bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective serotonin reuptake inhibitor citalopram ameliorates cognitive decline and protects against amyloid beta-induced mitochondrial dynamics, biogenesis, autophagy, mitophagy and synaptic toxicities in a mouse model of Alzheimer’s disease
Authors: Reddy Arubala P , Sawant Neha , Morton Hallie , Kshirsagar Sudhir , Bunquin Lloyd E , Yin Xiangling , Reddy P Hemachandra 
Published: March 2021

Abstract
In the current study, we investigated the protective role of citalopram against cognitive decline, impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective autophagy, mitophagy and synaptic dysfunction in APP transgenic mouse model of Alzheimer’s disease (ad). We treated 12-month-old wild-type (WT) and age-matched transgenic APP mice with citalopram for 2 months. Using Morris Water Maze and rotarod tests, quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed cognitive behavior, RNA and protein levels of mitochondrial dynamics, biogenesis, autophagy, mitophagy, synaptic, ad-related and neurogenesis genes in wild-type and APP mice treated and untreated with citalopram. Citalopram-treated APP mice relative to citalopram-untreated APP mice exhibited improved cognitive behavior. Increased levels of mRNA associated with mitochondrial fission and ad-related genes; decreased levels of fusion, biogenesis, autophagy, mitophagy, synaptic and neurogenesis genes were found in APP mice relative to WT mice. However, APP mice treated with citalopram compared to citalopram-untreated APP mice revealed reduced levels of the mitochondrial fission and ad-related genes and increased fusion, biogenesis, autophagy, mitophagy, synaptic and neurogenesis genes. Our protein data agree with the mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in APP mice; these were reversed in citalopram-treated APP mice. Further, Golgi-cox staining analysis revealed reduced dendritic spines in APP mice relative to WT mice. However, citalopram-treated APP mice showed significantly increased dendritic spines, indicating that citalopram enhances spine density, synaptic activity and improved cognitive function in APP mice. These findings suggest that citalopram reduces cognitive decline, Aβ levels and mitochondrial and synaptic toxicities and may have a strong protective role against mutant APP and Aβ-induced injuries in patients with depression, anxiety and ad.
Diminished Circulating Levels of Angiogenic Factors and Rage Ligands in Helminth–Diabetes Comorbidity and Reversal Following Anthelmintic Treatment
Authors: Rajamanickam Anuradha , Munisankar Saravanan , Menon Pradeep A , Nutman Thomas B , Babu Subash 
Published: March 2021

Abstract

Background
Various epidemiological and experimental studies propose that helminths could play a preventive role against the progression of type 2 diabetes mellitus (T2DM). T2DM induces microvascular and large vessel complications mediated by elevated levels of angiogenic factors and soluble receptor for advanced glycation end product (RAGE) ligands. However, the interactions between helminths and host angiogenic factors and RAGE ligands are unexplored.

Methods
To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss), and T2DM, we measured plasma levels of vascular endothelial growth factor (VEGF)–A, -C, and -D; angiopoietins 1 and 2 (Ang-1 and Ang-2); and their receptors VEGF-R1, -R2, and -R3 as well as soluble RAGE (sRAGE) and their ligands advanced glycation end products (AGEs), S100A12, and high mobility group box 1 (HMGB-1) in individuals with T2DM with or those without Ss infection. In Ss-infected individuals, we also measured the levels of aforementioned factors 6 months following anthelmintic therapy.

Results
Ss-infected individuals exhibited significantly decreased levels of VEGF-A, VEGF-C, VEGF-D, Ang-1, and Ang-2 and their soluble receptors VEGF-R1, -R2, and -R3, that increased following anthelmintic therapy. Likewise, Ss-infected individuals exhibited significantly decreased levels of AGEs and their ligands sRAGE, S100A12, and HMGB-1, which reversed following anthelmintic therapy.

