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Cervical cancer constitutes a significant health burden for women worldwide despite being preventable by vaccination and screening. Advanced stages of the disease are associated with a poor prognosis, and treatment approaches have seen little change over several decades, resulting in an overall survival rate of no more than 17 months. Additionally, there are limited options for second-line treatment. The urgent need for innovative and effective therapies to improve the outlook for this group of patients, along with an enhanced understanding of the interactions between the disease and the host’s immune system, has propelled immunotherapy into a rapidly advancing field with notable achievements. Among various immunotherapeutic approaches, immune checkpoint inhibitors emerge as the most advanced treatment option. Clinical trials assessing these inhibitors as single agents or in combination with chemotherapy show promising results. As immunotherapy begins to redefine standards of care for metastatic, recurrent, or persistent cervical cancer, this review addresses recent advances and current recommendations for its management in both first and second-line treatment. The goal is to provide insights into the evolving landscape of cervical cancer treatment, specifically focusing on immunotherapeutic interventions.

Abstract Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15–21); and 3) NAC treatment throughout all pregnancy (GD1–21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

Antecedentes: Reconocer oportunamente las alteraciones electrocardiográficas en COVID-19 permite obtener un diagnóstico rápido y preciso para instaurar un tratamiento oportuno. Objetivo: Describir las características electrocardiográficas en pacientes con COVID-19 en un hospital de tercer nivel. Método: Estudio descriptivo. Se evaluaron los hallazgos electrocardiográficos de pacientes con diagnóstico confirmado de COVID-19 mediante PCR o pruebas de amplificación molecular. Se incluyeron pacientes mayores de 18 años, hospitalizados en terapia intensiva y área COVID durante febrero a noviembre de 2021. Se utilizó estadística descriptiva, frecuencias y porcentajes, chi cuadrado para asociación de variables categóricas. Resultados: Se evaluaron 75 expedientes: 42 (56.0%) hombres y 33 (44.0%) mujeres; edades comprendidas entre los 20 y 110 años , media 54.84, DE: 14.99 años. Los principales hallazgos electrocardiográficos fueron ritmo cardiaco sinusal (94.7%), alteraciones en el segmento ST (7.7%), alteraciones en la onda P (12.0%), anomalías en la morfología del complejo QRS (13.4%) y alteraciones en la onda T (22.6%). Las complicaciones asociadas a COVID-19 fueron pericarditis (2.7%), hipertrofia ventricular izquierda (4.0%) y bloqueo auriculoventricular completo (4.0%). Se obtuvo una p = 0.001 en la relación de la onda T y la presencia de comorbilidades en pacientes infectados. Conclusión: Las principales alteraciones electrocardiográficas se relacionan con la repolarización tardía del corazón.

Abstract Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Sheet metal forming processes are widely used in applications such as those in the automotive or aerospace industries. Among them, punching is of great interest due to its high productivity and low operating cost. However, it is necessary to optimize these processes and adjust their parameters, such as clearance, shear force or tool geometry, to obtain the best finishes and minimize crack generation. Thus, the main objective of this research work is to optimize the punching process to achieve parts that do not require subsequent processes, such as deburring, by controlling the properties of the starting materials and with the help of tools such as design of experiments and simulations. In the present study, tensile tests were performed on three steels with different compositions and three sample geometries. The information obtained from these tests has allowed us to determine the parameters of the Johnson–Cook damage criteria. Moreover, punching was performed on real parts and compared with simulations to analyze the percentage of burnish surface. The results obtained show that the methodology used was correct and that it can be extrapolated to other types of die-cutting processes by reducing the percentage of surface fractures and predicting the appearance of cracks. Furthermore, it was observed that clearance has a greater influence than processing speed, while the minimum percentage of the burnish area was observed for the minimum values of clearance.

