Pub Date : 2024-11-26DOI: 10.1016/j.arcmed.2024.103127
Marlene López-Sánchez , Aleida Bautista-Santos , María del Pilar Milke-García , Aldo Allende-López , Rosalba Moreno-Alcántar , Segundo Morán
Background
Malnutrition in patients with liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) has been associated with adverse outcomes. However, there is little information on the incidence of HCC during the compensated phase of LC in relation to the nutritional status.
Aim
To evaluate the association between the incidence of HCC in compensated LC and their nutritional status.
Methods
Patients with compensated liver cirrhosis with no previous history of ascites, hepatic encephalopathy, or variceal bleeding attending the Gastroenterology outpatient service at Centro Medico Nacional Siglo XXI were included in a prospective cohort. Clinical and nutritional parameters were collected, including the Royal Free Hospital Subjective Global Assessment (RFH-SGA) as an indicator of protein-calorie malnutrition and the triceps skinfold thickness, which classified patients as having normal subcutaneous adipose tissue (SAT), above average SAT, and below average SAT. Follow-up was censored at the time of HCC diagnosis or LC decompensation.
Results
About 31/187 (16.0 %) and 22/187 (11.8 %) patients were categorized as having above- or below-average SAT at baseline, respectively. 10/187 patients (5.3 %) developed HCC during the compensated phase of LC at a median of 22 months (IQR: 10.0–36.75). A higher risk of HCC was observed in subjects below average SAT (HR: 4.064, CI 95 %: 1.012–16.317, p = 0.048). After adjusting the Cox models for age and α-fetoprotein at baseline, the statistical significance of the association between SAT and HCC was not modified.
Conclusion
These results suggest that decreased SAT may precede the diagnosis of HCC in compensated LC.
{"title":"Nutritional status and incidence of hepatocellular carcinoma in patients with compensated liver cirrhosis","authors":"Marlene López-Sánchez , Aleida Bautista-Santos , María del Pilar Milke-García , Aldo Allende-López , Rosalba Moreno-Alcántar , Segundo Morán","doi":"10.1016/j.arcmed.2024.103127","DOIUrl":"10.1016/j.arcmed.2024.103127","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition in patients with liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) has been associated with adverse outcomes. However, there is little information on the incidence of HCC during the compensated phase of LC in relation to the nutritional status.</div></div><div><h3>Aim</h3><div>To evaluate the association between the incidence of HCC in compensated LC and their nutritional status.</div></div><div><h3>Methods</h3><div>Patients with compensated liver cirrhosis with no previous history of ascites, hepatic encephalopathy, or variceal bleeding attending the Gastroenterology outpatient service at Centro Medico Nacional Siglo XXI were included in a prospective cohort. Clinical and nutritional parameters were collected, including the Royal Free Hospital Subjective Global Assessment (RFH-SGA) as an indicator of protein-calorie malnutrition and the triceps skinfold thickness, which classified patients as having <em>normal</em> subcutaneous adipose tissue (SAT), <em>above average</em> SAT, and <em>below average</em> SAT. Follow-up was censored at the time of HCC diagnosis or LC decompensation.</div></div><div><h3>Results</h3><div>About 31/187 (16.0 %) and 22/187 (11.8 %) patients were categorized as having above- or below-average SAT at baseline, respectively. 10/187 patients (5.3 %) developed HCC during the compensated phase of LC at a median of 22 months (IQR: 10.0–36.75). A higher risk of HCC was observed in subjects below average SAT (HR: 4.064, CI 95 %: 1.012–16.317, <em>p</em> = 0.048). After adjusting the Cox models for age and α-fetoprotein at baseline, the statistical significance of the association between SAT and HCC was not modified.</div></div><div><h3>Conclusion</h3><div>These results suggest that decreased SAT may precede the diagnosis of HCC in compensated LC.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 3","pages":"Article 103127"},"PeriodicalIF":4.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1016/j.arcmed.2024.103124
Elena Golovina , Juraj Kokavec , Dmitry Kazantsev , Oxana Yurikova , Martin Bajecny , Filipp Georgijevic Savvulidi , Radim Simersky , Rene Lenobel , Jorg Tost , Vit Herynek , Ludek Sefc , Marek Sebela , Pavel Klener , Zuzana Zemanova , Tomas Stopka , Karina Savvulidi Vargova
Background
Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155–5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research.
Methods
We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation.
Results
The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1).
