julilili42/papers huggingface dataset:
Cluster efficient pangenome graph construction with nf-core/pangenome
2024-05-15

Abstract Motivation Pangenome graphs offer a comprehensive way of capturing genomic variability across multiple genomes. However, current construction methods often introduce biases, excluding complex sequences or relying on references. The PanGenome Graph Builder (PGGB) addresses these issues. To date, though, there is no state-of-the-art pipeline allowing for easy deployment, efficient and dynamic use of available resources, and scalable usage at the same time. Results To overcome these limitations, we present nf-core/pangenome , a reference-unbiased approach implemented in Nextflow following nf-core’s best practices. Leveraging biocontainers ensures portability and seamless deployment in HPC environments. Unlike PGGB, nf-core/pangenome distributes alignments across cluster nodes, enabling scalability. Demonstrating its efficiency, we constructed pangenome graphs for 1000 human chromosome 19 haplotypes and 2146 E. coli sequences, achieving a two to threefold speedup compared to PGGB without increasing greenhouse gas emissions. Availability nf-core/pangenome is released under the MIT open-source license, available on GitHub and Zenodo, with documentation accessible at https://nf-co.re/pangenome/1.1.2/docs/usage . Contact simon.heumos@qbic.uni-tuebingen.de , sven.nahnsen@qbic.uni-tuebingen.de
Hemin-induced platelet activation is regulated via ACKR3 chemokine surface receptor - implications for passivation of vulnerable atherosclerotic plaque
2024-05-15

Abstract In vulnerable atherosclerotic plaques intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release of hemoglobin and free hemin. Hemin activates platelets and leads to thrombosis. Agonism of the inhibitory platelet receptor ACKR3 inhibits hemin-dependent platelet activation and thrombus formation. To characterize the effect of hemin and ACKR3 agonism on isolated human platelets, multi-color flow cytometry and classical experimental setup such as light transmission aggregometry and a flow chamber assay have been used. Hemin induces platelet aggregation and ex vivo platelet-dependent thrombus formation on immobilized collagen under low shear rate 500 s -1 indicating that free hemin is a strong activator for platelet-dependent thrombosis. Recently, we described that ACKR3 is a prominent inhibitory receptor of platelet activation. Specific ACKR3 agonists but not conventional antiplatelet compounds such as COX-1 inhibitor (indomethacin), ADP-receptor blocker (cangrelor), or PAR1 inhibitor (ML161) inhibit both hemin-dependent aggregation and thrombus formation. To further characterize the effect of hemin on platelet subpopulations we established a multi-color flow cytometry assay. We found that hemin induces procoagulant (CD42b pos / PAC-1 neg / AnnexinV pos ), aggregatory (CD42b pos / PAC-1 pos / AnnexinV neg ) and inflammatory (CD42b pos / CXCR4 pos /ACKR3 pos / AnnexinV pos ) platelet subpopulations. Treatment with ACKR3 agonists significantly decrease the formation of procoagulant and ACKR3 pos platelets in response to hemin. We conclude that hemin is a strong activator for the formation of procoagulant platelets and thrombus formation which is dependent on the function of ACKR3. Activation of ACKR3 through specific agonists may offer a therapeutic strategy to control vulnerability of atherosclerotic plaques in areas of IPH. Graphical abstract Intraplaque hemorrhages (IPH) results in hemolysis and liberation of iron containing heme and its oxidized metabolite hemin. Hemin activates platelets and has strong pro-thrombotic activity. Agonism of the atypical chemokine receptor 3 (ACKR3) inhibits hemin-induced platelet activation.
The Pleistocene Maritime Migration of Modern Humans in Northern Wallacea: The Cases of Topogaro in Sulawesi and Bubog in Mindoro
2024-05-15

Around 50,000 years ago, early modern humans migrated from Island Southeast Asia and via the Wallacean islands into the continent of Sahul in Oceania by several sea crossings. The Wallacean archipelago can be broadly divided into northern Wallacea comprising the northern Indonesian islands and most of the Philippine islands, except Palawan, and southern Wallacea with the southern Indonesian islands and Timor. This chapter focuses on the cases of early modern human maritime migration and resource use in northern Wallacea during the late Pleistocene. Of the Pleistocene sites in northern Wallacea, two important sites are presented and discussed: the Goa Topogaro cave complex in central Sulawesi, Indonesia, now dated to 42 ka, and the Bubog rock-shelter sites in Mindoro, Philippines, dated to at least 35 ka, based on our excavations. We discuss both localities in their regional context, as well as their role in maritime migration and seafaring in Wallacea and Sahul, and provide a comparison with other cases in the Ryukyu Islands, adjacent to northern Wallacea.
Reactivity of a Neutral Yttrium(III) Trimethyl Complex toward Brønsted and Lewis Acids
2024-05-15

