The University of Kansas Cancer Center is a National Cancer Institute-designated comprehensive cancer center. It is the only such designated cancer center in the state of Kansas. The cancer center’s mission, through its innovative approach to drug discovery, delivery, and development, is to transform cancer research and clinical care delivered in Kansas and western Missouri.KU Cancer Center operates as a matrix organization that includes: the University of Kansas Medical Center campuses in Kansas City, Wichita and Salina, the University of Kansas in Lawrence and its highly ranked School of Pharmacy (per NIH funding) and The University of Kansas Health System. The Stowers Institute for Medical Research and Children’s Mercy Kansas City are NCI consortium partners.KU Cancer Center places great emphasis on advancing discoveries in the laboratory to the patients’ bedside. The cancer center currently has five KU-invented anticancer agents in clinical trials. Two recent discoveries include Ciclopirox Prodrug for the treatment of bladder and other cancers, as well as a novel method to treat patients with acute Graft-versus-Host Disease.The KU Cancer Center has garnered an excellent reputation for its clinical trials work and contributed to significant national studies and participates in exclusive NCI clinical trial network groups, including the ETCTN and NCORP. At any given time, the cancer center has nearly 600 studies in various stages.KU Cancer Center researchers pay special attention to the unique needs of people living in its catchment area. Moreover, with the Children’s Mercy consortium partnership, KU Cancer Center has access to more than 95 percent of childhood cancer cases in the catchment area. The center’s outreach arm, the Masonic Cancer Alliance, leverages regional resources to promote and translate the latest evidence-based clinical and community health practices for patients close to their homes.Cancer Biology, which aims to enhance interdisciplinary collaboration among basic and clinical scientists and facilitate translational research involving the etiology, treatment and prevention of cancer.Cancer Prevention & Control, which seeks to identify new ways to prevent cancer and improve cancer outcomes, with a focus on high risk and underserved communities in KU Cancer Center’s catchment area.Drug Discovery, Delivery & Experimental Therapeutics, which aims to discover novel anticancer drugs active against novel drug targets and find new indications for currently marketed drugs. The Institute for Advancing Medical Innovations (IAMI), which includes pharmaceutical industry experts, expands the program’s capacity to support drug discovery efforts across the entire Cancer Center.KU Cancer Center has three research programs that focus on different aspects of cancer and leverage scientific depth and breadth provided by nationally recognized scientists:With world-class, transdisciplinary, expertise and technical capabilities in drug discovery and cellular immunotherapeutics, spearheaded by our national and international leaders in translational and clinical research, KUCC continues to develop paradigm-changing therapeutic advances through leveraging multidisciplinary discoveries that drive translational research results into clinical trials which enable a comprehensive approach to improve cancer outcomes and quality of life and lead to comprehensive efforts locally and nationally to reduce the burden of cancer, particularly for people living in our extensive catchment area.KUCC has a comprehensive clinical trial portfolio: including investigator-initiated trials (IIT) which emphasize KU-led novel scientific discovery/development, NCICTN national translational investigation trials, industry sponsored studies in multiple phases of development; as well as cooperative group, early concept proving phase I, II trials, many of which have the potential to lead to standard of care (SOC) changing phase III studies. Indeed, our collaboration with industry partners in new drug development and cellular therapeutic trials has led to the establishment of new clinical SOC and FDA approvals. In addition to our centers’ contributions into successful therapeutic clinical trials, we have trials employed to improve cancer prevention, and further the development and optimization of survivorship programs. Although KUCC clinical trials focus on patients' needs in the large KUCC catchment area, the results of our efforts have had far-reaching impacts nationally. Another high priority area of our research and clinical efforts at KUCC continues to be focused on defining disparities in access to cancer care and clinical trial enrollment for ethnic and racial, as well as socioeconomically disadvantaged populations in our catchment area. KUCC members have published extensively regarding these disparities and have multi-disciplinary efforts underway to positively impact these injustices. Since 2016 approximately 11–12% of KUCC new cancer patients have been enrolled to interventional clinical trials and, as a result, many of our patients have had the opportunity to contribute to advances in the field and potentially benefit from novel therapeutic strategies. It is our philosophy that clinical trials represent the best care for our patients, and our ultimate goal is that all patients who are referred to KUCC have available clinical trials for their consideration. Importantly, nearly 1/3 of our patients have participated in all cancer related studies including supportive interventional, supportive care, screening, service, diagnostic, and observational studies at KUCC. Approximately 120 clinical trials have opened, met enrollment goals, and subsequently closed each year (range 94–145) for the past 5 years with ~2,000 patients enrolled yearly . There are currently 327 open trials at KUCC including interventional trials composed of 36 phase I; 30 phase I/II; 79 phaseII; 12 phase II/III; 75 phase III: and 11 phase IV trials.Several examples of studies which represent KUCC cancer clinic trials include the following:An IIT of note involved a multi-PI Small Business Innovation Research grant supported by the NCI for the development of fosciclopirox for the treatment for high-risk non-muscle invasive bladder cancer. Bladder cancer is the fifth most common cancer in the United States, with over 83,000 new cases and over 17,000 deaths annually. In the KUCC catchment area, bladder cancer is the fourth most common cancer in men, and disproportionally impacts Black and Hispanic men. Discovered by KUCC scientists, fosciclopirox is a prodrug of ciclopirox, an FDA-approved topical antifungal agent with broad spectrum anticancer activity. Fosciclopirox is rapidly and completely converted to ciclopirox in the bloodstream where it subsequently undergoes renal elimination, selectively delivering ciclopirox to the entire urinary tract. KU investigators subsequently demonstrated in vitro and in vivo that ciclopirox was highly effective in killing human bladder cancer cells and established that intravenous administration of fosciclopirox at well tolerated doses in animals and humans results in urinary tract concentrations of ciclopirox which exceed those required to kill bladder cancer cells in vitro by > 50-fold. This KU-driven drug has been used in three phase 1 studies at KU and is also being researched in AML (Acute Myeloid Leukemia).Another IIT that grew from KUCC-led science and multi-disciplinary collaboration is a triple negative breast cancer (TNBC) trial. TNBC is associated with a worse prognosis compared to other breast cancer subtypes. Using data from the KU multi-site TNBC registry, established in collaboration with the Biospecimen Shared Resource (BSR) and SWOG phase III trial S9313, several homologous recombination deficiency and immune microenvironment related chemotherapy response biomarkers were identified. This work led to the design and conduct of the NCI-funded SWOG phase II trial S1416 and ongoing multi-site IIT of neoadjuvant platinum chemotherapy plus immunotherapy in TNBC. Completed biomarker work demonstrated a relationship between immune infiltrate and treatment response and the ongoing work is interrogating interaction of tissue immune microenvironment/genomics and blood-based minimal residual disease markers with response to chemotherapy with or without immunotherapy. The KUCC supported AIM-TNBC IIT will assess the value of ctDNA based MRD for adjuvant treatment intensification in patients with high-risk TNBC. A Phase I/II IIT study of an oral, class I PI3K alpha-specific inhibitor  in combination with nab-paclitaxel chemotherapy in patients with metastatic HER2-negative breast cancer was conducted at KUCC and demonstrated very encouraging efficacy with an objective response rate of 52%. The clinical study was accompanied by pharmacokinetic studies performed by the Clinical Pharmacology Shared Resource and translational studies of tissue and ctDNA biomarkers supported by the Biospecimen Shared Resource. Based on the preliminary clinical/translational/PK data generated at KUCC, a Phase III registration trial of this regimen in biomarker selected patients with TNBC is ongoing. Further translational work is also underway to study novel ctDNA technologies for longitudinal MRD monitoring and assessment of resistance mechanisms for alpelisib. PI3K inhibitor, alpelisib, will be studied in combination with a novel antibody-drug conjugate in an upcoming Phase I study at KUCC. This highlight addresses breast cancer, a KUCC catchment area priority, and demonstrates transdisciplinary collaboration.With the recognition of the broad anti-cancer efficacy of immune checkpoint inhibitors (ICI) in multiple advanced disease settings, a KUCC investigator pioneered a phase II study with combination chemotherapy and ICI in patients with adenocarcinoma of gastric, esophageal and gastro-esophageal junction (GEJ) in the peri-operative setting, which has the potential to lead to the standard of care management if efficacy is demonstrated by the phase III studies.KUCC was among the very first in the United States to be certified as a CAR-T (chimeric antigen receptor T cell) center for Novartis, Kite/Gilead, and Bristol Myers Squibb and KUCC was the lead enrolling site to the pivotal Juliet trial which led to FDA approval for third line treatment of Diffuse Large B cell lymphoma (DLBCL). Additionally, KUCC center was a lead enrolling site to a pivotal, phase 3 prospective, randomized clinical trial comparing CAR-T therapy to autologous stem cell transplant for patients with relapsed or refractory DLBCL. This study demonstrated an EFS and OS  advantage for CAR-T and led to FDA approval of CAR-T in the second line and changed the SOC in this clinical setting. Additionally, KUCC in partnership with the NCI and Children’s Mercy Hospital in Kansas City are pursuing a novel CAR-T construct that will target multiple different cell surface antigens using a single cell multi-antigen targeting CAR-T, thereby avoiding a common cause of treatment failure, i.e., antigen escape. Thus, KUCC has built and achieved national prominence for our CAR-T program. Further, KUCC holds several cell-therapy investigational new drug protocols (INDs) with the Food and Drug Administration and has initiated two corresponding investigator-initiated trials (IITs). The