Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

Noncovalent Interaction Boosts Performance and Stability of Organic Solar Cells Based on Giant-Molecule Acceptors.

Designing giant-molecule acceptors is deemed as an up-and-coming strategy to construct stable organic solar cells (OSCs) with high performance. Herein, two giant dimeric acceptors, namely, DYV and DYFV, have been designed and synthesized by linking two Y-series derivatives with a vinyl unit. DYFV exhibits more red-shifted absorption, down-shifted energy levels, and enhanced intermolecular packing than DYV because the intramolecular noncovalent interaction (H···F) of DYFV leads to better coplanarity of the backbone. The D18:DYFV film owns a distinct nanofibrous nanophase separation structure, a more dominant face-on orientation, and more balanced carrier mobilities. Therefore, the D18:DYFV OSC achieves a higher photoelectron conversion efficiency of 17.88% and a longer-term stability with a t80 over 45,000 h compared with the D18:DYV device. The study demonstrates that the intramolecular noncovalent interaction is a superior strategy to design giant-molecule acceptors and boost the photovoltaic performance and stability of the OSCs.

A-A Strategy Enables Desirable Performance of All-Polymer Solar Cells Fabricated with Nonhalogenated Solvents.

Most polymer acceptors have been designed by applying a D (electron-rich unit)-A (electron-deficient unit) strategy, which are principally processed with halogenated solvents to fabricate all-polymer solar cells (all-PSCs). Two novel polymer acceptors, containing an A-A type backbone, were designed and synthesized, which can be readily dissolved in o-xylene. The polymer PY-FBTA, comprising a Y6 derivative as the first A unit and a benzotriazole derivative as the second A unit, shows smaller dihedral angles in the backbone, stronger molecular interactions, higher LUMO level, more complementary absorption spectrum, and better morphology with PM6 than the polymer PY-DPP comprising a diketopyrrolopyrrole derivative as the second A unit. Accordingly, the PM6:PY-FBTA all-PSC achieves a higher PCE of 13.95% than the all-PSC based on PM6:PY-DPP (9.51%) for thoroughly improved Jsc (22.34 mA cm-2), Voc (0.963 V), and FF (64.84%) values, which are fabricated with o-xylene as the solvent. This work demonstrates that the A-A structure is a desirable strategy for designing polymer acceptors for efficient all-PSCs prepared with nonhalogenated solvents.

Two undescribed steroids from Munronia pinnata (Wall.) W. Theob.

Two undescribed steroids, named (15 R)-2,15-dihydroxypregna-1,4-dien-3,16-dione (1) and 2,15-dihydroxypregna-1,4,14-trien-3,16-dione (2), were isolated from the aerial parts of Munronia pinnata (Wall.) W. Theob. The structure elucidation of two compounds was performed by using spectroscopic methods and comparing the literature. Compound 2 exhibited inhibitory effect against PTP-1B with an IC50 value of 152.07 ± 3.33 µM, and compound 1 was inactive.

Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

CONTEXT: While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. OBJECTIVE: We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. METHODS: Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. RESULTS: Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. CONCLUSION: A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

Hyperkyphosis and mortality risk in older men: The osteoporotic fractures in men study.

INTRODUCTION: Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk. METHODS: Men aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity. RESULTS: During a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks-measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality. CONCLUSIONS: Increasing blocks-measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.

The complete mitochondrial genome of the jumping plant bug Halticus minutus Reuter, 1885 (Hemiptera: Miridae).

The complete mitochondrial genome of Halticus minutus was sequenced and analyzed in this study. The mitochondrial genome is 15,403 bp in size and comprises 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region (D-loop). The nucleotide composition of the mitogenome is 41.81% A, 32.50% T, 10.43% G, and 15.26% C. Despite only a few references available on the complete mitochondrial genome of Miridae, phylogenetic analysis suggested that H. minutus is most closely related to Nesidiocoris tenuis.

Properties of butyrylated lotus seed starch with butyryl groups at different carbon positions.