Conclusions
Our data suggest that Ss infection could play a beneficial role by limiting or delaying T2DM-related vascular complications.
Engineering Task-based Augmented Reality Guidance: Application to the Training of Aircraft Flight Procedures
Authors: Lallai Giorgia , Loi Zedda Giovanni , Martinie Célia , Palanque Philippe , Pisano Mauro , Spano Lucio Davide 
Published: March 2021

Abstract
Training operators to efficiently operate critical systems is a cumbersome and costly activity. A training program aims at modifying operators’ knowledge and skills about the system they will operate. The design, implementation and evaluation of a ‘good’ training program is a complex activity that requires involving multi-disciplinary work from multiple stakeholders. This paper proposes the combined use of task descriptions and augmented reality (AR) technologies to support training activities both for trainees and instructors. AR interactions offer the unique benefit of bringing together the cyber and the physical aspects of an aircraft cockpit, thus providing support to training in this context that cannot be achieved by software tutoring systems. On the instructor side, the LeaFT-MixeR system supports the systematic coverage of planed tasks as well as the constant monitoring of trainee performance. On the trainee side, LeaFT-MixeR provides real-time AR information supporting the identification of objects with which to interact, in order to perform the planned task. The paper presents the engineering principles and their implementation to bring together AR technologies and tool-supported task models. We show how these principles are embedded in LeaFT-MixeR system as well as its application to the training of flight procedures in aircraft cockpits.
DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases
Authors: Nagane Masaki , Yasui Hironobu , Kuppusamy Periannan , Yamashita Tadashi , Inanami Osamu 
Published: March 2021

Abstract
A post-exposure cohort study in Hiroshima and Nagasaki reported that low-dose exposure to radiation heightened the risk of cardiovascular diseases (CVD), such as stroke and myocardial infarction, by 14–18% per Gy. Moreover, the risk of atherosclerosis in the coronary arteries reportedly increases with radiation therapy of the chest, including breast and lung cancer treatment. Cellular senescence of vascular endothelial cells (ECs) is believed to play an important role in radiation-induced CVDs. The molecular mechanism of age-related cellular senescence is believed to involve genomic instability and DNA damage response (DDR); the chronic inflammation associated with senescence causes cardiovascular damage. Therefore, vascular endothelial cell senescence is believed to induce the pathogenesis of CVDs after radiation exposure. The findings of several prior studies have revealed that ionizing radiation (IR) induces cellular senescence as well as cell death in ECs. We have previously reported that DDR activates endothelial nitric oxide (NO) synthase, and NO production promotes endothelial senescence. Endothelial NO synthase (eNOS) is a major isoform expressed in ECs that maintains cardiovascular homeostasis. Therefore, radiation-induced NO production, a component of the DDR in ECs, may be involved in CVDs after radiation exposure. In this article, we describe the pathology of radiation-induced CVD and the unique radio-response to radiation exposure in ECs.
Carbon/nitrogen metabolism and stress response networks – calcium-dependent protein kinases as the missing link?
Authors: Alves Hugo L S , Matiolli Cleverson C , Soares Rafael C , Almadanim M Cecília , Oliveira M Margarida , Abreu Isabel A 
Published: March 2021

Abstract
Calcium-dependent protein kinases (CDPKs) play essential roles in plant development and stress responses. CDPKs have a conserved kinase domain, followed by an auto-inhibitory junction connected to the calmodulin-like domain that binds Ca2+. These structural features allow CDPKs to decode the dynamic changes in cytoplasmic Ca2+ concentrations triggered by hormones and by biotic and abiotic stresses. In response to these signals, CDPKs phosphorylate downstream protein targets to regulate growth and stress responses according to the environmental and developmental circumstances. The latest advances in our understanding of the metabolic, transcriptional, and protein–protein interaction networks involving CDPKs suggest that they have a direct influence on plant carbon/nitrogen (C/N) balance. In this review, we discuss how CDPKs could be key signaling nodes connecting stress responses with metabolic homeostasis, and acting together with the sugar and nutrient signaling hubs SnRK1, HXK1, and TOR to improve plant fitness.
Cardioembolic Stroke with Contraindications to Anticoagulation
Authors: LaHue Sara C. , Levin Morris 
Published: March 2021

