julilili42/papers huggingface dataset:
Genetic and Clinical Characterization of Danish Achromatopsia Patients
2023-03-10

Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945–2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: CNGA3; CNGB3; GNAT2; PDE6C and PDE6H; and novel variants were identified in CNGB3 and PDE6C. Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes.
YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression
2023-03-10

Abstract YgfB-mediated β-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa . We show that YgfB upregulates expression of the β-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antiterminator AlpA induces expression of the alpBCDE autolysis genes and of the peptidoglycan amidase AmpDh3. YgfB interacts with AlpA and represses the ampDh3 expression. Thus, YgfB indirectly prevents AmpDh3 from reducing the levels of cell wall-derived 1,6-anhydro-N-acetylmuramyl-peptides, required to induce the transcriptional activator AmpR in promoting the ampC expression and β-lactam resistance. Ciprofloxacin-mediated DNA damage induces AlpA-dependent production of AmpDh3 as previously shown, which should reduce β-lactam resistance. YgfB, however, counteracts the β-lactam enhancing activity of ciprofloxacin by repressing ampDh3 expression and lowering the benefits of this drug combination. Altogether, YgfB represents an additional player in the complex regulatory network of AmpC regulation.
The Influence of Disclosing the AI Potential Error to the User on the Efficiency of User–AI Collaboration
2023-03-10

User–AI collaboration is an increasingly common paradigm in assistive technologies. However, designers of such systems do not know whether communicating the AI’s accuracy is beneficial. Disclosing the accuracy could lead to more informed decision making or reduced trust in the AI. In the context of assistive technologies, understanding how design decisions affect User–AI collaboration is critical because less efficient User–AI collaboration may drastically lower the quality of life. To address this knowledge gap, we conducted a VR study in which a simulated AI predicted the user’s intended action in a selection task. Fifteen participants had to either intervene or delegate the decision to the AI. We compared participants’ behaviors with and without the disclosure of details on the AI’s accuracy prior to the system’s deployment while also varying the risk level in terms of decision consequences. The results showed that communicating potential errors shortened the decision-making time and allowed the users to develop a more efficient strategy for intervening in the decision. This work enables more effective designs of the interfaces for assistive technologies using AI.
Recurrent Acute Disseminated Encephalomyelitis (ADEM) after COVID-19-vaccination and after subsequent COVID-19-infection: A case report (part II)
2023-03-10

Acute disseminated encephalomyelitis (ADEM) is an autoimmune disorder of the central nervous system (CNS), which is commonly associated to previous viral infection or immunization. Cases of ADEM with a potential relationship to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have been reported. We recently published a rare case of a 65-year-old patient who suffered from a corticosteroid- and immunoglobulin-refractory multiple autoimmune syndrome including ADEM following Pfizer-BioNTech coronavirus disease (COVID)-19 vaccination, and whose symptoms largely resolved after repeated plasma exchange (PE). Four months later, the patient was diagnosed with SARS-CoV-2 omicron variant infection after experiencing mild upper respiratory tract symptoms. Few days later, the patient developed severe tetraparesis with magnetic resonance imaging (MRI) showing multiple new inflammatory contrast-enhancing lesions in the left middle cerebellar peduncle, cervical spinal cord, and ventral conus medullaris. Repeated cerebrospinal fluid (CSF) analyses indicated blood-brain barrier damage (increased albumin ratio) without signs of SARS-CoV-2 invasion (mild pleocytosis, no intrathecal antibody production). SARS-CoV-2 specific immunoglobulin G (IgG) were detected in serum and to a much lower degree in CSF with close correlation between both concentrations over time, reflecting antibody dynamics of vaccine- and infection-induced immune response, and blood-brain barrier patency. Daily PE therapy was initiated. Given the patient's lack of improvement after seven PE, treatment with rituximab was considered. After a first dose, however, the patient suffered epididymo-orchitis leading to sepsis, and declined rituximab continuation. At 3-months follow-up, clinical symptoms had dramatically improved. The patient regained walking ability without assistance. This case of recurrent ADEM after COVID-19-vaccination and after subsequent COVID-19-infection strongly supports the hypotheses of neuroimmunological complications in these conditions being promoted by a systemic immune response and mediated by molecular mimicry of, both, viral and vaccine SARS-CoV-2 antigens and CNS self-antigens.
Self-assembly and contraction of micron-scale DNA rings
2023-03-10