The objectives of this study were to investigate the properties of butyrylated lotus seed starch (LSB). LSB was prepared using an aqueous phase method and the substitution occurred at C2, C3, and C6. The surface of starch esters with high DS became rougher and more broken. Fourier transform infrared spectroscopy proved that the carbonyl group was successfully incorporated into the starch. The degree of crystallinity and molecular weight decreased as DS increased. Moreover, the thermal analysis and viscosity showed a lower gelatinization enthalpy and final viscosity of LSB compared with the unbutyrylated starch (LSB-0). The in vitro digestion characteristics showed that with different distributions at C2, C3, and C6, the content of resistant starch increased, indicating that LSB with higher DS had stronger resistance to digestion. This study revealed that the distribution of butyryl groups at different carbon positions was related to the properties.

Transcriptome analysis of eutopic endometrial stromal cells in women with adenomyosis by RNA-sequencing.

This study aimed to identify differentially expressed genes (DEGs) and molecular pathways in eutopic endometrial stromal cells (EuESCs) from adenomyosis (AM) patients and to provide a new insight into the disease mechanisms. The gene expression profiles in adenomyotic EuESCs (A-EuESCs) and normal ESCs (N-ESCs) were analyzed by RNA-sequencing (RNA-Seq) and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed to obtain insights into the functions of DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and their hub genes were identified. A total of 458 up-/363 down-regulated genes were identified in A-EuESCs versus N-ESCs. The GO enrichment analysis showed that these genes were significantly enriched in calcium-dependent cell-cell adhesion. The most significant term of the KEGG pathway analysis was cytokine-cytokine receptor interaction. There were 145 nodes in the PPI network of the 157 DEGs, which were identified in significant enrichment pathway by the KEGG pathway analysis in N-ESCs and A-EuESCs. The PPI network revealed that IL-6 was a central hub gene. Besides, IL-6 was found as a central hub gene in the pro-inflammatory/chemotactic subnetwork, and EGF was noted as a central hub gene in the angiogenesis subnetwork. Our study indicated the alterations of transcriptomic profiles in A-EuESCs and provided new insights into the pathogenesis of AM. The A-EuESCs in women with AM have fundamental abnormalities that may predispose to pro-invasion/migration and angiogenesis.

Polymerized Naphthalimide Derivatives as Remarkable Electron-Transport Layers for Inverted Organic Solar Cells.

Two polymerized naphthalimide derivatives, named as N-TBHOB and N-DBH, are prepared by quaternization. They exhibit excellent performance as electron-transport layers (ETLs) in inverted organic solar cells (i-OSCs). The results indicate N-TBHOB with a reticulated structure owns a superior performance on electron extraction, electron transport, thickness tolerance, and less carrier recombination compared with N-DBH with linear structure. The i-OSCs based on N-TBHOB with PTB7-Th:PC71 BM as the active layer achieve power conversion efficiencies (PCEs) of 10.72% and 10.03% under the thickness of 11 and 48 nm respectively, which indicates N-TBHOB possesses better thickness tolerance than most of organic ETLs in i-OSCs. N-TBHOB also shows more competent performance than N-DBH and ZnO in nonfullerene i-OSCs for comprehensively improved Jsc , Voc , and fill factor (FF) values. Its i-OSC with PM6:Y6 blend presents a high PCE of 16.78%. The study provides an efficient strategy to prepare ETLs by combining conjugated and nonconjugated units with a reticulated structure in the backbone for high-performance i-OSCs.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome.

AIMS: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. METHODS: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. RESULTS: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. CONCLUSIONS: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.

Influence of Dexmedetomidine on Diaphragm Function and Postoperative Outcomes in ICU Patients with Mechanical Ventilation.

