human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Summary Previous studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia .  Vaccination histories were compared in 439 children ( ages 0–14 ) diagnosed with acute lymphoblastic leukaemia ( ALL ) in nine Midwestern and Mid-Atlantic states ( USA ) between 1 January 1989 and 30 June 1993 and 439 controls selected by r and om-digit dialing and individually matched to cases on age , race and telephone exchange . Among matched pairs , similar proportions of cases and controls had received at least one dose of oral poliovirus ( 98 % ) , diphtheria – tetanus – pertussis ( 97 % ) , and measles – mumps – rubella ( 90 % ) vaccines . Only 47 % of cases and 53 % of controls had received any  Haemophilus influenzae type b ( Hib ) vaccine  ( relative risk ( RR ) = 0.73 ; 95 % confidence interval ( CI ) 0.50–1.06 ) . Although similar proportions of cases ( 12 % ) and controls ( 11 % ) received the polysaccharide Hib vaccine ( RR = 1.13 ; 95 % CI 0.64–1.98 ) , more controls ( 41 % ) than cases ( 35 % ) received the conjugate Hib vaccine ( RR = 0.57 ; 95 % CI 0.36–0.89 ) . Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL , our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia . Further studies are needed to confirm this association and , if confirmed , to eluci date the underlying mechanism The st and ard of care for most patients with non-muscle-invasive bladder cancer ( NMIBC ) is immunotherapy with intravesical Bacillus Calmette-Guérin ( BCG ) , which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit . Urologic best- practice guidelines and consensus reports have been developed and strengthened based on data on the timing , dose , and duration of therapy from r and omized clinical trials , as well as by critical evaluation of criteria for progression . However , these reports have not penetrated the community , and many patients do not receive appropriate therapy . Additionally , several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease . The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of exp and ed use for both advanced and , potentially , localized disease . To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer , the Society for Immunotherapy of Cancer ( SITC ) convened a Task Force of experts , including physicians , patient advocates , and nurses , to address issues related to patient selection , toxicity management , clinical endpoints , as well as the combination and sequencing of therapies . Following the st and ard approach established by the Society for other cancers , a systematic literature review and analysis of data , combined with consensus voting was used to generate guidelines . Here , we provide a consensus statement for the use of immunotherapy in patients with bladder cancer , with plans to up date these recommendations as the field progresses The potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study . A total of 162 patients ( 0 - 14 years old ) with newly diagnosed leukemia were rapidly ascertained during 1995 - 1999 , and 162 matched control subjects were r and omly selected from the birth registry . The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [ odds ratio ( OR ) = 2.8 ; 95 % confidence interval ( CI ) , 1.4 - 5.7 ] , and the exposure during year 2 was associated with the highest risk ( OR = 3.6 ; 95 % CI , 1.6 - 8.3 ) . The ORs for exposure to insecticides during the 3 months before pregnancy , pregnancy , and years 1 , 2 , and 3 were 1.8 ( 95 % CI , 1.1 - 3.1 ) , 2.1 ( 95 % CI , 1.3 - 3.5 ) , 1.7 ( 95 % CI , 1.0 - 2.9 ) , 1.6 ( 95 % CI , 1.0 - 2.7 ) , and 1.2 ( 95 % CI , 0.7 - 2.1 ) , respectively . Insecticide exposures early in life appear to be more significant than later exposures , and the highest risk was observed for exposure during pregnancy . Additionally , more frequent exposure to insecticides was associated with a higher risk . In contrast to insecticides , the association between herbicides and leukemia was weak and nonsignificant . Pesticides were also grouped based on where they were applied . Exposure to indoor pesticides was associated with an increased risk , whereas no significant association was observed for exposure to outdoor pesticides . The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure ABSTRACT Acellular vaccines against diphtheria-tetanus-pertussis ( acellular pertussis ) ( DTaP ) are being progressively introduced into vaccination programs worldwide , with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis ( whole-cell pertussis ) ( DTwP ) vaccine . The DTaP vaccine has an improved safety profile in infants , but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses . We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP ( n = 30 ) or DTwP ( n = 16 ) and by correlating these parameters , in particular cytokine responses , with expression of local side effects at the injection site . Large local reactions ( ≥50-mm diameter ) 24 to 72 h after receiving the DTaP booster occurred in 43 % of exclusively DTaP-primed children , in contrast to 6 % of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 ( IL-5 ) , IL-6 , and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically “ high Th2 responders ” as detected by in vitro responsiveness to polyclonal mitogen . Our findings suggest that priming during infancy with DTaP  promotes stable , boostable Th2-polarized immunity against vaccine antigens , which in a significant subset of children is subsequently associated with local reactions at the booster site . The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory We have recently shown that BCG ( Bacillus Calmette-Guérin ) vaccination  in