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Importance Georgia experienced an increase in maternal mortality (MM) during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which warrants further investigation.Objective This study aimed to assess associations between SARS-CoV-2 infection during pregnancy and MM, post-delivery intensive care unit (ICU) admission, and caesarean section (CS) delivery.Methods We performed a national birth registry-based cohort study including pregnant women who delivered between February 28, 2020 and August 31, 2022. Data was linked with Coronavirus disease (COVID-19) testing, vital, and immunization registries. Pregnant women were classified into three groups: confirmed SARS-CoV-2 infection from conception through 31 days before delivery, confirmed infection in the 30 days before or at delivery, and women negative for SARS-CoV-2 infection or without any test results (reference group). Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs).Results Among 111,278 pregnant women, 16,661 had confirmed infection during pregnancy; 7,304 were fully vaccinated against COVID-19. Compared to the reference group, those with confirmed infection in the 30 days before or at delivery experienced increased odds of MM (aOR: 45.5, 95% CI, 23.1–89.3), post-delivery ICU admission (aOR: 5.62, 95% CI, 4.37–7.22), and CS delivery (aOR: 1.12, 95% CI, 1.03–1.21).Conclusions Hence, pregnant women in Georgia with confirmed SARS-CoV-2 infection in the 30 days before or at delivery conferred an alarmingly higher risk of MM and post-delivery ICU admission. Additionally, results highlight that most women were not vaccinated against COVID-19. These findings should signal to stakeholders that adherence to public health preventive measures needs to be improved.

Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and IL2 injected metastases from patients with melanoma. Lesions that completely regressed following intralesional IL2 harbored increased fractions and densities of nonproliferating CD8+ T cells lacking expression of PD-1, LAG-3, and TIM-3 (PD-1−LAG-3−TIM-3−). Untreated lesions from patients who subsequently responded with complete eradication of all tumor cells in all injected lesions (individuals referred to herein as “extreme responders”) were characterized by proliferating CD8+ T cells with an exhausted phenotype (PD-1+LAG-3+TIM-3+), stromal B-cell aggregates, and expression of IFNγ and IL2 response genes. Loss of membranous MHC class I expression in tumor cells of untreated lesions was associated with resistance to IL2 therapy. We validated this finding in an independent cohort of metastatic melanoma patients treated with intralesional or systemic IL2. Our study suggests that intact tumor-cell antigen presentation is required for melanoma response to IL2 and describes a multidimensional and spatial approach to develop immuno-oncology biomarker hypotheses using routinely collected clinical biospecimens.

Supplementary Data from Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma

The negative consequences of fragmentation, infrastructure development, and urbanization on biodiversity are well known. However, careful urban planning can provide viable habitat for some species and communities. Generally, r-selected species are more likely to persist in urbanizing landscapes, while long lived, mobile species, such as turtles, are likely to decline toward extinction. Understanding species responses across urban gradients is important for developing mitigation planning. We used VHF telemetry to quantify ranging behavior of three-toed box turtles in fragmented urban forest patches and a semi-contiguous large rural forest in Saint Louis, Missouri. We then simulated movement trajectories based on empirical data from the two turtles with the largest and smallest home ranges, overlaid on forest cover and road network maps of Missouri, to quantify the state-wide probability of turtles encountering roads. Home range (HR) size varied from 1–250Ha. The mean home range estimate of rural turtles was > 9 times larger than that of urban turtles. Simulations indicated that the least mobile turtle (HR 1Ha) would have a 22% likelihood of encountering a road if placed randomly in suitable habitat anywhere in the state. The likelihood increased to 90% for the most mobile turtle (HR 250Ha), with 10 road crossings per year. High turtle mortality, range restriction and population fragmentation are likely even in rural areas. In urban cityscapes, large, roadless forest patches offer the highest conservation potential for this species.