OBJECTIVE: To probe into the influence of dexmedetomidine (DEX) on diaphragm function and postoperative outcomes of mechanically ventilated patients in the intensive care unit (ICU). METHODS: 84 patients with mechanical ventilation (MV) in the ICU of our hospital were selected as the research participants, including 38 patients in the control group (CG) sedated with midazolam (MZ) and 46 patients in the research group (RG) with DEX sedation. Ramsay sedation score, visual analogue scale (VAS), and restlessness score (RS) were used to evaluate their state before sedation (T0), as well as 2 h (T1), 6 h (T2), and 24 h (T3) after sedation, and the alterations of mean arterial pressure (MAP) and heart rate (HR) were recorded. Serum cortisol (Cor), adrenocorticotropic hormone (ACTH), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured before and 24 h after sedation. The end-inspiratory diaphragm thickness (DTei) and end-expiratory diaphragm thickness (DTee) were measured within 2 h after the initiation of MV and 5 min after the spontaneous breathing test (SBT), and the diaphragm thickening fraction (DTF) was calculated. Finally, the ventilator weaning, MV time, and the incidence of adverse reactions (ADs) of the two groups were counted. RESULTS: T0 and T3 witnessed no distinct difference in Ramsay, VAS, and RS scores between the two arms (P > 0.05), but at T1 and T2, RG had better sedation state and lower VAS and RS scores than CG (P < 0.05), with more stable vital signs (P < 0.05). After sedation, the contents of oxidative stress and inflammatory factors in RG were lower, while DTee, DTei, and DTF were higher, versus CG (P < 0.05). Moreover, RG presented higher success rate of first ventilator weaning, less MV time, and lower incidence of ADs than CG (P < 0.05). CONCLUSIONS: DEX is effective in mechanically ventilated patients in the ICU, which can protect patients against diaphragm function damage, improve the success rate of ventilator weaning, and benefit the postoperative outcome, with excellent and rapid sedation effect and less stress damage to patients.

Changes in Regional Fat Distribution and Anthropometric Measures Across the Menopause Transition.

CONTEXT: The relation between the menopause transition (MT) and changes in regional fat distribution is uncertain. OBJECTIVE: To determine whether the MT is associated with the development of central adiposity. DESIGN: Longitudinal analysis from the Study of Women's Health Across the Nation, spanning 1996-2013 (median follow-up 11.8 years). SETTING: Community-based. PARTICIPANTS: 380 women with regional body composition measures by dual energy X-ray absorptiometry. Mean baseline age was 45.7 years; racial/ethnic composition was 16% Black, 41% Japanese and 43% White. OUTCOMES: Changes in android, gynoid and visceral fat and waist and hip circumferences. RESULTS: Android fat increased by 1.21% per year (py) and 5.54% py during premenopause and the MT, respectively (each P < 0.05). Visceral and gynoid fat began increasing at the MT, annualized changes were 6.24% and 2.03%, respectively (each P < 0.05). Postmenopausal annual trajectories decelerated to 1.47% (visceral), 0.90% (android), and -0.87% (gynoid), (all non-zero, P < 0.05). Waist girth grew during premenopause (0.55% py), the MT (0.96% py), and postmenopause (0.55% py) (all non-zero, P < 0.05; not statistically different from each other). Hip girth grew during premenopause (0.20% py) and the MT (0.35% py) (each non-zero, P < 0.05; not statistically different from each other) and decelerated to zero slope in postmenopause. Results are for the White referent; there were statistically significant differences in some trajectories in Black and Japanese women. CONCLUSIONS: The MT is associated with the development of central adiposity. Waist or hip circumferences are less sensitive to changes in fat distribution.

Race/ethnic difference in trabecular bone score in midlife women: The Study of Women's Health Across the Nation (SWAN).

There was no difference in Trabecular Bone Score (TBS) comparing White and Black women after adjusting for body mass index (BMI) and diabetes status. Japanese women had lower TBS than White women. Our results diverge from established differences in fracture rates by race/ethnicity. INTRODUCTION: The TBS was developed as an indirect measure of vertebral bone microarchitecture derived from texture analysis of lumbar spine DXA scans. There is little information on race/ethnic differences in TBS. METHODS: We compared TBS in 656 White, 492 Black, and 268 Japanese pre- and early perimenopausal women. We used a beta version of TBS that accounts for tissue thickness using DXA measured soft tissue thickness rather than BMI. The relation between BMI and tissue thickness corrected TBS differed by BMI; we used a three-segment linear spline to adjust for BMI. RESULTS: The women were, on average, 46.5 years of age; 50% were premenopausal. In BMI and diabetes adjusted models, there was no difference in TBS between White and Black women. TBS was modestly (2%) lower in the Japanese women compared to White women, p = 0.04. In a sensitivity analysis, restricting the analysis to those with BMI 24-31 kg/m2, results were similar. CONCLUSIONS: TBS was similar in Black and White women after accounting for tissue thickness and adjusting for BMI, diabetes, and other covariates. The Japanese women had modestly lower TBS. These results diverge from established race/ethnic differences in fracture rates and areal bone mineral density, underscoring the need for further studies.

