julilili42/papers huggingface dataset:
Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT
2022-07-12

Abstract Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.
Quasi-periodic oscillations in precursor flares via seismic aftershocks from resonant shattering
2022-07-12

Context. GRB 211211A was accompanied by a kilonova, implying a merger origin for the event. A precursor flare, modulated by quasi-periodic oscillations at ≈22 Hz, was also seen ≈1 s prior to the main emission. Aims. It is suggested here that the precursor resulted from the resonant shattering of one star’s crust prior to coalescence. Seismic aftershocks and low-frequency torsional modes may emanate from the rupture site in this case, explaining the underlying oscillations. This interpretation is directly analogous to proposals for giant flares from soft gamma repeaters, where oscillations at similar frequencies have been observed, involving starquakes followed by crustal vibrations. Methods. Torsional mode properties were computed for sequences of slowly rotating, magnetised neutron stars in general relativity. Results. The ≈22 Hz modulations in the precursor matches that of nodeless, l = 2 torsional modes for a wide variety of stellar parameters. Global or discrete Alfvén modes are also viable candidates.
Rates of severe complications in patients undergoing colorectal surgery for deep endometriosis—a retrospective multicenter observational study
2022-07-12

Abstract Introduction Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries. Material and methods This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III–IV of the Clavien–Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40–59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared. Results The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates ( r Spearman = −0.115; P = 0.639) with a high variability of complications in low‐volume centers (group 1) . However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups. Conclusions A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings.
“It's My Country I'm Playing for”—A Biographical Study on National Identity Development of Youth Elite Football Players With Migrant Background
2022-07-12

Sport represents a prominent topic for public and scientific debates on national identity. Looking at Germany, public discourses on national belonging have primarily focused on national elite football and on German-born international football players with Turkish background. Representing the biggest ethnic community in Germany and being highly represented in German youth elite football, athletes with Turkish background are prime examples for the complexity and ambiguity of identity formations in modern immigration countries in general and in youth elite football in particular. Current research has particularly focused on national identity formations of (youth) elite players with migrant background. However, there is a lack of studies that address the process of national identity development in youth elite sport. For that reason, the study aimed to explore stories of national identity development from the perspective of youth football players with Turkish background in German youth elite football. By conducting 10 expert interviews and biographical mappings, we identified specific types, strands, and trajectories of national identity development. Overall, we identified three types of narratives on national identity development: “going with the nomination(s),” “reconsidering national belonging,” and “adding up chances”. Our findings illustrate that national identity development in youth elite sport is particularly shaped by youth elite sport and the national team question. Hence, the stories indicate that international careers not necessarily foster national identification with a nation but can also reduce feelings of national belonging sustainably.
Forging a New World Order? Interdisciplinary Perspectives on the Management of Metalworking and Ideological Change in the Late Bronze Age Carpathian Basin
2022-07-12

Abstract The Carpathian Basin was a highly influential centre of metalworking in the 2nd mil. BC. Nevertheless, despite the abundance of metal objects from the Late Bronze Age, the scarcity of contextually associated metalworking remains representing distinct phases of the metalworking cycle from this region is striking. Here, we explore Late Bronze Age metalworking through the lens of a uniquely complete metalworking assemblage from the site of Șagu from contexts spanning the sixteenth to early thirteenth century BC. This material provides insights into changes in craft organisation following socio-political change after the collapse of Middle Bronze Age tell-centred communities. Our approach combines analytical and experimental data together with contextual analysis of technical ceramics (crucible, mould, and furnace fragments) to reconstruct the metalworking chaîne opératoire and place Șagu in its broader cultural context. Analyses demonstrate clear technological choices in ceramic paste recipes and strong interlinkages between metallurgy and other crafts practised on site, from domestic pottery production to building structures. Experimental replications reveal important intrinsic and experiential aspects of metallurgical activities at Șagu. Evidence on the spatial organisation of metallurgical workflows (routine sequence of actions and decisions) suggests they incorporated a high degree of visibility, which marks a distinct change in the use of craft space compared to the context of densely occupied Middle Bronze Age tells nearby. Combined, our archaeometric, experimental, and contextual results illustrate how changes in metalworking activities in the Late Bronze Age Carpathian Basin were deeply embedded in an ideological shift in the aftermath of the breakdown of Middle Bronze Age tells and the emergence of new social structures.
Arctic Fe-Mn deposits from the Kara Sea: fast-growing refuges for cosmopolitan marine microorganisms under sharp changes of redox conditions
2022-07-12