Due to the substantial development of information and communications technology, the use of E-learning in higher education has become essential to boost teaching methods and enhance students' learning skills and competencies. E-learning in Software Engineering turns out to be increasingly interesting for scholars. In fact, researchers have worked to enhance modern Software Engineering education techniques to meet the required educational objectives. The aim of this article is to analyse the scientific production on E-learning Software Engineering education by conducting a bibliometric analysis of 10,603 publications, dating from 1954 to 2020 and available in the Scopus database. The results reveal some scientific production information, such as the temporal evolution of the publications, the most prolific authors, institutions and countries, as well as the languages used. Besides, the paper evaluates additional bibliometric parameters, including the authors' production, journal productivity, and scientific cooperation, among other bibliometric parameters. The subject of the current study has not been treated by any previous bibliometric studies. Our research is deeper and more specific; it covers a long period of 66 years and a large number of publications, thanks to the chosen search string containing the different spellings of the used terms. In addition, the literature is analysed using several tools such as Microsoft Excel, VOSviewer, and Python. The research findings can be used to identify the current state of E-learning Software Engineering Education, as well as to identify various research trends and the general direction of E-learning research.

This study was conducted to evaluate the effects of dietary free fatty acid (FFA) content and degree of fat saturation on production performance, lipid and calcium digestibility, and intestinal function of laying hens. For a 15-week period, a total of 144 laying hens (19 weeks old) were randomly assigned to 8 dietary treatments, which were obtained by gradually replacing crude soybean oil with soybean acid oil (AO), or crude palm oil with palm fatty acid distillate (FAD). Thus, there were 4 soybean and 4 palm diets with 6% added fat varying in their FFA percentage (10%, 20%, 30%, and 45%), following a 2 × 4 factorial design. Each treatment included 6 replicates with 3 birds per replicate. Average daily feed intake and final body weight were significantly higher in palm diets (P

Introducción: El cáncer de tiroides es la neoplasia maligna endocrina más común y su supervivencia es del 98%. La incidencia baja un 2.5% anualmente ya que se utilizan criterios más nuevos para diagnosticarlo. La biopsia por aspiración con aguja fina se utiliza en la evaluación inicial para la obtención de una muestra. El estudio histopatológico transoperatorio tiene una eficacia > 97% y ayuda a evitar disecciones innecesarias. El método diagnóstico de referencia es el estudio histopatológico definitivo. Objetivo: Determinar la sensibilidad y la especificidad del estudio histopatológico transoperatorio de tiroides en comparación con el reporte histopatológico definitivo en pacientes TIRADS 4 y 5. Método: Estudio observacional, comparativo, transversal y homodémico en pacientes operados de hemitiroidectomía a quienes se realizó estudio transoperatorio durante los años 2021 y 2022. Se utilizó estadística descriptiva y se compararon los resultados con el estudio histopatológico definitivo. Resultados: Fueron 46 pacientes (5 hombres y 46 mujeres), edad media 47.35 ± 13.83 años (rango: 22-70), relación por sexo mujer > hombre (8:1). El estudio transoperatorio, para TIRADS 4, posee una sensibilidad del 58.3% y una especificidad del 95.4%, con un valor predictivo positivo (VPP) del 87.5% y un valor predictivo negativo (VPN) del 80.7%; y para TIRADS 5, una sensibilidad del 83.3% y una especificidad del 100%, con un VPP del 100% y un VPN del 85.7%. Conclusiones: El estudio transoperatorio en pacientes con nódulo tiroideo en estadios avanzados TIRADS 5 posee unas mejores sensibilidad y especificidad que en los demás estadios previos.