Increase in C-Reactive Protein Predicts Increase in Rate of Bone Mineral Density Loss: The Study of Women's Health Across the Nation.

This longitudinal cohort study's aim was to detect whether larger increases in C-reactive protein (CRP) predict greater amounts of subsequent bone loss in women transitioning from premenopause to postmenopause. Participants were initially 42 to 52 years of age and premenopausal or early perimenopausal. The sample included 1431 women who were not using hormone therapy and whose CRP values were not consistent with acute inflammation. Individual fixed effects (IFE) models estimated the association of log2 CRP with subsequent bone mineral density (BMD) decline rate, adjusted for menopause transition (MT) stage (1: premenopausal or early perimenopausal; 2: late perimenopausal or early postmenopausal; or 3: late postmenopausal), body mass index, diabetes, smoking, alcohol, bone active medications, and anti-inflammatory medications. BMD decline at both the lumbar spine (LS) and femoral neck (FN) was faster for observations made in MT stage 2 than that during other stages (all p < .001). In adjusted IFE models, MT stage modified the relation between increase in CRP and BMD decline rate (interaction p values <.05). Each within-woman doubling of CRP was associated with a 0.09% faster yearly decline in FN BMD in MT stages 1 (p = .006) and 3 (p = .03), and 0.10% faster decline in LS BMD in MT stage 3 only (p = .007). Within-woman increases in CRP in premenopause and early perimenopause and in late postmenopause predict faster BMD decline in the next ~2 years, but the magnitude of CRP's effect is small. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Faster Lumbar Spine Bone Loss in Midlife Predicts Subsequent Fracture Independent of Starting Bone Mineral Density.

CONTEXT: Bone mineral density (BMD) decreases rapidly during menopause transition (MT), and continues to decline in postmenopause. OBJECTIVE: This work aims to examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. METHODS: The Study of Women's Health Across the Nation, a longitudinal cohort study, included 451 women, initially premenopausal or early perimenopausal, and those transitioned to postmenopause. Main outcome measures included time to first fracture after early postmenopause. RESULTS: In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone-detrimental or -beneficial medications, each SD decrement in lumbar spine (LS) BMD before MT was associated with a 78% increment in fracture hazard (P = .007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (P = .04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and an LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (P = .03). At the femoral neck, neither starting BMD nor rate of BMD decline was associated with fracture. CONCLUSION: At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with a below-median starting LS BMD and a faster-than-median LS BMD decline have the greatest fracture risk.

Longitudinal Assessment of Physical Activity and Cognitive Outcomes Among Women at Midlife.