Conclusions
We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
{"title":"Deficiency of miR-155 in leukemic B-cells results in cell cycle arrest and deregulation of MIR155HG/TP53INP1/CDKN1A/CCND1 network","authors":"Elena Golovina , Juraj Kokavec , Dmitry Kazantsev , Oxana Yurikova , Martin Bajecny , Filipp Georgijevic Savvulidi , Radim Simersky , Rene Lenobel , Jorg Tost , Vit Herynek , Ludek Sefc , Marek Sebela , Pavel Klener , Zuzana Zemanova , Tomas Stopka , Karina Savvulidi Vargova","doi":"10.1016/j.arcmed.2024.103124","DOIUrl":"10.1016/j.arcmed.2024.103124","url":null,"abstract":"<div><h3>Background</h3><div>Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155–5p (miR-155, <em>MIR155HG</em>), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research.</div></div><div><h3>Methods</h3><div>We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the <em>MIR155HG</em> gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation.</div></div><div><h3>Results</h3><div>The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator <em>p21/CDKN1A</em> and <em>Cyclin D1</em> (<em>CCND1</em>). We confirmed the overexpression of canonical miR-155 targets such as <em>PU.1, FOS, SHIP-1, TP53INP1</em> and revealed new potential targets (<em>FCRL5, ISG15,</em> and <em>MX1</em>).</div></div><div><h3>Conclusions</h3><div>We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the <em>MIR155HG/TP53INP1/CDKN1A/CCND1</em> axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 3","pages":"Article 103124"},"PeriodicalIF":4.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.arcmed.2024.103113
Jesus Hernandez-Juarez , Victor Manuel Dominguez-Reyes , Jaime Garcia-Chavez , Manuel Moreno-Hernandez , Paola Itzel Carmona-Olvera , Jose Antonio Alvarado-Moreno , Guillermo Espejo-Godinez , Julieta Espinoza-Islas , Karim Majluf-Cruz , Rodrigo Arreola-Diaz , Patricia Cruz-Puente , Guadalupe Ortiz-Torres , Berenice Sanchez-Jara , Cecilia Rodriguez-Castillejos , Rosa Elena Sosa-Camas , Patricia Gomez-Rosas , Gregorio Campos-Cabrera , Abraham Majluf-Cruz
Background
Von Willebrand disease (VWD), is the most common inherited bleeding disorder worldwide, but its diagnosis is complicated, expensive, and poorly evaluated in several countries.
Objective
To report our long-term experience with the diagnosis of VWD based on a cost-effective strategy.
Methods
We studied 802 Mexican patients, men and women, children, and adults, with clinical suspicion of VWD. The following tests were performed: blood count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, VWF antigen, ristocetin cofactor activity, collagen binding assay, ristocetin-induced platelet aggregation, FVIII activity, and VWF multimers analysis.
Results
VWD was diagnosed in 639 patients; 582 had type 1 VWD (91.1%). Type 2 VWD was found in 52 patients (8.1%). Type 2A was present in 25 cases (48.1%), while types 2B and 2 M accounted for 21 (40.4) and six (11.5%) cases, respectively. Type 3 VWD was present in five patients (0.8%). The mean age of patients with VWD was 25.3 years (range: 2–71) for males and 22.1 (range: 1–54) for females. The diagnosis was inconclusive in 40 cases (5.0%) and was discarded in 123 (15.3%). Blood group O was the most common among patients with VWD.
Conclusion
Using a low-cost diagnostic strategy, we confirmed that VWD is as common in Mexico as in other countries. Review of the patient's history is mandatory when VWD is suspected, although laboratory confirmation may be difficult and expensive. The consequences of a lack of accurate and timely diagnosis affect the promptness and quality of treatment.
{"title":"A ten-year experience with the diagnosis of von Willebrand disease in Mexico based on a cost-effective strategy","authors":"Jesus Hernandez-Juarez , Victor Manuel Dominguez-Reyes , Jaime Garcia-Chavez , Manuel Moreno-Hernandez , Paola Itzel Carmona-Olvera , Jose Antonio Alvarado-Moreno , Guillermo Espejo-Godinez , Julieta Espinoza-Islas , Karim Majluf-Cruz , Rodrigo Arreola-Diaz , Patricia Cruz-Puente , Guadalupe Ortiz-Torres , Berenice Sanchez-Jara , Cecilia Rodriguez-Castillejos , Rosa Elena Sosa-Camas , Patricia Gomez-Rosas , Gregorio Campos-Cabrera , Abraham Majluf-Cruz","doi":"10.1016/j.arcmed.2024.103113","DOIUrl":"10.1016/j.arcmed.2024.103113","url":null,"abstract":"<div><h3>Background</h3><div>Von Willebrand disease (VWD), is the most common inherited bleeding disorder worldwide, but its diagnosis is complicated, expensive, and poorly evaluated in several countries.</div></div><div><h3>Objective</h3><div>To report our long-term experience with the diagnosis of VWD based on a cost-effective strategy.</div></div><div><h3>Methods</h3><div>We studied 802 Mexican patients, men and women, children, and adults, with clinical suspicion of VWD. The following tests were performed: blood count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, VWF antigen, ristocetin cofactor activity, collagen binding assay, ristocetin-induced platelet aggregation, FVIII activity, and VWF multimers analysis.</div></div><div><h3>Results</h3><div>VWD was diagnosed in 639 patients; 582 had type 1 VWD (91.1%). Type 2 VWD was found in 52 patients (8.1%). Type 2A was present in 25 cases (48.1%), while types 2B and 2 M accounted for 21 (40.4) and six (11.5%) cases, respectively. Type 3 VWD was present in five patients (0.8%). The mean age of patients with VWD was 25.3 years (range: 2–71) for males and 22.1 (range: 1–54) for females. The diagnosis was inconclusive in 40 cases (5.0%) and was discarded in 123 (15.3%). Blood group O was the most common among patients with VWD.</div></div><div><h3>Conclusion</h3><div>Using a low-cost diagnostic strategy, we confirmed that VWD is as common in Mexico as in other countries. Review of the patient's history is mandatory when VWD is suspected, although laboratory confirmation may be difficult and expensive. The consequences of a lack of accurate and timely diagnosis affect the promptness and quality of treatment.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 2","pages":"Article 103113"},"PeriodicalIF":4.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.arcmed.2024.103128
Lauren A. Fowler , José R Fernández , Patrick M. O'Neil , Vibhu Parcha , Pankaj Arora , Naman S. Shetty , Michelle I. Cardel , Gary D. Foster , Barbara A Gower
Background
Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear.
