cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24492483
title: Systematic analysis of copy number variants of uncertain significance partially overlapping with the haploinsufficient or triplosensitive genes in clinical testing

description: <b>Background:</b> Copy number variants of uncertain significance (VUS) has brought much distress for patients and great counselling challenges for clinicians. Of these, a special type of VUS (HT-VUS), harbouring one or both breakpoints within the established haploinsufficient or triplosensitive genes, were considered to be more likely to cause clinical effects compared with other types of VUS. <b>Methods:</b> We retrospectively evaluated the properties and clinical significance of those HT-VUS samples in clinical testing for chromosome microarray analysis (CMA). <b>Results:</b> A total of 7150 samples were selected for HT-VUS screening, and 75 (1.05%) subjects with 75 HT-VUS were found. The majority of these HT-VUS were heterozygous duplications and chromosome X had the most HT-VUS. The prevalence of HT-VUS was 0.90% (28/3116) for prenatal low-risk samples, 1.18% (26/2196) for prenatal high-risk samples, 1.37% (10/728) for postnatal samples and 0.99% (11/1110) for early pregnancy loss samples. However, the incidence of HT-VUS was not statistically different between different groups. <b>Conclusions:</b> HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons (either the first or last exons) might be clinically neutral. Our study will be helpful for both interpretation and genetic counselling in the future. This study assessed the clinical impact and features of a special type of copy number variants of uncertain significance (HT-VUS) in samples from CMA retrospectively. Out of 7150 samples screened, 75 (1.05%) subjects had HT-VUS. Most HT-VUS were heterozygous duplications and chromosome X had the highest frequency of HT-VUS. HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons might be clinically neutral. This study would be helpful for future interpretation and genetic counselling.
DOI: 10.6084/m9.figshare.24492483.v1
title: Systematic analysis of copy number variants of uncertain significance partially overlapping with the haploinsufficient or triplosensitive genes in clinical testing

description: <b>Background:</b> Copy number variants of uncertain significance (VUS) has brought much distress for patients and great counselling challenges for clinicians. Of these, a special type of VUS (HT-VUS), harbouring one or both breakpoints within the established haploinsufficient or triplosensitive genes, were considered to be more likely to cause clinical effects compared with other types of VUS. <b>Methods:</b> We retrospectively evaluated the properties and clinical significance of those HT-VUS samples in clinical testing for chromosome microarray analysis (CMA). <b>Results:</b> A total of 7150 samples were selected for HT-VUS screening, and 75 (1.05%) subjects with 75 HT-VUS were found. The majority of these HT-VUS were heterozygous duplications and chromosome X had the most HT-VUS. The prevalence of HT-VUS was 0.90% (28/3116) for prenatal low-risk samples, 1.18% (26/2196) for prenatal high-risk samples, 1.37% (10/728) for postnatal samples and 0.99% (11/1110) for early pregnancy loss samples. However, the incidence of HT-VUS was not statistically different between different groups. <b>Conclusions:</b> HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons (either the first or last exons) might be clinically neutral. Our study will be helpful for both interpretation and genetic counselling in the future. This study assessed the clinical impact and features of a special type of copy number variants of uncertain significance (HT-VUS) in samples from CMA retrospectively. Out of 7150 samples screened, 75 (1.05%) subjects had HT-VUS. Most HT-VUS were heterozygous duplications and chromosome X had the highest frequency of HT-VUS. HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons might be clinically neutral. This study would be helpful for future interpretation and genetic counselling.
DOI: 10.6084/m9.figshare.23971772
title: Increased blood CD226<sup>-</sup> inflammatory monocytes with low antigen presenting potential correlate positively with severity of hemorrhagic fever with renal syndrome

description: Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. The proportion of CD226<sup>-</sup> iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (<i>p</i> &lt; 0.0001). In the acute phase, the proportion of CD226<sup>-</sup> iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226<sup>-</sup> iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226<sup>+</sup> iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226<sup>-</sup> macrophages, with decreased expression of I-A/I-E and CD80. CD226<sup>-</sup> iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.
DOI: 10.6084/m9.figshare.23971772.v1
title: Increased blood CD226<sup>-</sup> inflammatory monocytes with low antigen presenting potential correlate positively with severity of hemorrhagic fever with renal syndrome

description: Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. The proportion of CD226<sup>-</sup> iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (<i>p</i> &lt; 0.0001). In the acute phase, the proportion of CD226<sup>-</sup> iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226<sup>-</sup> iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226<sup>+</sup> iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226<sup>-</sup> macrophages, with decreased expression of I-A/I-E and CD80. CD226<sup>-</sup> iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.
DOI: 10.6084/m9.figshare.24299330
title: Diverse associations observed between pregnancy complications and RBC or plasma folates determined by an in-house developed LC-MS/MS method

