bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative risk score and in-hospital death following isolated myocardial revascularization surgery
Authors: Rosan Raphael Paris , Farsky Pedro Silvio , França João Ítalo Dias , Amato Vivian Lerner
Published: January 2022

Cardiovascular disease is the leading cause of death in Brazil. The risk of in-hospital death after coronary artery bypass grafting (CABG) can be assessed by identifying preoperative factors and quantified through scores. This investigation analyzed associated with mortality in the hospital phase after isolated CABG, to develop a preoperative risk score (PRS) for postoperative in-hospital death. This observational, retrospective, single-center study examined comorbidities and complementary exams of 9,826 patients who underwent isolated CABG between January 1, 1999 and December 31, 2017 were analyzed to identify their correlation with postoperative in-hospital death. A total of 9,826 patients were divided into the construction group (7,860; 80%) and validation group (1,966; 20%). The mean age of the patients was 62.43 years. Most patients were men (70.2%). Fifteen independently related factors were identified for hospital mortality. The final logistic model was calculated in the construction group with a C-statistic of 0.745 (95% confidence interval [CI], 0.720–0.770). In the validation group, the score was tested by obtaining an area under the receiver operating curve of 0.716 (95% [CI], 0.666–0.767). Death occurred in 489 patients (5%). The risk of death ranged from 1.2% in those considered to be low risk (PRS <85) to 16.3% among those considered to be very high risk (PRS >211). The PRS score satisfactorily discriminated among patients who exhibited low, intermediate, high, and very high risk of death in the postoperative period. PRS could serve as an auxiliary tool in the preoperative period for surgical teams.
IBD-related Malignancies Observed in 2015–2019 : 4 Years’ Results from the Prospective, Nationwide Hungarian Registry IBD-related Malignancies – Hungarian Registry
Authors: Milassin Ágnes , Rutka Mariann , Szűcs Mónika , Farkas Klaudia , Marcus Mark , Bor Renáta , Szántó Kata Judit , Nagy Ferenc , Szepes Zoltán , Lakatos László , Erdélyi Zsuzsanna , Szegedi László , Schäfer Eszter , Zaránd Attila , Fábián Anna , Bálint Anita , Molnár Tamás
Published: January 2022

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk to develop malignant neoplasms. Neither the exact mechanism, nor the frequency of different malignancies is completely clear. Our aim was to assess the IBD associated malignancies, to collect clinical and mortality data and to analyse possible risk factors. Methods: Data on malignancies developed between January 2015 and May 2019 in Hungarian IBD patients was recorded. Every member of the Hungarian Society of Gastroenterology was prospectively interviewed. The following data were collected: demographic data, disease characteristics, previous therapy, patient adherence, type and localisation of malignancies. Results: 140 IBD patients with newly diagnosed malignancies were reported. 61.4%, 35.7%, and 2.9% of the patients had ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis, respectively. The mean latency was 15.2±10.5 years. Colorectal cancer (CRC) was the most common cancer (49.6%, 70). 72.9% (51/70) of them was associated with UC, more than 80% had extensive (50.9%, 26) and left-sided (31.2%, 16) colitis. The most frequent CRC localisation was the rectosigmoid colon in UC (54.9%), and the rectum in CD (38.9%). The most common non-CRC malignancies were non-melanotic skin-cancer, haematological and pulmonary cancer. Disease duration at the time of the diagnosis of malignancy was lower (17.9±10.7 versus 12.6±9.7 years); mean age at the time of the death was higher (49.3±9.4 versus 64.3±16.4 years); and survival was longer after the diagnosis of extraintestinal malignancy than CRC (0.73±1.01 versus 1.2±0.8). Summary: CRC presented typically in the distal part of the colon by male UC patients with pancolitis or left-sided colitis with a long-standing disease course of IBD. The most common non-CRC malignancies were non-melanotic skin cancer, haematological cancer and lung cancer. Non-CRC malignancies developed typically in female patients, older than CRC patients with shorter disease-course of IBD and longer survival times.
Percepción y conocimiento sobre clima, factores de riesgo ambiental y salud. Colombia, 2015
Authors: Gómez Luis Carlos , Díaz Sonia Mireya , Muñoz Guerrero María Nathalia
Published: January 2022

El plan decenal de salud pública 2012 -2021 tiene dentro de sus componentes las situaciones en salud relacionadas con condiciones ambientales. Por lo tanto, fortalecer las capacidades básicas de las entidades territoriales en relación a factores ambientales tales como clima, agua, aire, tóxicos, entre otros, es prioritario para el país. De esta manera, se evaluaron los conocimientos, gestión y estructura de las entidades territoriales en cuanto a clima y factores de riesgo ambiental.
Se realizó un estudio descriptivo transversal basado en la información de una encuesta dirigida a las 36 entidades territoriales, diligenciada vía web que fue dividida en cuatro componentes: conocimiento, gestión, factores de riesgo ambiental - estructura y capacidad.
De acuerdo con la información suministrada por 28 de las 36 entidades territoriales, 82% (97) de los encuestados evidenciaron seguridad en los conceptos de cambio climático y 88% (115) en variabilidad climática, 21% (19) conocían la definición de tiempo atmosférico. En relación con las acciones de articulación intersectorial de las entidades territoriales solo un 23% (29) de los encuestados refiere haber realizado acuerdos o coordinación con otras entidades para trabajar clima y salud. 41%(52) refiere haber recibido solicitudes específicas del tema de clima y salud por la comunidad; este hecho es importante dado que las estrategias que se definan desde el nivel local y nacional pueden contar con gran participación de la comunidad.
Investigación de brote de infección respiratoria aguda grave inusitado en Centro de Bienestar del Anciano - Tuluá, Valle del Cauca, enero-febrero de 2017
Authors: Zabaleta Vanegas Angie Paola , Madero Reales Javier Alberto , Villamil Soledad , Victoria María Constanza , Pulido Dominguez Paola Andrea , Malo Sánchez Diana Carolina , Suárez Rangel Gloria Inés
Published: January 2022