Abstract Background and aim Maternal overweight and breastfeeding seem to have a significant impact on the gut microbiota colonization process, which co-occurs simultaneously with brain development and the establishment of the “microbiota-gut-brain axis”, which potentially may affect behavior later in life. This study aimed to examine the influence of maternal overweight, obesity and/or gestational diabetes on the offspring behavior at 3.5 years of age and its association with the gut microbiota already established at 18 months of life. Methods 156 children born to overweight (OV, n = 45), obese (OB, n = 40) and normoweight (NW, n = 71) pregnant women participating in the PREOBE study were included in the current analysis. Stool samples were collected at 18 months of life and gut microbiome was obtained by 16S rRNA gene sequencing. Behavioral problems were evaluated at 3.5 years by using the Child Behavior Checklist (CBCL). ANOVA, Chi-Square Test, ANCOVA, Spearman’s correlation, logistic regression model and generalized linear model (GLM) were performed. Results At 3.5 years of age, Children born to OV/OB mothers showed higher scores in behavioral problems than those born to NW mothers. Additionally, offspring born to OB mothers who developed gestational diabetes mellitus (GDM) presented higher scores in attention/deficit hyperactivity and externalizing problems than those born to GDM OV/NW mothers. Fusicatenibacter abundance found at 18 months of age was associated to lower scores in total, internalizing and pervasive developmental problems, while an unidentified genus within Clostridiales and Flavonifractor families abundance showed a positive correlation with anxiety/depression and somatic complaints, respectively. On the other hand, children born to mothers with higher BMI who were breastfed presented elevated anxiety, internalizing problems, externalizing problems and total problems scores; likewise, their gut microbiota composition at 18 months of age showed positive correlation with behavioral problems at 3.5 years: Actinobacteria abundance and somatic complaints and between Fusobacteria abundance and withdrawn behavior and pervasive developmental problems. Conclusions Our findings suggests that OV/OB and/or GDM during pregnancy is associated with higher behavioral problems scores in children at 3.5 years old. Additionally, associations between early life gut microbiota composition and later mental health in children was also found.

Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies. Methods: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L. Results: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed. Conclusions: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective. ClinicalTrials.gov registration number: NCT02400476.

Objetivo: Determinar la prevalencia de los principales factores de riesgo asociados a contractura capsular posterior a mamoplastia de aumento en un centro de referencia. Método: Estudio retrospectivo de 210 pacientes en el que se registraron variables sociodemográficas, escala clínica de Baker y resultados histopatológicos. Resultados: Se realizó el análisis estadístico de 210 pacientes; el 98.1% fueron mujeres. La edad promedio fue de 47 años (± 11), el índice de masa corporal 25 kg/m2 (± 10) y el inicio de los síntomas 13 años (± 8.5). Factores sociodemográficos: labores domésticas 63.3%. Alcoholismo 70% y tabaquismo 65.7%. El principal motivo de consulta fue dolor más deformidad, en el 81.6%. Los factores de riesgo con significancia estadística fueron el antecedente de traumatismo, con un 83.3% (p = 0.004), y el plano subglandular, con un 73.8% (p = 0.0115). Histopatología: cápsula fibrosa 81.4%. Conclusiones: La prevalencia de los factores de riesgo descritos es similar a lo reportado en la literatura. Solo para el antecedente de traumatismo y el plano subglandular hubo significancia estadística.

Presentamos el caso de un paciente de sexo masculino de 7 años de edad que acudió al servicio de urgencias con síntomas de cefalea expansiva y opresiva holocraneal, acompañados de náuseas, vómitos y posteriormente diplopía, ataxia y hemiparesia braquial derecha. Se le realizó resonancia magnética de cráneo con contraste, que evidenció una lesión a nivel del parénquima de la glándula pineal, la cual se sometió a toma de biopsia, diagnosticándose un tumor de células germinales no germinomatoso mixto con componentes de teratoma inmaduro y senos endodérmicos.

Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Antecedentes: El síndrome de Down es la anomalía cromosómica más frecuente y se asocia con defectos cardiacos congénitos, elementos clínicos de una alta morbilidad y mortalidad infantil. Objetivo: Describir los desenlaces clínicos de los pacientes con síndrome de Down sometidos a cirugía e intervencionismo como tratamiento de las cardiopatías congénitas en esta institución. Material y métodos: Estudio retrospectivo que incluyó pacientes menores de 18 años con síndrome de Down y patología cardiaca asociada durante los últimos 10 años. Las variables estudiadas fueron: peso, talla, sexo, edad, tipo de cardiopatía, procedimiento correctivo, tiempo de estancia intrahospitalaria y en unidad de terapia intensiva, morbilidad y mortalidad. Resultados: 368 pacientes pediátricos fueron llevados a corrección quirúrgica o intervencionista, de los cuales 197 (54%) pertenecían al sexo femenino, la mediana de edad fue de 24 meses (rango intercuartílico [RIQ]: 14-48) en el grupo quirúrgico y de 36 meses (RIQ: 17-85) en el intervencionista. Las cardiopatías congénitas más frecuentes fueron: persistencia del conducto arterioso (31%), comunicación interventricular (28%), canal atrioventricular (CAV) (20%), comunicación interauricular (16%) y tetralogía de Fallot con el 4% respectivamente. La estancia hospitalaria fue de 9 días (RIQ: 7-15) en el grupo quirúrgico y de 3 días (RIQ: 2-5) en el hemodinámico. Las morbilidades fueron infección postoperatoria en30 pacientes (14%) y en 19 pacientes (9%) bloqueo atrioventricular completo. La mortalidad global incluyendo tanto el quirúrgico como el intervencionista fue del 2%. Conclusiones: Los resultados terapéuticos, quirúrgicos e intervencionistas, enlos niños con síndrome de Down y cardiopatías congénitas han mejorado en forma muy satisfactoria. Es de destacar lamenor prevalencia del CAV en la población mexicana. Es indispensable realizar evaluación cardiológica a los niños consíndrome de Down y aquellos con cardiopatías congénitas llevarlos a corrección de manera oportuna para favorecer la sobrevida y calidad de vida.