Aims
With this cross-sectional study, we tested the hypothesis that racial disparities in T2D prevalence can be partially traced to heterogeneity in etiology, as indicated by genetic subtypes that reflect distinct T2D phenotypes.
Methods
Using a diverse sample of 361 US adults with T2D (69.5% women; 34.1% NHB; 13.9% Hispanic), we derived genetic risk scores (GRS) representing five distinct T2D pathophysiological pathways from 94 loci: β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. Genetic predisposition for insulin resistance (IR) was also assessed using a 52-SNP IR risk score.
Results
The β-cell and proinsulin scores (as median [IQR]) were higher among NHB participants relative to NHW and Hispanics (β-cell GRS [NHB, 0.842(0.784–0.887) vs. NHW, 0.762(0.702–0.835) and Hispanic, 0.772(0.717–0.848)]); proinsulin GRS (NHB, 1.006[0.973–1.070] vs. NHW, 0.969[0.853–1.044] and Hispanic, 0.976[0.901–1.048]), whereas the liver/lipid and 52-SNP IR scores were higher in both NHB and Hispanic participants versus NHW (liver/lipid GRS [NHB, 1.09(0.78–1.18) and Hispanic, 0.895(0.736–1.227) vs. NHW, 0.794(0.666–1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009–0.010] and Hispanic, 0.0096 [0.0092–0.0101] vs. NHW, 0.0090[0.0084–0.0095]).
Conclusions
Impaired β-cell function may underlie T2D etiology more profoundly in NHB, whereas hepatic dysfunction, lipid metabolism abnormalities, and genetic IR contribute to T2D etiology to a greater degree in both NHB and Hispanics. Further validation of these findings may form the basis for a personalized medicine approach to prevention and treatment of T2D.
背景：2 型糖尿病（T2D）在非西班牙裔黑人（NHB）和西班牙裔个体中的风险较高，其原因尚不清楚。目的：通过这项横断面研究，我们检验了以下假设：T2D 患病率的种族差异可部分归因于病因的异质性，如反映不同 T2D 表型的遗传亚型所示：我们利用 361 名患有 T2D 的美国成年人（69.5% 为女性；34.1% 为非裔美国人；13.9% 为西班牙裔美国人）的不同样本，从 94 个基因位点得出了代表五种不同 T2D 病理生理途径的遗传风险评分（GRS）：β 细胞、胰岛素原、肥胖、脂肪营养不良和肝脏/脂质。此外，还使用 52-SNP IR 风险评分对胰岛素抵抗（IR）的遗传易感性进行了评估：β细胞和胰岛素原评分（中位数[IQR]）在 NHB 参与者中高于 NHW 和西班牙裔（β细胞 GRS [NHB，0.842(0.784-0.887) vs. NHW，0.762-0.887]）。NHW，0.762(0.702-0.835) 和西班牙裔，0.772(0.717-0.848)]）；前胰岛素 GRS（NHB，1.006[0.973-1.070] vs. NHW，0.969[0.853-1.044] 和西班牙裔，0.976[0.901-1.0.048]），而 NHB 和西班牙裔参与者的肝脏/血脂和 52-SNP IR 评分均高于 NHW（肝脏/血脂 GRS [NHB, 1.09(0.78-1.18) and Hispanic, 0.895(0.736-1.227) vs. NHW, 0.794(0.666-1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009-0.010] and Hispanic, 0.0096 [0.0092-0.0101] vs. NHW, 0.0090[0.0084-0.0095]).Conclusions：结论：β细胞功能受损可能是非黑即白人群T2D病因的更深层次原因，而非黑即白人群和西班牙裔人群的肝功能异常、脂代谢异常和遗传性IR对T2D病因的影响程度更大。对这些发现的进一步验证可为预防和治疗 T2D 的个性化医学方法奠定基础。
{"title":"Genetic Risk Phenotypes for Type 2 Diabetes Differ with Ancestry in US Adults with Diabetes and Overweight/Obesity","authors":"Lauren A. Fowler , José R Fernández , Patrick M. O'Neil , Vibhu Parcha , Pankaj Arora , Naman S. Shetty , Michelle I. Cardel , Gary D. Foster , Barbara A Gower","doi":"10.1016/j.arcmed.2024.103128","DOIUrl":"10.1016/j.arcmed.2024.103128","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear.</div></div><div><h3>Aims</h3><div>With this cross-sectional study, we tested the hypothesis that racial disparities in T2D prevalence can be partially traced to heterogeneity in etiology, as indicated by genetic subtypes that reflect distinct T2D phenotypes.