Abstract The impact of biomineralization and redox processes on the formation and growth of ferromanganese deposits in the World Ocean remains understudied. This problem is particularly relevant for the Arctic marine environment where sharp seasonal variations of temperature, redox conditions and organics inflow significantly impact the biogenic and abiotic pathways of ferromanganese deposits formation. The microbial communities of the fast-growing Arctic Fe-Mn deposits have not been reported so far. Here, we describe the microbial diversity, structure and chemical composition of nodules, crust and their underlying sediments collected from three different sites of the Kara Sea. Scanning electron microscopy revealed a high abundance of microfossils and biofilm-like structures within the nodules. Phylogenetic profiling together with redundancy and correlation analyses revealed a positive selection for putative metal-reducers ( Desulfobacterota ), iron oxidizers ( Hyphomicrobiaceae and Scalinduaceae ), and Fe-scavenging Nitrosopumilaceae or Magnetospiraceae in the microenvironments of the Fe-Mn deposits from their surrounding benthic microbial populations. We hypothesize that in the Kara Sea, the nodules provide unique redox-stable microniches for cosmopolitan benthic marine metal-cycling microorganisms in an unsteady environment, thus focusing the overall geochemical activity of nodule-associated microbial communities and accelerating processes of ferromanganese deposits formation to uniquely high rates.
Current practice in diagnostic genetic testing of the epilepsies
2022-07-13

Abstract Epilepsy genetics is a rapidly developing field, in which novel disease‐associated genes, novel mechanisms associated with epilepsy, and precision medicine approaches are continuously being identified. In the past decade, advances in genomic knowledge and analysis platforms have begun to make clinical genetic testing accessible for, in principle, people of all ages with epilepsy. For this reason, the Genetics Commission of the International League Against Epilepsy (ILAE) presents this update on clinical genetic testing practice, including current techniques, indications, yield of genetic testing, recommendations for pre‐ and post‐test counseling, and follow‐up after genetic testing is completed. We acknowledge that the resources vary across different settings but highlight that genetic diagnostic testing for epilepsy should be prioritized when the likelihood of an informative finding is high. Results of genetic testing, in particular the identification of causative genetic variants, are likely to improve individual care. We emphasize the importance of genetic testing for individuals with epilepsy as we enter the era of precision therapy.
Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology – A Nationwide Survey
2022-07-13

Abstract With the increasing need for minimally invasive procedures based on lower complication rates, higher patient acceptance, and technical developments, there is a growing focus on the sound interventional training of young radiologists. This survey aimed to analyze the current situation in interventional radiology (IR) training in Germany to detect shortcomings and identify areas for improvement. From November 1–30, 2020, an online questionnaire was distributed to representative radiological associations and societies with the request to forward it to radiology residents and radiologists &lt; 40 years. The 44 questions covered six distinct areas from personal working conditions to the characterization of the IR department, training conditions, role of women in IR, and attendance at congresses/external training. A total of 330 participants completed the questionnaire. 77 % of participants expressed a high interest in IR, and 47 % could even imagine subspecializing in interventional radiology. Most institutions provided the necessary learning conditions and infrastructure. The rate of overall satisfaction with IR training conditions was 45 % (vs. a dissatisfaction rate of 39 %). However, females showed a lower satisfaction rate with their training environment than male participants (28 % vs. 51 %; P = 0.06). Positive correlations with work satisfaction were found for the presence and duration of the IR rotation, the number of partly independently/mentored performed interventions, and structured feedback. Moreover, the need for a structured training curriculum was expressed by 67 % of participants. Radiological residents and young radiologists expressed a high interest in interventional radiology, and they rate the infrastructure of German hospitals regarding IR as sufficient. However, they expressed the need for consistent IR rotations and better-structured resident and postgraduate education (curricula &amp; interviews). Interest in interventional radiology among radiological residents and young radiologists in Germany is high, but satisfaction with interventional radiology training leaves room for improvement. The most frequently mentioned aspects that can improve IR training were Citation Format
The exceptionally high diversity of small carnivorans from the Late Miocene hominid locality of Hammerschmiede (Bavaria, Germany)
2022-07-13

The present study deals with new material of carnivorans (Mustelidae, Mephitidae, Ailuridae, Potamotheriinae and Viverridae) from the basal Tortonian (Late Miocene, late Astaracian) hominid-bearing locality of Hammerschmiede (Bavaria, Germany). The small carnivoran fauna includes 20 species belonging to nine different subfamilies (Guloninae, Lutrinae, Mellivorinae, Potamotheriinae, Leptarctinae, Mephitinae, Simocyoninae, Genettinae and Viverrinae). The identified forms include: “ Martes ” sansaniensis , “ Martes ” cf. munki , “ Martes ” sp., Circamustela hartmanni n. sp., Laphyctis mustelinus , Guloninae indet., Eomellivora moralesi , Vishnuonyx neptuni , Paralutra jaegeri , Lartetictis cf. dubia , Trocharion albanense , Palaeomeles pachecoi , Proputorius sansaniensis , Proputorius pusillus , Alopecocyon goeriachensis , Simocyoninae indet., Potamotherium sp., Semigenetta sansaniensis , Semigenetta grandis and Viverrictis modica . The new species Circamustela hartmanni n. sp. is differentiated from the other members of the genus by its small size and the morphology of its dental cusps in the upper and lower carnassials. This is one of the highest reported taxonomic diversities for fossil small carnivorans in the Miocene of Europe, including also first and last occurrences for several genera and species. Additionally, the assemblage comprises some rare taxa such as Palaeomeles pachecoi and Eomellivora moralesi . An ecomorphological comparison of the discovered taxa reveals possible cases of competition and niche partitioning.
Getting fit for the Mathematical Olympiad: positive effects on achievement and motivation?
2022-07-13

