Demirwesth7123

Among 3311 adults (mean age 53.3 years, 63% female) 584 participants developed diabetes over a median of 7.7 years. After adjustment, 25(OH)D ≥20 compared to <12 ng/ml was associated with a HR 0.78 (95% CI 0.61, 1.00). Among participants with detectable 25(OH)D2 and 25(OH)D3 (n = 1671), 25(OH)D ≥ 20 ng/ml compared to <12 ng/ml was associated with a 35% (HR 0.65, 95% CI 0.46, 0.91) lower risk of diabetes.

Higher levels of 25(OH)D may be protective against the development of diabetes among AA individuals, particularly among those with detectable 25(OH)D2 and 25(OH)D3.

Higher levels of 25(OH)D may be protective against the development of diabetes among AA individuals, particularly among those with detectable 25(OH)D2 and 25(OH)D3.The need to design computing platforms with low water footprint and enhanced energy efficiency makes non-terrestrial computing platforms attractive. Large scale computing platforms in non-terrestrial environments are increasingly receiving attention. In this regard, underwater data centers (UDCs) are considered to have operational benefits due to their low cooling cost. Underwater data centers experience challenges due to marine heat waves. The occurrence of marine heat waves limits the amount of ocean water available for UDC cooling. This paper proposes a mechanism to detect marine heat waves, and ensure continued UDC functioning. The proposed mechanism utilizes reservoirs to store water and ensure continued functioning of underwater data center. In addition, the proposed research presents the reservoir as a service (RaaS) for ensuring UDC cooling. Furthermore, the presented research also describes modular form factor approach for UDC development. This is being done with the aim of enhancing UDC adoption and use in capital constrained contexts. The underwater data center operational duration is investigated. Evaluation shows that the proposed solution enhances the operational duration by an average of (5.5-12.3) % and (5.2-11.5) % given that marine heat waves span 10 epochs and 15 epochs during an operational phase, respectively.Acute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia characterized by unrestricted megakaryoblast proliferation and poor prognosis. Thrombopoietin receptor c-Mpl is a primary regulator of megakaryopoeisis and a potent mitogenic receptor. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however, the role of c-Mpl in AMKL progression remains largely unexplored. Here, we identified increased expression of a c-Mpl alternative splicing isoform, c-Mpl-del, in AMKL patients. We found that c-Mpl-del expression was associated with enhanced AMKL cell proliferation and chemoresistance, and decreased survival in xenografted mice, while c-Mpl-del knockdown attenuated proliferation and restored apoptosis. Interestingly, we observed that c-Mpl-del exhibits preferential utilization of phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in upregulation of GATA1 and downregulation of DDIT3-related apoptotic responses conducive to AMKL chemoresistance and proliferation. Thus, this study elucidates the critical roles of c-Mpl alternative splicing in AMKL progression and drug resistance, which may have important diagnostic and therapeutic implications for leukemia accelerated by c-Mpl-del overexpression.In the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of the proper target regions of regenerative axons is essential to uncover the modalities of adult reinnervation. In this study, we use mass spectrometry (MS)-based quantitative proteomics to address the proteomes of major nuclei of the adult visual system. These analyses reveal that guidance-associated molecules are expressed in adult visual targets. Moreover, we show that bilateral optic nerve injury modulates the expression of specific proteins. In contrast, the expression of guidance molecules remains steady. Finally, we show that regenerative axons are able to respond to guidance cues ex vivo, suggesting that these molecules possibly interfere with brain target reinnervation in adult. Using a long-distance regeneration model, we further demonstrate that the silencing of specific guidance signaling leads to rerouting of regenerative axons in vivo. Altogether, our results suggest ways to modulate axon guidance of regenerative neurons to achieve circuit repair in adult.The retinal pigment epithelium (RPE) plays an important role in the development of diabetic retinopathy (DR), a leading cause of blindness worldwide. Here we set out to explore the role of Akt2 signaling-integral to both RPE homeostasis and glucose metabolism-to DR. Using human tissue and genetically manipulated mice (including RPE-specific conditional knockout (cKO) and knock-in (KI) mice), we investigate whether Akts in the RPE influences DR in models of diabetic eye disease. We found that Akt1 and Akt2 activities were reciprocally regulated in the RPE of DR donor tissue and diabetic mice. Akt2 cKO attenuated diabetes-induced retinal abnormalities through a compensatory upregulation of phospho-Akt1 leading to an inhibition of vascular injury, inflammatory cytokine release, and infiltration of immune cells mediated by the GSK3β/NF-κB signaling pathway; overexpression of Akt2 has no effect. We propose that targeting Akt1 activity in the RPE may be a novel therapy for treating DR.The persistent difficulty in conceptualizing the relationship between addictive and other mental disorders stands out among the many challenges faced by the field of Psychiatry. The different philosophies and schools of thought about, and the sheer complexity of these highly prevalent clinical conditions make progress inherently difficult, not to mention the profusion of competing and sometimes contradictory terms that unnecessarily exacerbate the challenge. The lack of a standardized term adds confusion, fuels stigma, and contributes to a "wrong door syndrome" that captures the difficulty of not only diagnosing but also treating addictive and other mental disorders in an integrated manner. The World Association on Dual Disorders (WADD) proposes the adoption of the term "Dual Disorder" which, while still arbitrary, would help harmonize various clinical and research efforts by rallying around a single, more accurate, and less stigmatizing designation.How fast the Northern Hemisphere (NH) forest biome tracks strongly warming climates is largely unknown. Regional studies reveal lags between decades and millennia. Here we report a conundrum Deglacial forest expansion in the NH extra-tropics occurs approximately 4000 years earlier in a transient MPI-ESM1.2 simulation than shown by pollen-based biome reconstructions. Shortcomings in the model and the reconstructions could both contribute to this mismatch, leaving the underlying causes unresolved. The simulated vegetation responds within decades to simulated climate changes, which agree with pollen-independent reconstructions. Thus, we can exclude climate biases as main driver for differences. Instead, the mismatch points at a multi-millennial disequilibrium of the NH forest biome to the climate signal. Therefore, the evaluation of time-slice simulations in strongly changing climates with pollen records should be critically reassessed. Our results imply that NH forests may be responding much slower to ongoing climate changes than Earth System Models predict.

