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Introduction Material and Methods Results Conclusions Evidence suggests that gestational diabetes mellitus (GDM) is associated with subsequent cardiovascular disease; however, it is unclear what impact changes in screening and diagnostic criteria have had on the association of GDM with long‐term outcomes such as cardiovascular disease. The purpose of this study was to determine the association between GDM and subsequent cardiovascular disease during a period of rising gestational diabetes diagnosis in England. Specifically, associations were compared before and after 2008, when national guidelines supporting risk factor‐based screening were introduced.We conducted a cohort study using routinely collected data from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study consisted of persons aged 15–45 years with a livebirth or stillbirth between 1998 and 2017 and without a history of cardiovascular disease or pre‐pregnancy diabetes mellitus. Cox proportional hazards models, with propensity score weighting using matching weights, were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the association of GDM diagnosis in the first recorded pregnancy with subsequent cardiovascular disease.Among 232 315 individuals, the incidence of cardiovascular disease was 6.6 per 1000 person‐years among those with GDM and 2.2 per 1000 person‐years among those without GDM over a mean follow‐up duration of 5.8 years. The overall aHR, 95% CI was 1.91 (1.41, 2.60). Diagnosis of GDM increased over the study period, from 0.7% in 1998–99 to 5.3% in 2017. The effect size was not markedly different in the years before (1998–2007: adjusted HR 2.05, 95% CI 2.05 1.35, 3.12) and after 2008 (2008–2017: adjusted HR 1.79, 95% CI 1.15, 2.80).There was a strong association of GDM with cardiovascular disease after accounting for social and demographic factors and multiple comorbidities, and this association was present both before and after 2008, when national gestational diabetes screening criteria were established. [ABSTRACT FROM AUTHOR]

Aims: Metformin is increasingly used off‐label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes. Materials and Methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018. We included pregnancies of women who initiated metformin or insulin between 20 weeks gestation and pregnancy end. The primary outcome was a composite outcome of large for gestational age (LGA) and macrosomia. The secondary outcomes included small for gestational age (SGA), preterm birth, caesarean delivery, and hypertensive disorders during pregnancy (HDP). Inverse probability weighted‐Cox proportional hazards models were to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI), comparing those who initiated metformin versus insulin at cohort entry, accounting for baseline covariates. Results: Our cohort included pregnancies of 1297 women initiating metformin and of 895 women initiating insulin. Compared to insulin initiation, metformin initiation was associated with a decreased risk of LGA or macrosomia (HR 0.64, 95% CI 0.49, 0.78), Caesarean delivery (HR 0.83, 95% CI 0.69, 0.98), and preterm birth (HR 0.83, 95% CI 0.58, 1.08). The HRs for HDP and SGA were 0.92 (95% CI 0.57, 1.27) and 1.33 (95% CI 0.67, 2.00), respectively. Conclusions: Our study suggests that, compared to initiating insulin, initiating metformin is associated with decreased risks of adverse pregnancy outcomes among women with GDM. These findings provide important real‐world evidence regarding the use of metformin for GDM. [ABSTRACT FROM AUTHOR]

Background: While the benefits of levothyroxine are well‐established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention‐to‐treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non‐users (1:4) on time of diagnosis, gestational week of the first eligible trial and high‐dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results: Based on 159,177 eligible person‐trials (5781 women), the matched cohort included 181 initiators and 640 non‐initiators of levothyroxine, with 57 pregnancy losses occurring during follow‐up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid‐stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non‐initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56). Conclusions: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy. [ABSTRACT FROM AUTHOR]

