Ibrutinib followed by ofatumumab consolidation in previously untreated patients with chronic lymphocytic leukemia (CLL): GELLC-7 trial from the Spanish group of CLL (GELLC).

Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending. Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26). Findings: Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n = 80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively. Interpretation: These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response. Funding: The study was funded by Janssen that also supplied ibrutinib, whereas ofatumumab was supplied by Novartis.

Comparing the performances of SSR and SNP markers for population analysis in Theobroma cacao L., as alternative approach to validate a new ddRADseq protocol for cacao genotyping.

Proper cacao (Theobroma cacao L.) plant genotyping is mandatory for the conservation and use of the species genetic resources. A set of 15 international standard SSR markers was assumed as universal cacao genotyping system. Recently, different SNPs and SNP genotyping techniques have been exploited in cacao. However, a consensus on which to use has not been reached yet, driving the search for new approaches. To validate a new ddRADseq protocol for cacao genotyping, we compared the performances for population analysis of a dataset with 7,880 SNPs obtained from ddRADseq and the genotypic data from the aforementioned SSR set, using 158 cacao plants from productive farms and gene bank. Four genetic groups were identified with STRUCTURE and ADMIXTURE softwares using SSR and SNP data, respectively. Similarities of cacao ancestries among these groups allowed the identification of analogous pairs of groups of individuals, referred to as: G1SSR/G1SNP, G2SSR/G2SNP, G3SSR/G3SNP, G4SSR/G4SNP, whether SSRs or SNPs were used. Both marker systems identified Amelonado and Criollo as the most abundant cacao ancestries among all samples. Genetic distance matrices from both data types were significantly similar to each other according to Mantel test (p < 0.0001). PCoA and UPGMA clustering mostly confirmed the identified genetic groups. AMOVA and FST pairwise comparison revealed a moderate to very large genetic differentiation among identified groups from SSR and SNP data. Genetic diversity parameters from SSR (Hobs = 0.616, Hexp = 0.524 and PIC = 0.544) were higher than that from SNP data (0.288, 0.264, 0.230). In both cases, genetic groups carrying the highest Amelonado proportion (G1SSR and G1SNP) had the lowest genetic diversity parameters among the identified groups. The high congruence among population analysis results using both systems validated the ddRADseq protocol employed for cacao SNP genotyping. These results could provide new ways for developing a universal SNP-based genotyping system very much needed for cacao genetic studies.

Using ddRADseq to assess the genetic diversity of in-farm and gene bank cacao resources in the Baracoa region, eastern Cuba, for use and conservation purposes.

The Baracoa region, eastern Cuba, hosts around 80 % of the country cacao (Theobroma cacao L.) plantations. Cacao plants in farms are diverse in origin and propagation, with grafted and hybrid plants being the more common ones. Less frequent are plants from cuttings, TSH progeny, and traditional Cuban cacao. A national cacao gene bank is also present in Baracoa, with 282 accessions either prospected in Cuba or introduced from other countries. A breeding program associated with the gene bank started in the 1990s based on agro-morphological descriptors. The genetic diversity of cacao resources in Baracoa has been poorly described, except for traditional Cuban cacao, affecting the proper development of the breeding program and the cacao planting policies in the region. To assess the population structure and genetic diversity of cacao resources in Baracoa region, we genotyped plants from both cacao gene bank (CG) and cacao farms (CF) applying a new ddRADseq protocol for cacao. After data processing, two SNPs datasets containing 11,425 and 6,481 high-quality SNPs were generated with 238 CG and 135 CF plants, respectively. SNPs were unevenly distributed along the 10 cacao chromosomes and laid mainly in noncoding regions of the genome. Population structure analysis with these SNP datasets identified seven and four genetic groups in CG and CF samples, respectively. Clustering using UPGMA and principal component analysis mostly agree with population structure results. Amelonado was the predominant cacao ancestry, accounting for 49.22 % (CG) and 57.73 % (CF) of the total. Criollo, Contamana, Iquitos, and Nanay ancestries were detected in both CG and CF samples, while Nacional and Marañon backgrounds were only identified in CG. Genetic differentiation among CG (FST ranging from 0.071 to 0.407) was higher than among CF genetic groups (FST: 0.093-0.282). Genetic diversity parameters showed similar values for CG and CF samples. The CG and CF genetic groups with the lowest genetic diversity parameters had the highest proportion of Amelonado ancestry. These results should contribute to reinforcing the ongoing breeding program and updating the planting policies on cacao farms, with an impact on the social and economic life of the region.

