Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

Several lines of evidence pointed to an important role for CGRP in migraine. These included the anatomic colocalization of CGRP and its receptor in sensory fibers innervating pain‐producing meningeal blood vessels, its release by trigeminal stimulation, the observation of elevated CGRP in the cranial circulation during migraine with normalization concomitant with headache relief by sumatriptan, and translational studies with intravenous (IV) CGRP that evoked migraine only in migraineurs. The development of small molecule CGRP receptor antagonists (CGRP‐RAs) that showed clinical antimigraine efficacy acutely and prophylactically in randomized placebo‐controlled clinical trials subsequently gave definitive pharmacological proof of the importance of CGRP in migraine. More recently, CGRP target engagement imaging studies using a CGRP receptor PET ligand [11C]MK‐4232 demonstrated that there was no brain CGRP receptor occupancy at clinically effective antimigraine doses of telcagepant, a prototypic CGRP‐RA. Taken together, these data indicated that (1) the therapeutic site of action of the CGRP‐RAs was peripheral not central; (2) that IV CGRP had most likely evoked migraine through an action at sites outside the blood‐brain barrier; and (3) that migraine pain was therefore, at least in part, peripheral in origin. The evolution of CGRP migraine science gave impetus to the development of peripherally acting drugs that could modulate CGRP chronically to prevent frequent episodic and chronic migraine. Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use. Eptinezumab, a CGRP neutralizing antibody given IV, shows promise in late stage clinical development. Recently, orally administered next‐generation small molecule CGRP‐RAs have been shown to have safety and efficacy in acute treatment (ubrogepant and rimegepant) and prevention (atogepant) of migraine, giving additional CGRP‐based therapeutic options for migraine patients.
Profiling of Seed Proteome in Pea (Pisum sativum L.) Lines Characterized with High and Low Responsivity to Combined Inoculation with Nodule Bacteria and Arbuscular Mycorrhizal Fungi

Legume crops represent the major source of food protein and contribute to human nutrition and animal feeding. An essential improvement of their productivity can be achieved by symbiosis with beneficial soil microorganisms—rhizobia (Rh) and arbuscular mycorrhizal (AM) fungi. The efficiency of these interactions depends on plant genotype. Recently, we have shown that, after simultaneous inoculation with Rh and AM, the productivity gain of pea (Pisum sativum L) line K-8274, characterized by high efficiency of interaction with soil microorganisms (EIBSM), was higher in comparison to a low-EIBSM line K-3358. However, the molecular mechanisms behind this effect are still uncharacterized. Therefore, here, we address the alterations in pea seed proteome, underlying the symbiosis-related productivity gain, and identify 111 differentially expressed proteins in the two lines. The high-EIBSM line K-8274 responded to inoculation by prolongation of seed maturation, manifested by up-regulation of proteins involved in cellular respiration, protein biosynthesis, and down-regulation of late-embryogenesis abundant (LEA) proteins. In contrast, the low-EIBSM line K-3358 demonstrated lower levels of the proteins, related to cell metabolism. Thus, we propose that the EIBSM trait is linked to prolongation of seed filling that needs to be taken into account in pulse crop breeding programs. The raw data have been deposited to the ProteomeXchange with identifier PXD013479.
Decreased CSF Levels of ß-Amyloid in Patients With Cortical Superficial Siderosis