Aims: The contemporary prescription patterns of antidiabetic drugs following guideline changes recommending metformin as first‐line gestational diabetes (GDM) pharmacotherapy is underexplored. We aimed to examined use of metformin and insulin during pregnancy among women with GDM over 20 years in the United Kingdom. Methods: We conducted a population‐based cohort study using linked data from the Clinical Practice Research Datalink, its pregnancy register and Hospital Episode Statistics from 1998 to 2017. We included pregnancies of women without prior diabetes history who received GDM diagnosis or initiated an antidiabetic drug after 20 weeks gestation. Patient‐level and practice‐level characteristics were compared between metformin initiators and insulin initiators. We described trends of initiating metformin as first‐line treatment and described time to initiation of rescue insulin overall, and by body mass index among metformin initiators. Results: Our cohort included 5633 pregnancies from 5393 women with GDM, of whom 38.9% initiated pharmacotherapy (41% insulin, 59% metformin). Metformin prescriptions (as opposed to insulin) increased substantially, from <5% of pregnancies before 2007 to 42.5% in 2008. Over 85% of pregnancies that were prescribed pharmacotherapy were prescribed metformin as first‐line treatment in 2015. Among metformin initiators, 16% initiated rescue insulin, typically occurring within 40 days of metformin initiation. Choice of GDM pharmacotherapy varied by characteristics, including smoking, obesity, race/ethnicity and general practice regions. Conclusions: Metformin was the most prescribed medication for GDM, with large increases over the past 2 decades. The increasing use of oral‐antidiabetic drugs during pregnancy, consistent with other regions, highlights the need for future studies examining effectiveness and safety of antidiabetic drug use during pregnancy. [ABSTRACT FROM AUTHOR]

Treatment with a magnetic induced electric field (MIEF) under acidic conditions has proven to be an effective method for modifying pectin, enhancing its functional attributes. In this study, the effects of varying excitation voltages of MIEF under acidic conditions on the physicochemical, structural, and functional properties of citrus pectin (CP) were explored. The results demonstrated that compared to CP without MIEF treatment, MIEF-treated CP exhibited enhanced thermal stability, rheological behavior, emulsifying and gel-forming abilities, and antioxidant capacity. These improvements were attributed to higher degrees of esterification, reduced molecular weights, and increased levels of galacturonic acid and homogalacturonan in the structural backbone of the treated CP. Additionally, MIEF treatment under acidic conditions altered the surface morphology and crystalline structure of CP. Therefore, our findings suggest that applying moderate excitation voltages (150–200 V) during MIEF treatment can enhance the functional properties of CP, leading to the production of high-quality modified pectin. [Display omitted] • MIEF treatment under an acidic condition was used to modify citrus pectin (CP). • MIEF-assisted acid treatment CPs had higher GalA content and DE value, and lower M w. • MIEF-assisted acid treatment improved functional properties of CP. • Increasing excitation voltage resulted in the enhancement of the hydrolysis of CP. [ABSTRACT FROM AUTHOR]

Allium plants, including garlic, onions, shallots, and leeks, belong to the Alliaceae family and are utilized as vegetable, medicinal, and ornamental plants. These plants are consumed both raw and cooked and are noted in traditional medicine for their antibacterial, antitumor, and diuretic properties. Allium plants are a rich source of polyphenols, organosulfur compounds, flavonoids, alkaloids, and polysaccharides, which contribute to their health benefits. As consumer interest in the association between diet and health grows, there is an increasing market demand for foods that promote health, particularly those rich in dietary fiber or non-starch polysaccharides. Allium polysaccharides (APS) have molecular weights of 1 × 103–1 × 106 Da containing small amounts of pectin, glucofructan, or glycoproteins and large amounts of fructans. APS, despite its complex structure, is one of the principal active components of Allium plants but is often overlooked, which restricts its practical application. This paper provides a comprehensive overview of the extraction and purification, structural and functional characteristics, bioactivities, structure-function relationships, and chemical modifications of APS, as well as the effects of APS processing and storage. Additionally, this paper outlines future research directions for APS, which will inform its development and application in the food, pharmaceutical, and cosmetic industries. [Display omitted] • Extraction and purification methods of Allium polysaccharides (APS) were summarized. • Structural characteristics and chemical modifications of APS were introduced. • Diversified biological activities and underlying mechanisms of APS were elaborated. • Structure-function relationships of APS were comprehensively analyzed. [ABSTRACT FROM AUTHOR]

