julilili42/papers huggingface dataset:
COVID-19: Mechanistic Model of the African Paradox Supports the Central Role of the NF-κB Pathway
2021-09-21

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has expanded into a global pandemic, with more than 220 million affected persons and almost 4.6 million deaths by 8 September 2021. In particular, Europe and the Americas have been heavily affected by high infection and death rates. In contrast, much lower infection rates and mortality have been reported generally in Africa, particularly in the sub-Saharan region (with the exception of the Southern Africa region). There are different hypotheses for this African paradox, including less testing, the young age of the population, genetic disposition, and behavioral and epidemiological factors. In the present review, we address different immunological factors and their correlation with genetic factors, pre-existing immune status, and differences in cytokine induction patterns. We also focus on epidemiological factors, such as specific medication coverage, helminth distribution, and malaria endemics in the sub-Saharan region. An analysis combining different factors is presented that highlights the central role of the NF-κB signaling pathway in the African paradox. Importantly, insights into the interplay of different factors with the underlying immune pathological mechanisms for COVID-19 can provide a better understanding of the disease and the development of new targets for more efficient treatment strategies.
Ethics, Patents and Genome Editing: A Critical Assessment of Three Options of Technology Governance
2021-09-21

Current methods of genome editing have been steadily realising the once remote possibilities of making effective and realistic genetic changes to humans, animals and plants. To underpin this, only 6 years passed between Charpentier and Doudna’s 2012 CRISPR-Cas9 paper and the first confirmed (more or less) case of gene-edited humans. While the traditional legislative and regulatory approach of governments and international bodies is evolving, there is still considerable divergence, unevenness and lack of clarity. However, alongside the technical progress, innovation has also been taking place in terms of ethical guidance from the field of patenting. The rise of so-called “ethical licensing” is one such innovation, where patent holders’ control over genome editing techniques, such as CRISPR, creates a form of private governance over possible uses of gene-editing through ethical constraints built into their licensing agreements. While there are some immediately apparent advantages (epistemic, speed, flexibility, global reach, court enforced), this route seems problematic for, at least, three important reasons: 1) lack of democratic legitimacy/procedural justice, 2) voluntariness, wider/global coordination, and sustainability/stability challenges and 3) potential motivational effects/problems. Unless these three concerns are addressed, it is not clear if this route is an improvement on the longer, slower traditional regulatory route (despite the aforementioned problems). Some of these concerns seem potentially addressed by another emerging patent-based approach. Parthasarathy proposes government-driven regulation using the patent system, which, she argues, has more transparency and legitimacy than the ethical licensing approach. This proposal includes the formation of an advisory committee that would guide this government-driven approach in terms of deciding when to exert control over gene editing patents. There seem to be some apparent advantages with this approach (over traditional regulation and over the ethical licensing approach mentioned above—speed and stability being central, as well as increased democratic legitimacy). However, problems also arise—such as a “half-way house” of global democratic legitimacy that may not be legitimate enough whilst still compromising speed of decision-making under the “ethical licensing” approach). This paper seeks to highlight the various advantages and disadvantages of the three main regulatory options—traditional regulation, ethical licensing and Parthasarathy’s approach—before suggesting an important, yet realistically achievable, amendment of TRIPS and an alternative proposal of a WTO ethics advisory committee.
Visual phenomena associated with migraine and their differential diagnosis
2021-09-21

Patients with visual phenomena typically consult physicians from various medical specialties. A correct differential diagnosis can be made based on the history if the physician views the symptoms in their overall context to determine the particular disease entity that is responsible.
Investigating Middle Palaeolithic subsistence: zooarchaeological perspectives on the potential character of hominin climate refugia in Greece
2021-09-21