</div></div><div><h3>Methods</h3><div>Using a diverse sample of 361 US adults with T2D (69.5% women; 34.1% NHB; 13.9% Hispanic), we derived genetic risk scores (GRS) representing five distinct T2D pathophysiological pathways from 94 loci: β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. Genetic predisposition for insulin resistance (IR) was also assessed using a 52-SNP IR risk score.</div></div><div><h3>Results</h3><div>The β-cell and proinsulin scores (as median [IQR]) were higher among NHB participants relative to NHW and Hispanics (β-cell GRS [NHB, 0.842(0.784–0.887) vs. NHW, 0.762(0.702–0.835) and Hispanic, 0.772(0.717–0.848)]); proinsulin GRS (NHB, 1.006[0.973–1.070] vs. NHW, 0.969[0.853–1.044] and Hispanic, 0.976[0.901–1.048]), whereas the liver/lipid and 52-SNP IR scores were higher in both NHB and Hispanic participants versus NHW (liver/lipid GRS [NHB, 1.09(0.78–1.18) and Hispanic, 0.895(0.736–1.227) vs. NHW, 0.794(0.666–1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009–0.010] and Hispanic, 0.0096 [0.0092–0.0101] vs. NHW, 0.0090[0.0084–0.0095]).</div></div><div><h3>Conclusions</h3><div>Impaired β-cell function may underlie T2D etiology more profoundly in NHB, whereas hepatic dysfunction, lipid metabolism abnormalities, and genetic IR contribute to T2D etiology to a greater degree in both NHB and Hispanics. Further validation of these findings may form the basis for a personalized medicine approach to prevention and treatment of T2D.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 3","pages":"Article 103128"},"PeriodicalIF":4.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.arcmed.2024.103122
Jaime Gosálvez , Stephen D. Johnston , Ahinoa Prado , Carmen López-Fernández , Pablo Contreras , Javier Bartolomé-Nebreda , Mercedes González-Martínez , José Luis Fernández , Carlos García de la Vega , Alfredo Góngora
Background
Double- and single-strand DNA breaks (DSBs and SSBs, respectively) in spermatozoa, which emerge from intrinsic and extrinsic degenerative processes, are likely related to the underlying male pathology.
Aim
To determine whether the incidence of DSBs in the human ejaculate is a consistent predictor of whole sperm DNA fragmentation (W-SDF = SSBs + DSBs).
Methods
A correlation between the proportion of spermatozoa that showed whole W-SDF and those displaying only DSBs in DNA. Two patient cohorts were established: W-SDF ≤30% (low SDF; n = 153) and W-SDF ≥30% (high SDF; n = 222).
Results
An increasing level of W-SDF is associated with an increased incidence of DSBs in the ejaculate. When data from both the low and high W-SDF groups were combined, a linear relationship was observed, with DSBs increasing by 0.799 units for each unit increase in W-SDF. However, when the cohorts were analyzed separately, the relationships differed. In the low SDF group, DSBs increased linearly by 0.559 units for each unit increase in W-SDF. In the high SDF group, DSBs increased exponentially by 0.602 units per unit of W-SDF. Furthermore, the data dispersion between the two variables was significantly different between the cohorts, with the high SDF group showing 0.8 times greater variability than the low SDF group.
Conclusions
While the presence of DSBs in sperm is correlated with the W-SDF present in raw semen samples, the biological mechanisms responsible for DSBs are expressed in different proportions and/or at different levels in ejaculates with higher levels of DNA damage.