[Display omitted] • PFP-T and PFP-UM were slightly degraded after in vitro gastrointestinal digestion. • PFP-T and PFP-UM were obviously degraded and utilized by intestinal microorganisms. • PFP-T and PFP-UM effectively stimulated the proliferation of beneficial bacteria. • PFP-T yielded higher SCFAs content and had better prebiotic potential than PFP-UM. In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella , Megasphaera and Dialister , while suppressed the growth of harmful genera including Escherichia-Shigella , producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health. [ABSTRACT FROM AUTHOR]

Photoperiod/temperature‐sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms–2 (res3), as the male sterility of rvms–2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis. [ABSTRACT FROM AUTHOR]

The prevalent new-user design includes a broader study population than the traditional new-user approach that is frequently used in pharmacoepidemiologic research. In an article appearing in this issue (Am J Epidemiol. 2021;190(7):1341–1348) , Webster-Clark et al. describe the treatment initiator types included in the prevalent new-user design and contrast the causal questions assessed using a prevalent new-user design versus a new-user design. They further applied a series of simulation studies showing the importance of accounting for treatment history in addition to time since initiation of the comparator in the prevalent new-user design. In this commentary, we put their findings in the broader context with a discussion of the strengths and limitations of the prevalent new-user design and settings where it would be most useful. The prevalent new-user design and new-user design both address unique questions of clinical and public health importance. Real-world evidence generated by pharmacoepidemiologic research is increasingly being used by regulators and other knowledge users to inform their decision-making. Understanding the causal questions addressed by different designs is crucial in this process; the study by Webster-Clark et al. represents an important step in addressing this issue. [ABSTRACT FROM AUTHOR]

Purpose: Inversed probability weighted (IPW) estimators are commonly used to adjust for time-fixed or time-varying confounders. However, in high-dimensional settings, including all identified confounders may result in unstable weights leading to higher variance. We aimed to develop a visualization tool demonstrating the impact of each confounder on the bias and variance of IPW estimates, as well as the propensity score overlap.Methods: A SAS macro was developed for this visualization tool and we demonstrate how this tool can be used to identify potentially problematic confounders of the association of statin use after myocardial infarction on one-year mortality in a plasmode simulation study using a cohort of 39,792 patients from the UK (1998-2012).Results: Through the tool's output, we can identify problematic confounders (two instrumental variables) and important confounders by comparing the estimated psuedo MSE with that from the fully adjusted model and propensity score overlap plot.Conclusion: Our results suggest that the analytic impact of all confounders should be considered carefully when fitting IPW estimators. [ABSTRACT FROM AUTHOR]

While prepregnancy obesity increases risk of stillbirth, few studies have evaluated the role of newly developed obesity independent of long-standing obesity. Additionally, researchers have relied almost exclusively on parametric models, which require correct specification of an unknown function for consistent estimation. We estimated the association between incident obesity and stillbirth in a cohort constructed from linked birth and death records in Pennsylvania (2003–2013). Incident obesity was defined as body mass index (weight (kg)/height (m)2) greater than or equal to 30. We used parametric G-computation, semiparametric inverse-probability weighting, and parametric/nonparametric targeted minimum loss-based estimation (TMLE) to estimate the association between incident prepregnancy obesity and stillbirth. Compared with pregnancies from women who stayed nonobese, women who became obese prior to their next pregnancy were estimated to have 2.0 (95% confidence interval (CI): 0.5, 3.5) more stillbirths per 1,000 pregnancies using parametric G-computation. However, despite well-behaved stabilized inverse probability weights, risk differences estimated from inverse-probability weighting, nonparametric TMLE, and parametric TMLE represented 6.9 (95% CI: 3.7, 10.0), 0.4 (95% CI: 0.1, 0.7), and 2.9 (95% CI: 1.5, 4.2) excess stillbirths per 1,000 pregnancies, respectively. These results, particularly those derived from nonparametric TMLE, were highly sensitive to covariates included in the propensity score models. Our results suggest that caution is warranted when using nonparametric estimators to quantify exposure effects. [ABSTRACT FROM AUTHOR]

