To determine whether successful weight loss before ovarian stimulation with intrauterine insemination (OS-IUI) affects the risk of future pregnancy complications among women with obesity and ...unexplained infertility after fertility treatment.
Secondary analysis of the randomized controlled clinical trial Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility (FIT-PLESE).
Multiple academic health centers in the United States.
Three hundred seventy-nine women with obesity and unexplained infertility who underwent standard infertility treatment after a lifestyle intervention.
The FIT-PLESE trial evaluated whether prepregnancy lifestyle interventions (diet with weight loss medication and exercise vs. exercise alone) before OS-IUI improved the live birth rate among women with obesity and unexplained infertility. Although the primary outcome of FIT-PLESE was live birth rate, we compared the demographics and subsequent pregnancy complications of women who successfully lost some weight with those of women who did not lose any during the interventions.
Obstetric complications by groups were compared using χ2 and Fisher’s exact tests, and continuous variables were compared using Student’s t-tests. Logistic regression was used to assess the odds of preeclampsia after adjustment for the randomized treatment arm in FIT-PLESE.
There was a nonsignificant trend toward a lower risk of intrauterine growth restriction (4% vs. 16%, P = .124) and preterm delivery (6% vs. 15%, P = .343) among patients who lost at least some weight. The risk of preeclampsia was significantly lower (6% vs.35%, P = .002) in the weight loss group (odds ratio, 0.09; 95% confidence interval, 0.016–0.505; P = .006) after adjustment for treatment assignment.
Among women with obesity and unexplained infertility who had live births after fertility treatment, prepregnancy weight loss due to lifestyle interventions before OS-IUI was associated with a lower risk of preeclampsia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to ...the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for the prevention of hematogenous metastasis through the blockade of CD44high breast cancer cells (BCa) adhesion to E-selectin-expressing premetastatic endothelial niche. The current study focuses on developing a PEGylated E-selectin targeting thioaptamer with improved pharmaceutical properties. A serial deletion of stem-loops reveled that loop-1 and -2 (ESTA7) are the minimally effective backbone structure necessary to obtain inhibition of the E-selectin/CD44 interaction and shear resistant adhesion of CD44high BCa to E-selectin-expressing human endothelial cells (HMVECs) at a level equal to ESTA. Chemical conjugation of methoxy-polyethylene-glycol (PEG) at the sizes of 5 and 10 kDa did not interfere with ESTA7-mediated shear-resistant adhesion. However, in vivo study demonstrated that only 10 kDa PEG-conjugated ESTA7 (ESTA7-p10) retains the activity to inhibit metastases at a level equal to parental ESTA. Additionally, a single intravenous injection of ESTA7-p10 inhibited the development of lung, brain, and bone metastases of MDA-MB-231, through the blockade of E-selectin. Moreover, PEGylation led to an extension of elimination half-life and increase of AUC, resulting in superior inhibition of metastasis development compared to parental ESTA with a longer interval between dosing in a spontaneous metastasis model. Lastly, repeated intravenous administration of ESTA7-p10 was tolerated in mice, highlighting the potential prophylactic application of ESTA7-p10 for metastasis prevention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Male breast cancer (MBC) accounts for approximately 1% of all breast cancers, limiting the data characterizing clinicopathologic features and treatment outcomes in patients with MBC. This paucity of ...data has led to most of our treatment guidance being extrapolated from patients with female breast cancer (FBC). From 1998 to 2012, data were captured using the National Cancer Database to identify patients with nonmetastatic MBC (n = 23 305) and FBC (n = 2 678 061). Tumor and clinicopathologic features were obtained and compared. Patients with MBC were more likely to have invasive disease, T2-4 tumors, centrally located tumors, positive lymph nodes, estrogen receptor–positive or progesterone receptor–positive tumors, lymphovascular space invasion, and were less likely to have Her2/neu-positive or triple-negative tumors. All of these differences were statistically significant (P < .001). Treatment comparisons showed that patients with MBC were more likely to undergo mastectomy and less likely to undergo breast-conserving surgery with postoperative radiation utilization found to be less in patients with MBC, both as part of breast-conserving therapy (BCT) and for postmastectomy radiation treatment (PMRT) (P < .001). Stage-by-stage comparisons showed that median survival, 5-year, and 10-year overall survival (OS) rates are lower in patients with MBC vs patients with FBC (P < .001). The utilization of adjuvant radiation, both BCT and PMRT, was shown to improve 5- and 10-year OS (P < .001). Male breast cancer clinicopathologic features appear to be unfavorable in relation to