Abstract Contractile rings formed from cytoskeletal filaments mediate the division of cells. The reverse-engineering of synthetic contractile rings could shed light on fundamental physical principles of the ring self-assembly and dynamics independent of the natural protein-based compounds. Here, we engineer DNA nanotubes and crosslink them with a synthetic peptide-functionalized star-PEG construct. The star-PEG construct induces the formation of DNA nanotube bundles composed of several tens of individual DNA nanotubes. Importantly, the DNA nanotube bundles curve into closed micron-scale DNA rings in a high-yield one-pot self-assembly process resulting in several thousand rings per microliter. The crosslinked DNA rings can undergo contraction to less than half of their initial diameter by two distinct mechanisms, triggered by increasing molecular crowding or temperature. DNA-based contractile rings expand the toolbox of DNA nanotechnology and could be a future element of an artificial division machinery in synthetic cells.
Memory systems integration in sleep complements rapid systems consolidation in wakefulness
2023-03-10

Abstract Sleep benefits memory performance by fostering systems consolidation, a process that embeds memories into neocortical networks and renders them independent of the hippocampus. Recent evidence shows that memory rehearsal during wakefulness likewise initiates systems consolidation and rapidly engenders neocortical engrams. Here, we investigate the effect of sleep-dependent consolidation for memories that have undergone rapid systems consolidation during wakefulness. After sleep compared to wakefulness, we find better memory retention and higher functional brain activity during memory retrieval in the medial parietal cortex, which hosts memory representations after rehearsal, and in the striatum and thalamus. Increased striatal and thalamic contributions were correlated with higher retrieval performance. Furthermore, all three regions decreased their functional connectivity to the hippocampus specifically after sleep. These findings show that besides continuing of systems consolidation initiated during wakefulness, sleep also acts to integrate different memory systems. Thus, rehearsal-induced and sleep-dependent consolidation seem to be complementary in nature.
Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR
2023-03-10

In patients with FMR, after 6 months the reduction of MR was more stable with an increased number of implanted clips, which suggests that this specific patient collective may benefit from a higher number of clips.
Ravines and gullies, a review about impact valuation
2023-03-11

Abstract Gullies and ravines affect human lives and the environment in many countries worldwide, however, few studies have assessed the impacts of the damage caused by these large linear erosions and clarified their influencing parameters. This work systematizes available information about the variables relevant to analyze the impacts of ravines and gullies on socioeconomic conditions and ecosystem services. Based on keyword searches performed in the Scopus, Web of Science and Dimensions databases, more than 120 articles from 27 countries were identified that addressed and valuated these different types of impacts. Although many studies discuss the impacts of ravines and gullies, few studies have performed valuations of these impacts. We compiled the impacts in urban and rural areas, considering the changes caused by ravines and gullies throughout a hydrographic basin. The results allowed for the elaboration of a theoretical model of the possible impacts of gullies and ravines and how they can be valued. The results demonstrate that the most significant impacts, according to the literature, are in South America, Africa, China and India, which are related to disordered land occupation. In some cases, the lack of capacity to respond to environmental and social problems aggravates the scenario and leads to significant losses. Implementing the evaluation is challenging due to the high number of different forms of possible impacts, in the short, medium and long term, related to environmental, economic and social changes.
Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes
2023-03-11

Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time-course of healing. Their comparison to cancer transcriptomes revealed that a resolution phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer.
Natural IgG antibodies to β amyloid are decreased in patients with Parkinson’s disease
2023-03-11

