± 22.6 kg) and A2 (162.2 ± 22.9 kg) was greater (p < 0.05) than that of P1 (142.2 ± 25.6 kg) and P2 (146.5 ± 19.7 kg). Supplementation improved RTF, TT, and FT values over those measured in exercise alone (p < 0.05), while C levels in A2 (9.3 ± 3.8 µg/dL) were lower than P2 (11.7 ± 3.8 µg/dL, p < 0.05). Daily supplementation with SMI was well tolerated and may help optimize muscle adaptive responses to RET in men.

A Whole-Process Visible Strategy for the Preparation of Rhizomucor miehei Lipase with Escherichia coli Secretion Expression System and the Immobilization.

BACKGROUND: Rhizomucor miehei (RM) lipase is a regioselective lipase widely used in food, pharmaceutical and biofuel industries. However, the high cost and low purity of the commercial RM lipase limit its industrial applications. Therefore, it is necessary to develop cost-effective strategies for large-scale preparation of this lipase. The present study explored the high-level expression of RM lipase using superfolder green fluorescent protein (sfGFP)-mediated Escherichia coli secretion system. RESULTS: The sfGFP(-15) mutant was fused to the C-terminus of RM lipase to mediate its secretion expression. The yield of the fusion protein reached approximately 5.1 g/L with high-density fermentation in 5-L fermentors. Unlike conventional secretion expression methods, only a small portion of the target protein was secreted into the cell culture while majority of the fusion protein was still remained in the cytoplasm. However, in contrast to intracellular expression, the target protein in the cytoplasm could be transported efficiently to the supernatant through a simple washing step with equal volume of phosphate saline (PBS), without causing cell disruption. Hence, the approach facilitated the downstream purification step of the recombinant RM lipase. Moreover, contamination or decline of the engineered strain and degradation or deactivation of the target enzyme can be detected efficiently because they exhibited bright green fluorescence. Next, the target protein was immobilized with anion-exchange and macropore resins. Diethylaminoethyl sepharose (DEAE), a weak-basic anion-exchange resin, exhibited the highest bind capacity but inhibited the activity of RM lipase dramatically. On the contrary, RM lipase fixed with macropore resin D101 demonstrated the highest specific activity. Although immobilization with D101 didn't improve the activity of the enzyme, the thermostability of the immobilized enzyme elevated significantly. The immobilized RM lipase retained approximately 90% of its activity after 3-h incubation at 80 °C. Therefore, D101 was chosen as the supporting material of the target protein. CONCLUSION: The present study established a highly efficient strategy for large-scale preparation of RM lipase. This innovative technique not only provides high-purity RM lipase at a low cost but also has great potential as a platform for the preparation of lipases in the future.

Effect of methyl methacrylate concentrations on surface and thermal analysis of composite polymer polymethylmethacrylates with mesogen reactive RM82.

This research report of the synthesis of composite polymers from liquid crystal mesogen reactive (RM82) monomers with Methyl methacrylate (MMA). The purpose of this research is analysis the effect concentration of MMA on the surface and thermal of the composite polymer PMMA-RM82. The result of the morphological analysis of composite surfaces performed by polarization optical microscopy (POM) technique showed liquid crystal textures affected composition from two monomers. SEM images show that the surface of the RM82 liquid crystal has a shape resembling fibrous and blade-like crystals with a length of up to 10 µm (micrometers). Analysis thermal showed the heat released by the PMMA-RM82 increased with the increase in MMA weight percent. This affects the rapid crystallization process of PMMA-RM82 which of concentration MMA 30%-RM82 the heat released is almost twice as much as the heat released by MMA 5%-RM82. The absence of PMMA and RM82 peaks both endothermic and exothermic in PMMA-RM82 samples indicates that polymerization has occurred and a new product has formed. Analysis structure molecule by FTIR found that the IR spectral form of each variation in the weight percent of MMA was almost the same, but there was a spectral shift that showed that polymerization had occurred in PMMA-RM82 which was characterized by a reaction to the free radical C=C bond released by the photoinitiator. XRD pattern of composite PMMA-RM82 showed the peaks formed are located at scattering angles similar to RM82 but there is a decrease in intensity as the percent weight of MMA increases.

Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas.