En febrero de 2017, en hogar geriátrico de Tuluá, fueron reportadas muertes por IRA grave (IRAG). Se realizó investigación de campo para identificar la presencia de brote, establecer agente causal, identificar factores de riesgo y recomendar medidas de control y prevención para cortar cadena de transmisión. Se realizó estudio de brote con abordaje de serie de casos de IRA-IRAG entre enero y febrero 2017, usando registros clínicos, entrevistas a adultos mayores (AM) y cuidadores. Se evaluaron requisitos de acreditación del establecimiento. Se analizaron variables demográficas y clínicas. Fueron calculadas medidas de frecuencia, tendencia central y dispersión, comparación de medias y proporciones con nivel de significancia estadística (p<0,05). Se obtuvieron muestras de hisopado oro faríngeo en sintomáticos <10 días para estudio de laboratorio de panel viral. Se identificaron 26 casos: 18(69%) de IRA y 8(31%) de IRAG. Tasa de ataque (TA): 43%(26/53), entre cuidadores/enfermeras: 42%(3/7) y entre AM: 50%(23/46). La curva epidémica mostró una fuente propagada con inicio de síntomas
de primer caso el 11/01/2017. Tasa de letalidad: 19%(5/26), todos AM. Media de edad: 78 años (rango:32-100). Tasas de ataque por grupos de edad (p=0,05), lugar de habitación (p=0,75) y sexo (p=0,64) sin diferencias estadísticas. Una enfermera atiende ~40 am. Se observaron tosedores sin tapabocas, sin lavado de manos con jabón. Las muestras fueron negativas. Se confirmó brote de IRA/IRAG por fuente propagada, predominando gravedad en AM. Las condiciones locativas, sanitarias y baja cobertura de vacunación pudieron predisponer trasmisión. Se recomendó vacunar a toda la población, uso de protección respiratoria y educación.
Brote de leishmaniasis visceral en área periurbana en el municipio de Neiva, Huila. Situación de enero a julio de 2017
Authors: Torres Rodríguez Germán E. , Ojeda Polania Ángela , Bolaños Burbano Dahyana , García Ramos Andrea Tatiana , Blasquez Octavio , Hernández Bautista , Aya Nancy Milena , Torres Rojas Luis José , Quinche Germán , Becerra Silvia Lorena , Rojas María Clemencia , Vallejo Polanco Lilian , Lozano Polanco Carlos Alberto
Published: January 2022

Introducción: el febrero de 2017 se confirmó en Neiva un caso de leishmaniasis visceral en una menor de un año, procedente de la comuna 10, restableciéndose alerta de brote, luego de dos casos presentados en noviembrede2016.Enmarzode2017seconfirmóun segundo caso de leishmaniasis visceral en otro menor de un año, procedente de la comuna 9, confirmándose brote de leishmaniasis visceral en zona periurbana de Neiva. los objetivos del estudio de brote fueron: 1) Captar los casos y proporcionar manejo médico integral de manera temprana y oportuna y 2) Determinar los factores de riesgo, reservorios y el vector involucrados en la transmisión.
Metodología: confirmación de casos de leishmaniasis visceral mediante aspirado de medula ósea en pacientes que cumplían definición de caso. Se realizó investigación epidemiológica de caso, búsqueda activa comunitaria, búsqueda activa institucional, estudio de foco, control de reservorios y educación a la comunidad.
Resultados principales: se notificaron al Sivigila ocho casos de leishmaniasis visceral confirmados en menores de 2 años (incluyendo una muerte), procedentes de las comunas 10, 9, 8 y 2 entre enero y julio de 2017. En las comunas afectadas se confirmó la presencia de reservorios caninos con un 19,3 % de positividad para leishmaniasis de 347 caninos muestreados y se confirmó la presencia del vector Lutzomyia longipalpis.
Conclusiones: se mantiene la alerta de brote de leishmaniasis visceral en Neiva por la confirmación de ocho casos, con activación de focos existentes en las comunas 10, 9, 8 y 2, entre enero y julio de 2017.
Aumento inusitado de casos de malaria en Guainía, Colombia 2015 -2017
Authors: Salas Botero Daniela , Parra Córdoba Julietd Tatiana , Azcarate Vásquez Carlos Eric , Murcia Ramírez Carlos Humberto
Published: January 2022