Abstract The present study corroborates that the neutral tridentate N ‐ligand 1,4,7‐trimethyl‐triazacyclononane (Me 3 TACN) qualifies as a versatile platform to study selective ligand exchange with rare‐earth‐metal alkyl complexes, herein [(Me 3 TACN)YMe 3 ]. Treatment with Brønsted‐acidic bis(dimethylsilyl)amine, HN(SiHMe 2 ) 2 , gave selectively the mono‐exchanged heteroleptic complex [(Me 3 TACN)YMe 2 {N(SiHMe 2 ) 2 }]. Depending on the molecular ratio employed, the reaction of [(Me 3 TACN)YMe 3 ] with AlMe 3 resulted in the isolation/crystallization of [(Me 3 TACN)YMe 2 (AlMe 4 )] [1 : 1] or ion‐separated [(Me 3 TACN)YMe(AlMe 4 )][AlMe 4 ] [1 : 2] and [(Me 3 TACN)YMe(AlMe 4 )][Al 2 Me 7 ] [1 : 3]. Analogous reactions with the heavier group 13 methyls GaMe 3 and InMe 3 generated mixed methyl/tetramethylgallato complex [(Me 3 TACN)YMe 2 (GaMe 4 )] and ion‐separated [{(Me 3 TACN)YMe 2 } 2 { μ ‐Me}][InMe 4 ]. Finally, dimethylalane, HAlMe 2 , converted [(Me 3 TACN)YMe 3 ] into heteroaluminate [(Me 3 TACN)Y(HAlMe 3 ) 3 ], representing an AlMe 3 ‐supported, molecular yttrium trihydride complex. All compounds were investigated by single crystal X‐ray diffraction (SC‐XRD), homo‐ and heteronuclear ( 13 C, 27 Al, 89 Y, 115 In) NMR as well as IR spectroscopies and elemental analyses.
How Reasons-Focused Is the Categorical Imperative?
2024-05-15

Abstract According to Pauline Kleingeld’s account of Kant’s prohibition on using others merely as means, A uses B merely as a means if and only if (1) A uses B as a means in the service of realizing her ends, (2) without, as a matter of moral principle, making this use conditional on B’s consent, where (3) by “consent” is meant B’s genuine actual consent to being used, in a particular manner, as a means to A’s end. I suggest that there are two readings of what I refer to as her account’s “double reasons-focus”: whether A uses B merely as a means is either partly or fully determined by A’s reasons (moderate or radical reasons-focus in the criterion sense) and A’s reasons are either part of what the prohibition assesses or the only thing it assesses (moderate or radical reasons-focus in the object-of-assessment sense). I then argue that while it is unusual to interpret Kant’s prohibition as radically reasons-focused in both these senses, doing so is far from unmotivated and might constitute a fruitful move in the debate on the Categorical Imperative. I conclude by showing that this move would allow Kleingeld to dismiss what might otherwise seem like a problem for her account, namely that it cannot accommodate the possibility of non-instrumentalizing violations of perfect duty.
Traumatic Hip Dislocations in Children and Adolescents: Diagnostic Challenges and the Significance of MRI Imaging - A Multi-Center Study
2024-05-15

