"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastoma.

The development of targeted therapies offers new hope for patients affected by incurable cancer. However, multiple challenges persist, notably in controlling tumor cell plasticity in patients with refractory and metastatic illness. Neuroblastoma (NB) is an aggressive pediatric malignancy originating from defective differentiation of neural crest-derived progenitors with oncogenic activity due to genetic and epigenetic alterations and remains a clinical challenge for high-risk patients. To identify critical genes driving NB aggressiveness, we performed combined chromatin and transcriptome analyses on matched patient-derived xenografts (PDXs), spheroids, and differentiated adherent cultures derived from metastatic MYCN nonamplified tumors. Bone marrow kinase on chromosome X (BMX) was identified among the most differentially regulated genes in PDXs and spheroids versus adherent models. BMX expression correlated with high tumor stage and poor patient survival and was crucial to the maintenance of the self-renewal and tumorigenic potential of NB spheroids. Moreover, BMX expression positively correlated with the mesenchymal NB cell phenotype, previously associated with increased chemoresistance. Finally, BMX inhibitors readily reversed this cellular state, increased the sensitivity of NB spheroids toward chemotherapy, and partially reduced tumor growth in a preclinical NB model. Altogether, our study identifies BMX as a promising innovative therapeutic target for patients with high-risk MYCN nonamplified NB.

Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency.

Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.

Efectos del entrenamiento cluster sobre la hipertrofia muscular: una revisión sistemática / Effects of cluster training on muscle hypertrophy: a systematic review / Efeitos do treinamento em cluster na hipertrofia muscular: uma revisão sistemática

Resumen Objetivo: El objetivo de la presente revisión sistemática fue determinar los efectos del entrenamiento cluster sobre la hipertrofia muscular. Metodología: Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Pubmed, Scopus y Web of Science, utilizando las siguientes palabras clave: 'cluster training', 'rest Interval', 'rest pause', 'hypertrophy', 'resistance training' y 'cross sectional area'. Se incluyeron ensayos clínicos que utilizaron el entrenamiento cluster como intervención en personas mayores de 18 años de ambos sexos. Resultados: La revisión sistemática obtenida durante la búsqueda de las bases de datos consultadas arrojó un total de 23 artículos, potencialmente elegibles, de los cuales se tomó una muestra de 9, con los que se podían obtener resultados que respondían al objetivo de esta revisión. La cantidad de participantes de los 9 artículos elegibles fue de 172 sujetos. Los entrenamientos cluster permiten aumentar el volumen de entrenamiento y la intensidad sin provocar elevados niveles de fatiga, favoreciendo así el desarrollo de la hipertrofia muscular. Conclusiones: Los resultados de esta revisión sistemática sugieren que los entrenamientos cluster pueden ser una herramienta eficaz para el desarrollo de la hipertrofia muscular.

Abstract Objective: The aim of this systematic review was to determine the effects of cluster training on muscle hypertrophy. Methodology: A literature search was performed in the electronic databases Pubmed, Scopus and Web of Science, using the following keywords: 'cluster training', 'rest interval', 'rest pause', 'hypertrophy', 'resistance training' and 'cross sectional area'. We included clinical trials that used cluster training as an intervention in people over 18 years of age of both sexes. Results: The systematic review obtained during the search of the databases consulted yielded a total of 23 potentially eligible articles, of which a sample of 9 was taken from which results could be obtained that responded to the objective of this review. The number of participants from the 9 eligible articles was 172 subjects. Cluster workouts allow for increased training volume and intensity without causing high levels of fatigue, thus favoring the development of muscle hypertrophy. Conclusions: The results of this systematic review suggest that cluster training can be an effective tool for the development of muscle hypertrophy.