{"title":"Strong correlation between double-strand DNA Breaks and total sperm DNA fragmentation in the human ejaculate","authors":"Jaime Gosálvez , Stephen D. Johnston , Ahinoa Prado , Carmen López-Fernández , Pablo Contreras , Javier Bartolomé-Nebreda , Mercedes González-Martínez , José Luis Fernández , Carlos García de la Vega , Alfredo Góngora","doi":"10.1016/j.arcmed.2024.103122","DOIUrl":"10.1016/j.arcmed.2024.103122","url":null,"abstract":"<div><h3>Background</h3><div>Double- and single-strand DNA breaks (DSBs and SSBs, respectively) in spermatozoa, which emerge from intrinsic and extrinsic degenerative processes, are likely related to the underlying male pathology.</div></div><div><h3>Aim</h3><div>To determine whether the incidence of DSBs in the human ejaculate is a consistent predictor of whole sperm DNA fragmentation (W-SDF = SSBs + DSBs).</div></div><div><h3>Methods</h3><div>A correlation between the proportion of spermatozoa that showed whole W-SDF and those displaying only DSBs in DNA. Two patient cohorts were established: W-SDF ≤30% (low SDF; <em>n</em> = 153) and W-SDF ≥30% (high SDF; <em>n</em> = 222).</div></div><div><h3>Results</h3><div>An increasing level of W-SDF is associated with an increased incidence of DSBs in the ejaculate. When data from both the low and high W-SDF groups were combined, a linear relationship was observed, with DSBs increasing by 0.799 units for each unit increase in W-SDF. However, when the cohorts were analyzed separately, the relationships differed. In the low SDF group, DSBs increased linearly by 0.559 units for each unit increase in W-SDF. In the high SDF group, DSBs increased exponentially by 0.602 units per unit of W-SDF. Furthermore, the data dispersion between the two variables was significantly different between the cohorts, with the high SDF group showing 0.8 times greater variability than the low SDF group.</div></div><div><h3>Conclusions</h3><div>While the presence of DSBs in sperm is correlated with the W-SDF present in raw semen samples, the biological mechanisms responsible for DSBs are expressed in different proportions and/or at different levels in ejaculates with higher levels of DNA damage.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"55 8","pages":"Article 103122"},"PeriodicalIF":4.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.1016/j.arcmed.2024.103111
Carlos A. Ibáñez , Elena Zambrano
{"title":"Response to: Comment on “Impaired Ischemia-Reperfusion Responses in the Hearts of Aged Male and Female Offspring of Obese Rats”","authors":"Carlos A. Ibáñez , Elena Zambrano","doi":"10.1016/j.arcmed.2024.103111","DOIUrl":"10.1016/j.arcmed.2024.103111","url":null,"abstract":"","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 2","pages":"Article 103111"},"PeriodicalIF":4.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.arcmed.2024.103106
Sara Gloria Aguilar-Navarro , Alberto José Mimenza-Alvarado , Sara Gabriela Yeverino-Castro , Sandra Milena Caicedo-Correa , Carlos Cano-Gutiérrez
Frailty has been conceptualized not only as a physical disease, but also as a multidomain entity that encompasses a multimorbid status, disability, cognitive impairment, psychosocial risk factors, and even geriatric syndromes. In addition to physical ailments and depending on the diagnostic model. Standardized neuropsychological tests can identify cognitive deficiencies along with mild cognitive impairment, a pre-dementia stage characterized by memory and/or other cognitive domain impairments with relatively preserved instrumental activities of daily living. Hence, the possibility of cognitive frailty (CF), a construct that refers to physical frailty in concurrence with non-dementia cognitive decline, is proposed. The estimated prevalence of CF ranges from 10.3 to 42.8%. It is likely that the pathway to overt cognitive impairment, which does not yet involve physical function, begins with the asymptomatic early accumulation of progressive brain damage. Thus, timely detection strategies that target the initial phases of CF are warranted. The pathophysiological components of CF include dysregulation of the hypothalamic-pituitary axis stress response, imbalance in energy metabolism, impaired cardiovascular function, mitochondrial deterioration, and vascular age-related arterial stiffness. Changes that contribute to this disease can also occur at the cellular level, including overexpression of the renin-angiotensin-aldosterone system, activation of proinflammatory pathways, endothelial dysfunction, reduced nitric oxide production, and increased oxidative stress. Non-pharmacological interventions, that range from dietary and nutritional counseling to psychosocial therapy, are currently the main approaches. Both cognitive and physical training programs are considered to be the best researched and most useful multidomain interventions. Clinicians recognize CF as a valid concept that warrants prevention and treatment strategies supported by current research.
{"title":"Cognitive Frailty and Aging: Clinical Characteristics, Pathophysiological Mechanisms, and Potential Prevention Strategies","authors":"Sara Gloria Aguilar-Navarro , Alberto José Mimenza-Alvarado , Sara Gabriela Yeverino-Castro , Sandra Milena Caicedo-Correa , Carlos Cano-Gutiérrez","doi":"10.1016/j.arcmed.2024.103106","DOIUrl":"10.1016/j.arcmed.2024.103106","url":null,"abstract":"<div><div>Frailty has been conceptualized not only as a physical disease, but also as a multidomain entity that encompasses a multimorbid status, disability, cognitive impairment, psychosocial risk factors, and even geriatric syndromes. In addition to physical ailments and depending on the diagnostic model. Standardized neuropsychological tests can identify cognitive deficiencies along with mild cognitive impairment, a pre-dementia stage characterized by memory and/or other cognitive domain impairments with relatively preserved instrumental activities of daily living. Hence, the possibility of cognitive frailty (CF), a construct that refers to physical frailty in concurrence with non-dementia cognitive decline, is proposed. The estimated prevalence of CF ranges from 10.3 to 42.8%. It is likely that the pathway to overt cognitive impairment, which does not yet involve physical function, begins with the asymptomatic early accumulation of progressive brain damage. Thus, timely detection strategies that target the initial phases of CF are warranted. The pathophysiological components of CF include dysregulation of the hypothalamic-pituitary axis stress response, imbalance in energy metabolism, impaired cardiovascular function, mitochondrial deterioration, and vascular age-related arterial stiffness. Changes that contribute to this disease can also occur at the cellular level, including overexpression of the renin-angiotensin-aldosterone system, activation of proinflammatory pathways, endothelial dysfunction, reduced nitric oxide production, and increased oxidative stress. Non-pharmacological interventions, that range from dietary and nutritional counseling to psychosocial therapy, are currently the main approaches. Both cognitive and physical training programs are considered to be the best researched and most useful multidomain interventions. Clinicians recognize CF as a valid concept that warrants prevention and treatment strategies supported by current research.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 1","pages":"Article 103106"},"PeriodicalIF":4.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Success of assisted reproductive techniques depends on multiple factors including maternal endocrine status, hormonal balance, and paternal sperm quality. A comprehensive pre-treatment evaluation allows better prediction of outcomes and avoidance of unnecessary procedures and expenses.
