Effects of Aging Treatment on the Microstructures and Mechanical Properties of a TC18 Alloy.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

Two-stage stratified designs with survival outcomes and adjustment for misclassification in predictive biomarkers.

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.

MH-STRALP: A scoring system for prognostication in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common medical emergency and early assessment of its outcomes is vital for treatment decisions. AIM: To develop a new scoring system to predict its prognosis. METHODS: In this retrospective study, 692 patients with UGIB were enrolled from two centers and divided into a training (n = 591) and a validation cohort (n = 101). The clinical data were collected to develop new prognostic prediction models. The endpoint was compound outcome defined as (1) demand for emergency surgery or vascular intervention, (2) being transferred to the intensive care unit, or (3) death during hospitalization. The models' predictive ability was compared with previously established scores by receiver operating characteristic (ROC) curves. RESULTS: Totally 22.2% (131/591) patients in the training cohort and 22.8% (23/101) in the validation cohort presented poor outcomes. Based on the stepwise-forward Logistic regression analysis, eight predictors were integrated to determine a new post-endoscopic prognostic scoring system (MH-STRALP); a nomogram was determined to present the model. Compared with the previous scores (GBS, Rockall, ABC, AIMS65, and PNED score), MH-STRALP showed the best prognostic prediction ability with area under the ROC curves (AUROCs) of 0.899 and 0.826 in the training and validation cohorts, respectively. According to the calibration curve, decision curve analysis, and internal cross-validation, the nomogram showed good calibration ability and net clinical benefit in both cohorts. After removing the endoscopic indicators, the pre-endoscopic model (pre-MH-STRALP score) was conducted. Similarly, the pre-MH-STRALP score showed better predictive value (AUROCs of 0.868 and 0.767 in the training and validation cohorts, respectively) than the other pre-endoscopic scores. CONCLUSION: The MH-STRALP score and pre-MH-STRALP score are simple, convenient, and accurate tools for prognosis prediction of UGIB, and may be applied for early decision on its management strategies.

The effects of psychological distress after surgery in patients undergoing lumbar spinal fusion.

BACKGROUND: The aim of this study was to evaluate the psychological distress pre-operatively, at 3, 6, and 12 months in patients who underwent lumbar spine fusion surgery. METHODS: A total of 440 patients received instrumented lumbar spine fusion were enrolled. Psychological distress was evaluated using the Modified Somatic Perception Questionnaire (MSPQ) and the Modified Zung Depressive Index (ZDI). The results of lumbar fusion surgery were evaluated using the Oswestry Disability Index (ODI), the Japanese Orthopedic Association (JOA-29), and the visual analog scale (VAS). RESULTS: Psychological distress was reported among 23% of patients and 7, 5.5, and 4.0% of the patients preoperatively, at 3, 6, and 12 months after lumbar surgery, respectively. The mean MSPQ score decreased from 8.78 (before surgery) to 4.30, 3.52, and 3.43 at 3, 6 and 12 months in after surgery, respectively, in patients with psychological distress patients (p < 0.001). The mean ZDI score decreased from 17.78 to 12.48, 10.35, and 9.61 (p < 0.001). The mean ODI score decreased from 22.91 to 11.78, 10.13, and 9.96 (P < 0.001). The mean JOA score increased from 13.65 to 22.30, 23.43, and 23.61 (P < 0.001). The mean low back pain (LBP) VAS score decreased from 4.48 to 1.96, 1.52, and 1.51 (P < 0.001); moreover, the mean leg pain (LP) VAS score decreased from 5.30 to 1.30, 1.04, and 1.03 (P < 0.001). CONCLUSIONS: Patients with psychological distress may experience surgical intervention benefits equal to those of ordinary patients. Moreover, reduced pain and disability after surgical intervention may also alleviate psychological distress. Hence, we highly recommend that patients with psychological distress undergo surgical intervention as normal patients do, but appropriate screening measures and interventions are necessary.

