Impact of preoperative antibiotics and other variables on integrated microbiome-host transcriptomic data generated from colorectal cancer resections.

BACKGROUND: Integrative multi-omic approaches have been increasingly applied to discovery and functional studies of complex human diseases. Short-term preoperative antibiotics have been adopted to reduce site infections in colorectal cancer (CRC) resections. We hypothesize that the antibiotics will impact analysis of multi-omic datasets generated from resection samples to investigate biological CRC risk factors. AIM: To assess the impact of preoperative antibiotics and other variables on integrated microbiome and human transcriptomic data generated from archived CRC resection samples. METHODS: Genomic DNA (gDNA) and RNA were extracted from prospectively collected 51 pairs of frozen sporadic CRC tumor and adjacent non-tumor mucosal samples from 50 CRC patients archived at a single medical center from 2010-2020. The 16S rRNA gene sequencing (V3V4 region, paired end, 300 bp) and confirmatory quantitative polymerase chain reaction (qPCR) assays were conducted on gDNA. RNA sequencing (IPE, 125 bp) was performed on parallel tumor and non-tumor RNA samples with RNA Integrity Numbers scores ≥ 6. RESULTS: PERMANOVA detected significant effects of tumor vs nontumor histology (P = 0.002) and antibiotics (P = 0.001) on microbial ß-diversity, but CRC tumor location (left vs right), diabetes mellitus vs not diabetic and Black/African Ancestry (AA) vs not Black/AA, did not reach significance. Linear mixed models detected significant tumor vs nontumor histology*antibiotics interaction terms for 14 genus level taxa. QPCR confirmed increased Fusobacterium abundance in tumor vs nontumor groups, and detected significantly reduced bacterial load in the (+)antibiotics group. Principal coordinate analysis of the transcriptomic data showed a clear separation between tumor and nontumor samples. Differentially expressed genes obtained from separate analyses of tumor and nontumor samples, are presented for the antibiotics, CRC location, diabetes and Black/AA race groups. CONCLUSION: Recent adoption of additional preoperative antibiotics as standard of care, has a measurable impact on -omics analysis of resected specimens. This study still confirmed increased Fusobacterium nucleatum in tumor.

Core Measures for Congestive Heart Failure in a Tertiary Care Setting in Pakistan.

PURPOSE:  Heart failure presents a huge burden for individual patients and the healthcare system as a whole. This study aims to assess the adherence to these core measures as identified by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO)/ American Heart Association (AHA) by physicians of Pakistan. MATERIALS AND METHODOLOGY:  We conducted a cross-sectional study in Shifa International Hospital, Islamabad, Pakistan from the period of April 2013 to April 2016. Patients with a primary diagnosis of heart failure were drawn from a coding section of hospital's record department. Data was evaluated to assess how strictly doctors were following core measures identified by JCAHO/AHA for the given diagnosis. Inclusion criteria for this study were patients ≥ 17 years of age and patients with a primary diagnosis of heart failure according to New York Heart Association (NYHA) classification. Patients with congenital anomalies and structural heart wall problems, like sarcoidosis, hemochromatosis, and amyloidosis, were excluded from the study. RESULTS:  Mean ejection fraction (EF) was found to be 27.23 ± 11.72 percent. Symptoms assessment of heart failure was done in 16/421 (3.8%) patients according to NYHA classification and in 405/421 (96.2%) patients according to outpatient-based heart failure assessment based on physician's experience other than NYHA classification. Left ventricle ejection fraction (LVEF) was assessed in 411/421 (97%) patients. Out of these, 336/411 (81.7%) patients had EF < 40%. Mean EF was found to be significantly higher in females as compared to males (p < 0.001). Three hundred and thirty-six out of 411 (81.7%) patients with EF < 40% needed angiotensin converting enzyme inhibitors (ACEi) and beta-blocker (BB) prescriptions. ACEi were prescribed only to 230/336 (68.7%) patients and 248/336 (73.8%) patients were given BB with documented contraindication to ACEi and BB in 7.36% and 17% patients, respectively. There was no significant association between gender and mean duration of hospitalization (p = 0.411). No significant association was found between EF ≤ 40% and mean duration of hospitalization (p = 0.426). CONCLUSION:  We found that symptom assessment of congestive heart failure (CHF) patients, according to NYHA guidelines, are strikingly low. Also, a significant percentage of patients who need ACEi and BB are not prescribed the required medications despite echocardiography showing low left ventricular function.

Constraining Dark Matter Interactions with Pseudoscalar and Scalar Mediators Using Collider Searches for Multijets plus Missing Transverse Energy.

The monojet search, looking for events involving missing transverse energy (E_{T}) plus one or two jets, is the most prominent collider dark matter search. We show that multijet searches, which look for E_{T} plus two or more jets, are significantly more sensitive than the monojet search for pseudoscalar- and scalar-mediated interactions. We demonstrate this in the context of a simplified model with a pseudoscalar interaction that explains the excess in GeV energy gamma rays observed by the Fermi Large Area Telescope. We show that multijet searches already constrain a pseudoscalar interpretation of the excess in much of the parameter space where the mass of the mediator M_{A} is more than twice the dark matter mass m_{DM}. With the forthcoming run of the Large Hadron Collider at higher energies, the remaining regions of the parameter space where M_{A}>2m_{DM} will be fully explored. Furthermore, we highlight the importance of complementing the monojet final state with multijet final states to maximize the sensitivity of the search for the production of dark matter at colliders.