Sanctuary Site Research Articles

Examining the Outcomes of Palliative Oophorectomy of Ovarian Metastases in de-Novo Metastatic Colorectal Cancer and Its Association with RAS Mutation Status: Insights from a Single-Institution Perspective.

Ovarian metastasis occurs in 3-5% of patients with CRC. Ovaries are considered sanctuary sites and typically do not respond effectively to chemotherapy. Patients with KRAS mutation generally have a worse prognosis compared to those with KRAS wild type. This study will discuss the effect of palliative oophorectomy on survival rates for those patients compared to chemotherapy alone. This is a retrospective study; we reviewed the charts of patients diagnosed with metastatic colorectal cancer at KHCC between January 2015 and December 2022. Out of 862 patients, 50 patients were eligible for the study; Patients were divided into two groups based on their treatment type, the palliative oophorectomy group and the chemotherapy alone group. The primary endpoint was a three-year median overall survival rate between the two groups. The secondary endpoints included three-year median progression-free survival and the difference in survival rate between the groups based on KRAS and BRAF mutation status. In the oophorectomy group, the median overall survival (OS) was 19.3 months compared to 10.3 months in the chemotherapy alone group, with a P value of 0.05. Median progression-free survival (PFS) was also better in the oophorectomy group at 14.6 months compared to 9.4 months, with a P value of 0.59. For patients with KRAS mutation who underwent oophorectomy, the median OS was significantly better at 29.1 months compared to 10.3 months in the chemotherapy alone group, P value of 0.03. Our study indicates that palliative oophorectomy in metastatic CRC is associated with better survival. Even patients who harbor mutated KRAS, which typically have more aggressive disease behavior, showed better survival outcomes with oophorectomy compared to systemic chemotherapy alone.

The Black Continental African Soccer Club as a diasporic resource: (Not) playing to the whistle in men's recreational soccer

This study explores the centrality of the Black Continental African Soccer Club (BCASC) as a “diasporic resource” for members of the new African diaspora who play in an over-35 men's recreational soccer league in a Western Canadian city. Drawing from a multiyear ethnography, we critically examine how the BCASC serves as a crucial Black sporting institution for its members to collectively navigate anti-Black racism and the set of limits and pressures that come with being typecast as model minorities—the dominant representational figure for multiculturalism in the Canadian political economy—as they aspire to be, and live, as their fully fledged, and culturally authentic Black selves. Like other historic Black and ethnic sporting institutions, the BCASC and its related practices of fraternal sociality and solidarity serve as identity-affirming and redemptive, sanctuary sites where team members confront dominant and exclusionary forms of whiteness and its subordinating customs, all while palliating “homing desire” through nostalgic expressions of home.

Chlormethine Gel for Treatment of Patients with Mycosis Fungoides: Best Practices and Guidance to Clinicians.

Mycosis fungoides (MF) is the most common form of cutaneous Tcell lymphoma. While multiple guidelines provide treatment recommendations, there are currently no clear treatment algorithms for MF. Chlormethine gel is recommended by major treatment guidelines as a first-line option for stageIA-IIA disease, and, on the basis of these guidelines, used in combination with other therapies in patients with advanced-stage MF in clinical practice. To provide guidance regarding the use of chlormethine gel for patients with all stages of MF, based on clinical expertise. Opinions on best practices regarding the use of chlormethine gel were collected through discussions that involved eight clinicians with extensive experience in treating patients with MF. Chlormethine gel can be used as monotherapy in first- or second-line treatment of early-stage MF. In first-line, chlormethine gel monotherapy is prescribed for stageIA MF, and is particularly convenient for patients unable/unwilling to travel for hospital-based phototherapy, patients with thick plaques or palmoplantar involvement, when ultraviolet treatment is contraindicated, and for sanctuary sites. Chlormethine gel is also an appropriate first-line monotherapy for patients with stageIB or IIA MF; it may be used as part of combination regimens in these patients as well. For patients with late-stage MF, skin-directed treatments such as chlormethine gel should be combined with systemic therapies. Chlormethine gel is a safe and effective treatment option that can be used in all stages of MF, either as monotherapy or in combination, depending on disease stage and patient characteristics and needs.