healthy volunteers induces epigenetic reprogramming of monocytes , leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination . This phenomenon was named ‘ trained immunity ' . In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 ( Th1 ) and Th17 immune responses 1 year after vaccination . The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination , but these effects were less pronounced 1 year after vaccination . However , monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14 , Toll-like receptor 4 ( TLR4 ) and mannose receptor , and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 lig and lipopolysaccharide . The heterologous production of Th1 ( IFN-γ ) and Th17 ( IL-17 and IL-22 ) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination . In conclusion , BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses A series of 972 childhood malignancies was compared with a control series of healthy children matched for date and place of birth . Several variables were tested for possible aetiological significance . The information was obtained from the Finnish Cancer Registry and from the antenatal records of the mothers . No significant associations were found between the various types of malignancies and the variables studied . In the group consisting of all malignancies , a risk ratio of 2.0 could be significantly excluded for most variables . In the leukaemia group , both pelvic X‐ray and polio vaccination were associated with slightly elevated risk ratios , but the differences between this group and the matched controls were not statistically significant . BCG vaccination was performed during the perinatal period in 90 % of the children , but the proportion was the same in the study and control groups , and hence the hypothesis that this vaccination confers protection was not supported . The information is considered prospect i ve and relatively reliable , and the authors suggest that these data may be useful when more extensive series are compiled from various sources From 1949 to 1951 , a controlled trial of BCG vaccinations was conducted in Puerto Rico . The 191,827 children , 1 - 18 years of age , initially enrolled in the study were skin-tested with tuberculin to determine their eligibility for vaccination . A total of 82,269 children were classified as reactors and not vaccinated . Of the 109 , 558 nonreactors , 31,586 refused vaccination  , 50,634 were vaccinated with BCG  , and 27,338 were left unvaccinated as controls . We ascertained the incidence of cancer over an average follow-up period of 23.3 years in the latter two groups using the Puerto Rico Central Cancer Registry . By the end of December 1973 , a total of 77 cancers had been diagnosed among the controls and 150 among the vaccinees . The overall incidence of cancer among the two groups was similar . Although a number of differences existed between the vaccinee group and the controls in regard to the incidence of cancer at various " sites " , none of these differences was statistically significant . However , when cases of lymphosarcoma and Hodgkin 's disease were combined for analysis , a statistically significant excess of cases occurred among the vaccinees . We concluded that BCG vaccination had no protective effect on the subsequent development of cancer in this population . The slight excess of cases of lymphosarcoma and Hodgkin 's disease among the vaccinees raised the possibility that BCG may have had an adverse effect Objective . We report our experience with routine immunization of 89 premature infants in the neonatal intensive care unit because 1 ) a substantial number of them developed abnormal clinical signs , and 2 ) all but one of those who received diphtheria , tetanus , and whole-cell pertussis ( DTwP ) vaccine  responded with elevations of interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) concentrations that are otherwise characteristic of bacterial disease . Methodology . We hypothesized that the elevated IL-6 and CRP levels were solely a response to immunization and that treatment with antibiotics was not necessary . We performed this study in two consecutive parts . In part 1 , we prospect ively evaluated 79 consecutive premature infants who were immunized with DTwP , Haemophilusb conjugate vaccine , hepatitis B vaccine , and inactivated polio vaccine , ( Hib , HBV , and IPV ) .  IL-6 and CRP were determined before immunization and every 12 hours on three occasions after immunization . In part 2 , we studied an additional 10 infants who received acellular pertussis vaccine ( DTaP ) and who , 2 days later ,  received Hib , HBV , and IPV immunization simultaneously .  We followed the same schedule of IL-6 and CRP determinations as in part 1 . Results . In part 1 , 24 infants ( 30 % ) developed abnormal cardiorespiratory signs within 24 hours after immunization . CRP and IL-6 values rose to abnormal levels after immunization in all but one infant ; that infant was later shown to have a T-cell abnormality . In part 2 , 3 infants had abnormal cardiorespiratory signs after simultaneous immunization with Hib , HBV , and IPV , but not after DTaP. IL-6 and CRP levels remained normal in all 10 infants . Conclusions . Part 1 demonstrates clearly the temporal relationship between IL-6 and CRP increments after DTwP , Hib , HBV , and IPV vaccines . In part 2 ( DTaP was substituted for DTwP ) , there were no elevations of IL-6 or CRP , thus indicating that whole-cell pertussis component of DTwP was responsible for IL-6 and CRP elevations . Abnormal cardiorespiratory signs occurred frequently after immunizations in part 1 , but they were unrelated to the magnitude of IL-6 and CRP elevations . 