To investigate the potential of false inclusion of a close genetic relative in paternity testing by using computer generated families.
10000 computer-simulated families over three generations were ...generated based on genotypes using 15 short tandem repeat loci. These data were used in assessing the probability of inclusion or exclusion of paternity when the father is actually a sibling, grandparent, uncle, half sibling, cousin, or a random male. Further, we considered a duo case where the mother's DNA type was not available and a trio case including the mother's profile.
The data showed that the duo scenario had the highest and lowest false inclusion rates when considering a sibling (19.03 ± 0.77%) and a cousin (0.51 ± 0.14%) as the father, respectively; and the rate when considering a random male was much lower (0.04 ± 0.04%). The situation altered slightly with a trio case where the highest rate (0.56 ± 0.15%) occurred when a paternal uncle was considered as the father, and the lowest rate (0.03 ± 0.03%) occurred when a cousin was considered as the father. We also report on the distribution of the numbers for non-conformity (non-matching loci) where the father is a close genetic relative.
The results highlight the risk of false inclusion in parentage testing. These data provide a valuable reference when incorporating either a mutation in the father's DNA type or if a close relative is included as being the father; particularly when there are varying numbers of non-matching loci.
fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each
fusion variant are still largely unknown and ...require further investigation. RNA is the preferable template for the
fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the
fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that
-altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in
fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all
fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with
alterations.
To use a virtually simulated population, generated from published allele frequencies based on 15 short tandem repeats (STR), to evaluate the efficacy of trio sibship testing and sibling assignment ...for forensic purposes.
Virtual populations were generated using 15 STR loci to create a large number of related and unrelated genotypes (10,000 trio combinations). Using these virtual populations, the probability of related and unrelated profiles can be compared to determine the chance of inclusions of being siblings if they are true siblings and the chance of inclusion if they are unrelated. Two specific relationships were tested - two reference siblings were compared to a third true sibling (3S trio, sibling trio) and two reference siblings were compared to an unrelated individual (2S1U trio, non-sibling trio).
When the likelihood ratio was greater than 1, 99.87% of siblings in the 3S trio population were considered as siblings (sensitivity); 99.88% of non-siblings in the 2S1U trio population were considered as non-siblings (specificity); 99.9% of both populations were identified correctly as siblings and non-siblings; and the accuracy of the test was 99.88%.
The high sensitivity and specificity figures when using two known siblings compared to a putative sibling are significantly greater than when using only one known relative. The data also support the use of increasing number of loci allowing for greater confidence in genetic identification. The system established in this study could be used as the model for evaluating and simulating the cases with multiple relatives.
Diffusion models for text-to-image (T2I) synthesis, such as Stable Diffusion (SD), have recently demonstrated exceptional capabilities for generating high-quality content. However, this progress has ...raised several concerns of potential misuse, particularly in creating copyrighted, prohibited, and restricted content, or NSFW (not safe for work) images. While efforts have been made to mitigate such problems, either by implementing a safety filter at the evaluation stage or by fine-tuning models to eliminate undesirable concepts or styles, the effectiveness of these safety measures in dealing with a wide range of prompts remains largely unexplored. In this work, we aim to investigate these safety mechanisms by proposing one novel concept retrieval algorithm for evaluation. We introduce Ring-A-Bell, a model-agnostic red-teaming tool for T2I diffusion models, where the whole evaluation can be prepared in advance without prior knowledge of the target model. Specifically, Ring-A-Bell first performs concept extraction to obtain holistic representations for sensitive and inappropriate concepts. Subsequently, by leveraging the extracted concept, Ring-A-Bell automatically identifies problematic prompts for diffusion models with the corresponding generation of inappropriate content, allowing the user to assess the reliability of deployed safety mechanisms. Finally, we empirically validate our method by testing online services such as Midjourney and various methods of concept removal. Our results show that Ring-A-Bell, by manipulating safe prompting benchmarks, can transform prompts that were originally regarded as safe to evade existing safety mechanisms, thus revealing the defects of the so-called safety mechanisms which could practically lead to the generation of harmful contents. Our codes are available at https://github.com/chiayi-hsu/Ring-A-Bell.
Highlights • A sensitive and high throughput TaqMan based ALK qPCR assay was established. • High concordance between qPCR, FISH and IHC based ALK tests. • The qPCR assay can efficiently discriminate ...ALK rearrangement from overexpression. • The qPCR assay helps clarify the discrepancies between ALK FISH and IHC results.