Background: Cortical superficial siderosis (cSS) represents a key neuroimaging marker of cerebral amyloid angiopathy (CAA) that is associated with intracranial hemorrhages and cognitive impairment. Nevertheless, the association between cSS and core cerebrospinal fluid (CSF) biomarkers for dementia remain unclear. Methods: One hundred and one patients with probable (79%, 80/101) or possible (21%, 21/101) CAA according to the modified Boston criteria and mild cognitive impairment according to Petersen criteria were prospectively included between 2011 and 2016. CSF analyses of ß-amyloid 42, ß-amyloid 40, total tau and phosphorylated tau were performed using sandwich-type enzyme-linked immunosorbent-assay. All patients received MRI and Mini-Mental-State Examination (MMSE). Logistic regression analysis was used to adjust for possible confounders. Results: cSS was present in 61% (62/101). Of those, 53% (33/62) had disseminated cSS and 47% (29/62) focal cSS. ß-amyloid 42 was lower in patients with cSS than in patients without cSS (OR 0.2; 95% CI 0.08–0.6; p = 0.0052) and lower in patients with disseminated cSS than in those with focal cSS (OR 0.02; 95% CI 0.003–0.2; p = 0.00057). Presence of cSS had no association with regard to ß-amyloid 40, total tau and phosphorylated tau. Conclusions: Our results demonstrate that the presence and extent of cSS are associated with reduced CSF ß-amyloid 42 levels. Further studies are needed to investigate the underlying mechanisms of this association.
Clinical care gaps and solutions in diabetes and advanced chronic kidney disease: a patient-oriented qualitative research study.

BACKGROUND Patients with diabetes and advanced chronic kidney disease face a high health care burden. As part of a patient-oriented research initiative to identify ways to better support patients' diabetes care, we explored their health care experience and solutions for patient-centred diabetes care. METHODS We engaged 2 patients with advanced kidney disease and diabetes to join our multidisciplinary team as full research partners. They were involved in our design and conduct of the study, the analysis of the results and knowledge translation. We conducted qualitative interviews (1:1 semistructured interviews and focus groups) with patients with a history of both diabetes (type 1 or 2) and advanced kidney disease including those using dialysis. We identified overarching themes using individual and team analysis and conducted interviews until data saturation was reached. RESULTS Twelve participants were interviewed between October 2017 and February 2018. Six people were interviewed in 2 separate focus groups (consisting of 4 and 2 participants) and 6 participated in 1:1 interviews with our team. Participants described being burdened by medical appointments, strict conflicting diets, costly diabetes therapies and fragmented, siloed health care. They indicated that self-management support, education and coordinated diabetes care might better support their diabetes care. INTERPRETATION Patients with complex medical comorbidities face many challenges traversing a health care system organized around single diseases. Researchers and policy-makers should study and develop patient-centred diabetes care strategies to better support these high-risk patients.
Motivational and cognitive correlates of community integration in homeless veterans entering a permanent supported housing program.

Homelessness is a major public health problem, and serious mental illness (SMI) is highly prevalent in the homeless population. Although supported housing services-which provide permanent housing in the community along with case management-improve housing outcomes, community integration typically remains poor, and little is known about the underlying determinants of poor community integration postresidential placement. The general SMI literature has indicated that motivational and cognitive ability factors are key determinants of successful community integration, which provides a foundation for examining this issue. This study evaluated whether interview- and performance-based assessments of motivation, nonsocial and social-cognitive ability, and psychiatric symptoms were associated with community integration indices in 2 samples of homeless veterans either with (N = 96) or without (N = 80) a psychotic disorder who had recently been admitted to a supported housing program but who had not yet attained housing. Motivation indices, including experiential negative symptoms and defeatist performance attitudes, stood out as the most robust correlates (rs = -.30 to -.69) of community integration across both samples, particularly for social role participation. Demographics, general psychiatric symptoms, and nonsocial cognition showed generally weak relations with community integration, though social cognition showed a few relations. The consistent findings across samples point to the importance of motivational factors for understanding the determinants of poor community integration in this complex population. Further, interventions that target motivational challenges may have widespread usefulness for enhancing community integration outcomes beyond obtaining housing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The Australian Journal of Mathematical Analysis and Applications

Let q1 and q2 be univalent in∆ := {z : |z| < 1} with q1(0) = q2(0) = 1. We give some applications of first order differential subordination and superordination to obtain sufficient conditions for normalized analytic functions f with f(0) = f ′(0) = 1 to satisfy q1(z) ≺ z 2f ′(z) f2(z) ≺ q2(z).
Sex Differences in Sex Hormone Profiles and Prediction of Consciousness Recovery After Severe Traumatic Brain Injury