FBC and adjuvant radiation is shown beneficial in survival outcomes. Further investigation is needed to help guide future utilization and treatment with radiation, systemic, and endocrine manipulation in this small population of patients with MBC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Cervical cancer is caused by high-risk human papillomavirus (HPV) types and treated with conventional chemotherapy with surgery and/or radiation. HPV E6 and E7 proteins increase phosphorylation of ...retinoblastoma (Rb) by cyclin D1/cyclin dependent kinase (CDK)4/6 complexes. We hypothesized that cyclin D1 degradation by the SHetA2 drug in combination with palbociclib inhibition of CDK4/6 activity synergistically reduces phosphorylated Rb (phospho-Rb) and inhibits cervical cancer growth. The effects of these drugs, alone, and in combination, were evaluated in SiHa and CaSki HPV-positive and C33A HPV-negative cervical cancer cell lines using cell culture, western blots and ELISA, and in a SiHa xenograft model. Endpoints were compared by isobolograms, ANOVA, and Chi-Square. In all cell lines, combination indexes documented synergistic interaction of SHetA2 and palbociclib in association SHetA2 reduction of cyclin D1 and phospho-Rb, palbociclib reduction of phospho-Rb, and enhanced phospho-Rb reduction upon drug combination. Both drugs significantly reduced phospho-Rb and growth of SiHa xenograft tumors as single agents and acted additively when combined, with no evidence of toxicity. Dilated CD31-negative blood vessels adjacent to, or within, areas of necrosis and apoptosis were observed in all drug-treated tumors. These results justify development of the SHetA2 and palbociclib combination for targeting phospho-Rb in cervical cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•In March-July 2020, US unemployment benefits were raised by $600 a week.•Each 10% increase in benefits caused a 3.6% decline in job applications.•However, the increase in benefits did not decrease ...job vacancy creation.•Jobs were scarce at the time, with 26% fewer vacancies than in January-February 2020.•High benefits reduced competition for jobs, which was likely welfare-improving.
During the COVID-19 pandemic, the Federal Pandemic Unemployment Compensation (FPUC) increased US unemployment benefits by $600 a week. Theory predicts that FPUC should decrease job applications, while the effect on vacancy creation is ambiguous. We estimate the effect of FPUC on job applications and vacancy creation week by week, from March to July 2020, using granular data from the online jobs platform Glassdoor. We exploit variation in the proportional increase in benefits across local labor markets. To isolate the effect of FPUC, we flexibly allow for different trends in local labor markets differentially exposed to the COVID-19 crisis. We verify that trends in outcomes prior to the FPUC do not correlate with future increases in benefits, which supports our identification assumption. First, we find that a 10% increase in unemployment benefits caused a 3.6% decline in applications, but did not decrease vacancy creation; hence, FPUC increased labor market tightness (vacancies/applications). Second, we document that tightness was unusually depressed during the FPUC period. Altogether, our results imply that the positive effect of FPUC on tightness was likely welfare improving: FPUC decreased competition among applicants at a time when jobs were unusually scarce. Our results also help explain prior findings that FPUC did not decrease employment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vanderweele and Knol define biological interaction as an instance wherein “two exposures physically interact to bring about the outcome.” A hallmark of biological interaction is that the total ...effect, produced when factors act together, differs from the sum of effects when the factors operate independently. Epidemiologists construct statistical models to assess biological interaction. The form of the statistical model determines whether it is suited to detecting departures from additivity of effects or for detecting departures from multiplicativity of effects. A consensus exists that biological interaction should be assessed as a departure from additivity of effects.This paper compares three statistical models’ assessment of a data example that appears in several epidemiology textbooks to illustrate biological interaction in a binomial outcome. A linear binomial model quantifies departure from additivity in the data example in terms of differences in probabilities. It generates directly interpretable estimates and 95% confidence intervals for parameters including the interaction contrast (IC). Log binomial and logistic regression models detect no departure from multiplicativity in the data example. However, their estimates contribute to calculation of a “Relative Excess Risk Due to Interaction” (RERI), a measure of departure from additivity on a relative risk scale. The linear binomial model directly produces interpretable assessments of departures from additivity of effects and deserves wider use in research and in the teaching of epidemiology. Strategies exist to address the model’s limitations.
