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s' knowledge of positive health seeking behaviours with regard to menstrual disorders.We consider in this work a bicriteria scheduling problem on two different parallel machines with a periodic preventive maintenance policy. The two objectives considered involve minimization of job rejection costs and weighted sum of completion times. They are handled through a lexicographic approach, due to a natural hierarchy among the two objectives in the applications considered. The main contributions of this paper are first to present a new problem relevant to practice, second, to develop a mixed-integer-linear-program model for the problem, and third, to introduce two generalizable tabu-search metaheuristics relying on different neighborhood structures and solution spaces. Computational results for 120 instances (generated from a real case) are reported to empirically demonstrate the effectiveness of the proposed metaheuristics.Four novel triterpene glycosides, taimordisins A-D (1-4), were discovered from fresh fruits of Taiwanese Momordica charantia. The chemical framework and relative stereochemistry of these four natural products were isolated, purified, and determined by using various separation and spectroscopy techniques. Each of them features a unique bicyclic-fused or trifuso-centro-fused ring system. Notably, 1 and 2 are cucurbitane-based compounds possessing a new C-24 and C-2″ carbon-carbon linkage with 5-hydroxy-2-(hydroxymethyl)tetrahydro-4H-pyran-4-one and 6-(hydroxymethyl)tetrahydro-4H-pyran-3,4,4-triol units, respectively, and represented an unprecedented molecular skeleton. In terms of biosynthesis, they all originate from a common precursor 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-β-glucopyranoside. Of two sugar moieties, the one at 23-O-β-glucopyranoside grants each individual congener uniqueness likely through microbial symbiont-mediated intramolecular transformation into two major types of furo[2,3-b]pyranone and furo[3,2-c]pyranone derivatives. These new products possess desirable anti-inflammatory biological activities in addition to being generally regarded as safe.

To explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.

In the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.

A total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only ed followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.

gene variants are an important cause of familial short stature (FSS). Appropriate growth-promoting therapies effectively improve the patient height. Here, we report a therapeutic assessment of cases of seven families of FSS patients with heterozygous

variants. Our findings provide a valuable theoretical basis for the clinical diagnosis and treatment of this disease.

From December 2020 to June 2021, 32 FSS patients were examined in Tianjin Medical University General Hospital (Tianjin, China) by whole-exome sequencing to determine whether

variants were present. Their clinical data were summarized and scrupulously analyzed.

We found seven novel heterozygous

variants c.1051 + 2T > A, c.313T > C (p.S105P), c.2660C > G (p.S887X), c.2153C > A (p. T718K), c.7243delG (p.D2415Tfs

4), c.2911G > T (p.G971X), c.758-7T > C. All seven patients had proportionate short stature and mild skeletal dysplasia. Endocrine examination results were normal. Only one of the patients had an advanced bonis study, seven novel heterozygous variants in ACAN were discovered, which expanded the spectrum of the already established ACAN pathogenic variants. In FSS cohort, the proportion of ACAN variants accounted was large. The treatment with rhGH effectively increased the patient height, but further studies with longer follow-up periods and more extensive observations are required to elucidate the long-term effect.IntroductionSome patients with cervical dystonia (CD) receiving long-term botulinum neurotoxin (BoNT) therapy report early waning of treatment benefit before the typical 12-week reinjection interval.

This phase 4, open-label, randomized, noninferiority study (CD Flex; NCT01486264) compared 2 incobotulinumtoxinA injection schedules (Short Flex 8±2weeks; Long Flex 14±2weeks) in CD patients. Previous BoNT-responsive subjects who reported acceptable clinical benefit lasting<10weeks were recruited. Efficacy and safety were evaluated after 8 injection cycles. The primary endpoint was change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 4weeks after the eighth injection. Secondary endpoints included TWSTRS total and subscale scores. Immunogenicity was assessed in a subset of patients.

Two hundred eighty-two CD patients were randomized and treated (Short Flex, N=142; Long Flex, N=140), and 207 completed the study. Significant improvements in TWSTRS severity from study baseline to 4weeks after cycle 8 were observed in both the Short Flex (4.1 points;

<0.0001) and Long Flex (2.4 points;

=0.002) groups; Short Flex was noninferior to Long Flex (LS mean difference=1.4 points; 95% CI=[-2.9, 0.1]<Δ=2.0). Key secondary endpoints favored Short Flex intervals. Adverse events (AEs) were comparable between groups. There was no secondary loss of treatment effect.