Abstract
Identification of atrial fibrillation can provide the explanation for a stroke, but it is not always clear when to start anticoagulation in order to prevent another stroke. This chapter breaks down stroke risk and anticoagulation timing in patients with atrial fibrillation as a cause for stroke.
Joining a Collaborative
Authors: Meddings Jennifer , Chopra Vineet , Saint Sanjay 
Published: March 2021

Abstract
When hospitals join in a collaborative infection prevention project, they agree to work within the requirements and discipline of the sponsors. That includes providing baseline and monthly infection rate data to the collaborative leaders and committing some staff members to intense weekly phone talks with the collaborative experts and other coaching sessions. Ideally, a community emerges, both online and in-person. The community members exchange experiences and ideas related to the initiative, socialize, and establish a behavioral norm within each hospital that can help convince resisters, particularly physicians, to change their ways. To make up for the limited attention paid to the problems individual hospitals may encounter, some collaboratives provide a troubleshooting group of expert advisors. The collaborative approach has strong support from federal and state agencies, but some studies have questioned its effectiveness.
Haunted by Pain, Fatigue, and Insomnia
Authors: Doleys Daniel M. , Doleys Nicholas D. 
Published: March 2021

Abstract
The impact of an accident or injury, even if the physical consequences seem relatively minor in nature, can have a prolonged effect on an individual’s psychological well-being. Emotionally traumatic, early-life experiences, have been linked to certain chronic pain problems. Some patients are embarrassed by the effect and feel they should be mentally strong enough to overcome it. Others submit to it and become immobilized. It can significantly magnify the experience of pain. Recognition and treatment of posttraumatic stress disorder need not be overly complicated. Some cases may require referral to a specialist. Nightmares, flash backs, hypervigilance, and avoidance are common.
Something Doesn’t Seem Right
Authors: Doleys Daniel M. , Doleys Nicholas D. 
Published: March 2021

Abstract
This case depicts a situation wherein the facts do not seem to fit. In a hurried and busy clinical practice, one is glad to encounter what seems to be a pleasant patient. Patients with personality disorders, especially those with a borderline personality disorder (BPD), can be very deceptive. Their overall manner is often very congenial, until their expectations or requests are not met. Their presentation may be very different to the staff versus the clinician. Self-destructive (mutilation) behavior can be seen in the more severe cases. Female patients can be very disarming. Their objective, in the chronic pain setting, relates more to issues of control and manipulation than to receiving effective pain management. Treatment can be intensive and involve residential placement. Use of controlled substances can be very dangerous. Patient with BPD are best referred to a specialist.
How Can Someone Do This to Themselves?
Authors: Doleys Daniel M. , Doleys Nicholas D. 
Published: March 2021

Abstract
It is not uncommon to encounter patients who appear to exaggerate their pain complaints for one reason or another. However, these are to be differentiated form those diagnosed with malingering or factitious disorders (FD). Both can be difficult to identify. Malingerers engage in a willfully and deliberately attempt to misrepresent their situation for some type of gain. FD represents a group of patients with significant psychiatric problems. Their behavior often includes self-inflicted wounds, which need to be differentiated from actions that may reflect a suicide attempt, depression, or the self-injurious behavior related to dissociative disorder. The FD patient may well have an altered sensitivity to pain. Their treatment is complex and requires an experienced professional.
The “What If” and “Yes But” Syndrome
Authors: Doleys Daniel M. , Doleys Nicholas D. 
Published: March 2021

Abstract
Repeated requests for a definitive diagnosis, prognosis, and reassurance as to the positive outcome of a therapy made by some patients with chronic pain can be very exhausting to both patient and clinician—especially when it is clear that no amount of information will be satisfactory. The practitioner can easily feel like be asked to be a psychic or fortune teller. Pain catastrophizing (PC) has emerged as critical area of study. PC has been linked pain intensity, decreased function, and treatment outcomes, including the effect of pain medications such as opioids. It is most effectively addressed by the use of cognitive-behavioral therapy procedures. Learning how to apply these strategies in the context of the typical office visit can reduce the frustration level of the clinician and patient. In more severe cases, referral to behavioral specialist may to advisable.
The Abandoned Patient
Authors: Doleys Daniel M. , Doleys Nicholas D. 
Published: March 2021