AbstractAmid the rapid development of information communication technologies (ICTs), residents of future smart cities are expected to be exposed to unprecedented amounts of real-time information on a ...daily basis. The cognitive overload driven by an excess of complex information has become a potential issue. Nonetheless, standardized information systems are still widely used, despite individual differences in information intake. To set a foundation for the intelligent information systems of smart cities, this paper introduces methods and tools for a cognition-driven, personalized information system, which acknowledges individual differences in information preference and helps reduce the cognitive load in daily lives and at work. The proposed method includes the use of virtual reality (VR) to simulate complex tasks paired with the digital twin modeling of workers’ cognitive reactions to different information formats and contents in VR simulation. Collected data are then used to build a personal digital twins model of information-driven cognition, or Cog-DT. A human subject experiment was performed with a simulated industrial facility shutdown maintenance task as a proof of concept of Cog-DT. The latest neuroimaging technology and analysis methods were applied to model unique cognitive processes pertaining to information processing. Results indicate that cognitive activities driven by different information stimuli in the work context are distinguishable and modelable with Cog-DT methods and tools. This study is expected to contribute to digital twin literature by testing a human-centered, individual-level digital twin modeling method of cognitive activities. It also sets a preliminary foundation for developing personalized information systems for the smart cities of the future.
Erythromycin（ERY）,a widely used antibiotic,has recently been detected in municipal secondary effluents and poses serious threats to human health during wastewater reusing.In this study,the ...removal,fate,and degradation pathway of ERY in secondary effluent during soil aquifer treatment was evaluated via laboratory-scale SAT tests.Up to a 92.9%reduction of ERY in synthetic secondary effluent was observed in 1.0 m depth column system,which decreased to 64.7%when recharged with wastewater treatment plant secondary effluent.XRD-fractionation results demonstrated that the transphilic acid and hydrophobic acid fractions in secondary effluent compete for the adsorption sites of the packed soil and lead to a declined ERY removal.Moreover,aerobic biodegradation was the predominant role for ERY removal,contributing more than 60%reduction of ERY when recharged with synthetic secondary effluent.Destruction of 14-member macrocyclic lactone ring and breakdown of two cyclic sugars（L-cladinose and D-desosamine） were main removal pathways for ERY degradation,and produced six new intermediates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To determine the effect of tobacco cessation following laryngeal cancer diagnosis on response to first-line therapy, laryngectomy-free survival, and overall survival in patients who were current ...smokers at the time of diagnosis.
Retrospective, case-control study.
OU Stephenson Cancer Center, National Cancer Institute-Designated Cancer Center.
We included 140 patients diagnosed with laryngeal squamous cell carcinoma, who were current smokers at the time of diagnosis, and were treated with first-line definitive radiation or chemo/radiation with the intent to cure. The association between patient characteristics and treatment response was assessed using the χ
test and logistic regression analysis. Survival outcomes were analyzed using Kaplan-Meier methods and Cox proportional-hazards models.
Of the 140 current smokers, 61 patients (45%) quit smoking prior to treatment initiation. In adjusted logistic regression analysis, quitters had 3.7 times higher odds of achieving a complete response to first-line therapy than active smokers (odds ratio: 3.694 1.575-8.661; P = .003). In the adjusted Cox proportional-hazards model, quitters were 54% less likely to require salvage laryngectomy within 7 years of diagnosis than active smokers (hazard ratio: 0.456 0.246-0.848; P = .013). Quitters had a statistically significant increase in 7-year overall survival compared to active smokers (P = .02).
This is the first study to show that in newly diagnosed laryngeal cancer patients who are current smokers at the time of diagnosis, tobacco cessation significantly increases therapy response, laryngectomy-free survival, and overall survival. These data stress the importance of systematically incorporating tobacco cessation programs into laryngeal cancer treatment plans.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical ...management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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