GMOIT: a tool for effective screening of genetically modified crops.

BACKGROUND: Advancement in agricultural biotechnology has resulted in increasing numbers of commercial varieties of genetically modified (GM) crops worldwide. Though several databases on GM crops are available, these databases generally focus on collecting and providing information on transgenic crops rather than on screening strategies. To overcome this, we constructed a novel tool named, Genetically Modified Organisms Identification Tool (GMOIT), designed to integrate basic and genetic information on genetic modification events and detection methods. RESULTS: At present, data for each element from 118 independent genetic modification events in soybean, maize, canola, and rice were included in the database. Particularly, GMOIT allows users to customize assay ranges and thus obtain the corresponding optimized screening strategies using common elements or specific locations as the detection targets with high flexibility. Using the 118 genetic modification events currently included in GMOIT as the range and algorithm selection results, a "6 + 4" protocol (six exogenous elements and four endogenous reference genes as the detection targets) covering 108 events for the four crops was established. Plasmids pGMOIT-1 and pGMOIT-2 were constructed as positive controls or calibrators in qualitative and quantitative transgene detection. CONCLUSIONS: Our study provides a simple, practical tool for selecting, detecting, and screening strategies for a sustainable and efficient application of genetic modification.

Haemovigilance survey and screening strategy for arthropod-borne viruses in blood donors from Argentina.

Arthropod-borne viruses (arboviruses) count among emerging infections, which represent a major challenge for transfusion safety worldwide. To assess the risk of arboviruses-transmission by transfusion (ATT), we performed a survey to evaluate the potential threat for transfusion safety. Samples were retrospectively and randomly collected from donors who donated during the peak of dengue incidence in Cordoba (years: 2016 and 2019-2022). A cost-efficient strategy for molecular screening was implemented with a nucleic acid test (NAT) configured with Flavivirus and Alphavirus-universal degenerated primers targeting conserved gene regions. Besides, we evaluated the neutralizing antibody (NAb) prevalence by plaque reduction neutralization test (PRNT). A total of 1438 samples were collected. Among the NAT-screened samples, one resulted positive for Flavivirus detection. Subsequent sequencing of the PCR product revealed Saint Louis Encephalitis Virus (SLEV) infection (GeneBank accession number OR236721). NAb prevalence was 2.95% for anti-Dengue, 9.94% anti-SLEV, 1.09% anti-West Nile Virus, and 0% anti-Chikungunya. One of the NAb-positive samples also resulted positive for IgM against SLEV but negative by ARN detection. This is the first haemovigilance study developed in Argentina that evaluates the potential risk of ATT and the first research to determine the prevalence of NAb against Flavivirus through PNRT to avoid possible cross-reactions between Ab against Flavivirus. Herein, the finding of one SLEV-viremic donor and the detection of anti-SLEV IgM in a different donor demonstrated a potential threat for transfusion safety and emphasized the need for increased vigilance and proactive measures to ensure the safety of blood supplies.

The accuracy of the FIT in detecting advanced neoplasm is highest in young people aged 40 to 49 years: an analysis based on sex and age.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age. METHODS: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age. RESULTS: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40-49, 50-59, 60-69, and ≥ 70 age groups, respectively. CONCLUSIONS: The FIT detected ANs with highest accuracy in the 40-49 age group. Our research can provide guidance to formulate CRC screening strategies.

Desirable traits for a good biocontrol agent against fire blight disease.

AIMS: This study aimed to improve the screening strategy for the selection of biocontrol agents with high biocontrol efficacy against fire blight disease. METHODS AND RESULTS: A two-step screening procedure consisting of in-vitro laboratory tests and an ex-vivo test system using detached pear leaves was applied to 43 Bacillus strains originated from the rhizosphere and the aerial parts of apple and pear plants. The grouping of the studied strains and the tested traits based on the principal component analysis and the two-way hierarchical cluster analysis showed that siderophore production and biofilm formation are the most desirable traits in a Bacillus biocontrol agent to control fire blight disease and that rhizospheric originating strains are the most effective. CONCLUSIONS: In contrast to the previous screening strategies that are often insufficient to select the most suitable microorganisms, this study reported an improved strategy based on the microbial competition traits to select potential Bacillus biocontrol agents with high biocontrol efficacy against fire blight disease.