Introducción: La malaria es actualmente uno de los problemas de salud pública más graves en Colombia. El objetivo fue establecer las características de la Malaria en el departamento de Guainía entre 2015 y la semana epidemiológica 28 de 2017, así como la descripción de las características sociales, demográficas, clínicas y epidemiológicas, antecedentes de riesgo y las complicaciones.
Metodología: investigación descriptiva. La fuente de información se obtuvo a través de la notificación individual semanal de casos al SIVIGILA del evento malaria entre 2015 y la semana epidemiológica 28 de 2017.
Resultados principales: La malaria en el departamento del Guainía ha tenido una tendencia al incremento. P ara el 2015 en el municipio de Inírida se reportó un índice parasitario anual de 53, 49 y en el 2016 con 119,75 casos por cada 1000 habitantes en riesgo. 98,8% de los casos procedentes del exterior notificados por el departamento son de Venezuela.
Conclusiones: La malaria en Guainía entre 2015 y la semana epidemiológica 28 de 2017 5 reporta un incremento de cuatro veces entre el 2015 a 2016 y entre 2015 y 2016 de 122%;
El incremento de casos puede deberse al alto tránsito de personas en la frontera colombo-venezolana en razón a labores de minería, lo que dificulta encontrar los focos de transmisión, que se pueden encontrar tanto en Inírida, como en la zona rural de Guainía y en el estado de Amazonas en Venezuela.
Investigación de brote enfermedad diarreica aguda, Ipiales – Nariño, Semanas epidemiológicas 28 a 34 de 2017
Authors: Vela Santacruz Juan Carlos , Revelo Revelo Angélica María , Padilla Ana Victoría , Revelo Revelo Ana María , Rivera Estrada Lisseth Johanna , Díaz Muñoz Harold Antonio , Guerrero Osejo Mauricio , Tellez Salas Julián Mauricio , Rodríguez Silvia Angélica , Montenegro Diana Carolina , Peláez Carvajal Dioselina , Ayala Sotelo Martha Stella , Duarte Valderrama Carolina , Prieto Alvarado Franklyn Edwin
Published: January 2022

El aumento inusitado de consultas a las tres principales instituciones prestadoras de servicios de salud del municipio de Ipiales desde el 14 de julio de 2017, por un cuadro clínico consistente en diarrea, nauseas, vómito y dolor abdominal, generó una respuesta de investigación y control del evento, coordinada entre la Dirección Local de Salud y el Instituto Departamental de Salud de Nariño con el apoyo del Instituto Nacional de Salud.
Se configuró un brote de enfermedad diarreica aguda de etiología viral que afectó alrededor del 85% de los barrios de la cabecera municipal. Los hallazgos de la curva epidémica indicaron al inicio una fuente común siendo el agua suministrada a la población el vehículo y una segunda fase de transmisión mediante fuente propagada (persona a persona). La mayor proporción de casos se concentró en la población menor de cinco años. La proporción de casos con hospitalización mayor a 24 horas fue del 9,9 % del total de casos. No se presentaron casos graves ni mortalidad asociada. No se sobrepasó la capacidad de respuesta de la entidad territorial ni de la red de prestación de servicios de salud.
La principal condición de riesgo identificada fue el sistema de abastecimiento de agua y aunque no se logró identificar de manera específica una situación o evento desencadenante del brote, los hallazgos en las muestras biológicas y de agua, el comportamiento de la curva epidémica, así como los hallazgos sanitarios y ambientales permiten identificar qué múltiples factores relacionados con la fuente, la captación, tratamiento y distribución del sistema de acueducto principal del municipio, estuvieron implicados tanto en el origen como en la propagación del brote.
Comportamiento epidemiológico de los casos de intoxicaciones por metanol en Colombia, 2008 - 2015
Authors: Gamarra Cuellar Jorge Alberto , Muñoz Guerrero María Nathalia , Díaz Criollo Sonia Mireya , Gómez Ortega Luis Carlos
Published: January 2022

Introducción: Las intoxicaciones por metanol se encuentran dentro de las sustancias químicas mayormente involucradas en las intoxicaciones por sustancias químicas en nuestro país, teniendo en cuanta el grado de toxicidad nos encontramos frente a un evento que tiene la capacidad de generar una morbilidad y mortalidad importante.
Objetivos: identificar las características demográficas y sociales de la población colombiana intoxicada por metanol, medir el comportamiento de estas en el territorio colombiano, identificar el tipo de exposición y medir las muertes registradas durante los años 2008 a 2015, de acuerdo con la notificación realizada al Sistema de Vigilancia en Salud Pública (Sivigila).
Metodología: se llevó a cabo un estudio de tipo descriptivo retrospectivo, en el que se analizaron las variables de interés obtenidas de las bases de datos de casos registrados, calculando proporciones de datos nominales y tablas de frecuencias, así como análisis univariados y bivariados.
Resultados: dentro de los grupos de edad mayormente implicados en las intoxicaciones por medicamentos se encuentran los comprendidos entre los 15 a 29 años, presentando un tipo de exposición accidental y una vía de exposición oral; la confirmación por laboratorio en muy baja y solo el 44,3 % de los casos fueron hospitalizados.
Conclusiones: Las intoxicaciones con metanol se presentan principalmente en hombres, de la misma manera, la principal forma de afectación en la población es de tipo accidental, y se han notificado 32 muertes.
Comportamiento epidemiológico de los casos de intoxicaciones por plaguicidas en Colombia, 2008 - 2015
Authors: Muñoz Guerrero María Nathalia , Gamarra Cuellar Jorge Alberto , Gómez Ortega Luis Carlos , Díaz Criollo Sonia Mireya
Published: January 2022