Investigation on Mechanism of Microstructure Evolution during Multi-Process Hot Forming of GH4169 Superalloy Forging.

Typically, in the manufacturing of GH4169 superalloy forgings, the multi-process hot forming that consists of pre-deformation, heat treatment and final deformation is required. This study focuses on the microstructural evolution throughout hot working processes. Considering that δ phase can promote nucleation and limit the growth of grains, a process route was designed, including pre-deformation, aging treatment (AT) to precipitate sufficient δ phases, high temperature holding (HTH) to uniformly heat the forging, and final deformation. The results show that the uneven strain distribution after pre-deformation has a significant impact on the subsequent refinement of the grain microstructure due to the complex coupling relationship between the evolution of the δ phase and recrystallization behavior. After the final deformation, the fine-grain microstructure with short rod-like δ phases as boundaries is easy to form in the region with a large strain of the pre-forging. However, necklace-like mixed grain microstructure is formed in the region with a small strain of the pre-forging. In addition, when the microstructure before final deformation consists of mixed grains, dynamic recrystallization (DRX) nucleation behavior preferentially depends on kernel average misorientation (KAM) values. A large KAM can promote the formation of DRX nuclei. When the KAM values are close, a smaller average grain size of mixed-grain microstructure is more conductive to promote the DRX nucleation. Finally, the interaction mechanisms between δ phase and DRX nucleation are revealed.

Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

Exosomal miR-1202 mediates Brodmann Area 44 functional connectivity changes in medication-free patients with major depressive disorder: An fMRI study.

Previous large-sample postmortem study revealed that the expression of miR-1202 in brain tissues from Brodmann area 44 (BA44) was dysregulated in patients with major depressive disorder (MDDs). However, the specific in vivo neuropathological mechanism of miR-1202 as well as its interplay with BA44 circuits in the depressed brain are still unclear. Here, we performed a case-control study with imaging-genetic approach based on resting-state functional magnetic resonance imaging (MRI) data and miR-1202 quantification from 110 medication-free MDDs and 102 healthy controls. Serum-derived circulating exosomes that readily cross the blood-brain barrier were isolated to quantify miR-1202. For validation, repeated MR scans were performed after a six-week follow-up of antidepressant treatment on a cohort of MDDs. Voxelwise factorial analysis revealed two brain areas (including the striatal-thalamic region) in which the effect of depression on the functional connectivity with BA44 was significantly dependent on the expression level of exosomal miR-1202. Moreover, longitudinal change of the BA44 connectivity with the striatal-thalamic region in MDDs after antidepressant treatment was found to be significantly related to the level of miR-1202 expression. These findings revealed that the in vivo neuropathological effect of miR-1202 dysregulation in depression is possibly exerted by mediating neural functional abnormalities in BA44-striatal-thalamic circuits.

Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Enhanced home-field advantage in deep soil organic carbon decomposition: Insights from soil transplantation in subtropical forests.

Climate change affects microbial community physiological strategies and thus regulates global soil organic carbon (SOC) decomposition. However, SOC decomposition by microorganisms, depending on home-field advantage (HFA, indicating a faster decomposition rate in 'Home' than 'Away' conditions) or environmental advantage (EA, indicating a faster decomposition rate in warmer-wetter environments than in colder-drier environments) remains unknown. Here, a soil transplantation experiment was conducted between warmer-wetter and colder-drier evergreen broadleaved forests in subtropical China. Specifically, soil samples were collected along a 60 cm soil profile, including 0-15, 15-30, 30-45, and 45-60 cm layers after one year of transplantation. SOC fractions, soil chemical properties, and microbial communities were evaluated to assess where there was an HFA of EA in SOC decomposition, along with an exploration of internal linkages. Significant HFAs were observed, particularly in the deep soils (30-60 cm) (P < 0.05), despite the lack of a significant EA along a soil profile, which was attributed to environmental changes affecting soil fungal communities and constraining SOC decomposition in 'Away' conditions. The soils transplanted from warmer-wetter to colder-drier environments changed the proportions of Mortiereltomycota or Basidiomycota fungal taxa in deep soils. Furthermore, the shift from colder-drier to warmer-wetter environments decreased fungal α-diversity and the proportion of fungal necromass carbon, ultimately inhibiting SOC decomposition in 'Away' conditions. However, neither HFAs nor EAs were significantly present in the topsoil (0-30 cm), possibly due to the broader adaptability of bacterial communities in these layers. These results suggest that the HFA of SOC decomposition in deep soils may mostly depend on the plasticity of fungal communities. Moreover, these results highlight the key roles of microbial communities in the SOC decomposition of subtropical forests, especially in deep soils that are easily ignored.