Objective: The clinical course of unconsciousness after traumatic brain injury (TBI) is commonly unpredictable and it remains a challenge with limited therapeutic options. The aim of this study was to evaluate the early changes in serum sex hormone levels after severe TBI (sTBI) and the use of these hormones to predict recovery from unconsciousness with regard to sex. Methods: We performed a retrospective study including patients with sTBI. A statistical of analysis of serum sex hormone levels and recovery of consciousness at 6 months was made to identify the effective prognostic indicators. Results: Fifty-five male patients gained recovery of consciousness, and 37 did not. Of the female patients, 22 out of 32 patients regained consciousness. Male patients (n = 92) with sTBI, compared with healthy subjects (n = 60), had significantly lower levels of follicular stimulating hormone (FSH), testosterone and progesterone and higher levels of prolactin. Female patients (n = 32) with sTBI, compared with controls (n = 60), had significantly lower levels of estradiol, progesterone, and testosterone and significantly higher levels of FSH and prolactin. Testosterone significantly predicted consciousness recovery in male patients. Normal or elevated testosterone levels in the serum were associated with a reduced risk of the unconscious state in male patients with sTBI. For women patients with sTBI, sex hormone levels did not contribute to the prediction of consciousness recovery. Conclusion: These findings indicate that TBI differentially affects the levels of sex-steroid hormones in men and women patients. Plasma levels of testosterone could be a good candidate blood marker to predict recovery from unconsciousness after sTBI for male patients.
Transcranial Doppler ultrasound in vascular cognitive impairment-no dementia

Background Although cerebral white matter lesions (WMLs) are considered as a risk factor for vascular dementia, data on their impact on cerebral hemodynamics are scarce. We test and compare transcranial Doppler (TCD) features in WML patients with or without associated cognitive impairment. Methods A sample of non-demented elderly patients with WMLs was consecutively recruited. Mean blood flow velocity (MBFV), pulsatility index (PI), peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistivity index (RI) were recorded from the middle cerebral artery bilaterally. Global cognitive functioning, frontal lobe abilities, functional status, and WML severity were also assessed. Results 161 patients satisfying the clinical criteria for vascular cognitive impairment-no dementia (VCI-ND) were age-matched with 97 presenting WMLs without any cognitive deficit. VCI-ND patients exhibited a decrease in MBFV and EDV, as well as an increase in PI, RI, and PSV. Moreover, a significant correlation between all TCD parameters and the severity of executive dysfunction was observed, whereas PI, RI, and EDV were significantly correlated with the WML load. Conclusions VCI-ND showed a hemodynamic pattern indicative of cerebral hypoperfusion and enhanced vascular resistance. These changes may be considered as the TCD correlate of VCI-ND due to microcirculation pathology. TCD provides useful indices of the occurrence and severity of small vessel disease and executive dysfunction in elderly patients at risk of future dementia.
The Australian Journal of Mathematical Analysis and Applications

In this paper, we define the sequence spaces: [V,M, p, u, ∆], [V,M, p, u, ∆]0 and [V,M, p, u, ∆]∞, where for any sequence x = (xn), the difference sequence ∆x is given by ∆x = (∆xn)n=1 = (xn − xn−1)n=1. We also study some properties and theorems of these spaces. These are generalizations of those defined and studied by Savas and Savas [10] and some others before.
Multi-Source Remote-Sensing Monitoring of the Monsoonal Maritime Glaciers at Mt. Dagu, East Qinghai-Tibetan Plateau, China