Introducción: el contacto con plaguicidas tiene como consecuencia las intoxicaciones que se dan bien sea por su uso inapropiado, de forma accidental, ocupacional o incluso de uso intencional de manera homicida, donde se incluye el suicidio.
Objetivos: identificar las características demográficas y sociales de la población colombiana intoxicada por plaguicidas, medir el comportamiento de estas en el territorio colombiano, identificar el tipo de exposición y medir las muertes registradas durante los años 2008 a 2015, de acuerdo con la notificación realizada al Sistema de Vigilancia en Salud Pública (Sivigila).
Metodología: se llevó a cabo un estudio de tipo descriptivo retrospectivo, en el que se analizaron las variables de interés obtenidas de las bases de datos de casos registrados, calculando proporciones de datos nominales y tablas de frecuencias, así como análisis univariados y bivariados.
Resultados: las intoxicaciones por plaguicidas se presentaron mayor frecuencia en hombres con 38 379 casos (el 56,9 %), en las cabeceras municipales (el 56,3 %). El 53,6 % de los casos requirieron hospitalización y más del 59 % se presentaron con intencionalidad suicida. Los plaguicidas más asociados a las intoxicaciones reportadas fueron los insecticidas seguido de los rodenticidas, según su grupo químico, predominan los organofosforados, carbamatos y se utilizaron mezclas de plaguicidas principalmente en la intencionalidad suicida.
Conclusiones: Las intoxicaciones por plaguicidas se presentan principalmente en hombres, solteros en grupos de edad laboralmente activos, predominando la vía oral y el tipo de intencional suicida.
Fiber-Like Organization as a Basic Principle for Euchromatin Higher-Order Structure
Authors: Zakirov Amir N. , Sosnovskaya Sophie , Ryumina Ekaterina D. , Kharybina Ekaterina , Strelkova Olga S. , Zhironkina Oxana A. , Golyshev Sergei A. , Moiseenko Andrey , Kireev Igor I.
Published: January 2022

A detailed understanding of the principles of the structural organization of genetic material is of great importance for elucidating the mechanisms of differential regulation of genes in development. Modern ideas about the spatial organization of the genome are based on a microscopic analysis of chromatin structure and molecular data on DNA–DNA contact analysis using Chromatin conformation capture (3C) technology, ranging from the “polymer melt” model to a hierarchical folding concept. Heterogeneity of chromatin structure depending on its functional state and cell cycle progression brings another layer of complexity to the interpretation of structural data and requires selective labeling of various transcriptional states under nondestructive conditions. Here, we use a modified approach for replication timing-based metabolic labeling of transcriptionally active chromatin for ultrastructural analysis. The method allows pre-embedding labeling of optimally structurally preserved chromatin, thus making it compatible with various 3D-TEM techniques including electron tomography. By using variable pulse duration, we demonstrate that euchromatic genomic regions adopt a fiber-like higher-order structure of about 200 nm in diameter (chromonema), thus providing support for a hierarchical folding model of chromatin organization as well as the idea of transcription and replication occurring on a highly structured chromatin template.
The Effect of Temperature on Gonadal Sex Differentiation of Yesso Scallop Patinopecten yessoensis
Authors: Liu Tian , Li Ruojiao , Liu Liangjie , Wu Shaoxuan , Zhang Lijing , Li Yajuan , Wei Huilan , Shu Ya , Yang Yaxin , Wang Shi , Xing Qiang , Zhang Lingling , Bao Zhenmin
Published: January 2022

Many marine organisms are generally poikilotherms, making seawater temperature one of the most important environmental factors affecting gonadal sex differentiation. Mollusca is the second-largest animal phylum with diverse reproductive systems, but studies on the impact of temperature on sex differentiation are limited to a few sequential hermaphrodites. By combining morphological and molecular analyses, we investigated the effect of temperature on gonadal sex differentiation of a commercially important gonochoristic scallop Patinopecten yessoensis in the field and under laboratory conditions. Based on the relative expression of FoxL2 and Dmrt1L in the gonads of 6- to 12 month-old scallops, we found the scallops start to differentiate at 7 months old in September when the seawater temperature was 21°C. To eliminate the effect of factors other than temperature on sex differentiation, we compared the gonadal development of juvenile scallops at different temperatures (21, 16 and 11°C) under laboratory conditions. After 50 days of treatment, the 11°C group contain more germ cell types, and have higher sex differentiation rates than the 21°C group. But no obvious sex bias was observed. These results suggest that high temperature (21°C) inhibits sex differentiation, whereas low temperature (11°C) accelerates sex differentiation by 2 months for this cold-water species. It also supports juvenile P. yessoensis is gonochoristic rather than protandrous hermaphroditic. Our study addresses for the first time an environmental influence associated with genetic controls on scallop sex differentiation. It will facilitate a better understanding of how environmental factors affect gonadal development in poikilotherms, especially in the less studied molluscs.
Cholesterol Induces Pyroptosis and Matrix Degradation via mSREBP1-Driven Endoplasmic Reticulum Stress in Intervertebral Disc Degeneration
Authors: Yan Jiansen , Li Shuangxing , Zhang Yangyang , Deng Zhihuai , Wu Jiajun , Huang Zhengqi , Qin Tianyu , Xiao Yin , Zhou Jie , Xu Kang , Ye Wei
Published: January 2022