ABSTRACT It has long been proposed that during Pleistocene climatic perturbations the Balkan peninsula sustained refugial areas for fauna, flora, and potentially, hominins. In this study, we explore Middle Palaeolithic subsistence at the peninsula's southern end, Greece, and discuss how the evidence contributes to our understanding of the region's character as a refugium. We present new data from the recent reanalysis of the fauna from Asprochaliko rockshelter and the ongoing zooarchaeological investigations at Lakonis Cave 1 and compare them with published analyses from Klissoura Cave 1. We employ taxonomic abundance and diversity indices, as well as mortality profiles, to investigate hominin prey choice. Additional taphonomic observations provide further information on carcass exploitation. We examine changes in the faunal composition of the three sites in an attempt to identify the extent to which climate might have influenced resource availability and diversity in the region, stimulating resource intensification or diversification processes. Our results suggest that Middle Palaeolithic hominins consistently acquired high‐ranked prey through time. However, interregional differences in resource exploitation indicate that local topography and microclimate mediated prey choice and availability.
The Taphonomy of Echinoids
2021-09-21

The study of echinoid evolution, diversity, and ecology has always suffered from the fact that they are represented by taxa showing widely differing architectural designs of their multi-plated skeletons, inhabiting a large range of marine paleoenvironments, which result in highly varying taphonomic biases dictating their presence and recognition. This Element addresses the taphonomy of echinoids and includes: a general introduction to the morphological features of echinoids that play a role in their preservation; a review of processes which play an important role in the differential preservation of both regular and irregular echinoids including predation and transport; a summary of taphonomic pathways included in actualistic studies for recent sea urchins and then reconstructed for fossil taxa; and finally, a case study of the variation of echinoid taphonomy across a shelf gradient using the rich Miocene echinoid fauna of Sardinia.
Droplet condensation in the lattice gas with density functional theory
2021-09-21

A density functional for the lattice gas with next-neighbor attractions (Ising model) from fundamental measure theory is applied to the problem of droplet states in three-dimensional, finite systems. The density functional is constructed via an auxiliary model with hard lattice gas particles and lattice polymers to incorporate the attractions. Similar to previous simulation studies, the sequence of droplets changing to cylinders and to planar slabs is found upon increasing the average density ρ[over ̄] in the system. Owing to the discreteness of the lattice, additional effects in the state curve for the chemical potential μ(ρ[over ̄]) are seen upon lowering the temperature away from the critical temperature [oscillations in μ(ρ[over ̄]) in the slab portion and spiky undulations in μ(ρ[over ̄]) in the cylinder portion as well as an undulatory behavior of the radius of the surface of tension R_{s} in the droplet region]. This behavior in the cylinder and droplet region is related to washed-out layering transitions at the surface of liquid cylinders and droplets. The analysis of the large-radius behavior of the surface tension γ(R_{s}) gave a dominant contribution ∝1/R_{s}^{2}, although the consistency of γ(R_{s}) with the asymptotic behavior of the radius-dependent Tolman length seems to suggest a weak logarithmic contribution ∝lnR_{s}/R_{s}^{2} in γ(R_{s}). The coefficient of this logarithmic term is smaller than a universal value derived with field-theoretic methods.
Male or Female? - Influence of Gender Role and Sexual Attraction on Sex Categorization of Faces
2021-09-21

The categorization of dominant facial features, such as sex, is a highly relevant function for social interaction. It has been found that attributes of the perceiver, such as their biological sex, influence the perception of sexually dimorphic facial features with women showing higher recognition performance for female faces than men. However, evidence on how aspects closely related to biological sex influence face sex categorization are scarce. Using a previously validated set of sex-morphed facial images (morphed from male to female and vice versa), we aimed to investigate the influence of the participant’s gender role identification and sexual orientation on face sex categorization, besides their biological sex. Image ratings, questionnaire data on gender role identification and sexual orientation were collected from 67 adults (34 females). Contrary to previous literature, biological sex per se was not significantly associated with image ratings. However, an influence of participant sexual attraction and gender role identity became apparent: participants identifying with male gender attributes and showing attraction toward females perceived masculinized female faces as more male and femininized male faces as more female when compared to participants identifying with female gender attributes and attraction toward males. Considering that we found these effects in a predominantly cisgender and heterosexual sample, investigation of face sex perception in individuals identifying with a gender different from their assigned sex (i.e., transgender people) might provide further insights into how assigned sex and gender identity are related.
Comparative analysis of clinical outcome and quality of life between amputations and combined bone and flap reconstructions at the lower leg
2021-09-21

