Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.

The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines.

Harnessing preexisting influenza virus-specific immunity increases antibody responses against SARS-CoV-2.

In pandemic scenarios involving novel human pathogenic viruses, it is highly desirable that vaccines induce strong neutralizing antibodies as quickly as possible. However, current vaccine strategies require multiple immunization doses to produce high titers of neutralizing antibodies and are poorly protective after a single vaccination. We therefore wished to design a vaccine candidate that would induce increased protective immune responses following the first vaccine dose.

An model of recrudescence reveals developmental plasticity of the bradyzoite stage.

The classical depiction of the lifecycle is bradyzoite excystation conversion to tachyzoites, cell lysis, and immune control, followed by the reestablishment of bradyzoites and cysts. In contrast, we show that tachyzoite growth slows independent of the host immune response at a predictable time point following excystation. Furthermore, we demonstrate a host cell-dependent pathway of continuous amplification of the cyst-forming bradyzoite population.

Group 1 metabotropic glutamate receptor expression defines a T cell memory population during chronic Toxoplasma infection that enhances IFN-gamma and perforin production in the CNS.

Within the brain, a pro-inflammatory response is essential to prevent clinical disease due to Toxoplasma gondii reactivation. Infection in the immunocompromised leads to lethal Toxoplasmic encephalitis while in the immunocompetent, there is persistent low-grade inflammation which is devoid of clinical symptoms. This signifies that there is a well-balanced and regulated inflammatory response to T.

Access to care following Planned Parenthood's termination from Texas' Medicaid network: A qualitative study.

Objectives: This study aimed to explore Planned Parenthood Medicaid patients' experiences getting reproductive health care in Texas after the state terminated Planned Parenthood providers from its Medicaid program in 2021.

Study Design: Between January and September 2021, we recruited Medicaid patients who obtained care at Planned Parenthood health centers prior to the state termination using direct mailers, electronic messages, community outreach, and flyers in health centers. We conducted baseline and 2-month follow-up semistructured phone interviews about patients' previous experiences using Medicaid at Planned Parenthood and other providers and how the termination affected their care.

Minors' Experiences Accessing Confidential Contraception in Texas.

Purpose: Texas is one of 24 states that restricts minors' ability to obtain contraception without parental consent, unless they access confidential services at federally funded Title X clinics. This study explores Texas minors' reasons for and experiences seeking confidential contraception.

Methods: Between September 2020 and June 2021, we conducted in-depth phone interviews with 28 minors aged 15-17 years.

Evidence-based family planning services among publicly funded providers in Texas.

Background: Healthy Texas Women (HTW) is a fee-for-service family planning program that excludes affiliates of abortion providers. The HTW network includes providers who participate in Title X or the state Family Planning Program (FPP) and primary care providers without additional family planning funding (HTW-only). The objective of this study is to compare client volume and use of evidence-based practices among HTW providers.

Comparing preference for and use of medication abortion in Texas after policy changes in 2014 and 2018.

Objectives: Assess preferences for and use of medication abortion in Texas after implementation of two policy changes: a 2013 state law restricting medication abortion and the FDA label change for mifepristone in 2016 nullifying some of this restriction.

Study Design: We analyzed surveys conducted in 2014 and 2018 with abortion patients at 10 Texas abortion facilities. We calculated the percentage of all respondents with an initial preference for medication abortion by survey year, and the type of abortion obtained or planned to obtain among those who were at <10 weeks of gestation.

A genetic tool for the longitudinal study of a subset of post-inflammatory reactive astrocytes.

Astrocytes are vital support cells that ensure proper brain function. In brain disease, astrocytes reprogram into a reactive state that alters many of their cellular roles. A long-standing question in the field is whether downregulation of reactive astrocyte (RA) markers during resolution of inflammation is because these astrocytes revert back to a non-reactive state or die and are replaced.

Insurance Churn and Postpartum Health among Texas Women with Births Covered by Medicaid/CHIP.

Introduction: Insurance churn (changes in coverage) after childbirth is common in the United States, particularly in states that have not expanded Medicaid coverage. Although insurance churn may have lasting consequences for health care access, most research has focused on the initial weeks after a birth.

Methods: We analyzed data from a cohort study of postpartum Texans with pregnancies covered by public insurance (n = 1,489).