A new contingent screening strategy increased detection rate of trisomy 21 in the first trimester.

BACKGROUND: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. METHODS: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. RESULTS: When cut-off values of free beta subunit of human chorionic gonadotropin (free ß-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. CONCLUSIONS: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Cervical cancer (over-)screening in Europe: Balancing organised and opportunistic programmes.

AIMS: Cervical cancer (CC) over-screening has been understudied in Europe, yet is relevant for approaching inequalities in screening uptake. Focusing on countries' screening strategies (opportunistic systems versus organised programmes), we assess in which contexts CC over-screening is more prevalent, and which women are more likely to have engaged in cervical cancer screening (CCS) within the past year. METHODS: A two-level (multilevel) design among screening women (N = 80,761) nested in 31 European countries was used to analyse data from the second wave (2013-2015) of the European Health Interview Survey. We focused on over-screening, defined as screening more frequently than the three-yearly screening interval prescribed in the European guidelines - that is, having screened within the past year. RESULTS: Higher levels of over-screening were observed in opportunistic systems compared to systems with organised programmes. In opportunistic systems, women with a higher socioeconomic position had a higher likelihood of being screened within the past year than their socioeconomic counterparts. Moreover, these differences diminished under organised programmes. CONCLUSIONS: Contexts with organised CCS programmes are more efficiently reducing over-screening, and enforcing the European guidelines. We suggest that the physician-patient relationship is an essential pathway for explaining socioeconomic differences in CC (over-)screening and for future interventions.

Metabolic profiling of Qi-Yu-San-Long decoction in rat feces by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry combined with a post-targeted screening strategy.

Research into traditional Chinese medicine metabolism in feces is one of the key avenues to understanding the fate of traditional Chinese medicines in vivo. In this study, we used ultraperformance liquid chromatography-quadrupole time-of-flight MS in combination with a post-targeted screening strategy to identify the prototype components and metabolites in rat feces after oral administration. Based on our group's previous research, the component database of Qi-Yu-San-Long decoction (QYSLD) was established. Prototype components were screened from the fecal samples based on summarized chromatographic and MS behaviors. According to the chemical structure characteristics of related compounds, the possible metabolic pathways were inferred, and the metabolites related to QYSLD were predicted. We extracted ion chromatograms by predicting the m/z values of metabolite excimer ions and identified related metabolites based on their retention time and fragmentation behavior. A total of 93 QYSLD-related xenobiotics were confirmed or tentatively identified in rat fecal samples, and the results indicated that the main metabolic pathways of QYSLD were hydrolysis, deglycosylation, oxidation, reduction, decarboxylation, methylation and acetylation. This study presents a rapid method for identifying the prototype components and metabolites, and offers valuable insights into the biotransformation profiling of QYSLD in rat feces.

A study based on four immunoassays: Hepatitis C virus antibody against different antigens may have unequal contributions to detection.