Excellent Outcome of Myeloablative TBI-Based Allogeneic Stem Cell Transplant in Adult Patients with Acute Lymphocytic Leukemia in MRD Negative CR1: Results from a Retrospective Canadian Cohort

Excellent Outcome of Myeloablative TBI-Based Allogeneic Stem Cell Transplant in Adult Patients with Acute Lymphocytic Leukemia in MRD Negative CR1: Results from a Retrospective Canadian Cohort

Improved Automated Radiosynthesis of [18F]Dolutegravir: Toward Clinical Applications.

Positron emission tomography imaging using radiolabeled dolutegravir (DTG) is an interesting approach to understand the biodistribution of this antiretroviral drug at HIV-1 sanctuary sites. In the course of clinical translation, we depict herein an improved and pharmaceutically compliant radiosynthesis of [18F]DTG from an original tin precursor. The radiosynthesis was achieved in two steps by copper-mediated radiofluorination, followed by enol ether deprotection using a kit-based AllInOne module. Ready-to-inject [18F]DTG was obtained in 20 ± 5% (n = 12) decay-corrected radiochemical yield within 90 min, representing a 4-fold increase compared to the previously published three-step radiosynthesis. Quality control was carried out with three consecutive [18F]DTG productions according to the current European Pharmacopoeia guidelines, which include pH determination, identity and purity (chemical, radiochemical, and radionuclide) assessments, residual solvent quantification, dosage of lithium, copper, and tin traces, sterility and bacterial endotoxin tests. [18F]DTG (∼2 GBq) was obtained with a molar activity of 59 ± 2 GBq/μmol at the time of injection and was suitable for human applications.

Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study

Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study

DIVERSITY AND ABUNDANCE OF CORAL REEF FISHES, GIVING EMPHASIS ON THE LARGE PREDATORS AT CHAGAR HUTANG BAY, REDANG ISLAND

The Chagar Hutang Bay, located on Pulau Redang, Terengganu, serves as a critical nesting site for green sea turtles (Chelonia mydas). Despite its ecological significance, there remains a paucity of information regarding the diversity and abundance of coral reef fishes, particularly large predatory species, within the sanctuary site. To address this knowledge gap, the present study employed baited remote underwater video (BRUV) surveys to assess the fish assemblages across different reef zones, namely the shoreline, mid-reef, and fore-reef areas. A comprehensive analysis of nine one-hour BRUV surveys revealed a remarkable diversity of coral reef fishes, identifying 55 distinct species from 43 genera and 18 families. The fore-reef zone exhibited significantly higher fish density compared to other surveyed areas, underscoring its importance as a key habitat within the bay. Notably, large predatory fish species comprised 4.7% of the total fish abundance, with four predatory groups, including trevallies, groupers, blacktip reef sharks (Carcharhinus melanopterus) and barracudas, documented in Chagar Hutang Bay. Among these predators, the blacktip reef shark and the groupers emerged as the dominant species. This study provides valuable insights into the coral reef fish diversity and abundance in Chagar Hutang Bay, highlighting the presence of key predatory species and emphasizing the need for targeted conservation efforts to protect this ecologically significant marine habitat.

Viral-Host Interactions and Immune Responses in HIV-Infected Infants: A Review

Human Immunodeficiency Virus (HIV) infection in infants presents distinctive challenges due to their developing immune systems and unique viral-host interactions compared to adults. This review examines current knowledge on viral-host interactions and immune responses in HIV-infected infants, focusing on immune development, viral dynamics, and therapeutic implications. The immune system of infants undergoes rapid maturation during early life, influencing their susceptibility to HIV infection and responses to antiretroviral therapy (ART). Key aspects include thymic function, cytokine profiles, and the establishment of immune memory, which collectively shape immune responses against HIV. Viral dynamics in HIV-infected infants differ markedly from those in adults, characterized by high viral loads, diverse viral subtypes, and the early establishment of viral reservoirs within immune cells. These reservoirs, particularly in sanctuary sites like the central nervous system, pose challenges for achieving viral eradication and long-term remission. Effective management requires strategies to characterize and target these reservoirs, alongside early intervention to mitigate viral replication and preserve immune function. Advances in viral monitoring technologies and treatment regimens are essential for improving clinical outcomes and reducing the global burden of pediatric HIV infection. Keywords: HIV, infants, viral-host interactions, immune responses, immune development, viral dynamics, therapeutic interventions

