Miracle-dz/UniFAR-FTUs huggingface dataset:
A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside

Purpose: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells. Experimental Design: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo. Results: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate–pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC. Conclusions: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801–15. ©2013 AACR.
Circadian rhythms have significant effects on leaf-to-canopy gas exchange under field conditions

Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance and other cell and leaf level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole canopy fluxes remains uncertain and diurnal CO2 and H2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the CNRS Ecotron. Canopy and leaf level fluxes were constantly monitored under field-like environmental conditions, and also under constant environmental conditions (no variation in temperature, radiation or other environmental cues). Here we show first direct experimental evidence at canopy scales of circadian gas exchange regulation: 20-79% of the daily variation range in CO2 and H2O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance in commonly used stomatal conductance models. Overall, our results show that overlooked circadian controls affect diurnal patterns of CO2 and H2O fluxes in entire canopies and in field-like conditions, although this process is currently unaccounted for in models.
Low pre-exercise muscle glycogen availability offsets the effect of post-exercise cold water immersion in augmenting PGC-1 gene expression

We assessed the effects of post-exercise cold-water immersion (CWI) in modulating PGC-1 a mRNA expression in response to exercise commenced with low muscle glycogen availability. In a randomized repeated-measures design, nine recreationally active males completed an acute two-legged high-intensity cycling protocol (8 9 5 min at 82.5% peak power output) followed by 10 min of two-legged post-exercise CWI (8 ° C) or control conditions (CON). During each trial, one limb commenced exercise with low (LOW: < 300 mmol (cid:1) kg (cid:3) 1 dw) or very low (VLOW: < 150 mmol (cid:1) kg (cid:3) 1 dw) pre-exercise glycogen concentration, achieved via completion of a one-legged glycogen depletion protocol undertaken the evening prior. Exercise increased ( P < 0.05) PGC-1 a mRNA at 3 h post-exercise. Very low muscle glycogen attenuated the increase in PGC-1 a mRNA expression compared with the LOW limbs in both the control (CON VLOW ~ 3.6-fold vs. CON LOW ~ 5.6-fold: P = 0.023, ES 1.22 Large) and CWI conditions (CWI VLOW ~ 2.4-fold vs. CWI LOW ~ 8.0 fold: P = 0.019, ES 1.43 Large). Furthermore, PGC-1 a mRNA expression in the CWI-LOW trial was not signiﬁcantly different to the CON LOW limb ( P = 0.281, ES 0.67 Moder-ate). Data demonstrate that the previously reported effects of post-exercise CWI on PGC-1 a mRNA expression (as regulated systemically via b -adrenergic mediated cell signaling) are offset in those conditions in which local stressors (i.e., high-intensity exercise and low muscle glycogen availability) have already sufﬁciently activated the AMPK-PGC-1 a signaling axis. Additionally, data suggest that commencing exercise with very low muscle glycogen availability atten-uates PGC-1 a signaling.
Vitamin D Toxicity–A Clinical Perspective

Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration are the most often noted clinical symptoms of vitamin D toxicity (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its clinical manifestation, severe hypercalcemia, are related to excessive long-term intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of coincident disease that produces the active vitamin D metabolite locally. Although VDT is rare, the health effects can be serious if it is not promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT exist. Exogenous VDT is usually caused by the inadvertent or improper intake of extremely high doses of pharmacological preparations of vitamin D and is associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing. Endogenous VDT may develop from excessive production of an active vitamin D metabolite – 1,25(OH)2D in granulomatous disorders and in some lymphomas or from the reduced degradation of that metabolite in idiopathic infantile hypercalcemia. Endogenous VDT may also develop from an excessive production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams–Beuren syndrome. Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe. That phenomenon, called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism. Researchers have proposed many processes to explain VDT. Those processes include elevated activity of 1α-hydroxylase or inhibited activity of 24-hydroxylase, both leading to increased concentration of 1,25(OH)D; increased number of vitamin D receptors; and saturation of the capacity of vitamin D binding protein. Increased public awareness of vitamin D–related health benefits might increase the risk of VDT due to self-administration of vitamin D in doses higher then recommended for age and body weight or even higher than the established upper limit intake values. Consequently, the incidence of hypercalcemia due to hypervitaminosis D might increase.
Physical activity programs for older people in the community receiving home care services: systematic review and meta-analysis