Reactions of a bis-pyridyl-bis-amide ligand, N,N′-bis(pyridin-3-yl)-2,6-pyridinedicarboxamide (bppdca) with nickel(II) and cobalt(II) salts resulted in a tetragonal molecular cage, [Ni2(bppdca)4(SCN)4] (1), and a 1-D polymeric macrocyclic complex, [Co(bppdca)(SO4)(CH3OH)(DMF)] n ·nCH3OH (2) (DMF = N,N′-dimethylformamide). Compound 1 features a tetragonal cage-like structure. In each cage, four bppdca ligands are twisted in the same direction, which endow the cage with chirality. However, because the twist or screw directions of adjacent cages are contrary, 1 is a mesomer and exhibits no chirality on the whole. Compound 2 possesses a 1-D, double-chain structure containing Co4(SO4)4(bppdca)2 macrocyclic subunits. [ABSTRACT FROM PUBLISHER]

U-shaped tripyridyl ligand 2,6-bis(pyridine-4-carboxamido)pyridine (L) was synthesized and used to assemble metal complexes. The resulting new complexes [Mn(L)3(SCN)2]n (1) and [Co(L)3(SCN)2]n (2) are isostructural, crystallizing in the monoclinic C2/c space group. In compounds 1 and 2, each metal is in a slightly distorted octahedron ligated by six nitrogens from four L and two SCN-. Complexes 1 and 2 possess infinite 1-D zigzag polymeric chain structures where L adopts bridge and terminal coordination. These 1-D coordination polymers assemble into 3-D supermolecules of compounds 1 and 2 through hydrogen bonds. Fluorescence measurements and thermal analysis show that 1 emits strong fluorescence with a single broad band centered at 410 nm upon excitation at 357 nm and the polymeric chain structure is stable up to 340°C. [ABSTRACT FROM AUTHOR]

• Bone metastasis and the number of metastatic lesions > 3 were independent prognostic indicators for M1 NPC patients receiving PICT. • A new two-category M1 subdivision for patients receiving immuno-chemotherapy was generated based on the RPA analysis. • Liver metastasis was no longer an independent prognostic factor for M1 NPC patients receiving PICT. This study aims to better manage de novo metastatic nasopharyngeal carcinoma (NPC) patients receiving palliative immuno-chemotherapy (PICT), thereby easily determining individual survival outcomes. Patients with de novo metastatic NPC from four centers who received first-line PICT were included. We developed a nomogram for the pretherapy overall survival (OS) prediction using a logistic regression model in the training cohort (n = 296). We assessed the performance of this nomogram in a validation cohort. A total of 592 patients were included. The median follow-up time was 29.83 months. Bone metastasis (HR, 2.46; 95 % CI, 1.01–6.21; p = 0.049) and the number of metastatic lesions > 3 (HR, 2.78; 95 % CI, 1.24–6.24; p = 0.013) were independent prognostic indicators. A new two-category M1 subdivision was generated: M1a, defined by the absence of co-existing bone metastasis and the presence of more than three metastatic lesions; and M1b, characterized by the presence of co-existing bone metastasis and the presence of more than three metastatic lesions. The 3-year OS rates of patients with M1a vs. M1b were 87.1 % vs. 60.3 % (p < 0.001). The C-indexes were 0.652 and 0.581 in the training and validation cohorts. The 1-, 2-, and 3-year areas under the curve (AUC) were 0.69, 0.68, 0.68 in the training cohort and 0.64, 0.6, 0.6 in the validation cohort. DCA curves also indicated that the nomogram has good clinical utility. The proposed M1 subdivision provides good OS segregation for patients receiving PICT. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the relationship between incident obesity and stillbirth. The study involved women who became obese prior to a subsequent pregnancy. It analyzed the relationship between internal validity and external validity and the effect of pre-pregnancy obesity on the outcome of pregnancy.

