5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer.

Immune checkpoint inhibitors (ICIs) drastically improve therapeutic outcomes for lung cancer, but accurately predicting individual patient responses to ICIs remains a challenge. We performed the genome-wide profiling of 5-hydroxymethylcytosine (5hmC) in 85 plasma cell-free DNA (cfDNA) samples from lung cancer patients and developed a 5hmC signature that was significantly associated with progression-free survival (PFS). We built a 5hmC predictive model to quantify the 5hmC level and validated the model in the validation, test, and control sets.

Cell-Free DNA 5-Hydroxymethylcytosine Signatures for Lung Cancer Prognosis.

Accurate prognostic markers are essential for guiding effective lung cancer treatment strategies. The level of 5-hydroxymethylcytosine (5hmC) in tissue is independently associated with overall survival (OS) in lung cancer patients. We explored the prognostic value of cell-free DNA (cfDNA) 5hmC through genome-wide analysis of 5hmC in plasma samples from 97 lung cancer patients.

Thrombopoietin Receptor Agonists for Thrombocytopenia Secondary to HER2-Targeted Antibody Drug Conjugates.

Trastuzumab emtansine and trastuzumab deruxtecan are widely used in breast cancer and other solid tumor malignancies. Thrombocytopenia is a common adverse event associated with the use of these agents that can lead to a treatment delay, reduction in dose intensity, and discontinuation. The role of thrombopoietin receptor agonists (TPO-RA) remains unknown in this setting.

HER2-targeted antibody-drug conjugates for breast cancer: ancestry and dose adjustment for thrombocytopenia.

Background: Thrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding.

Methods: Subjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021.

Difficulties in Defining Oligometastatic Prostate Cancer: Implications for Clinical Trial Accrual and Community Practice Adoption of Metastasis-Directed Therapy Approaches.

Background: Metastasis-directed therapy is widely utilized for oligometastatic prostate cancer patients, but standard imaging does not always identify metastases definitively and, even with PSMA PET, there may be equivocal findings. Not all clinicians have access to detailed imaging review, particularly outside of academic cancer centers, and PET scan access is also limited. We sought to understand how imaging interpretation impacted recruitment to a clinical trial for oligometastatic prostate cancer.

A Practical Guide to Relugolix: Early Experience With Oral Androgen Deprivation Therapy.

Background: Relugolix is the newest form of androgen deprivation therapy (ADT) approved for prostate cancer. However, as an oral drug, several real-world concerns exist, particularly medication compliance, safety with other androgen receptor-targeted agents, and financial burden to patients.

Methods: A single institution retrospective chart review was conducted evaluating all patients who were prescribed relugolix for any prostate cancer indication from January 1, 2021 to January 31, 2022.

Recurrent small bowel obstruction caused by Burkitt lymphoma in an elderly man: a case report and review of the literature.

Background: Acute small bowel obstruction is a common surgical emergency usually caused by abdominal adhesions, followed by intraluminal tumors from metastatic disease. Although lymphomas have been known to cause bowel obstruction, Burkitt lymphoma is seldom reported to induce an obstruction in the adult population.

Case Presentation: A 78-year-old Hispanic man with a history of abdominal interventions presented to our hospital with abdominal pain.

Pancreatic adenocarcinoma with early esophageal metastasis: A case report and review of literature.

Background: Pancreatic adenocarcinoma is an aggressive malignancy with a high propensity to metastasize. Esophageal metastasis manifesting as dysphagia is rarely reported in the literature and has not to our knowledge been reported prior to the appearance of the primary disease.

Case Summary: A patient presented with progressive dysphagia to solids and a persistent earache.

Hyperprogressive NSCLC With Two Immune-Checkpoint Inhibitors.

Introduction: Immune-checkpoint inhibitors (ICIs) are transforming the modern era of cancer therapy. As new treatment options are becoming available, new patterns of disease behavior are manifesting. One such phenomenon, known as hyperprogressive disease (HPD), is a rare complication resulting in exponential disease progression on exposure to an ICI.

A Case of Histiocytic Sarcoma Arising from Mycosis Fungoides.

Histiocytic sarcoma (HS) is an uncommon malignant neoplasm arising from mature histiocytes and most commonly characterized by the immunophenotypic expression of CD68, CD163, or lysozyme. Although rare, HS arising as a second primary malignancy following hematolymphoid neoplasms has been reported. To our knowledge, this is the first reported case of HS occurring as a second primary malignancy in a patient with mycosis fungoides (MF), with the retained immunophenotype markers CD30 and CD4.

Macrophage Activation Syndrome Secondary to Underlying Sarcoidosis.

Hemophagocytic lymphohistiocytosis (HLH) due to an underlying rheumatologic condition is known as macrophage activation syndrome (MAS), a rare and serious complication that often has a delayed diagnosis. MAS can complicate any rheumatologic disease, although it is most prevalent in systemic juvenile idiopathic arthritis. MAS occurring as a sequela of sarcoidosis is seldom reported.

Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been increasingly widely used in relapsed and refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia [1, 2]. With its use becoming more common, there have been emerging case reports of opportunistic infections like cryptococcal infections [3-8]. These infections in patients receiving ibrutinib were mostly reported in patients with chronic lymphocytic leukaemia, who have poor immune reconstitution.

Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection.

HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells.

The human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL) response is critical in controlling HIV infection. Since the immune response does not eliminate HIV, it would be beneficial to develop ways to enhance the HIV-specific CTL response to allow long-term viral suppression or clearance. Here, we report the use of a protective chimeric antigen receptor (CAR) in a hematopoietic stem/progenitor cell (HSPC)-based approach to engineer HIV immunity.

CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.

Unlabelled: A unique aspect of human monocytes, compared to monocytes from many other species, is that they express the CD4 molecule. However, the role of the CD4 molecule in human monocyte development and function is not known. We determined that the activation of CD4 via interaction with major histocompatibility complex class II (MHC-II) triggers cytokine expression and the differentiation of human monocytes into functional mature macrophages.

Syndromic algorithms for detection of gambiense human African trypanosomiasis in South Sudan.

Background: Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan.

Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

Background: Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen.

Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.

Background: Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease.

Halophilic and halotolerant bacteria from river waters and shallow groundwater along the Rouge River of southeastern Michigan.

The use of sodium chloride to melt highway and road snow is believed to have a significant effect on the groundwater ecosystem of the rivers where the salt from the roads drain. As the river composition changes, the bacterial population also changes to favour those bacteria that are more suited to the higher salt concentrations. In this experiment, we surveyed the cultivable salt-loving organisms (halophiles) on three sites that encompass the Rouge River (Lotz; site 1, Lilly, site; 8, and Ford Field, site 9).

The efficacy of chloroquine for the treatment of acute, uncomplicated, Plasmodium falciparum malaria in Laos.

To assess the local efficacy of chloroquine for the treatment of acute, uncomplicated, Plasmodium falciparum malaria, children and adults from Sekong province (an area of Laos with a low intensity of transmission) were tested in a 28-day, in-vivo study. Complete data were collected from 88 of the 102 subjects enrolled between October 1999 and September 2000. After genotypic analysis to distinguish recrudescing infections from re-infections, 35 (39.

Cell death and neuronal recruitment in the high vocal center of adult male canaries are temporally related to changes in song.

Adult male canaries modify their song every year. Most of these changes occur during late summer and early fall, after the end of the breeding season, and in late winter, immediately before the onset of the next breeding season. The high vocal center (HVC) is an important nucleus in the brain pathway that controls this learned behavior.

Differential staphylococcal protein A-induced enhancement of natural killer cell activity of lymphocytes from HIV-seropositive individuals.

A decrease in Natural Killer (NK) cell activity is a common feature of the immune dysfunction found in patients with HIV-induced acquired immune deficiency syndrome (AIDS). We and others have shown earlier that staphylococcal protein A (SpA) preparations enhance NK cell activity against tumor targets. The present study was aimed at exploring whether the decreased NK activity of lymphocytes from HIV seropositive subjects could be modulated or restored in vitro by SpA.

CD8+ suppressor cells inhibit staphylococcal protein A-induced gamma interferon production by CD4+ lymphocytes.

We have previously demonstrated that purified soluble staphylococcal protein A (SpA) induces the synthesis of gamma interferon (gamma-IFN) by human peripheral blood lymphocytes (PBL), that CD4+ (T helper) cells represent the subpopulation responsible for this synthesis and that prostaglandin E2 (PGE2)-activated CD8+ (T suppressor/cytotoxic) cells have an inhibitory effect on this synthesis. The mechanisms implicated in this regulation remain to be defined, and could involve direct cell-to-cell contact among members of these subpopulations or may be due to a soluble mediator release by CD8+ suppressor cells. In this study, we explored the ability of PGE2 to activate CD8+ cells into either cytotoxic or suppressor cells and the mechanisms by which these cells regulate the SpA-induced gamma-IFN production by CD4+ cells.

Epstein-Barr virus receptor expression on human CD8+ (cytotoxic/suppressor) T lymphocytes.

In 1977 we showed that cells of a human lymphocytic leukaemia-derived T line (Molt-4) have receptors for Epstein-Barr virus (EBV). More recently, EBV-positive human T cell lymphomas have been recognized and human T cell lines containing the EBV genome have been established in vitro. To understand better the interaction of EBV with T cells, we decided to determine first whether human peripheral blood T lymphocytes express receptors for EBV.

Brain space for a learned task.

Forty-six adult male and female canaries were sacrificed, their brains were weighed and the volume of several brain nuclei reconstructed from the cresyl violet-stained material. Two forebrain vocal control nuclei, hyperstriatum ventrale, pars caudale (HVc) and nucleus robustus archistriatalis (RA), were approximately 4 and 3 times larger, respectively, in males than in females, confirming previous findings. There was no consistent right-left asymmetry in the volume of these nuclei in males and females.