Abstract The proportion of older adults is increasing around the world and most wish to live in their home until they die. To achieve this, many will require services in the home to remain living independently. To maintain function (ie, strength, balance, and endurance), physical activity needs to be undertaken on a regular basis, and is essential as a person ages. Unfortunately, as people age there is a tendency to reduce activity levels, which often leads to loss of function and frailty, and the need for home care services. This updated systematic review includes a mix of study methodologies and meta-analysis, and investigated the effectiveness of physical activity/exercise interventions for older adults receiving home care services. Eighteen studies including ten randomized controlled trials meeting the selection criteria were identified. Many of the studies were multi-factorial interventions with the majority reporting aims beyond solely trying to improve the physical function of home care clients. The meta-analysis showed limited evidence for effectiveness of physical activity for older adults receiving home care services. Future exercise/physical activity studies working with home care populations should consider focusing solely on physical improvements, and need to include a process evaluation of the intervention to gain a better understanding of the association between adherence to the exercise program and other factors influencing effectiveness.
Wildland Fires and the Environment: a Global Synthesis

Fire has been an agent of disturbance for thousands of years. Forest and wildland fires have occurred long before the advent of humans, shaping landscape structure, pattern and ultimately the species composition of ecosystems. The ecological role of fire is to influence several factors such as plant community development, soil nutrient availability and biological diversity. Forest and wildland fire is a vital and natural process that initiates natural cycles of vegetation succession and maintains ecosystem viability.
Evaluation of the Neuroprotective Effects of S(+)-Ketamine During Open-Heart Surgery

We compared the effect of S(+)-ketamine to remifentanil, both in combination with propofol, on the neurocognitive outcome after open-heart surgery in 106 patients. A battery of neurocognitive tests was administered before surgery and 1 and 10 wk after surgery. Fourteen patients (25%) in the control group and 10 patients (20%) in the S(+)-ketamine group had 2 or more tests with a cognitive deficit (decline by at least one preoperative SD of that test in all patients) 10 wk after surgery (P = 0.54). Z-scores were calculated for all tests. No significantly better performance could be detected in the S(+)-ketamine group, except for the Trailmaking B test 10 wk after surgery. We conclude that S(+)-ketamine offers no greater neuroprotection compared with remifentanil during open-heart surgery.
The Pleckstrin Homology Domain of Phospholipase C β Transmits Enzymatic Activation through Modulation of Membrane - Domain Orientation

Phospholipase C-beta (PLC β ) enzymes are activated by G α q and G βγ subunits and catalyze the hydrolysis of the minor membrane lipid phosphatidylinositol 4,5 bisphosphate (PI(4,5)P 2 ). Activation of PLC β 2 by G βγ subunits has been shown to be conferred through its N-terminal pleckstrin homology (PH) domain although the underlying mechanism is unclear. Also unclear are observations that the extent of G βγ activation differs on different membrane surfaces. In this study, we have identified a unique region of the PH domain of PLC β 2 domain (residues 71-88) which, when added to the enzyme as a peptide, causes enzyme activation similar to G βγ subunits. This PH domain segment interacts strongly with membranes composed of lipid mixtures but not those containing lipids with electrically neutral zwitterionic head groups. Moreso, addition of this segment perturbs interaction of the catalytic domain, but not the PH domain, with membrane surfaces. We monitored the orientation of the PH and catalytic domains of PLC by intermolecular fluorescence resonance energy transfer (FRET) using the G βγ activatable mutant, PLC β 2/ δ 1(C193S). We find an increase in FRET with binding to membranes with mixed lipids but not to those containing only lipids with electrically neutral head groups. These results suggest that enzymatic activation can be conferred through optimal association of the PH β 71-88 region to specific membrane surfaces. These studies allow us to understand the basis of variations of G βγ activation on different membrane surfaces. Phospholipases C are intracellular enzymes that catalyze of the PH domain mutants based on GRK2. We are indebted to Finly Philip for providing G βγ to Yuanjian Guo for providing some of the PLC chimera used of this work, to Dr.Mario Rebecchi for PLC δ 1, and to Dr Ravi.Iyengar for G β 86-105 and G β 86-105 (M101N). We like to thank Dr. Paxton Provitera and Louisa Dowal for helpful advice and criticism.
Incorporating Learned Depth Perception Into Monocular Visual Odometry to Improve Scale Recovery