Injection cycles<10weeks for incobotulinumtoxinA are effective (and noninferior to longer intervals) for treating CD patients with early waning of clinical benefit. Shorter injection intervals did not increase AEs or lead to loss of treatment effect.

Injection cycles less then 10 weeks for incobotulinumtoxinA are effective (and noninferior to longer intervals) for treating CD patients with early waning of clinical benefit. Shorter injection intervals did not increase AEs or lead to loss of treatment effect.

Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized.

The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets.

Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggressive and 26 metastatic papillary thyroid carcinoma (PTC) cases were used. Transcriptomics data were normalized and filtered identifying 9394 differentially expressed genes. The genes identified were subjected to pathway analysis using absGSEA identifying PTC related pathways. Three of the genes identified were validated on 508 thyroid cancer biopsies using RNAseq and TNMplot.

Pathway analysis revealed a total of 2193 differential pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. Pathways fontified FDA approved drugs including Vandetanib in addition to others that may prove useful in treating the disease.

Transcriptomics analysis identified putative prognostic targets including EGFR, PTK2B, BCL2, KCNQ1, KCNN4 and CACNA1D. EGFR, PTK2B and KCN44 were validated using thyroid cancer clinical biopsies. The drug search identified FDA approved drugs including Vandetanib in addition to others that may prove useful in treating the disease.

Pancreatic cancer is a common malignant tumor. Multiple studies have shown that procollagen lysyl-hydroxylase (PLOD) family genes were closely related to tumor progression and metastasis in a variety of human cancers. This study aimed to explore the prognosis and biological role of PLOD family genes in pancreatic adenocarcinoma (PAAD).

GEPIA, GEO, HPA, CCLE, Kaplan-Meier plotter, cBioPortal, LinkedOmics, DAVID6.8, STRING, and TIMER were employed to determine the prognostic values and biological function of PLOD family members in PAAD.

The mRNA and protein expression patterns of PLOD family members were noticeably up-regulated in PAAD compared with normal tissues. PLOD family gene expression was also up-regulated in pancreatic cancer cell lines. PLOD1 was correlated with histological and pathological grades of pancreatic cancer. PLOD2 was related to histological grade. The high expression of PLOD1-2 was correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. ALOD family genes could be potential prognostic biomarkers for PAAD.

The findings showed that individual PLOD genes or PLOD family genes could be potential prognostic biomarkers for PAAD.Changes in brain morphology, such as cortical thinning are of great value for understanding the trajectory of brain aging and various neurodegenerative diseases. In this work, we employed a generative neural network variational autoencoder (VAE) that is conditional on age and is able to generate cortical thickness maps at various ages given an input cortical thickness map. To take into account the mesh topology in the model, we proposed a loss function based on weighted adjacency to integrate the surface topography defined as edge connections with the cortical thickness mapped as vertices. Compared to traditional conditional VAE that did not use the surface topological information, our method better predicted "future" cortical thickness maps, especially when the age gap became wider. Our model has the potential to predict the distinctive temporospatial pattern of individual cortical morphology in relation to aging and neurodegenerative diseases.

The present study aimed to enhance understanding of continuity and stability of positive parenting of infants, across age and different settings in women with a history of depression who are at elevated risk for postpartum depression.

Mothers (

= 103) with a history of major depression and their infants were observed during 5-min play and feeding interactions when their infants were 3, 6, and 12 months of age. Summary scores representing mothers' positive parenting were computed separately for each age and context based on ratings of five parenting behaviors. Fimepinostat mw Mothers' depressive symptom levels were assessed at each infant age.

Continuity (consistency of level) and stability (consistency of rank order) were assessed across age and context at both the group and individual level. Across-age analyses revealed continuity in the play context and discontinuity in the feeding context, albeit only at the group level, as well as weak to moderate stability. Across-context analyses revealed higher positive parenting scores in play than feeding at all time points as well as weak to moderate stability.