This study aims to investigate dietary and nutritional biochemistry profiles of attention-deficit/hyperactivity disorder (ADHD) and to explore their potential relationship by path analysis. We enrolled 216 children with ADHD and 216 age-, height- and gender-matched controls from 31 elementary schools in Taiwan. Dietary intake of the participants was assessed using a food frequency questionnaire (FFQ). Fasting blood samples were collected to determine the serum levels of multiple nutritional markers. Moreover, we employed a structural equation model (SEM) to link diet, nutritional markers and ADHD. Compared to healthy control, ADHD children had significantly lower serum levels of vitamin B12, folate, vitamin B6, ferritin concentration, and monounsaturated fatty acids (MUFA), but higher levels of serum saturated fatty acids (SFA), n-6/n-3 fatty acid ratio, and inorganic phosphorous concentration. Children with ADHD had more intake of nutrient-poor foods such as high sugar and high fat foods, and had less intake of vegetable, fruit, protein-rich foods than their counterpart. SEM analysis showed that the poor nutritional biochemistry profiles linked the association between unhealthy dietary patterns and ADHD. In conclusion, an unhealthy dietary pattern may be a predecessor of the poor nutritional biochemistry status, and managing diet and nutrition conditions should be considered to improve ADHD symptoms in children. [ABSTRACT FROM AUTHOR]

In this study, we explored the use of magnetic-induced electric field (MIEF) treatment at various excitation voltages to assist three-phase partitioning (TPP) methods in extracting and separating pectic polysaccharides (PFPs) from the peel of fresh passion fruit (Passiflora edulis f. flavicarpa). The findings indicated that applying MIEF treatment prior to TPP separation significantly reduced the total sugar and galacturonic acid contents, as well as the degree of esterification of PFPs, with increasing excitation voltage. This treatment notably enhanced their yields and molecular weights. Although the MIEF treatment did not alter the monosaccharide composition of PFPs, it significantly modified their molar ratios of monosaccharides, thereby altering the backbone structure and neutral sugar side chains, which resulted in varied microstructures. Furthermore, especially at higher excitation voltages (≥300 V), the MIEF treatment improved the thermal stability, rheological, and emulsifying properties of PFPs. Consequently, our data suggest that the MIEF-assisted TPP method is a promising approach for the efficient and environmentally friendly preparation of pectic polysaccharides from plant materials. [Display omitted] • Magnetic-induced electric field (MIEF)-assisted three-phase partitioning was set up. • MIEF effectively increased the yield of passion fruit peel polysaccharides (PFPs). • MIEF treatment obviously affected physicochemical and structural properties of PFPs. • MIEF treatment at a high excitation voltage improved functional properties of PFPs. [ABSTRACT FROM AUTHOR]

In this study, the influences of various concentrations of β-cyclodextrin (β-CD) on the gelation properties of curdlan thermo-irreversible gels were evaluated. The results revealed that water-holding capacity and freeze-thaw stability of the curdlan/β-CD complex gels initially increased but then decreased with increasing β-CD concentration, with the curdlan gel containing 1 % (w / v) β-CD demonstrating the best performance. Moreover, textural characteristics including hardness, gumminess, cohesiveness, and chewiness exhibited similar trends, but springiness showed minor effect. Compared with the pure curdlan gel, the curdlan/β-CD mixed gels exhibited better elastic behavior and greater thermal stability but lower crystallinity. Additionally, scanning electron microscopy (SEM) images of the curdlan/β-CD composite gels revealed fine network structures with relatively continuous pores. The intermolecular hydrogen bonds between curdlan and β-CD were responsible for the enhanced gel properties. Thus, these data suggest that the inclusion of β-CD ameliorates the texture and stability of the curdlan gel by forming hydrogen bonds. • β-CD addition can improve the gel properties of curdlan thermo-irreversible gels. • The curdlan gel containing 1 % β-CD demonstrates the best gelling performance. • Curdlan/β-CD gels show fine network structures with continuous and uniform pores. • The hydrogen bond interaction is conducive to the formation of curdlan/β-CD gels. [ABSTRACT FROM AUTHOR]