Intervertebral disc degeneration (IDD) is closely associated with low back pain, but its underlying mechanism remains unclear. Cholesterol is an essential nutrient in mammalian cells. Alterations in cholesterol levels lead to impairments in cell physiology, such as cell proliferation and signal transduction. Previous clinical studies demonstrated that hypercholesterolemia could be a potential risk factor for IDD, but how cholesterol induces IDD remains unknown. The current study aimed to explore the regulatory role of cholesterol in IDD development and the potential underlying mechanisms. It was found that different forms of cholesterol levels were elevated in degenerative nucleus pulposus (NP) tissues in both humans and Sprague–Dawley rats. Rats fed a high cholesterol diet (HCD) exhibited degenerative features in the lumbar intervertebral disc compared with those fed a standard diet. Interestingly, this effect could be abolished by cholesterol-lowering drug atorvastatin. In NP cells treated with TNF-α and IL-1β, a significantly higher level of cholesterol was observed. These results suggested a pivotal role of cholesterol in the progression of IDD. We also observed accelerated pyroptosis in NP cells and extracellular matrix (ECM) degradation in the rat NP cells treated with exogenous cholesterol. We further demonstrated that endoplasmic reticulum stress was responsible for cholesterol-induced pyroptosis and ECM degradation. Moreover, RNA-seq analysis revealed that the mature form of SREBP1 (mSREBP1), an important regulator of lipid metabolism, is involved in regulating endoplasmic reticulum stress in knockdown experiments. In conclusion, this study demonstrated that cholesterol could induce pyroptosis in NP cells and ECM degradation by activating endoplasmic reticulum stress through stimulating mSREBP1 in IDD.
Discovery of SIRT7 Inhibitor as New Therapeutic Options Against Liver Cancer
Authors: Zhang Chen , Li Yaqi , Liu Bohao , Ning Chao , Li Yimin , Wang Ying , Li Zhuan
Published: January 2022

Optimal therapeutic strategies for liver cancer patients remain challenging due to the high recurrence rate after surgical resection and chemotherapy resistance. Emerging evidence has shown that epigenetic factor SIRT7 is involved in various aspects of cancer biology, while inactive SIRT7 reverses human cancer phenotype and suppresses tumor growth. In the present study, we predicted the SIRT7 structure by using the fold recognition (or threading) method and performed structure-based virtual screening to develop specific SIRT7 inhibitor by docking 939319 structurally diverse compounds with SIRT proteins. Compounds with high affinities to SIRT7 but low affinities to other SIRT proteins were chosen as candidates of specific SIRT7 inhibitor. Our leading compounds 2800Z and 40569Z showed strong interaction with SIRT7 protein, and specifically inhibited SIRT7 deacetylation activity in vitro. Our docking results also revealed that ARG-120, TRP-126, and HIS-187 were critical sites responsible for interaction of SIRT7 with small molecules. Mutations in the aforementioned sites significantly abolished interaction and inhibitory effects of compounds to SIRT7. In addition, in vivo data indicated that compounds 2800Z and 40569Z were able to induce apoptosis and increase chemosensitivity to sorafenib in human liver cancer. Our findings demonstrated targeting SIRT7 may offer novel therapeutic options for cancer management, and the value of compounds 2800Z and 40569Z as chemical probes for the study of SIRT7 biological functions as well as starting leads for the development of new therapeutic options against liver cancer.
Identification of Key Genes Related With Aspartic Acid Metabolism and Corresponding Protein Expression in Human Colon Cancer With Postoperative Prognosis and the Underlying Molecular Pathways Prediction
Authors: Sun Weixuan , Jia Chaoran , Zhang Xiaojun , Wang Zhaoyi , Li Yaping , Fang Xuedong
Published: January 2022

Objective: Colon cancer is one of the most frequent and lethal neoplasias. Altered metabolic activity is a well-known hallmark for cancer. The present study is aiming to screen key genes associated with tumor metabolism and construct a prognostic signature of colon cancer patients.

Methods: Glutamine- and UC- metabolism related genes were downloaded from GSEA MsigDB. Three key genes were screened by Cox regression analysis with data samples downloaded from TCGA and GSE29623 database. Consistent clustering based on the prognostic genes identified was employed to divide the colon cancer samples into two clusters with significant OS differences. The mRNA and protein expression of the key genes in colon tissues and matched adjacent noncancerous tissues of 16 patients were detected by IHC, qPCR, and Western blot to validate the constructed clustering model. GO, GSVA, and IPA were used to predict the relevant metabolic pathways.

Results: According to the three key genes identified, i.e., ASNS, CEBPA, and CAD, the cohort can be divided into two clusters with prognosis differences. Clinical specimen results confirmed that the risk model established was effective, and the different expression pattern of ASNS and CEBPA was correlated with TNM stage and lymph node metastasis, whilst that of CAD was correlated with post-operative tumor metastasis and recurrence. Molecular mechanism prediction indicated that CREB, insulin, and RNA Pol II were the key nodes affecting CEBPA and ASNS expression. Moreover, TIDE algorithm reflected the better immune response of the cluster with shorter OS. Further immune infiltration and checkpoints analyses provided important reference for clinicians to perform individualized immunotherapy.

Conclusion: Differential expression profile of three aspartic acid metabolic-associated genes, ASNS, CEBPA, and CAD, can be considered as a risk model with a good evaluation effect on the prognosis of colon cancer patients.
2-Methyl Nonyl Ketone From Houttuynia Cordata Thunb Alleviates LPS-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells
Authors: Wang Nan , Zhu Yanbin , Li Dandan , Basang Wangdui , Huang Yiqiu , Liu Kening , Luo Yuxin , Chen Lu , Li Chunjin , Zhou Xu
Published: January 2022