Resumo Objetivo: O objetivo desta revisão sistemática foi determinar os efeitos do treinamento em cluster na hipertrofia muscular. Metodologia: Realizou-se uma busca na literatura nas bases de dados eletrônicas Pubmed, Scopus e Web of Science, utilizando as seguintes palavras-chave: 'cluster training', 'rest interval', 'rest pause', 'hypertrophy', 'resistance training' e 'cross sectional area'. Foram incluídos ensaios clínicos que utilizaram o treinamento em cluster como intervenção em pessoas com mais de 18 anos de ambos os sexos. Resultados: A revisão sistemática realizada durante a busca nas bases de dados consultadas resultou em um total de 23 artigos potencialmente elegíveis, dos quais uma amostra de 9 foi selecionada para obter resultados que respondessem ao objetivo desta revisão. O número de participantes nos 9 artigos elegíveis foi de 172 indivíduos. Os treinos em cluster permitem um aumento no volume e na intensidade do treinamento sem causar altos níveis de fadiga, favorecendo assim o desenvolvimento da hipertrofia muscular. Conclusões: Os resultados desta revisão sistemática sugerem que o treinamento em cluster pode ser uma ferramenta eficaz para o desenvolvimento da hipertrofia muscular.

Relación entre la percepción de condición física y medidas antropométricas auto reportadas en estudiantes universitarios

La percepción de la condición física en estudiantes universitarios se refiere a cómo se ven a sí mismos en términos de su estado físico y salud. En esta etapa, las variables antropométricas pueden verse afectadas por estrés, cambios en hábitos de sueño y alimentación, y menor participación en actividades físicas, impactando el desempeño académico y salud general. El objetivo fue relacionar la percepción de la condición física con medidas antropométricas auto reportadas en estudiantes universitarios Esta Investigación es de tipo descriptivo-correlacional, de diseño observacional y corte transversal. Fueron evaluados 46 estudiantes universitarios de la ciudad de Talca. La condición física se midió por medio del International Fitness Scale (IFIS) y las medidas antropométricas por medio de auto reporte. La condición física general se relacionó de manera inversa con la circunferencia de cintura (r=-0,32; p=0,028), la circunferencia de cintura(r=-0,44; p=0,002) y el ICE (r=-0,43; p=0,003). Se observaron correlaciones inversas entre la condición cardiorrespiratoria con el IMC (p=0,008; r=-0,38), circunferencia de cintura e ICE (p=0,008; r=-0,38). La velocidad/agilidad se correlacionó de forma inversa con el índice de masa corporal (IMC) (p=0,001; r=-0,46), circunferencia de cintura (p=0,019; r=-0,34), cadera (p= 0,004; r= -0,40) y el ICE (p=0,004; r=-0,41). La flexibilidad se correlaciono de forma inversa con el IMC (p=0,041; r=-0,30), circunferencia de cintura (p=0,023; r=-0,33), índice cintura cadera (ICC) (p= 0,001; r=-0,45)). Por último, la fuera muscular no se correlaciono con las variables antropométricas. Se concluye que existe correlación inversa entre la percepción de la condición física y algunos autore portes de las medidas antropométricas.

The physical fitness perception of college students refers to how they see themselves in terms of their physical condition and health. In this stage, anthropometric variables may be affected by stress, changes in sleep and eating habits, and decreased participation in physical activities, impacting academic performance and general health. The objective of this study is to relate the perception of physical condition with self-reported anthropometric measures in university students. This is a descriptive-correlational, observational, cross-sectional research. Forty-six university students from the city of Talca were evaluated. Physical condition was measured by means of the International Fitness Scale (IFIS) and anthropometric measures by means of self-report. General physical condition was inversely related to waist circumference (r=-0.32; p=0.028), waist circumference (r=-0.44; p=0.002) and IFIS (r=-0.43; p=0.003). Inverse correlations were observed between cardiorespiratory fitness with BMI (p=0.008; r=-0.38), waist circumference and ECI (p=0.008; r=-0.38). Speed/agility was inversely correlated with body mass index (BMI) (p=0.001; r=-0.46), waist circumference (p=0.019; r=-0.34), hip (p= 0.004; r= -0.40) and ECI (p=0.004; r=-0.41). Flexibility was inversely correlated with BMI (p=0.041; r=-0.30), waist circumference (p=0.023; r=-0.33), waist hip index (WHI) (p= 0.001; r=-0.45)). Lastly, muscle was not correlated with the anthropometric variables. It is concluded that there is an inverse correlation between the perception of physical condition and some anthropometric measures.