Human Aurora kinases have three gene family members: Aurora-A, Aurora-B, and Aurora-C. It is not yet established what the specificity of these kinases are and what signals relayed by their reactions. ...Therefore, we employed small pool expression screening to search for downstream substrates of Aurora-A. Interestingly, all of the identified Aurora-A substrates were resistant to serve as substrates for Aurora-B or Aurora-C, suggesting that these Aurora family members may have distinct substrate specificity for propagation of diverse signaling pathways, even though they share a conserved catalytic kinase domain. Of the candidate substrates, Aurora-A could increase the functional activity of RalA. Mutational analysis revealed that RalA-Ser194 was the phosphorylation site for Aurora-A. Ectopic expression of V23RalA-WT could enhance collagen I-induced cell migration and anchorage-independent growth in Madin-Darby canine kidney (MDCK) Aurora-A stable cell lines. In contrast, overexpression of V23RalA-S194A in MDCK Aurora-A-stable cell lines abolished the intrinsic migration and transformation abilities of Aurora-A. To our knowledge, this is the first systematic search for the downstream substrates of Aurora-A kinase. Moreover, these results support the notion that Aurora-A may act in concert with V23RalA through protein phosphorylation on Ser194 to promote collagen I-induced cell motility and anchorage-independent growth in MDCK epithelial cells.
The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used.
...This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC.
This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed.
Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0-1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment.
The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD.
To evaluate the ICU mortality rate of mechanically ventilated hematopoietic stem cell transplantation (HSCT) recipients and to identify the factors that were associated with ICU mortality. The impact ...of surgical lung biopsy (SLB) in patients with unexplained pulmonary infiltrates was also evaluated.
Forty-one mechanically ventilated HSCT recipients admitted to the ICU during the study period were enrolled. The medical records were reviewed and data at ICU admission were analyzed. Data were compared between ICU survivors and nonsurvivors. The pathologic findings of SLB and the resulting impact on treatment were analyzed.
Eight patients (19.5%) survived the ICU stay, and seven (17%) lived to hospital discharge. The most common etiologies of ICU mortality included bacterial pneumonia, cytomegalovirus pneumonia, diffuse alveolar hemorrhage, sepsis, and aspergillosis. The factors associated with higher mortality were older age when performing HSCT, older age at ICU admission, higher acute physiology and chronic health evaluation (APACHE) II score, shock, higher respiratory rate, and higher heart rate at the time of ICU admission. Ten patients underwent SLB which resulted in treatment changes in five of them. Three patients had complications of SLB and one patient died of complications.
The ICU mortality rate of mechanically ventilated HSCT recipients was high. Factors associated with ICU mortality were older age, high APACHE II score, presence of shock, and higher respiratory or heart rate at the time of ICU admission. SLB might provide specific diagnosis in HSCT recipients with unexplained pulmonary infiltrates and aid modification of treatment.
Patients with diffuse pulmonary infiltrates (DPI), especially those who present with respiratory distress (RD), may benefit from early open lung biopsy (OLB) to guide management. Benefits of urgent ...OLB would be expected by saving the time to reach accurate specific diagnoses. The objectives of this study were (1) to evaluate the impact of OLB between patients presenting with and without RD, (2) to focus on the impact of an urgent OLB as compared to an elective OLB, and (3) to compare the different yields of specific diagnoses in the middle lobe or lingula as compared to the other lobes. Thirty-four patients (17 patients presented with RD and 17 patients did not) with an average age of 43 years who presented with DPI were selected to undergo an OLB. An urgent OLB was performed in 11unselected patients. Twelve specimens from the middle lobe or lingula were compared to 25 specimens from the other lobes. The impact of the OLB results on decision making did not differ significantly between patients with and without RD. Patients with RD suffered a higher in-hospital mortality rate, OLB-related complications, and longer mechanical ventilation requirements than the patients without RD. The impact on decision making and complications between urgent OLB and elective OLB was comparable. The diagnostic yield from biopsy sites in the middle lobe or lingula resembled those specimens from the other lobes. The authors conclude that OLB may play a role in decision making for patients with DPI. However, OLB makes no difference in decision making between patients with and without RD. Patients with RD undergoing OLB procedures may suffer a poorer outcome. Urgent OLB may not benefit patients with DPI in decision making. The biopsy site does not appear to affect the accuracy of the diagnostic yield from an OLB procedure.
Recent evidence from several relatively small nested case‐control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood ...cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere‐length associated genetic variants in a large study of 5,457 never‐smoking female Asian lung cancer cases and 4,493 never‐smoking female Asian controls using data from a previously reported genome‐wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere‐length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34–1.69) for upper
vs
. lower quartile of the weighted GRS,
p
value = 4.54 × 10
−14
) even after removing rs2736100 (
p
value = 4.81 × 10
−3
), a SNP in the
TERT
locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere‐associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.
What's new?
The possibility for a relationship between telomere length and cancer is intriguing, but many questions remain, including whether short or long telomeres are involved. Here, a genetic risk score derived from seven telomere‐length associated genetic variants revealed a positive association between telomere length and lung cancer risk in Asian women who never smoked. The genetic proxy was unaffected by reverse‐causation bias or environmental exposures. The differences in telomere length captured by the variants could aid in the identification of biological mechanisms that underlie the association between longer telomere length and increased lung cancer risk.
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