Abstract All around the world, there are numerous academic competitions (e.g., “Academic Olympiads”) and corresponding training courses to foster students’ competences and motivation. But do students’ competences and motivation really benefit from such courses? We developed and evaluated a course that was designed to prepare third and fourth graders to participate in the German Mathematical Olympiad. Its effectiveness was evaluated in a quasi-experimental pre- and posttest design ( N = 201 students). Significant positive effects of the training were found for performance in the academic competition (for both third and fourth graders) as well as mathematical competences as measured with a curriculum-oriented test (for fourth graders only). Differential effects across grade levels (with more pronounced positive effects in fourth-grade students) were observed for students’ math self-concept and task-specific interest in mathematics, pointing to possible social comparison effects.
Cell specialization in cyanobacterial biofilm development revealed by expression of a cell-surface and extracellular matrix protein
2022-07-13

Abstract Cyanobacterial biofilms are ubiquitous and play important roles in diverse environments, yet, understanding of the processes underlying development of these aggregates is just emerging. Here we report cell specialization in formation of Synechococcus elongatus PCC 7942 biofilms - a hitherto unknown characteristic of cyanobacterial multicellularity. We show that only a quarter of the cell population expresses at high levels the four-gene ebfG -operon that is required for biofilm formation. Almost all cells, however, are assembled in the biofilm. Detailed characterization of EbfG4 encoded by this operon revealed cell-surface localization as well as its presence in the biofilm matrix. Moreover, EbfG1-3 were shown to form amyloid structures such as fibrils and are thus likely to contribute to the matrix structure. These data suggest a beneficial ‘division of labour’ during biofilm formation where only some of the cells allocate resources to produce matrix proteins – ‘public goods’ that support robust biofilm development by the majority of the cells. Additionally, previous studies revealed the operation of a self-suppression mechanism that depends on an extracellular inhibitor, which supresses transcription of the ebfG -operon. Here we revealed inhibitor activity at an early growth stage and its gradual accumulation along the exponential growth phase in correlation with cell density. Data, however, do not support a threshold-like phenomenon known for quorum-sensing in heterotrophs. Together, data presented here demonstrate cell specialization and imply density-dependent regulation thereby providing novel insights into cyanobacterial communal behaviour. Graphical Abstract
Consent Modules for Data Sharing via the German Human Genome-Phenome Archive (GHGA)
2022-07-13

&amp;lt;p&amp;gt;The German Human Genome-Phenome Archive (GHGA)&amp;nbsp;is a research consortium which is currently&amp;nbsp;establishing a federated data infrastructure allowing the secure storage of and controlled access to omics and&amp;nbsp;related health data consented for scientific research use. This whitepaper contains guidance for Data&amp;nbsp;Submitters on how to update their consent forms&amp;nbsp;such that data may be shared via GHGA for secondary&amp;nbsp;research use.&amp;lt;/p&amp;gt;
“A Place of Rest at the Foot of the Altar”: Topological Categories and Correlations in Kierkegaard’s last Discourse at the Communion on Fridays
2022-07-13

Abstract This article describes a rhetorical characteristic of Kierkegaard’s thirteen Discourses “at the Communion” on Fridays (1848 – 1851), namely, their way of expressing religious truths, theological distinctions, and homiletic statements by a certain concept of space, place and movement, thus making them existentially accessible. It illustrates the fundamental meaning of this series of discourses and especially the last discourse for Kierkegaard’s entire work as an author. By focussing on the topological categories and correlations in the last discourse (1851), the article demonstrates the constitutive role of spatial terms and meanings and so discovers the theological topology of the series as a whole with its coincidences of soteriological, anthropological, liturgical, rhetorical, and existential movements—leading the listener/reader to the “place of rest at the foot of the altar.”
Regulation of synaptic connectivity in schizophrenia by mutual neuron-microglia interaction
2022-07-13

<title>Abstract</title> The examination of post-mortem brain tissue suggests synaptic loss as a central pathological hallmark of schizophrenia. Synaptic loss has been shown to be related to increased inflammation in the central nervous system. Aberrant activation of microglia, the immune cells of the human brain, may account for neuronal damage in schizophrenia. Induced pluripotent stem cells represent a promising tool for studying neuropsychiatric disease mechanisms. A recent challenge has been the development of protocols to derive microglia as well as neurons from schizophrenia patient-derived stem cells to better understand the mechanistic contribution of neuroinflammation to the disease. To address this, we present a co-culture model of neurons and microglia, both of human origin to show increased susceptibility of neurons to microglia-like cells derived from schizophrenia patients. Analysis of IBA-1 expression, NFκB signaling, transcription of inflammasome-related genes, and caspase-1 activation shows that enhanced, intrinsic inflammasome activation in patient-derived microglia exacerbates neuronal deficits such as synaptic loss in schizophrenia. Anti-inflammatory pretreatment of microglia with minocycline specifically rescued aberrant synapse loss in schizophrenia and reduced microglial activation. These findings open up possibilities for further research in larger cohorts, focused clinical work and longitudinal studies that could facilitate earlier therapeutic intervention.