This study investigated the effect of trehalose addition (0.5–2.0%) on the gelation properties of curdlan gels were investigated. The results demonstrated that the optimal gelation performance of curdlan-trehalose composite gel was determined at trehalose concentration of 1.0% with preferable water holding capacity, water absorption rate, and freeze-thaw stability. The gelation behavior of the curdlan-trehalose composite gel showed a more intense network structure with increasing storage modulus (G′), loss modulus (G″), and deceasing tan δ at the trehalose concentration in the range of 0%–1%. And the highest gel strength was also observed in 1% trehalose addition. Moreover, the structures characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), Low field nuclear magnetic resonance (LF-NMR) and scanning electron microscope analysis (SEM) all revealed that the addition of trehalose strengthened the hydrogen bonding interaction with curdlan to create a much denser network of composite gel, which would provide a better mechanistic insight of the curdlan-trehalose gel in practical application potentials in food and medicine. [Display omitted] • A novel curdlan-trehalose composite gel system was prepared and characterized. • Trehalose addition could enhance the gelling and rheological properties of composite gels. • The hydrogen bonding interaction dominated the formation of the composite gel. • 1.0% trehalose was the critical concentration for the optimal composite gel system. [ABSTRACT FROM AUTHOR]

Abstract: Through natural evaporation of the reaction solutions of ZnX2 (X=Cl−, CH3COO− and SCN−) and the ligand 2,6-bis(pyridine-4-carboxamido)pyridine (L), three new coordination compounds, [Zn(L)(Cl)2] n ·nCH3OH·nH2O (1), [Zn(L)(CH3COO)2]2 (2) and [Zn(L)3(SCN)2] n (3) have been obtained. In these zinc(II) complexes, ligand L displays various conformers and coordination modes to fabricate the helical chain of 1, the discrete dimer of 2 and the zigzag chain of 3, with the coordination number of ZnII varying from 4 for 1, 5 for 2 to 6 for 3. Through complementary amide hydrogen bonds, their structures are extended into chiral layers, 1D ribbons and a 3D supramolecular network, respectively. Interestingly, the coordination numbers of ZnII, as well as the molecular and supramolecular structures of the resulting coordination complexes, are obviously tuned with the X anion used. Additionally, the TGA of 1 and 2 as well as the fluorescence of the free ligand L and 1 were measured in the solid state. [Copyright &y& Elsevier]

• MRI-detected residual retropharyngeal lymph node significantly affects NPC survival outcomes. • We construct an easy-to-use tool for the pretherapy prediction of retropharyngeal lymph node. • The pretherapy prediction of residual retropharyngeal lymph node may facilitate clinical decision making. To evaluate the prognostic value of MRI-detected residual retropharyngeal lymph node (RRLN) at three months after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and second, to establish a nomogram for the pretherapy prediction of RRLN. We included 1103 patients with NPC from two hospitals (Sun Yat-Sen University Cancer Center [SYSUCC, n = 901] and Dongguan People's Hospital [DGPH, n = 202]). We evaluated the prognostic value of RRLN using Cox regression model in SYSUCC cohort. We developed a nomogram for the pretherapy prediction of RRLN using logistic regression model in SYSUCC training cohort (n = 645). We assessed the performance of this nomogram in an internal validation cohort (SYSUCC validation cohort, n = 256) and an external independent cohort (DGPH validation cohort, n = 202). RRLN was an independent prognostic factor for OS (HR 2.08, 95% CI 1.32–3.29), DFS (HR 2.45, 95% CI 1.75–3.42), DMFS (HR 3.31, 95% CI 2.15–5.09), and LRRFS (HR 3.04, 95% CI 1.70–5.42). We developed a nomogram based on baseline Epstein–Barr virus DNA level and three RLN status-related features (including minimum axial diameter, extracapsular nodal spread, and laterality) that predicted an individual's risk of RRLN. Our nomogram showed good discrimination in the training cohort (C-index = 0.763). The favorable performance of this nomogram was confirmed in the internal and external validation cohorts. MRI-detected RRLN at three months after IMRT was an unfavorable prognostic factor for patients with NPC. We developed and validated an easy-to-use nomogram for the pretherapy prediction of RRLN. [ABSTRACT FROM AUTHOR]