Mastitis is one of the most common diseases in dairy cows, causing huge economic losses to the dairy industry every year. Houttuynia Cordata Thunb (H.cordata) is a traditional Chinese herbal medicine that is widely used in clinical treatment. However, the therapeutic effect of 2-methyl nonyl ketone (MNK), the main volatile oil component in the aqueous vapor extract of H. cordata, on mastitis has been less studied. The purpose of this study was to investigate the protective effect and mechanism of MNK against lipopolysaccharide (LPS)-induced mastitis in vitro. The results showed that MNK pretreatment of the bovine mammary epithelial cell line (MAC-T) enhanced cell viability and inhibited LPS-induced reactive oxygen species (ROS) production and inflammatory response. MNK reduced the production of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor-α (TNF-α) by repressing LPS-induced activation of Toll-like receptor 4-nuclear factor-κB (TLR4-NF-κB) signaling pathway. In addition, MNK protected cells from inflammatory responses by blocking the downstream signaling of inflammatory factors. MNK also induced Heme Oxygenase-1 (HO-1) production by Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through AKT and extracellular signal-regulated kinase (ERK) pathways, thereby reducing LPS-induced oxidative damage for MAC-T cells. In conclusion, MNK played a protective role against LPS-induced cell injury. This provides a theoretical basis for the research and development of MNK as a novel therapeutic agent for mastitis.
A Correlation Study of the Microbiota Between Oral Cavity and Tonsils in Children With Tonsillar Hypertrophy
Authors: Xu He , Tian Bijun , Shi Weihua , Tian Jing , Zhang Xuexi , Zeng Jin , Qin Man
Published: January 2022

Tonsillar hypertrophy is a common disease in 3-to-6-year-old children, which may cause serve symptoms like airway obstruction. Microbiological factors play an important role in the etiology of tonsillar hypertrophy. As the starting point of digestive and respiratory tracts, the microbial composition of the oral cavity is not only unique but also closely related to the resident microbiota in other body sites. Here we reported a correlation study of the microbiota between oral cavity and tonsils in children with tonsillar hypertrophy. Saliva, supragingival plaque, and wiped samples from the tonsil surface were collected from both tonsillar hypertrophy patients and participants with healthy tonsils and were then analyzed using Illumina Miseq Sequencing of the 16S rRNA gene. In the tonsillar hypertrophic state, more genera were detected on the tonsil surface than in the tonsil parenchyma, with more intra-microbiota correlations. When tonsillar hypertrophy occurred, both the oral cavity and tonsil surface endured microbiome shift with increased genera category and more active bacterial interactions. Over half of the newly detected genera from the tonsillar hypertrophic state were associated with infection and inflammation process or exhibited antibiotic-resistant characters. Of each individual, the microbial composition and structure of saliva seemed more similar to that of the tonsil surface, compared with the supragingival plaque. In salivary microbiota, genus Johnsonella might be relative with the healthy state of tonsils, while Pseudoxanthomonas might be relative with tonsillar hypertrophy. Our study supported the link between oral microbiota with the healthy and hypertrophic states of tonsils and may provide new directions for future researches in the specific role of oral microbiota in the etiology of tonsil diseases.
In Vitro Modelling of Chlamydia trachomatis Infection in the Etiopathogenesis of Male Infertility and Reactive Arthritis
Authors: Filardo Simone , Di Pietro Marisa , Diaco Fabiana , Sessa Rosa
Published: January 2022

Chlamydia trachomatis is an obligate, intracellular bacterium responsible for a range of diseases of public health importance, since C. trachomatis infection is often asymptomatic and, hence, untreated, leading to chronic complications, including prostatitis, infertility, and reactive arthritis. The ample spectrum of diseases caused by C. trachomatis infection is reflected in its ability to infect and multiply within a wide range of different cell types. Cervical epithelial cells, to date, have been the most studied cellular infection model, highlighting the peculiar features of the host-cell inflammatory and immune responses to the infection. Herein, we provide the up-to-date evidence on the interaction between C. trachomatis and human prostate epithelial, Sertoli and synovial cells.
Association of Helicobacter pylori Infection With Carotid Atherosclerosis in a Northern Chinese Population: A Cross-Sectional Study
Authors: Zhang Pu , He Qian , Song Daiyu , Wang Yiying , Liu Xinyue , Ding Guoyong , Xing Weijia
Published: January 2022

Numerous studies have shown that Helicobacter pylori (HP) infection may be involved in the development of carotid atherosclerosis (CAS), but this conclusion is still controversial. The aim of this study was to explore whether there is a positive association between HP infection and CAS occurrence. We collected data on demographic characteristics, lifestyle, and disease history of the participants by questionnaire. We obtained clinical anthropometric data and blood samples of the participants from clinical examinations and laboratory work. The 13C urea breath test (13C-UBT) was performed to assess the HP infection status, and carotid ultrasonography was used to diagnose the CAS and plaque types. Univariate analysis and multivariate logistic regression were used to identify the relationship between HP infection and CAS. A total of 1,424 participants were recruited for this study. A total of 740 HP-positive individuals and 684 HP-negative individuals were identified, and 345 participants were diagnosed with CAS. The prevalence of CAS was higher in the HP-positive group (26.4%) than in the HP-negative group (21.7%) (P < 0.05). A significantly higher prevalence of carotid intima-media thickening, carotid plaque, and carotid stenosis was identified in the HP-positive group than in the HP-negative group (P < 0.05). There was no significant difference in the detection rate of unstable plaques between the HP-positive and HP-negative groups (P > 0.05). In multivariate models adjusted for covariates, HP infection showed a positive association with CAS, independent of other risk factors (ORs range: 1.283–1.333, P < 0.05). HP infection independently accounted for approximately 5% of the CAS risk in the absence of other cardiovascular risk factors. A positive association between HP infection and CAS was demonstrated in this study. HP infection might be an independent risk factor for CAS. Although the effect of HP infection on CAS observed in our study was less than that of traditional risk factors, we believe that this is an indispensable advance in the etiological study of CAS. These results imply that the microbial population might play an essential role in CAS, which provides a new perspective for the primary prevention of CAS.
Cardiovascular Imaging in Stress Cardiomyopathy (Takotsubo Syndrome)
Authors: Zghyer Fawzi , Botheju W. Savindu Pasan , Kiss Joshua E. , Michos Erin D. , Corretti Mary C. , Mukherjee Monica , Hays Allison G.
Published: January 2022