Abstract
The bane of existence for the clinician who treat patients with chronic pain, especially from a pharmacological perspective, is the “abandoned” patient. The incidence of this has significantly increased according to a 2016 Centers for Disease Control and Prevention report. Indented or not, this report has been used as the foundation for creating, if not imposing, restrictions on the prescribing of opioids The emphasis on total morphine equivalent dosing leaves little room for arguing quality of life issues. Clinicians are encouraged not to fear disciplinary action or prosecution when acting in the usual course of medical practice and offering appropriate documentation. The abandoned patient ranges along a continuum form the person informed that a medication will no longer be prescribed to those from a practice that has been discontinued to those who have committed some egregious violation of the medical agreement. In any case, it is important not to side-step your usual assessment process; prescribe only when you feel comfortable doing so. Under extreme circumstances, a short-term prescription at a low dose to safeguard against catastrophic events may be justified. As always, “trust, but verify.”
Fungal asthma among Ugandan adult asthmatics
Authors: Kwizera Richard , Bongomin Felix , Olum Ronald , Meya David B , Worodria William , Bwanga Freddie , Fowler Stephen J , Gore Robin , Denning David W , Kirenga Bruce J 
Published: March 2021

Abstract

Fungal sensitization is associated with poor asthma control. We aimed to determine the prevalence and factors associated with fungal asthma among Ugandan adults. Individuals aged ≥18 years with a new diagnosis of asthma in the last 12 months participating in the African Severe Asthma Program constituted the study population. Skin prick test results, clinical and demographic data were retrieved from the database, and serum Aspergillus fumigatus specific antibodies and total IgE were measured in stored blood. We enrolled 374 patients, median (IQR) age 34 (25–45) years, 286 (76.5%) females and 286 (76.5%) with severe asthma. Prevalence of Aspergillus fumigatus sensitization was 42.0% (95% CI: 37.1–47.0%), allergic bronchopulmonary aspergillosis (ABPA) 3.2% (1.8–5.5%), severe asthma with fungal sensitization (SAFS) 16% (12.7–20.1%) and allergic bronchopulmonary mycosis (ABPM) 2.9% (1.7–5.2%). Older age (55–64 years) (crude odds ratio (cOR) = 2.6), sensitization to at least one allergen (cOR = 9.38) and hypertension (cOR = 1.99) were significantly associated with Aspergillus sensitization, whereas tertiary education level (cOR = 0.29), severe depression (cOR = 0.15) and strong emotions (cOR = 0.47) were not. High occupational exposure to Aspergillus (cOR = 4.26) and contact with moulds (cOR = 14.28) were significantly associated with ABPA. Palpitations (cOR = 5.54), uncontrolled asthma (cOR = 3.54), eczema/dermatitis (cOR = 3.07), poor lung function (cOR = 2.11) and frequent exacerbations (cOR = 1.01) were significantly associated with SAFS. Eczema/dermatitis (cOR = 1.55) was significantly associated with ABPM, but cold weather trigger (cOR = 0.24) was not. Fungal asthma is a significant problem among Ugandans with asthma and should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy.

Lay Summary
This study showed that fungal asthma is a significant problem among Ugandans with asthma with a high prevalence. Fungal asthma should be considered in patients with uncontrolled asthma despite receiving optimal standard of care. This is the first modern attempt to define these endotypes of asthma in Africa.
New constraints on the 12CO(2–1)/(1–0) line ratio across nearby disc galaxies
Authors: den Brok J S , Chatzigiannakis D , Bigiel F , Puschnig J , Barnes A T , Leroy A K , Jiménez-Donaire M J , Usero A , Schinnerer E , Rosolowsky E , Faesi C M , Grasha K , Hughes A , Kruijssen J M D , Liu D , Neumann L , Pety J , Querejeta M , Saito T , Schruba A , Stuber S 
Published: March 2021