Objective: To identify the association of newly developed prepregnancy overweight and obesity with stillbirth and infant mortality.Methods: We studied subsequent pregnancies of mothers who were normal weight at fertilization of their first identified pregnancy, from a population-based cohort that linked birth registry with death records in Pennsylvania, 2003-2013. Women with newly developed prepregnancy overweight and obesity were defined as those whose body mass index (BMI) before second pregnancy was between 25 and 29.9 or 30 or higher, respectively. Our main outcomes of interest were stillbirth (intrauterine death at 20 weeks of gestation or greater), infant mortality (less than 365 days after birth), neonatal death (less than 28 days after birth) and postneonatal death (29-365 days after birth). Associations of both prepregnancy BMI categories and continuous BMI with each outcome were estimated by nonparametric targeted minimum loss-based estimation and inverse-probability weighted dose-response curves, respectively, adjusting for race-ethnicity, smoking, and other confounders (eg, age, education).Results: A cohort of 212,889 women were included for infant mortality analysis (192,941 women for stillbirth analysis). The crude rate of stillbirth and infant mortality in these final analytic cohorts were 3.3 per 1,000 pregnancies and 2.9 per 1,000 live births, respectively. Compared with women who stayed at a normal weight in their second pregnancies, those becoming overweight had 1.4 (95% CI 0.6-2.1) excess stillbirths per 1,000 pregnancies. Those becoming obese had 3.6 (95% CI 1.3-5.9) excess stillbirths per 1,000 pregnancies and 2.4 (95% CI 0.4-4.4) excess neonatal deaths per 1,000 live births. There was a dose-response relationship between prepregnancy BMI increases of more than 2 units and increased risk of stillbirth and infant mortality. In addition, BMI increases were associated with higher risks of infant mortality among women with shorter interpregnancy intervals (less than 18 months) compared with longer intervals.Conclusion: Transitioning from normal weight to overweight or obese between pregnancies was associated with an increased risk of stillbirth and neonatal mortality. [ABSTRACT FROM AUTHOR]

Background: This study examined variation between users of 'club' and 'hard' drugs in Taiwan in terms of prevalence of use and demographics and psychosocial characteristics.Methods: Data were derived from a survey of 17,837 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling. Participants completed a computer-assisted self-interview on tablet computers which covered use of legal substances, sedatives/hypnotics and prescription analgesics; use of illicit drugs/inhalants, risky sexual experiences; expectations of drugs; and psychological distress.Findings: Approximately 1.29% of respondents reported ever using an illicit drug in their lifetime; prevalence estimates of club drugs (mainly ketamine, marijuana, and ecstasy) were slightly higher than hard drugs (mainly methamphetamine and heroin). Concurrent use of legal substances, particularly problematic use of alcohol and tobacco, as well as non-medical use of prescription drugs, were strong correlates of illicit drug use in general, with club drug use exhibiting an extremely strong association with alcohol use. Club drug users were demographically different from hard drug users, including in terms of their gender, age, and level of educational attainment. They were also more likely to be divorced or widowed, to report risky sexual partnerships and more depressive symptoms than hard drug users.Conclusions: Our findings indicate drug type specific distinct psychosocial characteristics, which may warrant further attention in the design of treatment and intervention programs. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. Methods: The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. Results: Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3–4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. Conclusions: OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful. [ABSTRACT FROM AUTHOR]

Objectives: Nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) was designed to avoid solvent-related toxicities, and improve anti-tumor efficacy via increasing paclitaxel's intratumoral concentration and its uptake by tumor cells. This trial aimed to determine the safety and efficacy of induction NAB-paclitaxel combined with cisplatin followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and Methods: Patients with stage III-IVb NPC received NAB-paclitaxel (260mg/m2) combined with cisplatin (80mg/m2) intravenously on days 1 and 22, followed by cisplatin (80mg/m2) on days 43 and 64, concomitant with intensity-modulated radiation therapy. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-ONC-12002615.Results: From July 2010 to November 2013, 36 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 97.2% (eight complete responses [CRs] and 27 partial responses [PRs]) and 100% (30 CRs and six PRs) after two cycles of induction chemotherapy (ICT) and CCRT, respectively. With a median follow-up time of 45months, the estimated 3-year progression-free survival and cancer-specific survival were 86.1% (95% confidence interval [CI], 69.8-99.8%) and 91.7% (95% CI, 68.9-100.0%), respectively. The most frequent grade 3-4 toxicities were neutropenia (8.6%) and nausea (8.6%) after ICT and thrombocytopenia (34.3%) and leukopenia (28.6%) after CCRT.Conclusion: NAB-paclitaxel combined with cisplatin as an ICT regimen showed encouraging anti-tumor effects and manageable toxicities in LA-NPC. Further randomized controlled trials in phase III of NAB-paclitaxel in patients with LA-NPC are warranted. [ABSTRACT FROM AUTHOR]