—A growing interest in autonomous driving has led to a comprehensive study of visual odometry (VO). It has been well studied how VO can estimate the pose of moving objects by examining the images taken from onboard cameras. In the last decade, it has been proposed that deep learning under supervision can be employed to estimate depth maps and visual odometry (VO). In this paper, we propose a DPT (Dense Prediction Transformer)-based monocular visual odometry method for scale estimation. Scale-drift problems are common in traditional monocular systems and in recent deep learning studies. In order to recover the scale, it is imperative that depth estimation to be accurate. A framework for dense prediction challenges that bases its computation on vision transformers instead of convolutional networks is characterized as an accurate model that is utilized to estimate depth maps. Scale recovery and depth refinement are accomplished iteratively. This allows our approach to simultaneously increase the depth estimate while eradicating scale drift. The depth map estimated using the DPT model is accurate enough for the purpose of achieving the best efficiency possible on a VO benchmark, eliminating the scaling drift issue.
Exploring perspectives from stroke survivors, carers and clinicians on virtual reality as a precursor to using telerehabilitation for spatial neglect post-stroke

ABSTRACT Spatial neglect is a common and severe cognitive consequence of stroke, yet there is currently no effective rehabilitation tool. Virtual Reality (VR) telerehabilitation tools have the potential to provide multisensory and enjoyable therapies and remotely monitor adherence without the presence of a therapist at all times. Researchers and industry need to better understand end-user perspectives about these technologies to ensure these are acceptable and, ultimately, optimize adherence and efficacy. This study aims to explore end-user perspectives on the use of self-administered VR for spatial neglect in a university environment to identify barriers and facilitators prior to extending its use remotely as a telerehabilitation tool. We used a mixed-method design including focus groups, self-administered questionnaires and interviews with stroke survivors (N = 7), their carers (N = 3) and stroke clinicians (N = 6). End-user perspectives identified clarity of instructions, equipment (cost, available resources) and for some, level of experience with technology as barriers of use. Perceived facilitators were performance feedback, engagement and enjoyment, and psychological benefits associated with self-administered VR telerehabilitation. Overall, end-users were positive and interested in using VR telerehabilitation for spatial neglect. These perspectives enabled us to produce practical recommendations to inform development, enhance engagement and uptake of VR telerehabilitation and inform future studies.
Weaker HLA footprints on HIV in the unique and highly genetically admixed 1 host population of Mexico 2 3

27 HIV circumvents HLA class I-restricted CD8+ T cell responses through selection of 28 escape mutations that leave characteristic mutational "footprints" also known as 29 HLA-associated polymorphisms (HAPs) on HIV sequences at the population 30 level. While many HLA footprints are universal across HIV subtypes and human 31 populations, others can be region-specific as a result of the unique immunogenetic 32 background of each host population. Using a published probabilistic 33 phylogenetically-informed model, we compared HAPs in HIV Gag and Pol (PR-RT) 34 in 1,612 subtype B-infected, antiretroviral treatment-naïve individuals from Mexico 35 and 1,641 from Canada/USA. A total of 252 HLA class I allele subtypes were 36 represented, including 140 observed in both cohorts, 67 unique to Mexico and 45 37 unique to Canada/USA. At the predefined statistical threshold of q<0.2, 358 HAPs 38 (201 in Gag; 157 in PR-RT) were identified in Mexico, while 905 (534 in Gag and 39 371 in PR-RT) were identified in Canada/USA. HAP identified in Mexico included 40 both "canonical" HLA-associated escape pathways and novel associations, in 41 particular with HLA alleles enriched in Amerindian and mestizo populations. 42 on D ecem er 4, 2017 by gest http/jvi.asm . rg/ D ow nladed fom
Travelling to High Altitudes Could be Thrombogenetic!

People ascending to high altitude regions are at risk for a variety of health problems, commonly including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE) etc. Increasing travel to mountainous terrains has brought light to several other medical problems as well. It has been well recognized that a hypercoagulable state exists when a person is exposed to high altitude environment. This may manifest as early thromboembolic episodes, which may result in deep vein thrombosis (DVT) or acute pulmonary embolism (PE), which is a potentially fatal condition. The various effects of thrombosis include pulmonary thrombo-embolism (PTE), cerebral venous thrombosis, portal/splenic vein thrombosis, and deep vein thrombosis (DVT). Out of all these conditions, PTE is an extremely common and highly lethal condition that is a leading cause of death in all age groups. Exposure to high altitude (HA), either during air travels, ascension of mountains, or while engaging in sports activities results in hyper coagulability thus predisposing to thromboembolic events. Climbers staying at high altitudes for weeks also possess several risk factors for thromboembolism. A large number of environmental variables suggest that a single cause of HAinduced thromboembolic disorders (TED) may not exist, so that this peculiar phenomenon could be seen as a complex or multifactorial trait. In view of the greatly increased risk of getting deep venous thrombosis and pulmonary embolism at high altitude, it would be interesting to review the studies done so far for defining its cause and treatment. Thus the present review examines the risk of thrombosis at increasing elevations along with the possible underlying mechanisms, the diagnosis and treatment strategies.
Caenorhabditis elegans oocytes detect meiotic errors in the absence of canonical end-on kinetochore attachments