Stress cardiomyopathy (Takotsubo syndrome) is a reversible syndrome stemming from myocardial injury leading to systolic dysfunction and is usually noted in the setting of a stressful event, be it an emotional or physical trigger. While the exact pathophysiology behind stress cardiomyopathy is yet unknown, there is ample evidence suggesting that neurocardiogenic mechanisms may play an important role. Although historically stress cardiomyopathy was generally thought to be a relatively benign condition, there is growing recognition of the cardiovascular complications associated with it despite its reversibility. Our review aims to shed light onto key cardiovascular imaging modalities used to diagnose stress cardiomyopathy while highlighting the role that imaging plays in assessing disease severity, identifying complications, dictating treatment approaches, and in short-term and long-term prognosis.
Neutrophil-Platelet Interactions as Novel Treatment Targets in Cardiovascular Disease
Authors: Kaiser Rainer , Escaig Raphael , Erber Johanna , Nicolai Leo
Published: January 2022

Neutrophils and platelets are among the most abundant cell types in peripheral blood and characterized by high plasticity and a readily available reservoir of surface proteins and secretable granule contents. Receptor-mediated activation and granule release predispose both cell types for rapid responses to various stimuli. While neutrophils provide the first line of defense to microbial infections and platelets are known for their aggregatory functions in hemostasis and thrombosis, research of the past decade has highlighted that both cell types jointly shape local and systemic immune responses and clot formation alike. Concomitant activation of neutrophils and platelets has been observed in a variety of cardiovascular diseases, including arterial and venous thrombosis, atherosclerosis as well as myocardial infarction and ischemia-reperfusion injury. In this review, we describe the mechanisms by which neutrophils and platelets interact physically, how release of granule contents and soluble molecules by either cell type affects the other and how this mutual activation supports the efficacy of immune responses. We go on to describe how activated platelets contribute to host defense by triggering neutrophil extracellular trap (NET) formation in a process termed immunothrombosis, which in turn promotes local platelet activation and coagulation. Further, we review current evidence of hazardous overactivation of either cell type and their respective role in cardiovascular disease, with a focus on thrombosis, myocardial infarction and ischemia-reperfusion injury, and describe how neutrophils and platelets shape thromboinflammation in COVID-19. Finally, we provide an overview of therapeutic approaches targeting neutrophil-platelet interactions as novel treatment strategy in cardiovascular disease.
Serotonin—A Driver of Progressive Heart Valve Disease
Authors: Waldum Helge , Wahba Alexander
Published: January 2022

It is well known that some serotoninergic drugs and neuroendocrine tumors producing serotonin (5-HT) may induce valvular heart disease by stimulation of proliferation of valvular cells via interaction with a 5-HT receptor type 2B. Serotonin could play a role in the pathogenesis of progressive valvular disease for example as a complication of rheumatic fever, in patients with congenital bicuspid aortic valves or in degenerative aortic valve stenosis. The initial inflammation in acute rheumatic fever seems to affect both right and the left-side cardiac valves. Some patients develop chronic right-sided valve disease, particularly in connection with septum defects, though left-sided valves typically are predominantly affected, indicating that high flow velocity and systemic pressure close to the valves may be central in the pathogenesis. Serotonin is transported in granules in blood platelets. Changes in platelet number and concentrations of substances released from platelets in patients with valvular disease indicate that serotonin is released locally by shear stress when passing through an abnormal valve. Accordingly, any functional changes (like bicuspid aortic valves and changes secondary to degeneration) in the valves may progress due to locally released serotonin. Unfortunately, due to serotonin release by sampling and preparation of plasma, local serotonin assessment is not possible. Nevertheless, we suggest that serotonin may play a role in valvular disease in general and that patients may benefit from treatment reducing the effect of serotonin on the heart.
Influence of Right Ventricular Dysfunction on Outcomes of Left Ventricular Non-compaction Cardiomyopathy
Authors: Wang Wuwan , Chen Wei , Lin Xue , Fang Ligang
Published: January 2022

Background

Various adverse outcomes such as mortality and rehospitalization are associated with left ventricular non-compaction (LVNC). Due to data limitations, prospective risk assessment for LVNC remains challenging. This study aimed to investigate the influence of right ventricular (RV) dysfunction on the clinical outcomes of patients with LVNC through accurate and comprehensive measurements of RV function.

Methods and Results

Overall, 117 patients with LVNC (47.6 ± 18.3 years, 34.2% male) were enrolled, including 53 (45.3%) and 64 (54.7%) patients with and without RV dysfunction, respectively. RV dysfunction was defined as meeting any two of the following criteria: (i) tricuspid annular systolic excursions <17 mm, (ii) tricuspid S′ velocity <10 cm/s, and (iii) RV fractional area change (FAC) <35%. The proportion of biventricular involvement was significantly higher in patients with RV dysfunction than in controls (p = 0.0155). After a follow-up period of 69.0 [33.5, 96.0] months, 18 (15.4%) patients reached the primary endpoint (all-cause mortality), with 14 (26.4%) and 4 (6.3%) from the RV dysfunction group and normal RV function group, respectively. The Kaplan–Meier method and log-rank test revealed that patients with RV dysfunction had a higher risk of all-cause mortality than those in the control group (hazard ratio [HR]: 5.132 [2.003, 13.15], p = 0.0013). Similar results were obtained for patients with left ventricular ejection fraction (LVEF) <50% [HR, 6.582; 95% confidence interval (CI), 2.045–21.19; p = 0.0367]. The relationship between RV dysfunction and heart failure rehospitalization and implantation of implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy (CRT) was not statistically significant (both p > 0.05). The multivariable Cox proportional hazard modeling analysis showed that RV dysfunction (HR: 4.950 [1.378, 17.783], p = 0.014) and impaired RV global longitudinal strain (RVGLS) (HR: 1.103 [1.004, 1.212], p = 0.041) were independent predictors of mortality rather than increased RV end-diastolic area and decreased LVEF (both p > 0.05).