A percepção da aptidão física em estudantes universitários refere-se a como eles se veem em termos de sua condição física e saúde. Nessa fase, as variáveis antropométricas podem ser afetadas pelo estresse, por mudanças nos hábitos de sono e alimentação e pela diminuição da participação em atividades físicas, o que afeta o desempenho acadêmico e a saúde em geral. O objetivo foi relacionar a percepção da aptidão física com medidas antropométricas autorreferidas em estudantes universitários. Trata-se de uma pesquisa descritiva, correlacional, transversal e observacional. Foram avaliados 46 estudantes universitários da cidade de Talca. A condição física foi medida por meio da Escala Internacional de Aptidão Física (IFIS) e as medidas antropométricas por meio de autorrelato. A aptidão física geral foi inversamente relacionada à circunferência da cintura (r=-0,32; p=0,028), circunferência da cintura (r=-0,44; p=0,002) e IFIS (r=-0,43; p=0,003). Foram observadas correlações inversas entre a aptidão cardiorrespiratória com o IMC (p=0,008; r=-0,38), a circunferência da cintura e o ECI (p=0,008; r=-0,38). A velocidade/agilidade foi inversamente correlacionada com o índice de massa corporal (IMC) (p=0,001; r=-0,46), circunferência da cintura (p=0,019; r=-0,34), quadril (p= 0,004; r= -0,40) e ECI (p=0,004; r=-0,41). A flexibilidade foi inversamente correlacionada com o IMC (p=0,041; r=-0,30), a circunferência da cintura (p=0,023; r=-0,33), o índice cintura-quadril (WHI) (p= 0,001; r=-0,45). Por fim, a musculatura não foi correlacionada com as variáveis antropométricas. Concluise que há uma correlação inversa entre a percepção da condição física e algumas medidas antropométricas.

Relationship between appendicular muscular mass index and physical function in older people.

This study aimed to establish the relationship between the appendicular muscle mass index (AMMI), assessed from anthropometric variables, and the physical function of older people. Seventy-six older people participated in this study (72.03 ± 7.03 years). The participants underwent evaluations to determine their AMMI using anthropometry (weight, calf circumference, hip circumference, and knee height) and manual grip strength. Additionally, their physical function was evaluated using the 5-chair stand test, the 3-meter walk test, and the timed up and go test (TUG) to determine the strength of the lower limbs, the gait speed, and the dynamic balance, respectively. The results show that the AMMI did not present a significant relationship with the 5-chair stand test in both women (r = -0.135; p = 0.204) and men (r = -0.067; p = 0.349). The AMMI was moderately correlated with the gait speed in both women (r = 0.542; p < 0.001) and men (r = 0.556; p < 0.001). Finally, a statistical significance was observed in the relationship between the AMMI and the TUG test in women (r = -0.273; p = 0.047) and older men evaluated in this study (r = -0.284; p = 0.042). In conclusion, there is a relationship between the AMMI and both the dynamic balance and the gait speed. Therefore, the AMMI emerges as a potential public health assessment by enabling the clinical quantification of muscle mass and an estimation of physical function in the elderly population.

Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin.

Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.

A Novel Experimental Apparatus for Characterizing Flow Regime in Mechanically Stirred Tanks through Force Sensors.

Pressure fluctuations in a mixing tank can provide valuable information about the existing flow regime within the tank, which in turn influences the degree of mixing that can be achieved. In the present work, we propose a prototype for identifying the flow regime in mechanically stirred tanks equipped with four vertical baffles through the characterization of pressure fluctuations. Our innovative proposal is based on force sensors strategically placed in the baffles of the mixing tank. The signals coming from the sensors are transmitted to an electronic module based on an Arduino UNO development board. In the electronic module, the pressure signals are conditioned, amplified and sent via Bluetooth to a computer. In the computer, the signals can be plotted or stored in an Excel file. In addition, the proposed system includes a moving average filtering and a hierarchical bottom-up clustering analysis that can determine the real-time flow regime (i.e., the Reynolds number, Re) in which the tank was operated during the mixing process. Finally, to demonstrate the versatility of the proposed prototype, experiments were conducted to identify the Reynolds number for different flow regimes (static, laminar, transition and turbulent), i.e., 0≤Re≤ 42,955. Obtained results were in agreement with the prevailing consensus on the onset and developed from different flow regimes in mechanically stirred tanks.