ABSTRACT
Both the CO(2–1) and CO(1–0) lines are used to trace the mass of molecular gas in galaxies. Translating the molecular gas mass estimates between studies using different lines requires a good understanding of the behaviour of the CO(2–1)-to-CO(1–0) ratio, R21. We compare new, high-quality CO(1–0) data from the IRAM 30-m EMIR MultiLine Probe of the ISM Regulating Galaxy Evolution survey to the latest available CO(2–1) maps from HERA CO-Line Extragalactic Survey, Physics at High Angular resolution in Nearby Galaxies-ALMA, and a new IRAM 30-m M51 Large Program. This allows us to measure R21 across the full star-forming disc of nine nearby, massive, star-forming spiral galaxies at 27 arcsec (∼1–2 kpc) resolution. We find an average R21 = 0.64 ± 0.09 when we take the luminosity-weighted mean of all individual galaxies. This result is consistent with the mean ratio for disc galaxies that we derive from single-pointing measurements in the literature, $R_{\rm 21, lit}~=~0.59^{+0.18}_{-0.09}$. The ratio shows weak radial variations compared to the point-to-point scatter in the data. In six out of nine targets, the central enhancement in R21 with respect to the galaxy-wide mean is of order of ${\sim}10{-}20{{\ \rm per\ cent}}$. We estimate an azimuthal scatter of ∼20 per cent in R21 at fixed galactocentric radius but this measurement is limited by our comparatively coarse resolution of 1.5 kpc. We find mild correlations between R21 and carbon monoxide (CO) brightness temperature, infrared (IR) intensity, 70–160 µm ratio, and IR-to-CO ratio. All correlations indicate that R21 increases with gas surface density, star formation rate surface density, and the interstellar radiation field.
Monoceros OB4: a new association in Gaia DR2
Authors: Teixeira P S , Alves J , Sicilia-Aguilar A , Hacar A , Scholz A 
Published: March 2021

ABSTRACT
We use Gaia DR2 data to survey the classic Monoceros OB1 region and look for the existence of a dispersed young population, co-moving with the cloud complex. An analysis of the distribution of proper motions reveals a 20–30 Myr association of young stars, about 300–400 pc away from the far side of the Mon OB1 complex, along the same general line of sight. We characterize the new association, Monoceros OB4, and estimate it contains between 1400 and 2500 stars, assuming a standard initial mass function, putting it on par in size with NGC 2264. We find from the internal proper motions that Mon OB4 is unbound and expanding. Our results seem to unveil a larger and more complex Monoceros star formation region, suggesting an elongated arrangement that seems to be at least 300 × 60 pc.
Novelty and Convergence in Adaptation to Whole Genome Duplication
Authors: Bohutínská Magdalena , Alston Mark , Monnahan Patrick , Mandáková Terezie , Bray Sian , Paajanen Pirita , Kolář Filip , Yant Levi 
Published: March 2021

AbstractWhole genome duplication (WGD) can promote adaptation but is disruptive to conserved processes, especially meiosis. Studies in Arabidopsis arenosa revealed a coordinated evolutionary response to WGD involving interacting proteins controlling meiotic crossovers, which are minimized in an autotetraploid (within-species polyploid) to avoid missegregation. Here, we test whether this surprising flexibility of a conserved essential process, meiosis, is recapitulated in an independent WGD system, Cardamine amara, 17 My diverged from A. arenosa. We assess meiotic stability and perform population-based scans for positive selection, contrasting the genomic response to WGD in C. amara with that of A. arenosa. We found in C. amara the strongest selection signals at genes with predicted functions thought important to adaptation to WGD: meiosis, chromosome remodeling, cell cycle, and ion transport. However, genomic responses to WGD in the two species differ: minimal ortholog-level convergence emerged, with none of the meiosis genes found in A. arenosa exhibiting strong signal in C. amara. This is consistent with our observations of lower meiotic stability and occasional clonal spreading in diploid C. amara, suggesting that nascent C. amara autotetraploid lineages were preadapted by their diploid lifestyle to survive while enduring reduced meiotic fidelity. However, in contrast to a lack of ortholog convergence, we see process-level and network convergence in DNA management, chromosome organization, stress signaling, and ion homeostasis processes. This gives the first insight into the salient adaptations required to meet the challenges of a WGD state and shows that autopolyploids can utilize multiple evolutionary trajectories to adapt to WGD.