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Summary Previous studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia .  Vaccination histories were compared in 439 children ( ages 0–14 ) diagnosed with acute lymphoblastic leukaemia ( ALL ) in nine Midwestern and Mid-Atlantic states ( USA ) between 1 January 1989 and 30 June 1993 and 439 controls selected by r and om-digit dialing and individually matched to cases on age , race and telephone exchange . Among matched pairs , similar proportions of cases and controls had received at least one dose of oral poliovirus ( 98 % ) , diphtheria – tetanus – pertussis ( 97 % ) , and measles – mumps – rubella ( 90 % ) vaccines . Only 47 % of cases and 53 % of controls had received any  Haemophilus influenzae type b ( Hib ) vaccine  ( relative risk ( RR ) = 0.73 ; 95 % confidence interval ( CI ) 0.50–1.06 ) . Although similar proportions of cases ( 12 % ) and controls ( 11 % ) received the polysaccharide Hib vaccine ( RR = 1.13 ; 95 % CI 0.64–1.98 ) , more controls ( 41 % ) than cases ( 35 % ) received the conjugate Hib vaccine ( RR = 0.57 ; 95 % CI 0.36–0.89 ) . Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL , our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia . Further studies are needed to confirm this association and , if confirmed , to eluci date the underlying mechanism The st and ard of care for most patients with non-muscle-invasive bladder cancer ( NMIBC ) is immunotherapy with intravesical Bacillus Calmette-Guérin ( BCG ) , which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit . Urologic best- practice guidelines and consensus reports have been developed and strengthened based on data on the timing , dose , and duration of therapy from r and omized clinical trials , as well as by critical evaluation of criteria for progression . However , these reports have not penetrated the community , and many patients do not receive appropriate therapy . Additionally , several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease . The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of exp and ed use for both advanced and , potentially , localized disease . To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer , the Society for Immunotherapy of Cancer ( SITC ) convened a Task Force of experts , including physicians , patient advocates , and nurses , to address issues related to patient selection , toxicity management , clinical endpoints , as well as the combination and sequencing of therapies . Following the st and ard approach established by the Society for other cancers , a systematic literature review and analysis of data , combined with consensus voting was used to generate guidelines . Here , we provide a consensus statement for the use of immunotherapy in patients with bladder cancer , with plans to up date these recommendations as the field progresses The potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study . A total of 162 patients ( 0 - 14 years old ) with newly diagnosed leukemia were rapidly ascertained during 1995 - 1999 , and 162 matched control subjects were r and omly selected from the birth registry . The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [ odds ratio ( OR ) = 2.8 ; 95 % confidence interval ( CI ) , 1.4 - 5.7 ] , and the exposure during year 2 was associated with the highest risk ( OR = 3.6 ; 95 % CI , 1.6 - 8.3 ) . The ORs for exposure to insecticides during the 3 months before pregnancy , pregnancy , and years 1 , 2 , and 3 were 1.8 ( 95 % CI , 1.1 - 3.1 ) , 2.1 ( 95 % CI , 1.3 - 3.5 ) , 1.7 ( 95 % CI , 1.0 - 2.9 ) , 1.6 ( 95 % CI , 1.0 - 2.7 ) , and 1.2 ( 95 % CI , 0.7 - 2.1 ) , respectively . Insecticide exposures early in life appear to be more significant than later exposures , and the highest risk was observed for exposure during pregnancy . Additionally , more frequent exposure to insecticides was associated with a higher risk . In contrast to insecticides , the association between herbicides and leukemia was weak and nonsignificant . Pesticides were also grouped based on where they were applied . Exposure to indoor pesticides was associated with an increased risk , whereas no significant association was observed for exposure to outdoor pesticides . The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure ABSTRACT Acellular vaccines against diphtheria-tetanus-pertussis ( acellular pertussis ) ( DTaP ) are being progressively introduced into vaccination programs worldwide , with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis ( whole-cell pertussis ) ( DTwP ) vaccine . The DTaP vaccine has an improved safety profile in infants , but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses . We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP ( n = 30 ) or DTwP ( n = 16 ) and by correlating these parameters , in particular cytokine responses , with expression of local side effects at the injection site . Large local reactions ( ≥50-mm diameter ) 24 to 72 h after receiving the DTaP booster occurred in 43 % of exclusively DTaP-primed children , in contrast to 6 % of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 ( IL-5 ) , IL-6 , and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically “ high Th2 responders ” as detected by in vitro responsiveness to polyclonal mitogen . Our findings suggest that priming during infancy with DTaP  promotes stable , boostable Th2-polarized immunity against vaccine antigens , which in a significant subset of children is subsequently associated with local reactions at the booster site . The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory We have recently shown that BCG ( Bacillus Calmette-Guérin ) vaccination  in healthy