Discovery of a Double-Stapled Short Peptide as a Long-Acting HIV-1 Inactivator with Potential for Oral Bioavailability.

Different from most antiretroviral drugs that act as passive defenders to inhibit HIV-1 replication inside the host cell, virus inactivators can attack and inactivate HIV-1 virions without relying on their replication cycle. Herein, we describe the discovery of a hydrocarbon double-stapled helix peptide, termed D26. D26 is based on the HIV-1 gp41 protein lentiviral lytic peptide-3 motif (LLP3) sequence, which can efficiently inhibit HIV-1 infection and inactivate cell-free HIV-1 virions. It was noted that D26 was highly resistant to proteolytic degradation and exhibited a remarkably extended in vivo elimination half-life. Additionally, relative to its linear, nonstapled version, D26 exhibited much higher exposure in sanctuary sites for HIV-1. Amazingly, this lead compound also demonstrated detectable oral absorption. Thus, it can be concluded that D26 is a promising candidate for further development as a long-acting, orally applicable HIV-1 inactivator for the treatment of HIV-1 infection.

Can artificially induced habitat complexity alter macroinvertebrates diversity? A case study from a freshwater wetland ecosystem

Habitat complexity can enhance the resilience of wetlands against environmental stressors such as extreme weather events, pollution, and habitat loss. The introduction of artificial induced complexity (AIC) can play a significant role in reshaping the macroinvertebrate communities within wetland ecosystems by enhancing habitat quality in protected areas. Therefore, this study was designed to examine the variation of macroinvertebrates community structure in artificially induced complex sanctuary site (SS), partially protected (PP) and open sites (OS) from July 2019-April 2020. AIC in the sanctuary sites was established through the installation of cemented hexapods and ring pipes. Over the study period, a total of 665 macroinvertebrates were gathered, with 55.55% originating from SS, 31.14% from PP, and 18.21% from OS sites. The community consists mainly of Lymnaea acuminatatea and Tubifex tubifex, with the most abundant species being Limnodrillus hoffmeisteri and Branchiura sowerbyi. A notable positive impact of AIC was evident in the increased total abundance and diversity indices of macroinvertebrate communities. The Analysis of Similarity (ANOSIM) revealed significant distinctions in community structures among various intervention types, which was further corroborated by a non-metric multidimensional scaling (nMDS) plot. Similarity of Percentage Analysis (SIMPER) highlighted that Limnodrillus hoffmeisteri made the most significant contribution to the dissimilarity observed among the different intervention types. Canonical Correspondence Analysis (CCA) revealed a close association between the structure of the macroinvertebrate community and three key ecological factors: periphyton biomass, macrophyte cover, and sediment properties. These findings could offer a more effective approach for managers and policymakers engaged in the conservation of macroinvertebrates and the sustainable management of fisheries resources within wetland ecosystems.

Introducing the Concept of Sanctuary Sites in Ischemic Stroke.