Randomized trial promoting cancer genetic risk assessment when genetic counseling cost removed: 1-year follow-up.

PURPOSE: Cancer genetic risk assessment (CGRA) is recommended for women with ovarian and high-risk breast cancer. However, the underutilization of CGRA has long been documented, and cost has been a major barrier. In this randomized controlled trial, a tailored counseling and navigation (TCN) intervention significantly improved CGRA uptake at 6-month follow-up, compared with targeted print (TP) and usual care (UC). We aimed to examine the effect of removing genetic counseling costs on CGRA uptake by 12 months. METHODS: We recruited racially and geographically diverse women with breast and ovarian cancer from cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TCN received telephone-based psychoeducation and navigation. After 6 months, the trial provided free genetic counseling to participants in all arms. RESULTS: At 12 months, more women in TCN obtained CGRA (26.6%) than those in TP (11.0%; odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.56 to 4.89) and UC (12.2%; OR = 2.46, 95% CI = 1.41 to 4.29). There were no significant differences in CGRA uptake between TP and UC. The Kaplan-Meier curve shows that the divergence of cumulative incidence slopes (TCN vs UC, TCN vs TP) appears primarily within the initial 6 months. CONCLUSION: TCN significantly increased CGRA uptake at the 12-month follow-up. Directly removing the costs of genetic counseling attenuated the effects of TCN, highlighting the critical enabling role played by cost coverage. Future policies and interventions should address multilevel cost-related barriers to expand patients' access to CGRA. TRIAL REGISTRATION: This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT03326713. https://clinicaltrials.gov/ct2/show/NCT03326713.

The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis.

BACKGROUND: HPV is detected in up to 47% of CIN and up to 70% of cervical cancers. It can cause intraepithelial neoplasia, which can eventually progress to invasive carcinoma. Almost all cervical cancers are caused by HPV. Therefore, it is especially important to treat high-risk HPV. For patients who have undergone LEEP surgery, this procedure can effectively treat CIN. However, it has not been studied in a meta-analysis whether HPV remains after the surgery and whether residual HPV increases the recurrence risk of CIN. To address this gap, our study collected all relevant literature to investigate the residual rate of HPV and its potential influence on the recurrence rate of CIN. We aim to provide valuable recommendations for clinicians and patients. METHODS: The Cochrane Library, EMBASE, and PubMed databases were searched from the establishment of the database until October 2023. Stata 12.0 software was used for the statistical analysis. RESULTS: Twelve studies were included, with a total sample size of 1192 cases. The meta-analysis found that the recurrence rate of CIN was quite low [95% CI = 0.5% (0.001, 0.012); P = 0.006] when the margins were negative after LEEP and there was no residual HPV. When HPV was present, the recurrence rate of CIN was significantly higher [95% CI = 18% (0.089, 0.291), P = 0.000], even if the margins were negative. The recurrence rate of CIN with residual HPV was 3.6 times higher than the recurrence rate of CIN without residual HPV. The residual rate of HPV after LEEP with negative margins was 22.7% [95% CI (0.167, 0.294), P = 0.000], which remained relatively high. CONCLUSION: This meta-analysis found that the recurrence rate of CIN without residual HPV and with negative margins after LEEP was quite low, at 0.5%. However, when HPV was residual, the recurrence rate of CIN significantly increased to 18%, even if the margins were negative. The residual rate of HPV was 22.7%, even when the margins were negative after LEEP.

