Inclusion Ideals Associated to Uniformly Increasing Hypergraphs

In this paper,we introduce the monomial ideals I(H) associated to a special class of non uniform hypergraphs H(X; E; d) namely uniformly increasing hypergraphs. These ideals are named as inclusion ideals. In this paper, we discuss some algebraic properties of these inclusion ideals. In particular, we give an upper bound of the Castlenouvo-Mumford regularity of the special dual ideal I^[*](H) of the inclusion ideal.Comment: 6 pages, 1 figur

Dean flow-coupled inertial focusing in curved channels

Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force field to manipulate particles. In inertial microfluidics, dominant inertial forces cause particles to move across streamlines and occupy equilibrium positions along the faces of walls in flows through straight micro channels. In this study, we systematically analyzed the addition of secondary Dean forces by introducing curvature and show how randomly distributed particles entering a simple u-shaped curved channel are focused to a fixed lateral position exiting the curvature. We found the lateral particle focusing position to be fixed and largely independent of radius of curvature and whether particles entering the curvature are pre-focused (at equilibrium) or randomly distributed. Unlike focusing in straight channels, where focusing typically is limited to channel cross-sections in the range of particle size to create single focusing point, we report here particle focusing in a large cross-section area (channel aspect ratio 1: 10). Furthermore, we describe a simple u-shaped curved channel, with single inlet and four outlets, for filtration applications. We demonstrate continuous focusing and filtration of 10 mu m particles (with > 90% filtration efficiency) from a suspension mixture at throughputs several orders of magnitude higher than flow through straight channels (volume flow rate of 4.25ml/min). Finally, as an example of high throughput cell processing application, white blood cells were continuously processed with a filtration efficiency of 78% with maintained high viability. We expect the study will aid in the fundamental understanding of flow through curved channels and open the door for the development of a whole set of bio-analytical applications

Cancer Patterns in Quetta (1998-1999)

Introduction: Quetta, the capital of Baluchistan, is located at latitude 30,25; longitude 67.00. It has a population of 759,245; 425,474 males (56%) and 333,771 females (44%); Census 1998. The majority of residents are Persian or Baluchi speaking Baluchs. Methodology: The cancer cases from Quetta reported to the Karachi Cancer Registry were reviewed. The data included cases from the Aga Khan University Hospital (AKUH), Pathology Department (Quetta collection point) and health care facilities in Karachi. The residents of Baluchistan were ascertained and cancer cases residents of Quetta identified with the help of recorded addresses and retraceable telephone numbers. Results: During a 2-year period, 1st January 1998 to 31st December 1999 the Karachi Cancer Registry received 1077 cancer notifications from Quetta. Approximately half the cases were registered from the AKUH Quetta collection point. Others were the referral patterns in Karachi. The age-standardized incidence rate (ASR) of cancer, all sites (1998-99) was 137.0 for males and 92.8/100,000 for females. The commonest cancer in the males and females was cancer of the esophagus (lCD­10 categories C15; males- ASR 25.5, 17.2 %; females- ASR 23.4, 23.1%). One of the highest in the world, for both genders. Incidence of cancer breast in the females (lCD-10 categories C50; ASR 11.8, 13.3%) was low, Conclusion: The cancer data from Quetta is quite distinct from the cancer pattern of Karachi. It represents only a part of the cancer burden of Quetta; nonetheless it gives a glimpse into the cancer profile of Baluchistan. The high incidence of esophageal cancer indicates an extension of the geographical limits of the esophageal cancer belt

Cancer Esophagus Karachi 1995-2002:Epidemiology, Risk Factors and Trends

Objective: To study the trends of cancer esophagus in Karachi South during 1995-2002 and identify risk factors. Methods: Incident esophageal cancer cases recorded at the Karachi Cancer Registry for Karachi South, during 1st January 1995 to 31st December 2003 were reviewed. For maximum completion of data, incident cases registered from 1st January 1995 to 31st December 2002 were included for final analyses. Results: The Age Standardized Incidence Rates (ASIRs) of cancer esophagus in Karachi South for males were 6.5/100,000 (1995-1997) and 6.4/100,000 (1998-2002). In females the observed rates were 7.0/100,000 (1995-1997) and 8.6/100,000 (1998-2002). Conclusion: In the moderately high incidence, cancer esophagus zone of Karachi, the ASIRs in males remained stable during the last decade, but in females, an upward trend was observed suggesting a progressively higher exposure to risk factors in the latter. The potential risk factors in Karachi are use of all forms of tobacco, areca nut, infrequent consumption of raw fruits and vegetables and diet deficiencies. There is a necessity to actively control the proven risk factors and address the existence of other risk factors. The primary recommended strategy for the control of cancer esophagus would therefore be legislation against tobacco and areca nut in Pakistan and public health education. The risk factors of cancer esophagus identified in this article need to be further confirmed

Cancer Patterns in Karachi Division (1998-1999)