Methods
To examine the impact of female hormonal profiles and sperm DNA damage on the success of assisted reproduction, medical data were extracted from the clinical records of infertile couples including couples’ age and levels of maternal anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the DNA fragmentation index (DFI) in men. Any correlation between these parameters and clinical outcomes was investigated.
Results
DFI and FSH independently influenced the rate of high-quality embryos. A decrease in maternal age and PRL levels increased the rate of these embryos. On the other hand, an increase in maternal body mass index (BMI) or AMH levels was associated with a reduced chance of achieving high quality embryos. In addition, any reduction in PRL levels could be associated with a higher fertilization rate. FSH levels above the normal range contribute to a reduced rate of high-quality embryos. Overall, our findings demonstrate the complex interplay between different factors and their influence on fertilization success and emphasize the importance of optimizing these variables to achieve the best possible outcome.
Conclusion
Several factors can influence the outcome of infertility treatment. These factors include paternal DFI, maternal age, BMI, AMH, FSH, and PRL levels.
背景：辅助生殖技术的成功与否取决于多种因素，包括母体的内分泌状态、荷尔蒙平衡和父亲的精子质量。全面的治疗前评估可以更好地预测结果，避免不必要的程序和费用：为了研究女性荷尔蒙状况和精子 DNA 损伤对辅助生殖成功率的影响，我们从不孕夫妇的临床记录中提取了医疗数据，包括夫妇的年龄、母体抗穆勒氏管激素（AMH）、卵泡刺激素（FSH）、黄体生成素（LH）和催乳素（PRL）的水平，以及男性的 DNA 断裂指数（DFI）。研究还调查了这些参数与临床结果之间的相关性：结果：DFI 和 FSH 对优质胚胎率有独立影响。母体年龄和 PRL 水平的降低提高了优质胚胎率。另一方面，母体体重指数（BMI）或 AMH 水平的增加与获得优质胚胎的几率降低有关。此外，任何 PRL 水平的降低都可能与受精率的提高有关。FSH 水平超过正常范围会导致优质胚胎率降低。总之，我们的研究结果表明了不同因素之间复杂的相互作用及其对受精成功率的影响，并强调了优化这些变量以获得最佳结果的重要性：结论：有几个因素会影响不孕症治疗的结果。这些因素包括父亲的DFI、母亲的年龄、体重指数、AMH、FSH和PRL水平。
{"title":"Impact of maternal hormone profile and paternal sperm DNA fragmentation on clinical outcomes following assisted reproduction","authors":"Khashayar Aflatoonian , Fatemehsadat Amjadi , Nadia Sheibak , Maryam Moradi , Abbas Aflatoonian , Maryamsadat Tabatabaei , Katayon Berjis , Reza Aflatoonian , Zahra Zandieh","doi":"10.1016/j.arcmed.2024.103108","DOIUrl":"10.1016/j.arcmed.2024.103108","url":null,"abstract":"<div><h3>Background</h3><div>Success of assisted reproductive techniques depends on multiple factors including maternal endocrine status, hormonal balance, and paternal sperm quality. A comprehensive pre-treatment evaluation allows better prediction of outcomes and avoidance of unnecessary procedures and expenses.</div></div><div><h3>Methods</h3><div>To examine the impact of female hormonal profiles and sperm DNA damage on the success of assisted reproduction, medical data were extracted from the clinical records of infertile couples including couples’ age and levels of maternal anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the DNA fragmentation index (DFI) in men. Any correlation between these parameters and clinical outcomes was investigated.</div></div><div><h3>Results</h3><div>DFI and FSH independently influenced the rate of high-quality embryos. A decrease in maternal age and PRL levels increased the rate of these embryos. On the other hand, an increase in maternal body mass index (BMI) or AMH levels was associated with a reduced chance of achieving high quality embryos. In addition, any reduction in PRL levels could be associated with a higher fertilization rate. FSH levels above the normal range contribute to a reduced rate of high-quality embryos. Overall, our findings demonstrate the complex interplay between different factors and their influence on fertilization success and emphasize the importance of optimizing these variables to achieve the best possible outcome.</div></div><div><h3>Conclusion</h3><div>Several factors can influence the outcome of infertility treatment. These factors include paternal DFI, maternal age, BMI, AMH, FSH, and PRL levels.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"55 8","pages":"Article 103108"},"PeriodicalIF":4.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.arcmed.2024.103112
Han Do , Paula Diaz-Sylvester , Kathleen Groesch , Teresa Wilson , Kristen Delfino , J.Ricardo Loret de Mola , Andrea Braundmeier-Fleming
Problem
Endometriosis is associated with gastrointestinal (GI) and urogenital (UG) microbial dysbiosis in patients with endometriosis (P-EOSIS). Sexual partner exposure may contribute to microbial dysbiosis but has not been studied in P-EOSIS. We hypothesized that sexual partner number, hormonal and surgical therapy would affect GI/UG microbial dysbiosis in P-EOSIS.