Importance: The increasing prevalence of cognitive decline, impairment, and dementia spurs intense interest in cognitive preservation strategies. Objective: To explore the longitudinal association between physical activity (PA) and cognitive performance among women at midlife. Design, Setting, and Participants: This cohort study is an analysis from the Study of Women's Health Across the Nation. Enrollment occurred from 1996 through 1997, and follow-up extended into 2017. Included individuals were those who had undergone cognitive measures during the first 3 cognitive test visits and had at least 1 additional cognitive measurement. Stroke prior to baseline was an exclusion, and observations were censored for subsequent stroke. Data were analyzed from June 2018 through August 2019. Exposures: Engaging in sport or exercise PA (self-reported). Main Outcomes and Measures: The Symbol Digit Modalities Test (SDMT) was used to assess cognitive processing speed. The East Boston Memory Test-Delayed (EBMT-D) was used to measure verbal episodic memory. The digit span backwards (DSB) test was used to evaluate working memory. Results: Among 1718 women with a median (range) observation time of 11.9 (0.60-13.5) years, the mean (SD) baseline age was 45.7 (2.5) years. From baseline through age 61 years, mean change in SDMT score was -0.20 annually (95% CI, -0.26 to -0.15; P < .001). After age 61 years, the mean change in SDMT was -0.51 yearly (95% CI, -0.54 to -0.41; P < .001). Beginning at age 58 years of the mean change in EBMT was -0.03 yearly (95% CI, -0.04 to -0.02; P < .001). Starting at age 61 years, mean (SD) change in DSB was -0.03 annually (95% CI, -0.04 to -0.01; P = .001). When adjusted for attrition and practice effect, PA was associated with higher concurrent SDMT and EBMT scores and a smaller decrease in SDMT score. For each unit increment in PA, there was a 0.36 increment in concurrent SDMT score (95% CI, 0.14 to 0.59; P = .002) and a 0.10 increment in concurrent EBMT score (95% CI, 0.05 to 0.15; P < .001). Greater PA was associated with a smaller annual mean decrease in SDMT score (0.06 yearly; 95% CI, 0.02 to 0.09; P = .001). After additional adjustment for demographic characteristics, menopause symptoms, hormone therapy use, and the presence of diabetes and hypertension, PA was not associated with trajectories (ie, levels or slopes) of any cognitive outcome. Conclusions and Relevance: This cohort study found no association between greater PA levels and cognitive outcomes among women in midlife, unlike cohort studies that begin observations at later ages, which may be associated with confounding by reverse causation (ie, cognitive decline associated with an outcome of lower PA levels).

Knowledge-Powered Deep Breast Tumor Classification With Multiple Medical Reports.

Breast tumor classification with multiple medical reports such as B-ultrasound, Mammography (X-ray) and Nuclear Magnetic Resonance Imaging (MRI) is crucial to the intelligent cancer diagnosis system. Unlike the other domain texts, the medical reports have latent hierarchical syntactic structures and have hidden rich semantic information about the entities and relationships, which poses a great challenge of breast cancer classification. In this article, we proposed a Knowledge-powered Deep Breast Tumor Classification model (KDBTC), which takes the semantic information as a kind of prior knowledge and incorporated it into deep neural networks. Specially, our proposed model first uses Hierarchical Attention Bidirectional Recurrent Neural Networks (HA-BiRNNs) to encode the syntax-aware representation of medical reports in a hierarchical way. In the HA-BiRNN, a hierarchical neural network structure, consisting in two encoder layers of BiRNN (Bidirectional Recurrent Neural Networks), mirrors the hierarchical structure of medical reports, and a hierarchical attention mechanism, consisting of two levels attentions, attends to important elements within clinical report with word-level attention and sentence-level attention. Secondly, our model obtains the semantic information relevant to the medical reports from the clinical domain semantic tree, and encodes the semantic representation of medical reports by using Tree Structured Recurrent Neural Network with gated recursive units (Tree-GRUs). Finally, we classify breast tumors by combining both the syntax and semantic representations of medical reports. We evaluate our method on the real-world breast cancer medical reports, and results show that our method achieves higher performance on breast cancer classification.

Melatonin Patterns and Levels During the Human Menstrual Cycle and After Menopause.

CONTEXT: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging. OBJECTIVE: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging. METHODS: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA). RESULTS: In addition to the organized patterns of hormone metabolites (estrone conjugates [E1c], and pregnanediol glucuronide [PdG]) and gonadotropins that characterized ovulatory menstrual cycles, there was a late luteal rise in aMT6s. In NELA collections, there was no periodicity of E1c, PdG, gonadotropins, or aMT6s. The strongest predictors of aMT6s levels were PdG values 11 to 12 days prior to aMT6s (ß = 1.46, P = .001 and ß = 1.44, P = .001, respectively). E1c and gonadotropins were not statistically significantly associated with aMT6s. Mean aMT6s in premenopause was 53.5 ng/mL, greater than the mean of 37.4 ng/mL in postmenopausal samples from the same women (P = .0002). CONCLUSIONS: This study confirms a late luteal melatonin rise, likely signaled by progesterone, which may influence menstrual cycle pacemaker control. Melatonin declined from premenopause to postmenopause. A high correlation between menopause transition stage and age precludes distinction between the influences of ovarian and chronological aging.