Concrete incorporating supplementary cementitious materials: Temporal evolution of compressive strength and environmental life cycle assessment.

The use of Supplementary Cementitious Materials (SCMs) or industrial wastes as a partial replacement for cement in the production of concrete is an urgent need in the construction industry due to cement's growing environmental challenges and rising cost. In respect of this, we conducted research work on proportioning binary concrete mixes. Fly ash (FA) replaced 10 %, 20 %, and 30 % of the cement, while silica fume (SF) replaced 5 %, 10 %, and 15 % of the cement. A control concrete mix was also developed with 100 % cement and no SCM. The results showed no increase in compressive strength for FA concrete compared to control at the early age of 3-28 days, but a maximum increase in compressive strength of 4 % was discovered at a later age of 56 days for concrete with 20 % FA. For 5 % SF concrete, a considerable strength increase of 15 % was seen at the early age of 3 days. Like with FA concrete, 2 % improvement in strength was recorded at the later age of 56 days for 10 % SF concrete. This study further focused on the concrete's temporal evolution of compressive strength by developing a strength evolution model (SEM) using nonlinear regression analysis at a 95 % confidence level. Pearson correlation coefficient was used to determine the correlation between the model values and the experimental results. For comparison, the fib Model Code 2010 was applied to the experimental data, and a good agreement was observed among the proposed model, the fib Model values, and the experimental results. The proposed model can be expanded to address further regression-related problems. Finally, environmental life cycle assessment revealed that utilizing 10 %, 20 %, and 30 % of FA lowered Global Warming Potential (GWP) by 9 %, 19 %, and 29 %, respectively. Likewise, using 5 %, 10 %, and 15 % of SF reduced the GWP by 5 %, 9 %, and 14 %.

Real-World Experience in Hispanic Patients With Breast Cancer and Brain Metastases Using Different Prognostic Tools.

PURPOSE: Only a small percentage of Hispanic patients have been included in studies that developed prognostic models for breast cancer and brain metastases. Therefore, there is a clear need for tools tailored to this demographic. This study assesses the efficacy of common prognostic tools in a Hispanic population. METHODS AND MATERIALS: We retrospectively analyzed a data set of Hispanic patients with breast cancer and newly diagnosed brain metastases from 2009 to 2023 at a single referral center. For each prognostic tool, Kaplan-Meier curves were built. The performances of the models were compared using the area under the curve (AUC), C-statistic, and Akaike information criteria (AIC). RESULTS: Of 492 patients, the median time from breast cancer to brain metastasis diagnosis was 22.7 months (IQR, 12.1-53.3). The median overall survival was 11.6 months (95% CI, 9.9-13.4). All models were validated as prognostic tools (P < .001). The model with the better performance was the breast graded prognostic assessment (GPA; AIC, 402; AUC, 0.65), followed by the modified GPA (AIC, 406; AUC, 0.64), the disease-specific GPA (AIC, 407; AUC, 0.62), recursive partitioning analysis (AIC, 421; AUC, 0.62), and GPA (AIC, 422; AUC, 0.60). CONCLUSIONS: The breast GPA demonstrated superior accuracy in prognosticating outcomes for Hispanic patients with breast cancer and brain metastases. This underscores the critical importance of incorporating racial and ethnic diversity in creating and validating medical prognostic tools.

Heart Rate Variability Measurement through a Smart Wearable Device: Another Breakthrough for Personal Health Monitoring?

Heart rate variability (HRV) is a measurement of the fluctuation of time between each heartbeat and reflects the function of the autonomic nervous system. HRV is an important indicator for both physical and mental status and for broad-scope diseases. In this review, we discuss how wearable devices can be used to monitor HRV, and we compare the HRV monitoring function among different devices. In addition, we have reviewed the recent progress in HRV tracking with wearable devices and its value in health monitoring and disease diagnosis. Although many challenges remain, we believe HRV tracking with wearable devices is a promising tool that can be used to improve personal health.