Methods of Study
Urine, fecal and vaginal swabs from control (n = 15) and P-EOSIS (n = 33) were collected on the day of surgery (DOS) and ∼1–3 weeks post-surgical intervention (PSI).
Control and P-EOSIS were grouped based on hormonal therapy (HT) to determine the effect of HT on microbial profiles, Control (HT n = 8; no HT n = 7) and P-EOSIS (HT n = 18; no HT n = 15). Samples underwent DNA extraction and sequencing of the V4 region of 16S rRNA gene. Sequences were processed using QIIME2 and amplicon sequence variants (ASV) were analyzed for microbial differences. Pearson's and Spearman correlation analyses determined associations among microbial features and sexual partner exposure.
Results
P-EOSIS had microbial dysbiosis characterized by unique GI/UG bacteria and altered microbial richness and diversity. Hormonal and surgical intervention in P-EOSIS restored GI microbial diversity. Increased sexual partner exposure decreased GI/UG microbial diversity. P-EOSIS who had 10 or more sexual partners had greater microbial dysbiosis compared to 4–6 partners. Surgical intervention negatively correlated with sexual partner numbers and GI/UG microbial abundance.
Discussion
Increased sexual partner exposure may enhance microbial dysbiosis in P-EOSIS and diminish the effectiveness of HT and surgical interventions.
问题子宫内膜异位症患者（P-EOSIS）的胃肠道（GI）和泌尿生殖道（UG）微生物菌群失调与子宫内膜异位症有关。性伴侣接触可能会导致微生物菌群失调，但尚未对 P-EOSIS 进行研究。我们假设性伴侣数量、激素和手术治疗会影响 P-EOSIS 的消化道/子宫内膜微生物菌群失调。研究方法在手术当天（DOS）和手术后 1-3 周（PSI）收集对照组（n = 15）和 P-EOSIS 组（n = 33）的尿液、粪便和阴道拭子。对照组和P-EOSIS组根据激素疗法（HT）分组，以确定HT对微生物特征的影响，对照组（HT n = 8；无HT n = 7）和P-EOSIS组（HT n = 18；无HT n = 15）。样本进行了 DNA 提取和 16S rRNA 基因 V4 区域测序。使用 QIIME2 对序列进行处理，并分析扩增子序列变异（ASV）以确定微生物差异。Pearson和Spearman相关性分析确定了微生物特征与性伴侣暴露之间的关联。对P-EOSIS进行激素和手术干预可恢复消化道微生物多样性。性伴侣接触增加会降低消化道/胃肠道微生物多样性。与 4-6 个性伴侣相比，有 10 个或更多性伴侣的 P-EOSIS 微生物菌群失调程度更高。手术干预与性伴侣数量和 GI/UG 微生物丰富度呈负相关。讨论性伴侣暴露增加可能会加重 P-EOSIS 微生物菌群失调，降低 HT 和手术干预的效果。
{"title":"Influence of hormonal factors, number of sexual partners, surgical intervention on gastrointestinal and urogenital microbiota of patients endometriosis","authors":"Han Do , Paula Diaz-Sylvester , Kathleen Groesch , Teresa Wilson , Kristen Delfino , J.Ricardo Loret de Mola , Andrea Braundmeier-Fleming","doi":"10.1016/j.arcmed.2024.103112","DOIUrl":"10.1016/j.arcmed.2024.103112","url":null,"abstract":"<div><h3>Problem</h3><div>Endometriosis is associated with gastrointestinal (GI) and urogenital (UG) microbial dysbiosis in patients with endometriosis (P-EOSIS). Sexual partner exposure may contribute to microbial dysbiosis but has not been studied in P-EOSIS. We hypothesized that sexual partner number, hormonal and surgical therapy would affect GI/UG microbial dysbiosis in P-EOSIS.</div></div><div><h3>Methods of Study</h3><div>Urine, fecal and vaginal swabs from control (<em>n</em> = 15) and P-EOSIS (<em>n</em> = 33) were collected on the day of surgery (DOS) and ∼1–3 weeks post-surgical intervention (PSI).</div><div>Control and P-EOSIS were grouped based on hormonal therapy (HT) to determine the effect of HT on microbial profiles, Control (HT <em>n</em> = 8; no HT <em>n</em> = 7) and P-EOSIS (HT <em>n</em> = 18; no HT <em>n</em> = 15). Samples underwent DNA extraction and sequencing of the V4 region of 16S rRNA gene. Sequences were processed using QIIME2 and amplicon sequence variants (ASV) were analyzed for microbial differences. Pearson's and Spearman correlation analyses determined associations among microbial features and sexual partner exposure.</div></div><div><h3>Results</h3><div>P-EOSIS had microbial dysbiosis characterized by unique GI/UG bacteria and altered microbial richness and diversity. Hormonal and surgical intervention in P-EOSIS restored GI microbial diversity. Increased sexual partner exposure decreased GI/UG microbial diversity. P-EOSIS who had 10 or more sexual partners had greater microbial dysbiosis compared to 4–6 partners. Surgical intervention negatively correlated with sexual partner numbers and GI/UG microbial abundance.</div></div><div><h3>Discussion</h3><div>Increased sexual partner exposure may enhance microbial dysbiosis in P-EOSIS and diminish the effectiveness of HT and surgical interventions.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"55 8","pages":"Article 103112"},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1016/j.arcmed.2024.103114