BACKGROUND: All commercial Hepatitis C virus antibody (anti-HCV) assays use a combination of recombinant antigens to detect antibody response. Antibody responses to individual antigenic regions (core, NS3/4 and NS5) used in assays have not been investigated. METHODS: In this study, we quantified HCV viral load, tested anti-HCV with four commercial assays (Ortho-ELISA, Murex-ELISA, Architect-CMIA and Elecsys-ECLIA) in 682 plasma specimens. In antigenic region ELISA platform, microwells were coated with three antigens: core (c22-3), NS3/4 (c200) and NS5 individually. The signal-to-cutoff (S/Co) values of different assays, and antibody responses to individual antigens were compared. The specimens were divided into HCV RNA positive group, anti-HCV consistent group, and anti-HCV discrepant group. RESULTS: Anti-core and anti-NS3/4 were simultaneously detected in 99.2% of HCV RNA positive specimens and showed great consistency with total anti-HCV signals. Responses to the core region were more robust than those to the NS3/4 region in anti-HCV consistent group (p < 0.001). Anti-NS5 only occurred in companying with responses to the core and NS3/4 antigens, and failed to affect the final anti-HCV positive signals. In anti-HCV discrepant group, 39.0% of positive signals could not be traced back to any single antigenic region. CONCLUSION: Antibody responses to the core and NS3/4 antigens were stronger, whereas responses to the NS5 antigen were the weakest, indicating that individual antigenic regions played different roles in total anti-HCV signals. This study provides an impetus for optimizing commercial anti-HCV assays.

Spot specimen testing with GeneXpert MTB/RIF results compared to morning specimen in a programmatic setting in Cotonou, Benin.

BACKGROUND: The diagnosis of tuberculosis (TB) using smear microscopy has been based on testing two specimens: one spot and one early morning sputa. Recently, the World Health Organization (WHO) has recommended to replace, whenever possible, microscopy with GeneXpert® MTB/RIF performed on a single specimen. However, as the bacterial load is higher in early morning specimens than in spot specimens, one could expect lower sensitivity of GeneXpert® MTB/RIF performed only on spot specimens. In this study, we compared results of GeneXpert® MTB/RIF on spot specimens versus early morning specimens, under programmatic conditions in Cotonou, Benin. METHODS: From June to September 2018, all sputa received from presumptive TB patients at the Supranational Reference Laboratory for Tuberculosis of Cotonou were included in the study. From each patient, two specimens were collected (one spot and one early morning) and GeneXpert® MTB/RIF was performed on both specimens. RESULTS: In total, 886 participants were included in the study, of whom 737 provided both sputa and 149 (16.8%) gave only the spot specimen. For the 737 participants who provided both sputa, GeneXpert® MTB/RIF was positive for both specimens in 152 participants; for three participants GeneXpert® MTB/RIF was positive on spot specimen but negative on morning specimen while for another three, the test was positive on morning specimen but negative on spot specimen. The overall percentage of agreement was excellent (99.2%) with a positive and negative percent agreement greater than 98%. CONCLUSION: For TB diagnosis under programmatic conditions in Cotonou, GeneXpert® MTB/RIF in spot specimens gave similar results with the test in morning specimens. Performing GeneXpert® MTB/RIF in both specimens did not significantly increase the number of cases detected. To avoid losing patients from the diagnostic cascade, it is preferable to test sputa produced at the time of the first visit at the health center.

Epidemiological survey and screening strategy for dengue virus in blood donors from Yunnan Province.

BACKGROUND: Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies. METHODS: Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed. RESULTS: Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026). CONCLUSION: The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.

Cervical cancer screening programs and their context-dependent effect on inequalities in screening uptake: a dynamic interplay between public health policy and welfare state redistribution.

BACKGROUND: While organized and opportunistic cervical cancer screening (CCS) programs implemented across the European Union have increased participation rates, barriers to socioeconomically deprived women remain substantial, implying high levels of inequality in CCS uptake. AIM: This study assesses how the screening strategy (as a score based on the availability of organized population-based CCS programs), accessibility of the healthcare system (as an index of out-of-pocket expenditure as a proportion of total healthcare costs, public health expenditure as a percentage of total GDP, and general practitioner (GP) density per 10'000 inhabitants) and social protection (as a decommodification index), impact education- and income-based inequalities in CCS uptake. METHODS: A two-level design with 25-64-year-old women (N = 96'883), eligible for Pap smear screening, nested in 28 European countries, was used to analyze data from the European Health Interview Survey's second wave, using multilevel logistic regression modelling. RESULTS: Clear educational and income gradients in CCS uptake were found, which were smaller in countries with organized CCS programs, higher accessibility of the healthcare system and a higher level of decommodification. Furthermore, three-way interaction terms revealed that these gradients were smaller when organized CCS programs were implemented in countries with better accessibility of the healthcare system or a high level of decommodification. CONCLUSION: This study indicates that the combination of organized screening and high accessibility of the healthcare system or social protection is essential for having lower levels of inequality in CCS uptake. In such countries, the structural threshold for poorer and lower educated women to engage in CCS is lower. This may be explained by them having a better interaction with their GP, who may convince them of the screening test, lower out-of-pocket payments, and financial support to buffer against a disadvantageous position on the labor market.

Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China.

OBJECTIVES: To evaluate, in a Chinese population, the performance of a screening strategy for preterm pre-eclampsia (PE) using The Fetal Medicine Foundation (FMF)'s competing-risks model and to explore its clinical applicability in mainland China. METHODS: This was a prospective, multicenter, observational cohort study including 10 899 women with singleton pregnancy who sought prenatal care at one of 13 hospitals, located in seven cities in mainland China, between 1 December 2017 and 30 December 2019. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and maternal serum levels of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation were measured and converted into multiples of the median using Chinese reference ranges. Individualized risk for preterm PE was calculated using the FMF algorithm. Prior risk was calculated based on maternal demographic characteristics and obstetric history. We evaluated the efficiency of the screening strategy using various combinations of biomarkers and analyzed its predictive performance for a composite of placenta-associated adverse pregnancy outcomes, including PE, placental abruption, small-for-gestational age (SGA) and preterm birth, at fixed false-positive rates for preterm PE. RESULTS: We identified 312 pregnancies that developed PE, of which 117 cases were diagnosed as preterm PE (< 37 weeks' gestation). There were 386 pregnancies complicated by severe composite placenta-associated adverse outcome, including preterm PE, 146 cases of severe SGA (birth weight < 3rd percentile) neonate, 61 cases with placental abruption and 109 cases of early preterm birth < 34 gestational weeks. The triple-marker model containing biomarkers MAP, UtA-PI and PAPP-A achieved, at fixed false-positive rates of 10%, 15% and 20%, detection rates for preterm PE of 65.0%, 72.7% and 76.1%, respectively, and detection rates for severe composite placenta-associated adverse outcome of 34.7%, 41.7% and 46.4%, respectively. Replacing PAPP-A with PlGF or adding PlGF to the model did not improve the performance. Of women screening positive for preterm PE at a fixed 5% false-positive rate, an estimated 30% developed at least one placenta-associated adverse pregnancy outcome, including PE, placental abruption, SGA (birth weight < 10th percentile) and preterm birth < 37 weeks. CONCLUSIONS: The FMF competing-risks model for preterm PE was found to be effective in screening a mainland Chinese population. Women who screened positive for preterm PE had increased risk for other placenta-associated pregnancy complications. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[Expert consensus on early screening strategies for liver cancer in China].

Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Half of the annual newly diagnosed liver cancer cases come from China. A large number of clinical studies and practices have proved that early screening and early diagnosis can effectively reduce the 5-year total mortality of liver cancer. Therefore, it is extremely urgent to explore and establish customized liver cancer screening strategies for China. Based on the relevant domestic and foreign guidelines, clinical practice, and the latest advances in the research of the PreCar project, the expert from PreCar project(Prospective suRveillance for very Early hepatoCellular cARcinoma, PreCar), proposed novel strategies and procedures for early liver cancer screening in my country. The PreCar project aims to provide practical methods for early liver cancer screening and diagnosis, and to improve our national prophylactic level for liver cancer.

[Analysis of the factors influencing the elimination strategies with the current status of diagnosis and treatment of hepatitis C in hospital].