Correction: CD4+ T cells promote humoral immunity and viral control during Zika virus infection.

[This corrects the article DOI: 10.1371/journal.ppat.

CD4+ T cells promote humoral immunity and viral control during Zika virus infection.

Several Zika virus (ZIKV) vaccines designed to elicit protective antibody (Ab) responses are currently under rapid development, but the underlying mechanisms that control the magnitude and quality of the Ab response remain unclear. Here, we investigated the CD4+ T cell response to primary intravenous and intravaginal infection with ZIKV. Using the LysMCre+Ifnar1fl/fl (myeloid type I IFN receptor-deficient) C57BL/6 mouse models, we identified six I-Ab-restricted ZIKV epitopes that stimulated CD4+ T cells with a predominantly cytotoxic Th1 phenotype in mice primed with ZIKV.

A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited.

Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages.

Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results.

An IRF-3-, IRF-5-, and IRF-7-Independent Pathway of Dengue Viral Resistance Utilizes IRF-1 to Stimulate Type I and II Interferon Responses.

Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3Irf5Irf7 triple knockout [TKO]) survive DENV challenge.

Mapping and Role of the CD8 T Cell Response During Primary Zika Virus Infection in Mice.

CD8 T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8 T cell response in ZIKV-infected LysMCreIFNAR C57BL/6 (H-2) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8 T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated.

Twist1 induces CCL2 and recruits macrophages to promote angiogenesis.

The transcription factor Twist1 induces epithelial-mesenchymal transition and extracellular matrix degradation to promote tumor metastasis. Although Twist1 also plays a role in embryonic vascular development and tumor angiogenesis, the molecular mechanisms that underlie these processes are not as well understood. Here, we report a novel function for Twist1 in modifying the tumor microenvironment to promote progression.

High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.

Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Deletion or uniparental disomy of chromosome 7q were detected in 42 of 114 (37%) SMZLs but in only nine of 170 (5%) mature B-cell lymphomas (P < 0·00001). The presence of unmutated IGHV, genomic complexity, 17p13-TP53 deletion and 8q-MYC gain, but not 7q deletion, correlated with shorter overall survival of SMZL patients.

Genomic abnormalities acquired in the blastic transformation of splenic marginal zone B-cell lymphoma.

Among 20 cases of typical splenic marginal zone lymphoma (SMZL), two cases had blastic transformation. The genetic mechanisms underlying the morphologic transformation were investigated by comparing genetic changes in initial and blastic phases. A complex karyotype including trisomy of 3q and genomic gain of 17q22-q24 was seen in both cases at diagnosis.

Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features.

Introduction: Mantle cell leukemia (MCLeu) has been considered as a leukemic form of mantle cell lymphoma (MCL). However, the presence of certain features rarely observed in MCL, such as transformation to prolymphocytic leukemia (PLL) or indolent clinical course, suggests that MCLeu may represent a distinct disorder.

Methods: Seven cases of MCLeu with t(11;14)(q13;q32) and BCL1-IGH gene rearrangement were ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorders with leukemic expression.

Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) may present with either nodal or leukemic disease. The molecular determinants underlying this different biologic behavior are not known. This study compared the pattern of genetic abnormalities in patients with nodal and leukemic phases of MCL using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) for specific gene loci.

Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome.

We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT.

Ciprofibrate effects on carbohydrate and lipid metabolism in type 2 diabetes mellitus subjects.

Background And Aims: Atherosclerosis is the most common cause of morbidity and mortality in type 2 diabetes mellitus. Hyperglycemia, dyslipoproteinemia, arterial hypertension and coagulation abnormalities are the most important cardiovascular risk factors. Hypertriglyceridemia and low high density lipoprotein-cholesterol (HDLc) seem to be related with insulin resistance.

Variant three-way translocation of inversion 16 in AML-M4Eo confirmed by fluorescence in situ hybridization analysis.

The inv(16) and t(16;16) characterize a subgroup of acute myelomonocytic leukemia (AML) with distinct morphological features and a favorable prognosis. Both cytogenetic abnormalities result in a fusion of CBF beta at 16q22 and MYH11 gene at 16p13, whose detection by PCR and fluorescence in situ hybridization (FISH) is useful for diagnosis and monitoring of the disease. Variant translocations of inv(16)/t(16;16) are very rare and whether they are also associated with a favorable prognosis is unknown.