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75–10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects.

Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2–9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock–Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Antecedentes: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. Objetivo: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. Material y métodos: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. Resultados: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. Conclusiones: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Objetivo. Comparar la evolución de los pacientes hospitalizados infectados por SARS-CoV-2 que recibieron tratamiento a base de corticoesteroides frente a los pacientes que recibieron la terapia estándar. Método. Estudio de tipo retrospectivo, observacional y analítico. Se recolectaron los expedientes clínicos de las diferentes unidades de terapia intensiva y se obtuvieron datos de los pacientes confirmados de COVID-19, mayores de 18 años, que estuvieron hospitalizados. Se dividió la población en dos grupos: pacientes que recibieron tratamiento con corticoesteroides y pacientes que recibieron terapia estándar. Resultados. De un total de 1603 pacientes ingresados a hospitalización, 984 (62.9%) fallecieron. El resultado principal fue la identificación mediante razón de momios (odds ratio [OR]: 4.68; intervalo de confianza del 95% [IC95%]: 3.75-5.83; p = 0.001) como riesgo para defunción con uso de esteroides sistémicos, así como con uso de ventilación mecánica invasiva (OR: 2.26; IC95%: 1.80-2.82; p < 0.001). El sexo masculino fue el más afectado, con 1051 (65.6%) pacientes. La media de edad fue de 56 años (± 14). Conclusiones. El uso de corticoesteroides se asoció con mal pronóstico en los pacientes hospitalizados por COVID-19, en comparación con los que recibieron la terapia estándar.

Abstract Background Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA. Methods Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis. Results Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213–376] ng/ml, p

Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate

Abstract Diabetes Mellitus is a severe, chronic disease that occurs when blood glucose levels rise above certain limits. Over the last years, machine and deep learning techniques have been used to predict diabetes and its complications. However, researchers and developers still face two main challenges when building type 2 diabetes predictive models. First, there is considerable heterogeneity in previous studies regarding techniques used, making it challenging to identify the optimal one. Second, there is a lack of transparency about the features used in the models, which reduces their interpretability. This systematic review aimed at providing answers to the above challenges. The review followed the PRISMA methodology primarily, enriched with the one proposed by Keele and Durham Universities. Ninety studies were included, and the type of model, complementary techniques, dataset, and performance parameters reported were extracted. Eighteen different types of models were compared, with tree-based algorithms showing top performances. Deep Neural Networks proved suboptimal, despite their ability to deal with big and dirty data. Balancing data and feature selection techniques proved helpful to increase the model’s efficiency. Models trained on tidy datasets achieved almost perfect models.

Environment and personality interact determining the manner a subject behaves, but research on how to conceptualise and measure the environment is still scarce. This article addresses this issue presenting strong evidence on the reliability and validity of the Situational Strength at Work (SSW) Scale (Meyer et al., 2014) in Spanish-speaking work contexts. Through three studies, we found sound evidence for the four-factor structure of the situational strength’s construct, comprising clarity, consistency, constraints, and consequences, with adequate reliability for each factor. Results of studies also found that the instrument is invariant according to sex, country (Spain, Ecuador, Mexico), and occupation (salespeople, teachers, office workers). Convergent and discriminant validity were successfully tested, and exploratory graphical network analysis depicted satisfactory results. Theoretical and practical implications are pointed out, and it is concluded that the SSW scale is a suitable instrument for investigating situational strength at work cross-nationally in Spanish-speaking contexts.