Functional knee phenotypes appear to be more suitable for the Chinese OA population compared with CPAK classification: A study based on 3D CT reconstruction models.

PURPOSE: The aim of this study was to investigate the distribution of coronal plane alignment of the knee (CPAK) classification and functional knee phenotypes in a Chinese osteoarthritis (OA) population and to compare different lower limb alignment targets according to the distribution characteristics to find suitable total knee arthroplasty (TKA) bone cut strategies for the Chinese OA patients. METHODS: The computed tomography (CT) images were retrospectively collected and the three-dimensional (3D) models were reconstructed from 434 Chinese OA patients, including 93 males and 341 females, with a mean age of 66.4 ± 9.3 years. Femoral mechanical angle (FMA), tibial mechanical angle (TMA) and mechanical hip-knee-ankle angle (mHKA) were measured on the 3D models. Arithmetic hip-knee-ankle angle (aHKA) was calculated using FMA plus TMA, and joint line obliquity was calculated as 180 + TMA-FMA. The CPAK according to MacDessi and the functional knee phenotypes according to Hirschmann were performed. In addition, the suitable TKA bone cut strategies were explored according to the phenotypes and based on the characteristics of different alignment targets, such as mechanical alignment, anatomic alignment (AA), kinematic alignment, restricted KA (rKA) and adjusted MA (aMA). Statistical differences were determined using the independent-samples t-test or the two independent-samples Wilcoxon test, with p < 0.05 considered statistically significant. RESULTS: The Chinese OA population showed a varus alignment tendency (mHKA = 172.1° ± 7.2°), to which the TMA was a major contributor (TMA = 84.7° ± 4.4° vs. FMA = 91.3° ± 3.2°). The mHKA was on average 3.9° more varus than the aHKA. A total of 140 functional knee phenotypes were found and 45.6% were concentrated in VARFMA3°-NEUFMA0° to VARTMA3°-NEUTMA0°. More than 70% of patients had different FMA and TMA phenotypes. There were 92.9% of CPAK distributed in types I to IV, with type I accounting for 53.9%. The FMA phenotypes were less changed if the aMA and rKA were chosen, and the TMA phenotypes were less changed if the AA and rKA were chosen. CONCLUSION: Compared with the CPAK, the functional knee phenotypes were more suitable for the Chinese OA population with a wide distribution and a varus tendency, and it seemed more appropriate to choose aMA and rKA as TKA alignment targets for resection. LEVEL OF EVIDENCE: Level Ⅲ.

Corrigendum: Safety assessment of poly-ε-caprolactone in the treatment of primary spontaneous pneumothorax.

[This corrects the article DOI: 10.3389/fsurg.2024.1335144.].

Enabling Rapid and Stable Sodium Storage via a P2-Type Layered Cathode with High-Voltage Zero-Phase Transition Behavior.

Currently, a major target in the development of Na-ion batteries is the concurrent attainment of high-rate capacity and long cycling stability. Herein, an advanced Na-ion battery with high-rate capability and long cycle stability based on Li/Ti co-doped P2-type Na0.67 Mn0.67 Ni0.33 O2 , a host material with high-voltage zero-phase transition behavior and fast Na+ migration/conductivity during dynamic de-embedding process, is constructed. Experimental results and theoretical calculations reveal that the two-element doping strategy promotes a mutually reinforcing effect, which greatly facilitates the transfer capability of Na+ . The cation Ti4+ doping is a dominant high voltage, significantly elevating the operation voltage to 4.4 V. Meanwhile, doping Li+ shows the function in charge transfer, improving the rate performance and prolonging cycling lifespan. Consequently, the designed P2-Na0.75 Mn0.54 Ni0.27 Li0.14 Ti0.05 O2 cathode material exhibits discharge capacities of 129, 104, and 85 mAh g- 1 under high voltage of 4.4 V at 1, 10, and 20 C, respectively. More importantly, the full-cell delivers a high initial capacity of 198 mAh g-1 at 0.1 C (17.3 mA g-1 ) and a capacity retention of 73% at 5 C (865 mA g-1 ) after 1000 cycles, which is seldom witnessed in previous reports, emphasizing their potential applications in advanced energy storage.

