Tag: statistics

Anal Chim Acta. 2023 Oct 23;1279:341822. doi: 10.1016/j.aca.2023.341822. Epub 2023 Sep 15.

ABSTRACT

BACKGROUND: Accurate methods to assess DNA integrity are needed for many biomolecular methods. A multiplex digital PCR (dPCR) method designed for interspaced target sequences can be used to assess sequence integrity of large DNA strands. The ratio of single positive partitions versus double positive partitions is then used to calculate the sheared DNA strands. However, this simple calculation is only valid with low DNA concentration. We here describe a method based on probability calculations which enables DNA quality analysis in a large dynamic range of DNA concentrations.

RESULTS: Known DNA integrity percentages were mimicked using artificial double stranded DNA in low, intermediate and high DNA concentration scenarios, respectively 600, 12500 and 30000 copies of DNA per reaction. At low concentrations both methods were similar. However, at the intermediate concentration (12500 copies per reaction) the ratio based method started producing a larger error than the proposed probability calculation method with a mean relative error of 20.7 and 16.7 for the Bruner and the proposed method respectively. At the high concentration (30000 copies per reaction) only the proposed method provided accurate measurements with a mean relative error of 60.9 and 9.3 for the ratio based and the proposed method respectively. Furthermore, while both methods have a bias, it is constant for the proposed method, while it decreases with the integrity of the DNA for the ratio based method. The probability calculation equation was extended to 4 dimensions and a proof of concept experiment was performed, the data suggested that the 4 dimensional equation is valid.

SIGNIFICANCE AND NOVELTY: We here validate a method of estimating DNA integrity with dPCR using multiple probe combinations, allowing fast and flexible DNA integrity analysis. Additionally, we extend the method from 2 to 4 plex for more accurate DNA integrity measurements.

PMID:37827643 | DOI:10.1016/j.aca.2023.341822

Anal Chim Acta. 2023 Oct 23;1279:341781. doi: 10.1016/j.aca.2023.341781. Epub 2023 Sep 6.

ABSTRACT

A water-soluble negative sulfonic propyl ether β-CD polymer (SPE-β-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic substitution degree of each β-CD in SPE-β-CDP was statistically homogenized. The only one negative peak in electrophoretogram with indirect ultraviolate method proved its uniformity of electrophoretic behavior. There were 7.12 sulfonic substitution in β-CD unit and 164 μmole β-CD units in each gram of SPE-β-CDP, which corresponded a molecular weight of 7000 or more. Compared with monomer, SPE-β-CDP was lower effect on electrical current of CE, indicating a high concentration of SPE-β-CDP could be added. Its separation ability was verified by 12 chiral drugs. SPE-β-CDP also showed advantages of good water solubility, easy preparation and recovery to reduce the overall cost. However, five of 12 chiral drugs were hardly to be fully separated which was normal for any kind of chiral selector. A newly adjustable gravity mediated capillary electrophoresis (AGM-CE) technology was proposed and combined with SPE-β-CDP to enhance the chiral separation efficiencies of propranolol, salbutamol, omeprazole, ofloxacin and phenoxybenzamine which were markedly improved to 3.02, 1.17, 7.63, 4.14, and 2.81, respectively. Furthermore, its gradient mode (AGMg-CE) was also used to improve resolution through utilizing the zero mobility point, at which the effective apparent mobility of one racemate was zero. Resolutions of five chiral drugs were significantly improved, especially resolution of carvedilol changed from 0.43 to 1.0. These indicated SPE-β-CDP as chiral selector, AGM-CE and AGMg-CE as new CE technologies had a great potential in chiral separation.

PMID:37827633 | DOI:10.1016/j.aca.2023.341781

Anal Chim Acta. 2023 Oct 23;1279:341809. doi: 10.1016/j.aca.2023.341809. Epub 2023 Sep 8.