first IIT is investigating the safety and efficacy of Wharton’s jelly– derived Mesenchymal Stromal Cells (WJMSC) in graft versus host disease (GVHD). Additional trials explore the infusion of donor derived gamma delta T-cell infusion after haplo-identical stem cell transplant in patients with acute leukemia. The latter strategy seeks to prevent relapse after transplant, while avoiding the risk of untoward GVHD. Further, KUCC translational scientists are developing novel CAR-T constructs to target triple negative breast cancer and glioblastomas. There are currently 23 active clinical trials in KUCC using cellular therapeutics to target both hematologic and solid tumor cancers.In 2019, KUCC-MCA (Masonic Cancer Alliance) was selected as an NCI Community Oncology Research Program (NCORP) Minority/Underserved Community Site (UG1). The KUCC-MCA Rural NCORP leverages our 45+ year experience as a SWOG-member, 25-year experience providing oncology care via telemedicine, 15-year history of successfully conducting research in rural primary care settings, and 10-year experience opening and running clinical trials within rural healthcare networks. The overarching goal is to enhance capacity for increasing clinical trial accruals and participation of rural populations in cancer control, prevention, treatment, and care delivery clinical trials. In 2020, 183 patients were accrued to NCORP trials, outpacing the annual NCORP goal of 150 accruals. In 2020, we were awarded a Create Access to Targeted Cancer Therapy for Underserved Populations (CATCHUP 2020) grant to expand access to ETCTN trials for rural and underserved populations. KUCC was one of just eight NCI CCSGs to receive the CATCH-UP 2020 administrative supplement, and we were the only institution specifically cited for enrolling rural patients on clinical trials. This congressionally mandated P30 supplement aims to enhance access to targeted cancer therapies for minority/underserved populations. The CATCH-UP 2020 trials were opened at KUCC community sites and MCA (Masonic Cancer Alliance) outreach centers. The average time to activate these trials was 41 days and 55% were enrolled from rural/minority/underserved population/area.Fostering the growth and further development of the infrastructure to support clinical research is a continued area of emphasis for KUCC to ensure we maximize our impact on the catchment area. The KUCC clinic trial office (CTO) provides comprehensive support services that span the life cycle of cancer clinical trials from concept through manuscript. CTO services are available to all members of the Cancer Center’s research programs.The CTO provides centralized protocol management and reporting, with strong emphasis on data integrity, protocol compliance, education and training of CTO staff and investigators, and timelines for rapid trial submission and activation. The CTO supports KUCC investigators through the Disease Working Groups (DWG) to develop research portfolios that meet the needs of our catchment area. Enhancements to CTO operations enabled the growth of clinical research, with focus on investigator-initiated trials (IITs), early phase clinical trials and trials for underserved and rural populations. Cancer Center Program Leaders are integrated into CTO committees including the Clinical Research Steering Committee and IIT Steering Committee so that CTO functions best serve the needs of the individual programs and promote translation of KUCC science to the clinic. The CTO expansion and staff specialization has enabled a steady increase in clinical trial accrual. From 2016–2020, there were 13,575 accruals in interventional, observational, and ancillary/correlative studies. Accrual to interventional treatment clinical trials increased by 61% . Accrual to NCTN protocols increased overall by 111% . Our achievements led to our recognition as an NCTN “High-Performing Site,” and awards of an NCORP grant and CATCH UP 2020 supplement focused on rural and underserved populations. Our commitment to increase clinical trial outreach to local community sites and the Masonic Cancer Alliance resulted in a 62% increase in accruals . The creation of a dedicated IIT team within the CTO and the IIT Steering Committee resulted in an increase in accruals to interventional treatment IITs by 151% .As a key member of NCI comprehensive cancer centers, the success of clinical research at KUCC demonstrates how critical investigational clinical trials are in the war against cancer.


It is impossible to address the many complex needs of respiratory virus surveillance with a single system. Therefore, multiple surveillance systems and complementary studies must fit together as tiles in a “mosaic” to provide a complete picture of the risk, transmission, severity, and impact of respiratory viruses of epidemic and pandemic potential. Below we present a framework (WHO Mosaic Respiratory Surveillance Framework) to assist national authorities to identify priority respiratory virus surveillance objectives and the best approaches to meet them; to develop implementation plans according to national context and resources; and to prioritize and target technical assistance and financial investments to meet most pressing needs. Population expansion, travel patterns, and global trade also present an ongoing risk of new pandemics and a continuing need to strengthen early warning surveillance. To face these challenges, countries must now increase the number of effective surveillance approaches to address multiple surveillance objectives and extend partnerships for surveillance and collaborative analyses of data across sectors. Doing so will improve data for decision‐making during interpandemic periods and to help ensure that respiratory virus surveillance is both timely and scalable in emergencies.WHO Member States have requested a coordinated approach to the sustainable monitoring of respiratory viruses of epidemic and pandemic potential.The COVID‐19 pandemic generated innovations to support surveillance, including those related to improved point of care or self‐test diagnostic technologies, environmental surveillance, community participatory surveillance, and the rapid improvement in global genomic surveillance.Critically, national surveillance strategies must be directed by the objectives and information needs of local authorities, locally available resources, and feasibility within the populations under surveillance. Surveillance methods that can help address needed objectives include but are not limited to event‐based surveillance in health‐care facilities, the community, and at the animal–human interface; sentinel surveillance using standardized case definitions and integrated laboratory testing; strong networks of connected public health and clinical laboratories; efficient and comprehensive nationally notifiable disease surveillance systems; targeted surveillance in specific high‐risk settings and vulnerable populations; sustained health‐care capacity monitoring; and enhanced clinical surveillance, among others. Surveillance systems need to be complemented with high‐quality and timely outbreak investigations and studies to obtain information not routinely available from ongoing systems.There are also several structural or enabling factors that are critical to the success of any sustainable surveillance. These include strong governance and leadership, sustainable financing and workforce, and integration of data standards and appropriate innovations to promote timely and collaborative analyses of surveillance information from multiple sources. Given the complexity of the current respiratory surveillance landscape, national authorities now need an evidence‐based framework to help their countries rapidly Figure :identify priority respiratory virus surveillance objectives;identify the surveillance approaches that have been used to meet these objectives;prioritize required enhancements of existing surveillance;develop implementation plans according to the national context, resources, and needs;strengthen collaborative synergies between surveillance systems; andprioritize and target technical assistance and financial investments from partners2WHO Mosaic Respiratory Surveillance Framework) was developed by drawing on the experiences of a technical working group (TWG) that included WHO subject matter experts from more than 20 teams/departments at WHO headquarters and members from WHO regional offices (ROs) in all six WHO regions. To further obtain experiences and perspectives from countries of all socio‐economic levels, a secretariat supported WHO ROs as they worked with Country Offices and Ministry of Health partners to implement surveys and gather data on priority objectives, surveillance systems currently used to meet those objectives, and priority surveillance enhancements needed. The ROs also convened regional consultations and focused discussions with countries, informed by surveys, to obtain input for the global consultation. WHO headquarters then hosted a global consultation entitled “’Crafting the Mosaic’: Resilient surveillance systems for respiratory viruses of pandemic potential” on 10 & 11 May 2022. This consultation included 340 in‐person and online attendees including those working in surveillance at the country level, and representatives from WHO Country Offices, all six ROs, WHO headquarters, and external partner organizations. The framework incorporated iterative feedback from the TWG, the WHO COVID‐19 incident management team leadership, and external subject matter experts from the United States Centers for Disease Control and Prevention, the European Centre for Disease Prevention and Control, the Global Fund, the Bill and Melinda Gates Foundation, and the Rockefeller Foundation. The secretariat also collected case studies by working with WHO ROs to obtain examples of implementation of different surveillance systems and studies to meet priority objectives. These case studies provide national authorities with examples of the use of different systems to help them move from a theoretical to practical level.The mosaic surveillance framework .4The specific tools to help countries implement the mosaic surveillance framework will include those to help prioritize respiratory surveillance objectives, map existing systems to priority objectives; and to identify priority enhancements needed. However, associated tools will also help national authorities consider the need to strengthen broader enabling structures for surveillance in their countries.Our vision is that all countries develop well‐coordinated mosaics of multiple fit‐for‐purpose surveillance approaches that address priority surveillance objectives for influenza, SARS‐CoV‐2, RSV, and other respiratory viruses of epidemic and pandemic potential according to country context. Respiratory viruses serve as a prototypical example of the way surveillance systems can work together resiliently to provide a comprehensive picture of disease emergence, spread, and impact. There are several respiratory viruses that have important commonalities in terms of virological, epidemiological, and clinical surveillance approaches. However, there are areas where this framework has applicability beyond respiratory viruses and, in some cases, beyond respiratory pathogens. The next respiratory pandemic remains imminent, and the time is now to apply lessons learned to assure that newly strengthened and properly focused routine surveillance may better support epidemic, pandemic, and other emergency monitoring needs.JAM: Conceptualization, Methodology, Writing, Validation, and Leadership; IB: Conceptualization, Methodology, Writing, Validation, and Leadership; HCL: Methodology, Writing, and Validation; AWM: Writing, Methodology, and Validation; SCB: Conceptualization, Methodology, Validation, and Leadership.All authors have declared no conflicts of interest.More details on methodology and any data to inform the framework may be found at WHO Mosaic Respiratory Surveillance Framework.https://publons.com/publon/10.1111/irv.13122.The peer review history for this article is available at