Highly sensitive SERS platform for pathogen analysis by cyclic DNA nanostructure@AuNP tags and cascade primer exchange reaction.

The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.

Exposure to BTEX is associated with cardiovascular disease, dyslipidemia and leukocytosis in national US population.

BACKGROUND: Comprehensive research on the effects of individual benzene, toluene, ethylbenzene, and xylenes (BTEX) and their mixture measured in blood samples, on cardiovascular diseases (CVD) and related risk factors among the general population is limited. OBJECTIVES: To investigate the effects of blood individual and mixed BTEX on total CVD and its subtypes, lipid profiles, and white blood cell (WBC) count. METHODS: Survey-weighted multivariate logistic regression was used to examine the associations between blood individual and mixed BTEX with CVD and its subtypes in 17,007 participants from NHANES 1999-2018. The combined effect of BTEX mixture on CVD was estimated using weighted quantile sum modeling and quantile g-computation. Weighted multivariate linear regression assessed the effects of BTEX on lipid profiles and WBC, including its five-part differential count. RESULTS: In comparison to the reference quartile of BTEX mixture, individuals in the highest quartile had a significantly increased adjusted odds ratio of CVD risk (1.64, 95 % CI: 1.23 to 2.19, P for trend = 0.008). Positive associations were observed for benzene, toluene, ethylbenzene, and m-/p-xylene, demonstrating a monotonically increasing exposure-response relationship. Mixed BTEX was associated with congestive heart failure (CHF), angina pectoris, and heart attack. Individual benzene, toluene, and ethylbenzene were associated with CHF, while toluene, ethylbenzene, and all xylene isomers were linked to angina pectoris. Benzene, toluene, and o-xylene were associated with heart attack. Both mixed and individual BTEX showed positive associations with triglycerides, cholesterol, low-density lipoprotein, and WBC, including its five-part differential count, but a negative relationship with high-density lipoprotein. Subgroup analyses identified modifying effects of smoking, drinking, exercise, BMI, hypertension, and diabetes on the associations between specific toxicants and CVD risk. CONCLUSIONS: Exposure to BTEX was associated with cardiovascular diseases and cardiovascular risk factors. These findings emphasize the importance of considering blood BTEX levels when assessing cardiovascular health risks.

Real-time monitoring polymerization degree of organic photovoltaic materials toward no batch-to-batch variations in device performance.

Polymerization degree plays a vital role in material properties. Previous methodologies of molecular weight control generally cannot suppress or alleviate batch-to-batch variations in device performance, especially in polymer solar cells. Herein, we develop an in-situ photoluminescence system in tandem with a set of analysis and processing procedures to track and estimate the polymerization degree of organic photovoltaic materials. To support the development of this protocol, we introduce polymer acceptor PYT constructed by near-infrared Y-series small molecule acceptors via Stille polymerization, and shed light on the correlations between molecular weight, spectral parameters, and device efficiencies that enable the design of the optical setup and confirm its feasibility. The universality is verified in PYT derivatives with stereoregularity and fluoro-substitution as well as benzo[1,2-b:4,5-b']dithiophene-based polymers. Overall, our result provides a tool to tailor suitable conjugated oligomers applied to polymer solar cells and other organic electronics for industrial scalability and desired cost reduction.

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study.

BACKGROUND: Targeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19. METHODS: In this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored. RESULTS: Geometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49-1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia. CONCLUSIONS: Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo. GOV IDENTIFIER: NCT04469621, first posted on clinicaltrials.gov on July 14, 2020.