The topography of arterial territories has been defined using digital maps of supratentorial infarcts. Regions with a high probability of infarction (Pi) exist in the deep compartment due to a paucity of collaterals. However, less attention has been given to regions with a low Pi. Using published digital maps, patients with cortical stroke and documented vessel occlusion were included. Infarcts from T2-weighted magnetic resonance images were segmented and registered onto a standard brain template (Montreal Neurological Institute 152). Segmented magnetic resonance images were averaged to yield the Pi at a voxel level. The overall Pi for the combined arterial territories was calculated to ensure that Pi was in the range of 0 to 1. Sanctuary sites were identified as regions with Pi <0.1. There were 154 patients (63% men; median age, 69 years; and interquartile range, 57-78 years). The magnetic resonance imaging scan used for segmentation was performed at a median interval of 35 (interquartile range, 3-66) days after stroke onset. Sanctuary sites were present in the frontal (gyrus rectus, the paracentral lobule, and orbitofrontal and precentral gyrus), parietal (postcentral, supramarginal, and angular gyrus, superior and inferior parietal lobule, and precuneus and posterior cingulate), and occipital cortex (cuneus, middle, and superior occipital gyrus). We propose that following vessel occlusion, there are cortical regions with a low Pi, which we termed sanctuary sites. The anatomic basis for this observation is the compensatory capacity of leptomeningeal collaterals.

Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model

BackgroundNanoparticle-based drugs are new inventions in the management of the Human immunodeficiency virus (HIV) pandemic, especially resistant forms of the virus in anatomical sanctuary sites and organs such as the testis. However, safety issues must be resolved to attain the optimal potential of newer nano-drug formulations.AimThe study investigated the toxicological potential of synthesized Tenofovir Nanoparticles (TDF-N) on testicular indices when used for the prevention and treatment of HIV.MethodologyFifteen male Sprague–Dawley (SD) rats with weight ranging from 230 g to 250 g were randomly assigned into groups A (control, saline), B (TDF), and C (TDF-N). The testes were removed for sperm analysis and processed for H/E and PAS stains. Cell counts and cellular measurements; the diameter and the area of the testicular seminiferous tubules were measured using ImageJ and Leica software 2.0.ResultsA significant reduction (p < 0.05) in sperm count was noticed in the TDF-N group. Also observed in the TDF and TDF-N groups was a significant reduction (p < 0.05) in sperm motility and in the number of dead sperms compared with the control. Sperm abnormalities such as distorted basement membranes, loss of germ cells, hypocellular interstitium, and loss of spermatogenic series were increased in the TDF and TDF-N groups. There was also a significant reduction (p < 0.05) in the cell count, diameter, and area of seminiferous tubules observed in these groups.ConclusionTDF and TDF-N may be detrimental to the testis and testicular tissue, leading to significantly reduced sperm counts, motility, and ultimately–male fertility.

Whether the Corona Virus Has Completely Left the Human Body or Remains in the Body and Causes Other Viral Diseases

Whole viruses, also called virions, comprise either RNA or DNA surrounded by a protein coat. Those that persist in sanctuary sites can continue gradually infecting the cells around them. There they hijack the host cell(s) to make copies of themselves. RNA viruses such as hepatitis C virus5 and HIV6 can evade immune control and can continuously produce infectious virions throughout a patient’s life.

Motion Management: The Road Map to Accurate Radiation Treatment Delivery

Radiation therapy is a key contributor to positive outcomes in hematological malignancies. However, this is contingent on minimizing the exposure of critical normal organs. The introduction of computed tomography (CT) for radiation treatment planning and the development of sophisticated dose calculation algorithms has transformed the radiation therapy field and made it possible to transition from conventional involved-field radiation to modern involved-site radiation therapy. Thanks to rapid advances in drug discovery, treatment strategies for many hematological malignancies have evolved to incorporate targeted and cellular therapies, in some cases even allowing the replacement of chemotherapy. As a result, new opportunities have been created for radiation to address relapses after more lines of therapy, identify disease-involving sanctuary sites, and bridge to the subsequent therapy. When considering radiation in patients receiving novel therapies, who may also be more heavily pretreated, respecting the critical and normal structures at all costs is imperative. In this document, we will describe modern techniques used to deliver state-of-the-art radiation therapy and practical considerations to ensure the accurate treatment of the target while avoiding normal organs at risk.