In recent years, several papers have been published on cardiovascular (CV) involvement, risk, management, and treatment in systemic inflammatory arthritis (SIA), including rheumatoid arthritis, (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). An explanation for the increased interest in this topic is that although joint involvement is considered the principal manifestation of SIA, these diseases have also been associated with an enhanced burden of cardiovascular disease (CVD) ,2,3. PatThis editorial aims to discuss studies and review articles that have tried to improve our understanding of CV risk and its management in patients with systemic inflammatory athropathies in 2022. First, a review by M. Nurmohamed and his group  focused A study from Poland  confirmeFinally, a study evaluated the modifications of cholesterol efflux capacity (CEC) and the atherogenic cholesterol loading capacity (CLC) of serum lipoproteins in patients with AS and PsA before and after treatment with tumor necrosis factor inhibitors (TNFi) and/or methotrexate (MTX). The results demonstrated that in the SpA group, the total and high-density lipoprotein (HDL)–cholesterol increased after treatment, while lipoprotein(a) decreased and CLC was unchanged . TreatmeThe strengths of these studies include new useful findings for CV management in SIA patients  and are The studies have some limitations as they did not examine the impact of comorbidities such as depressive disorders on CV risk .In conclusion, these studies showed that CV involvement might be a pivotal cause of increased mortality in these patients, impacting SIA management and quality of life. Furthermore, the findings can raise doubts about the time of diagnosis and treatment starting  since the persistence of inflammation in patients with SIA, or pre-onset SIA increases the likelihood of developing—*-events. Clinicians should also focus on diagnosing CV comorbidity and check for CV risk factors to avoid incorrect management and treatment. However, the available tools and scores can underestimate CV risk in high-risk patients in clinical practice. Further benefits in analyzing the CV impact in SIA patients include identifying a potential easy screening and treatment approach in clinical practice.


Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future. In late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus was detected in Israel and the United States of America .,Vaccine-derived polioviruses are defined as viruses demonstrating a genetic divergence of > 1% nucleotide changes from the parent Sabin strain for types 1 and 3, or > 0.6% nucleotide changes for type 2 in the VP1 region of the nuceleotide.–Primary immunodeficiency disorders are genetic disorders in individuals who have an incomplete immune system.–Despite advancements in the diagnosis of immunodeficiency, the diagnosis and care of primary immunodeficiency disorders in India is still developing and requires better awareness and infrastructure if care is to be available countrywide. To overcome these challenges, the Indian Council of Medical Research has established the Centre for Advanced Research for Primary Immunodeficiency Disorders to train scientists and physicians, and to establish standardized diagnostic techniques and facilities.Current poliovirus surveillance in India is based on acute flaccid paralysis surveillance which can detect transmission of poliovirus by patients with paralysis. However, patients with primary immunodeficiency disorder not affected by paralysis may continue to shed vaccine-derived poliovirus for months and go undetected by acute flaccid paralysis surveillance. There is a risk that these patients can cause spillover circulation of poliovirus in the community, leading to circulating vaccine-derived poliovirus. This concern led the Strategic Advisory Group of Experts on Immunization and the Global Polio Eradication Initiative to recommend expanding poliovirus surveillance among people with primary immunodeficiency disorder, as a strategy for the period after certification of polio eradication.To address the issue, the Indian Council of Medical Research led a study to investigate poliovirus infection in children with primary immunodeficiency disorders.We therefore submitted a proposal to the WHO Polio Research Committee in Geneva to study the establishment of a surveillance and response network for immunodeficiency-related vaccine-derived poliovirus in India. The proposal was aligned with the Global Polio Eradication Initiative’s draft guidelines for implementing poliovirus surveillance among patients with primary immunodeficiency disorders.The study was conducted from January 2020 to December 2021 at seven sites at different medical institutes in India. The initial aim was to enrol 150 patients with diagnosed primary immunodeficiency disorder. We followed up patients whose stool samples were positive for enterovirus infection, as per the study protocol ; Fig. 1.Box 1Patients of any age with confirmed primary immunodeficiency disorder. Primary immunodeficiency disorders are a heterogeneous group of inherited disorders due to developmental defects or dysfunction of the immune system components.• Stool specimens.• Serum samples, for patients positive for immunodeficiency-related vaccine-derived poliovirus.• Patients already diagnosed with primary immunodeficiency disorder, routinely visiting the primary immunodeficiency disorder outpatient department of hospitals for check-up and intravenous immunoglobulin therapy. • Patients newly diagnosed with primary immunodeficiency disorder.• Phase 1: January 2020 to December 2021.• Phase 2: January 2022 to December 2023.• Patients confirmed with primary immunodeficiency of any age: (i) antibody disorder, including hypogammaglobulinaemia, agammaglobulinaemia, X-linked agammaglobulinaemia, and other antibody deficiencies; (ii) severe combined immunodeficiency disorder and other combined humoral and T-cell deficiencies; or (iii) others, including major histocompatibility complex deficiencies or immunodeficiency-centromeric facial-anomalies syndrome and others.• Patients attending the study medical institute for medical care.• Patients whose family provide consent for the study.Patients with transitory or secondary immunodeficiency; that is, related to infections including human immunodeficiency virus, chronic illness or treatment with immunosuppressive therapy.• Study site data includes case investigation details, sample collection details, number of cases enrolled and samples collected from the study sites.• Patient data includes demographic, clinical, virological and vaccination details.• Laboratory data includes case and sample records, test details and results, inventory and storage details.• Data on follow-up samples will be recorded for each patient, along with the data from enrolment.• Data will be analysed periodically for further follow-up.• Patients positive for immunodeficiency-related vaccine-derived poliovirus will be followed up immediately as per World Health Organization guidelines.The study received approval from the institutional ethical committee of the National Institute of Virology and the ethics review committees of all study sites and institutes. The study protocol was also approved by the ethics review committee of WHO Headquarters in Geneva. Free and informed consent of the patient or their legal guardian was obtained before enrolment.The first step was to identify medical institutes with the expertise and infrastructure to confirm primary immunodeficiency disorder at the immunological and molecular level. The National Institute of Immunohaematology and Bai Jerbai Wadia Hospital for Children, who had expertise in screening for inborn errors of immunity in patients nationwide, helped to identify centres in other areas of India that were already providing diagnosis and care for primary immunodeficiency disorders. As a result, five other hospitals situated in Bangalore, Hyderabad, Kozhikode, Lucknow and Mangalore were recruited to the study, to a total of seven sites, in a collaboration with the National Institute of Virology Mumbai Unit, National Institute of Immunohaematology and WHO . We arraBox 2Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh.Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra.Indian Council of Medical Research National Institute of Immunohaematology, Mumbai, Maharashtra.Calicut Medical College, Kozhikode, Kerala.Aster CMI, Bangalore, Karnataka.Kasturba Medical College, Mangalore, Karnataka.Nizam’s Institute of Medical Sciences, Hyderabad, Telangana.Post Graduate Institute of Medical Education & Research, Chandigarh.Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh.Sawai Maan Singh Medical College, Jaipur, Rajasthan.All India Institute of Medical Sciences, Rishikesh, Uttarakhand.Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh.King George's Medical University, Lucknow, Uttar Pradesh.Super Speciality Hospital, Noida, Uttar Pradesh.Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra.Indian Council of Medical Research National Institute of Immunohaematology, Mumbai, Maharashtra.All India Institute of Medical Sciences, Bhopal, Madhya Pradesh.Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha.All India Institute of Medical Sciences, Bhubaneswar, Odisha.Gauhati Medical College, Guwahati, Assam.Calicut Medical College, Kozhikode, Kerala.Aster Cauvery Medical Institute, Bangalore, Karnataka.Kasturba Medical College, Mangalore, Karnataka.Nizam’s Institute of Medical Sciences, Hyderabad, Telangana.Apollo Hospitals, Chennai, Tamil Nadu.Institute of Child Health, Chennai, Tamil Nadu.Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry.Christian Medical College, Vellore, Tamil Nadu.The study staff at the selected institutes across India comprised clinicians, focal persons and other medical staff, including field staff from the WHO national polio surveillance project. We conducted a one-day training at each hospital or medical institute for staff, with the involvement of the National Institute of Virology Mumbai Unit and WHO India Country Office. The training involved procedures for counselling patients, obtaining consent for participation, enrolment of patients, collection of patients’ data on forms, collection of stool samples and follow-up of patients. WHO polio surveillance field staff and the medical staff were trained to facilitate home collection of stool samples. The study required thorough coordination, extensive training, technical support, routine monitoring and regular follow-up between the team at the National Institute of Virology Mumbai Unit and the field sites. The National Institute of Virology Mumbai Unit was the main coordinating centre for the study and kept the records of patients enrolled and of the collection, follow-up and shipment of samples. The focal person at each study site coordinated with the Institute team about sample collection and transport issues and queries. The project was based on strong coordination among the Institute, study sites and WHO India Country Office. Since the study sites had different facilities for diagnosis and management of patients with primary immunodeficiency disorder, each site needed individual advice on patient enrolment and sample collection.Although our pilot study only enrolled children, for this study we included patients of all age groups. Clinicians at the study sites (the site investigators) identified suspected cases of primary immunodeficiency disorder based on the Jeffrey Modell Foundation warning signs for the diagnosis of primary immunodeficiency.Box 31. Four or more new ear infections within 1 year.2. Two or more serious sinus infections within 1 year.3. Two or more months on antibiotics with little effect.4. Two or more pneumonias within 1 year.5. Failure of an infant to gain weight or grow normally.6. Recurrent, deep skin or organ abscesses.7. Persistent thrush in mouth or fungal infection on the skin.8. Need for intravenous antibiotics to clear infections.9. Two or more deep-seated infections including septicaemia.10. A family history of primary immunodeficiency disorder.Source: Jeffrey Modell Foundation, 1993.We planned to collect stool samples from enrolled patients either at the hospital treating them  or at their home. For home collection, the patients were provided with stool containers and a carrier with frozen ice packs to transport samples and maintain cold chain. After enrolment, patients provided two samples 1 month apart that were stored at −20 °C. All samples collected at a given site during a month, along with the related documents, were sent to the National Institute of Virology Mumbai Unit for testing for enteroviruses. At the Institute, the stool samples were anonymized and stored at −20 °C until further processing, as per WHO guidelines.Focal persons assigned by the site investigators followed up patients regularly to obtain monthly consecutive samples (two samples from each person) and remind patients about the subsequent samples 15 days in advance. Patients whose samples were positive for polio or non-polio enteroviruses were subsequently followed up until two subsequent samples tested negative. Patients with primary immunodeficiency who tested negative for enteroviruses in two consecutive samples were followed up at 6-monthly intervals .The identification of a patient with primary immunodeficiency and confirmed poliovirus excretion was immediately notified to the respective site investigators and WHO India Country Office officials by the principal investigator. Key people were notified at the National Institute of Virology, WHO and the health ministry. Set guidelines were followed for counselling the patient and their close family about isolation of the patient, vaccination with inactivated poliovirus vaccine and procedures for discarding of faecal material. The results of the processed samples were provided within a month of collection to follow up the positive samples at monthly intervals.The case and community investigation of a positive case was handled by the WHO national polio surveillance field units with the support of the Indian Council of Medical Research and local health authority, coordinated by the health ministry. An investigation of the risks of spillover of immunodeficiency-related vaccine-derived poliovirus into the community was conducted. Stool samples of select children in the local area were tested for poliovirus excretion. The serum sample of the polio-positive child was tested for polio antibody titre. The protocol states that identified polio-positive patients would continue to be clinically managed by the study site at the discretion of the treating physician. The poliovirus antiviral agent  along with a protease inhibitor may be considered in future for treatment of polio-positive patients, subject to Indian regulatory approval. The case management would depend on the type of poliovirus isolated, the sequencing data and the presence of risk factors for community transmission.Data from the case investigation forms from all the study sites were entered electronically and compiled as a single master database at the National Institute of Virology Mumbai Unit. The database comprised patients’ demographic data, clinical history, symptoms and immunization status and the results of the sample analysis. The data were analysed periodically to monitor the progress of the study and the follow-up of samples. We recorded the frequency and percentage of patients with poliovirus and non-poliovirus enterovirus by type of primary immunodeficiency disorder, site, age and sex, with further characterization in terms of nucleotide changes, if relevant. The data were shared with the collaborating study sites and WHO country office India.We visited study sites to monitor various study-related activities. Monitoring focused on how sites managed the informed consent process with patients. Other important activities included assessing the availability of supplies at study sites, review of study-related documents and data management processes at sites. We also monitored the sample management in the study, including sample collection, storage and transport. The reasons behind loss to follow-up were also assessed to reduce patient attrition to the minimum.In countries using oral polio vaccine and where newborn screening is not available, as in India, it is important to screen and diagnose children with primary immunodeficiency disorder and create awareness about the consequences of oral polio vaccine in these children. However, the diagnosis of primary immunodeficiency disorder requires trained manpower and the necessary infrastructure at major hospitals to identify such cases. Therefore, working with clinicians and paediatricians is necessary to establish referral facilities in at least a few areas of the country so that the samples from more remote areas can be transferred and analysed to confirm the diagnosis. Parents residing in remote areas may find it inconvenient to travel to hospital sites to deposit stool samples. A system therefore needs to be developed for home collection of samples through local government health providers or existing national programmes. With the study institutes having different capacities, we faced several challenges related to collection, storage and transport of samples. Another challenge is the poor financial status of families, which deters many parents from follow-up hospital visits for expensive treatment such as bone marrow transplant after a diagnosis of primary immunodeficiency disorder in their child. The greatest challenge we faced was the coronavirus disease 2019 (COVID-19) pandemic which started just 4 months after the start of the study. The nation was placed under a strict lockdown for more than 2 months and most hospitals at the time were converted into COVID-19 care centres, which affected sample collection. Due to these challenges, we decided to involve staff from the national polio surveillance project. As a part of routine acute flaccid paralysis surveillance since 1997, these staff coordinate with district health officials to obtain stool samples for the polio surveillance system in India. Their networking experience across India facilitated sample collection and transport to our study sites in the districts and states or even across the border states during the COVID-19 pandemic . This exThe study has provided important data on the extent of excretion of polioviruses and non-polio enteroviruses among people with primary immunodeficiency in India. We were able to analyse these outcomes in terms of age, sex, primary immunodeficiency disorder type and study site. Another important outcome was our experience with the integration of primary immunodeficiency disorder surveillance with polio surveillance in India, due to the field involvement of the WHO polio surveillance team. Some key achievements of the project are: (i) establishment and expansion of a network for screening long-term poliovirus excretion in patients with primary immunodeficiency disorder in India; (ii) networking of these sentinel sites with diagnostic facilities for primary immunodeficiency disorder in India; (iii) support from the national polio surveillance project in coordination with sentinel sites and government sources for collection of stool samples from the homes of patients with primary immunodeficiency disorder; (iv) integration of primary immunodeficiency disorder screening with acute flaccid paralysis surveillance in India; (v) increased awareness among paediatricians and other related clinicians about the consequences of long-term excretion of poliovirus from patients with primary immunodeficiency disorder; (vi) increased awareness within the Indian health system of the importance of avoiding oral polio vaccine in children with primary immunodeficiency disorder; (vii) development of draft national guidelines for integration of primary immunodeficiency disorder surveillance into national polio surveillance; (viii) some insights gained into the epidemiology of primary immunodeficiency disorder in India and immunodeficiency-related vaccine-derived poliovirus excretors; and (ix) development of a primary immunodeficiency disorder registry with tracking and follow-up of patients.After learning from the first phase of the study, we expanded the surveillance to include additional referral hospitals in other areas of India by sensitizing clinicians to the issue, extending diagnostic testing and integrating the study with ongoing acute flaccid paralysis surveillance. The Polio Research Committee in Geneva, Switzerland, accepted this proposal of expansion to a second phase of the study which was planned to be conducted from January 2022 to December 2023. The study now has better geographical representation countrywide with the inclusion of 14 new study sites across India, to a total of 21 sites .23We plan to integrate the primary immunodeficiency disorder surveillance with the national acute flaccid paralysis surveillance to carry out long-term screening for polio and non-polioviruses in patients with primary immunodeficiencies. The immunological parameters such as cytokine responses and anti-polio antibody titres responsible for enterovirus replication and clearance of the virus will also be investigated as part of this study. The national registry of primary immunodeficiency disorders being developed by the Indian Council of Medical Research will help provide epidemiological data on people with primary immunodeficiency disorder in India. We hope that our experience will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance. The aim will be to reduce the risk of polio resurgence, to inform policy-makers working on polio eradication, and to contribute information to the global surveillance database on immunodeficiency-related vaccine-derived poliovirus.


