Variable number tandem repeats (VNTRs) account for significant genetic variation in many organisms. In humans, VNTRs have been implicated in both Mendelian and complex disorders, but are largely ...ignored by genomic pipelines due to the complexity of genotyping and the computational expense. We describe adVNTR-NN, a method that uses shallow neural networks to genotype a VNTR in 18 seconds on 55X whole genome data, while maintaining high accuracy. We use adVNTR-NN to genotype 10,264 VNTRs in 652 GTEx individuals. Associating VNTR length with gene expression in 46 tissues, we identify 163 "eVNTRs". Of the 22 eVNTRs in blood where independent data is available, 21 (95%) are replicated in terms of significance and direction of association. 49% of the eVNTR loci show a strong and likely causal impact on the expression of genes and 80% have maximum effect size at least 0.3. The impacted genes are involved in diseases including Alzheimer's, obesity and familial cancers, highlighting the importance of VNTRs for understanding the genetic basis of complex diseases.
Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the ...unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery.
This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses.
This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer.
ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.
Plasmonic logic gates provide a promising platform to realize diffraction‐unlimited all‐optical logic circuits. However, previous plasmonic logic gates suffer from narrow bandwidth and high loss. ...Here, broadband plasmonic logic gates are proposed and demonstrated using a unique design based on curved silver gratings. These logic gates can maintain a high intensity contrast ratio (29 dB) under front optical illumination. And, the broadband feature is achieved due to the feature of zero optical path difference from different positions of the curved grating to the output port. All the seven fundamental logic gates are demonstrated. In addition, different types of logic gates can be realized using the same device configuration. The possibility of multifunctionality makes these logic gates easy for device fabrication and system integration.
Plasmonic logic gates provide a promising platform to realize diffraction‐unlimited all‐optical logic circuits. Here, broadband plasmonic logic gates are proposed and demonstrated using a unique design based on curved silver gratings. All the seven fundamental logic gates have been demonstrated using the same device configuration. The possibility of multi‐functionality makes these logic gates easy for device fabrication and system integration.
Aims
Changes in global precipitation regimes are caused by an increase in the frequency of extremely wet and dry years inter-annually and extreme rainfall intensity intra-annually. However, the ...interactive effects of these precipitation variabilities remain relatively unclear.
Methods
To better understand the responses of semi-arid ecosystems to precipitation changes, a manipulative field experiment was conducted with multilevel annual precipitation amounts and precipitation allocation, at a temporal scale, within desert shrubland in the Mu Us Desert in northern China.
Results
With fewer, yet larger, precipitation events, the annual net primary production (ANPP) was found to increase in dry years. The annual precipitation amount and precipitation intervals affected the community ANPP. However, precipitation intervals only affected the ANPP in the context of low precipitation amounts. Extending the intervals between precipitation events significantly increased the ANPP of shrubs and weeds however decreased that of grasses. The nursery effect of shrubs on the herbs and competition between the grass and weeds can interfere with the response of the community ANPP to precipitation.
Conclusions
With a global shift toward precipitation regimes dominated by lower frequency and higher intensity, an increase in productivity in this desert shrubland ecosystem is expected, with shrubs largely dominating the community composition. This study advances the current understanding of how community productivity is shaped by the interaction between inter-annual precipitation amount and intra-annual precipitation distribution. Meanwhile, plant–plant interactions between different functional species also have essential roles in community productivity stabilization within the context of precipitation change.
This study investigates the phenomenon of light funneling through a subwavelength plasmonic slit, examining the corner effect resulting from the interaction between the incident wave and the ...round-trip wave within the slit. Our findings reveal an inconsistent relationship between transmittance and the size of the funneling area. Notably, constructive interference of the waves significantly enhances transmittance, leading to the unexpected emergence of a ring-like Poynting vector contour at the entrance corner of the slit. In cases where transmittance remains moderate and constructive interference continues to dominate, the light funneling area expands due to the presence of the ring. Furthermore, the extent of the ring expansion correlates with the enlargement of the funneling area, and the underlying mechanism can be elucidated through an examination of the dynamics of light fields and Poynting vectors.
Three new aglain derivatives (1–3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7–10), and three steroids (11–13) were isolated from Aglaia ...odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4–7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03–8.40 μM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.
Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with ...subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, 21 Asian, and 34 White patients. Mean age at diagnosis was significantly associated with subtype, with the youngest mean age (50 years) in MES and the oldest mean age (64 years) in LAR (
< 0.0005). Subtype was significantly associated with tumor grade (
= 0.0012) and positive lymph nodes (
= 0.021), with a marginally significant association of tumor stage (
= 0.076). In multivariate Cox-proportional hazards modeling, BLIS was associated with worst survival and LAR with best survival. Hispanics had a significantly higher proportion of BLIS (53%,
= 0.03), whereas Asians had a lower proportion of BLIS (19%,
= 0.05) and a higher proportion of LAR (38%,
= 0.06) compared to the average proportion across all groups. These differences in proportions of subtype across racial and ethnic groups may explain differences in their outcomes. Determining subtypes of TNBC facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors of TNBC prognosis for all races and ethnicities.
Associations have been reported of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both attention-deficit/hyperactivity disorder and the personality trait of novelty ...seeking. This polymorphism occurs in a 48-bp tandem repeat in the coding region of DRD4, with the most common allele containing four repeats (4R) and rarer variants containing 2-11. Here we show by DNA resequencing/haplotyping of 600 DRD4 alleles, representing a worldwide population sample, that the origin of 2R-6R alleles can be explained by simple one-step recombination/mutation events. In contrast, the 7R allele is not simply related to the other common alleles, differing by greater than six recombinations/mutations. Strong linkage disequilibrium was found between the 7R allele and surrounding DRD4 polymorphisms, suggesting that this allele is at least 5-10-fold "younger" than the common 4R allele. Based on an observed bias toward nonsynonymous amino acid changes, the unusual DNA sequence organization, and the strong linkage disequilibrium surrounding the DRD4 7R allele, we propose that this allele originated as a rare mutational event that nevertheless increased to high frequency in human populations by positive selection.
Male breast cancer (MBC) is an uncommon disease with a frequency of approximately one in 1000. Due to the rarity of MBC, it is understudied and its etiology is poorly understood. Our objectives are ...to determine the frequency of pathogenic mutations in
BRCA2
and
PALB2
in MBC cases and to investigate the correlations between mutation status and cancer phenotypes. Single strand conformation polymorphism analysis, direct sequencing, and multiplex ligation-dependent probe amplification were employed to screen for mutations in the BRCA2 gene, followed by direct sequencing of the PALB2 gene in
BRCA2
-negative MBC cases. Pathogenic
BRCA2
mutations were identified in 18 of the 115 MBC cases, including four of the ten cases (40%) from breast cancer families and 14 of the 105 cases (13%) unselected for family history of breast cancer. The difference in
BRCA2
-mutation frequencies between cases with and without family history of breast cancer was not statistically significant (
P
= 0.145), suggesting that family history is not a strong predictor of carrying a mutation in males. We observed a highly significant association of carrying a pathogenic
BRCA2
mutation with high tumor grade (
P
< 0.001) and a weak association with positive lymph nodes (
P
< 0.02). Of the 97
BRCA2
-negative MBC cases, we identified one
PALB2
mutation with confirmed pathogenicity and one mutation predicted to be pathogenic, a prevalence of pathogenic
PALB2
-mutation of 1–2%. Based on our results and previous studies, genetic testing for
BRCA2
should be recommended for any diagnosed MBC case, regardless of family history of breast cancer.
As master regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and indicates poor survival outcome. However, the role ...of HOXC10 in lung adenocarcinoma still unclear.
HOXC10 expression was evaluated in 63 primary lung adenocarcinoma tissues from our local hospital, and further systematically confirmed in lung cancer tissues from six GEO datasets (GSE19188, GSE31210, GSE10072, GSE7670, GSE32863, GSE30219), and Kaplan-Meier plotter database. The role of HOXC10 in lung cancer metastasis was further validated by cellular and molecular studies.
The expression of HOXC10 was significantly increased in human lung adenocarcinoma samples from Wuhu No.2 People's Hospital, about 4.219 times compared with normal tissues, and significantly correlated with TNM stage, lymph node, and distal metastasis. Upregulation of HOXC10 indicated a poor overall/relapse free survival of lung cancer patients from Wuhu No.2 People's Hospital, GEO datasets, and Kaplan-Meier plotter database, especially in patients with lung adenocarcinoma. Knockdown or ectopic expression assays confirmed that HOXC10 enhanced the phosphorylation of PI3K, regulated the expression of epithelial-to-mesenchymal transition (EMT) markers: MMP2/9, VCAM-1, vimentin and E-cadherin. Cellular study further confirmed that HOXC10 was required for migration, invasion and adhesion of lung cancer cells.
These findings suggest that HOXC10 plays a pivotal role in the metastasis of human lung cancer and highlight its usefulness as a potential prognostic marker or therapeutic target in human lung adenocarcinoma.
PDF