ABSTRACT

Intracellular metabolic profiling reveals real-time metabolic information useful for the study of underlying mechanisms of cells in particular conditions such as drug resistance. However, mass spectrometry (MS), one of the leading metabolomics technologies, usually requires a large number of cells and complex pretreatments. Surface enhanced Raman scattering (SERS) has an ultrahigh detection sensitivity and specificity, favorable for metabolomics analysis. However, some targeted SERS methods focus on very limited metabolite without global bioprofiling, and some label-free approaches try to fingerprint the metabolic response based on whole SERS spectral classification, but comprehensive interpretation of biological mechanisms was lacking. (95) RESULTS: We proposed a label-free SERS technique for intracellular metabolic profiling in complex cellular lysates within 3 min. We first compared three kinds of cellular lysis methods and sonication lysis shows the highest extraction efficiency of metabolites. To obtain comprehensive metabolic information, we collected a spectral set for each sample and further qualified them by the Pearson correlation coefficient (PCC) to calculate how many spectra should be acquired at least to gain the adequate information from a statistical and global view. In addition, according to our measurements with 10 pure metabolites, we can understand the spectra acquired from complex cellular lysates of different cell lines more precisely. Finally, we further disclosed the variations of 22 SERS bands in enzalutamide-resistant prostate cancer cells and some are associated with the androgen receptor signaling activity and the methionine salvage pathway in the drug resistance process, which shows the same metabolic trends as MS. (149) SIGNIFICANCE: Our technique has the capability to capture the intracellular metabolic fingerprinting with the optimized lysis approach and spectral set collection, showing high potential in rapid, sensitive and global metabolic profiling in complex biosamples and clinical liquid biopsy. This gives a new perspective to the study of SERS in insightful understanding of relevant biological mechanisms. (54).

PMID:37827617 | DOI:10.1016/j.aca.2023.341809

J Card Fail. 2023 Oct;29(10):1343-1344. doi: 10.1016/j.cardfail.2023.10.002.

NO ABSTRACT

PMID:37827599 | DOI:10.1016/j.cardfail.2023.10.002

Clin Radiol. 2023 Nov;78(11):832-838. doi: 10.1016/j.crad.2023.05.001. Epub 2023 Aug 14.

ABSTRACT

AIM: To investigate the reliability of post-mortem computed tomography (PMCT) in a case series of homicides involving blunt-force, sharp-force, and ballistic trauma.

MATERIALS AND METHODS: The study investigates 16 homicide cases that underwent PMCT before autopsy. Two radiologists assessed the PMCT examinations and the data were compared to the forensic pathology findings. Data were organised in broad categories: foreign bodies, external injuries, soft-tissue and organ injuries, fractures, air in cavities, fluid collections, random pathology, and wound track. Findings were organised by systems: head and neck, thorax, abdomen and pelvis, extremities. Cohen’s kappa statistics were used to assess observer agreement.

RESULTS: Six gunshot-related homicides (37.5%), seven sharp-force-related homicides (43.75%), two blunt-force-related deaths (12.5%), and one homicide due to mechanical asphyxia (1.25%) were analysed. A total of 64 fractures were reported by the pathologists, 67 by radiologist 1 and 68 by radiologist 2. Agreement was deemed substantial in all cases. Pathologists failed to report gas in cavities while radiologists underreported superficial injuries.

CONCLUSION: An overall observation was that less accurate findings were produced by the blinded radiologist in comparison to the non-blinded one. The extremeness of homicides obscured the interpretation of PMCT leading to the observed discrepancies. The combination of PMCT and autopsies is deemed optimal when investigating homicidal events.

PMID:37827593 | DOI:10.1016/j.crad.2023.05.001

Transfus Med Rev. 2023 Jul;37(3):150747. doi: 10.1016/j.tmrv.2023.150747. Epub 2023 Jun 16.

ABSTRACT

Secondary transmission of variant Creutzfeldt-Jakob disease (vCJD) can occur through blood transfusion or receipt of plasma-derived products. However, published reviews on this topic are outdated, focused on a single country or product type, or did not comprehensively review modeling studies on the risk of transfusion-transmission. We reviewed existing data on observed and modeled risks of transfusion-transmission of vCJD. To date, five patients are suspected to have acquired clinical vCJD or a vCJD infection after receiving a blood or plasma-derived product from a donor who later developed clinical vCJD. All of these cases received a nonleukodepleted blood-derived product in the United Kingdom between 1994 and 1999. Thus, all transfusion-associated cases occurred before the adoption of universal leukodepletion in 1999, which supports the preferential tropism of vCJD for leukocytes. In descriptive cohort studies, no cases of clinical vCJD were observed over ∼13 years of follow-up. In modeling studies, the risk of collecting a contaminated donation was generally <23 per million donations, that of infection was generally <10 per million transfusions or doses, and that of clinical vCJD was generally <2 per million transfusions or doses. These low risk estimates and the two-decade long absence of new cases of transfusion-associated vCJD suggest vCJD poses minimal risks to the safety of the blood supply. Furthermore, despite concerns of a second wave driven by individuals harboring a non-MM genotype at codon 129 of PRNP, there has been only 1 autopsy-confirmed case of clinical vCJD in an MV individual in 2016. The current trend to reassess or (in some countries) fully withdraw the blood donation criteria related to vCJD therefore seems justified, safe, and may significantly expand the donor base.

