Evaluation of viable dynamic treatment regimes in a sequentially randomized trial of advanced prostate cancer

We present new statistical analyses of data arising from a clinical trial designed to compare two-stage dynamic treatment regimes (DTRs) for advanced prostate cancer. The trial protocol mandated that patients be initially randomized among four chemotherapies, and that those who responded poorly be re-randomized to one of the remaining candidate therapies. The primary aim was to compare the DTRs' overall success rates, with success defined by the occurrence of successful responses in each of two consecutive courses of the patient's therapy. Of the 150 study participants, 47 did not complete their therapy as per the algorithm. However, 35 of them did so for reasons that precluded further chemotherapy, that is, toxicity and/or progressive disease. Consequently, rather than comparing the overall success rates of the DTRs in the unrealistic event that these patients had remained on their assigned chemotherapies, we conducted an analysis that compared viable switch rules defined by the per-protocol rules but with the additional provision that patients who developed toxicity or progressive disease switch to a non-prespecified therapeutic or palliative strategy. This modification involved consideration of bivariate per-course outcomes encoding both efficacy and toxicity.We used numerical scores elicited from the trial's principal investigator to quantify the clinical desirability of each bivariate per-course outcome, and defined one endpoint as their average over all courses of treatment. Two other simpler sets of scores as well as log survival time were also used as endpoints. Estimation of each DTR-specific mean score was conducted using inverse probability weighted methods that assumed that missingness in the 12 remaining dropouts was informative but explainable in that it only depended on past recorded data.We conducted additional worst-and best-case analyses to evaluate sensitivity of our findings to extreme departures from the explainable dropout assumption.Fil: Wang, Lu. University of Michigan; Estados UnidosFil: Rotnitzky, Andrea Gloria. Universidad Torcuato Di Tella. Departamento de Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lin, Xihong. Harvard University; Estados UnidosFil: Millikan, Randall. University of Texas; Estados UnidosFil: Thall, Peter. University of Texas; Estados Unido

Diagnostic value of radiomics in predicting Ki-67 and cytokeratin 19 expression in hepatocellular carcinoma: a systematic review and meta-analysis

BackgroundRadiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC.MethodsOriginal studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression.ResultsWe identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86–0.92) in the training set, and 0.87 (95% CI: 0.82–0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81–0.90) in the training set, and 0.79 (95% CI: 0.73–0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased.ConclusionRadiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953

Phase Modulation of (1T-2H)-MoSe2/TiC-C Shell/Core Arrays via Nitrogen Doping for Highly Efficient Hydrogen Evolution Reaction

Tailoring molybdenum selenide electrocatalysts with tunable phase and morphology is of great importance for advancement of hydrogen evolution reaction (HER). In this work, phase‐ and morphology‐modulated N‐doped MoSe2/TiC‐C shell/core arrays through a facile hydrothermal and postannealing treatment strategy are reported. Highly conductive TiC‐C nanorod arrays serve as the backbone for MoSe2 nanosheets to form high‐quality MoSe2/TiC‐C shell/core arrays. Impressively, continuous phase modulation of MoSe2 is realized on the MoSe2/TiC‐C arrays. Except for the pure 1T‐MoSe2 and 2H‐MoSe2, mixed (1T‐2H)‐MoSe2 nanosheets are achieved in the N‐MoSe2 by N doping and demonstrated by spherical aberration electron microscope. Plausible mechanism of phase transformation and different doping sites of N atom are proposed via theoretical calculation. The much smaller energy barrier, longer HSe bond length, and diminished bandgap endow N‐MoSe2/TiC‐C arrays with substantially superior HER performance compared to 1T and 2H phase counterparts. Impressively, the designed N‐MoSe2/TiC‐C arrays exhibit a low overpotential of 137 mV at a large current density of 100 mA cm−2, and a small Tafel slope of 32 mV dec−1. Our results pave the way to unravel the enhancement mechanism of HER on 2D transition metal dichalcogenides by N doping

A High-Rate Two-Dimensional Polyarylimide Covalent Organic Framework Anode for Aqueous Zn-Ion Energy Storage Devices

Rechargeable aqueous Zn-ion energy storage devices are promising candidates for next-generation energy storage technologies. However, the lack of highly reversible Zn2+-storage anode materials with low potential windows remains a primary concern. Here, we report a two-dimensional polyarylimide covalent organic framework (PI-COF) anode with high-kinetics Zn2+-storage capability. The well-organized pore channels of PI-COF allow the high accessibility of the build-in redox-active carbonyl groups and efficient ion diffusion with a low energy barrier. The constructed PI-COF anode exhibits a specific capacity (332 C g–1 or 92 mAh g–1 at 0.7 A g–1), a high rate capability (79.8% at 7 A g–1), and a long cycle life (85% over 4000 cycles). In situ Raman investigation and first-principle calculations clarify the two-step Zn2+-storage mechanism, in which imide carbonyl groups reversibly form negatively charged enolates. Dendrite-free full Zn-ion devices are fabricated by coupling PI-COF anodes with MnO2 cathodes, delivering excellent energy densities (23.9 ∼ 66.5 Wh kg–1) and supercapacitor-level power densities (133 ∼ 4782 W kg–1). This study demonstrates the feasibility of covalent organic framework as Zn2+-storage anodes and shows a promising prospect for constructing reliable aqueous energy storage devices