meiotic defects, demonstrating that errors can be detected in these cells and revealing a mechanism that regulates anaphase progression. This mechanism does not appear to rely on several components of the spindle assembly checkpoint but does require the kinetochore, as depleting kinetochore components prevents the error-induced anaphase delays. These findings therefore suggest that in this system, kinetochores could be involved in sensing meiotic errors using an unconventional mechanism that does not use canonical end-on attachments.
(2018). Midlatitude atmospheric circulation responses under 1.5 and 2.0g°C warming and implications for regional impacts. Earth

This study investigates the global response of the midlatitude atmospheric circulation to 1.5 and 2.0 ◦ C of warming using the HAPPI (Half a degree Additional warming, Prognosis and Projected Impacts) ensemble, with a focus on the winter season. this for regional of multi-model mean response of midlatitudes; Case explore the implications of possible the tails of the response
Expanded genetic screening in C . elegans identifies new regulators and 1 an inhibitory role for NAD + in axon regeneration 2 3

1 Section of Neurobiology, Division of Biological Sciences 8 2 Department of Cellular and Molecular Medicine, School of Medicine 9 University of California, San Diego 10 La Jolla, CA 92093, USA 11 3 Lead contact 12 4 Current address: Convergence Program of Material Science for Medicine and 13 Pharmaceutics, Hallym University, Chuncheon, 24252, South Korea 14 15 *Correspondence: yijin@ucsd.edu (Y.J. as lead contact), adchisholm@ucsd.edu (A.D.C.), 16 kwkim@hallym.ac. kr (K.W.K.) 17 18 Running title: New regulators of axon regeneration 19 20
The ability of early changes in motivation to predict later antidepressant treatment response

Introduction: Baseline values and early changes of emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception have not been studied to any extent in unipolar depression, although they could help to characterize different dimensions of illness that are harder to capture by clinicians, give new insights on how patients improve, and offer new early clinical markers for later treatment response. Methods: About 1,565 adult outpatients with major depressive disorder receiving agomelatine completed the clinician-rated 16-item quick inventory of depressive symptoms, Clinical Global Impression, and Multidimensional Assessment of Thymic States (MAThyS) rating scales at inclusion, Week 2 and Week 6. The MAThyS includes a 20-item self-rated visual analog scale (from inhibition [0] to activation [10], with [5] representing the usual state) leading to five a priori dimensions (emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception). Results: All MAThyS dimension scores increased from inclusion to Week 2 and from inclusion to Week 6 ( P , 0.001). Improvement was around 2 points (out of 10) for motivation, 1.5 points for psychomotor function, and 0.5 points for other dimensions. Motivation showed a trend to being more severely impaired at inclusion in future nonresponders ( t = 1.25, df = 1,563, P = 0.10). Its improvement at Week 2 was the most discriminating MAThyS dimension between future responders and nonresponders, and represents the best predictor of future response, with the highest area under the receptor operating characteristic curve (area under curve = 0.616, 95% confidence interval [0.588–0.643], P , 0.001). Finally, improvements in motivation correlated the most strongly with clinician-rated 16-item quick inventory of depressive symptoms improvement ( r =- 0.491, df = 1,563, P , 0.001). Conclusion: Motivation had the most capacity for early improvement, the best predictive value for response, and the largest global margin of progress in depressed outpatients. Assessing the evolution of self-reported motivation over time in major depressive disorder could offer an interesting complementary approach to predict response.
Morphological response and tumor shrinkage as predictive factors in metastatic colorectal cancer treated with rst-line capecitabine, oxaliplatin, and bevacizumab

Tomoyuki Nagaoka Ehime University Hospital Hiroki Osumi The Cancer Institute Hospital Teruko Ueno The Cancer Institute Hospital Akira Ooki The Cancer Institute Hospital Takeru Wakatsuki The Cancer Institute Hospital Izuma Nakayama The Cancer Institute Hospital Mariko Ogura The Cancer Institute Hospital Daisuke Takahari The Cancer Institute Hospital Keisho Chin The Cancer Institute Hospital Kiyoshi Matsueda The Cancer Institute Hospital Kensei Yamaguchi The Cancer Institute Hospital Eiji Shinozaki (  eiji.shinozaki@jfcr.or.jp ) The Cancer Institute Hospital