A Comparison of Clear Cell Sarcoma to Jaw and Salivary Tumors Bearing EWS Fusions.

OBJECTIVE: To review tumors identified as "clear cell sarcoma" in order to determine similarities to the rare EWS fusion positive jaw and salivary gland tumors clear cell odontogenic carcinoma (CCOC) and clear cell carcinoma of the salivary gland (CCC). METHODS: PubMed was used to collect all reports of clear cell sarcoma (CCS). Search parameters were "clear cell sarcoma" and "CCS." References in the publications were screened and cross-referenced. Data extracted included demographic characteristics, presenting signs and symptoms, radiographic findings, histological and immunohistochemical features and known molecular/genetic aberrations. RESULTS: Clear cell sarcoma has several similarities to CCOC and CCC. All three tumor types have similar histologic appearances including the presence of clear cells, as well as similar genetic profiles in that all harbor an EWSR1-CREB family fusions. Additionally, these tumors appear in soft tissue as well as bone, and can have a prolonged clinical course. CCS can appear anywhere in the body, including the head and neck region. All three tumors appear to have a predilection to women, although CCS may have a slight younger age of onset as compared to CCOC and CCC (3rd vs 5th decade of life, respectively). CONCLUSION: Gaining a better understanding of the similarities and differences between these three tumors may lead to a better understanding of each one.

Ureteral stent after PCNL: is leaving the threads through the percutaneous tract safe and better tolerated?

OBJECTIVE: To assess safety, urinary symptoms, and feasibility of JJ stent removal with exteriorized threads through the percutaneous tract after percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Prospective, transversal, comparative, experimental, randomized 1-to-1 cohort study in 52 patients who underwent "tubeless" PCNL from October 2020 to November 2022. Group A with threads through the urethra and Group B through the percutaneous tract. The validated USSQ (Ureteral Stent Symptom Questionnaire) was applied in the Urology office a week after the procedure, and the JJ stent was withdrawn by pulling the threads. Hemoglobin and urine culture, and pre- and post-surgery were evaluated. RESULTS: There is a statistically significant difference in favor of group B when comparing urinary symptoms (p = 0.008), body pain (p = 0.009), and general condition (p = 0.042), mainly for non-urgency incontinence, frequency of analgesic use, and dysuria. There were significant differences between groups (p = 0.028, p = 0.026, p = 0.027, respectively). There is no association with urinary infections (p = 0.603) nor an increased risk of bleeding (p = 0.321). CONCLUSION: The removal of the JJ stent with exteriorized threads through the percutaneous tract after PCNL in the office is a feasible and safe procedure if it is removed before 8 days and has better tolerance regarding the urinary symptoms.

Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients.

There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn's disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56-87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1-9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.

CIC-DUX4 Chromatin Profiling Reveals New Epigenetic Dependencies and Actionable Therapeutic Targets in CIC-Rearranged Sarcomas.

CIC-DUX4-rearranged sarcoma (CDS) is a rare and aggressive soft tissue tumor that occurs most frequently in young adults. The key oncogenic driver of this disease is the expression of the CIC-DUX4 fusion protein as a result of chromosomal rearrangements. CIC-DUX4 displays chromatin binding properties, and is therefore believed to function as an aberrant transcription factor. However, the chromatin remodeling events induced by CIC-DUX4 are not well understood, limiting our ability to identify new mechanism-based therapeutic strategies for these patients. Here, we generated a genome-wide profile of CIC-DUX4 DNA occupancy and associated chromatin states in human CDS cell models and primary tumors. Combining chromatin profiling, proximity ligation assays, as well as genetic and pharmacological perturbations, we show that CIC-DUX4 operates as a potent transcriptional activator at its binding sites. This property is in contrast with the repressive function of the wild-type CIC protein, and is mainly mediated through the direct interaction of CIC-DUX4 with the acetyltransferase p300. In keeping with this, we show p300 to be essential for CDS tumor cell proliferation; additionally, we find its pharmacological inhibition to significantly impact tumor growth in vitro and in vivo. Taken together, our study elucidates the mechanisms underpinning CIC-DUX4-mediated transcriptional regulation.

DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins.