Here, we present a set of algorithms using the Python programming language, that will allow using a routine for object detection and tracking in experimental videos. We developed a script, under the fundamentals of background subtraction and image thresholding (using the OpenCV package), that makes it possible to track a wide spectrum of animals under different conditions. We have validated this script through testing on semi-terrestrial and aquatic crustacean species and under different experimental scenarios (laboratory and field sampling and using video created under nocturnal and diurnal conditions). The open-source nature of the script allows for flexibility and scalability, so it can be easily customized and is thus transferable to other species/experiments in the context of behavioral ecology. The tracking script is easy customizable and free alternative to commercial video tracking systems and therefore, applicable to a wide variety of both educational and research programs.

Abstract Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP

Introducción: Nuestro objetivo era determinar si la influencia de las características clínicopatológicas pueden mejorar la predicción de metástasis en los ganglios linfáticos no centinelas (GLNC) a partir de un punto de corte de copias de ARNm determinado en la biopsia del ganglio linfático centinela (GLC). Métodos: Se realizó un estudio observacional retrospectivo incluyendo a un total de 824 pacientes con cáncer de mama T1-3, con axila clínica y ecográficamente negativa para metástasis en los ganglios axilares. Se les practicó una biopsia selectiva del GLC y estudio posterior mediante el método one step nucleic acid amplification (OSNA). Resultados: 118 precisaron una disección completa de los ganglios linfáticos axilares. 35,6% (42/118) tuvieron metástasis en GLNC y 64.4% (76/118) no presentaron metástasis en GLNC. La curva ROC del log de la carga tumoral total (CTT) presentó un área bajo la curva de 0.651 (95%; IC: 0.552-0.751). Se estableció las 7294 copias de ARNm de CK19 como punto de corte óptimo, con sensibilidad: 93%, especificidad: 63%, valor predictivo positivo: 44% y valor predictivo negativo: 91%. Al asociar los parámetros clinicopatológicos (multicentricidad, inmunohistoquímica (IHQ) agrupado y receptores de progesterona) obtenemos un área bajo la curva mejorada de 0.752 (95% intervalo de confianza [IC] 0.663-0.841). Conclusiones: Los factores clinicopatológicos deberían valorarse asociados al corte de copias de ARNm de la CTT de CK19 de los GLCs para mejorar la capacidad predictiva de afectación metastásica en los GLNCs.

BackgroundPatients with hormone receptor-positive, HER2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) are at a high risk of relapse. PENELOPE-B was a double-blind, placebo-controlled, phase III trial that investigated adding palbociclib (PAL) for thirteen 28-day cycles to adjuvant endocrine therapy (ET) in these patients. Clinical results showed no significant improvement in invasive disease-free survival with PAL.MethodsWe performed a pre-planned cost-effectiveness analysis of PAL within PENELOPE-B from the perspective of the German statutory health insurance. Health-related quality of life scores, collected in the trial using the EQ-5D-3L instrument, were converted to utilities based on the German valuation algorithm. Resource use was valued using German price weights. Outcomes were discounted at 3% and modeled with mixed-level linear models to adjust for attrition, repeated measurements, and residual baseline imbalances. Subgroup analyses were performed for key prognostic risk factors. Scenario analyses addressed data limitations and evaluated the robustness of the estimated cost-effectiveness of PAL to methodological choices.ResultsThe effects of PAL on quality-adjusted life years (QALYs) were marginal during the active treatment phase, increasing thereafter to 0.088 (95% confidence interval: −0.001; 0.177) QALYs gained over the 4 years of follow-up. The incremental costs were dominated by PAL averaging EUR 33,000 per patient; costs were higher in the PAL arm but not significantly different after the second year. At an incremental cost-effectiveness ratio of EUR 380,000 per QALY gained, PAL was not cost-effective compared to the standard-of-care ET. Analyses restricted to Germany and other subgroups were consistent with the main results. Findings were robust in the scenarios evaluated.ConclusionsOne year of PAL added to ET is not cost-effective in women with residual invasive disease after NACT in Germany.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Methods to induce analgesia and anesthesia for research purposes, handling, transport, or stunning have been used in 71 species of crustaceans. A non-systematic literature search was conducted on crustacean anesthetic methods. This review presents a comprehensive evaluation of drugs and non-chemical methods used to provide analgesia and anesthesia in many crustacean species rather than just decapod crustaceans. This information allows users to select an appropriate method or agent for their species of interest. We prepared an on-line tool based on datasette, a no-code open-source solution for simple web-based database frontends that allows exploration and downloading data by method, analgesic/anesthetic, species, life stage, or sex, as well as other data including environmental conditions (temperature, salinity, light), route of administration, dosage, and induction and recovery times. These values can be selected to filter the dataset and export it to CSV or JSON formats. Currently, several techniques and chemicals are, in our opinion, unsuitable for use as anesthetics in crustaceans, and the basis for these opinions are presented. Given the evidence of a pain-like experience in crustaceans, we propose that researchers should treat crustaceans humanely, applying the principles of good handling, care, and the management of stress and pain to safeguard their welfare.