Background Whether the waiting time for radical radiotherapy (WRT) detrimentally impacts nasopharyngeal carcinoma (NPC) prognosis is unclear. We estimated the influence of WRT on overall survival (OS) and disease-specific survival (DSS) of NPC. Patients and methods Patients were identified from prospectively maintained database. WRT was calculated from histological diagnosis to initiation of radiotherapy (RT). Survival analysis was estimated using Weibull parametric model and propensity score analysis (PSA). Recursive partitioning analysis (RPA) identified optimal WRT threshold via conditional inference trees to estimate the greatest survival differences based on randomly selected training and validation sets, and this process was repeated 1000 times to ensure threshold robustness. Sensitivity analysis estimated effects of potential unmeasured confounders. Results A total of 9896 patients were included. In multivariate analysis, WRT of 31–60°d, of 61–90°d and of greater than 90°d independently increased mortality risk compared to less than 30°d. Upon RPA, ranges of 30–35°d with the peak of 30°d were confirmed with 89% of simulations validating optimal thresholds. In threshold-based groups, adjusted hazard ratios (HRs) for WRT of greater than 30°d by both Weibull model and PSA were significantly higher than for WRT of less than 30°d [OS: HR = 1.13, 95% confidence interval (CI) 1.04–1.23, P = 0.003; DSS: HR = 1.15, 95% CI 1.05–1.26, P = 0.002]. Sensitivity analysis revealed robustness of results. Conclusions WRT independently affects survival. Increasing WRT beyond 30°d was most consistently detrimental to survival. WRT of NPC should be as short as reasonably achievable (ASARA). [ABSTRACT FROM AUTHOR]

Background: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.Methods: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.Results: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.Conclusion: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.Trial Registration: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060 . [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests a role for micro RNAs (mi RNAs) in regulating various processes of mammalian postnatal development and aging. To investigate the changes in blood-based mi RNA expression from preterm infants to adulthood, we compared 365 mi RNA expression profiles in a screening set of preterm infants and adults. Approximately one-third of the mi RNAs were constantly expressed from postnatal development to adulthood, another one-third were differentially expressed between preterm infants and adults, and the remaining one-third were not detectable in these two groups. Based on their expression in infants and adults, the mi RNAs were categorized into five classes, and six of the seven mi RNAs chosen from each class except one with age-constant expression were confirmed in a validation set containing infants, children, and adults. Comparing the chromosomal locations of the different mi RNA classes revealed two hot spots: the mi RNA cluster on 14q32.31 exhibited age-constant expression, and the one on 9q22.21 exhibited up-regulation in adults. Furthermore, six mi RNAs detectable in adults were down-regulated in older adults, and four chosen for individual quantification were verified in the validation set. Analysis of the network functions revealed that differentially regulated mi RNAs between infants and adults and mi RNAs that decreased during aging shared two network functions: inflammatory disease and inflammatory response. Four expression patterns existed in the 11 mi RNAs from infancy to adulthood, with a significant transition in ages 9-20 years. Our results provide an overview on the regulation pattern of blood mi RNAs throughout life and the possible biological functions performed by different classes of mi RNAs. [ABSTRACT FROM AUTHOR]

A 2D cadmium(II) coordination polymer with oxalate and 2,2'-bipyridine, [Cd2(bpy)(ox)2(H2O)2]n · nH2O, was synthesized and the single crystal structure was determined by X-ray crystallography. Thermal properties and the decomposition kinetics of the title complex were studied showing that the decomposition of this complex in N2 is a two-step process, A [image omitted]. Kinetic parameters were obtained. [ABSTRACT FROM AUTHOR]

Background: Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. Methods: Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway. Results: CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway. Conclusion: The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC. [ABSTRACT FROM AUTHOR]