OBJECTIVES: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with High Grade Gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. PATIENTS AND METHODS: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the Lineal Regression method.Those statistical analysis were carried out using the software SPSS v.17. RESULTS: 38 patients were included (average age: 61.1 years old). The general average survival period was 20.6 months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV)>3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6 months vs. 22.8 months, p = 0.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. CONCLUSIONS: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.

Genetic Map Construction Using F2 and RIL/DH Mapping Population.

Genetic mapping is the determination of the position and relative genetic distance between genes or molecular markers in the chromosomes of a particular species. The construction of genetic maps uses data from the genotyping of the mapping population. Among the different mapping populations used, two are relatively common: the F2 and recombinant inbred lines (RILs) obtained as a result of the controlled crossing of genetically diverse parental forms (e.g., inbred lines). Also, the dihaploid (DH) population is often used in plants, but obtaining DHs in different crops, including rye, is very difficult or even impossible. Any molecular marker system can be used for genotyping. Polymorphic markers are used for linkage analysis, differentiating parental forms with segregation in the mapping population, consistent with the appropriate single-gene model. A genetic map is a great source of information on a species and can be an exquisite tool for analyzing important quantitative traits (QT).This chapter presents the procedure of genetic map construction with two different algorithms using the JoinMap5.0 program. First, the Materials section briefly informs about the mapping program, showing how to obtain a mapping population and prepare data for mapping. Finally, the Methods section describes the protocol for the mapping procedure itself.

Emerging monoclonal antibody therapy for head and neck squamous cell carcinoma.

INTRODUCTION: The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, particularly among younger populations. It is projected that the number of new cases will increase by almost 50% by 2040, with market revenues expected to triple in the same period. Despite the recent introduction of immune checkpoint inhibitors (ICIs) into the therapeutic armamentarium, the vast majority of patients with recurrent and/or metastatic (R/M) HNSCC fail to derive durable benefits from systemic therapy. AREAS COVERED: This article aims to review the multiple monoclonal antibodies (mAbs) regimens currently under development, targeting various growth factors, immune checkpoints, immune costimulatory receptors, and more. EXPERT OPINION: So far, the combination of anti-EGFR and ICI appears to be the most promising, especially in HPV-negative patients. It will be interesting to confirm whether the arrival of antibody-drug conjugates and bispecific mAb can surpass the efficacy of anti-EGFR, as they are also being tested in combination with ICI. Furthermore, we believe that immune costimulatory agonists and various ICIs combination are worth monitoring, despite some initial setbacks.

Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-ß. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Valor pronóstico de la perfusión cerebral por RM en el estudio inicial de los gliomas de alto grado / Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas

Objetivos: Valorar si la perfusión tumoral en el estudio diagnóstico inicial de RM es un marcador pronóstico para la supervivencia en pacientes diagnosticados de gliomas de alto grado. Analizar los factores de riesgo que influyen en la mortalidad por gliomas de alto grado para poder cuantificar la supervivencia global esperada del paciente. Pacientes y métodos: Se seleccionaron las RM de todos los pacientes diagnosticados de glioma de alto grado en un hospital de tercer nivel entre los años 2017 y 2019. Se recogieron variables clínicas y tumorales. Se usó el análisis de supervivencia para determinar la asociación entre la perfusión tumoral y el tiempo de supervivencia. Se estudió la relación entre las variables recogidas y la supervivencia mediante el estadístico de Wald, cuantificando esta relación mediante la regresión de Cox. Por último, se analizó el tipo de relación existente entre la perfusión tumoral y la supervivencia a través del estudio de regresión lineal. Estos análisis estadísticos se realizaron con el software SPSS v.17. Resultados: Se incluyeron 38 pacientes (media de edad 61,1años). La supervivencia media global fue de 20,6meses. Se observó asociación entre la perfusión tumoral en la RM diagnóstica y la supervivencia global, mostrando el grupo con valores intratumorales de volumen sanguíneo cerebral relativo (rVSC) >3,0 una disminución significativa en el tiempo medio de supervivencia respecto al grupo con valores <3,0 (14,6meses vs 22,8meses, p=0,046). También han demostrado influir significativamente en la supervivencia media variables como la escala de Karfnosky y el tiempo de recidiva desde la intervención. Conclusiones: Se ha evidenciado que la perfusión tumoral por RM tiene valor pronóstico en el estudio inicial de los gliomas de alto grado.(AU)