Ongoing HIV replication in lymph node sanctuary sites in treated individuals contributes to the total latent HIV at a very slow rate

Ongoing HIV replication in lymph node sanctuary sites in treated individuals contributes to the total latent HIV at a very slow rate

Total marrow lymphoid irradiation IMRT treatment using a novel CT-linac

BackgroundA novel CT-linac (kilovolt fan-beam CT-linac) has been introduced into total marrow and lymphoid irradiation (TMLI) treatment. Its integrated kilovolt fan-beam CT (kV FBCT) can be used not only for image guidance (IGRT) but also to re-calculate the dose.PurposeThis study reported our clinical routine on performing TMIL treatment on the CT-linac, as well as dose distribution comparison between planned and re-calculated based on IGRT FBCT image sets.Methods11 sets of data from 5 male and 6 female patients who had underwent the TMLI treatment with uRT-linac 506c were selected for this study. The planning target volumes consist of all skeletal bones exclusion of the mandible and lymphatic sanctuary sites. A planned dose of 10 Gy was prescribed to all skeletal bones exclusion of the mandible in two fractions and 12 Gy in two fractions was prescribed to lymphatic sanctuary sites. Each TMLI plan contained two sub-plans, one dynamic IMRT for the upper body and the other VMAT for the lower extremity. Two attempts were made to obtain homogeneous dose in the overlapping region, i.e., applying two plans with different isocenters for the treatment of two fractions, and using a dose gradient matching scheme. The CT scans, including planning CT and IGRT FBCT, were stitched to a whole body CT scan for dose distribution evaluation.ResultsThe average beam-on time of Planupper is 30.6 min, ranging from 24.9 to 37.5 min, and the average beam-on time of Planlower is 6.3 min, ranging from 5.7 to 8.2 min. For the planned dose distribution, the 94.79% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 94.68% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). For the re-calculated dose distribution, the 92.17% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 90.07% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). The results showed that there is a significant difference (p < 0.05) between planning V10, V12 and delivery V10, V12. There is no significant difference (p > 0.05) between planned dose and re-calculated dose on selected organs, except for right lens (p < 0.05, Dmax). The actual delivered maximum dose of right lens is apparently larger than the planned dose of it.ConclusionTMLI treatment can be performed on the CT-linac with clinical acceptable quality and high efficiency. Evaluation of the recalculated dose on IGRT FBCT suggests the treatment was delivered with adequate target coverage.

Vanishing splendor: a comprehensive review of the decline in the original fish fauna of Lake Victoria

The presence of the non-native Nile perch (Lates niloticus) in Lake Victoria and the resulting ecological transformations have garnered significant attention from the scientific community. However, details regarding the timing, origin, and purpose of the fish introduction have remained elusive. This paper reviews fish fauna changes in Lake Victoria, investigates causes, and advocates for biodiversity conservation through diversity and sanctuary sites. It examines different historical periods to understand changes and guide effective conservation strategies. The introduction of Nile perch has led to a substantial decline and even extinction of many native fish species, particularly cichlids, resulting in ecological imbalances and economic challenges for local fishing communities. To address these pressing issues, ongoing conservation efforts are being implemented. These initiatives focus on promoting sustainable fishing practices, safeguarding critical habitats, and reintroducing native fish species. Furthermore, cage fish farming is being explored as a potential solution to alleviate pressure on wild populations, as suggested by various authors. Recommendations stemming from this study include conducting virtual population analysis for stock assessments of indigenous species, intensify conservation efforts, diversify fishing practices, expand cage fish farming, increase public awareness and education, and enhance policy and governance frameworks. By implementing these recommendations, there is optimism for the recovery and resilience of indigenous fish species in Lake Victoria, leading to the conservation of biodiversity and the promotion of sustainable livelihoods for local communities.

Children's Oncology Group blueprint for research: Acute lymphoblastic leukemia.