Patients undergoing complex extremity reconstructions, including flap transfer to the lower leg have better functionality and higher quality of life than amputated patients. These data emphasize the advantages of these procedures and justify reconstructive efforts for limb salvage. Level of Evidence III.Implications for RehabilitationAmputation and combined bone and flap reconstruction in severe injuries of the lower leg can imply functional disabilities even after successful treatment.Albeit longer hospitalizations, patients with complex reconstructions showed better functional outcomes and had a higher quality of life.Limb salvage showed better functional outcomes and a higher rate in reintegration to work as compared to limb amputation.These data emphasize the importance of complex bone and soft tissue reconstruction in this patient cohort.
Neuroprotective and cerebrovascular effects of endogenous N-Arachidonoyl-GABA and its putative Cox-2 metabolite – GABA conjugate with Prostaglandin E2
2021-09-21

Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAOmodel, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABAand its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions.
Patient Portals: Objectives, Acceptance, and Effects on Health Outcome – A Scoping Review of Reviews
2021-09-21

Patient portals provide patients access to their electronic health record and other functions as secure messaging. For over a decade, more and more patient portals are developed for various settings. The aim of this scoping review of reviews is to systematically search the literature for existing reviews to provide an overview of patient portals’ objectives, acceptance and effects on outcome. We followed the PRISMA Statement and its extension for scoping reviews, and searched for articles published in 2011–2021. The 19 included articles were considerably heterogeneous concentrating on health outcome or patient portal facilitators and barriers.
Faster Grasping of High-Calorie Food Objects in Virtual Reality
2021-09-21

Abstract Purpose : Attractive food elicits approaching behavior, which could be directly assessed in a combination of Virtual Reality (VR) with online motion-capture. Thus, VR enables the assessment of motivated approach and avoidance behavior towards food and non-food cues in controlled laboratory environments. Aim of this study was to test the specificity of a behavioral approach bias for high-calorie food in grasp movements compared to low-calorie food and neutral objects of different complexity, namely, simple balls and geometrically more complex tools. Methods : In a VR setting, healthy participants repeatedly grasped or pushed high-calorie food, low-calorie food, balls and office tools in randomized order with 30 item repetitions. All objects were rated for valence and arousal. Results : High-calorie food was less attractive and more arousing in subjective ratings than low-calorie food and neutral objects. Responses to high-calorie food were fastest only in grasp trials, but comparisons with low-calorie food and complex tools were inconclusive. Conclusion : A behavioral bias for food may be specific to high-calorie food objects, but more systematic variations of object fidelity are outstanding. The utility of VR in assessing approach behavior is confirmed in this study by exploring manual interactions in a controlled environment.
Opening the side exit pores of ClpP by lowering the pH of proteolytic chamber coupled with substrate hydrolysis
2021-09-21

Abstract The ClpP serine peptidase is a tetradecameric degradation machine involved in many physiological processes. It becomes a competent ATP-dependent protease with Clp-ATPases. Small chemical compounds, acyldepsipeptides (ADEPs), are known to cause dysregulation and activation of ClpP without ATPases, and have potential as novel antibiotics. Previously, structural studies of ClpP from various species revealed the structural details, conformational changes, and activation mechanism. Although product release by the side exit pores has been proposed, the detailed driving force for product release remains elusive. Here, we report crystal structures of ClpP from Bacillus subtilis (BsClpP) in unforeseen ADEP-bound states. Cryo-electron microscopy structures revealed various conformational states at different pH conditions. To understand the conformational change for product release, we investigated the relationship between substrate hydrolysis and the pH lowering process. Our data, together with previous findings, provide insight into the molecular mechanism of product release by ClpP self-compartmentalizing protease.
Effect of stimulus orientation and intensity on short-interval intracortical inhibition (SICI) and facilitation (SICF): A multi-channel transcranial magnetic stimulation study
2021-09-22

Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.
The Genomic Processes of Biological Invasions: From Invasive Species to Cancer Metastases and Back Again
2021-09-22

The concept of invasion is useful across a broad range of contexts, spanning from the fine scale landscape of cancer tumors up to the broader landscape of ecosystems. Invasion biology provides extraordinary opportunities for studying the mechanistic basis of contemporary evolution at the molecular level. Although the field of invasion genetics was established in ecology and evolution more than 50 years ago, there is still a limited understanding of how genomic level processes translate into invasive phenotypes across different taxa in response to complex environmental conditions. This is largely because the study of most invasive species is limited by information about complex genome level processes. We lack good reference genomes for most species. Rigorous studies to examine genomic processes are generally too costly. On the contrary, cancer studies are fortified with extensive resources for studying genome level dynamics and the interactions among genetic and non-genetic mechanisms. Extensive analysis of primary tumors and metastatic samples have revealed the importance of several genomic mechanisms including higher mutation rates, specific types of mutations, aneuploidy or whole genome doubling and non-genetic effects. Metastatic sites can be directly compared to primary tumor cell counterparts. At the same time, clonal dynamics shape the genomics and evolution of metastatic cancers. Clonal diversity varies by cancer type, and the tumors’ donor and recipient tissues. Still, the cancer research community has been unable to identify any common events that provide a universal predictor of “metastatic potential” which parallels findings in evolutionary ecology. Instead, invasion in cancer studies depends strongly on context, including order of events and clonal composition. The detailed studies of the behavior of a variety of human cancers promises to inform our understanding of genome level dynamics in the diversity of invasive species and provide novel insights for management.
Cyclosporine A Protects Retinal Explants against Hypoxia
2021-09-22

The retina is a complex neurological tissue and is extremely sensitive to an insufficient supply of oxygen. Hypoxia plays a major role in several retinal diseases, and often results in the loss of cells that are essential for vision. Cyclosporine A (CsA) is a widely used immunosuppressive drug. Furthermore, treatment with CsA has neuroprotective effects in several neurologic disorders. No data are currently available on the tolerated concentration of CsA when applied to the retina. To reveal the most effective dose, retinal explants from rat eyes were exposed to different CsA concentrations (1–9 μg/mL). Immunohistochemistry with brain-specific homeobox/POU domain protein 3a (Brn3a) and TUNEL staining was performed to determine the percentage of total and apoptotic retinal ganglion cells (RGCs), as well as the responses of micro- and macroglial cells. Furthermore, optical coherence tomography (OCT) scans were performed to measure the changes in retinal thickness, and recordings with multielectrode array (MEA) were performed to evaluate spontaneous RGC spiking. To examine the neuroprotective effects, retinas were subjected to a hypoxic insult by placing them in a nitrogen-streamed hypoxic chamber prior to CsA treatment. In the biocompatibility tests, the different CsA concentrations had no negative effect on RGCs and microglia. Neuroprotective effects after a hypoxic insult on RGCs was demonstrated at a concentration of 9 μg/mL CsA. CsA counteracted the hypoxia-induced loss of RGCs, reduced the percentage of TUNEL+ RGCs, and prevented a decrease in retinal thickness. Taken together, the results of this study suggest that CsA can effectively protect RGCs from hypoxia, and the administered concentrations were well tolerated. Further in vivo studies are needed to determine whether local CsA treatment may be a suitable option for hypoxic retinal diseases.