Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Birth rates among male cancer survivors and mortality rates among their offspring : a population-based study from Sweden

BACKGROUND: With improvements in treatment of cancer, more men of fertile age are survivors of cancer. This study evaluates trends in birth rates among male cancer survivors and mortality rates of their offspring. METHODS: From the Swedish Multi-generation Register and Cancer Register, we identified 84,752 men ≤70 years with a history of cancer, for which we calculated relative birth rates as compared to the background population(Standardized Birth Ratios, SBRs). We also identified 126,696 offspring of men who had cancer, and compared their risks of death to the background population(Standardized Mortality Ratio, SMRs). Independent factors associated with reduced birth rates and mortality rates were estimated with Poisson modelling. RESULTS: Men with a history of cancer were 23 % less likely to father a child compared to the background population(SBR 0.77, 95 % Confidence Interval[CI] 0.75-0.79). Nulliparous men were significantly more likely to father a child after diagnosis (SBR 0.81, 95 % CI 0.79-0.83) compared to parous men (SBR 0.68, 95 % CI 0.66-0.74). Cancer site(prostate), onset of cancer during childhood or adolescence, parity status at diagnosis(parous), current age(>40 years) and a recent diagnosis were significant and independent predictors of a reduced probability of fathering a child after diagnosis. Of the 126,696 children born to men who have had a diagnosis of cancer, 2604(2.06 %) died during follow up. The overall mortality rate was similar to the background population(SMR of 1.00, 95 %CI 0.96-1.04) and was not affected by the timing of their birth in relation to father's cancer diagnosis. CONCLUSION: Male cancer survivors are less likely to father a child compared to the background population. This is influenced by cancer site, age of onset and parity status at diagnosis. However, their offspring are not at an increased risk of death

Birth rates among male cancer survivors and mortality rates among their offspring : a population-based study from Sweden

BACKGROUND: With improvements in treatment of cancer, more men of fertile age are survivors of cancer. This study evaluates trends in birth rates among male cancer survivors and mortality rates of their offspring. METHODS: From the Swedish Multi-generation Register and Cancer Register, we identified 84,752 men ≤70 years with a history of cancer, for which we calculated relative birth rates as compared to the background population(Standardized Birth Ratios, SBRs). We also identified 126,696 offspring of men who had cancer, and compared their risks of death to the background population(Standardized Mortality Ratio, SMRs). Independent factors associated with reduced birth rates and mortality rates were estimated with Poisson modelling. RESULTS: Men with a history of cancer were 23 % less likely to father a child compared to the background population(SBR 0.77, 95 % Confidence Interval[CI] 0.75-0.79). Nulliparous men were significantly more likely to father a child after diagnosis (SBR 0.81, 95 % CI 0.79-0.83) compared to parous men (SBR 0.68, 95 % CI 0.66-0.74). Cancer site(prostate), onset of cancer during childhood or adolescence, parity status at diagnosis(parous), current age(>40 years) and a recent diagnosis were significant and independent predictors of a reduced probability of fathering a child after diagnosis. Of the 126,696 children born to men who have had a diagnosis of cancer, 2604(2.06 %) died during follow up. The overall mortality rate was similar to the background population(SMR of 1.00, 95 %CI 0.96-1.04) and was not affected by the timing of their birth in relation to father's cancer diagnosis. CONCLUSION: Male cancer survivors are less likely to father a child compared to the background population. This is influenced by cancer site, age of onset and parity status at diagnosis. However, their offspring are not at an increased risk of death

Photoacoustic Tomography Appearance of Fat Necrosis: A First-in-Human Demonstration of Biochemical Signatures along with Histological Correlation

10.3390/diagnostics12102456DIAGNOSTICS121

Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer

10.1007/s10549-021-06470-7BREAST CANCER RESEARCH AND TREATMENT1921131-14

Impact of contrast-enhanced mammography in surgical management of breast cancers for women with dense breasts: a dual-center, multi-disciplinary study in Asia

10.1007/s00330-022-08906-0EUROPEAN RADIOLOGY32128226-823

DNA methylation and breast cancer-associated variants

10.1007/s10549-021-06185-9BREAST CANCER RESEARCH AND TREATMENT1883713-72

Serial Tumor Molecular Profiling of Newly Diagnosed HER2-Negative Breast Cancers During Chemotherapy in Combination with Angiogenesis Inhibitors

10.1007/s11523-022-00886-xTARGETED ONCOLOGY173355-36