This research presents a precise evaluation of the recession of monsoonal maritime glaciers at Mt. Dagu, based on multi-source remote-sensing data of an aerial topographic map from 1966 and Landsat MSS, TM, ETM+, and OLI data from 1975 to 2017 for six sub-regions of the glacier covering 1.747±0.068 km<sup>2</sup> at present. The results show that: first, the area of glacier exhibits an exponentially decreasing trend and retreated as much as 5.094±0.301 km<sup>2</sup> during 1975–2017, with a shrinkage rate of 0.120±0.004 km<sup>2</sup>a<sup>−1</sup>. Second, the highest area shrinkage rates of glaciers are in the north, northwest, southwest, and south aspects. The largest retreat altitude of the glacier terminus is in the southwest aspect of region 2. Of which, the absolute retreat elevation is 303 m (from 4587 to 4890 m a.s.l.), at a mean rate of 7.2 m a<sup>−1</sup>. Third, the temperature has increased at a rate of 0.02754°C a<sup>−1</sup> (<inline-formula> <tex-math notation="LaTeX">$R^{2} = 0.6132$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$p < 0.05$ </tex-math></inline-formula>) by a total of 0.9°C (1961–2017), more higher than the region’s average increase. However, there is no significant increasing precipitation trend. The warm-dry trend is aggravated and this is the main reason for the glacier recession. Finally, the accelerated retreat presents a severe challenge to the sustainability of the glaciers and glacier-oriented tourism. Active intervention to maintain the glacier should be urgently considered.
GABE: Galaxy Assembly with Binary Evolution

We developed a new semi-analytic galaxy formation model: Galaxy Assembly with Binary Evolution (GABE). For the first time, we introduce binary evolution into semi-analytic models of galaxy formation by using the Yunnan-II stellar population synthesis model, which includes various binary interactions. When implementing our galaxy formation model onto the merger trees extracted from the Millennium simulation, it can reproduce a large body of observational results. We find that in the local universe, the model including binary evolution reduces the luminosity at optical and infrared wavelengths slightly, but it increases the luminosity at ultraviolet wavelengths significantly, especially in FUV band. The resulting luminosity function does not change very much over SDSS optical bands and infrared band, but the predicted colors are bluer, especially when the FUV band is under consideration. The new model allows us to explore the physics of various high energy events related to the remnants of binary stars, such as type Ia supernovae, short gamma-ray bursts and gravitational wave events, and their relation with host galaxies in a cosmological context.
Astrometric requirements for strong lensing time-delay cosmography

The time-delay between the arrival of photons of multiple images of time-variable sources can be used to constrain absolute distances in the Universe, and in turn obtain a direct estimate of the Hubble constant and other cosmological parameters. To convert the time-delay into distances, it is well known that the gravitational potential of the main deflector and the contribution of the matter along the line of sight need to be known to a sufficient level of precision. In this paper, we discuss a new astrometric requirement that is becoming important, as time-delay cosmography improves in precision and accuracy with larger samples, and better data and modelling techniques. We derive an analytic expression for the propagation of astrometric uncertainties on the multiple image positions into the inference of the Hubble constant and derive requirements depending on image separation and relative time-delay. We note that this requirement applies equally to the image position measurements and to the accuracy of the model in reproducing them. To illustrate the requirement, we discuss some example lensing configurations and highlight that, especially for time-delays of order 10 d or shorter, the relative astrometric requirement is of order milliarcseconds, setting a tight requirement on both measurements and models. With current optical infrared technology, astrometric uncertainties may be the dominant limitation for strong lensing cosmography in the small image-separation regime when high-precision time-delays become accessible.
Religiosity Dimensions and Disability-Free Life Expectancy in Taiwan

Objectives: Eight years of panel data are used to investigate the association between three dimensions of religiosity and total and disability-free life expectancy (TLE/DFLE) in Taiwan. Method: Data come from the 1999 “Taiwan Longitudinal Study on Aging” (TLSA; N = 4,440; Age 55+). Dimensions of religiosity are public, private, belief, and coping. Mortality is linked to a national database. Disability is activities of daily living (ADLs). TLE/DFLE estimates use the Stochastic Population Analysis for Complex Events (SPACE) software. Results: Those who engage in public and private religiosity live longer and more years disability-free than others, but proportion of life disability-free does not differ across levels of religiosity. Coping is less associated with TLE and DFLE. Coping however associates with more years disabled among men. Findings are robust to model specifications. Discussion: The way in which religiosity associates with health depends upon the definition. When it does associate, religiosity increases TLE and DFLE proportionately.
Research Progress on the Relationship between Vitamins and Diabetes: Systematic Review

Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the world. The current clinical drugs for diabetes may lead to adverse effects such as hypoglycemia and liver and abdominal distension and pain, which prompt people to explore new treatments for diabetes without side effects. The research objective of this review article is to systematically review studies on vitamins and diabetes and to explain their possible mechanism of action, as well as to assess the role of vitamins as drugs for the prevention and treatment of diabetes. To achieve our objective, we searched scientific databases in PubMed Central, Medline databases and Web of Science for articles, using “vitamin” and “diabetes” as key words. The results of numerous scientific investigations revealed that vitamin levels were decreased in humans and animals with diabetes, and vitamins show promise for the prevention and/or control of diabetes through anti-inflammation, antioxidation and the regulation of lipid metabolism. However, a few studies showed that vitamins had no positive effect on the development of diabetes. Currently, studies on vitamins in the treatment of diabetes are still very limited, and there are no clinical data to clarify the dose–effect relationship between vitamins and diabetes; therefore, vitamins are not recommended as routine drugs for the treatment of diabetes. However, we still emphasize the great potential of vitamins in the prevention and treatment of diabetes, and higher quality studies are needed in the future to reveal the role of vitamins in the development of diabetes.
Preoperative thromboprophylactic administration of low-molecular-weight-heparin significantly decreased the risk of intraoperative bleeding compared with heparin in patients undergoing video-assisted lobectomy for lung cancer.

Background Due to the threat from venous thromboembolism (VTE) after major thoracic surgery, especially for cancers, guidelines recommend either heparin sodium (unfractionated heparin) or low-molecular-weight-heparin (LMWH) for those patients at high risk of deep vein thrombosis (DVT). However, risk of bleeding remains a major concern for pre-operative administration of anti-coagulation agents. Therefore, this study aimed to compare the bleeding risk of preoperative administration of LMWH and heparin in patients undergoing video-assisted thoracic surgery (VATS) lobectomy for lung cancer. Methods A retrospective, single-center study was designed. A total of 130 patients diagnosed with lung cancer were included from August 2016 to January 2018. These patients were divided into two groups. The preoperative administration of heparin group (PH group) had received heparin 5,000 IU, BID (twice a day) both pre- and post-operatively. And the LMWH group (PL group) had received LMWH 4,000 IU, QD (once a day) both pre- and post-operatively. These anticoagulants would not be ceased until patient was discharged or 24-hour postoperative chest drainage volume exceeded 500 mL. Both preoperative and postoperative coagulation parameters including platelet count (PLT), hemoglobin value (HGB), international normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), postoperative drainage parameters and intraoperative bleeding volume were compared. Results A total of 62 patients were collected in PH group, while 68 patients comprised PL group. Preoperative coagulation parameters, hematologic data and demographic data were comparable. Preoperative duration of two agents (P=0.414), operation time (P=0.155), postoperative HGB (P=0.943), PLT (P=0.244), INR (P=0.469), PT (P=0.651), TT (P=0.407), FIB (P=0.151), drainage duration (P=0.800), duration of heparin and LMWH (P=0.778) were all comparable between the two groups. Compared with PL group, intraoperative bleeding volume (105.11 and 50.26, P<0.001) and postoperative mean drainage volume (251.52 and 216.90 mL, P=0.025) of PH group were significant more. Postoperative APTT (30.17 vs. 28.20 seconds, P=0.022) was significantly longer in PH group. Conclusions Compared with preoperative administration of heparin, preoperative thromboprophylactic administration of LMWH significantly decreased the risk of intraoperative bleeding in VATS lobectomy.