To explore the diagnostic clues and abnormality spectrum of heterotaxy syndrome by prenatal ultrasonography and postnatal verification.The prenatal ultrasonic data of 88 heterotaxy syndrome fetuses were analyzed retrospectively as left isomerism (LI) and right isomerism (RI). Prenatal ultrasound compared with the anatomical casting of the fetal body after labor induction, and the confirmatory postnatal diagnosis after delivery.Fetal LI showed typical malformations of gastric vesicles on different sides from the heart, absence of hepatic segment of the inferior vena cava (IVC), abdominal aorta (AO) parallel with the azygos vein (AV), bilateral left bronchus, bilateral left atrial appendages, and polysplenia; intracardiac malformations of AV septal defects (AVSD), single atrium (SA), left ventricular outflow tract obstruction (LVOTO), and double-outlet right ventricle (DORV); and cardiac conduction abnormalities of sinus bradycardia and AV blockage. Fetal RI reported typical malformations of gastric vesicles on different sides from the heart, juxtaposition of the IVC with AO, anomalous pulmonary venous connection (APVC), asplenia, and bilateral right atrial appendages; intracardiac malformations of AVSD, SA, single ventricle, pulmonary atresia and stenosis, and DORV. The postnatal verification revealed 3 malformations misdiagnoses and 4 malformations missed diagnoses in LI fetuses and 10 misdiagnoses and 8 missed diagnoses in RI fetuses.The proposed five-step prenatal ultrasonography has an important diagnostic value for the identification and classification of heterotaxy syndrome. The different sides of gastric vesicles and cardiac apex are important diagnostic clues for heterotaxy syndrome, featuring disconnected or hypoplastic IVC, typical complex cardiac malformation, and atrioventricular block in fetal LI, and shown APVC, juxtaposition of IVC and AO, and intracardiac malformations such as AVSD, DORV, and LVOTO in fetal RI. Heterotaxy syndrome (HS) is a rare and complex condition with abnormal arrangement of organs in relation to the left-right axis of the body, different from complete situs solitus or situs inversus which occurs 0.8 in 10,000 at live birth . OverallA combination of the cardiac sequential segmental method with the extracardiac characteristic sonography has been explored in HS fetuses , 14, in This retrospective study analyzed all HS fetuses diagnosed by the prenatal five-step approach using ultrasonography in Fujian Maternity and Child Health Hospital, Fujian Medical University between January 2014 and May 2022. Informed consent forms were obtained from the guardians of all study subjects. The Ethics Committee of Fujian Maternity and Child Health Hospital, Fujian Medical University (2014FY110700) approved the study. Data on prenatal diagnosis and postnatal follow-ups were obtained from the electronic medical record. Postnatal validation methods include anatomical casting and Ultrasonography. HS patients were excluded from the study if the data from antenatal or postnatal follow-ups were unavailable.All patients underwent ultrasound screening performed with GE Voluson E8 or E10, Siemens ACUSON S2000, Philips IE33 ultrasound machine with a 4–8 MHz transabdominal probe. Ultrasound settings for fetal echocardiography and pregnancy examination were set according to the parameters recommended by the manufacturer. Prenatal Ultrasound was performed according to the AIUM Performance of Fetal Echocardiography guideline . The diaFive step approach by Echocardiography: Step 1: The position of viscera and heart was examined to determine: (1) the position of abdominal organs, the course of the portal vein (PV), and the development of IVC and its position in relation to the abdominal aorta; (2) the position of the heart. Step 2: The systemic and pulmonary venous return was examined to detect: (1) the structure of IVC or the interrupted IVC with continuity of the azygos vein (AV). The latter was manifested as a “double vessel” sign in the chest and drainage of the umbilical vein to the right atrium in the sagittal view of the fetal abdomen on a color Doppler flow diagram, showing an absence of the upper part of the inferior vena cava; (2) the drainage characteristics of venous ducts (VD) and hepatic vein (HV) and their connection with atrium; (3) the location and number of superior vena cava and its connection with atrium; (4) the connection between the pulmonary vein and the atrium or systemic vein, and the centrifugal venous flow in the mediastinum or the hepatic inflow in the liver except the umbilical vein and portal vein. Step 3: Signs of any intracardiac malformations were examined for: (1) a common atrium; (2) a single ventricle, two symmetrical ventricles, or a ventricular septal defect ; (3) regurgitation in AV valve or a common AV valve in determining the type of AV valve and its connection with the ventricle; (4) blockage of the outflow tract; (5) defects in aortic and pulmonary artery trunks and branches; (6) displacement of aortic arch; (7) abnormalities in the position and blood flow direction of the ductus arteriosus. Step 4: The fetal heart rate and heart rhythm were measured. In case of abnormality, M-mode ultrasonography was performed to determine the type of arrhythmia. Step 5: Other abnormal signs were surveyed in the spleen, auricle, bronchus, gallbladder, and other organs. Postnatal verification.in vitro fixation. The main steps of the vascular casting were as follows: (1) the umbilical vein was separated, into which a tube was inserted, ligated, and fixed with a silk thread. Afterwards, normal saline was injected into the tube to rinse the blood vessels until the color of the heart and lungs turned lighter; (2) the rinsed samples were cast with epoxy resin, polyamide resin curing agent, and ethyl acetate as the main hardening materials, and red pigment as casting agent; (3) the thoracic and abdominal organs were subsequently removed and corroded in potassium hydroxide solution. The features of intracardiac malformation and systemic and pulmonary venous connection routes were observed after the molding. The samples were photographed and archived before and after casting, and the casting results were recorded. The pathological anatomic diagnosis was referred to the published standards . There were 4 cases of gender unknown in LI, and 5 cases in RI. The proportion of males and females in LI cases was similar , while the number of males was far more than females in RI cases .The flowchart of this study is shown in The spectrum of cardiovascular and extracardiac lesions screened prenatally. Typical extracardiac malformations by ultrasonography in the 33 LI fetuses were as follows: gastric vesicles on different sides from the heart, absence of hepatic segment of the IVC, a parallel arrangement of the abdominal AO and the (semi) AV ,B, and dOf the 26 terminated cases, 20 cases received autopsy (76.92%), and the remaining six cases underwent vascular casting (23.08%), which confirmed the prenatal diagnosis (100%). The typical malformations of LI included inconsistent positions of gastric vesicles and the heart, bilateral bi-lobar lungs, bilateral left atrial appendages, absence of a hepatic segment of IVC with dilatation of azygos or semi-azygos veins, intracardiac abnormalities , and extracardiac malformations . Postnatal pathological anatomy reported atypical left morphological structure in some cases: two cases (8%) of hypoplasia of the hepatic segment of the IVC turned out to be thin and narrow; three cases (12%) of small left atrial appendage and unclear morphological features did not feature bilateral left atrial appendage morphology; 10 cases (38%) of polysplenia at the back of stomach turned out basically normal; three cases (12%) of bilateral lobar insufficiency were not the typical bilateral bi-lobar lung. Two intracardiac malformations were misdiagnosed: one case of the single ventricle was mistaken as an unbalanced atrioventricular septal defect and one case of pulmonary atresia as pulmonary artery stenosis; four intracardiac malformations were overlooked, including one case of anomalous pulmonary venous connection and three cases of abnormal hepatic venous return. Among the extracardiac malformations, one case of type I biliary atresia was misdiagnosed as a choledochal cyst .As shown in Of the 46 terminated cases, 41 cases received autopsy, which confirmed the prenatal diagnosis, and 5 cases underwent vascular casting. The typical malformations of RI included the right heart, bilateral right atrial appendages , and APVOne case of the single ventricle was misdiagnosed as an unbalanced atrioventricular septal defect and one case of pulmonary atresia as pulmonary arterial stenosis. In four cases, the spleen was seen in the right posterior part of the stomach, which was misdiagnosed by prenatal ultrasonography. Three cases of APVC were misdiagnosed by ultrasonography, including one case of common vena cava atresia mistaken as complete APVC and two cases as mixed APVC ; four APP < 0.0001), although the double SVC was found in both LI and RI cases . The reflux characteristics of hepatic veins were observed. Only three LI cases (9%) had hepatic veins and venous ducts flowing into both atria separately, while 76% of RI cases reported hepatic veins flowing into both atria or one atrium separately. Compared with LI, RI showed more abnormal reflux of the hepatic vein and reported more cases of APVC (P < 0.05). The intracardiac malformations in LI included AVSD, single atrium, and left ventricular outflow tract obstruction, while the proportion of RI with intracardiac malformations was much higher, including pulmonary stenosis, pulmonary atresia (P < 0.05), and double-outlet right ventricle. Fifty-two percent of LI fetuses reported heart conduction problems, such as bradycardia and atrioventricular block, which were not found in the RI cases.The fetuses with LI or RI feature typical and shared ultrasound manifestations, especially in the systemic pulmonary venous circulation and cardiac malformations. All malformations of patients with LI and RI were recorded in The available literature has documented typical ultrasonic features in LI and RI during an ultrasound examination , 13. In In the current study, most of the RI fetuses reported APVC. Those who mixed APVC had multiple drainage sites, such as the atrium, portal vein, superior vena cava, and venous catheter. An accurate exploration of the drainage location can provide supportive information for surgical interventions . PreviouAtresia of the common pulmonary vein (ACPV) is a rare congenital cardiovascular malformation. The left and right pulmonary veins form a common pulmonary vena cava, which is not connected to the left atrium, right atrium, or other main body veins . As ACPVThe prognosis of HS is associated with combined intracardiac and extracardiac malformations. When the malformations only involve IVC absence without the complications of other malformations, or complicated with mild cardiac malformations, LI fetuses usually have an acceptable prognosis , 33, 34.In general, the gist of the five-step ultrasonic examination is to observe the location of the heart and gastric vesicles, the return of the systemic and pulmonary veins, intracardiac and extracardiac malformations and heart rhythm, especially spleen, liver and other organs. This set of ultrasonic procedures has an important diagnostic value for HS that could be verified by pathological anatomy. HS is caused by various genetic mutations that impact critical developmental pathways during embryogenesis. Characterization of the fetal organs by ultrasound provides diagnostic biomarkers for HS. Further investigation is imperative to provide information on the underlying mechanisms of this rare disease and improve future prenatal management and guidance.This study is a retrospective analysis of verified diagnoses. Many pregnant women chose termination of pregnancy instead of surgical intervention. We have limited clinical follow-ups. The findings of the patients are only based on the data derived from prenatal ultrasonography.The proposed five-step prenatal ultrasonic approach can produce an accurate prenatal diagnosis of HS, which would facilitate timely intervention, prenatal counselling and management. Anatomical casting helps improve the understanding of HS. The different sides of gastric vesicles and cardiac apex are important diagnostic indicators for HS. Disconnection or hypoplasia of IVC, characteristic of complex cardiac malformation, atrioventricular block and BASM are some indicators for left isomerism; For the right isomerism, the diagnostic clues include anomalous pulmonary venous connection, parallel IVC and AO, and intracardiac malformations, such as atrioventricular septal defect, double-outlet right ventricle, and right ventricular outflow tract obstruction.