BackgroundAdequate nutrient intake during the first few months of life plays a critical role on brain structure and function development.ObjectivesTo analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed.MethodsThe current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0–2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old.ResultsExperimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old.ConclusionsSupplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old.Clinical Trial Registrationhttps://www.clinicaltrials.gov/, identifier: NCT02094547.

Abstract In this paper, we present an experimental evaluation of the performance benefits provided by flexible duplexing, an access technique that allows uplink and downlink cells to coexist within the same time-frequency resource blocks. In order to replicate a wireless multi-tier network composed of 1 macro-cell and 2 small cells, a measurement campaign has been conducted using an indoor wireless testbed comprised of a total of 6 multiple-input multiple-output (MIMO) software-defined radio (SDR) devices. Since each cell has a single active user, each uplink/downlink configuration can be identified with a different interference channel, over which interference alignment (IA) is used as an inter-cell interference management technique and compared to other existing methods. The obtained results show that flexible duplexing clearly outperforms the conventional time-division duplex (TDD) access approach, where all cells operate synchronized either in uplink or dowlink mode. Additionally, interference alignment consistently provides better results in most of the interference regimes when compared to minimum mean square error (MMSE)-based schemes. The impact of channel estimate quality on the different communication strategies is also studied. It is worth highlighting that the presented over-the-air (OTA) experiments represent the first implementation of IA with real-time precoding and decoding.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Los adultos con cardiopatía congénita compleja, con fisiología univentricular y flujo pulmonar disminuido, constituyen un reto terapéutico. Muchos de ellos reciben tratamiento paliativo con fístula sistémico-pulmonar desde la etapa pediátrica. Dicha fístula puede presentar oclusión o estenosis y ocasionar deterioro de la capacidad funcional y clínica. Colocar una nueva fístula sistémico-pulmonar a través de una cirugía se considera de alto riesgo, por lo que el uso de stents a través de cateterismo cardíaco surge como una opción que ha tenido buenos resultados. Se describe el caso de un adulto con atresia tricúspide con fístula sistémico-pulmonar en la etapa pediátrica, quien acudió al servicio de urgencias por deterioro de su clase funcional y desaturación en aire ambiente de hasta un 64%; en la tomografía cardíaca se evidenció estenosis del tercio distal de la fístula sistémico-pulmonar, por lo que se decidió colocar, mediante cateterismo cardíaco intervencionista, dos stents (Express LD vascular 6 x 37 mm y 6 x 27 mm), luego de lo cual la saturación sistémica fue del 75%, por lo que se consideró exitosa la colocación de los dispositivos. La oclusión de estas fístulas es una complicación habitual, que genera disminución de la perfusión pulmonar con los subsecuentes síntomas respiratorios, disminución de la saturación y la oxigenación, cianosis y acidosis metabólica, y puede generar un evento que amenaza la vida si se presenta de manera aguda. La recanalización transcatéter de una fístula sistémico-pulmonar con stent es una alternativa adecuada para evitar un riesgo quirúrgico y arroja resultados óptimos.