We examined links among dietary patterns (DPs), insulin resistance (IR), and diabetes risk by heritage in the Hispanic Community Health Study/Study of Latinos.

Hispanics/Latinos of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American heritage aged 18-74 years and diabetes-free completed two 24 h dietary recalls at baseline (2008-2011) and provided 6-year follow-up data (2014-2017; n = 7774). We classified 6-year IR status [improved, unchanged (referent), worsened] using a 1-SD change in fasting insulin between visits and defined incident diabetes based on American Diabetes Association criteria. We derived heritage-specific DPs via principal factor analysis and estimated their associations with 6-year IR status (multinomial) and incident diabetes (binary) using complex survey-based logistic regression.

Five overarching DPs based on high-loading foods were shared by two or more heritage groups "Burger, Fries, & Soft Drinks"; "White Rice, Beans, & Red Meats"; "Fish & Wh and soft drinks and another characterized by higher intakes of white rice, beans, and red meats may be adversely associated with IR and diabetes risk in some Hispanic/Latino heritage groups. Future work is needed to offer more heritage-specific dietary guidance for diabetes prevention in this population.Fiber-based micro-endoscopes are a critically important tool for minimally-invasive deep-tissue imaging. However, current micro-endoscopes cannot perform three-dimensional imaging through dynamically-bent fibers without the use of bulky optical elements such as lenses and scanners at the distal end, increasing the footprint and tissue-damage. Great efforts have been invested in developing approaches that avoid distal bulky optical elements. However, the fundamental barrier of dynamic optical wavefront-distortions in propagation through flexible fibers limits current approaches to nearly-static or non-flexible fibers. Here, we present an approach that allows holographic, bend-insensitive, coherence-gated, micro-endoscopic imaging using commercially available multi-core fibers (MCFs). We achieve this by adding a partially-reflecting mirror to the distal fiber-tip, allowing to perform low-coherence full-field phase-shifting holography. We demonstrate widefield diffraction-limited reflection imaging of amplitude and phase targets through dynamically bent fibers at video-rate. Our approach holds potential for label-free investigations of dynamic samples.Androgen ablation therapy is the standard of care for newly diagnosed prostate cancer (PC) patients. PC that relapsed after hormonal therapy, referred to as castration-resistant PC (CRPC), often presents with metastasis (mCRPC) and is the major cause of disease lethality. The few available therapies for mCRPC include the Taxanes Docetaxel (DTX) and Cabazitaxel (CBZ). Alas, clinical success of Taxanes in mCRPC is limited by high intrinsic and acquired resistance. Therefore, it remains essential to develop rationally designed treatments for managing therapy-resistant mCRPC disease. The major effect of Taxanes on microtubule hyper-polymerization is a prolonged mitotic block due to activation of the Spindle Assembly Checkpoint (SAC). Taxane-sensitive cells eventually inactivate SAC and exit mitosis by mitotic catastrophe, resulting in genome instability and blockade of proliferation. Resistant cells remain in mitotic block, and, upon drug decay, resume mitosis and proliferation, underlying one resistance mechanism.