Intrinsically disordered regions (IDRs) in DNA-associated proteins are known to influence gene regulation, but their distribution and cooperative functions in genome-wide regulatory programs remain poorly understood. Here we describe DisP-seq (disordered protein precipitation followed by DNA sequencing), an antibody-independent chemical precipitation assay that can simultaneously map endogenous DNA-associated disordered proteins genome-wide through a combination of biotinylated isoxazole precipitation and next-generation sequencing. DisP-seq profiles are composed of thousands of peaks that are associated with diverse chromatin states, are enriched for disordered transcription factors (TFs) and are often arranged in large lineage-specific clusters with high local concentrations of disordered proteins and different combinations of histone modifications linked to regulatory potential. We use DisP-seq to analyze cancer cells and reveal how disordered protein-associated islands enable IDR-dependent mechanisms that control the binding and function of disordered TFs, including oncogene-dependent sequestration of TFs through long-range interactions and the reactivation of differentiation pathways upon loss of oncogenic stimuli in Ewing sarcoma.

Performance of point charge embedding schemes for excited states in molecular organic crystals.

Modeling excited state processes in molecular crystals is relevant for several applications. A popular approach for studying excited state molecular crystals is to use cluster models embedded in point charges. In this paper, we compare the performance of several embedding models in predicting excited states and S1-S0 optical gaps for a set of crystals from the X23 molecular crystal database. The performance of atomic charges based on ground or excited states was examined for cluster models, Ewald embedding, and self-consistent approaches. We investigated the impact of various factors, such as the level of theory, basis sets, embedding models, and the level of localization of the excitation. We consider different levels of theory, including time-dependent density functional theory and Tamm-Dancoff approximation (TDA) (DFT functionals: ωB97X-D and PBE0), CC2, complete active space self-consistent field, and CASPT2. We also explore the impact of selection of the QM region, charge leakage, and level of theory for the description of different kinds of excited states. We implemented three schemes based on distance thresholds to overcome overpolarization and charge leakage in molecular crystals. Our findings are compared against experimental data, G0W0-BSE, periodic TDA, and optimally tuned screened range-separated functionals.

Measurement of Cutting Temperature in Interrupted Machining Using Optical Spectrometry.

This research presents an experimental study focused on measuring temperature at the tool flank during the up-milling process at high cutting speed. The proposed system deals with emissivity compensation through a two-photodetector system and during calibration. A ratio pyrometer composed of two photodetectors and a multimode fiber-optic coupler is employed to capture the radiation emitted by the cutting insert. The pyrometer is calibrated using an innovative calibration system that addresses theoretical discrepancies arising from various factors affecting the measurement of cutting temperature. This calibration system replicates the milling process to generate a calibration curve. Experimentally, AISI 4140 steel is machined with coated tungsten carbide inserts, using cutting speeds of 300 and 400 m/min, and feed rates of 0.08 and 0.16 mm/tooth. The results reveal a maximum recorded cutting temperature of 518 °C and a minimum of 304 °C. The cutting temperature tends to increase with higher cutting speeds and feed rates, with cutting speed being the more influential factor in this increase. Both the pyrometer calibration and experimental outcomes yield satisfactory results. Finally, the results showed that the process and the device prove to be a convenient, effective, and precise method of measuring cutting temperature in machine processes.

Integrated Radiology, Pathology, and Pharmacy Program to Accelerate Access to Osimertinib.

PURPOSE: Targeted therapy yields superior outcomes relative to genotype-agnostic therapy for patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. Workflows that facilitate timely detection of EGFR mutations and early dispensation of osimertinib can improve management of this disease. METHODS: We developed an Integrated Radiology, Pathology, and Pharmacy Program to minimize delays in initiating osimertinib. The intervention consisted of parallel workflows coupling interventional radiology, surgical pathology, and analysis of nucleic acids from frozen tissue with early pharmacy engagement. We compared time to EGFR testing results and time to treatment for participating patients with those of historical cohorts. RESULTS: Between January 2020 and December 2021, 222 patients participated in the intervention. The median turnaround time from biopsy to EGFR results was 1 workday. Forty-nine (22%) tumors harbored EGFR exon 19 deletions or EGFR L858R. Thirty-one (63%) patients were prescribed osimertinib via the intervention. The median interval between osimertinib prescription and osimertinib dispensation was 3 days; dispensation occurred within 48 hours for 42% of patients. The median interval between biopsy and osimertinib dispensation was 5 days. Three patients received osimertinib within 24 hours of EGFR results. Compared with patients with EGFR-mutant non-small-cell lung cancer who were diagnosed through routine workflows, the intervention led to a significant reduction in median time between biopsy and EGFR results (1 v 7 days; P < .01) and median time to treatment initiation (5 v 23 days; P < .01). CONCLUSION: Combining radiology and pathology workflows with early parallel pharmacy engagement leads to a significant reduction in time to initiating osimertinib. Multidisciplinary integration programs are essential to maximize clinical utility of rapid testing.