description: As folates are essential for embryonic development and growth, it is necessary to accurately determine the levels of folates in plasma and red blood cells (RBCs) for clinical intervention. The aims of this study were to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of folates in plasma and RBCs and to examine the association between plasma and RBC folate concentrations and gestational diabetes mellitus (GDM), gestational hypertension (GH) and preeclampsia (PE). With the in-house developed LC-MS/MS, a retrospective cross-sectional study was conducted. The healthy pregnant women of first- (<i>n</i> = 147), second- (<i>n</i> = 84) and third-trimester (<i>n</i> = 141) or the women diagnosed with GDM (<i>n</i> = 84), GH (<i>n</i> = 58) or PE (<i>n</i> = 23), that were aged between 22 and 46 years old and registered at our institute, were subjected for measurement of folic acid (FA) and 5-methyltetrahydrofolate (5-MTHF), followed by appropriate statistical association analysis. The assay for simultaneous quantitation of FA and 5-MTHF in plasma and RBCs was linear, stable, with imprecision less than 15% and recoveries within ±10%. The lower limits of quantification for FA and 5-MTHF measurement in whole blood were 0.57 and 1.09 nmol/L, and in plasma were 0.5 and 1 nmol/L, respectively. In the association analysis, the patients with lower RBC folate level (&lt;906 nmol/L) presented higher risks of PE development (OR 4.861 [95% CI 1.411–16.505]) by logistic regression and restricted cubic spline (RCS) regression in a nonlinear fashion. In addition, higher level of plasma folates in pregnancy was significantly associated with GH risk but may be protective for the development of GDM. The in-house developed LC-MS/MS method for folates and metabolites in plasma or RBC showed satisfactory analytical performance for clinical application. Further, the levels of folates and metabolites were diversely associated with GDM, GH and PE development.
DOI: 10.6084/m9.figshare.24569933
title: Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel

description: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (<i>p</i> = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.
DOI: 10.6084/m9.figshare.24569933.v1
title: Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel

description: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (<i>p</i> = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.
DOI: 10.6084/m9.figshare.23794839
title: Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis

description: The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population. A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier’s ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations. The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: −0.98; 95% CI: −1.28, −0.69, p-value: &lt; 0.0001; I2: 100%), systolic (WMD: −3.73; 95% CI: −5.42, −2.04, p-value: &lt;0.0001; I2: 100%) and diastolic blood pressures (WMD: −0.66; 95% CI: −1.02, −0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: −3.17; 95% CI: −3.84, −2.49, p-value: &lt;0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: &lt;0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments. In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.
DOI: 10.6084/m9.figshare.23794839.v1
title: Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis

description: The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population. A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier’s ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations. The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: −0.98; 95% CI: −1.28, −0.69, p-value: &lt; 0.0001; I2: 100%), systolic (WMD: −3.73; 95% CI: −5.42, −2.04, p-value: &lt;0.0001; I2: 100%) and diastolic blood pressures (WMD: −0.66; 95% CI: −1.02, −0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: −3.17; 95% CI: −3.84, −2.49, p-value: &lt;0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: &lt;0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments. In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.
DOI: 10.6084/m9.figshare.24474502
title: Prognostic factors for pure ovarian immature teratoma and the role of adjuvant chemotherapy in stage I diseases

description: The prognostic factors for patients with pure ovarian immature teratoma (POIT) and the role of adjuvant chemotherapy in stage IA G2-G3 and IB-IC POIT remains controversial. We conducted a retrospective study of 155 POIT patients treated in our hospital between 2000 and 2022. The recurrence-free survival (RFS), disease-specific survival (DSS), and potential prognostic factors of POIT patients were evaluated. Subgroup analysis was conducted in stage I other than stage IA G1 POIT. The median age at diagnosis was 23.0 years (range: 4.0 − 39.0), and 126 (81.3%), 2 (1.3%), 26 (16.8%), and 1 (0.6%) patients had FIGO stage I, stage II, stage III, and stage IV disease, respectively. Twenty-three patients relapsed and five died of the diseases after a median follow-up of 7.6 years, with a 5-year RFS and DSS rate of 86.0% and 97.0%, respectively. Multivariate analysis showed that positive postoperative tumour markers (TM) were the risk factor for recurrence in the overall cohort (hazard ratio [HR] 4.058, 95% CI 1.175 − 14.019, <i>p</i> = 0.027) and subgroup (HR 10.237, 95% CI 2.175 − 48.179, <i>p</i> = 0.003), and FIGO stage II–IV was the only factor for DSS in overall cohort (HR 7.751, 95% CI 1.281 − 46.895, <i>p</i> = 0.026). In 110 patients subjected to subgroup analysis, 29 patients received surveillance without chemotherapy and 81 patients were administered adjuvant chemotherapy. Multivariate analysis revealed active surveillance significantly increased the recurrence rate (5-year RFS of 75.7% vs. 93.6%, HR 7.562, 95% CI 2.441 − 23.424, <i>p</i> &lt; 0.001) but not the death related to POIT (<i>p</i> = 0.338). Positive postoperative TM and FIGO stage II–IV were the prognostic factors for POIT. Active surveillance in stage I POIT of any grade may be practical for those with negative postoperative TM. Positive postoperative tumour markers and FIGO stage II–IV were the prognostic factors for pure ovarian immature teratoma. Active surveillance in stage I pure ovarian immature teratoma of any grade may be practical for those with negative postoperative tumor markers.