Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse.

Mouse models have been used extensively to study human coronary artery disease (CAD) or atherosclerosis and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of atherosclerosis has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand atherosclerosis pathogenesis between species by leveraging multiomics data. Specifically, we compared genetically driven and thus CAD-causal gene networks and pathways, by using human GWAS of CAD from the CARDIoGRAMplusC4D consortium and mouse GWAS of atherosclerosis from the Hybrid Mouse Diversity Panel (HMDP) followed by integration with functional multiomics human (STARNET and GTEx) and mouse (HMDP) databases. We found that mouse and human shared >75% of CAD causal pathways. Based on network topology, we then predicted key regulatory genes for both the shared pathways and species-specific pathways, which were further validated through the use of single cell data and the latest CAD GWAS. In sum, our results should serve as a much-needed guidance for which human CAD-causal pathways can or cannot be further evaluated for novel CAD therapies using mouse models.

Iatrogenic macular hole due to Nd:YAG-SLT laser: Case report and management: Nd:YAG-SLT laser iatrogenic macular hole.

PURPOSE: To report a case of a patient who suffered a full thickness macular hole (FTMH) due to the accidental utilization of the selective laser trabeculoplasty (SLT) mode of a dual mode laser. METHOD: Case report. RESULTS: A 69-year-old woman experienced vision loss in her left eye immediately after undergoing attempted Neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy using a Nd:YAG-SLT laser system. Post-injury visual acuity was 20/25 and 20/800 in the right and left eyes, respectively. Ophthalmic exam and multimodal imaging revealed multiple macular hemorrhages and an irregular FTMH. The patient required multiple surgeries including an autologous retinal transplant to achieve hole closure. CONCLUSIONS: Macular hole formation is a devastating consequence of inadvertent use of the SLT mode when performing a Nd:YAG laser capsulotomy with a Nd:YAG-SLT laser system. We emphasize the importance of ensuring the correct mode is selected for treatment to minimize the risk of retinal damage and permanent vision loss.

Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse.

Mouse models have been used extensively to study human coronary artery disease (CAD) or atherosclerosis and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of atherosclerosis has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand atherosclerosis pathogenesis between species by leveraging multiomics data. Specifically, we compared genetically driven and thus CAD-causal gene networks and pathways, by using human GWAS of CAD from the CARDIoGRAMplusC4D consortium and mouse GWAS of atherosclerosis from the Hybrid Mouse Diversity Panel (HMDP) followed by integration with functional multiomics human (STARNET and GTEx) and mouse (HMDP) databases. We found that mouse and human shared >75% of CAD causal pathways. Based on network topology, we then predicted key regulatory genes for both the shared pathways and species-specific pathways, which were further validated through the use of single cell data and the latest CAD GWAS. In sum, our results should serve as a much-needed guidance for which human CAD-causal pathways can or cannot be further evaluated for novel CAD therapies using mouse models.

The symptomatic breast services in a university hospital: pandemic peak compared to the pre-pandemic year and future implications.

BACKGROUND: COVID-19 infection led to a substantial overhaul of the symptomatic breast services within the UK. AIM: The purpose of this study was to evaluate the pattern of primary care referrals to the symptomatic one-stop clinic during the pandemic. This study also provides a snapshot of the workings of symptomatic breast services and the scope for improvements. METHODS: The data points were collected for 1 month during the peak of the pandemic (April 2020) and compared to corresponding data points for the same month in the previous year (April 2019). This was compared to the monthly data from Wales Cancer Network (WCN) data source. A hundred patients from each month over 2 years were evaluated to get a snapshot into the working of the breast clinic. RESULTS: A total of 516 patients were referred from primary care or General Practitioners (GPs), and were seen in the Hospital 'one-stop breast clinic' in April 2019. This number dropped to 330 patients during the peak of the pandemic in April 2020. Ninety percent of referrals from the GP were urgent suspected cancers or urgent referrals. This trend of referrals did not change over 2 years. There was a 5% and 7% cancer diagnosis rate in 2020 and 2019, respectively. CONCLUSIONS: Most patients were referred from GP as 'urgent' or 'urgent suspected cancer'. The cancer diagnosis rate reduced from 7 to 5% during the pandemic peak but the number of 'worried well' patients did not reduce. The total number of referrals reduced, which is predictive of increased demand in the future. The authors have suggested ways to meet this demand.