Public health survey systems are tools for informing public health programming and policy at the national, state, and local levels. Among the challenges states face with these kinds of surveys include concerns about the representativeness of communities of color and lack of community engagement in survey design, analysis, and interpretation of results or dissemination, which raises questions about their integrity and relevance.Using a data equity framework , the purpose of this project was to describe a formative participatory assessment approach to address challenges in Oregon Behavioral Risk Factor Surveillance System (BRFSS) and Student Health Survey (SHS) data system by centering community partnership and leadership in (1) understanding and interpreting data; (2) identifying strengths, gaps, and limitations of data and methodologies; (3) facilitating community-led data collection on community-identified gaps in the data; and (4) developing recommendations.Project team members' concerns, observations, and critiques are organized into six themes. Throughout this engagement process, community partners, including members of the project teams, shared a common concern: that these surveys reproduced the assumptions, norms, and methodologies of the dominant  scientific approach and, in so doing, created further harm by excluding community knowledges and misrepresenting communities of color.Meaningful community leadership is needed for public health survey systems to provide more actionable pathways toward improving population health outcomes. A data equity approach means centering communities of color throughout survey cycles, which can strengthen the scientific integrity and relevance of these data to inform community health efforts. For the past several years, most respondents (80%) participated using a cell phone.7These large-scale survey systems help guide state and local decisions to target services, address emergent health issues, inform legislation, secure grant funding, and measure progress toward public health objectives. Federal funding for some programs depends on states using CDC's BRFSS survey. For example, the 2019 CDC notice of funding opportunity required Oregon's asthma program to use data from BRFSS Core survey.9 For instance, CDC offers the possibility of adding an optional racial and ethnic oversample  to the primary sample. Other challenges include the high cost to implement the oversample, lack of estimates for smaller geographic areas, lengthy survey completion times,10 concerns about representativeness and data validity/relevance for communities of color, and lack of community engagement in survey design, analysis, and interpretation of results or dissemination.11The Oregon Health Authority (OHA) relies heavily on the BRFSS and SHS for guiding policy and programmatic decisions. Over the past few years, awareness has grown about challenges of the BRFSS and SHS, particularly related to communities of color.13 Oregon included this module in its 2016 survey cycle. In the 2022 survey cycle, 27 states included the BRFSS RTR module, while 42 states included the newly developed Social Determinants and Health Equity module, which collects data on employment and economic stability, food and housing insecurity, transportation, and access to health care, among other topics.14In the case of BRFSS, several optional modules can be added (at a cost) to the core survey. For instance, the Reactions to Race (RTR) module (first piloted in 2002) consists of six questions assessing socially assigned race, race consciousness, and perceptions of and reactions to differential treatment by race/ethnicity in health care and work settings.11However, community feedback in Oregon about the RTR indicates that the module does not go far enough in capturing factors related to racialized experiences  and does not address issues of economic insecurity, community violence, and institutional racism .16 National discourse on transforming public health data systems is ongoing.18 To address some of these issues locally, OHA and community partners are using a data equity framework  to guide public health modernization efforts.20The coronavirus disease 2019 (COVID-19) pandemic has made evident several other challenges (such as disruptions on data collection and processing and variations on definitions of race/ethnicity across states), highlighting the urgency of data accuracy and consistency; timely data dissemination; minimizing burden and maximizing safety; and data relevance, particularly for communities of color.21 The project team, consisting of OHA staff and community partners, used this opportunity to conduct a community-engaged process to elicit feedback on revising and updating Oregon's BRFSS and SHS systems. This collaborative journey demonstrates how data equity principles apply to survey modernization efforts. Project efforts were facilitated by OHA staff and the Research Justice Institute at the nonprofit Coalition of Communities of Color (CCC), whose work focuses on research and data justice and whose members include 19 culturally specific community-based organizations.22Public health modernization aims at creating an equity-centered public health system, including communicable disease protection, health promotion and disease/injury prevention, environmental health, and access to health services.21Using a formative participatory assessment approach, we describe the early stages of programmatic development and implementation of a system-wide survey modernization effort. Hence, one of our first decisions was to evaluate the design and implementation of the BRFSS and SHS, placing community engagement at the center of these efforts. The purpose of this community-centered project was to (1) better understand and interpret BRFSS and SHS data; (2) identify strengths, gaps, and limitations of BRFSS and SHS data and methodologies; (3) facilitate community-led data collection on identified gaps in the data and co-create more actionable survey questions; and (4) develop recommendations. In this article, we describe our work with African American, African Immigrant and Refugee, and Latinx populations as part of a broader effort to center communities of color in public health modernization efforts in Oregon.In the initial stages of this project, OHA staff assumed they could rely on existing community partnerships to find potential project team members. However, they realized that, while partnerships with community organizations existed within OHA units, they were effectively inaccessible and needed to be more cohesive and coordinated organization wide. Consequently, staff undertook outreach and recruitment efforts to find potential project team members. Project staff used a snowball methodology to develop a list of potential members for two culturally specific analytic project teams—one African American/African Immigrant and Refugee and one Latinx.Between October 2019 and March 2020, project staff connected with community-based organizations that had previously collaborated with Multnomah County Health Department, the OHA Office of Equity and Inclusion, and other OHA offices . They reviewed previous statewide internal and external community health data reports and a membership of the community-based Health Equity Researchers of Oregon group, to identify people with lived experience  and experience in public health and/or research. Individuals who met these criteria were interviewed between October 2019 and March 2020. Nine individuals were invited to participate in two small (four to five person) culturally specific project teams . Contracts and compensation for each team member were established.Teams met five times for 2 h each from May 2020 to April 2021 to review BRFSS and SHS data and methodologies, suggest and review additional requested analyses, discuss strengths, gaps, and limitations, identify topics for community-led data collection, review results of data collection, and develop recommendations . Areas oThe two project teams conducted the bulk of their work separately and came together for the last two meetings to review results of community-led data collection and provide recommendations for work in the future. The project teams decided to share their work together in one report because (1) the topic areas of interest/review overlapped significantly  and (2) the COVID pandemic limited the capacity for community engagement, and there was a desire to limit/integrate requests of community groups.During the scheduled meetings (May 2020–April 2021), project team members reviewed survey instruments, requested specific analyses of BRFSS and SHS data, interpreted results, identified knowledge gaps in the data, and suggested areas for community-led data collection. With guidance from the CCC facilitators, team members helped design community-led data collection, analysis, and interpretation of those results. Project teams explored (1) types of survey questions, (2) questionable wording, (3) whether data resonated with their experience and with local data, (4) concerns about the sample, (5) whether additional information was needed to understand the findings and provide important context that BRFSS and SHS lack, and (6) additional data sources relevant to the BRFSS and SHS data.(1)23Mental and behavioral health, especially access to care. These data were gathered through a statewide behavioral health survey of BIPOC communities.