Radiation exposure during distal and traditional radial coronary angiography and percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

OBJECTIVES: Previous studies show that the distal transradial approach (dTRA) is safe and effective for coronary angiography and percutaneous coronary intervention. However, the effect of dTRA on radiation exposure in the catheterization laboratory has not been characterized. The authors analyzed the available literature to compare the radiation exposure associated with dTRA vs the traditional radial approach (TRA). METHODS: A systematic review and meta-analysis of the scientific literature was conducted by using relevant terms to search the PubMed, Embase, and Cochrane Library databases from their inception until October 13, 2022, to identify randomized controlled trials (RCTs) comparing dTRA with TRA. The primary outcome was radiation exposure reported as fluoroscopy time, air kerma, or kerma-dose product. The standard mean difference (SMD) and its 95% confidence interval were used to summarize continuous variables. Random effect and meta-regression also were used for analyses. RESULTS: Among 484 studies identified, 7 were RCTs, with a total of 3427 patients (1712 dTRA, 1715 TRA). No difference was found between dTRA and TRA in radiation exposure quantified as fluoroscopy time (SMD -0.10 [-0.36, 0.15], P=.43) or air kerma (SMD -0.31 [-0.74, 0.13], P=.17). The overall estimate favored lower kerma-area product in the TRA (SMD 0.19 [0.08, 0.30], P=.0006). Meta-regression showed no correlation between fluoroscopy time and year of publication. CONCLUSIONS: Compared with TRA, dTRA was associated with significantly greater radiation exposure per the kerma-area product during interventional cardiology procedures, with no differences in fluoroscopy time and air kerma.

Outbreak of Serratia marcescens in the Neonatal Intensive Care Unit of a Tertiary Care Hospital in Mexico.

Introduction: We describe an outbreak of Serratia marcescens (S. marcescens) infection in the neonatal intensive care unit at Women's Hospital in Sinaloa, Mexico. Methods: In April 2021, an outbreak of S. marcescens infection was identified. A case was identified as any patient who tested positive for S. marcescens and showed signs of an infectious process. Results: S. marcescens was isolated from the blood cultures of 15 neonates with clinical signs of neonatal sepsis. Statistical analysis showed that all neonates had an invasive medical device. The problem was controlled after hospital hygiene and sanitation measures were strengthened. Conclusion: The study provides evidence of an outbreak of nosocomial bacteremia due to the cross-transmission of S. marcescens. The findings highlight the need for hospitals to implement strict hygiene measures, especially regarding hand washing, to prevent future outbreaks.

Review of the diet of Icterus pustulatus (Passeriformes: Icteridae) and a new prey, Oiketicus sp. (Lepidoptera: Psychidae) from Mexico

We report a case of predation on the basket worm Oiketicus sp. (Lepidoptera, Psychidae) by the Streak-backed Oriole (Icterus pustulatus) in the Municipality of Santa Cruz Xoxocotlán, Oaxaca, Mexico. The bird was photographed, and we describe the prey based on its basket, cephalic capsule, and fragments of thoracic segments. We describe the foraging strategy and provide a list of previously recorded food resources in the diet of I. pustulatus. This is the first documentation of a basket worm being consumed by I. pustulatus, which may be considered omnivorous.

Reportamos un caso de depredación sobre el gusano canasta Oiketicus sp. (Lepidoptera, Psychidae) por la calandria dorso rayado (Icterus pustulatus) en el Municipio de Santa Cruz Xoxocotlán, Oaxaca, México. El ave fue fotografiada y describimos la presa a partir de su canasta, cápsula cefálica y fragmentos de segmentos torácicos. Describimos la estrategia de forrajeo y presentamos una lista de recursos alimentarios previamente registrados en la dieta de I. pustulatus. Esta es la primera documentación de alimentación de un gusano canasta por parte de I. pustulatus, el cual puede ser considerada omnivora.

[Kawasaki disease and multisystem inflammatory syndrome in children. Differences, and similarities in a pediatric center in Mexico]. / Enfermedad de Kawasaki y síndrome inflamatorio multisistémico en niños. Diferencias y similitudes en un centro pediátrico de México.