Objective: A minimal cancer incidence data for Karachi, the largest city of Pakistan, is being presented here, for the years 1998-1999. The city has a population of 9,802,134; males 5,261,712 (52.6%) and females 4,540,422 (47.4%); census 19981. Methodology: A predominantly mixed (passive and active) registration system has evolved in Karachi, the data sources being the hospitals within the Karachi Division. The reported/retrieved cancer data sets at the Karachi Cancer Registry are checked, coded, computerised in an analytical format and analysed. Results: The incident cancer cases registered in Karachi, during the 2-year period, 1st January 1998 to 31st December 1999 were analysed. The age-standardised incidence rate (ASR) of cancer, all sites was 132.4/100,000 for the males. Cancer of the lung 10.8%; ASR 17.3 was the most frequently recorded malignancy, followed by oral cavity 10.5%; ASR 13.2 and larynx 5.0%; ASR 7.4. The age-standardised incidence rate (ASR) of cancer, all sites was 133.0/100,000 in the females. Cancer of the breast, 32.0%; ASR 40.7 was the most frequently recorded malignancy, followed by oral cavity 8.1%; ASR 11.7 and gall bladder 3.6%; ASR 5.5. Conclusion: The present data has been calculated with an estimated 15-20% probable under ascertainment. Tobacco-associated cancers in Karachi were responsible for 38.3% of the tumours diagnosed amongst the males. Two principal cancers, breast and oral cavity were responsible for 40.1% of the cancers in females. A rare finding was the high incidence of gall bladder cancer in the females. At present it is difficult to determine whether this indicates a genuine high risk or a selection bias. A continuous process of cancer registration to study the trends in the incidence and an adequate cancer control program are possible and essential for Pakistan and can be based on the pattern being practiced in Karachi

Ambient air quality standards and policies in eastern mediterranean countries: a review

Objectives: National ambient air quality standards (NAAQS) are critical tools for controlling air pollution and protecting public health. We designed this study to 1) gather the NAAQS for six classical air pollutants: PM(2.5), PM(10), O(3), NO(2), SO(2), and CO in the Eastern Mediterranean Region (EMR) countries, 2) compare those with the updated World Health Organizations Air Quality Guidelines (WHO AQGs 2021), 3) estimate the potential health benefits of achieving annual PM(2.5) NAAQS and WHO AQGs per country, and 4) gather the information on air quality policies and action plans in the EMR countries. Methods: To gather information on the NAAQS, we searched several bibliographic databases, hand-searched the relevant papers and reports, and analysed unpublished data on NAAQS in the EMR countries reported from these countries to the WHO/Regional office of the Eastern Mediterranean/Climate Change, Health and Environment Unit (WHO/EMR/CHE). To estimate the potential health benefits of reaching the NAAQS and AQG levels for PM(2.5), we used the average of ambient PM(2.5) exposures in the 22 EMR countries in 2019 from the Global Burden of Disease (GBD) dataset and AirQ+ software. Results: Almost all of the EMR countries have national ambient air quality standards for the critical air pollutants except Djibouti, Somalia, and Yemen. However, the current standards for PM(2.5) are up to 10 times higher than the current health-based WHO AQGs. The standards for other considered pollutants exceed AQGs as well. We estimated that the reduction of annual mean PM(2.5) exposure level to the AQG level (5 mug m(-3)) would be associated with a decrease of all natural-cause mortality in adults (age 30+) by 16.9%-42.1% in various EMR countries. All countries would even benefit from the achievement of the Interim Target-2 (25 mug m(-3)) for annual mean PM(2.5): it would reduce all-cause mortality by 3%-37.5%. Less than half of the countries in the Region reported having policies relevant to air quality management, in particular addressing pollution related to sand and desert storms (SDS) such as enhancing the implementation of sustainable land management practices, taking measures to prevent and control the main factors of SDS, and developing early warning systems as tools to combat SDS. Few countries conduct studies on the health effects of air pollution or on a contribution of SDS to pollution levels. Information from air quality monitoring is available for 13 out of the 22 EMR countries. Conclusion: Improvement of air quality management, including international collaboration and prioritization of SDS, supported by an update (or establishment) of NAAQSs and enhanced air quality monitoring are essential elements for reduction of air pollution and its health effects in the EMR

A subset of HLA-I peptides are not genomically templated: evidence for cis- and trans-spliced peptide ligands

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy

Urine cell-free DNA multi-omics to detect MRD and predict survival in bladder cancer patients

Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. A random forest model incorporating these urine cfDNA-derived factors with leave-one-out cross-validation was 87% sensitive for predicting residual disease in reference to gold-standard surgical pathology. Both progression-free survival (HR = 3.00, p = 0.01) and overall survival (HR = 4.81, p = 0.009) were dramatically worse by Kaplan-Meier analysis for patients predicted by the model to have MRD, which was corroborated by Cox regression analysis. Additional survival analyses performed on muscle-invasive, neoadjuvant chemotherapy, and held-out validation subgroups corroborated these findings. In summary, we profiled urine samples from 74 patients with localized bladder cancer and used urine cfDNA multi-omics to detect MRD sensitively and predict survival accurately

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study

BACKGROUND: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS AND FINDINGS: We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p \u3c 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD-positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4-38.9; p = 0.02) compared to utDNA MRD-negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD-positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point. CONCLUSIONS: utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future