Objectives: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with high grade gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. Patients and methods: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the lineal regression method.Those statistical analysis were carried out using the software SPSS v.17. Results: Thirty-eight patients were included (average age: 61.1years old). The general average survival period was 20.6months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV) >3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6months vs. 22.8months, P=.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. Conclusions: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.(AU)

Detección de la infiltración de la cadena mamaria interna en pacientes con cáncer de mama mediante PET/RM con 18F-FDG y sus implicaciones terapéuticas / Detection of internal mammary chain infiltration in breast cancer patients by [18F]FDG PET/MRI: Therapy implications

Objetivo: Evaluar la tasa de detección y la implicación terapéutica de la infiltración de la cadena mamaria interna (ICMI) mediante tomografía por emisión de positrones (PET) y resonancia magnética (RM) con 18F-fluorodesoxiglucosa (18F-PET/RM) en la estadificación de pacientes con cáncer de mama. Método: Estudio prospectivo, 41 mujeres con cáncer de mama (estadio ≥ IIB) estadificadas mediante 18F-FDG-PET/RM. Estudio en dos fases: imágenes mamarias (decúbito prono), cuerpo completo (supino). Estadificación TNM por consenso entre especialista en Medicina Nuclear y Radiología. Estudio vaso aferente (VA) a cadena mamaria interna (CMI) por RM mamaria. Correlación ICMI con edad, VA-CMI, estadificación T, cuadrante, infiltración axilar y a distancia. Revaloración terapéutica en comité multidisciplinar. Resultados: Tasa de detección de ICMN de 34% (14/41), siendo 8/14 < 55 años. Todas las 14 pacientes con ICMI muestran VA-CMI, en seis de ellas (43,9%) sin VA-axilar. De 27/41 sin ICMI, en 13 (48,1%) solo VA-axilar, en los 14 restantes (51,9%) VA-axilar y VA-CMI. Un total de 57% (8/14) son multicéntricos y 42% (6/14) focales, en cuadrantes internos en 4/6 (66,7%). En 1/14 (7,1%) solo ICMI, en 9/14 (64,3%) axilar y CMI y en 4/14 (28,6%) lesiones a distancia. Decisión del comité: sin tratamiento adicional en 27/41 (65,8%), radioterapia torácica en 10/41 (24,4%) y terapia sistémica en 4/41 (9,7%). Conclusión: La tasa de detección de la ICMI en la estadificación del cáncer de mama mediante 18F-FDG PET/RM es de 34%. Son factores asociados la edad, los tumores multicéntricos, los de cuadrantes internos, la existencia de VA-CMI, la estadificación NM. La evidencia de ICMI permite la individualización de la terapia, indicando la radioterapia torácica en 24,4%.(AU)

Objective: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. Methods: Prospective study including 41 women with breast cancer (stage ≥IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. Results: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). Conclusion: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging.The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.(AU)

Controversy in the initial nodal staging of rectal cancer (MRI or PET/CT?).

OBJECTIVE: To compare the usefulness of MRI and PET/CT in nodal staging (N) of patients with locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Retrospective study of patients with LARC, who completed their initial staging with PET/CT, between January-20 and March-23. Regional nodes were assessed, and N was determined using both techniques according to TNM criteria. Concordance between MRI and PET/CT was analyzed. The accuracy of both techniques was calculated for those patients who underwent direct surgery. Non-regional pelvic lymph nodes were evaluated by both modalities. RESULTS: Among the 73 patients, 48 were ultimately diagnosed with a locally advanced stage. Of these, 39 underwent neoadjuvant treatment (chemoradiotherapy) followed by surgery, and 9 direct surgery. In 25, the PET/CT extension study revealed distant disease, leading to systemic treatment. Weak concordance was observed between MRI and PET/CT in determining N (k=0.286; p<0.005). Out of 73 patients, 31(42%) exhibited concordance, and 42(58%) showed discordance. In 83% of the discordant cases, MRI overstaged compared to PET/CT, with 17 cases indicating nodal involvement (N+) by MRI and N0 by PET/CT. Diagnostic accuracy was 78% for both techniques. Sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 75%, 80%, and 75% for MRI, and 60%, 100%, 100%, and 67%, for PET/CT. PET/CT identified pelvic metastatic adenopathies in 8 patients that were not visible/doubtful by MRI. CONCLUSIONS: In the initial nodal staging of rectal cancer MRI overstages relative to PET/CT. Both modalities are complementary, PET/CT offers higher specificity and MRI higher sensitivity.