OBJECTIVE: To evaluate the differences and similarities in clinical picture, laboratory findings and outcomes between children's with Kawasaki Disease (KD) versus multisystem inflammatory syndrome (MIS-C). METHODS: We conducted a retrospective, comparative study from children with Kawasaki Disease (KD) hospi-talized in Sinaloa Pediatric Hospital from January 1, 2004, to March 31, 2020, and patients with multisystem inflammatory syndrome (MIS-C) according with World Health Organization (WHO) case definition criteria be-tween May 1, 2020 and May 31, 2021. Demographic characteristics, epidemiological data, clinical features, laboratory findings, type of treatment and clinical outcomes were compared among both groups. RESULTS: Eighty-one patients were included (62 patients with KD and 19 with MIS-C). several clinical and lab-oratory differences were found among these two entities. Median age was lower in KD vs. MIS-C (25 vs 79 months). Those finding more frequent in KD were male gender (64.5 vs. 47.4%), Mucocutaneous features (93.5 vs. 63.2%): Oral changes (83.9 vs. 63.2%) and extremity changes (77.4 vs. 57.9%); complete form of KD was (75.8 vs. 47.4%), Coronary artery aneurysm (16.1 vs. 11.8%). Secondly, findings that were more frequent in MIS-C than KD were Gastrointestinal involvement (89.4 vs. 9.6%), shock (57.9 vs. 3.2%), neurological symp-toms (63.1 vs. 11.2%), kidney involvement (52.6 vs. 16.1%), heart disease in general (52.9% vs 29%): Myocardial dysfunction (23.5 vs. 11.3%) and pericardial effusion (17.6 vs. 2.9%). Lymphocyte count (2.07 + 2.03 vs. 4.28 + 3.01/mm3), platelet count (197.89 + 187.51 vs. 420.37 + 200.08/mm3); serum albumin (2.29 + 0.65 vs. 3.33 + 0.06g/dL), and CPR (21.4 + 11.23 vs. 14.26 + 12.37 mg/dL). KD vs. MIS-C types of Treatment: IVIG (96.8 vs. 94.7%), systemic steroids (4.82 vs. 94.7%), IVIG resistance (19.4 vs. 15.8). Finally, mortality in KD was 0% and 5.3% in MIS-C. CONCLUSIONS: Similarities were found in both groups such as fever, rash, and conjunctivitis. Nevertheless, signifi-cant differences such as severity of clinical presentation with multi-organ involvement and worst inflammato-ry response were found more frequently in MIS-C group than KD group, requiring more fluid replacement, use of inotropic agents and higher steroids dosages. Also, mortality rate was higher in patients with MIS-C thanpatients with KD. Similar results have been observed in other studies where both disorders were compared.

OBJECTIVO: Evaluar las diferencias y similitudes en el cuadro clínico, los hallazgos de laboratorio y desenlaces médicos de pacientes pediátricos con enfermedad de Kawasaki versus síndrome inflamatorio multisistémico. MÉTODOS: Estudio comparativo y retrospectivo, efectuado en niños con enfermedad de Kawasaki, atendidos en el Hospital Pediátrico de Sinaloa, entre el 1 de enero de 2004 al 31 de marzo de 2020, y pacientes con sín-drome inflamatorio multisistémico (según los criterios de la Organización Mundial de la Salud), del 1 de mayo de 2020 al 31 de mayo de 2021. Se evaluaron las características demográficas, epidemiológicos y clínicas, además de los hallazgos de laboratorio, tipo de tratamiento y desenlaces clínicos en ambos grupos. RESULTADOS: Se incluyeron 81 pacientes: 62 con enfermedad de Kawasaki y 19 con síndrome inflamatorio mul-tisistémico. Se encontraron varias diferencias clínicas y de laboratorio en ambas alteraciones. La mediana de edad fue menor en pacientes con enfermedad de Kawasaki versus síndrome inflamatorio multisistémico (25 vs 79 meses). La mayoría de los pacientes con enfermedad de Kawasaki fueron hombres (64.5 vs 47.4%), con características mucocutáneas (93.5 vs 63.2%): cambios orales (83.9 vs 63.2%) y cambios en las extremidades (77.4 vs 57.9%); la forma completa de enfermedad de Kawasaki fue 75.8 vs 47.4%, concomitante con aneuris-ma de la arteria coronaria (16.1 vs 11.8%). Los hallazgos más frecuentes en sujetos con síndrome inflamatorio multisistémico fueron: afectación gastrointestinal (89.4 vs 9.6 %), choque (57.9 vs 3.2%), síntomas neurológicos (63.1 vs 11.2%), afectación renal (52.6 vs 16.1%) y cardiopatías en general (52.9 vs 29%): disfunción miocárdica (23.5 vs 11.3%) y derrame pericárdico (17.6 vs 2.9%). La concentración media de linfocitos fue: 2.07 + 2.03 vs4.28 + 3.01/mm3), plaquetas (197.89 + 187.51 vs 420.37 + 200.08/mm3); albúmina sérica (2.29 + 0.65 vs 3.33 + 0.06 g/dL) y PCR (21.4 + 11.23 vs 14.26 + 12.37 mg/dL). Los tratamientos en enfermedad de Kawasaki vssíndrome inflamatorio multisistémico: IVIG (96.8 vs 94.7%), corticosteroides sistémicos (4.82 vs 94.7%), resis-tencia a IVIG (19.4 vs 15.8). La mortalidad fue de 0 vs 5.3%. CONCLUSIONES: Se encontraron similitudes en cuanto a síntomas en ambos grupos (fiebre, exantema y conjun-tivitis); no obstante, hubo diferencias significativas respecto de las manifestaciones clínicas, con afección multiorgánico y peor respuesta inflamatoria en pacientes con síndrome inflamatorio multisistémico, incluso mayor requerimiento de reposición de líquidos, administración de agentes inotrópicos, dosis más altas de corticosteroides, y elevada tasa de mortalidad. Estos resultados se han observado en otros estudios, donde se compararon ambos trastornos.