(2)Health of youth. Information about this issue came from youth at a Portland-area high school, who gave input into the design of SHS questions.After reviewing the BRFSS and SHS data, project teams decided to focus the community-led data collection on two topic areas:Throughout this process of engaging with community partners and the project teams, a common concern was that BRFSS and SHS reproduce assumptions, norms, and methodologies of a White dominant, individual-centered culture and in so doing, run the risk of misrepresenting racial and ethnic minoritized populations, ultimately further eroding trust, increasing harm, and re-traumatizing communities. We further address these concerns in the 24; (3) need for actionable data (ability to drive policy and practice); (4) sample size/response rate (low number of respondents from communities of color); (5) integration of other data sources; and (6) translations and health literacy. These issues are bound together under one fundamental perspective: the BRFSS and SHSs are products of a dominant institutional culture that centers whiteness. As such, these data harm communities of color through misrepresentation and reinforcing narratives about individual shortcomings that perpetuate racialized stereotypes.20Project team members coalesced around six areas of concern: (1) Lack of meaningful context  missing an intersectional approachFirst, team members expressed concern that survey questions do not collect meaningful contextual information and exclusively focus on individual behavior. These types of questions, presented without context, place the entire responsibility of outcomes on the individual. Team members desired questions that contextualized individual outcomes within underlying socioecological conditions, and that highlighted the role and responsibility of institutions—historically and currently—in creating, perpetuating, and exacerbating health inequities. Team members expressed that the current BRFSS and SHS instruments required additional questions to be able to provide enough context to interpret data findings correctly  that shape people's everyday experiences and their ability to leverage power, resources, and opportunities.Actions that are biased, hostile, or violent toward others based on race are racist, and should be appropriately viewed and acted upon as such. Subsuming them under the concept of “bullying” clouds the dynamics of power at play. Similarly, harassment based on “perceived LGBT” status is reduced to “bullying,” while gender-based harassment is omitted entirely. Moreover, questions regarding “bullying” are presented separately , thus making no space for understanding intersectional dynamics of students' experiences.Third, both teams were consistent in their critique that BRFSS and SHS questions needed to be designed so that data collected can directly drive policy and practice. Members reiterated how these surveys need to focus on systemic  conditions rather than (solely or mostly on) individual behaviors or experiences. Furthermore, one team member said, “We don't need more detailed data about how Black folks experience even worse adverse childhood experiences—i.e., more toxic environments—we already know that. We need data that can help drive policy change.”Consistently, project teams reiterated that for data to be actionable, we need to include information that yields accurate insights about the systems  in which people are making (or trying to make) the best choices they can. In suboptimal environments strained by systemic oppression and historical racism, presenting survey results without this larger context, while focusing almost exclusively on how individuals “need to change their behaviors,” can lead to further blaming and traumatizing communities.25 which in turn would allow us to more routinely couple individual-level health behaviors with family-, neighborhood-, community-, institution-, and policy-related contexts.11 Due to small sample sizes, they questioned if the data make sense to the broader community or are representative and applicable beyond those that responded. Ultimately, they pointed out that the responsibility lays on OHA to lower barriers, and create welcoming spaces to bring people in.Fourth, team members were generally concerned with the low number of African American respondents across the different geographies in Oregon. They suggested African American community members should be able to participate in developing and administering the BRFSS and SHS.Fifth, integration with other data sources is key to further contextualize BRFSS and SHS data. For instance, the Latinx team noted that Latinx respondents were the least likely to report having received influenza vaccination (BRFSS 2020). The Latinx team did not believe this was due to cultural values that were anti-immunization/vaccines, but due to social barriers around access to health insurance/health services and the potential cost of immunizations. They wanted contextual data to help them make sense of the self-reported BRFSS results.26 ODE reported that about 75% of Latinx students enrolled in free and reduced lunch.27As another example, team members questioned the accuracy of data generated by asking students if they participate in free and reduced lunch programs. They noted that students may not know or want to share, and that this information is already collected by other agencies . In addition, in some areas, the entire school population qualifies for free and reduced lunch, but students are still asked that question at the beginning of the academic year. The teams' suspicions are supported by comparison of SHS data with ODE data on free and reduced lunch status. In 2019, while the SHS  found that 57% of Latinx 8th graders and 61% of Latinx 11th graders received free or reduced priced lunches at school,Sixth, ensuring that surveys are written and translated in accessible ways can lead to more representative and reliable findings. Team members wanted to make sure the amount of time it takes to draft and translate documents into accessible language is recognized and compensated accordingly. Different literacy  levels should be considered. How do we make sure we are using health terms and questions that are understandable and culturally relevant? If we use a term such as “Latinx,” how do we contextualize that language?Some Latinos may not understand (or agree with) it, so how can we be more inclusive? The Latinx team reviewed the translated (Spanish language) BRFSS and their translation methods. The group suggested an external advisory group should be established. Advisory members should come from various segments of the Latinx community, so they not only know the language but also the cultural context(s) in which specific words or phrases are used.This project has important implications for the practice of conducting large-scale public health surveys aimed at generating information used for knowledge creation and policy and programmatic development. Robust community engagement must be a linchpin of scientific integrity and relevance for BRFSS and SHS data collection, analysis, interpretation, dissemination, and use. To move in that direction, efforts should include several actions described below, which are fundamental for applying data justice principles to survey modernization processes.28 If data are not presented in an actionable way, how can public health agencies be held accountable by the communities they are meant to serve?First, survey design needs to produce questions that focus on systemic aspects of individual experience, be properly contextualized, and yield actionable data. Questions about individual behavior and experience must be presented with the context to avoid shifting entire responsibility to the individual and misrepresenting people's experiences and victim blaming, and to highlight the role institutions play in creating, perpetuating, and exacerbating health inequities.5 Recent research shows that, while public health surveillance and monitoring systems are integrating racism as a construct, they are still primarily ask individual-level questions.29 Our survey modernization process demonstrates that asking more relevant questions can be done with the active involvement of communities of color, acknowledging their knowledges and lived experiences. Moreover, centering communities of color is critical toward preventing further harm.Hence, we must ensure that BRFSS, SHS, and other survey systems ask relevant contextual questions so that their reports more accurately represent the experiences of communities of color. The fact that the types of questions asked in the BRFSS and SHS fall short of providing important contextual details is well known.31Second, it is important to build in time and resources necessary for relationship development between governmental public health and community partners in any surveillance/survey system, including long-term, sustained, and compensated community-led data collection and reporting efforts. Integrating and sustaining community leadership throughout all aspects of the survey cycle, from design through dissemination is a step toward sharing power with communities of color, centering their expertise, and visualizing their role as architects of their own health equity efforts.31 and at the federal level.29 A fundamental lesson from this work is that communities must be centered in all phases of survey modernization, from instrument design, data collection, analysis, and dissemination to decisions about how data about their communities will be used. Currently, findings from this project are being disseminated among OHA units, other agencies, and community partners, and several recommendations are being implemented .32This work highlights Oregon's efforts to meaningfully incorporate community perspectives into relevant large-scale public health survey systems. Similar efforts are also slowly starting to happen in other statesThe YDC (which started meeting in March 2022) is a new advisory unit within OHA to guide the OHA Public Health Division and the ODE on how to improve the SHS across content, analysis, reporting, and communication components, ensuring that the SHS is asking questions that are meaningful and relevant to students, their families, and communities across Oregon schools. The YDC is youth led and grounded in principles of youth-adult partnership. Two successes to date include the following: (1) The 2022 SHS included open-ended questions to provide greater context and inform policy and (2) the 2023 YDC cohort developed a video, analyzed data, and held a data party with the CCC researchers guiding coding, analysis, writing, and communication of findings with an equity lens.22 Following a data equity approach in our survey systems would greatly move us away from a primarily individual-focused behavioral approach.20 Efforts in Oregon may help to inform similar efforts in other states and at the national level. To uphold our commitment to health equity,31 public health survey systems need to become more context oriented, actionable, and accountable to the communities they serve.In summary, meaningful community leadership is needed for public health survey systems to provide more actionable pathways toward improving community health outcomes.