Objective: To understand the current status of screening, diagnosis, and treatment and analyze the factors influencing micro-elimination strategy, so as to achieve hepatitis C elimination in hospital. Methods: Anti-HCV and HCV RNA test results of patients from October 2017 to September 2020 were retrospectively analyzed. Anti-HCV positive rates and factors influencing different genders, ages, places of residence and departments were analyzed. After comparing anti-HCV-positive patients with HCV RNA-positive patients with duplicate entries in "Name" and "Date of birth", the data were divided into three categories: anti-HCV positive without HCV RNA test, HCV RNA positive in single test, and HCV RNA positive many times in multiple tests. The above three types of patients were followed-up by telephone. According to the hospital follow-up results, current status of diagnosis and treatment and the factors influencing the micro-elimination strategy of hepatitis C were studied and analyzed. The comparison of data between groups were performed using χ(2) or χ(2) continuity-correction test. Results: Anti-HCV positive detection rate was 1.34% (899/66 866). The positive rate of male patients aged 40 and over residing in cities was significantly higher than female patients under 40 years old residing in rural areas, and the difference was statistically significant (χ(2) = 55.178, 264.11, 36, 351, P < 0.05). There were 90 (10.02%) and 809 cases (89.98%) in outpatient and inpatient departments, respectively, with no statistically significant difference between the two (χ(2) = 0.002, P > 0.05). The total number of anti-HCV positive cases were 196 in Gastroenterology (22.0%), 75 in Respiratory and Critical Care Medicine (8.3%), 74 in Neurology (8.2%), 63 in Orthopedics (7.0%) and 55 in Endocrinology departments (6.1%), and the difference in the positive rate among different departments were also statistically significant (χ(2) = 271.585, P < 0.05). Among the 480 cases who were followed-up, 215 (44.79%) were lost to follow-up, 84 cases (39.07%) were unregistered, 77 cases (16.04%) were untreated, 15 cases (19.48%) were unaware of their state of illness, 46 cases (59.74%) were diagnosed without concern, 16 cases (20.78%) were diagnosed but did not take medicine, 60 cases were under treatment, and 29 cases were mostly on counterfeit drugs (48.33%). Conclusion: Comprehensive diagnosis and treatment education to non-specialist clinicians and timely manner regular follow-up of patients is a key factor and an important link to formulate a simple, easy and sustainable model to improve the efficiency of screening, diagnosis, and treatment of hepatitis C micro-elimination strategy in hospital. In addition, it will also play an important role in achieving the strategic goal of "eliminating hepatitis C as a public health threat by 2030".

Optimizing Strategies for Chlamydia trachomatis and Neisseria gonorrhoeae Screening in Men Who Have Sex With Men: A Modeling Study.

BACKGROUND: International guidelines recommend the systematic screening for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections in all men who have sex with men (MSM) who have engaged in unprotected sex. However, the optimal screening strategy remains unclear. We developed a modeling approach to optimize NG/CT screening strategy in MSM. METHODS: A compartmental model of NG/CT screening and infection was implemented. NG/CT anal, pharyngeal, and urine (APU) samples from MSM attending the sexually transmitted infections clinic were used to estimate the screening rate, prevalence, and incidence in a base case scenario. Different screening strategies (scenarios; S) were then evaluated: APU samples every 12 months (S1); APU samples every 3 months (S2); APU samples every 6 months (S3); anal and pharyngeal (AP) samples every 6 months (S4); and AP samples every 3 months (S5). RESULTS: We analyzed 2973 triplet APU samples from 1255 patients. We observed 485 NG and 379 CT diagnoses. NG/CT prevalence and incidence estimates were 12.0/11.1% and 40/29 per 100 person-years, respectively, in the base case scenario. As compared to S2, the reference strategy, the proportions of missed NG/CT diagnoses were 42.0/41.2% with S1, 21.8/22.5% with S3, 25.6/28.3% with S4, and 6.3/10.5% with S5, respectively. As compared to S2, S1 reduced the cost of the analysis by 74%, S3 by 50%, S4 by 66%, and S5 by 33%. The numbers needed to screen for catching up the missed NG/CT diagnoses were 49/67 with S1, 62/82 with S3, 71/87 with S4, and 143/118 with S5. CONCLUSIONS: S5 appears to be the best strategy, missing only 6.3/10.5% of NG/CT diagnoses, for a cost reduction of 33%.