Evaluation of large animal models for preclinical studies of heart failure with preserved ejection fraction using clinical score systems.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a complex, heterogeneous spectrum of pathologic features combined with average left ventricular volume and diastolic dysfunction. HFpEF is a significant public health problem associated with high morbidity and mortality rates. Currently, effective treatments for HFpEF represent the greatest unmet need in cardiovascular medicine. A lack of an efficient preclinical model has hampered the development of new devices and medications for HFpEF. Because large animal models have similar physiologic traits as humans and appropriate organ sizes, they are the best option for limiting practical constraints. HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach. Here, we review the large animal models of HFpEF reported to date and describe the methods that have been used to create HFpEF, including surgery-induced pressure overloading, medicine-induced pressure overloading, and diet-induced metabolic syndrome. In addition, for the first time to our knowledge, we use two established clinical HFpEF algorithms (HFA-PEFF and H2FPEF scores) to evaluate the currently available large animal models. We also discuss new technologies, such as continuous remote pressure monitors and inflatable aortic cuffs, as well as how the models could be improved. Based on current progress and our own experience, we believe an efficient large animal model of HFpEF should simultaneously encompass multiple pathophysiologic factors, along with multiorgan dysfunction. This could be fully evaluated through available methods (imaging, blood work). Although many models have been studied, only a few studies completely meet clinical score standards. Therefore, it is critical to address the deficiencies of each model and incorporate novel techniques to establish a more reliable model, which will help facilitate the understanding of HFpEF mechanisms and the development of a treatment.

Early Changes in Acute Myocardial Infarction in Pigs: Achieving Early Detection with Wearable Devices.

We examined the changes in variables that could be recorded on wearable devices during the early stages of acute myocardial infarction (AMI) in an animal model. Early diagnosis of AMI is important for prognosis; however, delayed diagnosis is common because of patient hesitation and lack of timely evaluations. Wearable devices are becoming increasingly sophisticated in the ability to track indicators. In this study, we retrospectively reviewed the changes in four variables during AMI in a pig model to assess their ability to help predict AMI onset. AMI was created in 33 pigs by 90-min balloon occlusion of the left anterior descending artery. Blood pressure, EKG, and lactate and cardiac troponin I levels were recorded during the occlusion period. Blood pressure declined significantly within 15 min after balloon inflation (mean arterial pressure, from 61 ± 8 to 50 ± 8 mmHg) and remained at this low level. Within 5 min of balloon inflation, the EKG showed ST-elevation in precordial leads V1-V3. Blood lactate levels increased gradually after occlusion and peaked at 60 min (from 1.48 to 2.53 mmol/L). The continuous transdermal troponin sensor demonstrated a gradual increase in troponin levels over time. Our data suggest that significant changes in key indicators (blood pressure, EKG leads V1-V3, and lactate and troponin levels) occurred at the onset of AMI. Monitoring of these variables could be used to develop an algorithm and alert patients early at the onset of AMI with the help of a wearable device.