The Emergence of a Polar Nematic Phase: A Chemist's Insight into the Ferroelectric Nematic Phase.

The discovery of a new polar nematic phase; the ferroelectric nematic, has generated a great deal of excitement in the field of liquid crystals. To date there have been around 150 materials reported exhibiting the ferroelectric nematic phase, in general, following three key archetypal structures with these compounds known as RM734, DIO and UUQU-4N. In this review, the relationship between the molecular structure and the stability of the ferroelectric nematic, NF, phase will be described from a chemist's perspective. This will look to highlight the wide variety of functionalities which have been incorporated into these archetypal structures and how these changes influence the transition temperatures of the mesophases present. The NF phase appears to be stabilised particularly by reducing the length of terminal alkyl chains present and adding fluorines laterally along the length of the molecular backbone. This review will look to introduce the background of the ferroelectric nematic phase before then showing the molecular structures of a range of materials which exhibit the phase, describing their structure-property relationships and therefore giving an up-to-date account of the literature for this fascinating new mesophase.

Characterization of a Novel N4-Methylcytosine Restriction-Modification System in Deinococcus radiodurans.

Deinococcus radiodurans is an extremophilic microorganism that possesses a unique DNA damage repair system, conferring a strong resistance to radiation, desiccation, oxidative stress, and chemical damage. Recently, we discovered that D. radiodurans possesses an N4-methylation (m4C) methyltransferase called M.DraR1, which recognizes the 5'-CCGCGG-3' sequence and methylates the second cytosine. Here, we revealed its cognate restriction endonuclease R.DraR1 and recognized that it is the only endonuclease specially for non-4C-methylated 5'-CCGCGG-3' sequence so far. We designated the particular m4C R.DraR1-M.DraR1 as the DraI R-M system. Bioinformatics searches displayed the rarity of the DraI R-M homologous system. Meanwhile, recombination and transformation efficiency experiments demonstrated the important role of the DraI R-M system in response to oxidative stress. In addition, in vitro activity experiments showed that R.DraR1 could exceptionally cleave DNA substrates with a m5C-methlated 5'-CCGCGG-3' sequence instead of its routine activity, suggesting that this particular R-M component possesses a broader substrate choice. Furthermore, an imbalance of the DraI R-M system led to cell death through regulating genes involved in the maintenance of cell survival such as genome stability, transporter, and energy production. Thus, our research revealed a novel m4C R-M system that plays key roles in maintaining cell viability and defending foreign DNA in D. radiodurans.

The efficacy of cetuximab plus PD-1 inhibitors as salvage therapy in PD-1 refractory patients with recurrent or metastatic head and neck squamous cell carcinoma.

Purpose: The prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) that are refractory to programmed cell death protein 1 (PD-1) immunotherapy is relatively poor. The salvage therapy was rarely investigated and urgently needed. Methods: We conducted a single center retrospective real-world study to explore the efficacy of cetuximab plus PD-1 inhibitors as salvage therapy in patients progressed from first-line immunotherapy. Results: In the present study, 28 eligible patients were included between October 2020 and May 2023. By the cut-off date (Sep 24th, 2023), the objective response rate (ORR) was 46.4% (95% CI, 29.5%-64.2%). Kaplan-Meier survival analysis revealed the median progression free survival (mPFS) in the study was 6.87 months (95% CI, 4.77-8.97 months), and median overall survival (mOS) was 9.67 months (95% CI, 4.79-14.55 months). Multivariate Cox regression analysis indicated that ECOG performance status and best response to salvage therapy was found to be the prognosis factor of salvage therapy. For the safety, the most common treatment related adverse events (TRAEs) were rash (72.1%), anemia (64.3%) and fatigue (46.5%) during the salvage therapy. The most common potential irAEs were hypothyroidism (25%), and pneumonitis (14.3%). Only 3 patients (10.7%) experienced grade 3 TRAEs, and no treatment-related deaths occurred. Conclusions: Our study showed the combination of cetuximab with PD-1 inhibitors might be a potential efficacy and safety choice in PD-1 refractory patients with R/M HNSCC which need further investigation.