Pulse oximetry screening in a midwifery-led maternity setting with high antenatal detection of congenital heart disease.

AIM: To assess local and individual factors that should be considered in the design of a pulse oximetry screening strategy in New Zealand's midwifery-led maternity setting. METHODS: An intervention study was conducted over 2 years. Three hospitals and four primary maternity units participated in the study. Post-ductal saturation levels were measured on well infants with a gestation of ≥35 weeks. Infant activity and age (hours) at the time of the test were recorded. RESULTS: Screening was performed on 16 644 of 27 172 (61%) eligible infants. The age at which the screening algorithm was initiated varied significantly among centres. The probability of achieving a pass result (saturations ≥95%) in the context of no underlying pathology ranged from .94 for an unsettled infant screened <4 hours of age to .99 (P < .001) when the test was performed after 24 hours on a settled infant. Forty-eight (0.3%) infants failed to reach saturation targets: 37 had significant pathology of which three had cardiac disease. CONCLUSION: Screening practices were influenced by the setting in which it was undertaken. Infant activity and age at the time of testing can influence saturation levels. Screening is associated with the identification of significant non-cardiac pathology.

Cancer incidence and mortality patterns in women with breast symptoms in the mammography screening programme: A matched cohort analysis.

Efforts to reduce mortality through early detection and diagnosis has intensified in the recent decade. An important risk factor, 'breast symptoms' reported by women during screening visit, remains overlooked. In this population based matched cohort study using Finnish National Breast Cancer Screening Program (FNBCSP), we assessed the association between breast symptoms reported at screening visit and the risk of cancer incidence and breast cancer mortality and all-cause mortality followed-up over a period of 24 years. For each visit with symptoms, non-symptomatic controls were matched (1:1 for lump and retraction; 1:2 for nipple discharge) based on age at screening visit, year of invitation, number of invited visits, and municipality of invitation. Women who reported lump or retraction had about two-fold risk of breast cancer incidence, three-fold risk of breast cancer mortality and all-cause mortality respectively as compared to women without respective symptoms (p-value<0.05). We found a substantial difference (p-value<0.05) in mortality rates throughout the follow-up period between symptomatic and asymptomatic group. In absolute terms, after the follow-up period for women who reported lump, 180 died from breast cancer as compared to 70 deaths in those without lump, per 10,000 person-years of follow-up, and 315 versus 160 all-cause deaths per 10,000 person-years in women with and without lump respectively. our study provides comprehensive evidence that women with breast symptoms remain in a higher risk of dying over a very long period. The findings indicate needs to develop improvements in the guidelines for screening and clinical services for women presenting with symptoms.

Tackling tumor heterogeneity and phenotypic plasticity in cancer precision medicine: our experience and a literature review.

The predominant cause of cancer mortality is metastasis. The major impediment to cancer cure is the intrinsic or acquired resistance to currently available therapies. Cancer is heterogeneous at the genetic, epigenetic, and metabolic levels. And, while a molecular-targeted drug may be pathway-precise, it can still fail to achieve wholesome cancer-precise toxicity. In the current review, we discuss the strategic differences between targeting the strengths of cancer cells in phenotypic plasticity and heterogeneity and targeting shared vulnerabilities of cancer cells such as the compromised integrity of membranous organelles. To better recapitulate subpopulations of cancer cells in different phenotypic and functional states, we developed a schematic combination of 2-dimensional culture (2D), 3-dimmensional culture in collagen I (3D), and mammosphere culture for stem cells (mammosphere), designated as Scheme 2D/3D/mammosphere. We investigated how the tumor suppressor maspin may limit carcinoma cell plasticity and affect their context-dependent response to drugs of different mechanisms including docetaxel, histone deacetylase (HDAC) inhibitor MS-275, and ionophore antibiotic salinomycin. We showed that tumor cell phenotypic plasticity is not an exclusive attribute to cancer stem cells. Nonetheless, three subpopulations of prostate cancer cells, enriched through Scheme 2D/3D/mammosphere, show qualitatively different drug responses. Interestingly, salinomycin was the only drug that effectively killed all three cancer cell subpopulations, irrespective of their capacity of stemness. Further, Scheme 2D/3D/mammosphere may be a useful model to accelerate the screening for curative cancer drugs while avoiding costly characterization of compounds that may have only selective toxicity to some, but not all, cancer cell subpopulations.