Perception of Parents of Thalassemic Child to Thalassemia in Pakistan.

Background Thalassemia is an inherited blood disorder characterized by reduced hemoglobin synthesis. Aim of our study is to assess the parental knowledge of thalassemia patients and their awareness regarding treatment and preventive measures against thalassemia. Methods It is an observational study done at Ali Zaib Foundation Thalassemia Center in Sahiwal, Pakistan, in May 2019. One hundred parents were enrolled in this study and a subjective questionnaire was used to collect data through direct structured survey method over a period of 30 days. Results There were parents of 62 (62%) male patients and 38 (38%) female patients, with a median age of 8.5 ± 6.2 years. Forty-three (43%) parents were illiterate while eight (8%) parents were highly educated. Sixty-six (66%) patients were born to parents with consanguineous marriages. Eighty-two (82%) parents were aware of thalassemia, 72 (72%) were aware of the risk of thalassemia due to cousin marriages, 76 (76%) parents were aware of the importance of prenatal diagnosis (PND), while 88 (88%) believed that a PND was beneficial. Fifty-two (52%) parents knew about thalassemia treatment, 80 (80%) were aware of the importance of blood screening, and 14 (14%) patients were receiving iron chelation therapy. Seventy-eight (78%) parents were aware of thalassemia prevention. All parents believed that the public requires awareness of the importance of premarital screening and PND. Conclusion Parental awareness regarding ß-thalassemia, its treatment and prevention is fair but far from ideal. Premarital screening, provision of accurate information to the public by professionals, and adequate screening and PND of at-risk families can significantly reduce the rates of thalassemias.

Gene networks and pathways for plasma lipid traits via multitissue multiomics systems analysis.

Genome-wide association studies (GWASs) have implicated ∼380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance, and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely, total cholesterol, high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides, from GWASs were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in "interferon signaling," "autoimmune/immune activation," "visual transduction," and "protein catabolism" were significantly associated with all lipid traits. In addition, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL; glutathione metabolism for HDL; valine, leucine, and isoleucine biosynthesis for total cholesterol; and insulin signaling and complement pathways for triglyceride. Finally, by using gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g., APOH, APOA4, and ABCA1) and novel (e.g., F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (coagulation factor II, thrombin) in 3T3-L1 and C3H10T1/2 adipocytes altered gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36; reduced intracellular adipocyte lipid content; and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

Rare Association of Pneumomediastinum With Bilateral Pneumothorax.

Pneumomediastinum with bilateral pneumothorax is a clinical entity caused by infections, malignancy, or trauma, as in our case. Some patients present with pneumomediastinum secondary to trauma have esophageal, laryngeal, or tracheal injuries. A 16-year-old boy presented in the emergency department with complaints of shortness of breath and bruise on the chest after a history of the road traffic accident. Bilateral chest tube thoracotomy was done. Pneumomediastinum was suspected on X-ray chest and confirmed on computed tomography of the chest, which showed bilateral pneumothorax with pneumomediastinum. The patient was conservatively managed and discharged after 10 days.

Network modeling of single-cell omics data: challenges, opportunities, and progresses.

Single-cell multi-omics technologies are rapidly evolving, prompting both methodological advances and biological discoveries at an unprecedented speed. Gene regulatory network modeling has been used as a powerful approach to elucidate the complex molecular interactions underlying biological processes and systems, yet its application in single-cell omics data modeling has been met with unique challenges and opportunities. In this review, we discuss these challenges and opportunities, and offer an overview of the recent development of network modeling approaches designed to capture dynamic networks, within-cell networks, and cell-cell interaction or communication networks. Finally, we outline the remaining gaps in single-cell gene network modeling and the outlooks of the field moving forward.