Supplementary Data from CpG Oligodeoxynucleotides Alter Lymphocyte and Dendritic Cell Trafficking in Humans

Purpose: CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown.Experimental Design: We conducted a phase I study of CpG-ODN (1018 ISS) given as a vaccine adjuvant with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce T-cell immunity to a peptide vaccine from the tumor-associated antigen hTERT.Results: The adjuvant effect was limited; only 1 of 16 patients showed a high-frequency hTERT-specific tetramer CD8+ T-cell response. However, CpG-ODN induced marked, transient peripheral blood lymphopenia. Biopsies showed dense lymphocytic infiltration at the vaccine site clustered around activated PDC. In vitro, CpG-ODN-treated PDC induced T-cell migration, showing that CpG-ODN stimulation of human PDC was sufficient to chemoattract T cells.Conclusions: Our results show that (a) CpG-ODN with GM-CSF may not be an effective adjuvant strategy for hTERT peptide vaccines but (b) GM-CSF/CpG-ODN causes a PDC-mediated chemokine response that recruits T-cell migration to the peripheral tissues. These findings suggest a novel therapeutic role for targeted injections of CpG-ODN to direct lymphocyte migration to specific sites such as the tumor bed.

Digital papillary adenocarcinoma is a malignant adnexal tumor with a predilection for acral sites. Hidradenoma is a benign solid and cystic sweat gland neoplasm with focal ductal and glandular differentiation and good outcomes. Hidradenomas can occur at acral sites and show papillary structures; for this reason, they are included in the differential diagnosis of digital papillary adenocarcinoma, and immunohistochemistry is a valuable tool in this scenario. We described a case of a 43-year-old man with an epithelial tumor showing papillary structures in the intermediate phalanx of the fourth finger. There was diffuse positivity for p63 and negativity for S100 protein, suggesting that this tumor was an acral hidradenoma with papillary structures.

Herpesviruses are found in free-living and captive chelonian populations, often in association with morbidity and mortality. To date, all known chelonian herpesviruses fall within the subfamily Alphaherpesvirinae. We detected a novel herpesvirus in 3 species of chelonians: a captive leopard tortoise ( Stigmochelys pardalis) in western TX, USA; a steppe tortoise ( Testudo [ Agrionemys] horsfieldii) found near Fort Irwin, CA, USA; and 2 free-living, three-toed box turtles ( Terrapene mexicana triunguis) found in Forest Park, St. Louis, MO. The leopard tortoise was coinfected with the tortoise intranuclear coccidian and had clinical signs of upper respiratory tract disease. The steppe tortoise had mucopurulent nasal discharge and lethargy. One of the three-toed box turtles had no clinical signs; the other was found dead with signs of trauma after being observed with blepharedema, tympanic membrane swelling, cervical edema, and other clinical signs several weeks prior to death. Generally, the branching order of the turtle herpesviruses mirrors the divergence patterns of their hosts, consistent with codivergence. Based on phylogenetic analysis, this novel herpesvirus clusters with a clade of viruses that infect emydid hosts and is likely of box turtle origin. Therefore, we suggest the name terrapene alphaherpesvirus 3 (TerAHV3) for the novel virus. This virus also has the ability to host-jump to tortoises, and previously documented herpesviral morbidity tends to be more common in aberrant hosts. The relationship between clinical signs and infection with TerAHV3 in these animals is unclear, and further investigation is merited.

Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and IL2 injected metastases from patients with melanoma. Lesions that completely regressed following intralesional IL2 harbored increased fractions and densities of nonproliferating CD8+ T cells lacking expression of PD-1, LAG-3, and TIM-3 (PD-1−LAG-3−TIM-3−). Untreated lesions from patients who subsequently responded with complete eradication of all tumor cells in all injected lesions (individuals referred to herein as “extreme responders”) were characterized by proliferating CD8+ T cells with an exhausted phenotype (PD-1+LAG-3+TIM-3+), stromal B-cell aggregates, and expression of IFNγ and IL2 response genes. Loss of membranous MHC class I expression in tumor cells of untreated lesions was associated with resistance to IL2 therapy. We validated this finding in an independent cohort of metastatic melanoma patients treated with intralesional or systemic IL2. Our study suggests that intact tumor-cell antigen presentation is required for melanoma response to IL2 and describes a multidimensional and spatial approach to develop immuno-oncology biomarker hypotheses using routinely collected clinical biospecimens.