Aritania S. Santos , Daniele Pereira Santos-Bezerra , Ludmila Rodrigues Pinto Ferreira , Silvia Y. Bando , Laís Isidoro Alves , Edecio Cunha-Neto , Maria Elizabeth Rossi da Silva
Background. Aims/hypothesis
The role of microRNAs (miRNAs) in the pathogenesis and progression of type 1 diabetes (T1D) has been described, but data remain scarce and conflicting.
Objectives
To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D.
Methods
We screened 10 serum miRNAs from 142 subjects divided into three groups: healthy individuals (control group; n = 52) and patients at different stages of T1D progression, from the initial immunological manifestation, presenting islet cell autoantibodies (AbP group; n = 39), to partial and severe beta cell damage in T1D (recent T1D group; n = 51).
Results
Three miRNAs (miR-200c-3p, miR-301a-3p, and miR-382–5p) were highly expressed in the AbP and/or recent T1D groups compared to the control group. Furthermore, in the AbP group, miR-301a-3p and miR-382–5p were positively correlated with insulin autoantibody levels and miR-382–5p was negatively correlated with C-peptide levels. In the recent T1D group, miR-200c-3p expression was positively correlated with IA-2A levels. Enrichment analysis of differentially expressed miRNAs showed their involvement in immune response, inflammatory pathways, proliferation/survival/apoptosis mechanisms, bacterial and viral infection, and insulin resistance.
Conclusion
Our data indicated that miR-200c-3p, miR-301a-3p, and miR-382–5p might be involved in T1D pathogenesis. Proliferative, metabolic, and immune responses were main pathways associated with serum miRNA target genes.
{"title":"Relevance of Circulating microRNA, and their Association with Islet Cell Autoantibodies in Type 1 Diabetes Pathogenesis","authors":"Aritania S. Santos , Daniele Pereira Santos-Bezerra , Ludmila Rodrigues Pinto Ferreira , Silvia Y. Bando , Laís Isidoro Alves , Edecio Cunha-Neto , Maria Elizabeth Rossi da Silva","doi":"10.1016/j.arcmed.2024.103114","DOIUrl":"10.1016/j.arcmed.2024.103114","url":null,"abstract":"<div><h3>Background. Aims/hypothesis</h3><div>The role of microRNAs (miRNAs) in the pathogenesis and progression of type 1 diabetes (T1D) has been described, but data remain scarce and conflicting.</div></div><div><h3>Objectives</h3><div>To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D.</div></div><div><h3>Methods</h3><div>We screened 10 serum miRNAs from 142 subjects divided into three groups: healthy individuals (control group; <em>n</em> = 52) and patients at different stages of T1D progression, from the initial immunological manifestation, presenting islet cell autoantibodies (AbP group; <em>n</em> = 39), to partial and severe beta cell damage in T1D (recent T1D group; <em>n</em> = 51).</div></div><div><h3>Results</h3><div>Three miRNAs (miR-200c-3p, miR-301a-3p, and miR-382–5p) were highly expressed in the AbP and/or recent T1D groups compared to the control group. Furthermore, in the AbP group, miR-301a-3p and miR-382–5p were positively correlated with insulin autoantibody levels and miR-382–5p was negatively correlated with C-peptide levels. In the recent T1D group, miR-200c-3p expression was positively correlated with IA-2A levels. Enrichment analysis of differentially expressed miRNAs showed their involvement in immune response, inflammatory pathways, proliferation/survival/apoptosis mechanisms, bacterial and viral infection, and insulin resistance.</div></div><div><h3>Conclusion</h3><div>Our data indicated that miR-200c-3p, miR-301a-3p, and miR-382–5p might be involved in T1D pathogenesis. Proliferative, metabolic, and immune responses were main pathways associated with serum miRNA target genes.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 2","pages":"Article 103114"},"PeriodicalIF":4.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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