Cure rates for acute lymphoblastic leukemia (ALL), the most common childhood cancer have steadily improved over the past five decades. This is due to intensifying systemic therapy, recognizing and treating the central nervous system as a sanctuary site, and implementing modern risk stratification to deliver varying intensities of therapy based on age, presenting white blood count, sentinel somatic genetics, and therapy response. Recently, numerous Children's Oncology Group trials have demonstrated the lack of benefit of intensifying traditional chemotherapy, providing evidence that new approaches are needed to cure the patients for whom cure has been elusive. Distinguishing those who require intensive or novel therapeutic approaches from others who will be cured with minimal therapy is key for future trials. Incorporating new genomic biomarkers and more sensitive measures of minimal/measurable residual disease provide opportunities to achieve these goals.

Population dynamics of immunological synapse formation induced by bispecific T cell engagers predict clinical pharmacodynamics and treatment resistance.

Effector T cells need to form immunological synapses (IS) with recognized target cells to elicit cytolytic effects. Facilitating IS formation is the principal pharmacological action of most T cell-based cancer immunotherapies. However, the dynamics of IS formation at the cell population level, the primary driver of the pharmacodynamics of many cancer immunotherapies, remains poorly defined. Using classic immunotherapy CD3/CD19 bispecific T cell engager (BiTE) as our model system, we integrate experimental and theoretical approaches to investigate the population dynamics of IS formation and their relevance to clinical pharmacodynamics and treatment resistance. Our models produce experimentally consistent predictions when defining IS formation as a series of spatiotemporally coordinated events driven by molecular and cellular interactions. The models predict tumor-killing pharmacodynamics in patients and reveal trajectories of tumor evolution across anatomical sites under BiTE immunotherapy. Our models highlight the bone marrow as a potential sanctuary site permitting tumor evolution and antigen escape. The models also suggest that optimal dosing regimens are a function of tumor growth, CD19 expression, and patient T cell abundance, which confer adequate tumor control with reduced disease evolution. This work has implications for developing more effective T cell-based cancer immunotherapies.

Primary testicular lymphoma demonstrates overexpression of the Wilms tumor 1 gene and different mRNA and miRNA expression profiles compared to nodal diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) shows a high degree of clinical and biological heterogeneity. Primary testicular lymphoma (PTL) is an extranodal variant of DLBCL associated with a higher risk of recurrence, including contralateral testicles and central nervous system sanctuary sites. Several molecular aberrations, including somatic mutation of MYD88, CD79B, and upregulation of NF-kB, PDL-1, and PDL-2, are thought to contribute to the pathogenesis and poor prognosis of PTL. However, additional biomarkers are needed that may improve the prognosis and help understand the PTL biology and lead to new therapeutic targets. RNA from diagnostic tissue biopsies of the PTL-ABC subtype and matched nodal DLBCL-ABC subtype patients was evaluated by mRNA and miRNA expression. Screening of 730 essential oncogenic genes was performed, and their epigenetic connections were examined using the nCounter PAN-cancer pathway, and Human miRNA assays with the nCounter System (NanoString Technologies). PTL and nodal DLBCL patients were comparable in age, gender, and putative cell of origin (p>0.05). Wilms tumor 1 (WT1) expression in PTL exceeded that in nodal DLBCL (>6-fold; p=0.01, FDR <0.01) and WT1 associated pathway genes THBS4, PTPN5, PLA2G2A, and IFNA17 were upregulated in PTL (>2.0-fold, p<0.01, FDR <0.01). Additionally, miRNAs targeting WT1 (hsa15a-5p, hsa-miR-16-5p, has-miR-361-5p, has-miR-27b-3p, has-miR-199a-5p, has-miR-199b-5p, has-miR-132-3p, and hsa-miR-128-3p) showed higher expression in PTL compared to nodal DLBCL (≥2.0-fold; FDR 0.01). Lower expression of BMP7, LAMB3, GAS1, MMP7, and LAMC2 (>2.0-fold, p<0.01) was observed in PTL compared to nodal DLBCL. This research revealed higher WT1 expression in PTL relative to nodal DLBCL, suggesting that a specific miRNA subset may target WT1 expression and impact the PI3k/Akt pathway in PTL. Further investigation is needed to explore WT1's biological role in PTL and its potential as a therapeutic target.