Models of Polaron Transport in Inorganic and Hybrid Organic-Inorganic Titanium Oxides.

Polarons are a type of localized excess charge in materials and often form in transition metal oxides. The large effective mass and confined nature of polarons make them of fundamental interest for photochemical and electrochemical reactions. The most studied polaronic system is rutile TiO2 where electron addition results in small polaron formation through the reduction of Ti(IV) d0 to Ti(III) d1 centers. Using this model system, we perform a systematic analysis of the potential energy surface based on semiclassical Marcus theory parametrized from the first-principles potential energy landscape. We show that F-doped TiO2 only binds polaron weakly with effective dielectric screening after the second nearest neighbor. To tailor the polaron transport, we compare TiO2 to two metal-organic frameworks (MOFs): MIL-125 and ACM-1. The choice of MOF ligands and connectivity of the TiO6 octahedra largely vary the shape of the diabatic potential energy surface and the polaron mobility. Our models are applicable to other polaronic materials.

Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer.

Background: Small cell lung cancer (SCLC) is an extremely aggressive cancer type with a patient median survival of 6-12 months. Epidermal growth factor (EGF) signaling plays an important role in triggering SCLC. In addition, growth factor-dependent signals and alpha-, beta-integrin (ITGA, ITGB) heterodimer receptors functionally cooperate and integrate their signaling pathways. However, the precise role of integrins in EGF receptor (EGFR) activation in SCLC remains elusive. Methods: We analyzed human precision-cut lung slices (hPCLS), retrospectively collected human lung tissue samples and cell lines by classical methods of molecular biology and biochemistry. In addition, we performed RNA-sequencing-based transcriptomic analysis in human lung cancer cells and human lung tissue samples, as well as high-resolution mass spectrometric analysis of the protein cargo from extracellular vesicles (EVs) that were isolated from human lung cancer cells. Results: Our results demonstrate that non-canonical ITGB2 signaling activates EGFR and RAS/MAPK/ERK signaling in SCLC. Further, we identified a novel SCLC gene expression signature consisting of 93 transcripts that were induced by ITGB2, which may be used for stratification of SCLC patients and prognosis prediction of LC patients. We also found a cell-cell communication mechanism based on EVs containing ITGB2, which were secreted by SCLC cells and induced in control human lung tissue RAS/MAPK/ERK signaling and SCLC markers. Conclusions: We uncovered a mechanism of ITGB2-mediated EGFR activation in SCLC that explains EGFR-inhibitor resistance independently of EGFR mutations, suggesting the development of therapies targeting ITGB2 for patients with this extremely aggressive lung cancer type.

Sexual orientation knowledge and attitudes and its association with therapy satisfaction among lesbian, gay, and bisexual + Hispanic Puerto Ricans.

This study aimed to examine the difference in therapy satisfaction between lesbian, gay, and bisexual + (LGB +) individuals and heterosexual individuals, and to identify the association between therapy satisfaction and the perception of knowledge and attitudes of their last therapist among the LGB + participants. Through an exploratory design with a comparative group, 125 LGB + and 75 heterosexual participants were recruited online by availability. Results indicate that the participants' sexual orientation has no significant relation on therapy satisfaction. However, there was a significant positive association between satisfaction with therapy and the LGB + participants' perception that their therapist demonstrated knowledge and positive attitudes. This research highlights the importance for continuous education and curriculum efforts on LGB + issues.

Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.