Evaluating active versus passive sources of human brucellosis in Jining City, China

Human brucellosis (HB) remains a serious public health concern owing to its resurgence across the globe and specifically in China. The timely detection of this disease is the key to its prevention and control. We sought to describe the differences in the demographics of high-risk populations with detected cases of HB contracted from active versus passive sources. We collected data from a large sample population from January to December 2018, in Jining City, China. We recruited patients that were at high-risk for brucellosis from three hospitals and Centers of Disease Control and Prevention (CDCs). These patients were classified into two groups: the active detection group was composed of individuals receiving brucellosis counseling at the CDCs; the passive detection group came from hospitals and high-risk HB groups. We tested a total of 2,247 subjects and 13.3% (299) presented as positive for HB. The positive rates for active and passive detection groups were 20.5% (256/1,249) and 4.3% (43/998), respectively (p < 0.001). The detection rate of confirmed HB cases varied among all groups but was higher in the active detection group than in the passive detection group when controlled for age, sex, ethnicity, education, career, and contact history with sheep or cattle (p < 0.05). Males, farmers, those with four types of contact history with sheep or cattle, and those presenting fever, hyperhidrosis and muscle pain were independent factors associated with confirmed HB cases in multivariate analysis of the active detection group. Active detection is the most common method used to detect brucellosis cases and should be applied to detect HB cases early and avoid misdiagnosis. We need to improve our understanding of brucellosis for high-risk populations. Passive HB detection can be supplemented with active detection when the cognitive changes resulting from brucellosis are low. It is important that healthcare providers understand and emphasis the timely diagnosis of HB

Interlayer gap widened α-phase molybdenum trioxide as high-rate anodes for dual-ion-intercalation energy storage devices

Employing high-rate ion-intercalation electrodes represents a feasible way to mitigate the inherent trade-off between energy density and power density for electrochemical energy storage devices, but efficient approaches to boost the charge-storage kinetics of electrodes are still needed. Here, we demonstrate a water-incorporation strategy to expand the interlayer gap of α- MoO3, in which water molecules take the place of lattice oxygen of α-MoO3. Accordingly, the modified α-MoO3 electrode exhibits theoretical-value-close specific capacity (963 C g−1 at 0.1mV s−1), greatly improved rate capability (from 4.4% to 40.2% at 100 mVs−1) and boosted cycling stability (from 21 to 71% over 600 cycles). A fast-kinetics dual-ion-intercalation energy storage device is further assembled by combining the modified α-MoO3 anode with an anion-intercalation graphite cathode, operating well over a wide discharge rate range. Our study sheds light on a promising design strategy of layered materials for high-kinetics charge storage

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

Abstract: Background: Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives: This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods: In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001-2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results: Median arsenic levels in 2001-2003 were higher among diabetic participants compared with non-diabetic ones (71.6 mu g/L vs. 12.5 mu g/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR) = 2.30, 95% confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95% CI 1.00-4.06; rs6766801, OR = 2.33, 95% CI 1.18-4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 mu g/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004)

Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

Background: Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters. Methods: In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn. Results: One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (23%, 95 % Confidence Interval (CI), 25 to20%), birthweight (2105 g, 95 % CI, 2188 to 222 g), and birth length (20.78 cm, 95 % CI, 21.30 to 20.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 mm/g, 95 % CI, 1 to 5 mm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort

Job burnout among primary healthcare workers during COVID-19 pandemic: cross-sectional study in China

ObjectiveThis study evaluated job burnout among primary healthcare workers (PHCWs) in China during the COVID-19 pandemic, explored its influencing factors, and examined PHCWs' preferences for reducing job burnout.MethodWe conducted a multicenter cross-sectional study in Heilongjiang, Sichuan, Anhui, Gansu, and Shandong Provinces. An electronic questionnaire survey was conducted through convenience sampling in communities from May to July 2022. We collected sociodemographic characteristics, job burnout level, job satisfaction, and preferred ways to reduce job burnout among PHCWs.ResultsThe job burnout rate among PHCWs in China was 59.87% (937/1565). Scores for each dimension of job burnout were lower among PHCWs who had a better work environment (emotional exhaustion OR: 0.60; depersonalization OR: 0.73; personal accomplishment OR: 0.76) and higher professional pride (emotional exhaustion OR: 0.63; depersonalization OR: 0.70; personal accomplishment OR: 0.44). PHCWs with higher work intensity (emotional exhaustion OR: 2.37; depersonalization OR: 1.34; personal accomplishment OR: 1.19) had higher scores in all job burnout dimensions. Improving work environments and raising salaries were the preferred ways for PHCWs to reduce job burnout.ConclusionStrategies should be developed to improve job satisfaction among PHCWs, enhance their professional identity, and alleviate burnout to ensure the effective operation of the healthcare system, especially during periods of overwork