<title>Abstract</title> <bold>Background</bold> Traumatic hip dislocations in children and adolescents are rare but associated with significant consequences such as secondary coxarthrosis and avascular necrosis of the femoral head. Delayed reductions are cited in the literature as a primary cause, mainly due to radiologically overlooked dislocations. The heterogeneous symptomatology and primary care in regular emergency departments complicate the diagnosis. This multi-center study aims to evaluate the various diagnostic steps and propose an improved algorithm for diagnosing traumatic hip dislocations in childhood. <bold>Methods</bold> This retrospective multi-center study included 76 patients aged up to 17 years with acute traumatic hip dislocations and open growth plates from 16 German hospitals. Exclusion criteria included insufficient data, positive history of hip dysplasia, and association with syndromal, neurological, or connective tissue disorders predisposing to hip dislocation. Analysis included anthropometric data and imaging (ultrasound, X-ray, MRI, CT) from 1979 to 2022. Examined parameters included gender, age, associated fractures, mechanisms of injury, initial care, time to reduction, associated injuries, and diagnostic modalities. Statistical analysis was performed using SPSS while strictly adhering to ethical guidelines. <bold>Results</bold> 76 patients met the inclusion criteria. Primary imaging showed a clear dominance in X-ray diagnostics in one plane 46% (n = 35) and two planes 39% (n = 30). In 87% of the cases (n = 66), dislocations were diagnosed during initial presentation. Dislocations were missed in 12% (n = 9), with seven children under the age of eight years old. Fifty percent of dislocations of those under four years old were not detected. Delayed reduction occurred in 12 children (15.8%), with 8 patients undergoing reduction more than 24 hours after trauma. The reason in 12% of the cases (n = 9) was an undetected dislocation in imaging. Dislocations were particularly commonly overlooked in conventional X-rays, whereas none were missed in MRI. Fifty-four patients (71%) had associated injuries, of which 57.9% (n = 44) were diagnosed only with MRI. <bold>Conclusion</bold> Successful primary diagnosis of traumatic hip dislocations, which are delayed in 15% of cases and carry an increased risk of femoral head necrosis, requires an algorithm, especially for young children where dislocations are often not automatically suspected. MRI plays a crucial role in the secondary diagnostic phase due to the high incidence of associated injuries. MRI provides a more precise depiction, especially of cartilaginous acetabular avulsions and soft tissue interpositions. These findings underscore the indispensable role of MRI diagnostics in traumatic hip dislocations and a unified diagnostic algorithm. <bold>Level of Evidence: IV</bold>
Dynamic Radial MR Imaging for Endoleak Surveillance after Endovascular Repair of Abdominal Aortic Aneurysms with Inconclusive CT Angiography: A Prospective Study
2024-05-15

Background/Objectives: To assess free-breathing, dynamic radial magnetic resonance angiography (MRA) for detecting endoleaks post-endovascular aortic repair (EVAR) in cases with inconclusive computed tomography angiography (CTA). Methods: This prospective single-center study included 17 participants (mean age, 70 ± 9 years; 13 males) who underwent dynamic radial MRI (Golden-angle RAdial Sparse Parallel-Volumetric Interpolated BrEath-hold, GRASP-VIBE) after inconclusive multiphasic CT for the presence of endoleaks during the follow-up of EVAR-treated abdominal aortic aneurysms. CT and MRI datasets were independently assessed by two radiologists for image quality, diagnostic confidence, and the presence/type of endoleak. Statistical analyses included interrater and intermethod agreement, and diagnostic performance (sensitivity, specificity, area under the curve (AUC)). Results: Subjective image analysis demonstrated good image quality and interrater agreement (k ≥ 0.6) for both modalities, while diagnostic confidence was significantly higher in MRA (p = 0.03). There was significantly improved accuracy for detecting type II endoleaks on MRA (AUC 0.97 [95% CI: 0.87, 1.0]) compared to CTA (AUC 0.66 [95% CI: 0.41, 0.91]; p = 0.03). Although MRA demonstrated higher values for sensitivity, specificity, AUC, and interrater agreement, none of the other types nor the overall detection rate for endoleaks showed differences in the diagnostic performance over CT (p ≥ 0.12). CTA and MRA revealed slight to moderate intermethod concordance in endoleak detection (k = 0.3–0.64). Conclusions: The GRASP-VIBE MRA characterized by high spatial and temporal resolution demonstrates clinical feasibility with good image quality and superior diagnostic confidence. It notably enhances diagnostic performance in detecting and classifying endoleaks, particularly type II, compared to traditional multiphase CTA with inconclusive findings.
The ground calibration of the HERMES-Pathfinder payload flight models
2024-05-15