A clinical practice-based evaluation of the RIETE score in predicting occult cancer in patients with venous thromboembolism.

The association between venous thromboembolism (VTE) and occult cancer is well established. However, the benefit of cancer screening in all VTE patients remains controversial. The Registro Informatizado Enfermedad TromboEmbólica (RIETE) score is a recently proposed risk score to identify VTE patients at high risk of occult cancer. We evaluated the performance of the RIETE score in a routine clinical setting comprising patients presenting with VTE between January 1 and December 31, 2014, at Danderyd University hospital. Out of 488 VTE patients, 47 (9.6%) patients received a new cancer diagnosis during a 24-month follow-up. After exclusion of patients with cancer diagnosed at baseline (≤ 10 days after VTE, n = 16), 472 patients were considered eligible for cancer screening. Among these 472 patients, 31 (6.6%) received a cancer diagnosis during follow-up. The cumulative incidence was high after both unprovoked (8.5%) and provoked (4.8%) VTE. The RIETE score was evaluated in 467 of these patients. Interestingly, a high RIETE score was not significantly associated with cancer diagnosis during follow-up (OR 1.78; 95% CI 0.85-3.63), which was mainly due to a poor performance in women (OR 1.04; 95% CI 0.30-2.83). In summary, we observed a relatively high incidence of occult cancer in both unprovoked and provoked VTE. The RIETE score performed poorly in identifying patients at high risk of occult cancer in our VTE population. Additional risk assessment models are warranted to identify VTE patients who would benefit from extensive cancer screening.

Vascular Parkinsonism in a Tertiary Care Stroke Prevention Clinic and the Development of a New Screening Strategy.

OBJECTIVES: To determine the prevalence of vascular parkinsonism (VasP) in a stroke prevention clinic (SPC). BACKGROUND: VasP can be defined by an onset of parkinsonism with prominent gait problems occurring within 1 year of stroke. METHODS: We created a screening strategy based on the Tanner Questionnaire (TQ), a validated scale for parkinsonism, and the creation of a 4-point Five-Minute Assessment Scale (FMAS) operationalizing Zijlmans' criteria for the diagnosis of VasP. Consecutive stroke patients were screened over a 12-month period using the TQ and the FMAS. SAS statistical software was used. RESULTS: Two hundred forty patients (52.5% females) were screened (mean age of 65 years, standard deviation, 14.5). Twenty-five percent of patients had a TQ score ≥ 4 with a median FMAS of 2. In this group, 32.6% (15/46) were found to have parkinsonism. Seventeen percent (8/46) were diagnosed with VasP having an FMAS of 4. Seventy-five of the participants obtained a TQ ≤ 3, with a median FMAS of 1. Only 1 patient in this group had parkinsonism (1.9%; 1/194). Using a cutoff of 4 points in the TQ resulted in a sensitivity of 93.8%, a specificity of 86.2% for parkinsonism, and a sensitivity of 100% with a specificity of 83% for VasP. Patients with FMAS = 4 (VasP) attained higher scores in the TQ with a median of 5 (Spearman rank correlation coefficient for the TQ and the FMAS (rs) = .447, P < .0005). CONCLUSIONS: We documented a prevalence of 3% (8/240) for VasP in an SPC. We propose a new, easier, and unified 2-step TQ-FMAS screening strategy for this condition.