Abstract Natural antibodies (nAbs) against aggregation-prone proteins have been found in healthy normal subjects. These proteins likely have a pathogenetic role in neurodegenerative diseases of ageing. They include the amyloid β (Aβ) protein which may play an important role in Alzheimer’s dementia (AD), and α-synuclein, a major determinant of Parkinson’s disease (PD). We measured nAbs to Aβ in a group of Italian patients with AD, vascular dementia, non-demented PD patients and healthy elderly controls. We found that Aβ antibody levels in AD were similar to age- and sex-matched controls, but contrary to our expectations, they were significantly reduced in PD. This may identify patients that could be more prone to amyloid aggregation.
Computing Bend-Minimum Orthogonal Drawings of Plane Series–Parallel Graphs in Linear Time
2023-03-11

Abstract A planar orthogonal drawing of a planar 4-graph G (i.e., a planar graph with vertex-degree at most four) is a crossing-free drawing that maps each vertex of G to a distinct point of the plane and each edge of G to a polygonal chain consisting of horizontal and vertical segments. A longstanding open question in Graph Drawing, dating back over 30 years, is whether there exists a linear-time algorithm to compute an orthogonal drawing of a plane 4-graph with the minimum number of bends. The term “plane” indicates that the input graph comes together with a planar embedding, which must be preserved by the drawing (i.e., the drawing must have the same set of faces as the input graph). In this paper we positively answer the question above for the widely-studied class of series–parallel graphs. Our linear-time algorithm is based on a characterization of the planar series–parallel graphs that admit an orthogonal drawing without bends. This characterization is given in terms of the orthogonal spirality that each type of triconnected component of the graph can take; the orthogonal spirality of a component measures how much that component is “rolled-up” in an orthogonal drawing of the graph.
Generation of a heterozygous and a homozygous CSF1R knockout line from iPSC using CRISPR/Cas9
2023-03-11

Mutations in Colony-stimulating factor 1 receptor (CSF1R) lead to CSF1R-related leukoencephalopathy, also known as Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rapidly progressing neurodegenerative disease with severe cognitive and motor impairment. In this study, a homozygous and a heterozygous CSF1R knockout induced pluripotent stem cell (iPSC) line were generated by CRISPR/Cas9-based gene editing. These in vitro models will provide a helpful tool for investigating the still largely unknown pathophysiology of CSF1R-related leukoencephalopathy.
AN INVESTIGATIVE ANALYSIS OF BASKETBALL INJURIES BY COLLEGE STUDENTS
2023-03-11

ABSTRACT Introduction Basketball is a sport with strong rivalry, being, therefore, a modality with great facility to cause sports injuries along its practice. Objective Investigate the status of sports injuries in college basketball for amateur students. Methods 480 college students who were not basketball experts were selected as research volunteers. The current status of sports injuries in the 12-week optional basketball course was investigated, and the main risk factors were analyzed. Results Among amateur male college students, the average playing age of third-grade male college students is higher than that of second-grade male college students, and the weekly playing frequency is lower than that of second-grade male college students. The incidence of basketball sports injuries among male college students who do not specialize in basketball from childhood to adulthood is up to 90.7%, and 85.5% during their college years. Conclusion In basketball sports, the most vulnerable parts of amateur male college students are the wrist joint, ankle joint, knee joint, leg, head and face, shoulder, waist, and back, respectively. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
Bitonic st-Orderings for Upward Planar Graphs: Splits and Bends in the Variable Embedding Scenario
2023-03-11