On the adoption of stricter energy efficiency standards for residential air conditioners: Case study Guayaquil, Ecuador.

Space cooling is the fastest-growing energy end-use in buildings worldwide, and Ecuador is no exception. Nevertheless, the last update of the Minimum Energy Performance Standards (MEPS) for air conditioners was in 2013 (EER 3.2W/W); since then, no new standards have been proposed in Ecuador. This study is the first assessment of stricter MEPS and estimation of benefits for the consumers and society of the residential sector in Guayaquil, Ecuador. The life cycle cost, payback time, net present value, electricity savings, and CO2 mitigation are the outputs from the Policy Analysis Modeling System (PAMS) methodology followed. The analysis considers future economic scenarios until 2035. Also, a new engineering approach based on linear optimization defines ACs designs in compliance with the proposed MEPS at the lowest cost. Therefore we can avoid setting less ambitious energy-efficiency targets when efficiency options are limited in the market (this is the Ecuadorian case). The analyzed MEPS are those proposed by UNEP and by the renewal program of inefficient equipment of the Ecuadorian Government. Our estimates show that AC demand can reach 17.3% of the total residential electricity demand in the business-as-usual scenario and 21.4% in the high economic growth scenario until 2035. Furthermore, the results show a significant gap between the proposed MEPS which can be progressively bridged. The best standard from the consumer perspective is EER 4.3W/W, while from the societal perspective, it is EER 5.5W/W. Stricter MEPS can reduce AC electricity demand and energy-related emissions between 5.7% and 31%, depending on the selected scenario. Therefore, stricter MEPS for AC represents a cost-effective option to reduce energy needs and emissions from air conditioners and a concrete action to support the national energy efficiency policies and nationally determined contributions for the residential sector.

Alternative technologies for the production of popped sorghum: a comparative study.

Sorghum is the fifth most harvested crop worldwide, being the popped sorghum as one of the most common snacks in India and some Asian regions. Therefore, this study evaluated how the processing method influences the microstructure, volumetric and textural properties of popped sorghum microstructure, volumetric and textural properties. White sorghum "Paloma" variety (11% moisture) was assessed, which was popped using three processing methods: microwave, pan-frying, and hot salt-frying using three temperature levels. Volumetric and yield characteristics were evaluated for the popped kernels, as their microstructure and texture profile. The popped sorghum obtained through the hot salt-frying method had a microstructure composed of polygonal cells. Also, it showed the best volumetric characteristics (volume), good expansion index, and high process yield. Finally, the hot salt-frying method showed better textural features associated with the attributes of a satisfactory product for consumers.

Antioxidant Activity, Total Phenolic, Tannin, and Flavonoid Content of Five Plants Used in Traditional Medicine in Penjamo, Guanajuato.

In Mexico, plants are commonly used to alleviate various ailments, including controlling some chronic degenerative diseases through the regular consumption of decoctions, infusions, and teas. However, there is little scientific evidence consolidating traditional medicine within health systems. Therefore, this work determined the phytochemical profile of the most used plants to treat various ailments (Cedro rojo, Cancerina, Ortiguilla, Hierba de la golondrina, Hierba de arlomo) and their general consumption as infusions. Aqueous and ethanolic extracts were generated, while the phytochemical compound content in the extracts obtained was quantified. The results indicate that the ethanolic extracts showed the highest phenolic compound and tannin content, with the highest contents for Cedro rojo (831.04 mg L-1 ) and Cancerina (864.80 mg L-1 ). The antioxidant activity was also determined, and a significant difference was observed (p<0.05). The extracts with the highest antioxidant capacity were the ethanolic extracts ranging from 250 to 907 µMET mL-1 , while the aqueous extracts ranged from 112 to 390 µMET mL-1 . The compounds identified by high-performance liquid chromatography characterization on the aqueous extracts highlighted the presence of chlorogenic acid>cinnamic acid>quercetin. In ethanolic extracts, the presence of chlorogenic acid>cinnamic acid>quercetin>gallic acid>ferulic acid>coumaric acid was highlighted. The correlation between bioactive compounds, type of extract, and antioxidant activity suggests a significant affinity of these phytochemical compounds for the ethanol solvent. The results indicate that these plants are good sources of antioxidant phenolics and can be incorporated for use as functional beverages. However, more studies are needed to corroborate their beneficial effect.