This work is the result of an international research effort to determine the main impacts of the COVID-19 pandemic on marine recreational fishing. Changes were assessed on (1) access to fishing, derived from lockdowns and other mobility restrictions; (2) ecosystems, because of alterations in fishing intensity and human presence; (3) the blue economy, derived from alterations in the investments and expenses of the fishers; and (4) society, in relation to variations in fishers’ health and well-being. For this, a consultation with experts from 16 countries was carried out, as well as an international online survey aimed at recreational fishers, that included specific questions designed to capture fishers’ heterogeneity in relation to behavior, skills and know-how, and vital involvement. Fishers’ participation in the online survey (5,998 recreational fishers in 15 countries) was promoted through a marketing campaign. The sensitivity of the fishers’ clustering procedure, based on the captured heterogeneity, was evaluated by SIMPER analysis and by generalized linear models. Results from the expert consultation highlighted a worldwide reduction in marine recreational fishing activity. Lower human-driven pressures are expected to generate some benefits for marine ecosystems. However, experts also identified high negative impacts on the blue economy, as well as on fisher health and well-being because of the loss of recreational fishing opportunities. Most (98%) of the fishers who participated in the online survey were identified as advanced, showing a much higher degree of commitment to recreational fishing than basic fishers (2%). Advanced fishers were, in general, more pessimistic about the impacts of COVID-19, reporting higher reductions in physical activity and fish consumption, as well as poorer quality of night rest, foul mood, and raised more concerns about their health status. Controlled and safe access to marine recreational fisheries during pandemics would provide benefits to the health and well-being of people and reduce negative socioeconomic impacts, especially for vulnerable social groups.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Abstract We present a dynamic model of competition in the media industry in which behavioral media outlets compete for the publication of scoops, and both the publication of scoops and their veracity determine an outlet’s future audience. We study the dynamics of the audiences of outlets and how those dynamics relate to two issues: how harsh a society is with the publication of false stories, and how similar media outlets are in their editorial standards for quality. For the case of a duopoly, we show that there is only one stable stationary state. In that equilibrium, the two outlets coexist and which one leads the market (the low-standard outlet or the high-standard outlet) depends on a combination of the two issues mentioned above. We then use numerical simulations to analyze the general case with more than two outlets. The numerical results corroborate most of the analytical insights gained for the duopoly case. We also use numerical simulations to draw up predictions on the number of outlets that will survive in the industry in the long run.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Background Neck pain has a high annual incidence and decreases the cervical active range of motion (ROM). Clinicians use various methods to evaluate cervical range of motion (CROM) that some of them have also been proposed to give instant feedback. Accordingly, this study aimed to examine the validity and reliability of Veloflex (VF) to measure the CROM by comparison with the cervical range of motion (CROM) device, and to examine their test-retest reliability. Methods Thirty-eight healthy and 20 symptomatic participants were evaluated. Cervical flexion-extension, side bending, and rotations were tested in two sessions, first by the CROM and VF and in the second only with the VF. To evaluate the concurrent validity and agreement between CROM and VF, Pearson correlation coefficient (r) and Bland–Altmann plots were used. Reliability were evaluated using intra-class correlation (ICC), standard error of measurement (SEM) and minimal detectable change (MDC). Results CROM and VF showed excellent correlation for all movements (r > 0.960). Both devices provided small mean ‘bias’ (≤1.29%) in all movements regarding CROM measures. The intra-rater and inter-rater reliability of the VF was excellent (ICC > 0.98). SEMs ranging from 0.72% to 2.38% and the MDC ranging from 1.22° to 2.60° in all participants. The results support the validity and reliability of VF to measure CROM. For its use, with a basic training is enough to get reliable measurements.

El espectro del ventrículo derecho hipoplásico es amplio y desafiante, ya que dependiendo de su variabilidad anatómica y funcionalidad se planteará qué tratamiento es el adecuado. Presentamos el caso de un lactante de sexo femenino, de 15 meses de edad, quien cursó asintomática, valorada en consulta de seguimiento por cianosis con saturación de oxígeno del 70%, motivo por el cual es referida a nuestra institución.

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10−4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies. This trial is registered with EudraCT n. 2007-002733-36 and ClinicalTrials.gov Identifier: NCT00545714.

Entrevista a José A. García-Arroyo