Abstract Bitonic st -orderings for st -planar graphs were introduced as a method to cope with several graph drawing problems. Notably, they have been used to obtain the best-known upper bound on the number of bends for upward planar polyline drawings with at most one bend per edge in polynomial area. For an st -planar graph that does not admit a bitonic st -ordering, one may split certain edges such that for the resulting graph such an ordering exists. Since each split is interpreted as a bend, one is usually interested in splitting as few edges as possible. While this optimization problem admits a linear-time algorithm in the fixed embedding setting, it remains open in the variable embedding setting. We close this gap in the literature by providing a linear-time algorithm that optimizes over all embeddings of the input st -planar graph. The best-known lower bound on the number of required splits of an st -planar graph with n vertices is <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>n</mml:mi> <mml:mo>-</mml:mo> <mml:mn>3</mml:mn> </mml:mrow> </mml:math> . However, it is possible to compute a bitonic st -ordering without any split for the st -planar graph obtained by reversing the orientation of all edges. In terms of upward planar polyline drawings in polynomial area, the former translates into <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>n</mml:mi> <mml:mo>-</mml:mo> <mml:mn>3</mml:mn> </mml:mrow> </mml:math> bends, while the latter into no bends. We show that this idea cannot always be exploited by describing an st -planar graph that needs at least <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>n</mml:mi> <mml:mo>-</mml:mo> <mml:mn>5</mml:mn> </mml:mrow> </mml:math> splits in both orientations. We provide analogous bounds for graphs with small degree. Finally, we further investigate the relationship between splits in bitonic st-orderings and bends in upward planar polyline drawings with polynomial area, by providing bounds on the number of bends in such drawings.
Bayesian lesion-deficit inference with Bayes factor mapping: Key advantages, limitations, and a toolbox
2023-03-12

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data.
Neurodegeneration, Mitochondria, and Antibiotics
2023-03-12

Neurodegenerative diseases are characterized by the progressive loss of neurons, synapses, dendrites, and myelin in the central and/or peripheral nervous system. Actual therapeutic options for patients are scarce and merely palliative. Although they affect millions of patients worldwide, the molecular mechanisms underlying these conditions remain unclear. Mitochondrial dysfunction is generally found in neurodegenerative diseases and is believed to be involved in the pathomechanisms of these disorders. Therefore, therapies aiming to improve mitochondrial function are promising approaches for neurodegeneration. Although mitochondrial-targeted treatments are limited, new research findings have unraveled the therapeutic potential of several groups of antibiotics. These drugs possess pleiotropic effects beyond their anti-microbial activity, such as anti-inflammatory or mitochondrial enhancer function. In this review, we will discuss the controversial use of antibiotics as potential therapies in neurodegenerative diseases.
Gender-Related Discrepancies in Short-Term Outcomes in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting Surgery
2023-03-12

The sex differences in patients undergoing off-pump coronary artery bypass grafting (OPCAB) surgery are still unclear. Our aim was to investigate the impact of gender on short-term outcomes in males and females after off-pump bypass procedures. Our research was designed as a double-center retrospective analysis. Generally, 343 patients (men (n = 255) and women (n = 88)) who underwent an OPCAB procedure were included in our study. To provide a statistical analysis of unequal cohorts, we created a propensity score-based matching (PSM) analysis (men, n = 61; women, n = 61). The primary endpoint was all-cause in-hospital mortality. Dialysis, transient ischemic attack (TIA), low cardiac output syndrome (LCOS), reoperation due to postoperative bleeding, wound infection and duration of hospital stay were secondary outcomes in our analysis. No significant differences were detected within the male and female groups regarding age (p = 0.116), BMI (p = 0.221), diabetes (p = 0.853), cardiogenic shock (0.256), STEMI (p = 0.283), NSTEMI (p = 0.555) and dialysis (p = 0.496). Males underwent significantly more frequently (p = 0.005) total-arterial revascularization with T-graft technique (p = 0.005) than females. In contrast, temporary pacer use was significantly higher (p = 0.022) in females compared to males. The in-hospital mortality rate was not significantly higher (p = 0.496) in the female group compared to the male group. Likewise, secondary outcomes did not differ significantly between the non-adjusted and the adjusted groups. Based on our findings, gender has no impact on short-term outcomes after OPCAB surgery.