PMID:37827587 | DOI:10.1016/j.tmrv.2023.150747

Eur Respir J. 2023 Oct 12:2201454. doi: 10.1183/13993003.01454-2022. Online ahead of print.

NO ABSTRACT

PMID:37827573 | DOI:10.1183/13993003.01454-2022

Heart. 2023 Oct 12:heartjnl-2023-323059. doi: 10.1136/heartjnl-2023-323059. Online ahead of print.

ABSTRACT

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology.

METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated.

RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15.

CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy.

TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.

PMID:37827559 | DOI:10.1136/heartjnl-2023-323059

Obstet Gynecol. 2023 Oct 12. doi: 10.1097/AOG.0000000000005412. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantify pandemic-related changes in obstetric intervention and perinatal outcomes in the United States.

METHODS: We carried out a retrospective study of all live births and fetal deaths in the United States, 2015-2021, with data obtained from the natality, fetal death, and linked live birth-infant death files of the National Center for Health Statistics. Analyses were carried out among all singletons; singletons of patients with prepregnancy diabetes, prepregnancy hypertension, and hypertensive disorders of pregnancy; and twins. Outcomes of interest included preterm birth, preterm labor induction or preterm cesarean delivery, macrosomia, postterm birth, and perinatal death. Interrupted time series analyses were used to estimate changes in the prepandemic period (January 2015-February 2020), at pandemic onset (March 2020), and in the pandemic period (March 2020-December 2021).

RESULTS: The study population included 26,604,392 live births and 155,214 stillbirths. The prepandemic period was characterized by temporal increases in preterm birth and preterm labor induction or cesarean delivery rates and temporal reductions in macrosomia, postterm birth, and perinatal mortality. Pandemic onset was associated with absolute decreases in preterm birth (decrease of 0.322/100 live births, 95% CI 0.506-0.139) and preterm labor induction or cesarean delivery (decrease of 0.190/100 live births, 95% CI 0.334-0.047) and absolute increases in macrosomia (increase of 0.046/100 live births), postterm birth (increase of 0.015/100 live births), and perinatal death (increase of 0.501/1,000 total births, 95% CI 0.220-0.783). These changes were larger in subpopulations at high risk (eg, among singletons of patients with prepregnancy diabetes). Among singletons of patients with prepregnancy diabetes, pandemic onset was associated with a decrease in preterm birth (decrease of 1.634/100 live births) and preterm labor induction or cesarean delivery (decrease of 1.521/100 live births) and increases in macrosomia (increase of 0.328/100 live births) and perinatal death (increase of 9.840/1,000 total births, 95% CI 3.933-15.75). Most changes were reversed in the months after pandemic onset.

CONCLUSION: The onset of the coronavirus disease 2019 (COVID-19) pandemic was associated with a transient decrease in obstetric intervention (especially preterm labor induction or cesarean delivery) and a transient increase in perinatal mortality.

PMID:37826851 | DOI:10.1097/AOG.0000000000005412

J Glob Health. 2023 Oct 13;13:06043. doi: 10.7189/jogh.13.06043.

ABSTRACT

BACKGROUND: The reported number of cases and deaths from common infectious diseases can change during major public health crises. We explored whether the coronavirus disease 2019 (COVID-19) had an impact on tuberculosis (TB) incidence and mortality in China based on routinely reported TB data.

METHODS: We used TB data used from the monthly national notifiable infectious disease reports in China from January 2015 to January 2023. Based on an interrupted time series (ITS) design, we applied Poisson and negative binomial regression models to assess the changes of reported TB incidence and mortality before and during the COVID-19 pandemic.

RESULTS: We found a significant and immediate decrease in the levels of both reported TB incidence (relative risk (RR) = 0.887; 95% confidence interval (CI) = 0.810-0.973) and mortality (RR = 0.448; 95% CI = 0.351-0.572) at the start of COVID-19 outbreak. During the pandemic, the slope of reported incidence decreased significantly (RR = 0.994; 95% CI = 0.989-0.999), while the slope of reported mortality increased sharply (RR = 1.032; 95% CI = 1.022-1.041) owing to an abrupt rise in reported mortality after January 2022.

CONCLUSIONS: Both TB incidence and mortality decreased immediately at the start of the COVID-19 pandemic. Over a longer period, the COVID-19 pandemic had contributed to a sustained and more significant decrease in reported incidence, and a delayed but sharp increase in reported mortality.

PMID:37824176 | DOI:10.7189/jogh.13.06043