Mitochondrial RNA methyltransferase TRMT61B is a new, potential biomarker and therapeutic target for highly aneuploid cancers.

Despite being frequently observed in cancer cells, chromosomal instability (CIN) and its immediate consequence, aneuploidy, trigger adverse effects on cellular homeostasis that need to be overcome by anti-stress mechanisms. As such, these safeguard responses represent a tumor-specific Achilles heel, since CIN and aneuploidy are rarely observed in normal cells. Recent data have revealed that epitranscriptomic marks catalyzed by RNA-modifying enzymes change under various stress insults. However, whether aneuploidy is associated with such RNA modifying pathways remains to be determined. Through an in silico search for aneuploidy biomarkers in cancer cells, we found TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. Accordingly, TRMT61B protein levels are increased in tumor cell lines with an imbalanced karyotype as well as in different tumor types when compared to control tissues. Interestingly, while TRMT61B depletion induces senescence in melanoma cell lines with low levels of aneuploidy, it leads to apoptosis in cells with high levels. The therapeutic potential of these results was further validated by targeting TRMT61B in transwell and xenografts assays. We show that TRM61B depletion reduces the expression of several mitochondrial encoded proteins and limits mitochondrial function. Taken together, these results identify a new biomarker of aneuploidy in cancer cells that could potentially be used to selectively target highly aneuploid tumors.

Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia.

Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca-/-) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10), they spontaneously developed OSCC with high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca-/-;K14cre;Trp53F2-10/F2-10 mice constitute the first animal model of spontaneous OSCC in FA.

Efficient and Fast Generation of Relevant Disease Mouse Models by In Vitro and In Vivo Gene Editing of Zygotes.

Knockout mice for human disease-causing genes provide valuable models in which new therapeutic approaches can be tested. Electroporation of genome editing tools into zygotes, in vitro or within oviducts, allows for the generation of targeted mutations in a shorter time. We have generated mouse models deficient in genes involved in metabolic rare diseases (Primary Hyperoxaluria Type 1 Pyruvate Kinase Deficiency) or in a tumor suppressor gene (Rasa1). Pairs of guide RNAs were designed to generate controlled deletions that led to the absence of protein. In vitro or in vivo ribonucleoprotein (RNP) electroporation rendered more than 90% and 30% edited newborn animals, respectively. Mice lines with edited alleles were established and disease hallmarks have been verified in the three models that showed a high consistency of results and validating RNP electroporation into zygotes as an efficient technique for disease modeling without the need to outsource to external facilities.

Assessment of In Vitro Cefiderocol Susceptibility and Comparators against an Epidemiologically Diverse Collection of Acinetobacter baumannii Clinical Isolates.

Cefiderocol is a catechol-substituted siderophore cephalosporin combining rapid penetration into the periplasmic space with increased stability against ß-lactamases. This study provides additional data on the in vitro antimicrobial activity of cefiderocol and commercially available comparators against an epidemiologically diverse collection of Acinetobacter baumannii clinical isolates. Antimicrobial susceptibility was tested using pre-prepared frozen 96-well microtiter plates containing twofold serial dilutions of: cefepime, ceftazidime/avibactam, imipenem/relebactam, ampicillin/sulbactam, meropenem, meropenem/vaborbactam, ciprofloxacin, minocycline, tigecycline, trimethoprim/sulfamethoxazole and colistin using the standard broth microdilution procedure in cation-adjusted Mueller-Hinton broth (CAMHB). For cefiderocol, iron-depleted CAMHB was used. A collection of 113 clinical strains of A. baumannii isolated from Argentina, Azerbaijan, Croatia, Greece, Italy, Morocco, Mozambique, Peru and Spain were included. The most active antimicrobial agents against our collection were colistin and cefiderocol, with 12.38% and 21.23% of non-susceptibility, respectively. A high proportion of multidrug-resistant (76.77%) and carbapenem-resistant (75.28%) A. baumannii isolates remained susceptible to cefiderocol, which was clearly superior to novel ß-lactam/ß-lactamase inhibitor combinations. Cefiderocol-resistance was higher among carbapenem-resistant isolates and isolates belonging to ST2, but could not be associated with any particular resistance mechanism or clonal lineage. Our data suggest that cefiderocol is a good alternative to treat infections caused by MDR A. baumanni, including carbapenem-resistant strains.