Conclusions

RV dysfunction is associated with the prognosis of patients with LVNC.
Imaging β-Cell Function Using a Zinc-Responsive MRI Contrast Agent May Identify First Responder Islets
Authors: Thapa Bibek , Suh Eul Hyun , Parrott Daniel , Khalighinejad Pooyan , Sharma Gaurav , Chirayil Sara , Sherry A. Dean
Published: January 2022

An imaging method for detecting β-cell function in real-time in the rodent pancreas could provide new insights into the biological mechanisms involving loss of β-cell function during development of type 2 diabetes and for testing of new drugs designed to modulate insulin secretion. In this study, we used a zinc-responsive MRI contrast agent and an optimized 2D MRI method to show that glucose stimulated insulin and zinc secretion can be detected as functionally active “hot spots” in the tail of the rat pancreas. A comparison of functional images with histological markers show that insulin and zinc secretion does not occur uniformly among all pancreatic islets but rather that some islets respond rapidly to an increase in glucose while others remain silent. Zinc and insulin secretion was shown to be altered in streptozotocin and exenatide treated rats thereby verifying that this simple MRI technique is responsive to changes in β-cell function.
Highly Efficient Genome Editing in Plant Protoplasts by Ribonucleoprotein Delivery of CRISPR-Cas12a Nucleases
Authors: Zhang Yingxiao , Cheng Yanhao , Fang Hong , Roberts Nathaniel , Zhang Liyang , Vakulskas Christopher A. , Niedz Randall P. , Culver James N. , Qi Yiping
Published: January 2022

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) mediated genome editing is a powerful approach for crop improvement. Traditional transformation methods based on plasmid delivery pose concerns associated with transgene integration and off-target effects. CRISPR delivered as ribonucleoproteins (RNPs) can prevent exogenous DNA integration, minimize off-target effects, and reduce cellular toxicity. Although RNP delivered CRISPR genome editing has been demonstrated in many plant species, optimization strategies that yield high editing efficiencies have not been thoroughly investigated. Using rice and citrus protoplast systems we demonstrated highly efficient genome editing using Cas12a delivered as RNPs. Four Cas12a variants, including LbCas12a, LbCas12a-E795L, AsCas12a, and AsCas12a Ultra, were investigated. Nearly 100% editing efficiency was observed for three out of four target sites by LbCas12a, LbCas12a-E795L, and AsCas12a Ultra, as measured by restriction fragment length polymorphism (RFLP) and verified by next generation sequencing of PCR amplicons. RNP delivery resulted in higher editing efficiencies than plasmid delivery at 32°C and 25°C. LbCas12a and LbCas12a-E795L demonstrated increased editing efficiencies in comparison to AsCas12a and AsCas12a Ultra, especially when used at lower RNP concentrations. In addition, we discovered that a 1:1 Cas12a:crRNA molar ratio is sufficient to achieve efficient genome editing. Nuclear localization signals (NLSs) are essential for efficient RNP-based genome editing. However, the different crRNA modifications tested did not significantly improve genome editing efficiency. Finally, we applied the Cas12a RNP system in citrus protoplasts and obtained similarly high editing efficiencies at the target site. Our study provides a comprehensive guideline for Cas12a-mediated genome editing using RNP delivery in plant cells, setting the foundation for the generation of transgene-free genome edited plants.
Single-Cell RNA Sequencing of Human Pluripotent Stem Cell-Derived Macrophages for Quality Control of The Cell Therapy Product
Authors: Jo Hye-Yeong , Seo Hyang-Hee , Gil Dayeon , Park YoungChan , Han Hyeong-Jun , Han Hyo-Won , Thimmulappa Rajesh K. , Kim Sang Cheol , Kim Jung-Hyun
Published: January 2022

Macrophages exhibit high plasticity to achieve their roles in maintaining tissue homeostasis, innate immunity, tissue repair and regeneration. Therefore, macrophages are being evaluated for cell-based therapeutics against inflammatory disorders and cancer. To overcome the limitation related to expansion of primary macrophages and cell numbers, human pluripotent stem cell (hPSC)-derived macrophages are considered as an alternative source of primary macrophages for clinical application. However, the quality of hPSC-derived macrophages with respect to the biological homogeneity remains still unclear. We previously reported a technique to produce hPSC-derived macrophages referred to as iMACs, which is amenable for scale-up. In this study, we have evaluated the biological homogeneity of the iMACs using a transcriptome dataset of 6,230 iMACs obtained by single-cell RNA sequencing. The dataset provides a valuable genomic profile for understanding the molecular characteristics of hPSC-derived macrophage cells and provide a measurement of transcriptomic homogeneity. Our study highlights the usefulness of single cell RNA-seq data in quality control of the cell-based therapy products.