The quest for global food security has long been a pressing challenge, as the world’s population continues to grow. One crucial aspect of addressing this challenge lies in maximizing crop yields through a deeper understanding of the intricate relationship between crop plant roots and their environment. Root systems play a fundamental role in nutrient uptake, water absorption, and anchoring plants into the soil. Recent advancements in agricultural research have shed light on the dynamic interactions occurring beneath the surface, uncovering the potential to enhance crop productivity and sustainability. In this Research Topic, we delve into the fascinating world of root-environment interactions and explore the latest breakthroughs and innovative approaches that hold promise for revolutionizing agricultural practices and meeting the demands of an ever-expanding population. Crop roots support establishment, development, and growth of plants that are the basis of human nutrition. To value the importance of crop root research, this Research Topic invited manuscripts of crop plants such as maize, rice, wheat, potato, soybean, and others summing up to four original research articles, two systematic review articles and one review article.Mazarei et al.’s identification of two candidate genes in soybean through transcription profiling, GmNAC19 and GmGRAB1. When overexpressed, GmNAC19 and GmGRAB1 resulted in greater root length and root biomass and seed yield doubled. In addition, overexpression of GmNAC19 resulted in greater drought tolerance. Similarly, a systematic review by Lopez et al. focused on how nutrient deficiencies, including nitrogen, phosphorus, and potassium, in arable crops affected root development. In a meta-analysis of fifty field experiments, root length and root biomass were reduced while root length per shoot biomass increased in nitrogen and phosphorus deficiency. The root to shoot ratio was increased in nitrogen deficiency. As a highlight of how roots play an important role in aboveground plant growth and performance, Zheng et al. performed a systematic review on drought stress through a bibliometric analysis from the last century. Historically, research on aboveground organs has dominated the literature. However, recently root research is getting more attention with the specific topics of root plasticity in drought and drought recovery emerging as large new areas of interest. The authors also highlight and summarize root responses to different phases of drought and stress recovery.The papers represent an eclectic mix that demonstrates the range of research on interactions with crop root systems and their dynamic environment. The highlights include Nawaz et al. describe root responses to soil compaction by field traffic on a maize field with sandy loam soil. Soil compaction caused by field traffic resulted in a shallow and denser hard pan in the top soil and subsequently greater root growth in the top 10 cm of soil and less growth between 10 to 30 cm soil depth. Compared to the non-trafficked control, genotypic differences were observed in root growth and yield reduction. Similarly, Skilleter et al. described responses of two contrasting potato cultivars to soil compaction. One genotype was relatively responsive to compaction stress and had reduced leaf area, root density, and yield, while the other genotype had less pronounced responses to compaction. The compacted soils generally contained more water and had a lower soil resistance.Root responses to soil compaction are also emerging as an important Research Topic. Sheldon and Munns reviewed root plasticity responses to salinity stress in staple cereal crops including wheat, maize, rice and barley. Cereal crops are usually classified as glycophytes, meaning salt-sensitive. However, variation in salt-tolerance within and between species is observed. They proposed a new ideotype for salt tolerance to reduce sodium uptake and minimize transport including a ligninfied layer in the root tissue, more lateral roots, deeper rooting, and larger cortical cells. Ning et al. also examined both root anatomical and architectural traits and described how IAA treatment enhances and accelerates root cortical aerenchyma formation. They used root rotation as a gravitropic stimulus to alter lateral root formation on the convex root side. This is a result of the accumulation of auxin in the pericycle of the convex root side resulting in the formation of more lateral roots but less and slower aerenchyma formation in rotated crown roots. Laser microdissection of cortical tissue from both concave and convex sides showed auxin-responsive gene expression decreased on the convex side of the root.In addition to compaction stress, plants also experience a wide range of other abiotic stresses. Increasing Crop Yield: The Interaction of Crop Plant Roots with Their Environment, we hope the readers can gain a better appreciation of the intricacies of root interactions to the dynamic soil environment and how these responses influence plant growth and yield. The exploration of crop plant root-environment interactions has illuminated the path towards sustainable agriculture and global food security. The papers presented in this Research Topic collectively emphasize the critical role of root systems in supporting crop growth and call for continued research and innovation to grow our understanding of the function and genetic control of roots. While understanding and optimizing root systems hold great promise for the development of more productive crops that require less inputs, including fertilizer and irrigation, and that are more resilient to stress, the measurement and manipulation of root traits is challenging. The role of roots in plant function, growth, and ultimately yield performance depends on a number of factors including the choice of crop, soil properties, climatic conditions, management practices, and interactions among and between root and shoot traits. The investigations of root responses to environmental factors sheds light on the need for tailored management practices and the importance of root traits as tools to mitigate yield losses. Yield stability or increase in yield potential will be aided by engaging cutting-edge technologies like precision agriculture, advanced breeding techniques, and genomics to optimize root systems to local environments. By unraveling the secrets of root-environment interactions, we can pave the way for a sustainable and food-secure future.With the seven papers in this Research Topic on JK, HS, and ST jointly wrote the manuscript, revised the text and approve of its publication.


The disease caused by pathogenic fungi is the main cause of postharvest loss of fresh fruits. The formulation of disease control strategies greatly depends on the understanding of pathogenic mechanism of fungal pathogens and control strategy. In recent years, based on the application of various combinatorial research methods, some pathogenic genes of important postharvest fungal pathogens in fruit have been revealed, and their functions and molecular regulatory networks of virulence have been explored. These progresses not only provide a new perspective for understanding the molecular basis and regulation mechanism of pathogenicity of postharvest pathogenic fungi, but also are beneficial to giving theoretical guidance for the creation of new technologies of postharvest disease control. Here, we synthesized these recent advances and illustrated conceptual frameworks, and identified several issues on the focus of future studies. Botrytis cinerea, Penicillium spp., Monilinia spp., Alternaria alternata, Rhizopus stolonifer, Trichothecium roseum, Fusarium spp., Colletotrichum spp., and so on. Among them, B. cinerea has been considered as the second most important plant pathogenic fungus (just follows Magnaporthe oryzae) because it is able to cause gray mold disease in various horticultural crops, resulting in over a billion dollars of losses every year in the world, and also serves as a model system to reveal molecular mechanism of pathogenicity of postharvest pathogens  are responsible for the full virulence , ceratoplatanin protein (BcSpl1), xyloglucanase (BcXYG1) and BcIEB can produce local necrosis when applied to plants in an isolated form  play an important role for the successful establishment of necrotrophic fungi at the initial phase of infection. In n et al. . Both ofB. cinerea. Botrydial is produced in infected plant tissues, and can cause the withering of plant  superoxide anion (•O2−), hydroxyl radical (•OH) and hydrogen (H2O2), are small molecules with high oxidative activity, and usually produced as byproducts of metabolic processes in organisms , including singlet oxygen  are short regulatory nonconding RNAs that silence target genes with fully or partially complementary sequences  kinase BcRim15 mediated by kinase BcSch9  can interact specifically with cis-acting elements in gene promoter region, and regulate the spatio-temporal expression of target gene. Son et al. systematically analyzed the phenotypes of 657 TF mutants of CLPT1) in C. lindemuthianum led to a lethal phenotype  induced the secretion of protein related to proteolysis, and higher pH level  induced more cell wall degrading enzymes  and PeSAT (sulfate adenylyltransferase)  involved in autophagy  responsible for patulin biosynthesis in P. expansum were down-regulated upon the exogenous application with luteolin, further indicating that luteolin is promising to be developed as an alternative agent for controlling fungal pathogen and mycotoxin production.Due to the importance of ROS equilibrium systems in fungi, they have become one of the first-choice targets for many exogenous antifungal substances. For example, borates have been proved to be effective in controlling many postharvest pathogens, such as P. expansum -proteins  are the most important weapon employed by the pathogenic fungi against the immune response of fruit hosts. Therefore, the profile of extracellular proteins is a good candidate for unraveling the unknown interaction mechanisms between postharvest pathogenic fungi and fruit hosts in the future investigation. The identification of more and more pathogenic genes will provide theoretical basis for formulating targeted control strategies for postharvest diseases of fruits. It will be an important research direction in the future to achieve effective control of postharvest diseases through targeted regulation of key pathogenic genes.