volunteers induces epigenetic reprogramming of monocytes , leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination . This phenomenon was named ‘ trained immunity ' . In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 ( Th1 ) and Th17 immune responses 1 year after vaccination . The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination , but these effects were less pronounced 1 year after vaccination . However , monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14 , Toll-like receptor 4 ( TLR4 ) and mannose receptor , and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 lig and lipopolysaccharide . The heterologous production of Th1 ( IFN-γ ) and Th17 ( IL-17 and IL-22 ) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination . In conclusion , BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses A series of 972 childhood malignancies was compared with a control series of healthy children matched for date and place of birth . Several variables were tested for possible aetiological significance . The information was obtained from the Finnish Cancer Registry and from the antenatal records of the mothers . No significant associations were found between the various types of malignancies and the variables studied . In the group consisting of all malignancies , a risk ratio of 2.0 could be significantly excluded for most variables . In the leukaemia group , both pelvic X‐ray and polio vaccination were associated with slightly elevated risk ratios , but the differences between this group and the matched controls were not statistically significant . BCG vaccination was performed during the perinatal period in 90 % of the children , but the proportion was the same in the study and control groups , and hence the hypothesis that this vaccination confers protection was not supported . The information is considered prospect i ve and relatively reliable , and the authors suggest that these data may be useful when more extensive series are compiled from various sources From 1949 to 1951 , a controlled trial of BCG vaccinations was conducted in Puerto Rico . The 191,827 children , 1 - 18 years of age , initially enrolled in the study were skin-tested with tuberculin to determine their eligibility for vaccination . A total of 82,269 children were classified as reactors and not vaccinated . Of the 109 , 558 nonreactors , 31,586 refused vaccination  , 50,634 were vaccinated with BCG  , and 27,338 were left unvaccinated as controls . We ascertained the incidence of cancer over an average follow-up period of 23.3 years in the latter two groups using the Puerto Rico Central Cancer Registry . By the end of December 1973 , a total of 77 cancers had been diagnosed among the controls and 150 among the vaccinees . The overall incidence of cancer among the two groups was similar . Although a number of differences existed between the vaccinee group and the controls in regard to the incidence of cancer at various " sites " , none of these differences was statistically significant . However , when cases of lymphosarcoma and Hodgkin 's disease were combined for analysis , a statistically significant excess of cases occurred among the vaccinees . We concluded that BCG vaccination had no protective effect on the subsequent development of cancer in this population . The slight excess of cases of lymphosarcoma and Hodgkin 's disease among the vaccinees raised the possibility that BCG may have had an adverse effect Objective . We report our experience with routine immunization of 89 premature infants in the neonatal intensive care unit because 1 ) a substantial number of them developed abnormal clinical signs , and 2 ) all but one of those who received diphtheria , tetanus , and whole-cell pertussis ( DTwP ) vaccine  responded with elevations of interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) concentrations that are otherwise characteristic of bacterial disease . Methodology . We hypothesized that the elevated IL-6 and CRP levels were solely a response to immunization and that treatment with antibiotics was not necessary . We performed this study in two consecutive parts . In part 1 , we prospect ively evaluated 79 consecutive premature infants who were immunized with DTwP , Haemophilusb conjugate vaccine , hepatitis B vaccine , and inactivated polio vaccine , ( Hib , HBV , and IPV ) .  IL-6 and CRP were determined before immunization and every 12 hours on three occasions after immunization . In part 2 , we studied an additional 10 infants who received acellular pertussis vaccine ( DTaP ) and who , 2 days later ,  received Hib , HBV , and IPV immunization simultaneously .  We followed the same schedule of IL-6 and CRP determinations as in part 1 . Results . In part 1 , 24 infants ( 30 % ) developed abnormal cardiorespiratory signs within 24 hours after immunization . CRP and IL-6 values rose to abnormal levels after immunization in all but one infant ; that infant was later shown to have a T-cell abnormality . In part 2 , 3 infants had abnormal cardiorespiratory signs after simultaneous immunization with Hib , HBV , and IPV , but not after DTaP. IL-6 and CRP levels remained normal in all 10 infants . Conclusions . Part 1 demonstrates clearly the temporal relationship between IL-6 and CRP increments after DTwP , Hib , HBV , and IPV vaccines . In part 2 ( DTaP was substituted for DTwP ) , there were no elevations of IL-6 or CRP , thus indicating that whole-cell pertussis component of DTwP was responsible for IL-6 and CRP elevations . Abnormal cardiorespiratory signs occurred frequently after immunizations in part 1 , but they were unrelated to the magnitude of IL-6 and CRP elevations . 
    Output:
    