<title>Abstract</title> HERMES-Pathfinder is a space-borne mission based on a constellation of six nano-satellites flying in a low-Earth orbit. The 3U CubeSats, to be launched in early 2025, host miniaturized instruments with a hybrid Silicon Drift Detector/scintillator photodetector system, sensitive to both X-rays and gamma-rays. A seventh payload unit is installed onboard SpIRIT, an Australian-Italian nano-satellite developed by a consortium led by the University of Melbourne and launched in December 2023. The project aims at demonstrating the feasibility of Gamma-Ray Burst detection and localization using miniaturized instruments onboard nano-satellites. The HERMES flight model payloads were exposed to multiple well-known radioactive sources for spectroscopic calibration under controlled laboratory conditions. The analysis of the calibration data allows both to determine the detector parameters, necessary to map instrumental units to accurate energy measurements, and to assess the performance of the instruments. We report on these efforts and quantify features such as spectroscopic resolution and energy thresholds, at different temperatures and for all payloads of the constellation. Finally we review the performance of the HERMES payload as a photon counter, and discuss the strengths and the limitations of the architecture.
The End is the Beginning is the End: The closed-loop learning analytics framework
2024-05-16

This article provides a comprehensive review of current practices and methodologies within the field of learning analytics, structured around a dedicated closed-loop framework. This framework effectively integrates various aspects of learning analytics into a cohesive framework, emphasizing the interplay between data collection, processing and analysis, as well as adaptivity and personalization, all connected by the learners involved and underpinned by educational and psychological theory. In reviewing each step of the closed loop, the article delves into the advancements in data collection, exploring how technological progress has expanded data collection methods, particularly focusing on the potential of multimodal data acquisition and how theory can inform this step. The processing and analysis step is thoroughly reviewed, highlighting a range of methods including machine learning and AI, and discussing the critical balance between prediction accuracy and interpretability. The adaptivity and personalization step examines the current state of research, underscoring significant gaps and the necessity for theory-informed, personalized learning interventions. Overall, the article underscores the importance of interdisciplinarity in learning analytics, advocating for the integration of insights from various fields to address challenges such as ethical data usage and the creation of quality learning experiences. This framework and review aim to guide future research and practice in learning analytics, promoting the development of effective, learner-centric educational environments driven by balancing data-driven insights and theoretical understanding.
Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site
2024-05-16

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus &gt;6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0–1), functional independence (mRS score 0–2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score &gt;6 (mRS score 0–1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22–3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08–2.51]) but not in those with NIHSS score ≤6 (mRS score 0–1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49–1.64]; mRS score 0–2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30–1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11–20.28]; NIHSS score &gt;6: aOR, 1.98 [95% CI, 1.08–3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score &gt;6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.
Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair
2024-05-16

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ versus p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.
Shadows of rotating hairy Kerr black holes coupled to time periodic scalar fields with a nonflat target space
2024-05-16

We study the shadows cast by rotating hairy black holes with two nontrivial time-periodic scalar fields having a nonflat Gaussian curvature of the target space spanned by the scalar fields. Such black holes are a viable alternative to the Kerr black hole, having a much more complicated geodesic structure and resulting shadows. We investigate how a nontrivial Gauss curvature alters the pictures for different amounts of scalar hair around the black holes, quantified by a normalized charge. Our results show that for high values of this charge, close to a boson star limit, chaotic shadows are observed with multiple small disconnected components for all considered Gaussian curvatures. For moderately large amounts of scalar hair and corresponding normalized charge, although the shadows still exhibit chaotic behavior, a dominant shadow component emerges, the size and shape of which are substantially influenced by the Gaussian curvature. For instance, highly chaotic shadows for flat target space, start developing a large central shadow region with the increase of the Gauss curvature even for black holes with substantially heavy scalar hair. For lower values of the normalized charge, the shadows resemble qualitatively the Kerr black hole while the Gaussian curvature has a small impact on their properties.
Mobilizing grievances in the internet age: The case of national online petitioning in South Korea, 2017–2022
2024-05-16

Which kinds of grievances garner support from the public on online platforms? Focusing on national online petitioning, one of the forms of direct democracy in contemporary politics, we examine the content and characteristics of petitions that succeeded in attracting public attention and support. Using our comprehensive data on online petitions that were submitted to the executive office between 2017 and 2022 in South Korea, our analysis yields three important findings. First, a mix of post-materialist topics such as human rights and gender equality and materialist topics such as safety and environment turn out to be salient among petitions that meet the signature threshold. Second, online petitions the contents of which reveal either moral emotions or Confucian attitudes are more likely to gain public support compared to others. Third, keywords that are related to moral claims asking for the apprehension of perpetrators on behalf of victims, such as ‘victim,’ ‘perpetrator,’ ‘kid,’ and ‘punishment,’ appear most frequently inside the petitions that cross the signature threshold. Such findings provide implications for understanding both the potentials and limitations of national online petitioning in contemporary democracies.